Asian Pacific Journal of Cancer Prevention

Mollaie, Hamid Reza;Monavari, Seyed Hamid Reza;Arabzadeh, Seyed Ali Mohammad;Shamsi-Shahrabadi, Mahmoud;Fazlalipour, Mehdi;Afshar, Reza Malekpour 7045

https://doi.org/10.7314/APJCP.2013.14.12.7045 PDF KSCI

Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

Shan, Wu-Lin;Ma, Xiao-Ling 7057

https://doi.org/10.7314/APJCP.2013.14.12.7057 PDF KSCI

The discovery of the immunodeficient mice has provided a tool for establishing animal models as hosts for in vivo analysis of AML. Various model systems have been established in the last few decades, and it is essential that murine AML models are developed to exploit more specific, targeted therapeutics. In this review, we concentrate on the models of AML and discuss the development of immunodeficiency models for understanding of leukemogenesis, describe those now available and their values and document the methods used for establishing and identifying AML mice models, as well as factors influencing engraftment of human AML in immunodeficient mice. Thus, the function of this article is to provide clinicians and experimentalists with a chronological, comprehensive appraisal of all AML model systems.

John, Lisha Jenny;Muttappallymyalil, Jayakumary 7065

https://doi.org/10.7314/APJCP.2013.14.12.7065 PDF KSCI

Background: Tobacco use is one of the leading causes of preventable death across the world today and the smoking rates among men in the Arab world are amongst the highest in the world. Smoking of dokha, a traditional Arab tobacco is common in some of the Middle East countries such as the United Arab Emirates and Iran. This review focuses on the prevalence, pattern and health effects of dokha use in the Middle East. For this purpose an electronic search was performed in the following databases and websites: MEDLINE, EMBASE, Proquest and Google scholar up to December 2012. The search strategy was based on Internet search for the synonyms of dohka or midwakh. From the results of the review it emerged that younger people are the most common users of dokha. Hence effective outreach health education programs, targeting adolescents, especially school students before they take up the habit of smoking, may thus curb the emergence of the problem.

Zhang, Yuan-Yuan;Liu, Hao 7069

https://doi.org/10.7314/APJCP.2013.14.12.7069 PDF KSCI

Programmed cell death is a basic cellular process that is critical to maintaining tissue homeostasis. In contrast to apoptosis, necrosis was previously regarded as an unregulated and uncontrollable process. However, as research has progressed, necrosis, also known as necroptosis or programmed necrosis, is drawing increasing attention, not least becasu of its possible impications for cancer research. Necroptosis exhibits a unique signaling pathway that requires the involvement of receptor interaction protein kinases 1 and 3 (RIP1 and RIP3), mixed lineage kinase domain-like (MLKL), and phosphoglycerate mutase 5 (PGAM5) and can be specifically inhibited by necrostatins. Not only does necroptosis serve as a backup cell death program when apoptosis is inhibited, but it is now recognized to play a pivotal role in regulating various physiological processes and the pathogenesis of a variety of human diseases such as ischemic brain injury, immune system disorders and cancer. The control of necroptosis by various defined trigger factors and signaling pathways now offers the opportunity to target this cellular process for therapeutic purposes. The purpose of this paper is to review current findings concerning the connections between various trigger factors and the RIP1/RIP3 signaling pathway as it relates to necroptosis.

Ara, Syeda Arshiya;Arora, Vini;Zakaullah, Syed;Raheel, Syed Ahmed;Rampure, Prakash;Ashraf, Sajna 7075

https://doi.org/10.7314/APJCP.2013.14.12.7075 PDF KSCI

Background: Oral submucosal fibrosis (OSMF) is one of the most prevalent premalignant conditions in India which is easy to diagnose but difficult to manage. At present it is considered as irreversible and incurable. It has also been referred to as an epidemic in India. Aims and Objectives: To correlate the frequency and duration of habits with clinical staging, functional staging and histopathological grading and to correlate the clinical and functional staging with histopathological grading. Materials and Methods: The study included a total of 90 subjects, 80 with OSMF in the experimental group and 10 patients in the control group. Patient personal history was recorded with chewing habits, including frequency and duration of chewing. The site of keeping the quid, time duration and whether he/she swallows it or spits it were also noted. Clinical staging was done on the presence of palpable fibrous bands. Functional staging was accomplished by measuring mouth opening. Incisional biopsy was done for all the patients for histopathological examination. Histopathological grading was according to Pindborg and Sirsat. Results: The experimental group comprised 71 males and 9 females, the majority of which were in the age group of 21-30 years. Correlation of habits with clinical staging, functional staging and histopathological grading were significant (p<0.05). Clinical and functional staging did not correlate with histopathological grading, but the correlation of clinical and functional staging was highly significant (p<0.01). Conclusions: The widespread habit of chewing gutkha is a major risk factor for OSMF, especially in the younger age group. In this study, it was found that with increase in the duration and frequency of the habit the severity of the disease increased.

Cao, Zhong-Qing;Shen, Zan;Huang, Wei-Yi 7081

https://doi.org/10.7314/APJCP.2013.14.12.7081 PDF KSCI

MicroRNAs have been demonstrated to regulate proliferation and apoptosis in many types of cancers, but biological functions in osteosarcomas remain relatively unknown. Here, we found expression of miR-802 to be up-regulated in osteosarcoma tissues in comparison with adjacent normal tissues. Enforced expression of miR-802 was able to promote cell proliferation in U2OS and MG63 cells, while miR-802 antisense oligonucleotides (antisense miR-802) inhibited cell proliferation. At the molecular level, our results further revealed that expression of p27, a negative cell-cycle regulator, was negatively regulated by miR-802. Therefore, the data reported here indicate that miR-802 is an important regulator in osteosarcoma, our findings contributing to a better understanding of important mis-regulated miRNAs in this tumour type.

Xu, Tong-Peng;Zhu, Can-Hong;Zhang, Jian;Xia, Rui;Wu, Feng-Lei;Han, Liang;Shen, Hua;Liu, Ling-Xiang;Shu, Yong-Qian 7085

https://doi.org/10.7314/APJCP.2013.14.12.7085 PDF KSCI

Objective: Published data have shown that microRNAs (miRNAs) could play a potential role as diagnostic and prognostic indicators in cancers. Data for the predictive value of microRNA-155 are inconclusive. The aim of the present analysis was therefore to evaluate the role of miR-155 in prognosis for patients with a variety of carcinomas. Methods: Relevant studies were identified by searching PubMed and EMBASE. Data were extracted from studies comparing overall survival (OS), recurrence-free survival (RFS) or cancer-specific survival (CSS) in patients with carcinoma with higher miR-155 expression and those with lower levels. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of miR-155 for clinical outcome were calculated. Results: A total of 15 studies were included. The pooled hazard ratio (HR) for OS of higher miR-155 expression in cancerous tissue was 1.89 (95% CI: 1.20-2.99, P=0.006), which could markedly predict poorer survival in general cancer. For RFS/CSS, elevated miR-155 was also associated with poor prognosis of cancer (HR=1.50, 95% CI: 1.10-2.05, P=0.01). On subgroup analysis, the pooled HR for OS in non-small cell lung cancer (NSCLC) was 2.09 (95% CI: 0.68-6.41, P > 0.05), but for RFS/CSS was 1.28 (95% CI: 1.05-1.55, P=0.015), with statistical significance; the pooled HRs for OS and RFS/CSS in digestive system neoplasms were 3.04 (95% CI: 1.48-6.24, P=0.003) and 2.61 (95% CI: 1.98-3.42, P<0.05), respectively. Conclusions: The results indicated that the miR-155 expression level plays a prognostic role in patients with cancer, especially NSCLCs and digestive system carcinomas.

Areeshi, Mohammed Yahya 7091

https://doi.org/10.7314/APJCP.2013.14.12.7091 PDF KSCI

DNA repair capacity is crucial in maintaining cellular functions and homeostasis. However, it can be altered based on DNA sequence variations in DNA repair genes and this may lead to the development of many diseases including malignancies. Identification of genetic polymorphisms responsible for reduced DNA repair capacity is necessary for better prevention. Homologous recombination (HR), a major double strand break repair pathway, plays a critical role in maintaining the genome stability. The present study was performed to determine the frequency of the HR gene XRCC3 Exon 7 (C18067T, rs861539) polymorphisms in Saudi Arabian population in comparison with epidemiological studies by "MEDLINE" search to equate with global populations. The variant allelic (T) frequency of XRCC3 (C>T) was found to be 39%. Our results suggest that frequency of XRCC3 (C>T) DNA repair gene exhibits distinctive patterns compared with the Saudi Arabian population and this might be attributed to ethnic variation. The present findings may help in high-risk screening of humans exposed to environmental carcinogens and cancer predisposition in different ethnic groups.

Li, Xiao-Hui;Huang, Mei-Ling;Wang, Shi-Miao;Wang, Qing 7095

https://doi.org/10.7314/APJCP.2013.14.12.7095 PDF KSCI

Histone deacetylase (HDAC) inhibitors of cyclic peptide have been proved to be the most complex but the most stable and relative efficient inhibitors because of their large cap region. In this paper, a series of studies were carried out to evaluate the efficacy of synthetic bicyclic tetrapeptide inhibitors 1-5 containing hydroxamic acid referring molecular docking, anti-proliferation, morphology and apoptosis. Docking analysis, together with enzyme inhibitory results, verified the selective capability of inhibitor 4 to HDAC4, which might closely related to haematological tumorigenesis, with Phe227, Asp115, Pro32, His198 and Ser114 participating into hydrophobic interactions and Van der Waals force which was familiar with former study. Moreover, inhibitor 4 inhibited K562 cell line at the $IC_{50}$ value of 1.22 ${\mu}M$ which was 51-67 times more efficient than that for U937 and HL60 cell lines. Inhibitor 4 exhibited the cell cycle-arrested capability to leukemia at S phase or G2/M phase as well as apoptosis-induced ability in different degrees. Finally, we considered that bicyclic tetrapeptide inhibitors were promising inhibitors used in cancer treatment and inhibitor 4 could prevent K562 cell line well from proliferation, arrest cell cycle and induce K562 towards apoptosis to achieve the goals of reversing cancer cells which could become a potential leukemia therapeutic agent in the future.

Zhu, Wen-Jiang;Huang, Chu-Ying;Li, Chuan;Peng, Wei;Wen, Tian-Fu;Yan, Lv-Nan;Li, Bo;Wang, Wen-Tao;Xu, Ming-Qing;Yang, Jia-Yin;Jiang, Li 7101

https://doi.org/10.7314/APJCP.2013.14.12.7101 PDF KSCI

Background: The prognosis of patients with hepatocellular carcinoma (HCC) after curative resection varies greatly. Few studies had investigated the risk factors for early recurrence (recurrence-free time ${\leq}$ 1 year) of hepatitis B virus (HBV)-related HCCs meeting Milan criteria. Methods: A retrospective analysis was performed on the 224 patients with HCC meeting Milan criteria who underwent curative liver resection in our center between February 2007 and March 2012. The overall survival (OS) rate, recurrence-free survival (RFS) rate and risk factors for early recurrence were analyzed. Results: After a median follow-up of 33.3 months, HCC reoccurred in 105 of 224 patients and 32 died during the period. The 1-, 3- and 5-year OS rates were 97.3%, 81.6% and 75.6% respectively, and the 1-, 3- and 5-year RFS rates were 73.2%, 53.7% and 41.6%. Cox regression showed alpha-fetoprotein (AFP) > 800 ng/ml (HR 2.538, 95% CI 1.464-4.401, P=0.001), multiple tumors (HR 2.286, 95% CI 1.123-4.246, P=0.009) and microvascular invasion (HR 2.518, 95% CI 1.475-4.298, P=0.001) to be associated with early recurrence (recurrence-free time ${\leq}$ 1-year) of HCC meeting Milan criteria. Conclusions: AFP > 800 ng/ml, multiple tumors and microvascular invasion are independent risk factors affecting early postoperative recurrence of HCC. In addition resection appears capable of replacing liver transplantation in some situations with safety and a better outcome.

Kubota, Hiroki;Taguchi, Kazumi;Kobayashi, Daichi;Naruyama, Hiromichi;Hirose, Masahito;Fukuta, Katsuhiro;Kubota, Yasue;Yasui, Takahiro;Yamada, Yasuyuki;Kohri, Kenjiro 7107

https://doi.org/10.7314/APJCP.2013.14.12.7107 PDF KSCI

Malignant bowel obstruction (MBO), an occasional complication in patients with advanced urological cancer, causes gastrointestinal symptoms such as nausea and vomiting leading to suffering which severely impairs quality of life (QOL). Drug therapy, especially octreotide, a synthetic analog of somatostatin, is reportedly effective in controlling the symptoms of MBO. In the present study, we administered octreotide to urological cancer patients with MBO and evaluated the improvement of subjective symptoms, oral intake, and nasogastric intubation. Fourteen terminally ill urological cancer patients suffering with MBO were included (age range 55-92, 10 male, 4 female). Octreotide was administered at $300{\mu}g/day$ to those patients subcutaneously as a continuous injection. Significant improvements in subjective symptoms were observed in thirteen patients (92.8%), and ten patients (71.4%) were able to resume oral intake. Four patients required nasogastric drainage before the administration of octreotide, but nasogastric intubation was discontinued in all these cases after the use of octreotide. Early initiation of octreotide resulted in better improvement of MBO symptoms, and no adverse event was observed in any of the patients. These results revealed that $300{\mu}g/day$ dose of octreotide is safe and effective for managing gastrointestinal symptoms of terminally ill urological cancer patients with MBO. We also recommend starting the treatment with ocreotide as soon as MBO is diagnosed.

Zhu, Zhen-Li;Zhang, Jun;Chen, Mei-Lan;Li, Ke 7111

https://doi.org/10.7314/APJCP.2013.14.12.7111 PDF KSCI

Introduction: Trastuzumab, an HER2-targeting agents, has shown efficacy in metastatic HER2-positive breast cancer patients. Single-agent clinical trials have evaluated therapeutic regimens using trastuzumab for metastatic breast cancer patients. The aim of our study is to evaluate the efficacy and safety of trastuzumab in combination with chemotherapy or hormone therapy in HER2-positive metastatic breast cancer patients. Methods: A literature research was conducted in PubMed and to identify appropriate studies from relevant reviews. Randomized controlled trials comparing chemotherapy or hormone therapy regimens in combination with trastuzumab were eligible. Dadta on clinical outcomes, including safety, efficacy, and patient characteristics were collected. Results: Seven articles describing five trials were included in our systematic review and meta-analysis. Partners of trastuzumab included in trials were anthracycline, paclitaxel, docetaxel, anastrozole and letrozole. The addition of trastuzumab to chemotherapy improved the overall survival (HR=0.79, 95%CI 0.65-0.96), while to hormone therapy did not (HR=0.85 95%CI 0.56-1.30). All trastuzumab-containing regimens increased cardiac toxicity (RR=3.37, 95%CI 1.26-9.02) and grade III-IV adverse events. Conclusions: Our study supports the addition of trastuzumab to chemotherapy which is effective and tolerated for metastatic breast cancer with HER2+ patients. Of note, more adverse events will occur followed the use of trastuzumab, especially cardiac toxicity, with two treatment regimens.

Cheung, Rex 7117

https://doi.org/10.7314/APJCP.2013.14.12.7117 PDF KSCI

Background: This study hypothesized living in a poor neighborhood decreased the cause specific survival in individuals suffering from carcinoid carcinomas. Surveillance, Epidemiology and End Results (SEER) carcinoid carcinoma data were used to identify potential socioeconomic disparities in outcome. Materials and Methods: This study analyzed socioeconomic, staging and treatment factors available in the SEER database for carcinoid carcinomas. The Kaplan-Meier method was used to analyze time to events and the Kolmogorov-Smirnov test to compare survival curves. The Cox proportional hazard method was employed for multivariate analysis. Areas under the receiver operating characteristic curves (ROCs) were computed to screen the predictors for further analysis. Results: There were 38,546 patients diagnosed from 1973 to 2009 included in this study. The mean follow up time (S.D.) was 68.1 (70.7) months. SEER stage was the most predictive factor of outcome (ROC area of 0.79). 16.4% of patients were un-staged. Race/ethnicity, rural urban residence and county level family income were significant predictors of cause specific survival on multivariate analysis, these accounting for about 5% of the difference in actuarial cause specific survival at 20 years of follow up. Conclusions: This study found poorer cause specific survival of carcinoid carcinomas of individuals living in poor and rural neighborhoods.

Wu, Qiang;Zhao, Yi-Bing;Sun, Zhi-Hua;Ni, Jing;Wu, Yu-Zhong;Shao, Heng-Hua;Qu, Jun-Wei;Huang, Xin-En 7121

https://doi.org/10.7314/APJCP.2013.14.12.7121 PDF KSCI

Aim: To examine lymph nodes obtained after lipolysis and liposuction of subcutaneous fat of the inguinal region of female vulvar cancer patients to explore the feasibility of clinical application. Methods: The field of operation was on the basis of the range of the conventional resection of inguinal lymph nodes. We injected lipolysis liquid fanwise, started liposuction after 15-20 minutes; then the subcutaneous fatty tissue was sucked out clearly by suction tube. We selected the first puncture holes located on 2-3 cm part below anterior superior spine, the others respectively being located 3cm and 6cm below the first for puncturing into the skin, imbedding a trocar to intorduce $CO_2$ gas and the specular body, and excise the lymph nodes by ultrasonic scalpel. The surgical field chamber was set with negative pressure drainage and was pressured with a soft saline bag after surgery. Results: A lacuna emerged from subcutaneous of the inguinal region after lipolysis and liposuction, with a wide fascia easily exposed at the bottom where lymph nodes could be readily excised. The number of lymph nodes of ten patients excised within the inguinal region on each side was 4-18. The excised average number of lymph nodes was 11 when we had mature technology. Conclusion: Most of adipose tissue was removed after lipolysis and liposuction of subcutaneous tissue of inguinal region, so that the included lymph nodes were exposed and easy to excise by endoscope. This surgery avoided the large incision of regular surgery of inguinal region, the results indicating that this approach is feasible and safe for used as an alternative technology.

Zhang, Shan-Chun;Jin, Wen;Liu, Hui;Jin, Ming-Juan;Chen, Ze-Xin;Ding, Zhe-Yuan;Zheng, Shuang-Shuang;Wang, Li-Juan;Yu, Yun-Xian;Chen, Kun 7127

https://doi.org/10.7314/APJCP.2013.14.12.7127 PDF KSCI

The primary aim of this study was to evaluate the relationship of single nucleotide polymorphisms (SNPs) in ribosomal protein SA (RPSA) gene with colorectal cancer (CRC). A case-control study including 388 controls and 387 patients with CRC was conducted in a Chinese population. Information about socio-demography and living behavior factors was collected by a structured questionnaire. Three SNPs (rs2133579, rs2269349, rs7641291) in RPSA gene were genotyped by Illumina SnapShot method. Multiple logistic regression models were used for assessing the joint effects between tea consumption and SNPs on CRC. The subjects with rs2269349 CC genotype had a decreased risk for CRC (OR=0.60; 95%CI = 0.37-0.99), compared with TT/CT genotype after adjustment for covariates. A similar association of rs2269349 with rectal cancer was observed (OR=0.49; 95%CI=0.24-1.00). Further analyses indicated that this SNP could modify the protective effect of tea drinking on CRC. Among the subjects with rs2269349 TT/CT or rs2133579 AA/GA, there was a marginal significantly lower risk of CRC (OR and 95%CI: 0.63 and 0.39-1.01 for rs2269349; 0.64 and 0.40-1.02 for rs2133579) in tea-drinking subjects in comparison to non-tea-drinking subjects. Mutants in the RPSA gene might be associated with genetic susceptibility to CRC and influence the protective effect of tea consumption in the Chinese population.

Cheung, Min Rex 7133

https://doi.org/10.7314/APJCP.2013.14.12.7133 PDF KSCI

Background: We studied Surveillance, Epidemiology and End Results (SEER) breast cancer data of Georgia USA to analyze the impact of socio-economic factors on the disparity of breast cancer treatment outcome. Materials and Methods: This study explored socio-economic, staging and treatment factors that were available in the SEER database for breast cancer from Georgia registry diagnosed in 2004-2009. An area under the receiver operating characteristic curve (ROC) was computed for each predictor to measure its discriminatory power. The best biological predictors were selected to be analyzed with socio-economic factors. Survival analysis, Kolmogorov-Smirnov 2-sample tests and Cox proportional hazard modeling were used for univariate and multivariate analyses of time to breast cancer specific survival data. Results: There were 34,671 patients included in this study, 99.3% being females with breast cancer. This study identified race and education attainment of county of residence as predictors of poor outcome. On multivariate analysis, these socio-economic factors remained independently prognostic. Overall, race and education status of the place of residence predicted up to 10% decrease in cause specific survival at 5 years. Conclusions: Socio-economic factors are important determinants of breast cancer outcome and ensuring access to breast cancer treatment may eliminate disparities.

Dong, Ji-Rui;Guo, Nan;Zhao, Jian-Pu;Liu, Pin-Duo;Feng, Hui-Hong;Li, Yan 7137

https://doi.org/10.7314/APJCP.2013.14.12.7137 PDF KSCI

Several studies have shown that nemo-like kinase (NLK) plays a vital role in apoptosis of cancer cells. The present research concerned effects and mechanisms of Taxol on NLK knockdown human laryngeal cancerHep-2 cell lines in vitro. Using RNAi, methyl-thiazoltetrazolium (MTT) assays, real-time RT-PCR, Western blotting and flow cytometry analysis, growth and the cell cycle progression of NLK knockdown Hep-2 cells and expression of downstream molecules were observed. Cell growth was obviously suppressed in the Taxol treated group (P<0.001, 48 hours). Cell numbers of combined Taxol-based chemotherapy with lentivirus mediated RNAi treatment group (Lv-shNLK+Taxol goup) were significantly different from NLK-specific siRNA lentivirus infected group (Lv-shNLK group) (p<0.001). Flow cytometry analysis revealed that Lv-shNLK+Taxol caused the G0/G1-phase DNA content to decrease from 44.1 to 3.33% (p<0.001) and the S-phase DNA content to increase from 38.4 to 82.0% (p<0.001), in comparison with the Lv-shNLK+Taxol group. Immunoblot analysis showed that knockdown of NLK led to significant reduction in the levels of cyclin D1, PCNA and PARP, whereas cyclin B1 was elevated in. Cell growth was also obviously suppressed in the Hep-2 cell line, knockdown of NLK making them more sensitive to Taxol treatment. NLK is expected to become a target of new laryngeal cancer gene therapies.

