Asian Pacific Journal of Cancer Prevention

Pandurangan, Ashok Kumar;Esa, Norhaizan Mohd 5543

https://doi.org/10.7314/APJCP.2013.14.10.5543 PDF KSCI

Colorectal cancer (CRC), a complex multi-step process involving progressive disruption of homeostatic mechanisms controlling intestinal epithelial proliferation/inflammation, differentiation, and programmed cell death, is the third most common malignant neoplasm worldwide. A number of promising targets such as inducible nitric acid (iNOS), cyclooxygenase (COX)-2, NF-E2-related factor 2 (Nrf2), $Wnt/{\beta}$-catenin, Notch and apoptotic signaling have been identified by researchers as useful targets to prevent or therapeutically inhibit colon cancer development. In this review article, we aimed to explore the current targets available to eliminate colon cancer with an update of dietary and non-nutritional compounds that could be of potential use for interaction with regulatory molecules to prevent CRC.

Lachumy, Subramanion Jothy;Oon, Chern Ein;Deivanai, Subramanian;Saravanan, Dharmaraj;Vijayarathna, Soundararajan;Choong, Yee Siew;Yeng, Chen;Latha, Lachimanan Yoga;Sasidharan, Sreenivasan 5553

https://doi.org/10.7314/APJCP.2013.14.10.5553 PDF KSCI

Plants play important roles in human life not only as suppliers of oxygen but also as a fundamental resource to sustain the human race on this earthly plane. Plants also play a major role in our nutrition by converting energy from the sun during photosynthesis. In addition, plants have been used extensively in traditional medicine since time immemorial. Information in the biomedical literature has indicated that many natural herbs have been investigated for their efficacy against lethal irradiation. Pharmacological studies by various groups of investigators have shown that natural herbs possess significant radioprotective activity. In view of the immense medicinal importance of natural product based radioprotective agents, this review aims at compiling all currently available information on radioprotective agents from medicinal plants and herbs, especially the evaluation methods and mechanisms of action. In this review we particularly emphasize on ethnomedicinal uses, botany, phytochemistry, mechanisms of action and toxicology. We also describe modern techniques for evaluating herbal samples as radioprotective agents. The usage of herbal remedies for combating lethal irradiation is a green anti-irradiation approach for the betterment of human beings without high cost, side effects and toxicity.

Rao, Sree Vidya Krishna;Mejia, Gloria;Roberts-Thomson, Kaye;Logan, Richard 5567

https://doi.org/10.7314/APJCP.2013.14.10.5567 PDF KSCI

The prevalence of oral cancers (OC) is high in Asian countries, especially in South and Southeast Asia. Asian distinct cultural practices such as betel-quid chewing, and varying patterns of tobacco and alcohol use are important risk factors that predispose to cancer of the oral cavity. The aim of this review is to provide an update on epidemiology of OC between 2000 and 2012. A literature search for this review was conducted on Medline for articles on OC from Asian countries. Some of the articles were also hand searched using Google. High incidence rates were reported from developing nations like India, Pakistan, Bangladesh, Taiwan and Sri Lanka. While an increasing trend has been observed in Pakistan, Taiwan and Thailand, a decreasing trend is seen in Philippines and Sri Lanka. The mean age of occurrence of cancer in different parts of oral cavity is usually between 51-55 years in most countries. The tongue is the leading site among oral cancers in India. The next most common sites in Asian countries include the buccal mucosa and gingiva. The 5 year survival rate has been low for OC, despite improvements in diagnosis and treatment. Tobacco chewing, smoking and alcohol are the main reasons for the increasing incidence rates. Low socioeconomic status and diet low in nutritional value lacking vegetables and fruits contribute towards the risk. In addition, viral infections, such as HPV and poor oral hygiene, are other important risk factors. Hence, it is important to control OC by screening for early diagnosis and controlling tobacco and alcohol use. It is also necessary to have cancer surveillance at the national-level to collect and utilise data for cancer prevention and control programs.

Satpute, Pranali Shirish;Hazarey, Vinay;Ahmed, Riyaz;Yadav, Lalita 5579

https://doi.org/10.7314/APJCP.2013.14.10.5579 PDF KSCI

Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the "drivers" of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.

Verit, Fatma Ferda;Yucel, Oguz 5589

https://doi.org/10.7314/APJCP.2013.14.10.5589 PDF KSCI

The aim of this review article was to evaluate the relationship and the possible etiological mechanisms between endometriosis, leiomyoma (LM) and adenomyosis and gynecological cancers, such as ovarian and endometrial cancer and leiomyosarcoma (LMS). MEDLINE was searched for all articles written in the English literature from July 1966 to May 2013. Reports were collected systematically and all the references were also reviewed. Malignant transformation of gynecologic benign diseases such as endometriosis, adenomyosis and LM to ovarian and endometrial cancer remains unclear. Hormonal factors, inflammation, familial predisposition, genetic alterations, growth factors, diet, altered immune system, environmental factors and oxidative stress may be causative factors in carcinogenesis. Early menarche, low parity, late menopause and infertility have also been implicated in the pathogenesis of these cancers. Ovarian cancers and endometriosis have been shown to have common genetic alterations such as loss of heterozygosity (LOH), PTEN, p53, ARID1A mutations. MicroRNAs have also been implicated in malignant transformation. Inflammation releases proinflammatory cytokines, and activates tumor associated macrophages (TAMS) and nuclear factor kappa b (NF-KB) signaling pathways that promote genetic mutations and carcinogenesis. MED12 mutations in LM and smooth muscle tumors of undetermined malignant potential (STUMP) may contribute to malignant transformation to LMS. A hyperestrogenic state may be shared in common with pathogenesis of adenomyosis, LM and endometrial cancer. However, the effect of these benign gynecologic diseases on endometrial cancer should be studied in detail. This review study indicates that endometriosis, LM, adenomyosis may be associated with increased risk of gynecological cancers such as endometrial and ovarian cancers. The patients who have these gynecological benign diseases should be counseled about the future risks of developing cancer. Further studies are needed to investigate the relationship between STUMPs, LMS and LM and characteristics and outcome endometrial carcinoma in adenomyotic patients.

