권호 표지

Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (APOCP)

  • Monthly
  • /
  • 1513-7368(pISSN)
  • /
  • 2476-762X(eISSN)

Domain

  • Health Sciences ＞ Development of Pharmaceutical

Aim & Scope

Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.

KSCI

Volume 15 Issue 11

  1. Li, Wang;Liu, Hong-Ying;Jia, Zi-Ru;Qiao, Pan-Pan;Pi, Xi-Tian;Chen, Jun;Deng, Lin-Hong 4377
    https://doi.org/10.7314/APJCP.2014.15.11.4377 PDF KSCI
    According to the World Health Organization (WHO), 1.37 million people died of lung cancer all around the world in 2008, occupying the first place in all cancer-related deaths. However, this number might be decreased if patients were detected earlier and treated appropriately. Unfortunately, traditional imaging techniques are not sufficiently satisfactory for early detection of lung cancer because of limitations. As one alternative, breath volatile organic compounds (VOCs) may reflect the biochemical status of the body and provide clues to some diseases including lung cancer at early stage. Early detection of lung cancer based on breath analysis is becoming more and more valued because it is non-invasive, sensitive, inexpensive and simple. In this review article, we analyze the limitations of traditional imaging techniques in the early detection of lung cancer, illustrate possible mechanisms of the production of VOCs in cancerous cells, present evidence that supports the detection of such disease using breath analysis, and summarize the advances in the study of E-noses based on gas sensitive sensors. In conclusion, the analysis of breath VOCs is a better choice for the early detection of lung cancer compared to imaging techniques. We recommend a more comprehensive technique that integrates the analysis of VOCs and non-VOCs in breath. In addition, VOCs in urine may also be a trend in research on the early detection of lung cancer.
  2. Sultana, Sabira;Asif, Hafiz Muhammad;Nazar, Hafiz Muhammad Irfan;Akhtar, Naveed;Rehman, Jalil Ur.;Rehman, Riaz Ur. 4385
    https://doi.org/10.7314/APJCP.2014.15.11.4385 PDF KSCI
    Cancer is the most deadly disease that causes the serious health problems, physical disabilities, mortalities, and morbidities around the world. It is the second leading cause of death all over the world. Although great advancement have been made in the treatment of cancer progression, still significant deficiencies and room for improvement remain. Chemotherapy produced a number of undesired and toxic side effects. Natural therapies, such as the use of plant-derived products in the treatment of cancer, may reduce adverse and toxic side effects. However, many plants exist that have shown very promising anticancer activities in vitro and in vivo but their active anticancer principle have yet to be evaluated. Combined efforts of botanist, pharmacologist and chemists are required to find new lead anticancer constituent to fight disease. This review will help researchers in the finding of new bioactive molecules as it will focus on various plants evaluated for anticancer properties in vitro and in vivo.
  3. Topcul, Mehmet;Cetin, Idil 4395
    https://doi.org/10.7314/APJCP.2014.15.11.4395 PDF KSCI
    Nowadays there are several limitations in cancer treatment. One of these is the use of conventional medicines which not only target cancer cells and thus also cause high toxicity precluding effective treatment. Recent elucidation of mechanisms that cause cancer has led to discovery of novel key molecules and pathways which have have become successful targets for the treatments that eliminate only cancer cells. These so-called targeted therapies offer new hope for millions of cancer patients, as briefly reveiwed here focusing on different types of agents, like PARP, CDK, tyrosine kinase, farnysyl transferase and proteasome inhibitors, monoclonal antibodies and antiangiogenic agents.
  4. Gupta, Rakesh Kumar;Patel, Amit Kumar;Shah, Niranjan;Choudhary, Arun Kumar;Jha, Uday Kant;Yadav, Uday Chandra;Gupta, Pavan Kumar;Pakuwal, Uttam 4405
    https://doi.org/10.7314/APJCP.2014.15.11.4405 PDF KSCI
    Reactive oxygen species (ROS), highly reactive molecules, are produced by living organisms as a result of normal cellular metabolism and environmental factors, and can damage nucleic acids and proteins, thereby altering their functions. The human body has several mechanisms to counteract oxidative stress by producing antioxidants. A shift in the balance between oxidants and antioxidants in favor of oxidants is termed as "oxidative stress". Paradoxically, there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known about the initial and direct regulation of signaling molecules by ROS, or what we term the "oxidative interface." This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases and PI3 kinase), ROS homeostasis, and antioxidant gene regulation (Ref-1 and Nrf-2). This review also deals with classification as well as mechanisms of formation of free radicals, examining their beneficial and deleterious effects on cellular activities and focusing on the potential role of antioxidants in preventing and repairing damage caused by oxidative stress. A discussion of the role of phytochemical antioxidants in oxidative stress, disease and the epigenome is included.
  5. Asif, Hafiz Muhammad;Sultana, Sabira;Akhtar, Naveed;Rehman, Jalil Ur.;Rehman, Riaz Ur. 4411
    https://doi.org/10.7314/APJCP.2014.15.11.4411 PDF KSCI
    Breast cancer is the most common cancer in females all over the world with approximately one million new cases each year as well as one of second leading causes of death among females. In Pakistan, the most frequently diagnosed cancer among females is also breast cancer, accounting for nearly one in nine female patients. Its incidence in Pakistan is 2.5 times higher than that in neighboring countries like Iran and India. The risk factors associated with breast cancer are age, family history, early menarche, intake of combined estrogen and progestin menopausal hormones, alcohol consumption, physical inactivity, low socioeconomic status and lack of awareness regarding the disease. This mini-review article aims to provide awareness about breast cancer as well as an updated knowledge about the prevalence, risk factors and disease knowledge of breast cancer in Pakistan.
  6. Huang, Li-Ming;Shi, Xi;Yan, Dan-Fang;Zheng, Min;Deng, Yu-Jie;Zeng, Wu-Cha;Liu, Chen;Lin, Xue-De 4417
    https://doi.org/10.7314/APJCP.2014.15.11.4417 PDF KSCI
    ERCC2 is an essential component of the nucleotide excision repair pathway which is involved in the effective maintenance of genome integrity. Association studies on ERCC2 polymorphisms and glioma risk have yielded inconclusive results. This meta-analysis was performed to gain a better insight into the relationship between ERCC2 polymorphisms and glioma risk. A systematic literature search updated to December 2, 2013 was performed in the Pubmed and EMBASE databases. Crude pooled odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were used to estimate the association between ERCC2 polymorphisms and glioma risk under a suitable effect model according to heterogeneity. All analyses were performed using Review Manager 5 (version 5.2) and STATA (version 12.0). The combined results demonstrated rs13181 to be significantly associated with glioma risk (G allele versus T allele: OR=1.15, 95% CI=1.05-1.26, P=0.002; dominant model: OR=1.22, 95% CI=1.07-1.39, P=0.002; recessive model: OR=1.18, 95% CI=0.98-1.41, P=0.070). We also found that rs13181 acts in an allele dose-dependent manner (GG versus TT: OR=1.30, 95% CI=1.07-1.57, P=0.009; TG versus TT: OR=1.20, 95%=CI 1.05-1.37, P=0.009; trend test, P=0.004). However, no evidence was found in analyses for the association between other 3 ERCC2 polymorphisms (rs238406, rs1799793, and rs1052555) and susceptibility to glioma development. Our meta-analysis suggests that rs13181 is significantly associated with glioma risk in an allele dose-dependent manner, whereas, 3 other ERCC2 polymorphisms (rs238406, rs1799793, and rs1052555) may have no influence.
  7. Xu, Heng;Tian, Yan-Na;Dun, Bo-Ying;Liu, Hai-Tao;Dong, Guang-Kuo;Wang, Jin-Hua;Lu, Shang-Su;Chen, Bo;She, Jin-Xiong 4423
    https://doi.org/10.7314/APJCP.2014.15.11.4423 PDF KSCI
    A novel monoclonal antibody (mAb), known as AC10364, was identified from an antibody library generated by immunization of mice with human carcinoma cells. The mAb recognized proteins in lysates from multiple carcinoma cell lines. Cell cytotoxicity assays showed that AC10364 significantly inhibited cell growth and induced apoptosis in multiple carcinoma cell lines, including Bel/fu, KATO-III and A2780. Compared with mAb AC10364 or chemotherapeutic drugs alone, the combination of mAb AC10364 with chemotherapeutic drugs demonstrated enhanced growth inhibitory effects on carcinoma cells. These results suggest that mAb AC10364 is a promising candidate for cancer therapy.
  8. Kruk, Joanna 4429
    https://doi.org/10.7314/APJCP.2014.15.11.4429 PDF KSCI
    Background: Although the nutritional may exert effect on the breast cancer risk, it is not clear whether the role diet is the same in sedentary and physically active women. The aim of this study was to evaluate the association between fruit, vegetable and carbohydrate intake and the risk of breast cancer among Polish women considering their physical activity level. Materials and Methods: A case-control study was conducted that included 858 women with histological confirmed breast cancer and 1,085 controls, free of any cancer diagnosis, aged 28-78 years. The study was based on a self-administered questionnaire to ascertain physical activity, dietary intake, sociodemographic characteristics, reproductive factors, family history of breast cancer, current weight and high, and other lifestyle factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in unconditional logistic regression analyses including a broad range of potential confounders. Results: With comparison of the highest vs lowest quartile of intake, strong significant associations were observed for total vegetables (OR=0.37, 95%CI=0.20-0.69 P for trend <0.01 and OR=0.53, 95%CI=0.29-0.96, P for trend <0.02), and total fruits (OR=0.47, 95%CI=0.25-0.87, P for trend <0.05 and OR=0.47, 95%CI=0.24-0.90, P for trend <0.02) among women characterized by the lowest and the highest quartile of physical activity. No associations were observed for total carbohydrate intake. Additional analysis showed a positive association for sweets and desert intake among women in the lowest quartile of physical activity (OR=3.49, 95%CI=1.67-7.30, P for trend <0.009) for extreme quartiles of intake comparing to the referent group. Conclusions: The results suggest that a higher consumption of vegetable and fruit may be associated with a decreased risk of breast cancer, especially among women who were low or most physically active throughout their lifetimes. These findings do not support an association between diet high in carbohydrate and breast cancer. However, a higher intake of sweets and deserts may by associated with an increased risk of breast cancer among women who were less physically active.
  9. Akbari, Zahra;Safari-Alighiarloo, Nahid;Haghighi, Mahdi Montazer;Vahedi, Mohsen;Mirtalebi, Hanieh;Azimzadeh, Pedram;Milanizadeh, Saman;Shemirani, Atena Irani;Nazemalhosseini-Mojarad, Ehsan;Aghdaei, Hamid Asadzadeh;Zali, Mohammad Reza 4437
    https://doi.org/10.7314/APJCP.2014.15.11.4437 PDF KSCI
    SMAD7 has been identified as a functional candidate gene for colorectal cancer (CRC). SMAD7 protein is a known antagonist of the transforming growth factor beta ($TGF-{\beta}$) signaling pathway which is involved in tumorigenesis. Polymorphisms in SMAD7 may thus alter cancer risk. The aim of this study was to investigate the influence of a SMAD7 gene polymorphism (rs2337107) on risk of CRC and clinicopathological features in an Iranian population. In total, 210 subjects including 105 patients with colorectal cancer and 105 healthy controls were recruited in our study. All samples were genotyped by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of colorectal cancer and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs2337107and the risk of colorectal cancer. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). Although there was not any association between genotypes and disorder, CT was the most common genotype in this population. This genotype prevalence was also higher in the patients with well grade (54.9%) and colon (72.0%) tumors. Our results provide the first evidence that this polymorphism is not a potential contributor to the risk of colorectal cancer and clinicopathological features in an Iranian population, and suggests the need of a large-scale case-control study to validate our results.