Abdullah, Adina;Abdullah, Khatijah Lim;Yip, Cheng Har;Teo, Soo-Hwang;Taib, Nur Aishah;Ng, Chirk Jenn 7143

https://doi.org/10.7314/APJCP.2013.14.12.7143 PDF KSCI

Background: The survival outcomes for women presenting with early breast cancer are influenced by treatment decisions. In Malaysia, survival outcome is generally poor due to late presentation. Of those who present early, many refuse treatment for complementary therapy. Objective: This study aimed to explore the decision making experiences of women with early breast cancer. Materials and Methods: A qualitative study using individual in-depth interviews was conducted to capture the decision making process of women with early breast cancer in Malaysia. We used purposive sampling to recruit women yet to undergo surgical treatment. A total of eight participants consented and were interviewed using a semi-structured interview guide. These women were recruited from a period of one week after they were informed of their diagnoses. A topic guide, based on the Ottawa decision support framework (ODSF), was used to facilitate the interviews, which were audio recorded, transcribed and analysed using a thematic approach. Results: We identified four phases in the decision-making process of women with early breast cancer: discovery (pre-diagnosis); confirmatory ('receiving bad news'); deliberation; and decision (making a decision). These phases ranged from when women first discovered abnormalities in their breasts to them making final surgical treatment decisions. Information was vital in guiding these women. Support from family members, friends, healthcare professionals as well as survivors also has an influencing role. However, the final say on treatment decision was from themselves. Conclusions: The treatment decision for women with early breast cancer in Malaysia is a result of information they gather on their decision making journey. This journey starts with diagnosis. The women's spouses, friends, family members and healthcare professionals play different roles as information providers and supporters at different stages of treatment decisions. However, the final treatment decision is influenced mainly by women's own experiences, knowledge and understanding.

Zhang, Yi-Xia;Wang, Xue-Mei;Kang, Shu;Li, Xiang;Geng, Jing 7149

https://doi.org/10.7314/APJCP.2013.14.12.7149 PDF KSCI

Objective: Increasing scientific evidence suggests that common variants in the PALB2 gene may confer susceptibility to breast cancer, but many studies have yielded inconclusive results. This meta-analysis aimed to derive a more precise estimation of the relationship between PALB2 genetic variants and breast cancer risk. Methods: An extensive literary search for relevant studies was conducted in PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CNKI and CBM databases from their inception through September 1st, 2013. A meta-analysis was performed using the STATA 12.0 software and crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Six case-control studies were included with a total of 4,499 breast cancer cases and 6,369 healthy controls. Our meta-analysis reveals that PALB2 genetic variants may increase the risk of breast cancer (allele model: OR>1.36, 95%CI: 1.20~1.52, P < 0.001; dominant model: OR>1.64, 95%CI: 1.42~1.91, P < 0.001; respectively). Subgroup analyses by ethnicity indicated PALB2 genetic variants were associated with an increased risk of breast cancer among both Caucasian and Asian populations (all P < 0.05). No publication bias was detected in this meta-analysis (all P > 0.05). Conclusion: The current meta-analysis indicates that PALB2 genetic variants may increase the risk of breast cancer. Thus, detection of PALB2 genetic variants may be a promising biomarker approach.

Zhou, Can;Ren, Yu;Wang, Ke;Liu, Jie;He, Jian-Jun;Liu, Pei-Jun 7155

https://doi.org/10.7314/APJCP.2013.14.12.7155 PDF KSCI

Background and Objective: Rectal washout with saline solution may theoretically prevent anastomotic recurrence in patients with resectable rectal cancer, although exact clinical effects have not yet been determined. In order to derive a more precise estimation of the relationship, the present meta-analysis was performed. Method: Relevant studies were identified by a search of Medline, Embase and Google Website with no restrictions to September 1, 2013, and included in the systematic review and meta-analysis. Results: 5 trials (642 participants) were included to assess the association between rectal washout with saline solution and anastomotic recurrence. The rate of anastomotic recurrence (AR) was 6.23% (40/642), with the pooled OR derived from the five studies being 0.32 (95 % CI=0.15-0.70, P=0.004). The pooled OR derived from the TME and radical resection subgroups were 0.72 (95%CI=0.16-3.12, P=0.66) and 0.51 (95%CI=0.13-1.96, P=0.32), respectively. Conclusion: Results from this analysis show that intra-operative rectal washout with mere saline solution largely reduces the risk of anastomotic recurrences in patients with resectable rectal cancer.

Norlaili, Abdul Aziz;Fatihah, Mohd Amin;Daliana, Nik Farid Nik;Maznah, Dahlui 7161

https://doi.org/10.7314/APJCP.2013.14.12.7161 PDF KSCI

Breast cancer is the most common cancer among women globally. This study was conducted to compare the awareness of breast cancer and the practice of breast self-examination (BSE), clinical breast examination (CBE) and mammography screening among rural females in Pahang and Perak. A cross-sectional study was carried out in five selected rural districts of Pahang and Perak. Two hundred and fifty households were randomly selected and interviewed face to face using a semi-structured questionnaire. The majority of residents from both states were Malay, aged between 50 and 60 years and had a secondary level of education. Malay women aged 40-49 years and women with a higher level of education were significantly more aware of breast cancer (p<0.05). About half of these women practiced BSE (60.7%) and CBE (56.1%), and 7% had underwent mammography screening. The results of this study suggest that women in Pahang and Perak have good awareness of breast cancer and that more than half practice BSE and CBE. The women's level of education appears to contribute to their level of knowledge and health behaviour. However, more effort is needed to encourage all women in rural areas to acquire further knowledge on breast cancer.

Piao, Jin-Mei;Shin, Min-Ho;Kim, Hee Nam;Cui, Lian-Hua;Song, Hye-Rim;Kweon, Sun-Seog;Choi, Jin-Su;Kim, Young-Chul;Oh, In-Jae;Kim, Kyu-Sik 7165

https://doi.org/10.7314/APJCP.2013.14.12.7165 PDF KSCI

Purpose: The aim of this study was to evaluate any association of GSTM1 and GSTT1 null genotypes with the risk of lung cancer in a South Korean population. Methods: We conducted a large-scale, population-based case-control study including 3,933 lung cancer cases and 1,699 controls. Genotypes of GSTM1 and GSTT1 were determined using real-time polymerase chain reaction. Results: In logistic regression analysis adjusted for age and smoking, we did not find any association between GSTM1 or GSTT1 and LC risk in women. However, in men, the GSTM1 and GSTTI null genotypes were borderline associated with risk (OR=1.18, 95% CI=0.99-1.41 for GSTM1, OR=1.18, 95% CI=0.99-1.41 for GSTT1), and combined GSTM1 and GSTT1 null genotypes conferred an increased risk for LC in men (OR=1.39, 95% CI=1.08-1.78). The OR for the GSTT1 null genotype was greater in subjects aged 55 years old or younger (OR=1.45, 95% CI=1.09-1.92 for men; OR=1.36, 95% CI=0.97-1.90 for women), than in those over age 55 (OR=1.03, 95% CI=0.83-1.27 for men; OR=0.86, 95% CI=0.66-1.12 for women) in both genders (p for interaction <0.05). Conclusions: In the Korean population, the GSTM1 and GSTT1 null genotypes are risk factors for LC in men; the GSTT1 null genotype has a more prominent effect on LC risk in younger people (age 55 years and under) than in older individuals.

Cao, Jie;Huang, Xin-En;Liu, Jin;Wu, Xue-Yan;Lu, Yan-Yan 7171

https://doi.org/10.7314/APJCP.2013.14.12.7171 PDF KSCI

Purpose: To compare the safety and efficacy of first-line chemotherapy regimen with or without doxorubicin in treating patients with advanced soft tissue sarcoma (STS). Patients and Methods: We retrospectively analyzed a cohort of 56 patients histologically confirmed with STS who were treated at Jiangsu Cancer Hospital and Research Institute from July 2011 to June 2012.The basic element of first line chemotherapy contained epirubicin in group B and lacked epirubicin in group A. Response was assessed using RECIST criteria. The Kaplan-Meier method was used to estimate progress free survival (PFS). Results: According to RECIST criteria, patients in group treated by chemotherapy without epirubicin, the objective response (OR) ratio was 6.5 % (CR0%+PR6.5%). Disease control rate (DCR=CR+PR+SD) was 25.8% with a median follow-up of 14.6 months, including 2 patients achieving a partial response (PR 6.5%) and a stable response (SD 19.4%) in 6. In group B with epirubicin based regimens, no patient had complete response, PR (28 %) was observed in 7 and SD (24 %) in 6. DCR was observed in 13 patients (52%). By Fisher's exact test, the DCR difference between the two groups was statistically significant (p=0.046). In group A, median PFS was 3.0 months (95%CI:2.1-3.8), compared with 4.0 months (95% CI:3.03-4.97) in group B (p=0.0397 by log-rank test). Epirubicin based chemotherapy and ECOG performance status 0-1 were identified as favorable factors for progression in our cohort of patients. Differences of nonhematologic and hematologic toxicities were not statistically significant between the two groups, and the addition of epirobicin was not associated with cardiac toxicity (p=0.446). Conclusion: Our study demonstrates that epirubicin-based chemotherapy is effective and well tolerated, and is superior to chemotherapy without epirubicin regarding efficacy. Therefore it is recommended that epirubicin-based chemotherapy should be considered as first line for patients with advanced STS.

Lin, Mei-Gui;Liu, Li-Ping;Li, Chen-Yin;Zhang, Meng;Chen, Yuling;Qin, Jian;Gu, Yue-Yu;Li, Zhi;Wu, Xin-Lin;Mo, Sui-Lin 7179

https://doi.org/10.7314/APJCP.2013.14.12.7179 PDF KSCI

Background and Aims: Scutellaria is one of the most popular traditional Chinese herbal remedies against various human diseases, including cancer. In this study, we examined the active effects of Scutellaria extract and its main flavonoid constituents on the proportion of side population cells within human multiple myeloma cell line RPMI8226 in vitro and explored the potential molecular mechanisms involved. Materials and Methods: The contents of flavonoids in ethanolic extract of Scutellaria baicalensis Georgi were determined using high performance liquid chromatography. The antiproliferative effect of the ethanolic extract on RPMI-8226 was determined by CCK assay. Apoptosis was measured by annexin combining with propidium iodide in a flow cytometer. Cell cycle analysis was performed by propidium iodide staining in combination with flow cytometry analysis. Hoechst 33342 exclusion assay was used for the identification of side population within RPMI8226 cells. The expression of ABCG2 protein was assessed by Western blotting assay. Results: The content of major flavonoids constitutents of Scutellaria extract was baicalin (10.2%), wogonoside (2.50%), baicalein (2.29%), and wogonin (0.99%), respectively. The crude Scutellaria extract did not show significant anti-proliferative effect, apoptosis induction and cell cycle arrest in RPMI-8226 within the concentrations of $1-75{\mu}g/mL$. However, the ethanolic extract, baicalein, wogonin and baicalin reduced the side population cells in RPMI-8226, and data showed that baicalein and wogonin had stronger inhibitory effects. Correspondingly, they also exhibited significant effects on decreasing the expression level of ABCG2 protein in RPMI-8226 in vitro. Conclusions: Our results for the first time demonstrated a novel mechanism of action for Scutellaria extract and its main active flavonoids, namely targeting SP cells by modulating the expression of ABCG2 protein. This study provides an insight for new therapeutic strategies targeting cancer stem cells of multiple myeloma.

Wahid, Mussarat;Mahjabeen, Ishrat;Baig, Ruqia Mehmood;Kayani, Mahmood Akhtar 7187

https://doi.org/10.7314/APJCP.2013.14.12.7187 PDF KSCI

Most of the exogenous and endogenous chemical compounds are metabolized by enzymes of xenobiotic processing pathways, including the phase I cytochrome p450 species. Carcinogens and their metabolites are generally detoxified by phase II enzymes like glutathione-S-transferases (GST). The balance of enzymes determines whether metabolic activation of pro-carcinogens or inactivation of carcinogens occurs. Under certain conditions, deregulated expression of xenobiotic enzymes may also convert endogenous substrates to metabolites that can facilitate DNA adduct formation and ultimately lead to cancer development. In this study, we aimed to test the association between deregulation of metabolizing genes and brain tumorigenesis. The expression profile of metabolizing genes CYP1A1 and GSTP1 was therefore studied in a cohort of 36 brain tumor patients and controls using Western blotting. In a second part of the study we analyzed protein expression of GSTs in the same study cohort by ELISA. CYP1A1 expression was found to be significantly high (p<0.001) in brain tumor as compared to the normal tissues, with ~4 fold (OR=4, 95%CI=0.43-37) increase in some cases. In contrast, the expression of GSTP1 was found to be significantly low in brain tumor tissues as compared to the controls (p<0.02). This down regulation was significantly higher (OR=0.05, 95%CI=0.006-0.51; p<0.007) in certain grades of lesions. Furthermore, GSTs levels were significantly down-regulated (p<0.014) in brain tumor patients compared to controls. Statistically significant decrease in GST levels was observed in the more advanced lesions (III-IV, p<0.005) as compared to the early tissue grades (I-II). Thus, altered expression of these xenobiotic metabolizing genes may be involved in brain tumor development in Pakistani population. Investigation of expression of these genes may provide information not only for the prediction of individual cancer risk but also for the prevention of cancer.

Suprasert, Prapaporn;Chalapati, Wadwilai 7193

https://doi.org/10.7314/APJCP.2013.14.12.7193 PDF KSCI

Ovarian cancer patients need a surveillance program for the detection of tumor progression after completion of treatment. The methods generally consist of history taking, physical examination, tumor marker monitoring and imaging. However, the details of recurrence detection with each method are not well defined. To clarify this issue, ovarian cancer patients who achieved complete or partial responses and developed tumor progression at the follow up time between January 2004 and December 2010 in University Hospital Chiang Mai, Thailand, were reviewed. Clinical data, CA 125 level and imaging results at the tumor progression time were recorded and analyzed. There were 144 ovarian cancer patients meeting the inclusion criteria with the mean age of 51 years and 62.5% of them were in an advanced stage. Complete response was achieved in 89 patients (61.8%) after primary treatment. The median progression free survival and overall survival were 15.5 months and 37.5 months, respectively. Abnormal symptoms presented in 49.3% of the studied patients and 59.7% developed physical examination abnormalities. In addition, CA 125 was elevated in 89.6% while in 74.3% of tumor progression was identified by CT-scan. Short treatment time period and a high level of CA 125 were significant independent prognostic factors in these patients. In conclusion, careful history taking, physical examination and monitoring of CA 125 levels are important methods for tumor progression detection in a surveillance program for epithelial ovarian cancer patients.

Wan, Hui-Fang;Yu, Le-Han;Wu, Jin-Lan;Tu, Shuo;Zhu, Wie-Feng;Zhang, Xia-Li;Wan, Fu-Sheng 7197

https://doi.org/10.7314/APJCP.2013.14.12.7197 PDF KSCI

Aim: To investigate the effects of diallyl trisulfide (DT) on apoptosis of cisplatin (DDP)-resistant human epithelial ovarian cancer SKOV-3 cells (SKOV-3/DDP), and the role of p53 upregulated modulator of apoptosis (PUMA). Methods: SKOV-3/DDP cells were randomly divided into control, DT, DPP and DPP+DT groups, which were treated with DT or combined DT and DDP. All cells were incubated for 48 h. and apoptosis rates were assessed by flow cytometry. mRNA and protein expression of PUMA, Bax and Bcl-2 was determined by RT-PCR and Western blot assays, respectively. Results: Compared with control group, the apoptosis rates of SKOV-3/DDP cells in DT groups were obviously increased, with dose-dependence (P < 0.05), the mRNA and protein expressions of PUMA, Bax also being up-regulated (P < 0.05), while those of Bcl-2 were down-regulated (P < 0.05). Compared with DT groups, the apoptosis rate in the DDP+DT group was significantly increased (P < 0.05). After knockdown of PUMA with specific siRNA, the apoptosis rate of SKOV-3/DDP cells was obviously decreased (P < 0.05). Conclusion: DT can promote the apoptosis of SKOV-3/DDP cells with PUMA playing a critical role.

Li, Feng-Ying;Ren, Xiao-Bin;Xie, Xin-You;Zhang, Jun 7203

https://doi.org/10.7314/APJCP.2013.14.12.7203 PDF KSCI

Recent studies suggested that the ovarian cancers with negative excision repair cross-complementation group 1 enzyme (ERCC1) expression have a better response to platinum-based chemotherapy than those with positive ERCC1 expression. The objective of this study was to evaluate whether ERCC1 expression is associated with response to platinum-based chemotherapy in ovarian cancers. MEDLINE, PubMed, Web of Science and CNKI databases were used for searching studies relating to ERCC1 protein expression and response to platinum-based chemotherapy in ovarian cancers. Statistical analysis was based on the method for a fixed effects meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals for ERCC1 protein expression and response to platinum-based chemotherapy were generated. Publication bias was investigated with Begg's test. Five studies involving 306 patients with ovarian cancer were included. Compared to patients with positive ERCC1 expression, those with negative ERCC1 expression had a better response to platinum-based chemotherapy. The pooled OR was 5.264 (95% CI: 2.928-9.464, P < 0.001) and publication bias was not found (P = 0.904). The result was similar in both in Asians and Caucasians (P < 0.001 and P = 0.028, respectively). ERCC1 protein expression status is significantly associated with response to platinum-based chemotherapy in ovarian cancers.

Gang, Moonhee;Kim, Jong Im;Oh, Kyong Ok;Li, Chun Yu;Song, Youngshin 7207

https://doi.org/10.7314/APJCP.2013.14.12.7207 PDF KSCI

Background: Despite the efficacy of regular mammograms, the incidence and mortality rate of breast cancer have been increasing in China. Insufficient studies on the factors affecting mammography adherence in Chinese married women have been conducted. The purpose of the present study was to explore the factors associated with adherence to guidelines for regular mammography among Chinese married women. Materials and Methods: The participants were recruited conveniently and included Chinese and Korean Chinese women who were married, living at Yanbian City in China. Demographic information, status regarding eight risk factors of breast cancer, health responsibility, and perceived benefits/barriers of mammography were obtained. Descriptive analyses, t-test, and multivariate analysis were performed. Hierarchical logistic regression was conducted to explore the factors associated with regular mammography adherence in Chinese and Korean Chinese subgroups. Results: About 24% of the sample population was adherent in going for regular mammography. The adherent group was significantly more educated, had more children, and had a lower proportion experiencing early menarche and a greater menopausal proportion than the non-adherent group. The final model using logistic regression analysis showed that being Chinese [OR=2.199 (1.224-3.951)], having no or one child [OR=4.879 (1.835-12.976)], early menarche [OR=3.515 (1.057-11.694)], being menopausal [OR=3.120 (0.965-10.088)], aged 40-49 [OR=2.374 (1.099-5.124)], having low education [OR=0.400 (0.211-0.765)], and perceiving greater benefits in doing mammography [OR=1.080 (1.014-1.151)] were significantly associated with mammography adherence, after controlling for covariates. Conclusions: Sociocultural sensitive intervention for minorities should be emphasized when improving the adherence of regular mammography. Intervention tailored for women with lower education should be delivered and the benefits of mammography should be propagated to women in rural areas of China.

Liu, Hong-Zhou;Peng, Jie;Zheng, Fang;Wang, Chun-Hong;Han, Ming-Jun 7215

https://doi.org/10.7314/APJCP.2013.14.12.7215 PDF KSCI

Background: Variation in metabolic genes is regarded as an important factor in processes leading to cancer. However, the effect of GSTT1 null genotype is divergent in the form of lung cancer. Methods: Studies were conducted at different research databases from 1990 to 2013 and the total odds ratio (OR) and 95% confidence interval (CI) were calculated for lung cancer. Review Manager 5.2 and STATE 12 are employed. Results: Total OR value is calculated from 17 articles with 2,118 cases and 2,915 controls. We discovered no significant increase in lung cancer risk among subjects carrying GSTT1 null genotype [OR = 1.15; 95% CI 0.97-1.36] in this meta-analysis. Conclusion: The GSTT1 deletion polymorphism does not have a significant effect on the susceptibility to lung cancer overall in China.

Wu, Bing-Li;Luo, Lie-Wei;Li, Chun-Quan;Xie, Jian-Jun;Du, Ze-Peng;Wu, Jian-Yi;Zhang, Pi-Xian;Xu, Li-Yan;Li, En-Min 7221

https://doi.org/10.7314/APJCP.2013.14.12.7221 PDF KSCI

Background: Fascin, an actin-bundling protein forming actin bundles including filopodia and stress fibers, is overexpressed in multiple human epithelial cancers including esophageal squamous cell carcinoma (ESCC). Previously we conducted a microarray experiment to analyze fascin knockdown by RNAi in ESCC. Method: In this study, the differentially expressed genes from mRNA expression profilomg of fascin knockdown were analyzed by multiple bioinformatics methods for a comprehensive understanding of the role of fascin. Results: Gene Ontology enrichment found terms associated with cytoskeleton organization, including cell adhesion, actin filament binding and actin cytoskeleton, which might be related to fascin function. Except GO categories, the differentially expressed genes were annotated by 45 functional categories from the Functional Annotation Chart of DAVID. Subpathway analysis showed thirty-nine pathways were disturbed by the differentially expressed genes, providing more detailed information than traditional pathway enrichment analysis. Two subpathways derivated from regulation of the actin cytoskeleton were shown. Promoter analysis results indicated distinguishing sequence patterns and transcription factors in response to the co-expression of downregulated or upregulated differentially expressed genes. MNB1A, c-ETS, GATA2 and Prrx2 potentially regulate the transcription of the downregulated gene set, while Arnt-Ahr, ZNF42, Ubx and TCF11-MafG might co-regulate the upregulated genes. Conclusions: This multiple bioinformatic analysis helps provide a comprehensive understanding of the roles of fascin after its knockdown in ESCC.