Gao, Fei;Zhang, Jin-Ming;Wang, Zhan-Guo;Peng, Wei;Hu, Hui-Ling;Fu, Chao-Mei 5599

https://doi.org/10.7314/APJCP.2013.14.10.5599 PDF KSCI

With the high morbidity and mortality caused by cancer, finding new and more effective anti-cancer drugs is very urgent. In current research, biotransformation plays a vital role in the research and development of cancer drugs and has obtained some achievements. In this review, we have summarized four applications as follows: to exploit novel anti-cancer drugs, to improve existing anti-cancer drugs, to broaden limited anti-cancer drug resources and to investigate correlative mechanisms. Three different groups of important anti-cancer compounds were assessed to clarify the current practical applications of biotransformation in the development of anti-cancer drugs.

Nassiri, Mohammadreza;Kooshyar, Mohammad Mahdi;Roudbar, Zahra;Mahdavi, Morteza;Doosti, Mohammad 5609

https://doi.org/10.7314/APJCP.2013.14.10.5609 PDF KSCI

Background: Colorectal cancer is the third most common cancer in both men and women in the world and the second leading cause of cancer-related deaths. The incidence of colorectal cancer has increased in Iran in the past three decades and is now considered as a serious problem for our society. This cancer has two types hereditary and non-hereditary, 80% of cases being the latter. Considering that the relationship between SNPs with diseases is a concern, many researchers believed that they offer valuable markers for identifying genes responsible for susceptibility to common diseases. In some cases, they are direct causes of human disease. One SNP can increase risk of cancer, but when considering the rate of overlap and frequency of DNA repair pathways, it might be expected that SNP alone cannot affect the final result of cancer, although several SNPs together can exert a significant influence. Therefore identification of these SNPs is very important. The most important loci which include mutations are: MLH1, MSH2, PMS2, APC, MUTYH, SMAD7, STK11, $XRCC_3$, $DNMT_1$, MTHFR, Exo1, $XRCC_1$ and VDR. Presence of SNPs in these genes decreases or increases risk of colorectal cancer. Materials and Methods: In this article we reviewed the Genes and SNPs associated with non-hereditary and hereditary of colorectal cancer that recently were reported from candidate gene y, meta-analysis and GWAS studies. Results: As with other cancers, colorectal cancer is associated with SNPs in gene loci. Generally, by exploring SNPs, it is feasible to predict the risk of developing colorectal cancer and thus establishing proper preventive measures. Conclusions: SNPs of genes associated with colorectal cancer can be used as a marker SNP panel as a potential tool for improving cancer diagnosis and treatment planning.

Shahab, Sadaf;Shamsi, Tahir Sultan;Ahmed, Nuzhat 5615

https://doi.org/10.7314/APJCP.2013.14.10.5615 PDF KSCI

Nucleophosmin (NPM1) is a protein of highly conserved nature which works as a molecular chaperone and is mostly found in nucleoli. NPM also involved in the maturation of preribosomes and duplication of centrosomes. Furthermore, it is also active in control and regulation of the ARF-p53 tumor suppressor pathway. A high rate of incidence and prognostic involvement is reported by various authors in AML patients. In AML it behaves as a favorable prognostic marker. NPM mutations are more frequently associated with normal-karyotype AML and are usually absent in patients having abnormal or poor cytogenetic. NPM mutations are not frequent in other hematopoietic tumors. Two main types of mutations have been described to date. Both of these cause abnormal cytoplasmic localization of NPM1. Their high incidence rate in normal karyoptype and their favorable nature m ake those mutations hot spot or front face mutations which should be checked before treatment starts.

Singh, Jagtar;Jayaraj, Rama;Baxi, Siddhartha;Ramamoorthi, Ramya;Thomas, Mahiban 5621

https://doi.org/10.7314/APJCP.2013.14.10.5621 PDF KSCI

Mucosal head and neck cancers are squamous cell carcinomas that develop in the upper-aero digestive epithelium. Together they constitute the sixth most common cancer with an estimated 900,000 new cases and 350,000 deaths each year reported worldwide. The risk factors are tobacco, alcohol and human papillomavirus (HPV). Our research team initially reported a high incidence rate of HNC in the indigenous population of the Northern Territory. Mortality rates also vary in the Australian States and Territories, with particularly high mortality observed in the Northern Territory. There is a paucity of incidence studies of HNC for the Australian States and Territories. Therefore this review primarily focuses on variation in incidence and mortality iacross the country and highlights specifically the high incidence and mortality in the Northern Territory. Attention is also given to sex-specific incidence and mortality rates.