  10. Wang, Ya-Dong;Zhai, Wen-Long;Wang, Hai-Yu;Xia, Xiang-Qun 4443
    https://doi.org/10.7314/APJCP.2014.15.11.4443 PDF KSCI
    Background: A number of studies have reported the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with susceptibility to hepatocellular carcinoma (HCC). However, the results were inconsistent and inconclusive. The aim of this study was to comprehensively explore the association of XRCC1 Arg399Gln variant with HCC risk. Materials and Methods: Systematic searches of PubMed, Elsevier, Science Direct, CNKI and Chinese Biomedical Literature Database were performed. Pooled odds ratio (OR) with 95% confidence intervals (CI) was calculated to estimate the strength of association. Results: Overall, we observed an increased HCC risk among subjects carrying XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln genotypes (OR=1.20, 95%CI: 1.05-1.38, OR=1.16, 95%CI: 1.05-1.28, and OR=1.14, 95%CI: 1.04-1.24, respectively) based on 20 studies including 3374 cases and 4633 controls. In subgroup analysis, we observed an increased risk of XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln polymorphisms for HCC in hospital-based study (OR=1.25, 95%CI: 1.03-1.51, OR=1.21, 95%CI: 1.07-1.36 and OR=1.18, 95%CI: 1.06-1.31, respectively) and in Asian population (OR=1.19, 95%CI: 1.03-1.38, OR=1.17, 95%CI: 1.04-1.30 and OR=1.14, 95%CI: 1.04-1.25, respectively). Limiting the analysis to the studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased HCC risk among Gln/Gln, Arg/Gln and Gln/ Gln+Arg/Gln genotype carriers (OR=1.17, 95%CI: 1.05-1.29, OR=1.12, 95%CI: 1.00-1.25 and OR=1.11, 95%CI: 1.02-1.21, respectively). Conclusions: This updated meta-analysis results suggest that XRCC1 Arg399Gln variants may contribute to HCC risk. Well-designed studies with larger sample size were required to further verify our findings.
  11. Wang, Yin;Zhang, Fu-Cheng;Wang, Yao-Jun 4449
    https://doi.org/10.7314/APJCP.2014.15.11.4449 PDF KSCI
    Aim: Helicobacter pylori (H. pylori) have been considered as a risk factor for many cancers. We conducted this meta-analysis to clarify the association between H. pylori infection and the risk of pancreatic cancer. Methods: We searched the Medicine/Pubmed and Embase databases, studies about the association between H. pylori infection and pancreatic cancer published up to Jan.2014 were included. Finally, a total of 9 studies were used for this a meta-analysis. The odds ratios (ORs) and 95% confidence interval (95%CI) of H. pylori infection on pancreatic cancer with respect to control groups were evaluated. Two authors independently assessed the methodological quality and extracted data. This meta-analysis was conducted using software, state (version 12.0) to investigate heterogeneity among individual studies and to summarize the studies. Using the fixed-effects or random-effects model, depending on the absence or presence of significant heterogeneity. Sensitivity analysis was performed to assess the influence of each individual study on the pooled ORs by omitting a single study each time. Publication bias was evaluated by funnel plot, using Egger's and Begg's tests. Results: There was no significant association between H. pylori infection and pancreatic cancer risk in the summary ORs,(OR=1.06, 95%CI: 0.74-1.37) through the random-effect method, but heterogeneity among studies was significant ($I^2$=58.9%), so we put the studies into two subgraphs (eastern and western). The results about western (OR=1.14 95%CI:0.89, 1.40) showed heterogeneity among the western countries of $I^2$=6.6%, with no significant association between Hp+ and pancreatic cancer, but the eastern countries (OR=0.62, 95%CI:0.49, 0.76), $I^2$=0, suggested that decreasing pancreas-cancer risk in subjects with Hp+ infection. Simultaneously, 7 studies examined CagA+ strains was (OR=0.84 95%CI:0.63, 1.04), $I^2$=36% with the random-effect method, subgraphs indicated that CagA+ could decrease the risk of pancreatic cancer in the eastern subjects (OR=0.66, 95%CI:0.52-0.80), but the association was not statistically significant in the western subjects (OR=0.95, 95%CI:0.73, 1.16). Conclusion: Hp+ and CagA+ infection are associated with a decreased risk of pancreatic cancer in eastern populations but have no significant associations in western countries.
  12. Hejazi, Seyed Hesam;Ahangari, Ghasem;Pornour, Majid;Deezagi, Abdolkhaleagh;Aminzadeh, Saeed;Ahmadkhaniha, Hamid Reza;Akbari, Mohamad Esmail 4455
    https://doi.org/10.7314/APJCP.2014.15.11.4455 PDF KSCI
    Breast cancer is a serious and potentially lethal multi-factor disease among 40-50 aged women in both developed and developing countries. Also, various studies have pointed to roles of neurotransmitters like serotonin in development of cancers, through action on various types of receptors. This study was conducted to evaluate serotonin receptor (5HT2AR and 5HT3AR) genes expression in peripheral blood mononuclear cells (PBMCs) of breast cancer patients in comparison with the healthy people and in the MCF7 cell line. Peripheral blood samples were obtained from 30 patients and 30 healthy individuals. Total RNA was extracted from PBMCs and MCF-7 cells. and 5HT2AR and 5HT3AR were detected by RT-PCR techniques. Finally, serotonin receptor gene expression variation in breast cancer patients and MCF-7 cells were determined by real time-PCR. This latter indicated significant promotion in expression of 5HT3AR and 5HT2AR in PBMCs in breast cancer patients but expression of 5HT2AR in the MCF-7 cell line was significantly decreased. In conclusion, after performing complimentary tests, determine of gene expression changes in serotonin receptors (5HT2AR and 5HT3AR) may be useful as a new approach in treatment of breast cancer based on use of antagonists.
  13. Abebaw, Wubejig;Kibret, Mulugeta;Abera, Bayeh 4459
    https://doi.org/10.7314/APJCP.2014.15.11.4459 PDF KSCI
    Background: Gastric cancer is the second leading cause of cancer-related deaths worldwide and infection with H. pylori is considered essential for its development. Helicobacter pylori infects more than 50% of the world's population with higher prevalence in developing countries than developed countries. The prevalence of H. pylori varies in different societies and geographical locations. The objectives of this study were to estimate the seroprevalence and determine the risk factors of H. pylori infection in dyspeptic patents in Ethiopia. Materials and Methods: A cross-sectional study involving 209 dyspeptic patients was carried out from February 15 to April 30, 2013. Five to ten ml venous blood was collected from each dyspeptic patient and analyzed for detection of Helicobacter pylori immunoglobulin (IgG). The socio-demographic characteristic, hygienic practices, alcohol consumption, sources of drinking water and types of latrine were also obtained with a pre-tested questionnaire. Results: The overall seroprevalence of Helicobacter pylori was 72.2%. There was statistically significant difference in the prevalence of H. pylori among age groups (p=0.02). Seroprevalence of H. pylori was higher in those patients who used unprotected surface water (76.4%) than those with access to piped tap water (65.9%). There was also statistically significant differences in prevalence of H. pylori with the habit of hand washing before meal (p=0.01) and alcohol consumption (p=0.001). Conclusions: The prevalence of H. pylori was high in the study area and increased with age of dyspeptic patients. Alcohol consumption and the type of drinking water are risk factors that have associations with the prevalence of H. pylori. Molecular epidemiological techniques can show a true picture of H. pylori and improvement in the drinking water quality is recommended.
  14. Zhang, Li;Lin, Yong;Li, Jin-ke 4465
    https://doi.org/10.7314/APJCP.2014.15.11.4465 PDF KSCI
    HPV type-specific detection may promote cervical screening program and vaccination development worldwide. We conduct a study comparing HPV Hybrid capture II (HC II) Test and Hybribio GenoArray test, a newly developed HPV type-specific assay, in patients with cervical epithelial neoplasm. Results showed a good concordance in cervical HPV detection between two tests (kappa value 0.80, p<0.05, McNemar test). Our study may promote utilization of type-specific HPV detection that is helpful for cervical cancer screening and vaccination.
  15. Wang, Xu;Ling, Li;Su, Hong;Cheng, Jian;Jin, Liu 4467
    https://doi.org/10.7314/APJCP.2014.15.11.4467 PDF KSCI
    Background: We aimed to comprehensively review the evidence for using sputum DNA to detect non-small cell lung cancer (NSCLC). Materials and Methods: We searched PubMed, Science Direct, Web of Science, Chinese Biological Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang, Vip Databases and Google Scholar from 2003 to 2013. The meta-analysis was carried out using a random-effect model with sensitivity, specificity, diagnostic odd ratios (DOR), summary receiver operating characteristic curves (ROC curves), area under the curve (AUC), and 95% confidence intervals (CI) as effect measurements. Results: There were twenty-two studies meeting the inclusion criteria for the meta-analysis. Combined sensitivity and specificity were 0.62 (95%CI: 0.59-0.65) and 0.73 (95%CI: 0.70-0.75), respectively. The DOR was 10.3 (95%CI: 5.88-18.1) and the AUC was 0.78. Conclusions: The overall accuracy of the test was currently not strong enough for the detection of NSCLC for clinical application. Dscovery and evaluation of additional biomarkers with improved sensitivity and specificity from studies rated high quality deserve further attention.
  16. Ozfiliz, Pelin;Arisan, Elif Damla;Coker-Gurkan, Ajda;Obakan, Pinar;Eralp, Tugce Nur;Dinler-Doganay, Gizem;Palavan-Unsal, Narcin 4475
    https://doi.org/10.7314/APJCP.2014.15.11.4475 PDF KSCI
    Background: Cisplatin, a DNA damaging agent, induces apoptosis through increasing DNA fragmentation. However, identification of intrinsic resistance molecules against Cisplatin is vital to estimate the success of therapy. Bag-1 (Bcl-2-associated anthanogene) is one anti-apoptotic protein involved in drug resistance impacting on therapeutic efficiency. Elevated levels of this protein are related with increase cell proliferation rates, motility and also cancer development. For this reason, we aimed to understand the role of Bag-1 expression in Cisplatin-induced apoptosis in HeLa cervix cancer cells. Cisplatin decreased cell viability in time- and dose-dependent manner in wt and Bag-1L+HeLa cells. Although, $10{\mu}M$ Cisplatin treatment induced cell death within 24h by activating caspases in wt cells, Bag-1L stable transfection protected cells against Cisplatin treatment. To assess the potential protective role of Bag-1, we first checked the expression profile of interacting anti-apoptotic partners of Bag-1. We found that forced Bag-1L expression prevented Cisplatin-induced apoptosis through acting on Mcl-1 expression, which was reduced after Cisplatin treatment in wt HeLa cells. This mechanism was also supported by the regulation of heat shock protein (Hsp) family members, Hsp90 and Hsp40, which were involved in the regulation Bag-1 interactome including several anti-apoptotic Bcl-2 family members and c-Raf.