Yun, Young Ho;Lee, Myung Kyung;Bae, Yeonmin;Shon, Eun-Jung;Shin, Bo-Ram;Ko, Hyonsook;Lee, Eun Sook;Noh, Dong-Young;Lim, Jae-Young;Kim, Sung;Kim, Si-Young;Cho, Chi-Heum;Jung, Kyung Hae;Chun, Mison;Lee, Soon Nam;Park, Kyong Hwa;Chang, Yoon Jung 7229

https://doi.org/10.7314/APJCP.2013.14.12.7229 PDF KSCI

Background: To determine whether the Health Partner Program is effective in training long-term cancer survivors to be health coaches. Materials and Methods: We randomly assigned cancer survivors who were selected through a rigorous screening process to either the Health Partner Program or the waiting-list control group. The program consisted of 8 weeks of training in health management, leadership, and coaching. At baseline, 8, and 16 weeks, we measured primary outcomes using the Seven Habit Profile (SHP), the Korean Leadership Coaching Competency Inventory (KCCI), Ed Diner's Satisfaction with Life Scale (SWLS), and the Posttraumatic Growth inventory (PTGI) and secondary outcomes using the Hospital Anxiety and Depression Scale (HADS), the Impact of Event Scale-Revised (IES-R), and the Medical Outcomes Study (MOS) short form 36-item questionnaire (SF-36). Results: We recruited 70 subjects and randomly assigned 34 to the intervention group. The Sharpen the Saw habit of the SHP increased significantly more in intervention group than in the control group (p=0.049), as did most PTGI factors. The intervention group also showed a significantly greater enhancement of vitality (p=0.015) and mental health (p=0.049) SF-36 scores but no improvement in KCCI, SWLS, HADS, or IES-R scores. The intervention group also showed a greater clinically meaningful improvement in the "Think Win-Win" of SHP (p=0.043) and in the personal strength score (p=0.025) and total score (p=0.015) of the PTGI. Conclusions: Long-term cancer survivors can benefit from the Health Partner Program to become health coaches.

Panda, Rajmohan;Persai, Divya;Mathur, Manu;Sarkar, Bidyut Kanti 7237

https://doi.org/10.7314/APJCP.2013.14.12.7237 PDF KSCI

Background: Smokeless tobacco use in South Asia is believed to be a significant contributor to morbidity and mortality. In India, only a few studies involving health educational intervention by health care providers have demonstrated reduction in smokeless tobacco usage. In the present study we assessed the cessation efforts towards smokeless tobacco by physicians in two high tobacco prevalence states of India. The study also identified opportunities and barriers for integration of tobacco cessation services in routine practices of physicians. Materials and Methods: This mixed method study involved qualitative (phase I) and quantitative research study (phase II). In phase I, 59 in-depth interviews with physicians were conducted. In phase II, a quantitative study conducted among 238 physicians. An inductive approach was followed to analyze qualitative data using ATLAS. Ti software. The Chi-square test was employed to test the association between different variables of interest using SPSS version 17. Results: The majority of physicians related only respiratory problems and cancer with smokeless tobacco. Other major health effects like cardio-vascular problems, oral diseases, and effects on reproductive and neonatal health were recognized only by a few physicians. The age-group of 10-19 years was identified as most vulnerable to smokeless tobacco use. Less than one-third of physicians reported recording smokeless tobacco history of all patients. Findings indicated that less than half of physicians provided information on harmful health effects of smokeless tobacco with regard to specific diseases. Conclusions: The study revealed a low level of knowledge of physicians about harmful effects of tobacco and their suboptimal engagement in tobacco control practices. The study indicates the need of capacity building initiatives to equip physicians with skills in tobacco cessation.

Chen, Fang-Chun;Zhang, Fan;Zhang, Zhi-Jiao;Meng, Si-Ying;Wang, Yang;Xiang, Xue-Rong;Wang, Chun;Tang, Yu-Ying 7243

https://doi.org/10.7314/APJCP.2013.14.12.7243 PDF KSCI

Numerous studies have been conducted regarding association between TNF-${\alpha}$ and oral cancer risk, but the results remain controversial. The present meta-analysis is performed to acquire a more precise estimation of relationships. Databases of Pubmed, the Cochrane library and the China National Knowledge Internet (CNKI) were retrieved until August 10, 2013. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated with fixed- or random-effect models. The heterogeneity assumption was assessed by I-squared test. Among the eight included case-control studies, all were focused on TNF-${\alpha}$-308G>A and four also concerned the TNF-${\alpha}$-238G>A polymorphism. It was found that oral cancer risk were significant decreased with the TNF-${\alpha}$-308G>A polymorphism in the additive genetic model (GG vs. AA, OR=0.19, 95% CI: [0.04, 1.00], P=0.05, I2=68.9%) and the dominant genetic model (GG+GA vs. AA, OR=0.22, 95% CI: [0.06, 0.82], P=0.03, I2=52.4%); however, no significant association was observed in allele contrast (G vs. A, OR=0.70, 95% CI: [0.23, 2.16], P=0.54, I2=95.9%) and recessive genetic models (GG vs. GA+AA, OR=0.72, 95% CI: [0.33, 1.57], P=0.41, I2=93.1%). For the TNF-${\alpha}$-238G>A polymorphism, significant associations with oral cancer risk were found in the allele contrast (G vs. A, OR=2.75, 95% CI: [1.25, 6.04], P=0.01, I2=0.0%) and recessive genetic models (GG vs. GA+AA, OR=2.23, 95%CI: [1.18, 4.23], P=0.01, I2=0.0%). Conclusively, this meta-analysis indicates that TNF-${\alpha}$ polymorphisms may contribute to the risk of oral cancer. Allele G and the GG+GA genotype of TNF-${\alpha}$-308G>A may decrease the risk of oral cancer, while allele G and the GG genotype of TNF-${\alpha}$-238G>A may cause an increase.

Fan, Jin-Hu;Wang, Jian-Bing;Jiang, Yong;Xiang, Wang;Liang, Hao;Wei, Wen-Qiang;Qiao, You-Lin;Boffetta, Paolo 7251

https://doi.org/10.7314/APJCP.2013.14.12.7251 PDF KSCI

Objectives: To estimate the proportion of liver cancer cases and deaths due to infection with hepatitis B virus (HBV), hepatitis C virus (HCV), aflatoxin exposure, alcohol drinking and smoking in China in 2005. Study design: Systemic assessment of the burden of five modifiable risk factors on the occurrence of liver cancer in China using the population attributable fraction. Methods: We estimated the population attributable fraction of liver cancer caused by five modifiable risk factors using the prevalence data around 1990 and data on relative risks from meta-analyses, and large-scale observational studies. Liver cancer mortality data were from the 3rd National Death Causes Survey, and data on liver cancer incidence were estimated from the mortality data from cancer registries in China and a mortality/incidence ratio calculated. Results: We estimated that HBV infection was responsible for 65.9% of liver cancer deaths in men and 58.4% in women, while HCV was responsible for 27.3% and 28.6% respectively. The fraction of liver cancer deaths attributable to aflatoxin was estimated to be 25.0% for both men and women. Alcohol drinking was responsible for 23.4% of liver cancer deaths in men and 2.2% in women. Smoking was responsible for 18.7% and 1.0%. Overall, 86% of liver cancer mortality and incidence (88% in men and 78% in women) was attributable to these five modifiable risk factors. Conclusions: HBV, HCV, aflatoxin, alcohol drinking and tobacco smoking were responsible for 86% of liver cancer mortality and incidence in China in 2005. Our findings provide useful data for developing guidelines for liver cancer prevention and control in China and other developing countries.

Kochhar, Ajay Kumar;Jindal, Umesh;Singh, Karandeep 7257

https://doi.org/10.7314/APJCP.2013.14.12.7257 PDF KSCI

To determine the pattern of disease in patients presenting with breast lumps and to determine the sensitivity and specificity of fine needle aspiration cytology of benign and malignant diseases as a diagnostic tool by correlating with histopathology findings. This retrospective study was carried out in the Department of Pathology, Maharaja Agrasen Medical College, Agroha, from Jan 2008 to April 2012. Fine needle aspiration cytology was performed on 370 cases and out of these 52 cases were received in the Department for histopathological examination. Fibroadenoma was the most common disease encountered, in 88 (24%), with a peak incidence in second and third decade of life. Fibrocystic disease was second, being common in the third and fourth decades of life. Peak incidences of duct ectasia, granulomatous and tubercular mastitis were seen in the third decade. Gynaecomastia showed two peak incidences in second and sixth decades of life. Out of total 370 cases undergoing fine needle aspiration, benign cases were 316 (85.4%), malignant and suspicious were 54 (14.6%) and 10 (2.70%) respectively. Out of total 22 histological confirmed malignant lesions 19 were interpreted as malignant cytologically while two as suspicious and one as benign. All thirty histologically confirmed benign cases were diagnosed as benign cytologically. The sensitivity, specificity, positive and negative predictive values were 98%, 100%, 100% and 96.4% respectively. FNA cytology is highly accurate for diagnosis of breast masses. However, the clinician should correlate FNA cytological results with physical examination and imaging findings to prevent false negative and false positive events and to obtain optimal management of their patients.

Ranjan Das, Bibhu;Tangri, Rajiv;Ahmad, Firoz;Roy, Arnab;Patole, Kamlakar 7261

https://doi.org/10.7314/APJCP.2013.14.12.7261 PDF KSCI

Recent genome wide sequencing has identified mutations in IDH1/IDH2 predominantly in grade II-III gliomas and secondary glioblastomas which are associated with favorable clinical outcome. These mutations have become molecular markers of significant diagnostic and prognostic relevance in the assessment of human gliomas. In the current study we evaluated IDH1 (R132) and IDH2 (R172) in 32 gliomas of various grades and tumor subtypes. Sequencing analysis revealed R132H mutations in 18.7% tumors, while none of the cases showed IDH2 (R172) mutations. The frequency of IDH1 mutations was higher in females (21.4%) than males (11.1%), and it was significantly higher in younger patients. Histological analyses demonstrated presence of necrosis and micro vascular proliferation in 69% and 75% respectively. Interestingly, IDH1 mutations were predominantly present in non-necrotic tumors as well as in cases showing microvascular proliferation. Of the six IDH1 positive cases, three were glioblastomas (IV), and one each were anaplastic oligoastrocytoma (III), anaplastic oligodendroglioma III (n=1) and diffuse astrocytoma. In conclusion, IDH1 mutations are quite frequent in Indian glioma patients while IDH2 mutations are not observed. Since IDH mutations are associated with good prognosis, their use in routine clinical practice will enable better risk stratification and management of glioma patients.

Wang, Hao;Gui, Shu-Yu;Chen, Fei-Hu;Zhou, Qing;Wang, Yuan 7265

https://doi.org/10.7314/APJCP.2013.14.12.7265 PDF KSCI

Objective: The present study was designed to investigate the probable mechanisms of synthetic retinoid 4-amino-2-tri-fluoromethyl-phenyl ester (ATPR) inhibition of the proliferation and migration of A549 human lung carcinoma cells. Materials and Methods: After the A549 cells were treated with different concentrations of ATPR or all-trans retinoic acid (ATRA) for 72 h, scratch-wound assays were performed to assess migration. Immunofluorescence was used to determine the distribution of CAV1 and $RXR{\alpha}$, while expression of CAV1, MLCK, MLC, P38, and phosphorylation of MLC and P38 were detected by Western blotting. Results: ATPR could block the migration of A549 cells. The relative migration rate of ML-7 group had significantly decreased compared with control group. In addition, ATPR decreased the expression of a migration related proteins, MLCK, and phosphorylation of MLC and P38. ATPR could also influence the expression of RARs or RXRs. At the same time, CAV1 accumulated at cell membranes, and $RXR{\alpha}$ relocated to the nucleus after ATPR treatment. Conclusions: Caveolae may be implicate in the transport of ATPR to the nucleus. Change in the expression and distribution of $RXR{\alpha}$ may be implicated in ATPR inhibition of A549 cell proliferation. The mechanisms of ATPR reduction in A549 cell migration may be associated with expression of MLCK and phosphorylation of MLC and P38.

Liu, Jin-Fei;Xie, Hao-Jun;Cheng, Tian-Ming 7271

https://doi.org/10.7314/APJCP.2013.14.12.7271 PDF KSCI

Objective: To investigate the association between the gene polymorphisms of angiotensin-converting enzyme (ACE) and digestive system cancer risk. Method: A search was performed in Pubmed, Medline, ISI Web of Science and Chinese Biomedical (CBM) databases, covering all studies until Sep 1st, 2013. Statistical analysis was performed by using Revman5.2 and STATA 12.0. Results: A total of 15 case-control studies comprising 2,390 digestive system cancer patients and 9,706 controls were identified. No significant association was found between the I/D polymorphism and digestive cancer risk (OR=0.93, 95%CI = (0.75, 1.16), P=0.53 for DD+DI vs. II). In the subgroup analysis by ethnicity and cancer type, no significant associations were found for the comparison of DD+DI vs. II. Results from other comparative genetic models also indicated a lack of associations between this polymorphism and digestive system cancer risks. Conclusions: This meta-analysis suggested that the ACE D/I polymorphism might not contribute to the risk of digestive system cancer.

Mandal, Sanjeet Kumar;Singh, Thaudem Tomcha;Sharma, Takhenchangbam Dhaneshor;Amrithalingam, Venkatesan 7277

https://doi.org/10.7314/APJCP.2013.14.12.7277 PDF KSCI

Background: Globally, there have been important changes in trends amongst gender, histology and smoking patterns of lung cancer cases. Materials and Methods: This retrospective study was conducted on 466 patients with lung cancer who were registered in Regional Cancer Center, Regional Institute of Medical Sciences, Manipur from January 2008 to December 2012. Results: Most were more than 60 years of age (67.8%) with a male: female ratio of 1.09:1. Some 78.8% of patients were chronic smokers with male smoker to female smoker ratio of 1.43:1. Consumption of alcohol was found in 29.4%, both smoking and alcohol in 27.5%, betel nut chewing in 37.9% and tobacco chewing in 25.3%. A history of tuberculosis was present in 16.3% of patients. The most frequent symptom was coughing (36.6%) and most common radiological presentation was a mass lesion (70%). Most of the patients had primary lung cancer in the right lung (60.3%). The most common histological subtype was squamous cell carcinoma (49.1%), also in the 40-60 year age group (45.9%), more than 60 year age group (51.6%), males (58.1%) and females (41.8%). As many as 91.9% of squamous cell carcinoma patients had a history of smoking. About 32.5% of patients had distant metastasis at presentation with brain (23.8%) and positive malignant cells in pleural effusions (23.1%) as common sites. The majority of patients were in stage III (34.4%), stage IV (32.5%) and stage II (30.2%). Conclusions: Our analysis suggests that the gender gap has been narrowed such that about half of the patients diagnosed with lung cancer are women in this part of India. This alarming rise in female incidence is mainly attributed to an increased smoking pattern. Squamous cell carcinoma still remains the commonest histological subtype. Most of the patients were elderly aged and presented at locally or distantly advanced stages.

Karimy, Mahmood;Niknami, Shamsaddin;Heidarnia, Ali Reza;Hajizadeh, Ebrahim;Shamsi, Mohsen 7283

https://doi.org/10.7314/APJCP.2013.14.12.7283 PDF KSCI

Background: Tobacco use among adolescents is a major public health concern, and identifying predictors of smoking is necessary for planning prevention programs. The present study examined the relationship between refusal self efficacy, self esteem, smoking refusal skills and water pipe (hookah) smoking among Iranian male adolescents. Materials and Methods: A cross-sectional study was conducted with 380 Iranian male adolescents aged between 15-19 years selected by multistage sampling. The participants completed an anonymous, voluntary, self-report questionnaire. Variables independently associated with water pipe (WP) smoking were identified by multiple logistic regression analysis. Results: The mean age of the participants was $16.7{\pm}1.3$ years. The prevalence of WP smoking was 17.3%. Logistic regression analysis revealed that knowledge (OR=0.56; 95% CI: (0.37-0.79), attitude (OR=0.69; 95% CI: (0.52-0.89), self esteem (OR=0.67; 95% CI: (0.55-0.82), smoking refusal skills (OR=0.73; 95% CI: (0.55-0.87), and self efficacy (OR=.82; 95% CI: (0.61-0.93) were all signifcant prediting facotrs for adolescents WP smoking. Conclusions: The findings have implications for public health interventions. Indeed, self efficacy and smoking refusal skills should be considered when developing tailored measures for the prevention of WP smoking among adolescents.

Yu, Min;Niu, Zhi-Min;Wei, Yu-Quan 7289

https://doi.org/10.7314/APJCP.2013.14.12.7289 PDF KSCI

We here document discovery of a new and simple model of tumor seeding involving the mouse peritoneum. Irradiated tumor cells administered by i.p. injection provided effective vaccination against peritoneal carcinomatosis and distal metastasis with colorectal carcinomas. In flow cytometric analysis, CD4+ and CD8+ T lymphocytes, macrophages and myeloid-derived suppressor cells (MDSCs), which are easy to obtain in the peritoneal cavity, were revealed to have significant differences between immunized and non-immunized mice and these contributed to antitumor responses. We also observed that both serum and peritoneal lavage fluid harvested from immunized mice showed the presence of CT26-specific autoantibodies. In addition, increase in level of TGF-${\beta}1$ and IL-10 in serum but a decrease of TGF-${\beta}1$ in peritoneum was found. Taken together, these findings may provide a new vaccine strategy for the prevention of peritoneal and even systemic metastasis of carcinomas through induction of an autoimmune response in the peritoneum.

Zhang, Ji;Wu, Xiao-Bin;Fan, Jian-Jun;Mai, Li;Cai, Wei;Li, Dan;Yuan, Cheng-Fu;Bu, You-Quan;Song, Fang-Zhou 7295

https://doi.org/10.7314/APJCP.2013.14.12.7295 PDF KSCI

Lung cancer is the most common cause of cancer-related death in the world. The main types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), the latter including squamous cell carcinoma (SCC), adenocarcinoma and large cell carcinoma. NSCLCs account for about 80% of all lung cancer cases. Microcephalin (MCPH1), also called BRIT1 (BRCT-repeat inhibitor of hTERT expression), plays an important role in the maintenance of genomic stability. Recently, several studies have provided evidence that the expression of MCPH1 gene is decreased in several different types of human cancers. We evaluated the expression of protein MCPH1 in 188 lung cancer and 20 normal lung tissues by immunohistochemistry. Positive MCPH1 staining was found in all normal lung samples and only some cancerous tissues. MCPH1-positive cells were significantly lower in lung carcinoma compared with normal tissues. Furthermore, we firstly found that MCPH1 expression in lung adenocarcinoma is higher than its expression in squamous cell carcinoma. Change in MCPH1 protein expression may be associated with lung tumorigenesis and may be a useful biomarker for identification of pathological types of lung cancer.

Frie, Kirstin Grosse;Ramadas, Kunnambath;Anju, Gopan;Mathew, Beela Sara;Muwonge, Richard;Sauvaget, Catherine;Thara, Somanathan;Sankaranarayanan, Rengaswamy 7301

https://doi.org/10.7314/APJCP.2013.14.12.7301 PDF KSCI

Background: Conspicuous differences in participation rates for breast self-examination (BSE), clinical breast examination (CBE), and referral for further investigations have been observed indicating involvement of a number of different factors. This study analysed determinants for participation in different levels of the breast cancer screening process in Indian females. Materials and Methods: An intervention group of 52,011 women was interviewed in a breast cancer screening trial in Trivandrum district, India. In order to assess demographic, socio-economic, reproductive, and cancer-related determinants of participation in BSE, CBE, and referral, uni- and multi-variate logistic regression was employed. Results: Of the interviewed women, 23.2% reported practicing BSE, 96.8% had attended CBE, and 49.1% of 2,880 screen-positives attended referral. Results showed an influence of various determinants on participation; women who were currently not married or who had no family history of cancer were significantly less likely to attend the screening process at any level. Conclusions: Increasing awareness about breast cancer, early detection methods, and the advantages of early diagnoses among women, and their families, as well as health care workers offering social support, could help to increase participation over the entire screening process in India.

Hyun, Min Kyung;Jung, Kyung Hae;Yun, Young Ho;Kim, Young Ae;Lee, Woo Jin;Do, Young Rok;Lee, Keun Seok;Heo, Dae Seog;Choi, Jong Soo;Kim, Sam Yong;Kim, Heung Tae;Hong, Seok-Won 7309

https://doi.org/10.7314/APJCP.2013.14.12.7309 PDF KSCI

Aim: To investigate factors that affect the place of death (POD) of terminal cancer patients. Materials and Methods: We recruited 702 consecutive patients (${\geq}18$ years) from 12 centers during July 2005 to October 2006, and 481 completed the questionnaire. In April 2011, we linked the data for 96.0% (n=462) of the deceased patients to the POD using the 2005-2009 death certificate data of Korea's National Statistical Office. The primary outcome variable was POD, and the predictive value of variables pertaining to patients and caregivers was evaluated using univariate and multivariate analyses. Results: Most patients died in a hospital (91.5%, n=441) and age, education, preference for place of terminal care, wish to use hospice/palliative care services, terminal cancer awareness, time between diagnosis and death, and global quality-of-life subscale of the EORTC QLQ-C30 of patients, and education and preference for place of terminal care of caregivers were significant predictors in univariate analyses. On multivariate analysis, patients and caregivers who preferred hospital/palliative care as the terminal care option over home care [adjusted odds ratio (aOR), 2.68; 95% confidential interval (CI), 1.18-7.04 and aOR: 2.65; 95%CI: 1.15-6.09 for patient and caregiver preferences, respectively] and caregivers who were highly educated (aOR, 3.19; 95%CI, 1.44-7.06) were predictors of POD. Conclusions: Most of the terminal cancer patients died in a hospital. Our findings indicate that major predictors of hospital deaths are preference of both the patient and caregiver for hospital/palliative care as the terminal care option and higher education of the caregiver.