Shaukat, Uzma;Ismail, Muhammad;Mehmood, Nasir 5625

https://doi.org/10.7314/APJCP.2013.14.10.5625 PDF KSCI

Occurrence of breast cancer is related to genetic as well as cultural, environmental and life-style factors. Variations in diversity of these factors among different ethnic groups and geographical areas emphasize the immense need for studies in all racial-ethnic populations. The incidence of breast cancer in Pakistan is highest in Asians after Jews in Israel and 2.5 times higher than that in neighboring countries like Iran and India, accounting for 34.6% of female cancers. The Pakistani population is deficient in information regarding breast cancer etiology and epidemiology, but efforts done so far had suggested consanguinity as a major risk factor for frequent mutations leading to breast cancer and has also shed light on genetic origins in different ethnic groups within Pakistan. World-wide research efforts on different ethnicities have enhanced our understanding of genetic predisposition to breast cancer but despite these discoveries, 75% of the familial risk of breast cancer remains unexplained, highlighting the fact that the majority of breast cancer susceptibility genes remain unidentified. For this purpose Pakistani population provides a strong genetic pool to elucidate the genetic etiology of breast cancer because of cousin marriages. In this review, we describe the known breast cancer predisposition factors found in the local Pakistani population and the epidemiological research work done to emphasize the importance of exploring factors/variants contributing to breast cance, in order to prevent, cure and decrease its incidence in our country.

Tan, Pei-Xin;Du, Sha-Sha;Ren, Chen;Yao, Qi-Wei;Yuan, Ya-Wei 5631

https://doi.org/10.7314/APJCP.2013.14.10.5631 PDF KSCI

Cochlea hair cell death is regarded to be responsible for the radiation-induced sensorineural hearing loss (SNHL), which is one of the principal complications of radiotherapy (RT) for head and neck cancers. In this mini-review, we focus on the current progresses trying to unravel mechanisms of radiation-induced hair cell death and find out possible protection. P53, reactive oxygen species (ROS) and c-Jun N-terminal kinase (JNK) pathways have been proposed as pivotal in the processes leading to radiation hair cell death. Potential protectants, such as amifostine, N-acetylcysteine (NAC) and epicatechin (EC), are claimed to be effective at reducing radiation-inducedhair cell death. The RT dosage, selection and application of concurrent chemotherapy should be pre-examined in order to minimize the damage to cochlea hair cells.

Xie, Yuan-Jie;Long, Zhi-Feng;He, Xiu-Sheng 5637

https://doi.org/10.7314/APJCP.2013.14.10.5637 PDF KSCI

The definite molecular mechanisms underlying the genesis of nasopharyngeal carcinomas (NPCs) remain to be completely elucidated. miRNAs are small non-coding RNAs which are implicated in cell proliferation, apoptosis, and even carcinogenesis through negatively regulating gene expression post-transcriptionally. EBV was the first human virus found to express miRNAs. EBV-encoded BART-miRNAs and dysregulated cellular miRNAs are involved in carcinogenesis of NPC by interfering in the expression of viral and host cell genes related to immune responses and perturbing signal pathways of proliferation, apoptosis, invasion, metastasis and even radio-chemo-therapy sensitivity. Additional studies on the roles of EBV-encoded miRNAs and cellular miRNAs will provide new insights concerning the complicated gene regulated network and shed light on novel strategies for the diagnosis, therapy and prognosis of NPC.

Tao, Han-Chuan;Wang, Hai-Xiao;Dai, Min;Gu, Cheng-Yu;Wang, Qun;Han, Ze-Guang;Cai, Bing 5645

https://doi.org/10.7314/APJCP.2013.14.10.5645 PDF KSCI

Src homology 2 domain containing (SHC) is a proto-oncogene which mediates cell proliferation and carcinogenesis in human carcinomas. Here, the SHC SH2-domain binding protein 1 (SHCBP1) was first established to be up-regulated in human hepatocellular carcinoma (HCC) tissues by array-base comparative genome hybridization (aCGH). Meanwhile, we examine and verify it by quantitative real-time PCR and western blot. Our current data show that SHCBP1 was up-regulated in HCC tissues. Overexpression of SHCBP1 could significantly promote HCC cell proliferation, survival and colony formation in HCC cell lines. Furthermore, knockdown of SHCBP1 induced cell cycle delay and suppressed cell proliferation. Furthermore, SHCBP1 could regulate the expression of activate extracellular signal-regulated kinase 1/2 (ERK1/2) and cyclin D1. Together, our findings indicate that SHCBP1 may contribute to human hepatocellular carcinoma by promoting cell proliferation and may serve as a molecular target of cancer therapy.

Qiu, Yu;Zhao, Ya-Kun;Yuan, Gang-Jun;Zhu, Qing-Guo 5651

https://doi.org/10.7314/APJCP.2013.14.10.5651 PDF KSCI

Objective: Major histocompatibility complex class I chain-related A (MICA) is a stress-inducible glycoprotein that can be shed as a soluble protein. This study was conducted to determine the expression of MICA in renal cell carcinoma (RCC) and examine the clinical relevance of soluble MICA (sMICA) in this disease. Methods: Immunohistochemistry and real-time PCR analyses were performed to assess the expression of MICA in 48 pairs of RCC and adjacent normal renal tissues. Serum levels of sMICA were measured in 48 RCC patients, 12 patients with benign renal tumors, and 20 healthy individuals. The correlations between sMICA levels and clinicopathological parameters were analyzed and the diagnostic performance of sMICA in RCC was evaluated. Results: RCCs exhibited elevated expression of MICA compared to adjacent normal tissues. Serum concentrations of sMICA were significantly greater in RCC patients ($348.5{\pm}32.5pg/ml$) than those with benign disease ($289.3{\pm}30.4pg/ml$) and healthy controls ($168.4{\pm}43.2pg/ml$) and significantly correlated with advanced tumor stage, lymph node metastasis, distant metastasis, vascular invasion, and higher histological grade. Using a cut-off point of 250 pg/ml, sMICA demonstrated a specificity and sensitivity of 63.2% and 75.6%, respectively, in distinguishing between RCC and benign renal tumors. Conclusion: MICA expression is upregulated in RCC and increased serum sMICA levels predict aggressive tumor behavior. However, the applicability of sMICA alone is limited in distinguishing RCC from benign renal tumors.