  17. Kumaran, Aswathy;Guruvare, Shyamala;Sharan, Krishna;Rai, Lavanya;Hebbar, Shripad 4483
    https://doi.org/10.7314/APJCP.2014.15.11.4483 PDF KSCI
    Purpose: To assess chemoradiation related acute morbidity in women with carcinoma cervix and to find and correlation between hematologic toxicity and organ system specific damage. Materials and Methods: A prospective study was carried out between August 2012 and July 2013 enrolling 79 women with cancer cervix receiving chemo-radiotherapy. Weekly assessment of acute morbidity was done using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 and the toxicities were graded. Results: Anemia [77 (97.5%)], vomiting [75 (94.8%)] and diarrhea [72 (91.1%)], leukopenia [11 (13.9%)], cystitis [28 (35.4%], dermatitis [19 (24.1%)] and fatigue [29 (36.71%)] were the acute toxicities noted. The toxicities were most severe in $3^{rd}$ and $5^{th}$ week. All women could complete radiotherapy except two due to causes unrelated to radiation morbidity; seven (8.86%) had to discontinue chemotherapy due to leukopenia and intractable diarrhea. Though there was no correlation between anemia and other toxicities, it was found that all with leukopenia had diarrhea. Conclusions: Chemoradiation for cancer cervix is on the whole well tolerated. Leukopenia and severe diarrhea were the acute toxicities that compelled discontinuation of chemotherapy in two women. Though anemia had no correlation with gastrointestinal toxicity, all of those with leukopenia had diarrhea.
  18. Zhang, Chun-Pu;Li, Hua-Qing;Zhang, Wei-Tao;Liu, Ming-Hui;Pan, Wen-Jing 4487
    https://doi.org/10.7314/APJCP.2014.15.11.4487 PDF KSCI
    Objective: To explore the clinical manifestations and imaging characteristics of gliomatosis cerebri to raise the awareness and improve its diagnostic accuracy for patients. Materials and Methods: Clinical data, imaging characteristics and pathological examination of 12 patients with GC from Jan., 2008 to Jan., 2012 were analyzed retrospectively. Results: Patients with GC were clinically manifested with headache, vomiting, repeated seizures, fatigue and unstable walking, most of whom had more than 2 lesions involving in parietal lobe, followed by temporal lobe, frontal lobe, periventricular white matter and corpus callosum. Magnetic resonance imaging (MRI) showed diffuse distribution, T1-weighted images (T1WI) with equal and low signals and T2-weighted images (T2WI) with bilateral symmetrical high diffuse signals. There was no reinforcement by enhancement scanning and signals were different in diffusion-weighted images (DWI). The higher the tumor staging, the stronger the signals. Pathological examination showed neuroastrocytoma in which tumor tissues were manifested by infiltrative growth in blood vessels and around neurons. Conclusions: In clinical diagnosis of GC, much attention should be paid to the diffuse distribution of imaging characteristics, incomplete matching between clinical and imaging characteristics and confirmation by combining with histopathological examination.
  19. Wang, Feng;Fang, Ping;Hou, Dan-Yang;Leng, Zai-Jun;Cao, Le-Jie 4493
    https://doi.org/10.7314/APJCP.2014.15.11.4493 PDF KSCI
    Background: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) can predict the clinical response to tyrosine kinase inhibitor (TKI) therapy. However, EGFR mutations may be different in primary tumors (PT) and metastatic lymph nodes (MLN). The aim of this study was to compare EGFR mutations between PT and the corresponding MLN in NSCLC patients, and provide some guidelines for clinical treatment using TKI therapy. Materials and Methods: A systematic review and meta-analysis was performed with several research databases. Relative risk (RR) with the 95% confidence interval (CI) were used to investigate the EGFR mutation status between PT and the corresponding MLN. A random-effects model was used. Results: 9 publications involving 707 patients were included in the analysis. It was found that activation of EGFR mutations identified in PT and the corresponding MLN was 26.4% (187/707) and 19.9% (141/707), respectively. The overall discordance rate in our meta-analysis was 12.2% (86/707). The relative risk (RR) for EGFR mutation in PT relative to MLN was 1.33 (95%CI: 1.10-1.60; random-effects model). There was no significant heterogeneity between the studies ($I^2$=5%, p=0.003). Conclusions: There exists a considerable degree of EGFR mutation discrepancy in NSCLC between PT and corresponding MLN, suggesting that tumor heterogeneity might arise at the molecular level during the process of metastasis.
  20. Haris, Khalilah;Ismail, Samhani;Idris, Zamzuri;Abdullah, Jafri Malin;Yusoff, Abdul Aziz Mohamed 4499
    https://doi.org/10.7314/APJCP.2014.15.11.4499 PDF KSCI
    Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with $58.6{\mu}g/ml$ for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.
  21. Sharma, Mousumi;Sharma, Jagannath Dev;Sarma, Anupam;Ahmed, Shiraj;Kataki, Amal Chandra;Saxena, Rahul;Sharma, Dilutpal 4507
    https://doi.org/10.7314/APJCP.2014.15.11.4507 PDF KSCI
    Background: Breast cancer is a heterogeneous disease comprising of distinct biological subtypes with many targeted prognostic biomarkers having therapeutic implications. However, no specific targeted therapy for triple negative breast cancer has been discovered to date and hence further research is needed. Aim: The aim and objectives of the present study were to examine the prevalence of triple negative breast cancer (TNBC) in North-East India and to compare the clinicopathological parameters in two study groups defined by immunohistochemistry (IHC) - "TNBC" and "Others". Materials and Methods: We carried out a retrospective study in a cohort of 972 patients diagnosed with invasive breast carcinoma in the Department of Pathology, Dr. B. Borooah Cancer Institute, a Regional Cancer Centre for treatment and research, Guwahati, for a period of 3 years and 10 months from January 2010 to October 2013. Based on IHC findings, patients were divided into two groups - "TNBC" and "Others". All relevant clinicopathological parameters were compared in both. TNBC were defined as those that were estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative while those positive for any of these markers were defined as "Others". Results: In this study, out of total 972 cases 31.9% (310 cases) were defined as TNBC and 662 cases (68.1%) as "Others" based on IHC markers. Compared to the "Others" category, TNBC presented at an early age (mean 40 years), were associated with high grade large tumours and high rate of node positivity, IDC NOS being the most common histological subtype in TNBC. Conclusions: TNBC accounts for a significant portion of breast cancers in this part of India and commonly present at younger age and tend to be large high grade tumours.
  22. Cao, Yu-Wen;Fu, Xin-Ge;Wan, Guo-Xing;Yu, Shi-Ying;Cui, Xiao-Bin;Li, Li;Jiang, Jin-Fang;Zheng, Yu-Qin;Zhang, Wen-Jie;Li, Feng 4513
    https://doi.org/10.7314/APJCP.2014.15.11.4513 PDF KSCI
    The prevalence of BRCA1 gene mutations in breast cancer differs between diverse ethnic groups. Relatively little information is known about patterns of BRCA1 mutations in early-onset breast cancer in women of Uighur or Han descent, the major ethnic populations of the Xinjiang region in China. The aim of this study was to identify BRCA1 mutations in Uighur and Han patients with early-onset (age <35 years), and sporadic breast cancer for genetic predisposition to breast cancer. For detection of BRCA1 mutations, we used a polymerase chain reaction single-stranded conformation polymorphism approach, followed by direct DNA sequencing in 22 Uighur and 13 Han women with early-onset sporadic breast cancer, and 32 women with benign breast diseases. The prevalence of BRCA1 mutations in this population was 22.9% (8/35) among early-onset sporadic breast cancer cases. Of these, 31.8% (7/22) of Uighur patients and 7.69% (1/13) of Han patients were found to have BRCA1 mutations. In 7 Uighur patients with BRCA1 mutations, there were 11 unique sequence alterations in the BRCA1 gene, including 4 clearly disease-associated mutations on exon 11 and 3 variants of uncertain clinical significance on exon 11, meanwhile 4 neutral variants on intron 20 or 2. None of the 11 BRCA1 mutations identified have been previously reported in the Breast Cancer Information Core database. These findings reflect the prevalence of BRCA1 mutations in Uighur women with early-onset and sporadic breast cancer, which will allow for provision of appropriate genetic counseling and treatment for Uighur patients in the Xinjiang region.
  23. Liu, Jia;Wu, Ning;Ma, Lei-Na;Zhong, Jia-Teng;Liu, Ge;Zheng, Lan-Hong;Lin, Xiu-Kun 4519
    https://doi.org/10.7314/APJCP.2014.15.11.4519 PDF KSCI
    Oleanolic acid (OA) is a nutritional component widely distributed in various vegetables. Although it has been well recognized for decades that OA exerts certain anti-tumor activity by inducing mitochondria-dependent apoptosis, it is still unclear that what molecular signaling is responsible for this effect. In this study, we employed cancer cell lines, A549, BXPC-3, PANC-1 and U2OS to elucidate the molecular mechanisms underlying OA anti-tumor activity. We found that activation of MAPK pathways, including p-38 MAPK, JNK and ERK, was triggered by OA in both a dose and time-dependent fashion in all the tested cancer cells. Activation was accompanied by cleavage of caspases and PARP as well as cytochrome C release. SB203580 (p38 MAPK inhibitor), but not SP600125 (JNK inhibitor) and U0126 (ERK inhibitor), rescued the pro-apoptotic effect of OA on A549 and BXPC-3 cells. OA induced p38 MAPK activation promoted mitochondrial translocation of Bax and Bim, and inhibited Bcl-2 function by enhancing their phosphorylation. OA can induce reactive oxygen species (ROS)-dependent ASK1 activation, and this event was indispensable for p38 MAPK-dependent apoptosis in cancer cells. In vivo, p38 MAPK knockdown A549 tumors proved resistant to the growth-inhibitory effect of OA. Collectively, we elucidated that activation of ROS/ASK1/p38 MAPK pathways is responsible for the apoptosis stimulated by OA in cancer cells. Our finding can contribute to a better understanding of molecular mechanisms underlying the antitumor activity of nutritional components.
  24. Ozturk, Candan;Bektas, Murat;Mert, Ozlem 4527
    https://doi.org/10.7314/APJCP.2014.15.11.4527 PDF KSCI
    Background: This descriptive and cross-sectional study aimed to investigate effects of cigarette smoking across three generations and perceptions of the smoking-cancer relationship on the cigarette smoking status of Turkish university students. Materials and Methods: The study sample comprised of 434 university students studying in different departments of a university. Data were collected using a socio-demographic data collection form and the Decisional Balance Scaleqand evaluated using the Mann-Whitney U test, CHAID and multiple regression analyses. Results: The average age of the students participating in the study is 19.6+.5.0, some 11.3% of the students reporting that they smoked cigarettes. No statistically significant relationship was ascertained between the cigarette smoking statuses of the students based on the cigarette smoking status of their grandparents (p=0.144). but there was alink to that of their parents (p=0.002). The difference between the cigarette smoking ratios of the students based on their perceptions of smoking-cancer relationship was statistically significant (p<0.001). Believing that there is a relationship between smoking and cancer decreased likelihood of cigarette smoking 3.7 fold. Cigarette smoking by grandparents, and believing that there is a relationship between smoking and cancer, and cigarette smoking by parents explained 8.3% of the cigarette smoking status of the students. Conclusions: While cigarette smoking by grandparents only indirectly influences cigarette smoking by the students, believing that there is a relationship between smoking and cancer, and cigarette smoking by parents are influential variables in determining cigarette smoking by Turkish students.