Zhang, Mei-Xiang;Xu, Yi-Jun;Zhu, Ming-Chen;Yan, Feng 7315

https://doi.org/10.7314/APJCP.2013.14.12.7315 PDF KSCI

Background: The metastasis gene osteopontin (OPN) is subject to alternative splicing, which yields three messages, osteopontin-a, osteopontin-b and osteopontin-c. Osteopontin-c is selectively expressed in invasive, but not in noninvasive tumors. In the present study, we examined the expression of OPN-c in esophageal squamous cell carcinomas (ESCCs) and assessed its value as a diagnostic biomarker. Methods: OPN-c expression was assessed by immunohistochemistry in 63 ESCC samples and correlated with clinicopathologic factors. Expression was also examined in peripheral blood mononuclear cells (PBMCs) from 120 ESCC patients and 30 healthy subjects. The role of OPN-c mRNA as a tumor marker was investigated by receiver operating characteristic curve (ROC) analysis. Results: Immunohistochemistry showed that OPN-c was expressed in 30 of 63 cancer lesions (48%)and significantly associated with pathological T stage (P=0.038) and overall stage (P=0.023). Real time PCR showed that OPN-c mRNA was expressed at higher levels in the PBMCs of ESCC patients than in those of healthy subjects (P<0.0001) with a sensitivity as an ESCC biomarker of 86.7%. Conclusion: Our findings suggest that expression of OPN-c is significantly elevated in ESCCs and this upregulation could be a potential diagnostic marker.

Chen, Wan-Qing;Liang, Di;Zhang, Si-Wei;Zheng, Rou-Shou;He, Yu-Tong 7321

https://doi.org/10.7314/APJCP.2013.14.12.7321 PDF KSCI

Objective: To estimate the incidence and mortality rates for pancreatic cancer in China. Methods: After checking and reviewing the cancer registry data in 2009 from 72 cancer registry centers, we divided cancer registry areas into urban and rural areas. Incidence/mortality rates, age-specific incidence/mortality rates, age-standardized incidence/mortality rates, proportions, and cumulative incidence/mortality rates for pancreatic cancer were calculated. Results: The total number of newly diagnosed pancreatic cancer cases and deaths in 2009 were 6,220 and 5,650, respectively. The crude incidence rate in all cancer registry areas was 7.28/100,000 (males 8.24, females 6.29). The age-standardized incidence rate by Chinese standard population (ASR) was 3.35/100,000, with ranking at 7th among all cancers. Pancreatic cancer incidence rate was 8.19/100,000 in urban areas whereas it was 5.41/100 000 in rural areas. Cancer mortality rate in all cancer registry areas was 6.61/100,000 (males 7.45; females 5.75), with ranking at 6th among all cancers, and 7.42/100 000 in urban but 4.94/100000 in rural areas. Conclusions: Pancreatic cancer incidence and mortality rates have shown a gradual increase in China. Owing to the difficulty of early diagnosis, identification of high-risk population and modification of risk factors are important to reduce the burden of pancreatic cancer.

Ozsurekci, Yasemin;Oncel, Eda Karadag;Bayhan, Cihangul;Celik, Melda;Ozkaya-Parlakay, Aslinur;Arvas, Mehmet;Ceyhan, Mehmet 7325

https://doi.org/10.7314/APJCP.2013.14.12.7325 PDF KSCI

Background: Human papillomavirus (HPV) is one of the most common sexually transmitted infectious agents, and the effectiveness of vaccine delivery programs will depend largely upon whether providers recommend vaccines. The objectives of this study were to examine pediatrician characteristics, knowledge, and attitudes associated with HPV and HPV immunization. Materials and Methods: Attendees of the national pediatric meeting in 2011, were asked to complete a questionnaire that, aside from demographic information, elicited level of agreement with statements regarding HPV, its related diseases, and HPV vaccination. It also documented attitudes and beliefs about HPV vaccination. Results: Of the 480 attendees, 226 (47%) filled in the questionnaire. The level of pediatrician HPV-related knowledge varied. The majority (78%) were aware that HPV infection is the most common sexually transmitted infection, while 51% were unaware that a condom is ineffective protection against HPV infection. Between 60-80% of respondents were aware of the effectiveness of HPV vaccination for women. On the other hand, only 10% were aware of reasons why men should be vaccinated against HPV. The majority (75%) of Turkish pediatricians were likely to recommend HPV vaccination to their daughter, if they had one. Seventy percent of pediatricians agreed that the HPV vaccination should be added to the National Immunization Program (NIP) in Turkey. However, the respondents documented concerns about the cost of the vaccination. Conclusions: Increasing pediatricians' knowledge and awareness of HPV and HPV vaccination may assist with the implementation of an effective NIP.

Gupta, Satrudhan Pd;Mittal, Ankush;Sathian, Brijesh;Jha, Dipendra Kumar 7331

https://doi.org/10.7314/APJCP.2013.14.12.7331 PDF KSCI

Aim: To investigate associations of fasting insulin and glucose levels in serum with hepatocellular carcinoma risk. Materials and Methods: This hospital based study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Nepalese Army Institute of Health Sciences, between 1st December, 2011 and 31st June, 2013. The variables collected were age, fasting plasma glucose, fasting plasma insulin and ALT. Quantitative determination of human insulin concentrations was accomplished by chemiluminescence enzyme immunoassay. Results: Of the total 220 subjects enrolled in our present study, 20 cases were of HCC and 200 were healthy controls. The maximum number of cases of hepatocellular carcinoma in category cutpoints of fasting insulin levels fell in the range of >6.10 ${\mu}U/ml$. The highest insulin levels (>6.10 ${\mu}U/ml$) were seen to be associated with an 2.36 fold risk of HCC when compared with fasting insulin levels of (<2.75 ${\mu}U/ml$). Furthermore, the insulin levels (2.75-4.10 ${\mu}U/ml$) of category cutpoints also conferred a 1.57 fold risk for HCC when compared with lowest fasting insulin levels of (<2.75 ${\mu}U/ml$). Conclusions: The effect of an insulin level in increasing HCC risk appeared consistent, influencing incidence, risk of recurrence, overall survival, and treatment-related complications in HCC patients.

Hu, Yan-Xia;Li, Min;Jia, Xiao-Hui;Du, Qu-Xiao;Miao, Feng-Tai;Yao, Li;Shen, Ji-Duo 7335

https://doi.org/10.7314/APJCP.2013.14.12.7335 PDF KSCI

There is increasing evidence that natural killer (NK) cells play an important role in antitumor immunity following dendritic cell (DC) vaccination. Little is known, however, about the optimal stimulation of DCs by epitopes and NK interactions for cytotoxicity in tumors. In this study, DC cells activated by the HPV16E7.49-57 epitope and LPS were co-cultured with NK cells in vitro, and then used ot immunize mice to study CTL activity of TC-1, which constitutively expresses HPV16E6E7, with an LDH release assay. Cytotoxicity in mice immunized with DC loaded with epitope HPVE7.49-57 vaccine co-cultured with NK was enhanced significantly (p<0.01). In conclusion, talk-across between DC and NK cells enhances their functions, also improving cytotoxicity againsttumor cells, suggesting that activated DC-NK by epitopes has potential application for cancer-specific immuno-cellular therapy.

Liang, Ai-Ling;Zhang, Ting-Ting;Zhou, Ning;Huang, Di-Nan;Liu, Xin-Guang;Liu, Yong-Jun;Tu, Zhi-Guang 7339

https://doi.org/10.7314/APJCP.2013.14.12.7339 PDF KSCI

To analyze the effects of a new unknown peptide DEF on the growth of tumor cells, a fused polypeptide TAT-DV1-DEF was designed and synthesized. The lung adenocarcinoma cell line GLC-82 treated with TAT-DV1-DEF was analyzed with a cell counting kit 8, and the location of polypeptides in cells was observed under laser confocal microscopy. The efficiency of polypeptide transfection and changes in nuclear morphology were analyzed by flow cytometry and fluorescence microscopy, respectively. Finally, the mechanism of tumor cell growth inhibition was evaluated by Western blotting. We found that TAT-DV1-DEF could significantly inhibit the growth of the lung adenocarcinoma cell line GLC-82, but not the normal human embryonic kidney cell line HEK-293. Polypeptides were found to be mostly localized in the cytoplasm and some mitochondria. The efficiency of polypeptide transfection in the two cell types was approximately 99%. Apoptotic nuclei were observed under fluorescence microscopy upon treatment with polypeptides and DAPI staining. Western blot analyses indicated that the polypeptide inhibition of tumor cell growth was apoptosis dependent. In the present study, we demonstrated that fused polypeptides could induce apoptosis of the lung adenocarcinoma cell line GLC-82, indicating that the new unknown peptide DEF has antitumor effects.

Abdelgawad, Iman Attia;Mossallam, Ghada Ibrahim;Radwan, Noha Hassan;Elzawahry, Heba Mohammed;Elhifnawy, Niveen Mostafa 7345

https://doi.org/10.7314/APJCP.2013.14.12.7345 PDF KSCI

Background: Because of the high prevalence of hepatocellular carcinoma (HCC) in Egypt, new markers with better diagnostic performance than alpha-feto protein (AFP) are needed to help in early diagnosis. The aim of this work was to compare the clinical utility of both serum and mRNA glypican3 (GPC3) as probable diagnostic markers for HCC among Egyptian patients. Materials and Methods: A total of 60 subjects, including 40 with HCC, 10 with cirrhosis and 10 normal controls were analyzed for serum GPC3 (sGPC3) by ELISA. GPC-3 mRNA from circulating peripheral blood mononuclear cells was amplified by RT-PCR. Both markers were compared to some prognostic factors of HCC, and sensitivity of both techniques was compared. Results: Serum glypican-3 and AFP were significantly higher in the HCC group compared to cirrhotic and normal controls (p<0.001). Sensitivity and specificity were (95% each) for sGlypican-3, (82.5% and 85%) for AFP, and (100% and 90%) for Glypican3 mRNA, and (80% and 95%) for double combination between sGPC3 and AFP respectively. Conclusion: Both serum GPC-3 and GPC-3mRNA are promising diagnostic markers for early detection of HCC in Egyptian patients. RT- PCR proved to be more sensitive (100%) than ELISA (95%) in detecting glypican3.

Ozbek, Emin;Otunctemur, Alper;Sahin, Suleyman;Dursun, Murat;Besiroglu, Huseyin;Koklu, Ismail;Polat, Emre Can;Erkoc, Mustafa;Danis, Eyyup;Bozkurt, Muammer 7351

https://doi.org/10.7314/APJCP.2013.14.12.7351 PDF KSCI

Background: Metabolic syndrome (MetS) is a multifactorial disease characterized by impaired glucose tolerance/diabetes, obesity, high triglyceride levels, low HDL levels, and hypertension. In this study we evaluate the relationship between tumor size and grade, and presence of the metabolic syndrome in patients with renal cell carcinoma. Materials and Methods: Between 2007-2013, radical nephrectomy was performed for 310 patients with renal tumors in our clinic and those with pathology reported renal cell carcinoma were enrolled and divided into two groups, with and without metabolic syndrome diagnosed on the basis of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria. The relationship between tumor size and grade of the two groups (Fuhrman nuclear degree) was evaluated statistically. Results: The metabolic syndrome was found in 70 patients, with a mean age of 65.5 (40-87), as compared to 58.8 (31-84) years in the non-metabolic syndrome group. Tumor size over 7 cm was found in 54% and 33%, respectively, and tumor grade over Fuhrman 3 in 56% and 32% of patients. Patients with metabolic syndrome had significantly higher tumor size and grade (p<0.05). In the presence of hypertension, diabetes and high triglyceride levels, significant assocations were again observed (p<0.05). Tumor size and degree also increased with increasing body mass index but this was not statistically significant (p>0.05). Conclusions: Renal cancer is more aggressive in patients with metabolic syndrome. Lifestyle and risk factors were revealed to be significant influences in renal cancer patients.

Zhang, Bin;Hao, Guang-Yu;Gao, Fang;Zhang, Jian-Zu;Zhou, Cheng-Jiang;Zhou, Li-She;Wang, Ying;Jia, Yan-Bin 7355

https://doi.org/10.7314/APJCP.2013.14.12.7355 PDF KSCI

Several lines of evidence support the notion that MUC1 is often aberrantly expressed in gastric cancer, and it is a ligand for Helicobacter pylori. Genetic variation in MUC1 gene may confer susceptibility to H. pylori infection and gastric cancer. We assessed the association of common polymorphisms in MUC1 gene with H. pylori infection and non-cardia gastric cancer using an LD-based tag SNP approach in north-western Chinese Han population. A total of four SNPs were successfully genotyped among 288 patients with non-cardia gastric cancer and 281 age- and sex-matched controls. None of the tested SNPs was associated with H. pylori infection. SNP rs9426886 was associated with a decreased risk of non-cardia gastric cancer, but lost significance after adjustment for multiple testing. Overall, our data indicated that common genetic variations in MUC1 gene might not make a major contribution to the risk of H. pylori infection and non-cardia gastric cancer in our studied population.

Zhang, Xiao-Dan;Zhao, Qing-Yu;Fang, Yi;Chen, Guan-Xuan;Zhang, Hui-Fang;Zhang, Wen-Xiao;Yang, Xiao-Ping 7359

https://doi.org/10.7314/APJCP.2013.14.12.7359 PDF KSCI

Objective: To assess the effects of perioperative comprehensive supportive care interventions on outcome of Chinese esophageal cancer patients in a prospective study. Methods: 60 patients with primary esophageal carcinoma were randomized into an intervention group (IG, n=31) and a control group (CG, n=29). The Chinese version of symptom checklist-90 (SCL-90) was adopted to assess their psychological status. The interventions, including health education, psychological support, stress management, coping strategies and behavior training, were carried out in 3 phases (preoperative, postoperative I and postoperative II), and psychological effects were thereafter evaluated accordingly before surgery, and 1 week, 4 weeks and 24 weeks post-surgery. Medical costs were estimated at discharge. Survival of patients was estimated each year post-surgery. General health status and satisfaction-with-hospital were surveyed by a follow-up questionnaire 4 years post-surgery. Results: All the subjects demonstrated higher scores in the preoperative phase than the normal range of Chinese population concerning 7 psychological domains including somatization, obsessive-compulsive, depression, anxiety, hostility, phobic anxiety and paranoid ideation. Although no significant difference was observed between the two groups at admission, the scores of IG, which tended to decrease at a faster rate, were generally lower than those of CG at weeks 1, 4 and 24 post-surgery. The length of hospital stay and medical costs of IG were significantly less than those of CG and satisfaction-with-hospital was better. However, there was no significant difference in 4-year survival or health status between two groups. Conclusions: Appropriate perioperative comprehensive supportive care interventions help to improve the psychological state of Chinese patients with esophageal carcinoma, to reduce health care costs and to promote satisfaction of patients and their families with hospital.

Berk, Veli;Kaplan, Mehmet Ali;Tonyali, Onder;Buyukberber, Suleyman;Balakan, Ozan;Ozkan, Metin;Demirci, Umut;Ozturk, Turkan;Bilici, Ahmet;Tastekin, Didem;Ozdemir, Nuriye;Unal, Olcun Umit;Oflazoglu, Utku;Turkmen, Esma;Erdogan, Bulent;Uyeturk, Ummugul;Oksuzoglu, Berna;Cinkir, Havva Yesil;Yasar, Nurgul;Gumus, Mahmut 7367

https://doi.org/10.7314/APJCP.2013.14.12.7367 PDF KSCI

Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-${\beta}$) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

Wang, Hsiu-Ho;Wu, Shiao-Ying 7371

https://doi.org/10.7314/APJCP.2013.14.12.7371 PDF KSCI

Aims: The study targeted the HPV vaccine knowledge and perceived risk of cervical cancer among female college students in Taiwan as well as the relationship between knowledge of the HPV vaccine and perceived risk of cervical cancer. Materials and Method: The results of this study on female college students are described using descriptive and correlation designs. A convenience sampling approach was employed with a self-filling structured questionnaire. Results: A total of 150 students completed the questionnaire. Values were 7.49 for the mean HPV vaccine knowledge scale and 18.0 for their mean perceived risk of cervical cancer scale. HPV vaccine knowledge was positively correlated with perceived risk of cervical cancer. Conclusions: The findings of this study can serve as a reference for future HPV prevention in Taiwan.

Tang, Yue;Xuan, Xiao-Yan;Li, Min;Dong, Zi-Ming 7375

https://doi.org/10.7314/APJCP.2013.14.12.7375 PDF KSCI

The main aim of this study was to investigate the roles of GST-${\pi}$ and $pol{\beta}$ genes in the chemoresistance of esophageal carcinoma cells. Eukaryotic expression vectors containing each gene were constructed and transfected into EC9706 cells, and the biological effects of the two genes assessed based on a resistance index. We additionally investigated the in vitro and in vivo anti-resistance effects of GST-${\pi}$ and $pol{\beta}$ genes using recombinant lentiviruses carrying siRNAs against the two genes. Our results showed that upregulation of GST-${\pi}$ and $pol{\beta}$ genes suppresses chemosensitivity of esophageal carcinoma cells to cisplatin, while downregulation of these two genes with RNAi technology reverses this chemoresistance. Multi-site injection of recombinant lentivirus targeting the GST-${\pi}$ gene into transplanted cDDP tumors effectively reversed their chemoresistant phenotype. However, the same treatment against the $pol{\beta}$ gene did not lead to significant efficacy against chemoresistance.

Sedighi, Abdolazim;Hamed, Ehsan Akbari;Mohammadian, Kamal;Behnood, Sepideh;Kalaghchi, Bita 7381

https://doi.org/10.7314/APJCP.2013.14.12.7381 PDF KSCI

Background: Male breast cancer accounts for less than 1% of all cancer in men and only around 1% of all diagnosed breast cancer. Despite a significant raise in the last 25 years, it still remains a rare disease. Materials and Methods: We conducted a retrospective study from 2004-2011 with 21 male breast cancer patients. We aimed to analyze the epidemiologic data (age, personal and family history), tumor characteristics (size, histological type, location, TNM stage, receptors), surgery, adjuvant chemotherapy and radiation therapy, hormonal therapy and survival (relapse, follow up, death) who reffered to our center with breast cancer. Results: The median age was $49.2{\pm}14.2$ years (range 30-83 years). A family history of breast cancer was noted in four cases. The main clinical complaint was a retroareolar mass in 85.7%of patients (n=18). Histologically, 85.7% (n=18)were invasive ductal carcinoma and 4.7% (n=1) had ductal carcinoma in situ and 9.4% (n=2) had mixed histology including invasive medullary and ductal carcinoma. Hormonal therapy was delivered to 16 cases (76.1%) due to ER or PR positivity. During median follow up of 30 months (3-84 month), distant metastases were evident in 4 cases (19%). During the follow-up period, only one patient died due to metastatic disease. The mean time to recurrence detection was 30 months. Conclusions: The percentage of cases of male breast cancer is very low compared to breast cancer in females, explaining why very few investigations have been conducted in Iran. Limited coverage in the literature make gender-specific findings difficult so future research of this entity involving multi-institutional cooperation and longer follow up is essential to provide new insights about the biological and clinical factors of this rare cancer.

Shen, Fang;Wu, Chun-Xiao;Yao, Yu;Peng, Peng;Qin, Zhi-Yong;Wang, Yin;Zheng, Ying;Zhou, Liang-Fu 7385

https://doi.org/10.7314/APJCP.2013.14.12.7385 PDF KSCI

Background: Only few epidemiological data on primary central nervous system (CNS) tumors in Shanghai have been reported. Methods: All cases of primary CNS tumors that were registered at Center for Disease Control and Prevention (CDC) were collected (1973-2007: urban Shanghai; 2003-2007: whole Shanghai city). Trends were analyzed using joinpoint analysis and rates were stratified by age, gender and region. Histological data were collected from both CDC and Huashan Hospital. Results: From 1973 to 2007, the five-year average incidence rate in urban Shanghai increased in both genders, especially in the elderly population. Joinpoint analysis showed the age-adjusted incidence rate for males increased first but then plateaued, whilst rates for females continued increasing over the 35 years. For the five-year status quo (2003-2007), rural had a higher age-adjusted incidence rate than urban populations, and females higher than males, especially those with advanced age. According to CDC (2003-2007) and Huashan Hospital (1951-2011), the two most common histological subtypes were neuroepithelial tumors (with male predominance) and meningiomas (with female predominance). Conclusions: In Shanghai, a steadily increased incidence rate of primary CNS tumors was observed in general, and in the elderly and female population in particular.

Kang, Min;Liu, Wen-Qi;Qin, Yu-Tao;Wei, Zhu-Xin;Wang, Ren-Sheng 7395

https://doi.org/10.7314/APJCP.2013.14.12.7395 PDF KSCI

Objective: The long-term efficacy of microwave hyperthermia combined with chemoradiotherapy in treating nasopharyngeal carcinoma (NPC) with metastatic foci in cervical lymph nodes was evaluated. Methods: A total of 154 cases of N2 or N3 stage NPC were randomized into two groups: hyperthermia group (76 cases) and control group (78 cases). Both received cisplatin chemotherapy and radiotherapy. In addition, the hyperthermia group further received microwave hyperthermia to the metastatic cervical nodes with different patterns (before or after radiotherapy), heating temperatures (T90< $43^{\circ}C$ and $T90{\geq}43^{\circ}C$) and hyperthermia episodes (< 4 times, 4-10 times and > 10 times). Results: The 3-month and 5-year complete response (CR) rates of cervical lymph nodes in the hyperthermia group were significantly higher than those in the control group. The 5-year disease-free survival (DFS) rate and the 3-year / 5-year overall survival rate in the hyperthermia group were also significantly higher. There was no significant difference in 5-year metastatic rates. In the hyperthermia group, the 3-month and 5-year CR rates of T90< $43^{\circ}C$ treatment were significantly lower than with $T90{\geq}43^{\circ}C$ treatment. The CR rate was highest when the hyperthermia was performed 4-10 times. There were no significant differences in 3-month and 5-year CR rates between hyperthermia before or after radiotherapy treatment. Conclusion: Microwave hyperthermia combined with chemoradiotherapy can increase local control, DFS and 3, 5-year overall survival rates of patients with N2 ~ N3 stage NPC. The heating temperature should be over $43^{\circ}C$ with hyperthermia repeated 4-10 times.