Balasubramaniam, Ganesh;Saoba, Sushama Laxman;Sarhade, Monika Nilesh;Kolekar, Suvarna Anand 5657

https://doi.org/10.7314/APJCP.2013.14.10.5657 PDF KSCI

In India, among males, leukemia rates vary across the country. The present unmatched hospital-based case-control study conducted at Tata Memorial Hospital included subjects registered between the years 1997-99. There were 246 leukemia cases and 1,383 normal controls. Data on demographics, lifestyle, diet and occupation history were recorded. Cigarette (OR=2.1) and bidi smoking (OR=3.4) showed excess risk for leukemia. Odds ratios were 3.9 for fish-eaters, 0.40 for chilli eaters, 1.5 for milk drinkers and 0.60 for coffee drinkers, compared to non-drinkers/eaters. However, neither exposure to use of pesticides nor cotton dust showed any excess risk for leukemia.

Tamgue, Ousman;Chai, Cheng-Sen;Hao, Lin;Zambe, John-Clotaire Daguia;Huang, Wei-Wei;Zhang, Bin;Lei, Ming;Wei, Yan-Ming 5663

https://doi.org/10.7314/APJCP.2013.14.10.5663 PDF KSCI

The histone methyltransferase EZH2 (enhancer of zeste homolog 2) plays critical roles in prostate cancer (PCa) development and is a potential target for PCa treatment. Triptolide possesses anti-tumor activity, but it is unknown whether its therapeutic effect relates with EZH2 in PCa. Here we described EZH2 as a target for Triptolide in PCa cells. Our data showed that Triptolide suppressed PCa cell growth and reduced the expression of EZH2. Overexpression of EZH2 attenuated the Triptolide induced cell growth inhibition. Moreover, Triptolide treatment of PC-3 cells resulted in elevated mRNA levels of target genes (ADRB2, CDH1, CDKN2A and DAB2IP) negatively regulated by EZH2 as well as reduced mRNA levelsan of EZH2 positively regulated gene (cyclin D1). Our findings suggest the PCa cell growth inhibition mediated by Triptolide might be associated with downregulation of EZH2 expression and the subsequent modulation of target genes.

Hasan, Tarique Noorul;Shafi, Gowhar;Syed, Naveed Ahmed;Alsaif, Mohammed Abdullah;Alsaif, Abdulaziz Abdullah;Alshatwi, Ali Abdullah 5671

https://doi.org/10.7314/APJCP.2013.14.10.5671 PDF KSCI

Incidence of breast cancer shows geographical variation, even within areas of ethnic homogeneity. Saudi Arabia has witnessed an increase in occurrence of breast cancer in its unexplored ethnic populations over the past few years. We aimed at determining whether any association exists between single nucleotide polymorphisms in breast cancer associated gene 1 (BRCA1) and breast cancer associated gene 2 (BRCA2) and the risk of breast cancer. TaqMan based Real Time Polymerase chain reaction genotyping assays were used to determine the frequency of single nucleotide polymorphisms in BRCA1 (rs799917) and BRCA2 (rs144848) in a group of 100 breast cancer patients and unaffected age matched controls of Saudi Arabian origin. The present data revealed that neither BRCA1 nor the BRCA2 studied variant show any significant association with the disease. This study failed to find any role of the concerned variants in breast cancer either as risk or as prognostic factors. The small number of patients registered was one of the limitations of this study. In summary, comparison of mutation profile with other ethnic populations and regions reflected both differences and similarities indicating co-exposure to a unique set of risk factors. The differences could be due to exposure to particular environmental carcinogens; different lifestyle, reproductive pattern; dietary or cultural practices of Saudi Arabian women that need further investigations.

Ding, Jing;Tang, Jie;Chen, Xin;Men, Hai-Tao;Luo, Wu-Xia;Du, Yang;Ge, Jun;Li, Cong;Chen, Ye;Cheng, Ke;Qiu, Meng;Liu, Ji-Yan 5675

https://doi.org/10.7314/APJCP.2013.14.10.5675 PDF KSCI

Background: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and mortality of patients with some cancers. Insulin like growth factor (IGF) and insulin receptor (IR) signaling axes play important roles in both cancer and diabetes development. We aimed to explore the expression characteristics of proteins in IGF/IR axis in non-small cell lung cancer (NSCLC) cases with preexisting T2DM. Methods: Fifty-five NSCLC patients with preexisting T2DM were retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio. The expression of proteins in IGF/IR axis was detected by immunohistochemical staining. Clinicopathological data were collected to analyze their relationship with the protein expression. Results: Both IGF 1 receptor (IGF-1R) and insulin receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM group, compared with those without T2DM. The high expression of IGF-1R and IRS-2 were found to be negatively associated with lymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found more in the subgroup whose T2DM duration was more than 4 years. No difference was detected in the expression of IRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or without T2DM. Conclusion: Our study found higher expression of IGF-1R and IRS-2 proteins in NSCLC patients with preexisting T2DM, and that there was an association with early stage NSCLC, which suggested that IGF signaling may play an important early event in development of NSCLC associated with diabetes.