  25. Qi, Yu;Li, Xin;Zhao, Song;Han, Yong 4535
    https://doi.org/10.7314/APJCP.2014.15.11.4535 PDF KSCI
    Objective: To explore the value of porous titanium alloy plates for chest wall reconstruction after resection of chest wall tumors. Materials and Methods: A total of 8 patients with chest wall tumors admitted in our hospital from Jan. 2006 to Jan. 2009 were selected and underwent tumor resection, then chest wall repair and reconstruction with porous titanium alloy plates for massive chest wall defects. Results: All patients completed surgery successfully with tumor resection-induced chest wall defects being $6.5{\times}7cm{\sim}12{\times}15.5$ cm in size. Two weeks after chest wall reconstruction, only 1 patient had subcutaneous fluidify which healed itself after pressure bandaging following fluid drainage. Postoperative pathological reports showed 2 patients with costicartilage tumors, 1 with squamous cell carcinoma of lung, 1 with lung adeno-carcinoma, 1 with malignant lymphoma of chest wall, 2 with chest wall metastasis of breast cancers and 1 with chest wall neurofibrosarcoma. All patients had more than 2~5 years of follow-up, during which time 1 patient with breast cancer had surgical treatment due to local recurrence after 7 months and none had chest wall reconstruction associated complications. The mean survival time of patients with malignant tumors was ($37.3{\pm}5.67$) months. Conclusions: Porous titanium alloy plates are safe and effective in the chest wall reconstruction after resection of chest tumors.
  26. Zheng, Nai-Gang;Wang, Jun-Ling;Yang, Sheng-Li;Wu, Jing-Lan 4539
    https://doi.org/10.7314/APJCP.2014.15.11.4539 PDF KSCI
    Since the epigenetic alteration in tumor cells can be reversed by the dietary polyphenol quercetin (Q) or butyrate (B) with chemopreventive activity, suggesting that Q or B can be used for chemopreventive as well as therapeutic agent against tumors. In this study the polyphenol flavonoid quercetin (Q) or sodium butyrate (B) suppressed human esophageal 9706 cancer cell growth in dose dependent manner, and Q combined with B (Q+B) could further inhibit Eca9706 cell proliferation than that induced by Q or B alone, compared with untreated control group (C) in MTT assay. The reverse expressions of global DNMT1, $NF-{\kappa}Bp65$, HDAC1 and Cyclin D1 were down-regulated, while expressions of caspase-3 and $p16INK4{\alpha}$ were up-regulated, compared with the C group in immunoblotting; the down-regulated HDAC1-IR (-immunoreactivity) with nuclear translocation, and up-regulated E-cadherin-IR demonstrated in immunocytochemistry treated by Q or B, and Q+B also displayed further negatively and positively modulated effects compared with C group. The order of methylation specific (MS) PCR of $p16INK4{\alpha}$: C>B/Q>Q+B group, while the order of E-cadherin expression level was contrary, Q+B>Q/B>C group. Thus, Q/B, especially Q+B display reverse effect targeting both altered DNA methylation and histone acetylation, acting as histone deacetylase inhibitor mediated via epigenetic-$NF-{\kappa}B$ cascade signaling.
  27. Chen, Ji-Dong;Xiong, Yan-Qun;Dong, Ke;Luo, Jun;Yue, Lin-Xian;Chen, Qin 4545
    https://doi.org/10.7314/APJCP.2014.15.11.4545 PDF KSCI
    Objective: To investigate the changes of serum vascular endothelial growth factor (VEGF), soluble interleukin-2 receptor (SIL-2R) and hepatocyte growth factor (HGF) contents in patients with primary hepatocellular carcinoma (HCC) before and after percutaneous microwave coagulation therapy (PMCT) and determine their clinical significance. Materials and Methods: Fasting venous blood (3 mL) from 81 patients with primary HCC diagnosed by pathology was collected in the mornings 1 day before PMCT, and 1 day, 7 days and 1 month after PMCT, and then the serum was separated and stored in $-70^{\circ}C$. The contents of VEGF, SIL-2R and HGF were detected by enzyme linked immunosorbent assay (ELISA). Results: The serum VEGF, SIL-2R and HGF contents in 81 patients with primary HCC had obviously dynamic changes before and after PMCT. By comparison to 1 day after PMCT with pre-operation, there was no statistical significance regarding VEGF and SIL-2R contents (P>0.05), but HGF content showed significant difference (P<0.01). Compared with pre-operation, VEGF, SIL-2R and HGF contents 7 days and 1 month after PMCT all manifested significant differences (P<0.01). By comparison to 7 days with 1 month after PMCT, there was no statistical significance regarding the VEGF content (P>0.05), whereas SIL-2R and HGF contents showed significant change (P<0.01). Conclusions: The contents of serum VEGF, SIL-2R and HGF have obviously dynamic changes in primary HCC before and after PMCT, and their joint detection is expected to be an effective hematologic evaluation index of PMCT for primary HCC.
  28. Sezgin, Gulay;Acipayam, Can;Ozkan, Ayse;Bayram, Ibrahim;Tanyeli, Atila 4549
    https://doi.org/10.7314/APJCP.2014.15.11.4549 PDF KSCI
    Background: Infection is a serious cause of mortality in febrile neutropenia of pediatric cancer patients. Recently, monotherapy has replaced the combination therapy in empirical treatment of febrile neutropenia. Since there has been no reported trial comparing the efficacy of meropenem and piperacillin-tazobactam (PIP/TAZ) monotherapies, the present retrospective study was conducted to compare safety and efficacy in febrile neutropenic children with cancer. Materials and Methods: Charts of febrile, neutropenic children hospitalized at our center between March 2008 and April 2011 for hemato-oncological malignancies were reviewed. Patients received PIP/TAZ 360 mg/kg/day or meropenem 60 mg/kg/day intravenously in three divided doses. Duration of fever and neutropenia, absolute neutrophil count, modification, and success rate were compared between the two groups. Resolution of fever without antibiotic change was defined as success and resolution of fever with antibiotic change or death of a patient was defined as failure. Modification was defined as changing the empirical antimicrobial agent during a febrile episode. Results: Two hundred eighty four febrile neutropenic episodes were documented in 136 patients with a median age of 5 years. In 198 episodes meropenem and in 86 episodes PIP/TAZ were used. Duration of fever and neutropenia, neutrophil count, sex, and primary disease were not different between two groups. Success rates and modification rate between two groups showed no significant differences (p>0.05). Overall success rate in the meropenem and PIP/TAZ groups were 92.4% and 91.9% respectively. No serious adverse effects occurred in either of the groups. Conclusions: Meropenem and PIP/TAZ monotherapy are equally safe and effective in the initial treatment of febrile neutropenia in children with cancer.
  29. Al-Jamal, Hamid AN;Jusoh, Siti Asmaa Mat;Yong, Ang Cheng;Asan, Jamaruddin Mat;Hassan, Rosline;Johan, Muhammad Farid 4555
    https://doi.org/10.7314/APJCP.2014.15.11.4555 PDF KSCI
    Background: Silencing due to methylation of suppressor of cytokine signaling-3 (SOCS-3), a negative regulator gene for the JAK/STAT signaling pathway has been reported to play important roles in leukemogenesis. Imatinib mesylate is a tyrosine kinase inhibitor that specifically targets the BCR-ABL protein and induces hematological remission in patients with chronic myeloid leukemia (CML). Unfortunately, the majority of CML patients treated with imatinib develop resistance under prolonged therapy. We here investigated the methylation profile of SOCS-3 gene and its downstream effects in a BCR-ABL positive CML cells resistant to imatinib. Materials and Methods: BCR-ABL positive CML cells resistant to imatinib (K562-R) were developed by overexposure of K562 cell lines to the drug. Cytotoxicity was determined by MTS assays and $IC_{50}$ values calculated. Apoptosis assays were performed using annexin V-FITC binding assays and analyzed by flow cytometry. Methylation profiles were investigated using methylation specific PCR and sequencing analysis of SOCS-1 and SOCS-3 genes. Gene expression was assessed by quantitative real-time PCR, and protein expression and phosphorylation of STAT1, 2 and 3 were examined by Western blotting. Results: The $IC_{50}$ for imatinib on K562 was 362nM compared to 3,952nM for K562-R (p=0.001). Percentage of apoptotic cells in K562 increased upto 50% by increasing the concentration of imatinib, in contrast to only 20% in K562-R (p<0.001). A change from non-methylation of the SOCS-3 gene in K562 to complete methylation in K562-R was observed. Gene expression revealed down-regulation of both SOCS-1 and SOCS-3 genes in resistant cells. STAT3 was phosphorylated in K562-R but not K562. Conclusions: Development of cells resistant to imatinib is feasible by overexposure of the drug to the cells. Activation of STAT3 protein leads to uncontrolled cell proliferation in imatinib resistant BCR-ABL due to DNA methylation of the SOCS-3 gene. Thus SOCS-3 provides a suitable candidate for mechanisms underlying the development of imatinib resistant in CML patients.
  30. Xu, Yan-Song;Zhao, Bo;Long, Chen-Yan;Li, Hui;Lu, Xing;Liu, Gang;Tang, Xiao-Zhun;Tang, Wei-Zhong 4563
    https://doi.org/10.7314/APJCP.2014.15.11.4563 PDF KSCI
    Background: To evaluate relationship between the cyclooxygenase-2 promoter 765G/C polymorphism and digestive cancer risk in China. Materials and Methods: A literature search through February 2014 was performed using PubMed, Chinese Biomedical Literature Database (CBM) and China National Knowledge Infrastructure (CNKI) databases, and a meta-analysis was performed with RevMan 5.2 software for odds ratios and 95%CIs. Results: In total, 9 articles with 3,263 cases and 4,858 controls were included in this meta-analysis. The pooled OR (95%CIs) in the co-dominant model (GC vs GG) was 1.56 [1.19, 2.06], and in the dominant model ((CC+GC) vs GG), the pooled OR was 1.59 [1.21, 2.09] in overall cancers. In the subgroup analysis, stratified by cancer type, significant associations were found that the-765C allele had increased pancreatic cancer and gastric risk. No significant liver cancer and colorectal cancer risk of COX-2 -765G/C polymorphism was found. Conclusions: These findings suggest that COX-2-765*C is related to cancer susceptibility and may increase gastric and pancreatic cancer risk.
  31. Wan, Fang;Chen, Xin;Dong, Li-Fan;Cheng, Yue-Hong;Long, Jing-Pei 4567
    https://doi.org/10.7314/APJCP.2014.15.11.4567 PDF KSCI
    Background: This systemic analysis was conducted to evaluate the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic breast cancer as first or second line chemotherapy. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with breast cancer were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In first line pemetrexed based regimens, 10 clinical studies which including 513 patients with advanced breast cancer were considered eligible for inclusion. For second line pemetrexed based chemotherapy, 5 clinical studies which including 281 patients with advanced breast cancer were considered eligible. Systemic analysis suggested that, in all patients, pooled RR was 32.6% (167/513) in pemetrexed based first line regimens, and 13.9 % (39/281) in pemetrexed based second line regimens. Major adverse effects were neutropenia, leukopenia, fatigue, and anemia in pemetrexed based first line treatment; and lymphopenia, neutropenia, leukopenia, as well as anemia in second line chemotherapy. One treatment related death occurred with pemetrexed based second line treatment. Conclusion: This systemic analysis suggests that pemetrexed based first line regimens are associated with a reasonable response rate and acceptable toxicity, however with low response rate for treating patients with metastatic breast cancer when is used in the second line.