Hyun, Min Kyung;Hwang, Jin Seub;Kim, Jin Hee;Choi, Ji Eun;Jung, Sung Young;Bae, Jong-Myon 7401

https://doi.org/10.7314/APJCP.2013.14.12.7401 PDF KSCI

Aim: To compare survival outcomes after whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and WBRT plus SRS combination therapy in Korea, by performing a quantitative systematic review. Materials and Methods: We searched 10 electronic databases for reports on Korean patients treated with WBRT or SRS for brain metastases published prior to July 2010. Independent reviewers screened all articles and extracted the data. When a Kaplan-Meier survival curve was available, median survival time and standard errors were calculated. Summary estimates for the outcomes in each study were calculated using the inverse variance random-effects method. Results: Among a total of 2,761 studies, 20 studies with Korean patients (n=1,053) were identified. A combination of 12 studies (n=566) with WBRT outcomes showed a median survival time of 6.0 months (95%CI: 5.9-6.2), an overall survival rate of 5.6% (95%CI: 1-24), and a 6-month survival rate of 46.5% (95%CI: 37.2-56.1). For nine studies (n=412) on SRS, the median survival was 7.9 months (95%CI: 5.1-10.8), and the 6-month survival rate was 63.1% (95%CI: 49.8-74.8). In six studies (n=75) using WBRT plus SRS, the median survival was 10.7 months (95%CI: 4.7-16.6), and the overall and 6-month survival rates were 16.8% (95%CI: 6.2-38.2) and 85.7% (95%CI: 28.3-96.9), respectively. Conclusions: WBRT plus SRS showed better 1-year survival outcome than of WBRT alone for Korean patients with metastatic brain tumors. However, the results of this analysis have to be interpreted cautiously, because the risk factors of patients were not adjusted in the included studies.

Memon, Zahid Ali;Shaikh, Anum Nizamuddin;Rizwan, Sundus;Sardar, Maimoona Batool 7409

https://doi.org/10.7314/APJCP.2013.14.12.7409 PDF KSCI

Background: Delay in diagnosis of breast cancer is associated with a poorer survival and a pivotal contribution to this delayed diagnosis comes from patient delay in presenting at a clinic. Reasons involved must be evaluated in order to decrease this reducible delay. Objectives: i) To evaluate the reasons for patient delay in diagnosis of breast cancer; ii) to investigate any association with other variables. Materials and Methods: A 6 month cross sectional study (from July 2012 to Dec 2012), was carried out in Surgical and Oncology Units of Civil Hospital, Karachi. A total of 100 females diagnosed with breast cancer of any histological type were interviewed after informed consent and relevant data were collected. Due ethical clearance was obtained. Results: Mean age was $47.5{\pm}12.1$ years with a range from 25-77 years. Mean duration of delay was $5.13{\pm}4.8$ months, from shortest 1 month to longest 36 months. Duration of delay was observed to be no delay (<1 month) in 28%, short delay (1-3 months) in 30% and long delay (>3 months) in 42% of patients. Considering the symptoms as "harmless" (39%) was the most frequent reason of delay followed by "temporary" (20%) and the "use of traditional methods" (12%). Most common reason for later approaches was an increase in the size of the lump (41%). Statistically significant association (p-value <0.05) of longer patient delay was obtained with being single, being illiterate, painless breast lump as the first symptom, negative family history of breast cancer and vague attribution of the symptoms. Conclusions: Significant delay in approach to health care facility was observed in our study due to variable reasons given by women. Sufficient awareness regarding breast cancer, its symptoms and favorable effects of a timely diagnosis on prognosis must be imparted to our general population.

Qin, Li-Li;Wang, Qin-Rong;Wang, Qian;Yao, Hong;Wen, Li-Jun;Wu, Li-Li;Ping, Na-Na;Xie, Jun-Dan;Chen, Mei-Yu;Chen, Su-Ning 7415

https://doi.org/10.7314/APJCP.2013.14.12.7415 PDF KSCI

The diagnosis of latent Mycobacterium tuberculosis infection (LTBI) is recommended in hematological malignancy patients and before hematopoietic stem cell transplantation (Guidelines for the prevention and management of infectious complications of solid organ transplantation, 2004). Compared to traditional methods such as tuberculin skin test (TST), T-SPOT.TB has been shown to be more specific. In the present study we enrolled 536 patients for whom T-SPOT.TB was performed, among which 295 patients also received the TST test. The agreement (79%) between T-SPOT.TB and TST was poor (x=0.274, P<0.001). The patients with positive T-SPOT.TB results numbered 62 (11.6%), in which only 20 (48.8%) of the 41 receiving the TST test had positive results. A majority of the patients with T-SPOT.TB positive results had some other evidence ofTB, such as TB history, clinical symptoms and an abnormal chest CT scan. Active TB was found in 9 patients, in which 2 had negative TST results. We followed up the patients and no one developed active TB. Our study suggested that the T-SPOT.TB may be more useful for screening LTBI and active TB in hematological malignancy patients and hematopoietic stem cell transplant recipients than the TST test.

Chen, Qi;Xia, Hong-Wei;Ge, Xiao-Jun;Zhang, Yu-Chen;Tang, Qiu-Lin;Bi, Feng 7421

https://doi.org/10.7314/APJCP.2013.14.12.7421 PDF KSCI

Background: Colorectal cancer is the fourth most common cancer worldwide and the second leading cause of cancer-related death. FOLFOX is the most common regimen used in the first-line chemotherapy in advanced colorectal cancer, but only half of the patients respond to this regimen and we have almost no clue in predicting resistance in such first-line application. Methods: To explore the potential molecular biomarkers predicting the resistance of FOLFOX regimen as the first-line treatment in advanced colorectal cancer, we screened microRNAs in serum samples from drug-responsive and drug-resistant patients by microarrays. Then differential microRNA expression was further validated in an independent population by reverse transcription and quantitative real-time PCR. Results: 62 microRNAs expressing differentially with fold-change >2 were screened out by microarray analysis. Among them, 5 (miR-221, miR-222, miR-122, miR-19a, miR-144) were chosen for further validation in an independent population (N=72). Our results indicated serum miR-19a to be significantly up-regulated in resistance-phase serum (p=0.009). The ROC curve analysis showed that the sensitivity of serum miR-19a to discriminate the resistant patients from the response ones was 66.7%, and the specificity was 63.9% when the AUC was 0.679. We additionally observed serum miR-19a had a complementary value for cancer embryonic antigen (CEA). Stratified analysis further revealed that serum miR-19a predicted both intrinsic and acquired drug resistance. Conclusions: Our findings confirmed aberrant expression of serum miR-19a in FOLFOX chemotherapy resistance patients, suggesting serum miR-19a could be a potential molecular biomarker for predicting and monitoring resistance to first-line FOLFOX chemotherapy regimens in advanced colorectal cancer patients.

Alishahi, Ailin;Roshan, Valiollah Dabidi;Hedayyati, Mehdi 7427

https://doi.org/10.7314/APJCP.2013.14.12.7427 PDF KSCI

Aims: To examine the pretreatment effects of regular aerobic training on the IGF system (IGF-I, IGFBP-3 and IGF/IGFBP) and doxorubicin(DOX) induced hepatotoxicity in rats. Materials and Methods: Forty-eight male rats were divided into groups:(1) control+placebo (2) $control+DOX_{10}mg{\cdot}kg^{-1}$ (3) $control+DOX_{20}mg{\cdot}kg^{-1}$ (4) training+placebo (5) $training+DOX_{10}mg{\cdot}kg^{-1}$ (6) $training+DOX_{20}mg{\cdot}kg^{-1}$. Hepatotoxicity was induced by DOX with dosages of 10 and 20 $mg{\cdot}kg^{-1}$. The rats in groups 4, 5 and 6 performed treadmill running of 25-54 min/day and 15-20 m/min, 5 days/wk for 6 wks. At the end of the aerobic training protocol, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, $DOX_{10}mg{\cdot}kg^{-1}$ and $DOX_{20}mg{\cdot}kg^{-1}$, respectively. Results: Administration of $DOX_{20}mg{\cdot}kg^{-1}$ caused a significant increase in IGF-1 and IGF-1/IGFBP-3, an insignificant decrease in IGFBP-3, as compared to the control+placebo group. However, after six weeks of aerobic training and DOX treatment with $10mg{\cdot}kg^{-1}$ and or/ $20mg{\cdot}kg^{-1}$ an insignificant decrease in IGF-1, an insignificant increase in IGFBP-3 and a significant decrease in IGF-1/IGFBP-3 were detected, in comparison to $C+DOX_{10}$ and $C+DOX_{20}$. Conclusions: Hepatotoxicity of doxorubicin is dose-dependent and pretreatment with regular aerobic training may improve DOX-induced hepatotoxicity by up-regulation of IGFBP3.

Chen, Hao;Luo, Yao-Ling;Zhang, Lin;Tian, Li-Zhen;Feng, Zhi-Ting;Liu, Wan-Li 7433

https://doi.org/10.7314/APJCP.2013.14.12.7433 PDF KSCI

Aim: To identify new biomarkers for NPC diagnosis with an anti-EBV Western blot test kit. Methods: Serum samples from 64 NPC patients and healthy subjects with four specific VCA-IgA/EA-IgA profiles were tested with an anti-EBV Western blot test kit from EUROIMMUN AG. Proteins were quantified with scores of intensity visually assigned to the protein bands. The markers which showed statistical differences between the NPC and non-NPC subjects were further evaluated in another 32 NPC patients and 32 controls in comparison with established biomarkers including VCA-IgA, EA-IgA, EBV-related protein IgG, and EBV DNA. Results: Among the markers screened, EA-D p45-IgG showed a statistically significant difference (p < 0.05) between NPC and non-NPC subjects with VCA-IgA positivy. In 32 VCA-IgA positive NPC patients and 32 control subjects, the diagnostic accuracy of EA-D p45-IgG was 78.1% with a positive predictive value of 77.8% and a negative predictive value of 78.6%. In the verification experiment, the specificity and sensitivity of EA-D p45-IgG were 75.0% and 90.6 %, respectively. Conclusions: EA-D p45-IgG might be a potential biomarker for NPC diagnosis, especially among VCA-IgA positive subjects.

Hao, Zhen-Feng;Ao, Jun-Hong;Zhang, Jie;Su, You-Ming;Yang, Rong-Ya 7439

https://doi.org/10.7314/APJCP.2013.14.12.7439 PDF KSCI

Aim: ATF3, a member of the ATF/CREB family of transcription factors, has been found to be selectively induced by calcineurin/NFAT inhibition and to enhance keratinocyte tumor formation, although the precise role of ATF3 in human skin cancer and possible mechanisms remain unknown. Methods: In this study, clinical analysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was accumulated in skin cancer tissues. Functional assays demonstrated that ATF3 significantly promoted skin cancer cell proliferation. Results: Mechanically, ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of p53 expression. Moreover, the promotion effect of ATF3 on skin cancer cell proliferation was dependent on the p53-Stat3 signaling cascade. Conclusion: Together, the results indicate that ATF3 might promote skin cancer cell proliferation and enhance skin keratinocyte tumor development through inhibiting p53 expression and then activating Stat3 phosphorylation.

Uyeturk, Ummugul;Tatli, Ali Murat;Gucuk, Sebahat;Oksuzoglu, Berna;Ulas, Arife;Avci, Nilufer;Ozbay, Mehmet Fatih;Gunduz, Seyda;Akinci, Muhammed Bulent;Salim, Derya Kivrak;Sonmez, Ozlem Uysal;Akdag, Fatma;Ergenc, Hasan 7445

https://doi.org/10.7314/APJCP.2013.14.12.7445 PDF KSCI

Background: Breast cancer (BC) is the one of the most common cancers in women. It is also a leading cause of death. Unfortunately, some patients initially present with distant metastases and are diagnosed with stage IV disease that is nearly always, by then, incurable. This retrospective analysis investigated the risk factors for stage IV BC that may underlie such late presentation. Materials and Methods: In all, 916 patients with BC who visited the medical oncology polyclinic of eight different centres in Turkeybetween December 2011 and January 2013 were analysed. Results: A total of 115 patients (12.6%) presented with stage IV disease. In univariate analysis; to comparing these with patients at other stages, no statistical difference was found for median diagnosis age or age at menarche (p=0.611 and p=0.820), whereas age at menopause and age at first live birth were significant (p=0.018 and p=0.003). No difference was detected in terms of accompanying diseases, use of oral contraceptives and hormone replacement therapy, smoking, alcohol consumption and the rate of family history of BC between the patients (p=0.655, p=0.389, p=0.762, p=0.813, p=0.229, p=0.737). However, screening methods were employed less often, the rate of illiteracy was higher, and the rate of other cancers was higher in patients with stage IV BC (p=0.022, p=0.022, p=0.018). No statistical difference was observed between the patients in terms of tumour histopathology, and status of oestrogen receptor, progesterone receptor, or human epidermal growth factor-2 receptor (p=0.389, p=0.326, p=0.949, p=0.326). Grade 3 tumours were more frequent in patients with stage IV disease (p<0.001). On multivariate analysis, risk factors for stage IV breast cancer at the time of presentation were found to be age at first live birth and educational level (p=0.003 and p=0.047). Conclusions: Efforts should be made to perform mammography scans, in particular, at regular intervals through national training programs for all women, particularly those with family histories of breast and other types of cancer, and to establish early diagnosis of BC long before it proceeds to stage IV. Additionally, women's education had better be upgraded. In order to make women aware of BC, national education-programmes must be organised.

Sohng, Hee Yon;Kuniyuki, Alan;Edelson, Jane;Weir, Rosy Chang;Song, Hui;Tu, Shin-Ping 7451

https://doi.org/10.7314/APJCP.2013.14.12.7451 PDF KSCI

Background: Understanding and enhancing change capabilities, including Practice Adaptive Reserve (PAR), of Community Health Centers (CHCs) may mitigate cancer-related health disparities. Materials and Methods: Using stratified random sampling, we recruited 232 staff from seven CHCs serving Asian Pacific Islander communities to complete a self-administered survey. We performed multilevel regression analyses to examine PAR composite scores by CHC, position type, and number of years worked at their clinic. Results: The mean PAR score was 0.7 (s.d. 0.14). Higher scores were associated with a greater perceived likelihood that clinic staff would participate in an evidence-based intervention (EBI). Constructs such as communication, clinic flow, sensemaking, change valence, and resource availability were positively associated with EBI implementation or trended toward significance. Conclusions: PAR scores are positively associated with perceived likelihood of clinic staff participation in cancer screening EBI. Future research is needed to determine PAR levels most conducive to implementing change and to developing interventions that enhance Adaptive Reserve.

Simayi, Dilixia;Yang, Lan;Li, Feng;Wang, Ying-Hong;Amanguli, A.;Zhang, Wei;Mohemaiti, Meiliguli;Tao, Lin;Zhao, Jin;Jing, Ming-Xia;Wang, Wei;Saimaiti, Abudukeyoumu;Zou, Xiao-Guang;Maimaiti, Ayinuer;Ma, Zhi-Ping;Hao, Xiao-Ling;Duan, Fen;Jing, Fang;Bai, Hui-Li;Liu, Zhao;Zhang, Lei;Chen, Cheng;Cong, Li;Zhang, Xi;Zhang, Hong-Yan;Zhan, Jin-Qiong;Zhang, Wen Jie 7459

https://doi.org/10.7314/APJCP.2013.14.12.7459 PDF KSCI

Background: Some 60 years after introduction of the Papanicolaou smear worldwide, cervical cancer remains a burden in developing countries where >85% of world new cases and deaths occur, suggesting a failure to establish comprehensive cervical-cancer control programs. Effective interventions are available to control cervical cancer but are not all affordable in low-income settings. Disease awareness saves lives by risk-reduction as witnessed in reducing mortality of HIV/AIDS and smoking-related cancers. Subjects and Methods: We initiated a community-based awareness program on cervical cancer in two low-income Muslim Uyghur townships in Kashi (Kashgar) Prefecture, Xinjiang, China in 2008. The education involved more than 5,000 women from two rural townships and awareness was then evaluated in 2010 and 2011, respectively, using a questionnaire with 10 basic knowledge questions on cervical cancer. Demographic information was also collected and included in an EpiData database. A 10-point scoring system was used to score the awareness. Results: The effectiveness and feasibility of the program were evaluated among 4,475 women aged 19-70 years, of whom >92% lived on/below US$1.00/day. Women without prior education showed a poor average awareness rate of 6.4% (164/2,559). A onetime education intervention, however, sharply raised the awareness rate by 4-fold to 25.5% (493/1,916). Importantly, low income and illiteracy were two reliable factors affecting awareness before or after education intervention. Conclusions: Education intervention can significantly raise the awareness of cervical cancer in low-income women. Economic development and compulsory education are two important solutions in raising general disease awareness. We propose that implementing community-based awareness programs against cervical cancer is realistic, locally affordable and sustainable in low-income countries, which may save many lives over time and, importantly, will facilitate the integration of comprehensive programs when feasible. In this context, adopting this strategy may provide one good example of how to achieve "good health at low cost".

Yang, Li;Sun, Ming-Jun;Liu, Jing-Wei;Xu, Qian;Yuan, Yuan 7467

https://doi.org/10.7314/APJCP.2013.14.12.7467 PDF KSCI

Background: Polymorphisms of genes encoding cytokines could be potential biomarkers to predict risk of gastric cancer (GC). Here, we investigated the association between the IL-6 -6331 (T/C, rs10499563) polymorphism in its promoter region and GC risk. Methods: In this case-control study of 215 GC cases and 518 non-cancer controls, the IL-6 -6331 (T/C, rs10499563) polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Individuals with the TC or CC genotype were associated with a significantly decreased risk of GC (OR=0.710, 95%CI: 0.504-0.999, P=0.049) compared with TT wild-type carriers. Ther C allele was also associated with significantly decreased risk of GC (OR=0.715, 95%CI: 0.536-0.954, P=0.023) compared with the T allele. In the stratification analysis, TC or CC genotypes were associated with significantly decreased GC risk in subgroups of males, people older than 60, and H. pylori-positive cases. However, no significant interaction was observed for TC or CC genotypes with H. pylori infection. On stratification with the Lauren classification, TC or CC genotypes were associated with significantly decreased risk of diffuse-type GC (OR=0.497, 95%CI: 0.266-0.925, P=0.027), also in subgroups of males, people older than 60, and H. pylori-positive cases. Conclusions: The IL-6 -6331 (T/C, rs10499563) polymorphism is associated with genetic susceptibility of GC and may have the potential to predict GC risk.

Rani, Mukta;Nischal, Anuradha;Sahoo, Ganesh Chandra;Khattri, Sanjay 7473

https://doi.org/10.7314/APJCP.2013.14.12.7473 PDF KSCI

The G-protein coupled receptor 87 (GPR87) is a recently discovered orphan GPCR which means that the search of their endogenous ligands has been a novel challenge. GPR87 has been shown to be overexpressed in squamous cell carcinomas (SCCs) or adenocarcinomas in lungs and bladder. The 3D structure of GPR87 was here modeled using two templates (2VT4 and 2ZIY) by a threading method. Functional assignment of GPR87 by SVM revealed that along with transporter activity, various novel functions were predicted. The 3D structure was further validated by comparison with structural features of the templates through Verify-3D, ProSA and ERRAT for determining correct stereochemical parameters. The resulting model was evaluated by Ramachandran plot and good 3D structure compatibility was evidenced by DOPE score. Molecular dynamics simulation and solvation of protein were studied through explicit spherical boundaries with a harmonic restraint membrane water system. A DRY-motif (Asp-Arg-Tyr sequence) was found at the end of transmembrane helix3, where GPCR binds and thus activation of signals is transduced. In a search for better inhibitors of GPR87, in silico modification of some substrate ligands was carried out to form polar interactions with Arg115 and Lys296. Thus, this study provides early insights into the structure of a major drug target for SCCs.

Wang, Yue-Yun;Li, Li;Wei, Sheng;Peng, Ji;Yuan, Shi-Xin;Xie, Jian-Sheng;Liu, Zhi-Hua 7483

https://doi.org/10.7314/APJCP.2013.14.12.7483 PDF KSCI

Purpose: Human papillomavirus (HPV) infection plays an important role in the development of cervical cancer, but the prevalence of HPV infection in women of Shenzhen city remains unclear. The present study was performed to describe the change of cervical HPV infection in females who participated in voluntary cervical cancer screening from 2006 to 2010 in Shenzhen city, China. Methods: A total of 4, 413 women were recruited. HPV infections were genotyped by polymerase chain reaction (PCR) and reversed dot blot hybridization in Shenzhen Maternity and Child Health Hospital. Results: The prevalence of HPV infection was 13.8%. The five most commonly found HPV types were HPV16 (3.47%), HPV58 (1.68%), HPV33 (1.38%), HPV43 (1.36%) and HPV18 (1.27%). The secular trends of major HPV type-specific were diverse. Among of them, the prevalence of HPV18 increased sharply while others increased slowly or even decreased in the period. The change of total HPV, single HPV and multiple HPV infection were similar during the five years. Conclusions: Our findings suggested that HPV infection is common with HPV16 and HPV 58 as the primary subtypes in women in Shenzhen city.The prevalence of HPV 18 infection is increasing faster than any others, which will lead it to be one of the main subtypes in this city in the future.

Lv, Zheng;Zhang, Tian-Yuan;Yin, Jie-Chao;Wang, Hui;Sun, Tian;Chen, Li-Qun;Bai, Fu-Liang;Wu, Wei;Ren, Gui-Ping;Li, De-Shan 7489

https://doi.org/10.7314/APJCP.2013.14.12.7489 PDF KSCI

This study was conducted to investigate enhancement of anti-tumor effects of the lentogenic Newcastle disease virus Clone30 strain (NDV rClone30) expressing cytosine deaminase (CD) gene against tumor cells and in murine groin tumor-bearing models. Cytotoxic effects of the rClone30-CD/5-FC on the HepG2 cell line were examined by an MTT method. Anti-tumor activity of rClone30-CD/5-FC was examined in H22 tumor-bearing mice. Compared to the rClone30-CD virus treatment alone, NDV rClone30-CD/5-FC at 0.1 and 1 MOIs exerted significant cytotoxic effects (P<0.05) on HepG2 cells. For treatment of H22 tumor-bearing mice, recombinant NDV was injected together with 5-FC given by either intra-tumor injection or tail vein injection. When 5-FC was administered by intra-tumor injection, survival for the rClone30-CD/5-FC-treated mice was 4/6 for 80 days period vs 1/6, 0/6 and 0/6 for the mice treated with rClone30-CD, 5-FC and saline alone, respectively. When 5-FC was given by tail vein injection, survival for the rClone30-CD/5-FC-treated mice was 3/6 vs 2/6, 0/6 and 0/6 for the mice treated with rClone30-CD, 5-FC or saline alone, respectively. In this study, NDV was used for the first time to deliver the suicide gene for cancer therapy. Incorporation of the CD gene in the lentogenic NDV genome together with 5-FC significantly enhances cell death of HepG2 tumor cells in vitro, decreases tumor volume and increases survival of H22 tumor-bearing mice in vivo.