Sipetic-Grujicic, Sandra;Murtezani, Zafir;Ratkov, Isidora;Grgurevic, Anita;Marinkovic, Jelena;Bjekic, Milan;Miljus, Dragan 5681

https://doi.org/10.7314/APJCP.2013.14.10.5681 PDF KSCI

Background: To compare breast cancer incidence and mortality trends in Central Serbia between males and females in the period 1999-2009. Materials and Methods: In this descriptive study, mortality data were obtained from the National Statistics Institute and morbidity data were derived from Institute of Public Health of Serbia for the period of interest. Results: Breast cancer is a leading cancer in the female population of Central Serbia, whereas in male population it is not on the list of 10 leading localizations, concerning both incidence as well as mortality. In the period 1999-2009 the average standardized incidence rates of breast cancer were 60.5/100,000 in women and 1.4/100,000 in men, while average standardized mortality rates were 20.4/100,000 and 0.4/100,000. The average standardized incidence and mortality rates were about 45 times higher in females than males. Male breast cancer comprises approximately 2.1% of all breast cancer cases. The average age-specific mortality and incidence rates increased with age in both sexes. In the observed period standardized mortality rates of breast cancer increased significantly only in men ($y=0.320+0.0215{\times}$, p=0.044). Conclusions: The increase of breast cancer incidence in both sexes and mortality in men, indicate an urgent need for Serbian health professionals to apply existing cancer control and preventive measures. Male breast cancer is more present than in other world regions, with an outstanding increase of mortality, which demands a timely identification (screening) and adequate treatment. A national policy including mammography should be considered in the light of the newest findings.

Zhu, Shan;Yao, Feng;Li, Wen-Huan;Wan, Jin-Nan;Zhang, Yi-Min;Tang, Zhao;Khan, Shahzad;Wang, Chang-Hua;Sun, Sheng-Rong 5687

https://doi.org/10.7314/APJCP.2013.14.10.5687 PDF KSCI

Type 2 diabetes mellitus (T2DM) has contributed to advanced breast cancer development over the past decades. However, the mechanism underlying this contribution is poorly understood. In this study, we determined that high glucose enhanced proteasome activity was accompanied by enhanced proliferation, migration and invasion, as well as suppressed apoptosis, in human breast cancer MCF-7 cells. Proteasome inhibitor bortezomib (BZM) pretreatment mitigated high glucose-induced MCF-7 cell growth and invasion. Furthermore, high glucose increased protein kinase C delta ($PKC{\delta}$)-phosphorylation. Administration of the specific $PKC{\delta}$ inhibitor rottlerin attenuated high glucose-stimulated cancer cell growth and invasion. In addition, $PKC{\delta}$ inhibition by both rottlerin and $PKC{\delta}$ shRNA significantly suppressed high glucose-induced proteasome activity. Our results suggest that $PKC{\delta}$-dependent ubiquitin proteasome system activation plays an important role in high glucose-induced breast cancer cell growth and metastasis.

Koca, Dogan;Ozdemir, Oguzhan;Akdeniz, Huseyin;Unal, Olcun Umit;Yilmaz, Ugur 5693

https://doi.org/10.7314/APJCP.2013.14.10.5693 PDF KSCI

Background: Changes in the attitudes and behavior of relatives of breast cancer patients concerning cancer prevention and screening after diagnosis in a loved one were evaluated. Materials and Methods: Forty-three questions were used to collect data from the relatives of the breast cancer patients who had been living with their relatives for at least one year. Results: The study group was composed of 171 female relatives (median age: 43, range: 17-82 yr). After the patients were diagnosed with breast cancer, changes in the attitudes and behavior of their relatives toward the prevention and screening of cancer were evident in 78 (45.6%) of the study participants (e.g. eating habits, quit or reduced smoking, exercise habits). In addition, it was noted that some characteristics of the relatives had different effects on different attitudes and behavior. Conclusions: Awareness on breast cancer among the relatives of breast cancer patients is useful for the management of health and social problems that can be seen in these individuals. At the same time, this information could help countries determine whether their actual level of healthcare for early cancer diagnosis, prevention, and screening are adequate.

Cai, Yong;Wang, Ji-Ying;Liu, Hui 5699

https://doi.org/10.7314/APJCP.2013.14.10.5699 PDF KSCI

Objective: To investigate the clinical effects of whole brain radiotherapy concomitant with targeted therapy for brain metastasis in non-small cell lung cancer (NSCLC) patients with chemotherapy failure. Materials and Methods: Of the 157 NSCLC patients with chemotherapy failure followed by brain metastasis admitted in our hospital from January 2009 to August 2012, the combination group (65 cases) were treated with EGFR-TKI combined with whole brain radiotherapy while the radiotherapy group (92 cases) were given whole brain radiotherapy only. Short-term effects were evaluated based on the increased MRI in brain 1 month after whole brain radiotherapy. Intracranial hypertension responses, hematological toxicity reactions and clinical effects of both groups were observed. Results: There were more adverse reactions in the combination group than in radiotherapy group, but no significant differences were observed between the two groups in response rate (RR) and disease control rate (DCR) (P>0.05). Medium progression free survival (PFS), medium overall survival (OS) and 1-year survival rate in combination group were 6.0 months, 10.6 months and 42.3%, while in the radiotherapy group they were 3.4 months, 7.7 months and 28.0%, respectively, which indicated that there were significant differences in PFS and OS between the two groups (P<0.05). Additionally, RPA grading of each factor in the combination group was a risk factor closely related with survival, with medium PFS in EGFR and KRAS mutation patients being 8.2 months and 11.2 months, and OS being 3.6 months and 6.3 months, respectively. Conclusions: Whole brain radiotherapy concomitant with target therapy is favorable for adverse reaction tolerance and clinical effects, being superior in treating brain metastasis in NSCLC patients with chemotherapy failure and thus deserves to be widely applied in the clinic.