  32. Anand, Sudhaa;Nath, Badari;Saraswathy, Radha 4571
    https://doi.org/10.7314/APJCP.2014.15.11.4571 PDF KSCI
    Diabetes, a comprehensive genetic disease, is principally due to the deregulation of glucose levels in the blood. In addition to contemporary epidemiological studies, systematic substantiation suggests that long-term diabetes leads to cancers due to a variety of reasons. In this study, blood samples were collected with informed consent from confirmed type I diabetic (T1DM, n=25) and type II Diabetic patients (T2DM, n=25) with equal numbers of controls. Further depending on the lifestyle habits they were subdivided into smokers/non-smokers and alcoholics/non-alcoholics. Chromosomal assays were performed for these cases and it was found that there was a significant increase in chromosomal aberration frequency in diabetic patient groups who are exposed to smoking and alcohol than that of normal diabetic groups (T1DM and T2DM). On the other hand, patient groups who were non-smoking and non-alcoholics also showed higher chromosomal aberrations when compared to that of controls. While the mechanisms for these increased chromosomal aberrations in diabetic groups are not clear, they may be due to increased oxidative stress leading to oxidative damage and resulting in genomic instability, which in turn may contribute to an increased risk for cancer.
  33. Alvur, Tuncay Muge;Cinar, Nursan;Oncel, Selim;Akduran, Funda;Dede, Cemile 4575
    https://doi.org/10.7314/APJCP.2014.15.11.4575 PDF KSCI
    Turkey protects its entire population of 75 million people with all the MPOWER measures at the highest level. The aim of this study is to make a comparison of smoking and addiction data obtained from Sakarya University students in 2005-6 and 2012-13. A total of 4,200 (2,500 and 1,700 for each academic year) students at Sakarya University in Sakarya, Turkey, were randomly selected for sampling purposes. The selected participants represented Sakarya University students. Data were collected using a pretested anonymous and confidential, self-completed questionnaire which took 15-20 minutes to complete and Fagerstrom Test for nicotine dependence. Chi-squared, Spearman correlation, and binary logistic regression tests were used to define associations, if any. The level of significance was kept at alpha=0.05. Smoking prevalance dropped by 8.5% (from 26.9% to 18.5%). Male gender, older age, high family smoking index, low self-rated school success, and high peer smoker proportion were common variables that have correlation with smoking status. In the binary logistic regression test the highest contributor to "being a smoker" was found to be the rate of peer smokers. Having all friends smoking puts the student a a 47.5 and 58.0 times higher risk for smoking for males and females, respectively. Our results suggest an admirable diminution of smoking prevalance among Sakarya University students, which can be attributed to MPOWER protection.
  34. Han, Ye;Xue, Xiao-Feng;Shen, Hu-Gang;Guo, Xiao-Bo;Wang, Xu;Yuan, Bin;Guo, Xing-Po;Kuang, Yu-Ting;Zhi, Qiao-Ming;Zhao, Hong 4583
    https://doi.org/10.7314/APJCP.2014.15.11.4583 PDF KSCI
    Objective: Beclin-1 has recently been observed as an essential marker of autophagy in several cancers. However, the prognostic role of Beclin-1 in colorectal neoplasia remains controversial. Our study aimed to evaluate the potential association between Beclin-1 expression and the outcome of colorectal cancer patients. Materials and Methods: All related studies were systematically searched in Pubmed, Embase, Springer and Chinese National Knowledge Infrastructure databases (CNKI), and then a meta-analysis was performed to determine the association of Beclin-1 expression with clinical outcomes. Finally, a total of 6 articles were included in our analysis. Results: Our data showed that high Beclin-1 expression in patients with CRC was associated with poor prognosis in terms of tumor distant metastasis (OR=2.090, 95%CI=1.061-4.119, p=0.033) and overall survival (RR=1.422, 95%CI=1.032-1.959, p=0.031). However, we did not found any correlation between Beclin-1 over-expression and tumor differentiation (OR=1.711, 95%CI=0.920-3.183, p=0.090). In addition, there was no evidence of publication bias as suggested by Egger's tests for tumor distant metastasis (p=1.000), differentiation (p=1.000) and OS (p=0.308). Conclusions: Our present meta-analysis indicated that elevated Beclin-1 expression iss associated with tumor metastasis and a poor prognosis in patients with CRC. Beclin-1 might serve as an efficient prognostic indicator in CRC, and could be a new molecular target in CRC therapy.
  35. Lai, Er-Yong;Chen, Zhen-Guo;Zhou, Xuan;Fan, Xiao-Rong;Wang, Hua;Lai, Ping-Lin;Su, Yong-Chun;Zhang, Bai-Yu;Bai, Xiao-Chun;Li, Yun-Feng 4589
    https://doi.org/10.7314/APJCP.2014.15.11.4589 PDF KSCI
    The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including colorectal cancer (CRC). DEPTOR is an mTOR inhibitor whose expression is negatively regulated by mTOR. However, the role of DEPTOR in the development of CRC is not known. The aim of this study was to investigate the expression of DEPTOR and mTORC1 activity (P-S6) in a subset of CRC patients and determine their relation to tumor differentiation, invasion, nodal metastasis and disease-free survival. Here, Immunohistochemical expression of P-S6 (S235/236) and DEPTOR were evaluated in 1.5 mm tumor cores from 90 CRC patients and in 90 samples of adjacent normal mucosa by tissue microarray. The expression of P-S6 (S235/236) was upregulated in CRC, with the positive rate of P-S6 (S235/236) in CRC (63.3%) significantly higher than that in control tissues (36.7%, 30%) (p<0.05). P-S6 (S235/236) also correlated with high tumor histologic grade (p=0.002), and positive nodal metastasis (p=0.002). In contrast, the expression level of DEPTOR was correlated with low tumor histological grade (p=0.006), and negative nodal metastasis (p=0.001). Interestingly, P-S6 (S235/236) expression showed a significant negative association with the expression of DEPTOR in CRC (p=0.011, R= -0.279). However, upregulation of P-S6 (S235/236) (p=0.693) and downregulation of DEPTOR (p=0.331) in CRC were not significantly associated with overall survival. Thus, we conclude that expression of DEPTOR negatively correlates with mTORC1 activity and tumor progression in CRC. DEPTOR is a potential marker for prognostic evaluation and a target for the treatment of CRC.
  36. Kharameh, Zahra Taheri;Foroozanfar, Sahar;Zamanian, Hadi 4595
    https://doi.org/10.7314/APJCP.2014.15.11.4595 PDF KSCI
    Background: Colorectal cancer is a serious health problem. Early detection of colorectal cancer is crucial for treatment and reducing mortality. Beliefs related to colorectal cancer have been found to be a factor in a person's decision about colorectal cancer screening programs. To determine such beliefs, a valid and reliable instrument is necessary. Objective:The aim of this study was to adapt and determine the psychometric properties of the Persian version of Champion's Health Belief Model Scale of breast cancer screening in the measurement of beliefs toward colorectal cancer (CRC) screening. Materials and Methods: The 'forward-backward' procedure was applied to translate the instrument from English into Persian. This study was conducted in Iran from June 2012 to May 2013. A convenience sample of 200 individuals aged 50 years and older was recruited from the population at the outpatient clinics in the three teaching hospitals. Validity was assessed using content, face and construct validity. To test reliability, the internal consistency was assessed by using Cronbach's alpha coefficient and test-retest (intraclass correlation coefficient) analyses. Exploratory factor analysis was used to assess the construct validity and determine the factors of adapted Champion's Health Belief Model Scale. Results: The mean age of the participants were 62.5 years (SD=10.8 years) and the majority of them (75.5 percent) were female. The results of exploratory factor analysis indicated a six-factor solution for the questionnaire (benefits, motivation and confidence, seriousness, susceptibility, emotional barriers and background barriers) that jointly accounted for 55.52% of variance observed. Cronbach's alpha of the subscales ranged from 0.57 to 0.89 and test-retest reliability ranged from 0.81 to 0.93 indicating a good range of reliability. Conclusions: The findings of this study suggest that the Persian version of Champion's Health Belief Model Scale of CRC screening has good psychometric properties and could be an appropriate measure for health beliefs related to CRC screening in national and international studies.
  37. Pintha, Komsak;Yodkeeree, Supachai;Pitchakarn, Pornsirit;Limtrakul, Pornngarm 4601
    https://doi.org/10.7314/APJCP.2014.15.11.4601 PDF KSCI
    Red rice contains pharmacological substances including phenolics, oryzanol, tocotrienol and tocopherol. Recently, red rice extract has been employed as a source of antioxidants for inhibition of tumor growth. This study was carried out to evaluate the anti-invasion effects of red rice extract fractions on cancer cells. It was found that at $100{\mu}g/ml$ of crude ethanolic extract (CEE), hexane fraction (Hex) and dichloromethane fraction (DCM) could reduce HT1080 and MDA-MB-231 cancer cell invasion. Hex and DCM revealed higher potency levels than CEE, whereas an ethyl acetate fraction (EtOAc) had no effect. Gelatin zymography revealed that Hex decreased the secretion and activity of matrix metalloproteinase-2 and -9 (MMP-2 and-9). In contrast, the DCM fraction exhibited slightly effect on MMPs secretion and had no effect on MMPs activity. Collagenase activity was significantly inhibited by the Hex and DCM fractions. High amounts of ${\gamma}$-oryzanol and ${\gamma}$-tocotrienol were found in the Hex and DCM fractions and demonstrated an anti-invasion property. On the other hand, proanthocyanidin was detected only in the CEE fraction and reduced MDA-MB-231 cells invasion property. These observations suggest that proanthocyanidin, ${\gamma}$-oryzanol and ${\gamma}$-tocotrienol in the red rice fractions might be responsible for the anti invasion activity. The red rice extract may have a potential to serve as a food-derived chemotherapeutic agent for cancer patients.
  38. Yan, De-Qi;Liu, Yong-Qi;Li, Ying-Dong;Li, Dou;Cheng, Xiao-Li;Wu, Zhi-Wei 4609
    https://doi.org/10.7314/APJCP.2014.15.11.4609 PDF KSCI
    Background: To investigate tumor inhibition effects and mechanisms of Angelica sinensis and Sophorae flavescentis ait decoction (ASSF) combined with diamine-dichloroplatinum (DDP). Materials and Methods: Bodyweight, tumor inhibition rate and q value were calculated for single ASSF or ASSF combined with DDP on H22 carcinoma xenograft KM mice. Biochemical methods for serum LDH, AST, ALT, and AKP, ELISA method for serum HIF-$1{\alpha}$, pathological assessemnt of thymus, immunohistochemistry detection of tumor tissue caspase3 and mutant p53 protein, and qRT-PCR detection of bax/ bcl-2 mRNA were applied. Results: Compared with DDP control group, the bodyweight increased in ASSF-DDP group (p<0.01). Tumor inhibition rates for DDP, ASSF, ASSF-DDP were 62.7%. 43.7% and 71.0% respectively, with a q value of 0.90. Compared with other groups, thymus of DDP control group had obvious pathological injury (p<0.01), serum LDH, AST, ALT, AKP increased significantly in DDP control group (p<0.01), while serum HIF-$1{\alpha}$ was increased in the model control group. Compared with this latter, the expression of mutant p53 protein and bcl-2 mRNA were decreased in all treatment groups (p<0.01), but there were no statistical difference between DDP control p and ASSF-DDP groups. The expression of caspase3 protein and bax mRNA was increased in all treatment groups, with statistical differences between the DDP and ASSF-DDP groups (p<0.01). Conclusions: ASSF can inhibit bodyweight decrease caused by DDP, can inhibit tumor growth synergistically with DDP mainly through increasing serum HIF-$1{\alpha}$ and pro-apoptotic molecules such as caspase 3 and bax, rather than through decreasing anti-apoptotic mutant p53 and bcl-2. ASSF can reduce DDP toxicity due to decreasing the release of LDH, AST, ALT, AKP into blood and enhancing thymus protection.