Yap, Ning Yi;Ng, Keng Lim;Ong, Teng Aik;Pailoor, Jayalakshmi;Gobe, Glenda Carolyn;Ooi, Chong Chien;Razack, Azed Hassan;Dublin, Norman;Morais, Christudas;Rajandram, Retnagowri 7497

https://doi.org/10.7314/APJCP.2013.14.12.7497 PDF KSCI

Background: This study concerns clinical characteristics and survival of renal cell carcinoma (RCC) patients in University Malaya Medical Centre (UMMC), as well as the prognostic significance of presenting symptoms. Materials and Methods: The clinical characteristics, presenting symptoms and survival of RCC patients (n=151) treated at UMMC from 2003-2012 were analysed. Symptoms evaluated were macrohaematuria, flank pain, palpable abdominal mass, fever, lethargy, loss of weight, anaemia, elevated ALP, hypoalbuminemia and thrombocytosis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic significance of these presenting symptoms. Kaplan Meier and log rank tests were employed for survival analysis. Results: The 2002 TNM staging was a prognostic factor (p<0.001) but Fuhrman grading was not significantly correlated with survival (p=0.088). At presentation, 76.8% of the patients were symptomatic. Generally, symptomatic tumours had a worse survival prognosis compared to asymptomatic cases (p=0.009; HR 4.74). All symptoms significantly affect disease specific survival except frank haematuria and loin pain on univariate Cox regression analysis. On multivariate analysis adjusted for stage, only clinically palpable abdominal mass remained statistically significant (p=0.027). The mean tumour size of palpable abdominal masses, $9.5{\pm}4.3cm$, was larger than non palpable masses, $5.3{\pm}2.7cm$ (p<0.001). Conclusions: This is the first report which includes survival information of RCC patients from Malaysia. Here the TNM stage and a palpable abdominal mass were independent predictors for survival. Further investigations using a multicentre cohort to analyse mortality and survival rates may aid in improving management of these patients.

Feng, Dan-Qin;Huang, Bo;Li, Jing;Liu, Jing;Chen, Xi-Min;Xu, Yan-Mei;Chen, Xin;Zhang, Hai-Bin;Hu, Long-Hua;Wang, Xiao-Zhong 7501

https://doi.org/10.7314/APJCP.2013.14.12.7501 PDF KSCI

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of hematopoietic stem cell scarrying the Philadelphia (Ph) chromosome and an oncogenic BCR-ABL1 fusion gene. The tyrosine kinase inhibitor (TKI) of BCR-ABL1 kinase is a treatment of choice for control of CML. Objective: Recent studies have demonstrated that miRNAs within exosomes from cancer cells play crucial roles in initiation and progression. This study was performed to assess miRNAs within exosomes of K562 cells. Methods: miRNA microarray analysis of K562 cells and K562 cell-derived exosomes was conducted with the 6th generation miRCURYTM LNA Array (v.16.0). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also carried out. GO terms and signaling pathways were categorized into 66 classes (including homophilic cell adhesion, negative regulation of apoptotic process, cell adhesion) and 26 signaling pathways (such as Wnt). Results: In exosomes, 49 miRNAs were up regulated as compared to K562 cells, and two of them were further confirmed by quantitative real-time PCR. There are differentially expressed miRNAs between K562 cell derived-exosomes and K562 cells. Conclusion: Selectively expressed miRNAs in exosomes may promote the development of CML via effects on interactions (e.g. adhesion) of CML cells with their microenvironment.

Zhao, Hao;Yin, Jie-Yun;Yang, Wan-Shui;Qin, Qin;Li, Ting-Ting;Shi, Yun;Deng, Qin;Wei, Sheng;Liu, Li;Wang, Xin;Nie, Shao-Fa 7509

https://doi.org/10.7314/APJCP.2013.14.12.7509 PDF KSCI

To assess the risk of cancers associated with sleep duration using meta-analysis of published cohort studies, we performed a comprehensive search using PubMed, Embase and Web of Science through October 2013. We combined hazard ratios (HRs) from individual studies using meta-analysis approaches. A random effect dose-response analysis was used to evaluate the relationship between sleep duration and cancer risk. Subgroup analyses and sensitivity analyses were also performed. Publication bias was evaluated using Funnel plots and Begg's test. A total of 13 cohorts from 12 studies were included in this meta-analysis, which included 723, 337 participants with 15, 156 reported cancer outcomes during a follow-up period ranging from 7.5 to 22 years. The pooled adjusted HRs were 1.06 (95% CI: 0.92, 1.23; P for heterogeneity =0.003) for short sleep duration, 0.91 (95% CI: 0.78, 1.07; P for heterogeneity <0.0001) for long sleep duration. In subgroup analyses stratified by cancer type, long duration of sleep showed an inverse relation with hormone-related cancer (HR=0.79; 95% CI: 0.65, 0.97; P for heterogeneity =0.009) and a greater risk of colorectal cancer (HR=1.29; 95% CI: 1.09, 1.52; P for heterogeneity =0.346). Further meta-analysis on dose-response relationships showed that the relative risks of cancer were 1.00 (95% CI: 0.99, 1.01; P for linear trend=0.9151) for one hour of sleep increment per day, and 1.00 (95% CI: 0.98, 1.01; P for linear trend=0.7749) for one hour of sleep increment per night. No significant dose-response relationship between sleep duration and cancer was found on non-linearity testing (P=0.5053). Our meta-analysis suggests a positive association between long sleep duration and colorectal cancer, and an inverse association with incidence of hormone related cancers like those in the breast. Studies with larger sample size, longer follow-up times, more cancer types and detailed measure of sleep duration are warranted to confirm these results.

Talaiezadeh, Abdolhassan;Tabesh, Hamed;Sattari, Alireza;Ebrahimi, Shahram 7517

https://doi.org/10.7314/APJCP.2013.14.12.7517 PDF KSCI

Background: Cancer incidence rates are increasing particularly in developing countries. It is crucial for policy makers to know basic cancer epidemiology in each region to design comprehensive prevention plans. There have hitherto been no population-based data available for cancer in Khuzestan province. The present report is a first from the regional population-based cancer registry for the period of 2002-2009. Materials and Methods: Data were collected retrospectively reviewing all new cancer patients whom were registered in Khuzestan province cancer registry during an 8-year period (2002-2009). All cases were coded based on the ICD-O-3 coding system and collected data were computerized using SPSS (Chicago, IL) software, version 11.5. The age standardized incidence rates (ASRs) per 100,000 person-year for all cancers were computed using the indirect method of standardization to the world population. Results: During the 8-year study period, 16,801 new cancer cases were registered. Based on the computed ASRs, the five most frequent malignancies in females were breast (26.4 per 100,000), skin (13.6), colorectal (5.72), stomach (4.31) and bladder(4.07) and in males, the five most frequent were skin (16.0 per 100,000), bladder (10.7),prostate (7.64), stomach (7.17), and colorectal (6.32).The ASR for all malignancies in women was 92.5 per 100,000, and that for men was 87.4. Conclusions: The observed patterns from the analysis of Khuzestan cancer registry data will lead to better understanding of the epidemiology of various malignancies in this part ofthe country and consequently provide a useful guide for authorities to make efficacious decisions and policies about a cancer control program for south-west Iran.

Lv, Ying-Tao;Du, Pei-Juan;Wang, Qiao-Yan;Tan, Yuan;Sun, Zong-Bin;Su, Zhong-Liang;Kang, Cong-Min 7523

https://doi.org/10.7314/APJCP.2013.14.12.7523 PDF KSCI

Thymidylate synthase (TS) catalyzes the transfer of a methyl group from methylenetetrahydrofolate to dUMP to form dTMP. It is a primary target in the chemotherapy of colorectal cancers and some other neoplasms. In order to obtain pure protein for analysis of structure and biological function, an expression vector TS-pET28b (+) was constructed by inserting wild-type human thymidylate synthase (hTS) cDNA into pET28b (+). Then an expression strain was selected after transformation of the recombined plasmid into Rosetta (DE3). Fusion protein with His-tag was efficiently expressed in the form of inclusion bodies after IPTG induction and the content was approximately 40.0% of total bacteria proteins after optimizing expression conditions. When inclusion bodies were washed, dissolved and purified by Ni-NTA under denatured conditions, the purity was up to 90%. On SDS-PAGE and West-blotting, the protein band was found to match well with the predicted relative molecular mass-36kDa. Bioactivity was 0.1 U/mg. The results indicated that high-level expression of wild-type hTS cDNA can be achieved in prokaryotes with our novel method, facilitating research into related chemotherapy.

Song, Wei-Feng;Wang, Lei;Huang, Wei-Yi;Cai, Xun;Cui, Jiu-Jie;Wang, Li-Wei 7529

https://doi.org/10.7314/APJCP.2013.14.12.7529 PDF KSCI

Background and Aims: MicroRNA-21 (miR-21) is reported to be overexpressed and to contribute to proliferation, apoptosis and gemcitabine resistance in pancreatic ductal adenocarcinomas (PDACs). The aims of this study were to explore regulation of miR-21 expression by epigenetic change and its impact on chemoresistance and malignant properties of of pancreatic cancer. Materials and methods: We retrospectively collected 41 cases of advanced pancreatic cancer patients who were sensitive or resistant to gemcitabine and assessed levels of serum circulating miR-21 for correlation with cytotoxic activity. Histone acetylation in the miR-21 promoter was also studied in gemcitabine-sensitive and gemcitabine-resistant PDAC cells. Gemcitabine-resistant HPAC and PANC-1 cells were transfected with pre-miR-21 precursors (pre-miR-21) and antisense oligonucleotides (anti-miR-21), and were treated with TSA. Finally, invasion and metastasis assays were performed and alteration in mir-21, PTEN, AKT and pAKT level was evaluated in these cells. Results: Serum miR-21 levels were increased in gemcitabine-resistant PDAC patients compared with gemcitabine-sensitive subjects. The miR-21 levels were increased in 6 PDAC cells treated with gemcitabine significantly, associated with 50% inhibitory concentrations ($IC_{50}s$). Histone acetylation levels at miR-21 promoter were increased in PDAC cells after treatment with gemcitabine. Enhanced invasion and metastasis, increased miR-21 expression, decreased PTEN, elevated pAKT level were demonstrated in gemcitabine-resistant HPAC and PANC-1 cells. Pre-miR-21 transfection or TSA treatment further increased invasion and metastasis ability, decreased PTEN, and elevated pAKT levels in these two lines. In contrast, anti-miR-21 transfection could reverse invasion and metastasis, and PTEN and pAKT expressions induced by gemcitabine. Conclusions: MiR-21 upregulation induced by histone acetylation in the promoter zone is associated with chemoresistance to gemcitabine and enhanced malignant potential in pancreatic cancer cells.

Banjerdpongchai, Ratana;Khaw-on, Patompong 7537

https://doi.org/10.7314/APJCP.2013.14.12.7537 PDF KSCI

Background: Terpinen-4-ol, a monoterpene, is found as the main component of essential oil extracts from many plants. In this study apoptotic and autophagic types of cell death induced by terpinen-4-ol and associated mechanisms were investigated in human leukemic HL-60 cells. Materials and Methods: The cytotoxicity of human leukemic U937 and HL-60 cells was determined by MTT assay. Cytochrome c release, expression of Bax, Bcl-2, Bcl-xl and cleaved Bid were determined by Western blotting. Cell morphology was examined under a transmission electron microscope. LC3-I/II, ATG5 and Beclin-1 levels were detected by immunoblotting. Results: Terpinen-4-ol exhibited cytotoxicity to human leukemic HL-60 but not U937 cells. The apoptotic response to terpinen-4-ol in HL-60 cells was due to induction of cytochrome c release from mitochondria and cleavage of Bid protein after the stimulation of caspase-8. There was a slightly decrease of Bcl-xl protein level. The characteristic cell morphology of autophagic cell death was demonstrated with multiple autophagosomes in the cytoplasm. At the molecular level, the results from Western blot analysis showed that terpinen-4-ol significantly induced accumulation of LC3-I/II, ATG5 and Beclin-1, regulatory proteins required for autophagy in mammalian cells. Conclusions: Terpinen-4-ol induced-human leukemic HL-60 cell death was via both autophagy and apoptosis.

Gao, Ying;Huang, Yu-Bei;Liu, Xue-Ou;Chen, Chuan;Dai, Hong-Ji;Song, Feng-Ju;Wang, Jing;Chen, Ke-Xin;Wang, Yao-Gang 7543

https://doi.org/10.7314/APJCP.2013.14.12.7543 PDF KSCI

Objective: To evaluate associations between tea consumption, alcohol drinking and physical activity and breast cancer risk among Chinese females. Methods: Three English databases (PubMed, ScienceDirect and Wiley) and three Chinese databases (CNKI, WanFang and VIP) were independently searched by 2 reviewers up to December 2012, complemented by manual searches. The quality of included studies was assessed with the Newcastle-Ottawa Scale items. Random-effects models were used to estimate the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Potential publication bias was estimated through Egger's and Begg's tests. Heterogeneity between studies was evaluated with $I^2$ statistics. Results: Thirty-nine studies involving 13,204 breast cancer cases and 87,248 controls were identified. Compared with non-drinkers, regular tea drinkers had decreased risk (OR=0.79, 95%CIs: 0.65-0.95; $I^2$=84.9%; N=16). An inverse association was also found between regular physical activity and breast cancer risk (OR=0.73, 95%CIs: 0.63-0.85; $I^2$=77.3%; N=15). However, there was no significant association between alcohol drinking and breast cancer risk (OR=0.85, 95%CIs: 0.72-1.02; $I^2$=63.8%; N=26). Most of the results from the subgroup analysis were consistent with the main results. Conclusion: Tea consumption and physical activity are significantly associated with a decreased risk of breast cancer in Chinese females. However, alcohol drinking may not be associated with any elevation of risk.

Ma, Guo-Jian;Gu, Rong-Min;Zhu, Ming;Wen, Xu;Li, Jin-Tian;Zhang, Yuan-Ying;Zhang, Xiao-Mei;Chen, Sen-Qing 7551

https://doi.org/10.7314/APJCP.2013.14.12.7551 PDF KSCI

Tumor-associated microRNAs have been detected in serum or plasma, but whether plasma microRNA-21 (miR-21) could be a potential circulating biomarker for gastric cancer (GC) prognosis in Chinese is still uncertain. Real-time quantitative reverse transcription PCR (qRT-PCR) was employed in this study to compare the relative expression of miR-21 between pre-operative and post-operative paired plasmas from 42 patients with primary GCs. The results showed that the expression levels of miR-21 in the post-operative plasmas were significantly reduced by an average of 18.2 times in all patients when compared to the pre-operative plasmas, and by 22.1 times in the subgroup of patients without family history, while only 1.76 times in the subgroup of patients with a family history. With respect of clinicopathological characteristics, the plasma miR-21 expression was highly associated with differentiation degree and lymph node metastasis rate. The results suggested plasma miR-21 could be a novel potential biomarker for GC prognosis and evaluation of surgery outcomes, especially in patients without a family history.

Sundaramoorthy, Rajiv;Srinivasan, Vasanth;Gujar, Jidnyasa;Sen, Ayantika;Sekar, Nishu;Abilash, Valsala Gopalakrishnan 7555

https://doi.org/10.7314/APJCP.2013.14.12.7555 PDF KSCI

Background: Beedi rollers are exposed to unburnt tobacco dust through cutaneous and pharyngeal route and it is extremely harmful to the body since it is carcinogenic in nature and can cause cancer during long exposure. This indicates that occupational exposure to tobacco imposes considerable genotoxicity among beedi workers. Materials and Methods: In the present study, 27 beedi workers and age and sex matched controls were enrolled for clinical, cytogenetics and molecular analysis. Clinical features were recorded. The workers were in the age group of 28-67 years and were workers exposure from 8-60 years. Blood samples were collected from workers and control subjects and lymphocyte cultures were carried out by using standard technique, slides were prepared and 50 metaphases were scored for each sample to find the chromosomal abnormalities. For molecular analysis the genomic DNA was extracted from peripheral blood, to screen the variations in gene, the exon 1 of CYP1A1 gene was amplified by polymerase chain reaction (PCR) and then screened with Single Strand Conformation Polymorphism (SSCP) analysis. Results: A statistically significant increase was observed in the frequencies of chromosomal aberrations in exposed groups when compared to the respective controls and variations observed in Exon 1 of CYP1A1(Cytochrome P450, family 1, subfamily A, polypeptide 1) gene. Conclusions: This study shows that, the toxicants present in the beedi that enter into human body causes disturbance to normal state and behavior of the chromosomes which results in reshuffling of hereditary material causing chromosomal aberrations and genomic variations.

Hossein, Ghamartaj;Keshavarz, Maryam;Ahmadi, Samira;Naderi, Nima 7561

https://doi.org/10.7314/APJCP.2013.14.12.7561 PDF KSCI

Galectin-3 (Gal-3) is a carbohydrate-binding protein which is thought to be involved in cancer progression but its contribution to epithelial ovarian cancer (EOC) remains unclear. The present study sought to determine the role of Gal-3 in chemoresistance of the human SKOV-3 ovarian cancer cell line to paclitaxel (PTX) using recombinant human Gal-3 (rhGal-3) and PectaSol-C modified citrus pectin (Pect-MCP) as a specific Gal-3 competitive inhibitor. Our results showed 41% increased cell proliferation, 36% decreased caspase-3 activity and 33.6% increased substrate-dependent adhesion in the presence of rhGal-3 compared to the control case (p<0.001). Treatment of cells with a non-effective dose of PTX (100nM) and 0.1% Pect-MCP in combination revealed synergistic cytotoxic effects with 75% reduced cell viability and subsequent 3.9-fold increase in caspase-3 activity. Moreover, there was 39% decrease in substrate-dependent adhesion compared to control (p<0.001). These results suggest that inhibition of Gal-3 could be a useful therapeutic tool for combination therapy of ovarian cancer.

Xiang, Li;Wang, Yan;Xu, Bing-Qing;Wu, Jing-Bo;Xia, Yun-Fei 7569

https://doi.org/10.7314/APJCP.2013.14.12.7569 PDF KSCI

Background: The purpose of this article is to present preliminary results of simultaneous boost irradiation radiotherapy for locally advanced nasopharyngeal carcinoma (NPC). Methods: Fifty-eight patients who underwent simultaneous boost irradiation radiotherapy for NPC in Cancer Center of Sun Yat-sen University between September 2004 and December 2009 were eligible. Acute and late toxicities were scored weekly according to the Radiation Therapy Oncology Group (RTOG) acute and late radiation morbidity scoring schemes. An especial focus was on evidence of post-radiation brain injury. Also quality of life was analysed according to the EORTC (European Organisation for Research and Treatment of Cancer) recommendations. Discrete variables were compared by ${\chi}^2$ test. The Kaplan-Meier method was used to calculate the survival rates and generate survival curves. Results: A total of 58 patients with a mean follow-up time of 36 months completed clinical trials.Fifty-seven patients (98.3) achieved complete remission in the primary sites and cervical lymph nodes, with only one patient (1.7%) showing partial remission.The most frequently observed acute toxicities during the concurrent chemoradiotherapy were mucositis and leucopenia. Four patients (6.9%) had RTOG grade 3 mucositis, whereas four patients (6.9%) had grade 3 leucopenia. No patient had grade 4 acute toxicity. Three (5.17%) of the patients exhibited injury to the brain on routine MRI examination, with a median observation of 32 months (range, 25-42months). All of them were RTOG grade 0. The 3-year overall, regional-free and distant metastasis-free survival rates were 85%, 94% and 91%, respectively. Conclusion: Simultaneous boost irradiation radiotherapy is feasible in patients with locally advanced nasopharyngeal carcinoma. The results showed excellent local control and overall survival, with no significant increase the incidence of radiation brain injury or the extent of damage. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.

Guo, Xu-Guang;Xia, Yong 7577

https://doi.org/10.7314/APJCP.2013.14.12.7577 PDF KSCI

The interleukin-18 promoter -607C>A gene polymorphism may be related to nasopharyngeal carcinoma (NPC) risk but the results of individual studies remain conflicting. A meta-analysis including 1,886 subjects from five individual studies was therefore performed to provide a more accurate estimation. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were evaluated by fixed- or random-effects models. A significant relationship between interleukin-18 promoter -607C>A gene polymorphism and NPC was found in a dominant genetic model (OR: 1.351, 95% CI: 1.089-1.676, P=0.006, $P_{heterogeneity}$=0.904), a homozygote model (OR: 1.338, 95% CI: 1.023-1.751, P=0.034, $P_{heterogeneity}$=0.863), and a heterozygote model (OR: 1.357, 95% CI: 1.080-1.704, P=0.009, $P_{heterogeneity}$=0.824). No significant association was detected in either an allelic genetic model (OR: 1.077, 95% CI: 0.960-1.207, 0.207, $P_{heterogeneity}$=0.844) or a recessive genetic model (OR: 1.093, 95% CI: 0.878-1.361, P=0.425, $P_{heterogeneity}$=0.707). In conclusion, a significant association was found between interleukin-18 promoter -607C>A gene polymorphism and NPC risk. Individuals with the C allele of interleukin-18 promoter -607C>A gene polymorphism have a higher risk of NPC development.

Hartavi, Mustafa;Kurt, Ender;Oral, Barbaros;Olmez, Omer Fatih;Cubukcu, Erdem;Deligonul, Adem;Avci, Nilufer;Manavoglu, Osman 7583

https://doi.org/10.7314/APJCP.2013.14.12.7583 PDF KSCI

Background: Suppressor of cytokine signaling (SOCS)-1 acts as a key regulator of many cytokine signaling pathways and its abnormal expression has been identified in several human malignancies, suggesting potential roles in carcinogenesis. The aim of this study was to investigate any association between the functional SOCS-1 -1478CA>del polymorphism and colorectal cancer (CC) as well as age at onset in a Turkish clinical sample. Materials and Methods: A total of 122 subjects were enrolled in this case-control study (70 CC cases and 52 controls). The SOCS-1 -1478CA>del polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The odds ratio of the del allele for CC relative to the CA allele was not significantly different between the groups (OR=0.71, 95% CI=0.41-1.22, p=0.27). This result did not change after adjustment for age and sex on multivariable regression analysis (OR=0.84, 95% CI=0.59-1.34, p=0.53). When the SOCS-1 -1478CA>del polymorphism was analyzed among CC patients in relation to the age at disease onset, we found no significant differences between subjects with the del/del, CA/del, and CA/CA genotypes. Conclusions: The results of our study did not point towards a major role of the SOCS-1 -1478CA>del polymorphism in the pathogenesis of CC in Turkish subjects.