Aldahmash, Abdullah;Atteya, Muhammad;Elsafadi, Mona;Al-Nbaheen, May;Al-Mubarak, Husain Adel;Vishnubalaji, Radhakrishnan;Al-Roalle, Ali;Al-Harbi, Suzan;Manikandan, Muthurangan;Matthaei, Klaus Ingo;Mahmood, Amer 5705

https://doi.org/10.7314/APJCP.2013.14.10.5705 PDF KSCI

Background: Embryonic stem cells (ESCs) have the potential to form teratomas when implanted into immunodeficient mice, but data in immunocompetent mice are limited. We therefore investigated teratoma formation after implantation of three different mouse ESC (mESC) lines into immunocompetent mice. Materials and Methods: BALB/c mice were injected with three highly germline competent mESCs (129Sv, BALB/c and C57BL/6) subcutaneously or under the kidney capsule. After 4 weeks, mice were euthanized and examined histologically for teratoma development. The incidence, size and composition of teratomas were compared using Pearson Chi-square, t-test for dependent variables, one-way analysis of variance and the nonparametric Kruskal-Wallis analysis of variance and median test. Results: Teratomas developed from all three cell lines. The incidence of formation was significantly higher under the kidney capsule compared to subcutaneous site and occurred in both allogeneic and syngeneic mice. Overall, the size of teratoma was largest with the 129Sv cell line and under the kidney capsule. Diverse embryonic stem cell-derived tissues, belonging to the three embryonic germ layers, were encountered, reflecting the pluripotency of embryonic stem cells. Most commonly represented tissues were nervous tissue, keratinizing stratified squamous epithelium (ectoderm), smooth muscle, striated muscle, cartilage, bone (mesoderm), and glandular tissue in the form of gut- and respiratory-like epithelia (endoderm). Conclusions: ESCs can form teratomas in immunocompetent mice and, therefore, removal of undifferentiated ESC is a pre-requisite for a safe use of ESC in cell-based therapies. In addition the genetic relationship of the origin of the cell lines to the ability to transplant plays a major role.

Cao, Xue-Yuan;Jia, Zhi-Fang;Cao, Dong-Hui;Kong, Fei;Jin, Mei-Shan;Suo, Jian;Jiang, Jing 5713

https://doi.org/10.7314/APJCP.2013.14.10.5713 PDF KSCI

Background: DNA methyltransferase-3a (DNMT3a) plays significant roles in embryogenesis and the generation of aberrant methylation in carcinogenesis. This study aimed to investigate associations between single nucleotide polymorphisms (SNPs) of the DNMT3a gene and risk of Helicobacter pylori infection, gastric atrophy and gastric cancer. Methods: The subjects comprised 447 patients with gastric cancer; 111 individuals with gastric atrophy and 961 healthy controls. Two SNPs (rs1550117 and rs13420827) of the DNMT3a gene were genotyped by Taqman assay. DNMT3a expression was analyzed in cancer tissues from 89 patients by tissue microarray technique. Odds ratio (ORs) and 95% confidence intervals were calculated by multivariate logistic regression. Results: Among healthy controls, risk of H.pylori infection was significantly higher in subjects with the rs1550117 AA genotype, compared to those with GG/AG genotypes of DNMT3a [OR=2.08, (95%CI: 1.02-4.32)]. However, no significant correlation was found between the two SNPs and risk of developing gastric atrophy or gastric cancer. In addition, no increase in DNMT3a expression was observed in the gastric cancer with H.pylori infection. Conclusions: This study revealed that DNMT3a rs1550117 polymorphism is significantly associated with an increased risk of H. pylori infection, but did not support any evidence for contributions of DNMT3a rs1550117 and rs13420827 to either gastric atrophy or gastric cancer. The biological roles of DNMT3a polymorphisms require further investigation.

Farshori, Nida Nayyar;Al-Sheddi, Ebtesam Saad;Al-Oqail, Mai Mohammad;Musarrat, Javed;Al-Khedhairy, Abdulaziz Ali;Siddiqui, Maqsood Ahmed 5719