  39. Zhang, Ling;Song, Fang-Fang;Huang, Yu-Bei;Zheng, Hong;Song, Feng-Ju;Chen, Ke-Xin 4617
    https://doi.org/10.7314/APJCP.2014.15.11.4617 PDF KSCI
    Background: Several studies have previously focused on associations between the (GT)n repeat polymorphism of the heme oxygenase-1 (HO-1) gene promoter region and risk of cancers, but results are complex. We conducted the present meta-analysis to integrate relevant findings and evaluate the association between HO-1(GT)n repeat polymorphism and cancer susceptibility. Materials and Methods: Published literature was retrieved from the PubMed/MEDLINE, EMBASE and ISI Web of Science databases before November 2013. For all alleles and genogypes, odds ratios were pooled to assess the strength of the associations using either fixed-effects or random-effects models according to heterogeneity. Subgroup analysis was conducted according to ethnicity and histopathology. Results: A total of 10 studies involving 2,367 cases and 2,870 controls were identified. The results showed there was no association between HO-1 (GT)n repeat polymorphism and the cancer risk both at the allelic and genotypic level. However, in the stratified analysis, we observed an increased risk of squamous cell carcinoma in persons carrying the LL genotype and the LL+LS genotype as compared with those carrying the SS genotype. When the LS and SS genotypes were combined, the odds ratio for squamous cell carcinoma in LL-genotype carriers, were also significantly increased. No publication bias was observed. Conclusions: The LL genotype and L-allele carrying genotypes (LL+LS) of HO-1 (GT)n repeat polymorphism are potential genetic factors for developing squamous cell carcinoma. More large and well-designed studies are required for further validations.
  40. Mehta, Dhaval Tushar;Annamalai, Thangavelu;Ramanathan, Arvind 4623
    https://doi.org/10.7314/APJCP.2014.15.11.4623 PDF KSCI
    Background: The epidermal growth factor receptor (EGFR) plays a vital role in the activation and inactivation of receptor tyrosine kinases. Mutations in exons 19 and 21 of EGFR are commonly found to be associated with non small cell lung carcinoma and triple negative breast cancer, enhancing sensitivity to EGFR targeting chemotherapeutic agents. Since amplification and prolonged activation of EGFR molecules have been identified in oral squamous cell carcinomas (OSCC), we investigated whether OSCCs carried mutations in exons 19 and 21 of EGFR to their incidence. Materials and Methods: Tumor chromosomal DNA isolated from forty surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking exons 19 and 21 of the EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Data analysis of the EGFR exon 19 and 21 coding sequences did not show any mutations in the forty OSCC samples that were analyzed. Conclusions: To the best of our knowledge, this is the first study to have investigated the genetic status of exons 19 and 21 of EGFR in Indian OSCCs and identified that mutation in EGFR exon 19 and 21 may not contribute towards their genesis. The absence of mutations also indicates that oral cancerous lesions may not be as sensitive as other cancers to chemotherapeutic agents targeting EGFR.
  41. Usuda, Katsuo;Sagawa, Motoyasu;Motono, Nozomu;Ueno, Masakatsu;Tanaka, Makoto;Machida, Yuichiro;Maeda, Sumiko;Matoba, Munetaka;Kuginuki, Yasuaki;Taniguchi, Mitsuru;Tonami, Hisao;Ueda, Yoshimichi;Sakuma, Tsutomu 4629
    https://doi.org/10.7314/APJCP.2014.15.11.4629 PDF KSCI
    Background: Diffusion-weighted imaging (DWI) makes it possible to detect malignant tumors based on the diffusion of water molecules. However, it is uncertain whether DWI has advantages over FDG-PET for distinguishing malignant from benign pulmonary nodules and masses. Materials and Methods: One hundred-forty-three lung cancers, 17 metastatic lung tumors, and 29 benign pulmonary nodules and masses were assessed in this study. DWI and FDG-PET were performed. Results: The apparent diffusion coefficient (ADC) value ($1.27{\pm}0.35{\times}10^{-3}mm^2/sec$) of malignant pulmonary nodules and masses was significantly lower than that ($1.66{\pm}0.58{\times}10^{-3}mm^2/sec$) of benign pulmonary nodules and masses. The maximum standardized uptake value (SUVmax: $7.47{\pm}6.10$) of malignant pulmonary nodules and masses were also significantly higher than that ($3.89{\pm}4.04$) of benign nodules and masses. By using optimal cutoff values for ADC ($1.44{\times}10^{-3}mm^2/sec$) and for SUVmax (3.43), which were determined with receiver operating characteristics curves (ROC curves), the sensitivity (80.0%) of DWI was significantly higher than that (70.0%) of FDG-PET. The specificity (65.5%) of DWI was equal to that (65.5%) of FDG-PET. The accuracy (77.8%) of DWI was not significantly higher than that (69.3%) of FDG-PET for pulmonary nodules and masses. As the percentage of bronchioloalveolar carcinoma (BAC) component in adenocarcinoma increased, the sensitivity of FDG-PET decreased. DWI could not help in the diagnosis of mucinous adenocarcinomas as malignant, and FDG-PET could help in the correct diagnosis of 5 out of 6 mucinous adenocarcinomas as malignant. Conclusions: DWI has higher potential than PET in assessing pulmonary nodules and masses. Both diagnostic approaches have their specific strengths and weaknesses which are determined by the underlying pathology of pulmonary nodules and masses.
  42. Zhang, Yi;Wang, Peng;Zhou, Xing-Chun;Bao, Guo-Qiang;Lyu, Zhuo-Ming;Liu, Xiao-Nan;Wan, Shao-Gui;He, Xian-Li;Huang, Qi-Chao 4637
    https://doi.org/10.7314/APJCP.2014.15.11.4637 PDF KSCI
    Background: Hypoxia-inducible factor $1{\alpha}$ (HIF-$1{\alpha}$) plays an important role in regulating cell survival and angiogenesis, which are critical for tumor growth and metastasis. Genetic variations of HIF1A have been shown to influence the susceptibility to many kinds of human tumors. Increased expression of HIF-$1{\alpha}$ has also been demonstrated to be involved in tumor progression. However, the prognostic value of single nucleotide polymorphisms (SNPs) inthe HIF1A gene remains to be determined in most cancer types, including colorectal cancer (CRC). In this study, we sought to investigate the predictive role of HIF1A SNPs in prognosis of CRC patients and efficacy of chemotherapy. Materials and Methods: We genotyped two functional SNPs in HIF1A gene using the Sequenom iPLEX genotyping system and then assessed their associations with clinicopathological parameters and clinical outcomes of 697 CRC patients receiving radical surgery using Cox logistic regression model and Kaplan Meier curves. Results: Generally, no significant association was found between these 2 SNPs and clinical outcomes of CRC. In stratified analysis of subgroup without adjuvant chemotherapy, patients carrying CT/TT genotypes of rs2057482 exhibited a borderline significant association with better overall survival when compared with those carrying CC genotype [Hazard ratio (HR), 0.47; 95% confidence interval (95% CI): 0.29-0.76; P < 0.01]. Moreover, significant protective effects on CRC outcomes conferred by adjuvant chemotherapy were exclusively observed in patients carrying CC genotype of rs2057482 and in those carrying AC/CC genotype of rs2301113. Conclusions: Genetic variations in HIF1A gene may modulate the efficacy of adjuvant chemotherapy after surgery in CRC patients.
  43. Zhang, Bai-Lin;He, Na;Huang, Yu-Bei;Song, Feng-Ju;Chen, Ke-Xin 4643
    https://doi.org/10.7314/APJCP.2014.15.11.4643 PDF KSCI
    Background: For decades, studies have been performed to evaluate the association between ABO blood groups and risk of cancer. However, whether ABO blood groups are associated with overall cancer risk remains unclear. We therefore conducted a meta-analysis of observational studies to assess this association. Materials and Methods: A search of Pubmed, Embase, ScienceDirect, Wiley, and Web of Knowledge databases (to May 2013) was supplemented by manual searches of bibliographies of key retrieved articles and relevant reviews. We included case-control studies and cohort studies with more than 100 cancer cases. Results: The search yielded 89 eligible studies that reported 100,554 cases at 30 cancer sites. For overall cancer risk, the pooled OR was 1.12 (95%CI: 1.09-1.16) for A vs. non- A groups, and 0.84 (95%CI: 0.80-0.88) for O vs. non-O groups. For individual cancer sites, blood group A was found to confer increased risk of gastric cancer (OR=1.18; 95%CI: 1.13-1.24), pancreatic cancer (OR=1.23; 95%CI: 1.15-1.32), breast cancer (OR=1.12; 95%CI: 1.01-1.24), ovarian cancer (OR=1.16; 95%CI: 1.04-1.27), and nasopharyngeal cancer (OR=1.17; 95%CI: 1.00-1.33). Blood group O was found to be linked to decreased risk of gastric cancer (OR=0.84; 95%CI: 0.80-0.88), pancreatic cancer (OR=0.75; 95%CI: 0.70-0.80), breast cancer (OR=0.90; 95%CI: 0.85-0.95), colorectal cancer (OR=0.89; 95%CI: 0.81-0.96), ovarian cancer (OR=0.76; 95%CI: 0.53-1.00), esophagus cancer (OR=0.94; 95%CI: 0.89-1.00), and nasopharyngeal cancer (OR=0.81; 95%CI: 0.70-0.91). Conclusions: Blood group A is associated with increased risk of cancer, and blood group O is associated with decreased risk of cancer.
  44. Hakim, Luqman;Alias, Ekram;Makpol, Suzana;Ngah, Wan Zurinah Wan;Morad, Nor Azian;Yusof, Yasmin Anum Mohd 4651
    https://doi.org/10.7314/APJCP.2014.15.11.4651 PDF KSCI
    The development of chemopreventive approaches using a concoction of phytochemicals is potentially viable for combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferative effects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil) against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growth of HCT 116 cells more potently ($IC_{50}$ of 3mg/mL) in comparison to Gelam honey ($IC_{50}$ of 75mg/mL). Combined treatment of the two compounds (3mg/mL ginger+75mg/mL Gelam honey) synergistically lowered the $IC_{50}$ of Gelam honey to 22mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibiting effects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggested that individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition, treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dose-dependently while treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes. Combination index analysis showed the combination effect of both natural compounds to be synergistic in their inhibitory action against HCT 116 colon cancer cells (CI 0.96 < 1). In conclusion, combined treatment of Gelam honey and ginger extract could potentially enhance the chemotherapeutic effect of 5-FU against colorectal cancer.