Atrkar-Roushan, Zahra;Kazemnejad, Anoshirvan;Mansour-Ghanaei, Fariborz;Zayeri, Farid 7587

https://doi.org/10.7314/APJCP.2013.14.12.7587 PDF KSCI

Background: Cancers of gastric and esophagus are the most frequent gastrointestinal (GI) tract cancers in Iran. This study aimed to analyze time trends of GI tract cancers in Guilan province by gender and age to provide solid scientific evidence for cancer prevention and control. Materials and Methods: The data were obtained from the Guilan Cancer Registry System and Guilan Provincial Health Center, over the 15 year period between 1997 and 2011. Crude incidence and age standardized (AS)incidence rates were calculated and annual percent change was estimated by Joinpoint software for long term trend analysis. Results: During the study period, 8,332 cases of GI malignances with a male to female ratio of 1:1.73 were registered in Guilan province. The AS rates for esophageal, gastric, colon and rectal cancers were 5.97, 14.5, 7.59 and 3.58 per 105 respectively. While the trend was declining and relatively constant for esophageal and gastric cancer, respectively, the incidence trend for colon and rectal cancers was of increase over the period of the study. Conclusions: The results indicated that the incidence of GI cancers was relatively low in Guilan province compared to neighboring provinces. An effective cancer control program including prevention measures, early detection and effective treatment needs to be implemented to reduce cancer morbidity and mortality.

Zhang, Bin;Zhou, Ai-Fen;Zhu, Chang-Cai;Zhang, Ling;Xiang, Bing;Chen, Zhong;Hu, Rong-Hua;Zhang, Ya-Qi;Qiu, Lin;Zhang, Yi-Ming;Xiong, Chao-Du;Du, Yu-Kai;Shi, Yu-Qin 7595

https://doi.org/10.7314/APJCP.2013.14.12.7595 PDF KSCI

Cervical cancer is a serious public health problem in developing countries. We investigated possible risk factors for cervical cancer in rural areas of Wuhan China using a matched case-control study with 33 women diagnosed with cervical cancer and 132 healthy women selected from the same area as matched controls. A questionnaire, which included questions about general demography conditions, environmental and genetic factors, the first sexual intercourse, first marriage age, age at first pregnancy, pregnancy first child's age, female personal health history, social psychological factors, dietary habits, smoking and alcohol status and other living habits was presented to all participants. At the same time, HPV infection of every participant was examined in laboratory testing. Results showed HPV infection (P<0.000, OR=23.4) and pregnancy first child's age (P<0.000, OR=13.1) to be risk factors for cervical cancer. Menopause (P=0.003, OR=0.073) was a protective factor against cervical cancer. However, there was no indication of associations of environmental (drinking water, insecticide, disinfectant) genetic (cancer family history), or life-style factors (smoking status, alcohol status, physical training, sleep quality), including dietary habits (intake of fruit and vegetable, meat, fried food, bean products and pickled food) or social psychological factors with cervical cancer. The results suggest that the risk of cervical cancer in Chinese rural women may be associated with HPV infection, menopause and the pregnancy first child's age.

Zhou, Jing;Luo, Yan-Hong;Wang, Ji-Rong;Lu, Bin-Bin;Wang, Ke-Ming;Tian, Ye 7601

https://doi.org/10.7314/APJCP.2013.14.12.7601 PDF KSCI

Background: Gambogenic acid is a major active compound of gamboge which exudes from the Garcinia hanburyi tree. Gambogenic acid anti-cancer activity in vitro has been reported in several studies, including an A549 nude mouse model. However, the mechanisms of action remain unclear. Methods: We used nude mouse models to detect the effect of gambogenic acid on breast tumors, analyzing expression of apoptosis-related proteins in vivo by Western blotting. Effects on cell proliferation, apoptosis and apoptosis-related proteins in MDA-MB-231 cells were detected by MTT, flow cytometry and Western blotting. Inhibitors of caspase-3,-8,-9 were also used to detect effects on caspase family members. Results: We found that gambogenic acid suppressed breast tumor growth in vivo, in association with increased expression of Fas and cleaved caspase-3,-8,-9 and bax, as well as decrease in the anti-apoptotic protein bcl-2. Gambogenic acid inhibited cell proliferation and induced cell apoptosis in a concentration-dependent manner. Conclusion: Our observations suggested that Gambogenic acid suppressed breast cancer MDA-MB-231 cell growth by mediating apoptosis through death receptor and mitochondrial pathways in vivo and in vitro.

Nessa, Ashrafun;Nahar, Khadiza Nurun;Begum, Shirin Akhter;Anwary, Shahin Ara;Hossain, Fawzia;Nahar, Khairun 7607

https://doi.org/10.7314/APJCP.2013.14.12.7607 PDF KSCI

Background: Cervical cancer continues to be a major problem in Bangladesh with approximately 18,000 new cases annually of which over 10,000 women die from it. Visual inspection of the cervix after 3-5% acetic acid (VIA) application is a simple and easy to learn method for cervical cancer screening, although cytology-based screening is more often applied in developed countries where it has successfully reduced the prevalence of cervical cancer. Objective: To compare the efficacy of VIA and cytology-based primary methods for cervical cancer screening in Bangladesh. Materials and Methods: This hospital based comparative study was conducted at the VIA centre and Colposcopy Clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU) from October 2008 to October 2010. Results: Among 650 women, 74 (11.4%) were VIA+ve and 8 (1.2%) had abnormalities in their Pap smear reports. During colposcopy, 38 (7.7%) women had different grades of CIN and 4 (0.6%) had cervical cancer. The gold standard histology findings proved 20 women had CIN I, 14 had CIN II/II and 4 had cervical cancer. Among the 38 histology diagnosed abnormalities, VIA test could identify 30 abnormalities including two cervical cancers. However, Pap smear could detect only 8 cases of histological abnormalities (2 low grade and 6 had high grade lesion) and it missed all the cervical cancer cases. The sensitivity and specificity of VIA were 88.9% and 52.1%. The positive predictive value (PPV) and negative predictive value (NPV) were 41.0%, and 92.6% respectively. Moreover, the sensitivity, specificity, PPV and NPV of Pap smear were 33.3%, 95.8%, 75.0% and 79.3%, respectively. Conclusions: VIA test should be used as the primary screening tool even with its low sensitivity and specificity in low resource countries like Bangladesh. False positive results may be greater, but overtreatment can be minimized by colposcopy evaluation of the VIA positive women.

Chen, Yao-Sheng;Xu, Song-Xin;Ding, Yan-Bing;Huang, Xin-En;Deng, Bin 7613

https://doi.org/10.7314/APJCP.2013.14.12.7613 PDF KSCI

Background and Aims: Helicobacter pylori infection may be associated with an increased risk of colorectal carcinoma. However, as most studies on this subject were relatively small in size and differed at least partially in their designs, their results remain controversial. In this study, we aimed to carry out a meta-analysis to evaluate the potential association of H. pylori infection with colorectal adenoma and adenocarcinoma risk, covering all of the different testing methods. Methods: We conducted a search in PubMed, Medline, EBSCO, High Wire Press, OVID, and EMBASE covering all published papers up to March 2013. According to the established inclusion criteria, essential data were then extracted from the included studies and further analyzed by a systematic meta-analysis. Odds ratios were employed to evaluate the relationship between H. pylori infection and the risk of colorectal neoplasms. Results: Twenty-two studies were included, and the odds ratio for the association between H. pylori infection and colorectal cancer was 1.49 (95% confidence interval 1.30-1.72). No statistically significant heterogeneity was observed. Publication bias was ruled out. Conclusion: The pooled data suggest H. pylori infection indeed increases the risk of colorectal adenoma and adenocarcinoma.

Pazhoomand, Reza;Keyhan, Elahe;Banan, Mehdi;Najmabad, Hossein;Karimlou, Masoud;Khodadad, Faranak;Iraniparast, Alireza;Feiz, Farnaz;Majidzadeh, Keivan;Bahman, Ideh;Moghadam, Fatemeh Aghakhani;Sobhani, Atoosa Madadkar;Abedin, Seyedeh Sedigheh;Muhammadnejad, Ahad;Behjat, Farkhondeh 7621

https://doi.org/10.7314/APJCP.2013.14.12.7621 PDF KSCI

Human epidermal growth factor receptor (HER) status is an important prognostic factor in breast cancer. There is no globally accepted method for determining its status, and which method is most precise is still a matter of debate. We here analyzed HER2 mRNA expression by quantitative reverse transcription-PCR (qRT-PCR) and HER2 DNA amplification using multiplex ligation-dependent probe amplification (MLPA). In parallel, we performed a routine evaluation of HER2 protein by immunohistochemistry (IHC). To assess the accuracy of the RT-PCR and MLPA techniques, a combination of IHC and fluorescence in situ hybridization (FISH) was used, substituting FISH when the results of IHC were ambiguous (2+) and for those IHC results that disagreed with MLPA and qRT-PCR, this approach being termed IHC-FISH. The IHC results for four samples were not compatible with the MLPA and qRT-PCR results; the MLPA and qRT-PCR results for these samples were confirmed by FISH. The correlations between IHC-FISH and qRT-PCR or MLPA were 0.945 and 0.973, respectively. The ASCO/CAP guideline IHC/FISH correlation with MLPA was (0.827) and with RT-PCR was (0.854). The correlations between the IHC results (0, 1+ as negative, and 3+ as positive) and qRT-PCR and MLPA techniques were 0.743 and 0.831, respectively. Given the shortcomings of IHC analysis and greater correlations between MLPA, qRT-PCR, and FISH methods than IHC analysis alone with each of these three methods, we propose that MLPA and real-time PCR are good alternatives to IHC. However a suitable cut-off point for qRTPCR is a prerequisite for determining the exact status of HER2.

Verim, Aysegul;Ozkan, Nazli;Turan, Saime;Korkmaz, Gurbet;Cacina, Canan;Yaylim, Ilhan;Isbir, Turgay 7629

https://doi.org/10.7314/APJCP.2013.14.12.7629 PDF KSCI

Background: Cylin D1(CCDN1) is an important regulator of the cell cycle whose alterations are thought to be involved in cancer development. There have been many studies indicating CCDN1 amplification or over-expression in a variety of cancer types. In addition to gene amplification, the G870A polymorphism may be related with altered CCDN1 activity, and therefore with cancer development. This hypothesis has been tested in different cancer types but results have been contradictory. We therefore aimed to investigate any relationship between CCDN1 A870G genotypes and laryngeal squamous cell cancer development and progression. Materials and Methods: A total of 68 Turkish patients with primary laryngeal squamous cell cancer and 133 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the CCDN1 genotypes. Results: No significant association was detected between CCDN1 genotypes and laryngeal squamous cell cancer (LxSCCa) development. Similarly CCDN1 genotypes were not related to clinical parameters of Lx SCCa. However, there was a very significant association between CCDN1 G allele and presence of perineural invasion (p=0.003; OR: 1.464; CI% 1.073-1.999). CCDN1 G allele frequency was significantly higher in the individuals with perineural invasion (85.7%) when compared to those without (58.5%). The 2 patients who died of disease were both found to possess the GG genotype. Conclusions: These results pose a controversy in suggesting a protective role of the G allele against LxSCCa development and support the association of CCDN1 gene GG genotype with mortality in patients with LxSCCa.

Baser, Eralp;Togrul, Cihan;Ozgu, Emre;Ayhan, Sevgi;Caglar, Mete;Erkaya, Salim;Gungor, Tayfun 7635

https://doi.org/10.7314/APJCP.2013.14.12.7635 PDF KSCI

Background: Sperm-associated antigen 9 (SPAG9) has been recently proposed as a novel biomarker for early diagnosis of several human tumors, including ovarian, cervical and breast cancers. Its clinical value remains to be clarified for endometrial cancer (EC). In this study, we investigated the utility of serum SPAG9 levels in diagnosis of EC and its association with important clinicopathological parameters. Materials and Methods: This cross-sectional study was performed at a tertiary women's referral center in Ankara, Turkey. Preoperative serum samples were collected from patients surgically treated for endometrial cancer between June 2012-April 2013. Similar aged women with a biopsy proven benign endometrium were used as controls. Serum SPAG9 levels were measured with an enzyme-linked immunosorbent assay (ELISA) method and assessed for links with clinicopathological factors. Receiver operating characteristic (ROC) curve analysis was performed to assess power of SPAG9 levels for EC prediction. P values less than 0.05 were considered statistically significant. Results: A total of 63 women with EC and 27 with benign endometrium were included in the study. Mean age in the EC group was $58.7{\pm}1.1$. Median SPAG9 levels in the EC and control groups were 18.3 (range, 12.7-53.8) and 14.1 (range, 4.3-65.3), respectively (p<0.001). A cut-off value of 17 ng/ml for SPAG9 predicted presence of malignant endometrium with 74% sensitivity and 83% specificity [Area under curve (AUC)=0.82, p<0.001]. SPAG9 levels did not demonstrate any significant association with histological type, FIGO stage, tumor grade, size, myometrial invasion, lymphovascular space invasion, cervical involvement, adnexal involvement, peritoneal cytology or lymph node status (all p>0.05). Conclusions: Testing for SPAG9 may be useful for early detection of EC in asymptomatic high-risk women. Its role in post-treatment follow-up and early detection of recurrence should be assessed in future trials.

Vithana, Palatiyana Vithanage Sajeewanie Chiranthika;Hemachandra, Nilmini Nilangani;Ariyaratne, Yasantha;Jayawardana, Pushpa Lalani 7639

https://doi.org/10.7314/APJCP.2013.14.12.7639 PDF KSCI

Background: Breast cancer is the most common cancer diagnosed among women in Sri Lanka. Early detection can lead to reduction in morbidity and mortality. The objective here was to identify perceptions of public health midwives (PHMs) on the importance of early detection of breast cancer and deficiencies of and suggestions on improving existing breast cancer early detection services provided through Well Woman Clinics. Materials and Methods: A qualitative study using four focus group discussions (FGDs) were conducted among 38 PHMs in the Gampaha district in Sri Lanka and the meetings were audio-recorded, transcribed and analyzed using constant comparison and identifying themes and categories. Results: All the PHMs had a firm realization on the need of breast cancer early detection. The four FGDs among PHMs revealed non-availability of guidelines, inadequacy of training, lack of skills and material to provide health education, inability to provide privacy during clinical examination, shortage of stationery, lack of community awareness and motivation. The suggestions for the improvements of the programme identified in FGDs were capacity building of PHMs, making availability of guidelines, rescheduling clinics, improving the supervision, strengthening the monitoring, improving coordination between clinical and preventive sectors, and improving community awareness. Conclusions: Results of the FGDs can provide useful information on components to be improved in breast cancer early detection services. Study recommendations were training programmes at basic and post basic levels on a regular basis and supervision for the sustainance of the breast cancer early detection program.

Engin, Huseyin;Bilir, Cemil;Tekin, Ishak Ozel 7645

https://doi.org/10.7314/APJCP.2013.14.12.7645 PDF KSCI

Background: Immune functions and their relation to prognosis in breast cancer patients have become areas of great interest in recent years. Correlations between survival outcomes and peripheral blood flow cytometry parameters are therefore of interest. Here we focused on patients with non-metastatic breast cancer (BC). Materials and Methods: A total of 29 patients with pathological confirmed breast carcinoma and flow cytometry data were assessed for overall survival (OS) and progression free survival (PFS). Results: The median age of the patients was 54 years (range, 29-83). Multivariate analysis revealed that OS was significantly associated with absolute cytotoxic T cell count (95%CI, coef 2.26, p=0.035), tumor size (95%CI, coef -14.5, p 0.004), chemotherapy (95%CI, coef 12.9, p 0.0001), MFI of CD4 (95%CI, coef -5.1, P 0.04), MFI of HLA DR (95%CI, coef -5.9, p 0.008) and tumor grade (95%CI, coef -13, P 0.049) with R-Sq(adj)=67%. Similar findings were obtained for PFS. Conclusions: OS and PFS were significantly associated with tumor grade, tumor size, chemotherapy, MFI of CD4, HLA DR and absolute cytotoxic T cell count. The study revealed that MFI of basic CD markers and absolute cytotoxic T cell number may be a prognostic factors in women with non-metastatic BC.

Keyhani, Elahe;Muhammadnejad, Ahad;Behjati, Farkhondeh;Sirati, Fereidoon;Khodadadi, Faranak;Karimlou, Masoud;Moghaddam, Fatemeh A.;Pazhoomand, Reza 7651

https://doi.org/10.7314/APJCP.2013.14.12.7651 PDF KSCI

Background: Breast cancer is the most common malignancy among women in both developed and developing countries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens the public health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimens poses a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumab in breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose a priority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumor angiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics (including simultaneous mutations of TP53 and HER-2 genes). Materials and Methods: Age, axillary lymph nodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined and correlations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathological characteristics were evaluated. Results: There were significant associations between simultaneous mutations of HER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2 subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than 50 years. Conclusions: Our results demonstrated that patients with simultaneous mutations of HER-2 and p53 genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligible for obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breast cancer for treatment with anti-angiogenic drugs in LMCs.

Chong, Vui Heng;Bakar, Suriawati;Sia, Rusanah;Lee, James;Kassim, Norhayati;Rajak, Lubna;Abdullah, Muhd Syafiq;Chong, Chee Fui 7657

https://doi.org/10.7314/APJCP.2013.14.12.7657 PDF KSCI

Background: This study concerns uptake and results of colorectal cancer (CRC) screening of government servant as part of the Health Screening Program that was conducted in Brunei Darussalam in 2009. Materials and Methods: Government servants above the age of 40 or with family history of CRC were screened with a single fecal occult blood test (FIT, immunohistochemistry). Among 11,576 eligible subjects, 7,360 (66.9%) returned their specimen. Subjects with positive family history of CRC (n=329) or polyps (n=135) were advised to attend clinics to arrange screening. All the subjects with positive FIT (n=142, 1.9%) were referred to the endoscopy unit for counselling for screening colonoscopy. Results: Overall only 17.7% of eligible subjects attended for screening; 54.9% (n=79/142) of positive FIT, 8.8% (n=29/329) of positive family history of CRC and none with history of polyps (n=0/135). Of these, only 54 patients (50.5%) agreed for colonoscopy, 52 (48.6%) declined as they were asymptomatic, and one was not offered (0.9%) due to his very young age. On screening colonoscopy, 12.9% (n=7) had advanced lesions including a sigmoid carcinoma in situ and six advanced polyps. The other findings included non advanced polyps (n=21), diverticular (n=11) and hemorrhoids (n=26). One patient who missed his screening colonoscopy appointment re-presented two years later and was diagnosed with advanced right sided CRC. All the advanced lesions were detected in patients with positive FIT, giving a yield of 20.5% for advanced lesions including cancers in the 5.1% FIT positive subjects. Conclusions: Our study showed screening for CRC even with a single FIT was effective. However, the uptake rate was poor with just over half of the patients agreeing to screening colonoscopy. Measures to increase public awareness are important. Since one limitation of our study was the relatively small sample size, larger studies should be conduced in future.

Andsoy, Isil Isik;Gul, Asiye;Sahin, Aysegul Oksay;Karabacak, Hanife 7663

https://doi.org/10.7314/APJCP.2013.14.12.7663 PDF KSCI

Background: Skin cancer is a global health problem that can be prevented by protective behavior promoted by nurses. In Turkey, only few studies have examined current knowledge of nurses related to skin cancer and to reveal their attitudes towards sun exposure and current protective behavior. Materials and Methods: This descriptive cross-sectional study was performed from March 11 to May 30, 2013 with a study sample of 310 nurses working in two state hospitals located in Karab$\ddot{u}$k and Safranbolu. Results: Mean age of the nurses was $30.3{\pm}6.89$ years and 96.1% of them had graduated with a Bachelor degree. The participants were predominantly female (n=284). Knowledge level about skin cancer was significantly higher for females compared to males. Conclusions: Nurses do not have sufficient knowledge about skin cancer and are not adequately protecting themselves from ultraviolet light, the primary risk factor for skin cancer. While they demonstrated a responsible attitude towards avoiding sunburn and the need for adequate sun protection, they do not fully appreciate the extent to which the sun can cause skin cancer and that they lack full understanding about the need to protect the skin from burning and to avoid long term sun exposure in Turkey.

Srisuttayasathien, Manasawee;Khemapech, Nipon 7669

https://doi.org/10.7314/APJCP.2013.14.12.7669 PDF KSCI

Background: The hypothesis that patients who primarily progress on two consecutive chemotherapy regimens without evidence of clinical benefit may opt for supportive care was investigated. The purpose was to determine the quality of life in recurrent ovarian cancer patients choosing to receive salvage chemotherapy in addition to supportive care or palliative care alone. A secondary objective was to evaluate factors that affect quality of life in ovarian cancer patients. Materials and Methods: A descriptive study was conducted in patients who had histological confirmed epithelial ovarian cancer and failed to respond to at least one regimen of chemotherapy, coming for treatment at the King Chulalongkorn Memorial Hospital in Bangkok, Thailand over a six-month period from August 2012-March 2013. Each patient was asked to complete the FACT-G and a general personal questionnaire. The median quality of life score was analyzed. The Mann Whitney U Test was used to compare the difference between salvage chemotherapy and palliative care groups, and the Kruskal Wallis was used to evaluate other variables. Results: Thirty-eight ovarian cancer patients were identified who failed to respond to chemotherapy. Of the 38, 30 chose salvage chemotherapy and eight palliative care for further treatment. By histology the carcimnomas were predominantly endometrioid subtype and poorly differentiated. The majority of patients in this study had FIGO stage III, and ECOG status 0-1. The median quality of life score was 76.3 (35.8-94.0), with no significant differences between the groups. Factors associated with the quality of life were the ECOG score and number of chemotherapeutic courses. Conclusions: In the setting of refractory or recurrent epithelial ovarian cancer, patients who receive salvage chemotherapy have comparable quality of life scores with patients treated with palliative care alone, providing a contrast with previous studies.