https://doi.org/10.7314/APJCP.2013.14.10.5719 PDF KSCI

Pharmacological and preventive properties of Petroselinum sativum seed extracts are well known, but the anticancer activity of alcoholic extracts and oil of Petroselinum sativum seeds on human breast cancer cells have not been explored so far. Therefore, the present study was designed to investigate the cytotoxic activities of these extracts against MCF-7 cells. Cells were exposed to 10 to $1000{\mu}g/ml$ of alcoholic seed extract (PSA) and seed oil (PSO) of Petroselinum sativum for 24 h. Post-treatment, percent cell viability was studied by 3-(4, 5-dimethylthiazol-2yl)-2, 5-biphenyl tetrazolium bromide (MTT) and neutral red uptake (NRU) assays, and cellular morphology by phase contrast inverted microscopy. The results showed that PSA and PSO significantly reduced cell viability, and altered the cellular morphology of MCF-7 cells in a concentration dependent manner. Concentrations of $50{\mu}g/ml$ and above of PSA and $100{\mu}g/ml$ and above of PSO were found to be cytotoxic in MCF-7 cells. Cell viability at 50, 100, 250, 500 and $1000{\mu}g/ml$ of PSA was recorded as 81%, 57%, 33%, 8% and 5%, respectively, whereas at 100, 250, 500, and $1000{\mu}g/ml$ of PSO values were 90%, 78%, 62%, and 8%, respectively by MTT assay. MCF-7 cells exposed to 250, 500 and $1000{\mu}g/ml$ of PSA and PSO lost their typical morphology and appeared smaller in size. The data revealed that the treatment with PSA and PSO of Petroselinum sativum induced cell death in MCF-7 cells.

Li, Jie;Yang, Chun-Xu;Mei, Zi-Jie;Chen, Jing;Zhang, Shi-Min;Sun, Shao-Xing;Zhou, Fu-Xiang;Zhou, Yun-Feng;Xie, Cong-Hua 5725

https://doi.org/10.7314/APJCP.2013.14.10.5725 PDF KSCI

Cancer patients often suffer from local tumor recurrence after radiation therapy. Cell cycling, an intricate sequence of events which guarantees high genomic fidelity, has been suggested to affect DNA damage responses and eventual radioresistant characteristics of cancer cells. Here, we established a radioresistant lung cancer cell line, A549R, by exposing the parental A549 cells to repeated ${\gamma}$-ray irradiation with a total dose of 60 Gy. The radiosensitivity of A549 and A549R was confirmed using colony formation assays. We then focused on examination of the cell cycle distribution between A549 and A549R and found that the proportion of cells in the radioresistant S phase increased, whereas that in the radiosensitive G1 phase decreased. When A549 and A549R cells were exposed to 4 Gy irradiation the total differences in cell cycle redistribution suggested that G2-M cell cycle arrest plays a predominant role in mediating radioresistance. In order to further explore the possible mechanisms behind the cell cycle related radioresistance, we examined the expression of Cdc25 proteins which orchestrate cell cycle transitions. The results showed that expression of Cdc25c increased accompanied by the decrease of Cdc25a and we proposed that the quantity of Cdc25c, rather than activated Cdc25c or Cdc25a, determines the radioresistance of cells.

Ensani, Fereshteh;Enayati, Ladan;Rajabiani, Afsaneh;Omranipour, Ramesh;Alavi, Nasrinalsadat;Mosahebi, Sara 5731

https://doi.org/10.7314/APJCP.2013.14.10.5731 PDF KSCI

Background: The object of this study was to examine whether a new protocol including step-sectioning and immunohistochemistry (IHC) staining of axillary sentinel nodes (SN) would lead to detection of more metastases in patients with breast cancer. Materials and Methods: Sixty-nine tumor free sentinel lymph nodes were examined. Step frozen sectioning was performed on formalin fixed SN and stained both by hematoxylin and eosin (H and E) and cytokeratin markers using IHC. Any tumoral cell in IHC stained slides were considered as a positive result. Metastases up to 0.2 mm were considered as isolated tumor cells and 0.2 up to 2 mm as micrometastasis. Results: Mean age of the patients was $48.7{\pm}12.2$ years. Step sectioning of the SN revealed 11 involved by metastasis which was statistically significant (p<0.001). Furthermore, 15 (21.7%) of the patients revealed positive results in IHC staining for pan-CK marker and this was also statistically significant (p=0.001). Ten patients had tumoral involvement in lymph nodes harvested from axillary dissection and 4 out of 15 lymph nodes with positive result for CK marker were isolated tumor cells. However, 4 of 10 patients with tumor positive lymph nodes in axillary dissection were negative for CK marker and in contrast 6 of the pan-CK positive SN were in patients with tumor-free axillary lymph nodes. Conclusions: Both IHC and step sectioning improve the detection rate of metastases. Considering the similar power of these two methods, we recommend using either IHC staining or step sectioning for better evaluation of harvested SNs.

Yu, Qing;Yu, Xiong-Fei;Zhang, Shou-De;Wang, Hao-Hao;Wang, Hai-Yong;Teng, Li-Song 5735

https://doi.org/10.7314/APJCP.2013.14.10.5735 PDF KSCI

Background: A number of studies have investigated the association between increased pretreatment serum C-reactive protein (CRP) levels and the prognosis of gastric cancer. However, due to the inconsistent results, whether the serum CRP level can be a prognostic factor in primary gastric cancer remains controversial. Methods: We searched Medline, PubMed, Embase and the Cochrane Central Register of Controlled Trials for relevant high-quality reports. A meta-analysis was carried out using the included studies to assess the association between pretreatment serum CRP level and overall survival (OS) in patients with gastric cancer. Correlation analyses were conducted to evaluate the relationship between serum CRP and tumor characteristics such as tumor node metastasis (TNM) stage and recurrence. Results: Twelve reports involving 2,597 patients with gastric cancer were included. Primary meta-analysis indicated a significant association between elevated CRP level and poor OS (HR 1.77, 95% CI 1.56-2.00). Subgroup analyses showed no single factor could alter the primary results when we divided the included studies by "number of patients", "max follow-up period", "TNM stage", "treatment" and "cut-off value". Correlation analyses showed that serum CRP level was significantly related to TNM stage (OR 2.96, 95% CI 2.22-3.93) and tumor recurrence (OR 1.81, 95% CI 1.21-2.71). Conclusions: We demonstrated that increased pretreatment serum CRP level (${\geq}10mg/L$) was significantly associated with poor prognosis in gastric cancer patients, either in early or advanced stages.