  45. Laidi, Fatna;Bouziane, Amal;Lakhdar, Amina;Khabouze, Samira;Amrani, Mariam;Rhrab, Brahim;Zaoui, Fatima 4659
    https://doi.org/10.7314/APJCP.2014.15.11.4659 PDF KSCI
    The tumor marker CA 15-3 is one of the most import reliable for metastatic breast cancer monitoring. While it is generally assessed in serum of patients, blood sampling is an invasive method compared to saliva sampling which is simple and could be an alternative to blood according to many studies. The aim of this investigation was to assess the relationship between serum and salivary concentrations of the protein CA 15-3 in patients with breast cancer and healthy asymptomatic volunteers. A case-control study was conducted with 60 women: 29 breast cancer patients from the Maternity Hospital Souissi Rabat (Morocco) and 31 healthy asymptomatic women. The CA 15-3 concentrations in saliva and serum samples were assessed using an enzyme immune assay (EIA kits) and comparison between cases and controls was made by the Mann-Whitney test. The correlation between serum and saliva CA 15-3 concentration was tested using Pearson correlation. The comparison result of CA15-3 concentration in saliva and serum level in cases and controls was not statistically significant (p>0.05). However, the correlation between salivary and serum CA 15-3 concentration was positive and statistically significant (r=0.27, p=0.03). In conclusion, the positive correlation between salivary and serum expression found in our study suggests that saliva could be an alternative to blood sampling to help breast cancer monitoring.
  46. Yang, Xiao-Li;Zhang, Cheng-Dong;Wu, Hua-Yu;Wu, Yong-Hu;Zhang, Yue-Ning;Qin, Meng-Bin;Wu, Hua;Liu, Xiao-Chun;Lina, Xing;Lu, Shao-Ming 4663
    https://doi.org/10.7314/APJCP.2014.15.11.4663 PDF KSCI
    Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor. We here investigated its effects on proliferation and apoptosis of the CNE2 carcinoma cell line, and attempted to establish genome-wide DNA methylation alteration due to differentially histone acetylation status. After cells were treated by TSA, the inhibitory rate of cell proliferation was examined with a CCK8 kit, and cell apoptosis was determined by flow cytometry. Compared to control, TSA inhibited CNE2 cell growth and induced apoptosis. Furthermore, TSA was found to induce genome-wide methylation alteration as assessed by genome-wide methylation array. Overall DNA methylation level of cells treated with TSA was higher than in controls. Function and pathway analysis revealed that many genes with methylation alteration were involved in key biological roles, such as apoptosis and cell proliferation. Three genes (DAP3, HSPB1 and CLDN) were independently confirmed by quantitative real-time PCR. Finally, we conclude that TSA inhibits CNE2 cell growth and induces apoptosis in vitro involving genome-wide DNA methylation alteration, so that it has promising application prospects in treatment of NPC in vivo. Although many unreported hypermethylated/hypomethylated genes should be further analyzed and validated, the pointers to new biomarkers and therapeutic strategies in the treatment of NPC should be stressed.
  47. Gao, Shun-Li;Wang, Li-Zhong;Liu, Hai-Ying;Liu, Dan-Li;Xie, Li-Ming;Zhang, Zhi-Wei 4671
    https://doi.org/10.7314/APJCP.2014.15.11.4671 PDF KSCI
    Background: MicroRNA-200a (miR-200a) has been reported to regulate tumour progression in several tumours but little is known about its role in neuroblastoma. Our aim was to investigate the potential role and mechanism of miR-200a in neuroblastomas. Materials and Methods: Expression levels of miR-200a in tissues were determined using RT-PCR. The effect of miR-200a and shAP-$2{\gamma}$ on cell viability was evaluated using MTS assays, and target protein expression was determined using Western blotting and RT-PCR. Luciferase reporter plasmids were constructed to confirm direct targeting. Results were reported as mean${\pm}$S.E.M and differences were tested for significance using the 2-tailed Students t-test. Results: We determined that miR-200a expression was significantly lower in neuroblastoma tumors than the adjacent non-cancer tissue. Over-expression of miR-200 are reduced cell viability in neuroblastoma cells and inhibited tumor growth in mouse xenografts. We identified AP-$2{\gamma}$ as a novel target for miR-200a in neuroblastoma cells. Thus miR-200a targets the 3'UTR of AP-$2{\gamma}$ and inhibits its mRNA and protein expression. Furthermore, our result showed that shRNA knockdown of AP-$2{\gamma}$ in neuroblastoma cells results in significant inhibit of cell proliferation and tumor growth in vitro, supporting an oncogenic role of AP-$2{\gamma}$ in neuroblastoma. Conclusions: Our study revealed that miR-200a is a candidate tumor suppressor in neuroblastoma, through direct targeting of AP-$2{\gamma}$. These findings re-enforce the proposal of AP-$2{\gamma}$ as a therapeutic target in neuroblastoma.
  48. Albasri, Abdulkader Mohammed;El-Siddig, Abeer Abdalla;Hussainy, Akbar Shah;Alhujaily, Ahmed Safar 4677
    https://doi.org/10.7314/APJCP.2014.15.11.4677 PDF KSCI
    Background: This study aimed to characterize the histopathological pattern of lymph node pathology among Saudi patients and to highlight the age and gender variations of these lesions as base line data. Materials and Methods: We retrospectively analyzed the data from lymph node biopsy specimens received at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia from January 2006 to December 2013. Results: Of the 289 lymph node biopsy specimens received, 154 (53.3%) were from males and 135 (46.7%) from females giving a male: female ratio of 1.14:1. Age of the patients ranged from 2.5 to 96 years with a mean age 33.9 years. The commonest lymph node group affected was the cervical (30.4%) followed by axillary (9.7%) and inguinal (8.7%). Malignant lymphoma [71 Hodgkin's disease (HD), 57 non Hodgkin's lymphoma (NHL)] 128 (44.3%), reactive hyperplasia 68 (23.5%), and tuberculosis 41 (14.2%) were the common causes of lymph node enlargement. While HD, reactive hyperplasia and tuberculosis were commonest in young adult patients (10-29 years old) and rare above the age of 50 years; NHL was the predominant cause of lymph node enlargement above 50 years. Conclusions: Lymph node biopsy plays an important role in establishing the cause of lymphadenopathy. Among the biopsied nodes, lymphomas were the most common (44.3%) followed by non-specific reactive hyperplasia (23.5%) and tuberculous lymphadenitis (14.2%).
  49. Tan, Mona Poh-Choo;Sitoh, Nadya Ying-Yue;Sim, Amanda Shi-Ting 4683
    https://doi.org/10.7314/APJCP.2014.15.11.4683 PDF KSCI
    Background: Breast conservation treatment (BCT) has long been recognised to provide survival outcomes equivalent to mastectomy for the treatment of breast cancer. However, published reports of BCT rates in Asian communities are lower than those from Western countries. This study sought to investigate the eligibility and utilisation of BCT in a predominantly Asian population. Materials and Methods: All patients treated surgically by a single surgeon at a private medical facility between 2009 and 2011 were included in the study. Patients were deemed to have successful BCT if they underwent breast conserving surgery with pathologic clear margins and completed all recommended adjuvant treatment. Those who did not complete adjuvant treatment were excluded from the analysis. Results: Data from a total of 161 patients who underwent treatment during the study period were analysed. The mean age was 48.8 years. One hundred and six patients (65.8%) were of Chinese ethnicity, 12 were Indian (7.5%), 11 were Malay (6.8%), 18 were Caucasian (11.2%) and 14 (8.7%) were of other Asian ethnicity. One hundred and thirty-eight women (85.7%) underwent BCT. Of the 23 (14.3%) who underwent mastectomy, 8 (5.4%) elected to undergo a mastectomy despite being eligible for BCT. In total, it was assessed that 146 of 161 patients (90.7%) were eligible for BCT and utilisation was 94.5%. Conclusions: In this study, eligibility, utilisation of BCT and eventual successful breast conservation rates are similar to published rates in Western communities. Additional research is needed to investigate the reasons for the lower published BCT rates in Asian countries and determine ways to improve them.
  50. Liu, Chang;Jiang, Zheng;Deng, Qian-xi;Zhao, Ya-nan 4689
    https://doi.org/10.7314/APJCP.2014.15.11.4689 PDF KSCI
    Background: A great number of studies have shown that cytochrome P450 1A1 (CYP1A1) genetic polymorphisms, CYP1A1 Msp I and CYP1A1 Ile/Val, might be risk factors for digestive tract cancers, including esophageal cancer (EC), gastric cancer (GC), hepatic carcinoma (HC), as well as colorectal cancer (CC), but the results are controversial. In this study, a meta-analysis of this literature aimed to clarify associations of CYP1A1 genetic polymorphisms with digestive tract cancers susceptibility in Chinese populations. Materials and Methods: Eligible case-control studies published until December 2013 were retrieved by systematic literature searches from PubMed, Embase, CBM, CNKI and other Chinese databases by two investigators independently. The associated literature was acquired through deliberate search and selection based on established inclusion criteria. Fixed-effects or random-effects models were used to estimate odds ratios (ORs and 95%CIs). The meta-analysis was conducted using Review Manager 5.2 and Stata 12.0 softwares with stability evaluated by both stratified and sensitivity analyses. Moreover, sensitivity analysis and publication bias diagnostics confirmed the reliability and stability. Results: Eighteen case-control studies with 1,747 cases and 2,923 controls were selected for CYP1A1 MspI polymorphisms, and twenty case-control studies with 3, 790 cases and 4, 907 controls for the CYP1A1 Ile/Val polymorphisms. Correlation associations between CYP1A1 Ile/Val polymorphisms and digestive tract cancers susceptibility were observed in four genetic models in the meta-analysis (GG vs AA:OR= 2.03, 95%CI =1.52- 2.72; AG vs AA: OR=1.26, 95%CI =1.07-1.48; [GG+AG vs AA] :OR =1.42, 95%CI=1.20-1.68, [GG vs AA+AG]:OR=1.80, 95%CI =1.40-2.31). There was no association between CYP1A1 Msp I polymorphisms and digestive tract cancers risk. Subgroup analysis for tumor type showed a significant association of CYP1A1 Ile/Val genetic polymorphisms with EC in China. However, available data collected by the study failed to reveal remarkable associations of GC or HC with CYP1A1 Ile/Val genetic polymorphisms and EC, GC or CC with CYP1A1 MspI genetic polymorphisms. Conclusions: Our results indicated that CYP1A1 Ile/Val genetic polymorphisms, but not CYP1A1 Msp I polymorphisms, are associated with an increased digestive tract cancers risk in Chinese populations. Additional well-designed studies, with larger sample size, focusing on different ethnicities and cancer types are now warranted to validate this finding.