Chittmittrapap, Salyavit;Chieochansin, Thaweesak;Chaiteerakij, Roongruedee;Treeprasertsuk, Sombat;Klaikaew, Naruemon;Tangkijvanich, Pisit;Komolmit, Piyawat;Poovorawan, Yong 7675

https://doi.org/10.7314/APJCP.2013.14.12.7675 PDF KSCI

Background: A missense mutation in exon 7 (R249S) of the p53 tumor suppressor gene is characteristic of aflatoxin B1 (AFB1) exposure. AFB1 is believed to have a synergistic effect on hepatitis virus B (HBV) carcinogenesis. However, results of studies comparing R249S prevalence among patients are conflicting. The aim of this study was to determine the prevalence of the R249S mutation in hepatocellular carcinoma (HCC) patients with or without positive HBsAg. Materials and Methods: Paraffin embedded liver tissues were obtained from 124 HCC patients who underwent liver resection and liver biopsy in King Chulalongkorn Memorial Hospital. Restriction fragment length polymorphism (RFLP) was utilized to detect the R249S mutation. Positive results were confirmed by direct sequencing. Results: Sixty four (52%) patients were positive for HBsAg and 18 (15%) were anti-HCV positive. 12 specimens tested positive by RFLP. Ten HCC patients (8.1%) were confirmed to be R249S positive by Sanger sequencing (AGG to AGT). Out of these 10, six were HBsAg positive, and out of the remaining 4, two were anti-HCV positive. The R249S prevalence among HCC patients with positive HBsAg was 9.4% compared to 6.7% for HBsAg negative samples. Patients with the R249S mutation were younger ($55{\pm}10$ vs $60{\pm}13$ year-old) and tended to have a more advanced Edmonson-Steiner grade of HCC, although differences did not reach statistical significance. Conclusions: Our study shows moderate prevalence of aflatoxin B1-related p53 mutation (R249S) in HCC with or without HBsAg. HBsAg positive status was not associated with R249S prevalence.

Tuncel, Tolga;Karagoz, Bulent;Haholu, Aptullah;Ozgun, Alpaslan;Emirzeoglu, Levent;Bilgi, Oguz;Kandemir, Emin Gokhan 7681

https://doi.org/10.7314/APJCP.2013.14.12.7681 PDF KSCI

Background: Human leukocyte antigen (HLA)-G-positive gastric cancers are associated with poor survival, but links with tumor escape mechanisms remain to be determined. Materials and Methods: We used immunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52 gastric cancer patients. Results: There were 29 cancer-related deaths during the follow-up period. Kaplan-Meier analysis indicated that patients with HLA-G-positive (n=16) primary tumors had a significantly poorer prognosis than patients with HLA-G-negative tumors (n=36, p=0.008). The median survival time was 14 months and 47 months, respectively. Patients with high numbers of Tregs and low numbers of CD8+T lymphocytes in the primary tumor had a poorer prognosis than those with low numbers of Tregs and high numbers of CD8+T lymphocytes (p=0.034, p=0.043). Multivariate Cox proportional hazard regression analysis showed that HLA-G expression (hazard ratio: 2.662; 95% confidence interval: 1.242-5.723; p=0.012) and stage (hazard ratio: 2.012;95% confidence interval: 1.112-3.715; p=0.041) were independent unfavorable factors for patient survival. Conclusions: We found a significant positive correlation between HLA-G expression and the number of tumor infiltrating Tregs (p=0.01) and a negative correlation with the number of CD8+T lymphocytes (p=0.041). HLA-G may protect gastric cancer cells from cytolysis by inducing Foxp3+Treg lymphocytes and suppressing CD8+T lymphocytes.

Choi, Kyung-Hyun;Park, Sang Min;Lee, Kiheon;Kim, Kyae Hyung;Park, Joo-Sung;Han, Seong Ho 7685

https://doi.org/10.7314/APJCP.2013.14.12.7685 PDF KSCI

Background: Management of hypertension and diabetes in cancer survivors is an important issue; however, not much is known about the level of management of such chronic disease in Korea. This study therefore assessed the prevalence, awareness, control, and treatment of hypertension and diabetes in Korean cancer survivors compared to non-cancer survivors. Materials and Methods: A cross-sectional design was employed, wherein data were obtained from standardized questionnaires completed by 943 cancer survivors and 41,233 non-cancer survivors who participated in the Fourth and Fifth Korea National Health and Nutrition Examination Surveys (2007-2011). We calculated adjusted proportions for prevalence and management of hypertension and diabetes in non-cancer survivors and cancer survivors. We also assessed the associated factors with prevalence and management of cancer survivors. Results: Cancer survivors are more likely than the general population to have higher prevalence, awareness, treatment, and control of hypertension. However, diabetic management was not significantly higher in cancer survivors than in non-cancer survivors, despite their having a higher prevalence. Several factors, such as, age, drinking, years since cancer diagnosis, self-perceived health status, and specific cancer types were found to affect to management of hypertension and diabetes. Conclusions: These data suggest that cancer survivors appear to be better than non-cancer survivors at management of hypertension, but not diabetes. There is a need for healthcare providers to recognize the importance of long-term chronic disease management for cancer survivors and for the care model to be shared between primary care physicians and oncologists.

Baskaran, Pryma;Subramanian, Pathmawathi;Rahman, Rasnah Abdul;Ping, Wong Li;Taib, Nur Aishah Mohd;Rosli, Roshaslina 7693

https://doi.org/10.7314/APJCP.2013.14.12.7693 PDF KSCI

Aims: A main reason for increasing incidence of cervical cancer worldwide is the lack of regular cervical cancer screening. Coverage and uptake remain major challenges and it is crucial to determine the perceived susceptibility to cervical cancer, as well as the benefits of, and barriers to, cervical cancer screening among women. Materials and Methods: A cross-sectional survey was conducted among 369 women attending an outpatient centre in Malaysia and data were collected by administering a self-report questionnaire. Results: The majority of the participants (265, 71.8%) showed good level of perception of their susceptibility to cervical cancer. Almost all responded positively to four statements about the perceived benefits of cervical cancer screening (agree, 23.1% or strongly agree, 52.5%), whereas negative responses were received from most of the participants (agree, 29.9%or strongly agree, 14.6 %) about the eleven statements on perceived barriers. Significant associations were observed between age and perceived susceptibility($x^2$=9.030, p=0.029); between employment status (p<0.001) as well as ethnicity and perceived benefits (p<0.05 [P=0.003]); and between education and perceived barriers to cervical cancer screening (p<0.001). Conclusions: Perceived susceptibility, including knowledge levels and personal risk assessment, should be emphasized through education and awareness campaigns to improve uptake of cervical cancer screening in Malaysia.

Keat, Chan Huan;Ghani, Norazila Abdul 7701

https://doi.org/10.7314/APJCP.2013.14.12.7701 PDF KSCI

Background: In a prospective cohort study of antiemetic therapy conducted in Malaysia, a total of 94 patients received low emetogenic chemotherapy (LEC) with or without granisetron injections as the primary prophylaxis for chemotherapy-induced nausea and vomiting (CINV). This study is a retrospective cost analysis of two antiemetic regimens from the payer perspective. Materials and Methods: This cost evaluation refers to 2011, the year in which the observation was conducted. Direct costs incurred by hospitals including the drug acquisition, materials and time spent for clinical activities from prescribing to dispensing of home medications were evaluated (MYR 1=$0.32 USD). As reported to be significantly different between two regimens (96.1% vs 81.0%; p=0.017), the complete response rate of acute emesis which was defined as a patient successfully treated without any emesis episode within 24 hours after LEC was used as the main indicator for effectiveness. Results: Antiemetic drug acquisition cost per patient was 40.7 times higher for the granisetron-based regimen than for the standard regimen (MYR 64.3 vs 1.58). When both the costs for materials and clinical activities were included, the total cost per patient was 8.68 times higher for the granisetron-based regimen (MYR 73.5 vs 8.47). Considering the complete response rates, the mean cost per successfully treated patient in granisetron group was 7.31 times higher (MYR 76.5 vs 10.5). The incremental cost-effectiveness ratio (ICER) with granisetron-based regimen, relative to the standard regimen, was MYR 430.7. It was found to be most sensitive to the change of antiemetic effects of granisetron-based regimen. Conclusions: While providing a better efficacy in acute emesis control, the low incidence of acute emesis and high ICER makes use of granisetron as primary prophylaxis in LEC controversial.

Gucuk, Sebahat;Uyeturk, Ummugul 7707

https://doi.org/10.7314/APJCP.2013.14.12.7707 PDF KSCI

Aims: To evaluate breast self examination (BSE) practice and the effect of a training program conducted by healthcare professionals on BSE. Materials and Methods: Women were randomized into control and test groups with both groups completing a questionnaire and three independent interviews where their BSE practices were evaluated. Results: In all, 39.5% of the participants were previously provided information on BSE by healthcare professionals while 25.8% had no knowledge of BSE prior to enrollment. Compared to those informed about BSE through other means such as television, radio, and the internet, the scores of the first, second, and third visits were higher (p<0.05) in individuals who received BSE education from healthcare professionals and hospitals. Conclusions: BSE training provided by healthcare professionals may increase early breast cancer diagnosis and treatment rates by improving BSE awareness and practice.

Lan, Vo Thi Thuong;Thuan, Ta Bich;Thu, Doan Minh;Uyen, Nguyen Quynh;Ha, Ngo Thi;To, Ta Van 7713

https://doi.org/10.7314/APJCP.2013.14.12.7713 PDF KSCI

DNA methylation is considered a promising biomarkers for diagnosis of cancer in general and of ovarian cancer in particular. In our study, we validated the accuracy of methylation specific polymerase chain reaction (MSP) to analyze the methylation pattern of BRCA1, RASSF1A and ER in 59 and 10 Vietnamese patients with epithelial ovarian cancer (EOC) and benign ovarian tumors, respectively. We found methylation of BRCA1, RASSF1A and ER in 11/59 (18.6%), 40/59 (67.8%) and 15/59 (25.4%) of EOC cases, while methylation of BRCA1 was only detected in 2/10 (20%) benign ovarian patients. Forty five out of the 59 EOCs (78%) demonstrated methylation at one or more genes. The methylation frequency of RASSF1A was significantly associated with EOC (p<0.0005). No significant association was observed between methylation status of these genes and the clinical and pathological parameters of tumors collected from Vietnamese women suffering from ovarian cancer.

Karami, Hadi;Baradaran, Behzad;Esfahani, Ali;Estiar, Mehrdad Asghari;Naghavi-Behzad, Mohammad;Sakhinia, Masoud;Sakhinia, Ebrahim 7719

https://doi.org/10.7314/APJCP.2013.14.12.7719 PDF KSCI

Background: Overexpression of survivin, a known inhibitor of apoptosis, is associated with tumor progression and drug resistance in numerous malignancies, including leukemias. The aim of this study was to investigate the effect of a specific survivin small interference RNA (siRNA) on proliferation and the sensitivity of HL-60 acute myeloid leukemia (AML) cells to the chemotherapeutic drug etoposide. Materials and Methods: The cells were transfected with siRNAs using Lipofectamine $^{TM}2000$ transfection reagent. Relative survivin mRNA and protein levels were measured by quantitative real-time PCR and Western blotting, respectively. Trypan blue exclusion assays were performed to monitor tumor cell proliferation after siRNA transfection. The cytotoxic effects of etoposide and survivin siRNA, alone and in combination, on leukemic cells were determined using MTT assay. Apoptosis was assessed by ELISA cell death assay. Results: Survivin siRNA markedly reduced both mRNA and protein expression levels in a time-dependent manner, leading to distinct inhibition of cell proliferation and increased spontaneous apoptosis. Surprisingly, survivin siRNA synergistically increased the cell toxic effects of etoposide. Moreover, survivin down-regulation significantly enhanced its induction of apoptosis. Conclusions: Our study suggests that down-regulation of survivin by siRNA can trigger apoptosis and overcome drug resistance of leukemia cells. Therefore, survivin siRNA may be an effective adjuvant in AML chemotherapy.

Park, Eun Young;Lim, Min Kyung;Yang, Wonho;Yun, E Hwa;Oh, Jin-Kyoung;Jeong, Bo Yoon;Hong, Soon Yeoul;Lee, Do-Hoon;Tamplin, Steve 7725

https://doi.org/10.7314/APJCP.2013.14.12.7725 PDF KSCI

Objective: The purpose of this study was to evaluate secondhand smoke (SHS) exposure inside selected public places to provide basic data for the development and promotion of smoke-free policies. Methods: Between March and May 2009, an SHS exposure survey was conducted. $PM_{2.5}$ levels and air nicotine concentrations were measured in hospitals (n=5), government buildings (4), restaurants (10) and entertainment venues (10) in Seoul, Republic of Korea, using a common protocol. Field researchers completed an observational questionnaire to document evidence of active smoking (the smell of cigarette smoke, presence of cigarette butts and witnessing people smoking) and administered a questionnaire regarding building characteristics and smoking policy. Results: Indoor $PM_{2.5}$ levels and air nicotine concentrations were relatively higher in monitoring sites where smoking is not prohibited by law. Entertainment venues had the highest values of $PM_{2.5}$(${\mu}g/m^3$) and air nicotine concentration(${\mu}g/m^3$), which were 7.6 and 67.9 fold higher than those of hospitals, respectively, where the values were the lowest. When evidence of active smoking was present, the mean $PM_{2.5}$ level was 104.9 ${\mu}g/m^3$, i.e., more than 4-fold the level determined by the World Health Organization for 24-hr exposure (25 ${\mu}g/m^3$). Mean indoor air nicotine concentration at monitoring sites with evidence of active smoking was 59-fold higher than at sites without this evidence (2.94 ${\mu}g/m^3$ vs. 0.05 ${\mu}g/m^3$). The results were similar at all specific monitoring sites except restaurants, where mean indoor $PM_{2.5}$ levels did not differ at sites with and without active smoking evidence and indoor air nicotine concentrations were higher in sites without evidence of smoking. Conclusion: Nicotine was detected in most of our monitoring sites, including those where smoking is prohibited by law, such as hospitals, demonstrating that enforcement and compliance with current smoke-free policies in Korea is not adequate to protect against SHS exposure.

Boonlikit, Sarawan 7731

https://doi.org/10.7314/APJCP.2013.14.12.7731 PDF KSCI

Aim: To compare the agreement of screening breast mammography plus ultrasound and reviewed mammography alone in asymptomatic women. Materials and Methods: All breast imaging data were obtained for women who presented for routine medical checkup at National Cancer Institute (NCI), Thailand from January 2010 to June 2013. A radiologist performed masked interpretations of selected mammographic images retrieved from the computer imaging database. Previous mammography, ultrasound reports and clinical data were blinded before film re-interpretation. Kappa values were calculated to assess the agreement between BIRADS assessment category and BIRADS classification of density obtained from the mammography with ultrasound in imaging database and reviewed mammography alone. Results: Regarding BIRADS assessment category, concordance between the two interpretations were good. Observed agreement was 96.1%. There was moderate agreement in which the Kappa value was 0.58% (95%CI; 0.45, 0.87). The agreement of BI-RADS classification of density was substantial, with a Kappa value of 0.60 (95%CI; 0.54, 0.66). Different results were obtained when a subgroup of patients aged ${\geq}60$ years were analyzed. In women in this group, observed agreement was 97.6%. There was also substantial agreement in which the Kappa value was 0.74% (95%CI; 0.49, 0.98). Conclusions: The present study revealed that concordance between mammography plus ultrasound and reviewed mammography alone in asymptomatic women is good. However, there is just moderate agreement which can be enhanced if age-targeted breast imaging is performed. Substantial agreement can be achieved in women aged ${\geq}60$. Adjunctive breast ultrasound is less important in women in this group.

Romus, Ilhami;Triningsih, F.X. Ediati;Mangunsudirdjo, Sagiri;Harijadi, Ahmad 7737

https://doi.org/10.7314/APJCP.2013.14.12.7737 PDF KSCI

Background: Human papilloma virus infection is associated with genesis and malignant potential of cervical cancer. E6 and E7 oncogens are known to bind to p53 and retinoblastoma gene products, abrogating their functions as tumor suppressors, leading to an abnormal cell cycle machinery. Roles of the p53 homolog p63 have also been postulated, E6 expression leading to TAp63b degradation allowing anchorage independent growth. Molecular studies correlated with clinicopathological factors are important to determine prognosis and treatment strategies, but results have been controversial and need to be clarified. Aim: To investigate expression of p53 and p63 in cervical squamous cell carcinomas in correlation with age, FIGO staging, morphology, and cancer cell proliferation. Materials and Methods: Expression of p53 and p63 immunohistochemical staining in a total of 56 paraffin-embedded tissues of cervical squamous cell carcinomas from Dr. Sardjito General Hospital Indonesia, was evaluated for correlation with clinicopathological parameters. The Mann-Whitney test was used to compare the percentage of p53 and p63 expression with patient age, FIGO staging and morphology and to compare mean p53 and p63 expression. The Spearman correlation test was applied to correlate p53 and p63 expression with that of Ki-67. A p-value of <0.05 was considered statistically significant. Results: There were significant associations between p53 expression with age (p=0.019) and FIGO staging (p=0.026), but not with with morphology or Ki-67 expression. There were no links between p63 expression and age, morphology, FIGO staging or Ki-67. Conclusions: This study indicated that p53 has a prognostic value in cervical squamous cell carcinomas given the relation with FIGO staging.

Phungrassami, Temsak;Funsian, Amporn;Sriplung, Hutcha 7743

https://doi.org/10.7314/APJCP.2013.14.12.7743 PDF KSCI

Background: To study the pattern of patient load, personnel and equipment resources from 30-years experience in Southern Thailand. Materials and Methods: This retrospective study collected secondary data from the Division of Therapeutic Radiology and Oncology and the Songklanagarind Hospital Tumor Registry database, Faculty of Medicine, Prince of Songkla University, during the period of 1982-2012. Results: The number of new patients who had radiation treatment gradually increased from 121 in 1982 to 2,178 in 2011. Shortages of all kinds of personnel were demonstrated as compared to the recommendations, especially in radiotherapy technicians. In 2011, Southern Thailand, with two radiotherapy centers, had 0.44 megavoltage radiotherapy machines (cobalt or linear accelerator) per million of population. This number is suboptimal, but could be managed cost-effectively by prolonging machine operating times during personnel shortages. Conclusions: This study identified a discrepancy between workload and resources in one medical school radiotherapy center in Southern Thailand. This information is crucial for future strategic planning both regionally and nationally.

Mohammadi, Shooka;Sulaiman, Suhaina;Koon, Poh Bee;Amani, Reza;Hosseini, Seyed Mohammad 7749

https://doi.org/10.7314/APJCP.2013.14.12.7749 PDF KSCI

Nutritional status and dietary intake play a significant role in the prognosis of breast cancer and may modify the progression of disease. The aim of this study was to determine the influence of nutritional status on the quality of life of Iranian breast cancer survivors. Cross-sectional data were collected for 100 Iranian breast cancer survivors, aged 32 to 61 years, attending the oncology outpatient clinic at Golestan Hospital, Ahvaz, Iran. Nutritional status of subjects was assessed by anthropometric measurements, Patient-Generated Subjective Global Assessment (PG-SGA) and three non-consecutive 24-hour diet recalls. The European Organization of Research and Treatment of Cancer Quality of Life form (EORTC QLQ-C30) was used to assess quality of life. Ninety-four percent of the survivors were well-nourished, 6% were moderately malnourished or suspected of being malnourished while none were severely malnourished. Prevalence of overweight and obesity was 86%. Overall, participants had an inadequate intake of vitamin D, E, iron and magnesium according to dietary reference intake (DRI) recommendations. Survivors with better nutritional status had better functioning scales and experienced fewer clinical symptoms. It appears important to provide educational and nutritional screening programs to improve cancer survivor quality of life.

Mohammadzadeh, Niloofar;Safdari, Reza;Rahimi, Azin 7757

https://doi.org/10.7314/APJCP.2013.14.12.7757 PDF KSCI

Physicians, in order to study the causes of cancer, detect cancer earlier, prevent or determine the effectiveness of treatment, and specify the reasons for the treatment ineffectiveness, need to access accurate, comprehensive, and timely cancer data. The cancer care environment has become more complex because of the need for coordination and communication among health care professionals with different skills in a variety of roles and the existence of large amounts of data with various formats. The goals of health care systems in such a complex environment are correct health data management, providing appropriate information needs of users to enhance the integrity and quality of health care, timely access to accurate information and reducing medical errors. These roles in new systems with use of agents efficiently perform well. Because of the potential capability of agent systems to solve complex and dynamic health problems, health care system, in order to gain full advantage of E- health, steps must be taken to make use of this technology. Multi-agent systems have effective roles in health service quality improvement especially in telemedicine, emergency situations and management of chronic diseases such as cancer. In the design and implementation of agent based systems, planning items such as information confidentiality and privacy, architecture, communication standards, ethical and legal aspects, identification opportunities and barriers should be considered. It should be noted that usage of agent systems only with a technical view is associated with many problems such as lack of user acceptance. The aim of this commentary is to survey applications, opportunities and barriers of this new artificial intelligence tool for cancer care information as an approach to improve cancer care management.

Parashari, Aditya;Singh, Veena 7761

https://doi.org/10.7314/APJCP.2013.14.12.7761 PDF KSCI

Alternative strategies such as visual inspection of cervix with acetic acid, are real time, economical and easily implemented methods for cervical cancer screening. However, variable sensitivity and specificity have been observed in various community based studies. The possible reasons could include variation in man power training, light source used for visualization, and preparation of diluted (4-5%) acetic acid and its storage. A standardized protocol for training, teaching material (easy to understand in the local language) for trainees, supervision and reinforcement by intermittent and supplementary training to check the quality of their observation, a standard protocol for preparation dilute acetic acid and its storage and a standard good light source (equivalent to day light) are needed to minimize the variation in sensitivity and specificity of VIA in community settings.

Xie, Qiang;Wang, Shi-Cun 7763

https://doi.org/10.7314/APJCP.2013.14.12.7763 PDF KSCI

Asian Pacific Journal of Cancer Prevention

Domain

Aim & Scope

2017

2016

2015

2014

2013

2012

Volume 14 Issue 12