  51. Mo, Cui-Ju;Peng, Qi-Liu;He, Yu;Wang, Jian;Xie, Li;Li, Tai-Jie;Li, Shan;Qin, Xue 4697
    https://doi.org/10.7314/APJCP.2014.15.11.4697 PDF KSCI
    Background: Interleukin-16 (IL-16) is a multifunctional cytokine which plays a key role in inflammatory and autoimmune diseases as well as in cancer. Genetic polymorphisms of IL-16 have been implicated in susceptibility to cancer. However, associations remain inconclusive. The present meta-analysis was therefore carried out to establish a more conclusive association of IL-16 polymorphisms with cancer risk. Materials and Methods: Relevant studies were searched through the PubMed, Embase, Web of Science, Google Scholar and Wan fang electronic databases updated in October 2013. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to assess the association between IL-16 polymorphisms and cancer risk. Results: Eight eligible studies (rs4778889 T/C: 8, rs11556218 T/G: 7, rs4072111 C/T: 6) that met our selection criteria were included. The meta-analysis indicated that rs11556218 T/G was associated with a significant increased risk of cancer (G vs. T, OR=1.321, 95% CI=1.142-1.528, P<0.001; TG vs. TT, OR=1.665, 95% CI=1.448-1.915, P<0.001; GG+TG vs. TT, OR=1.622, 95% CI=1.416-1.858, P<0.001),as well as nasopharyngeal carcinoma and colorectal cancer. Furthermore, in the subgroup of Chinese, significant associations were found between rs11556218 polymorphism and cancer risk. There was no statistically significant association between the other two variants (rs4778889, rs4072111) and risk of cancer. Conclusions: This meta-analysis suggests that the IL-16 rs11556218 polymorphism is associated with increased cancer risk. Large well-designed studies involving various cancer types and different populations are now needed.
  52. Sufian, Saira Naz;Masroor, Imrana;Mirza, Waseem;Hussain, Zainab;Hafeez, Saima;Sajjad, Zafar 4705
    https://doi.org/10.7314/APJCP.2014.15.11.4705 PDF KSCI
    Objective: To determine the accuracy of magnetic resonance imaging (MRI) in detection of metastasis in pelvic and para-aortic lymph nodes from different gynecological malignancies. Materials and Methods: This retrospective cross sectional analytic study was conducted at the Department of Diagnostic Radiology, Aga Khan University Hospital Karachi Pakistan from January 2011 to December 2012. A sample of 48 women, age range between 20-79 years, fulfilling inclusion criteria were included. All patients had histopathologically proven gynecological malignancies in the cervix, endometrium or ovary and presented for a pretreatment MRI to our radiology department. Results: MRI was 100% sensitive and had a 100% positive predictive value to detect lymph node metastasis in lymph nodes with spiculated margins and 100% sensitive with a 75% positive predictive value to detect lymph node metastasis in a lymph node with lobulated margins. The sensitivity and positive predictive value of MRI to detect heterogeneous nodal enhancement were 100% and 75% respectively. Conclusions: Our study results reinforce that MRI should be used as a modality of choice in the pretreatment assessment of lymph nodes in proven gynaecological malignancies in order to determine the line of patientmanagement, distinguishing surgical from non-surgical cases.
  53. Ayyildiz, Talat;Dolar, Enver;Ugras, Nesrin;Dizdar, Oguzhan Sitki;Adim, Saduman Balaban;Yerci, Omer 4711
    https://doi.org/10.7314/APJCP.2014.15.11.4711 PDF KSCI
    Introduction: Adiponectin (ApN) is a complement C1q-related protein, mainly secreted from adipose tissue, that signals through ApN receptor1 (Adipo-R1) and ApN receptor 2 (Adipo-R2). Low serum ApN concentrations are associated with obesity-related malignancies. However, there are very few studies on any prognostic role of ApN receptors in gastric cancer. Objectives: The aim of this study is to investigate the relationship between AdipoR1/R2 expression and early/advanced stage gastric cancer in terms of clinicopathologic characteristics and survival. Materials and Methods: Eighteen patients with early and 39 with advanced stage gastric cancer who underwent surgical gastric resection were included in this study. Results: Adipo-R1 expression was low in 2 of the 18 patients with early stage gastric cancer (11.1%), while 4 had low Adipo-R2 expression (22.2%). In those with advanced stage gastric cancer, 7 of 39 had low Adipo-R1 expression (17.9%) and 16 had low Adipo-R2 expression (41%). Adipo-R2 expression was significantly higher (p=0.011) in moderately differentiated tumors when compared to well-differentiated tumors. While there was nearly a statistically significant relationship between TNM stage (T, tumor size; N, regional lymph node; M, whether distant metastases exist) and Adipo-R2 expression (p=0.054), there was no relationship between Adipo-R1/-R2 expression with tumor stage and survival. Conclusion: Adipo-R1/-R2 expression has no prognostic significance of in early/advanced stage gastric cancer.
  54. Madan, Renu;Pathy, Sushmita;Subramani, Vellaiyan;Sharma, Seema;Mohanti, Bidhu Kalyan;Chander, Subhash;Thulkar, Sanjay;Kumar, Lalit;Dadhwal, Vatsla 4717
    https://doi.org/10.7314/APJCP.2014.15.11.4717 PDF KSCI
    Background: Dosimetric comparison of two dimensional (2D) radiography and three-dimensional computed tomography (3D-CT) based dose distributions with high-dose-rate (HDR) intracavitry radiotherapy (ICRT) for carcinoma cervix, in terms of target coverage and doses to bladder and rectum. Materials and Methods: Sixty four sessions of HDR ICRT were performed in 22 patients. External beam radiotherapy to pelvis at a dose of 50 Gray in 27 fractions followed by HDR ICRT, 21 Grays to point A in 3 sessions, one week apart was planned. All patients underwent 2D-orthogonal and 3D-CT simulation for each session. Treatment plans were generated using 2D-orthogonal images and dose prescription was made at point A. 3D plans were generated using 3D-CT images after delineating target volume and organs at risk. Comparative evaluation of 2D and 3D treatment planning was made for each session in terms of target coverage (dose received by 90%, 95% and 100% of the target volume: D90, D95 and D100 respectively) and doses to bladder and rectum: ICRU-38 bladder and rectum point dose in 2D planning and dose to 0.1cc, 1cc, 2cc, 5cc, and 10cc of bladder and rectum in 3D planning. Results: Mean doses received by 100% and 90% of the target volume were $4.24{\pm}0.63$ and $4.9{\pm}0.56$ Gy respectively. Doses received by 0.1cc, 1cc and 2cc volume of bladder were $2.88{\pm}0.72$, $2.5{\pm}0.65$ and $2.2{\pm}0.57$ times more than the ICRU bladder reference point. Similarly, doses received by 0.1cc, 1cc and 2cc of rectum were $1.80{\pm}0.5$, $1.48{\pm}0.41$ and $1.35{\pm}0.37$ times higher than ICRU rectal reference point. Conclusions: Dosimetric comparative evaluation of 2D and 3D CT based treatment planning for the same brachytherapy session demonstrates underestimation of OAR doses and overestimation of target coverage in 2D treatment planning.
  55. Sathian, Brijesh;Nagaraja, Sharath Burugina;Banerjee, Indrajit;Sreedharan, Jayadevan;De, Asis;Roy, Bedanta;Rajesh, Elayedath;Senthilkumaran, Subramanian;Hussain, Syed Ather;Menezes, Ritesh George 4723
    https://doi.org/10.7314/APJCP.2014.15.11.4723 PDF KSCI
    Background: Breast cancer is the second most common cancer in the world and by far the most frequent cancer among women. Objective: The present study was undertaken to assess the awareness of breast cancer warning signs and screening methods among the women of Pokhara valley, Nepal. Materials and Methods: A cross-sectional questionnaire survey was carried out in a community setting with the female population. The questionnaire was administered in face-to-face interviews by trained research assistants. Results: Nepalese women demonstrated poor awareness of warning signs like a breast lump, lump under the armpit, bleeding or discharge from the nipple, pulling of the nipple, changes in the position of the nipple, nipple rash, redness of the breast skin, changes in the size of the breast or nipple, changes in the shape of the breast or nipple, pain in the breast or armpit, and dimpling of the breast skin. While 100% of nurses were aware about breast self-examination(BSE), mammography and warning signs of breast cancer. Levels of knowledge were significantly poorer in women with other occupations. Graduates were more aware about BSE, mammogram and warning signs of breast cancer compared to those with other educational levels. Conclusions: The findings indicated that the level of awareness of breast cancer, including knowledge of warning signs and BSE, is sub-optimal among Nepalese women.
  56. Mansouri, Safae;Naim, Asmaa;Glaria, Luis;Marsiglia, Hugo 4727
    https://doi.org/10.7314/APJCP.2014.15.11.4727 PDF KSCI
    Background: Breast cancers are becoming more frequently diagnosed at early stages with improved long term outcomes. Late normal tissue complications induced by radiotherapy must be avoided with new breast radiotherapy techniques being developed. The aim of the study was to compare dosimetric parameters of planning target volume (PTV) and organs at risk between conformal (CRT) and intensity-modulated radiation therapy (IMRT) after breast-conserving surgery. Materials and Methods: A total of 20 patients with early stage left breast cancer received adjuvant radiotherapy after conservative surgery, 10 by 3D-CRT and 10 by IMRT, with a dose of 50 Gy in 25 sessions. Plans were compared according to dose-volume histogram analyses in terms of PTV homogeneity and conformity indices as well as organs at risk dose and volume parameters. Results: The HI and CI of PTV showed no difference between 3D-CRT and IMRT, V95 gave 9.8% coverage for 3D-CRT versus 99% for IMRT, V107 volumes were recorded 11% and 1.3%, respectively. Tangential beam IMRT increased volume of ipsilateral lung V5 average of 90%, ipsilateral V20 lung volume was 13%, 19% with IMRT and 3D-CRT respectively. Patients treated with IMRT, heart volume encompassed by 60% isodose (30 Gy) reduced by average 42% (4% versus 7% with 3D-CRT), mean heart dose by average 35% (495cGy versus 1400 cGy with 3D-CRT). In IMRT minimal heart dose average is 356 cGy versus 90cGy in 3D-CRT. Conclusions: IMRT reduces irradiated volumes of heart and ipsilateral lung in high-dose areas but increases irradiated volumes in low-dose areas in breast cancer patients treated on the left side.
  57. Wu, Jing-Jing;Wang, Xin-Hua;Li, Ling;Li, Xin;Zhang, Lei;Sun, Zhen-Chang;Fu, Xiao-Rui;Ma, Wang;Chang, Yu;Zhang, Xu-Dong;Han, Li-Juan;Zhang, Ming-Zhi 4733
    https://doi.org/10.7314/APJCP.2014.15.11.4733 PDF KSCI
    Purpose: We developed and evaluated a regimen including fotemustine, teniposide and dexamethasone (FTD) for treating patients with central nervous system (CNS) lymphoma based on pharmacokinetic properties of individual agents and in combination. Patients and Methods: In a comparison study, 8 patients with primary CNS lymphoma (PCNSL) and 8 with secondary CNS lymphoma (SCNSL) were treated with FTD (comprising fotemustine 100 mg/m2, 1h infusion, day 1; teniposide 60 mg/m2, >0.5 h infusion, on day 2, 3, 4; dexamethasone 40 mg, 1h infusion, on day 1, 2, 3, 4 and 5; and methotrexate 12 mg, cytosine arabinoside 50 mg plus dexamethasone 5 mg intrathecally, on day 2 and 7). Cycles were repeated every 3 weeks. After response assessment, patients received whole brain radiotherapy. Results: Of the 8 PCNSL patients, 4 (50%) achieved CR and 3 (38%) PR, an overall response rate of 88%. Four patients (50%) were in continuing remission at the end of this study after a median follow-up of 30 months (range 10 to 56 months). Of the 8 SCNSL patients the overall response rate was 63% (CR+PR: 38%+25%). All responses were achievable with predictable toxicity mainly reflecting reversible myelosuppression. Conclusion: This study suggests that FTD could be an effective treatment for CNS lymphoma, and is worthy of further evaluation.