Dutta, Anand;Girotra, Mohit;Merchant, Nipun;Nair, Padmanabhan;Dutta, Sudhir Kumar 5741

https://doi.org/10.7314/APJCP.2013.14.10.5741 PDF KSCI

Background: Heat-shock protein70 (HSP70) are intracellular protein chaperones, with emerging evidence of their association with various diseases. We have previously reported significantly elevated plasma-HSP70 (pHSP70) in pancreatic cancer. Current methods of pHSP70 isolation are ELISA-based which lack specificity due to cross-reactivity by similarities in the amino-acid sequence in regions of the protein backbone resulting in overestimated HSP70 value. Materials and Methods: This study was undertaken to develop a methodology to capture all isoforms of pHSP70, while further defining their tyrosine and serine phosphorylation status. Results: The methodology included gel electrophoresis on centrifuged supernatant obtained from plasma incubated with HSP70 antibody-coupled beads. After blocking non-specific binding sites, blots were immunostained with monoclonal-antibody specific for human-HSP70, phosphoserine and phosphotyrosine. Conclusions: Our novel immunocapture approach has distinct advantages over the commercially available methods of pHSP70 quantification by allowing isolation of molecular aggregates of HSP70 with additional ability to precisely distinguish phosphorylation state of HSP70 molecules at serine and tyrosine residues.

Tang, Qing-Feng;Ji, Qing;Tang, Yu;Hu, Song-Jiao;Bao, Yi-Jie;Peng, Wen;Yin, Pei-Hao 5747

https://doi.org/10.7314/APJCP.2013.14.10.5747 PDF KSCI

Golgi phosphoprotein 2 (GOLPH2) is a very important biomarker in a variety of diseases. Its biological function is not clear, particularly in gastric cancer. To investigate the role of GOLPH2 in human gastric cancer, and determine its effect on the Th1 lymphocyte response, its expression and that of IL-12A were measured by real-time PCR and immunohistochemistry. The relationship between GOLPH2 and IL-12A was analysed statistically. The effect of GOLPH2 on the Th1 lymphocyte response was investigated with an in vitro co-culture system. The results showed that in human gastric cancer, the expression of GOLPH2 was significantly higher and the expression of IL-12A was lower than in normal gastric mucosal tissues, and the expression levels of GOLPH2 and IL-12A were negatively correlated. In addition, obvious down-regulation of the Th1 response was observed when lymphocytes were co-cultured with gastric cancer SGC7901 cells over-expressing GOLPH2. GOLPH2 down-regulated the expression of IL-12A, and inhibited the expression of TNF-${\alpha}$ and IFN-${\gamma}$. The results indicated that GOLPH2 down-regulates the Th1 response via suppression of IL-12A in human gastric cancer, and this might provide a target for the prevention and treatment.

Basu, Partha;Dutta, Sankhadeep;Begum, Rakiba;Mittal, Srabani;Dutta, Paromita Das;Bharti, Alok Chandra;Panda, Chinmay Kumar;Biswas, Jaydip;Dey, Bindu;Talwar, Gursaran Prashad;Das, Bhudev Chandra 5753

https://doi.org/10.7314/APJCP.2013.14.10.5753 PDF KSCI

Curcumin and curcumin containing polyherbal preparations have demonstrated anti-microbial and antiviral properties in pre-clinical studies. Till date no therapeutic intervention has been proved to be effective and safe in clearing established cervical human papillomavirus (HPV) infection. The present study evaluated the efficacy of Basant polyherbal vaginal cream (containing extracts of curcumin, reetha, amla and aloe vera) and of curcumin vaginal capsules to eliminate HPV infection from cervix. Women were screened by Pap smear and HPV DNA test by PCR. HPV positive women without high grade cervical neoplasias (N=287) were randomized to four intervention arms to be treated with vaginal Basant cream, vaginal placebo cream, curcumin vaginal capsules and placebo vaginal capsules respectively. All subjects were instructed to use one application of the assigned formulation daily for 30 consecutive days except during menstruation and recalled within seven days of the last application for repeat HPV test, cytology and colposcopy. HPV clearance rate in Basant arm (87.7%) was significantly higher than the combined placebo arms (73.3%). Curcumin caused higher rate of clearance (81.3%) than placebo though the difference was not statistically significant. Vaginal irritation and itching, mostly mild to moderate, was significantly higher after Basant application. No serious adverse events were noted.

Pan, Yan;Zhao, Lei;Chen, Xing-Miao;Gu, Yong;Shen, Jian-Gang;Liu, Lu-Ming 5761

https://doi.org/10.7314/APJCP.2013.14.10.5761 PDF KSCI

The potential correlation of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with hepatocellular carcinoma (HCC) susceptibility is ambiguous. Taking account of inconsistent results of previous meta-analyses and new emerging literatures, we conducted a meta-analysis covering 15 case-control datasets to evaluate the relationship. Relevant studies from Medline, Embase and CNKI were retrieved. A fixed-effect model or a random-effect model, depending on between-study heterogeneity, were applied to estimate the association between XRCC1 polymorphism Arg399Gln and HCC risk with the results presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). In accordance with Hardy-Weinberg equilibrium, 15 studies with data for 6,556 individuals were enrolled in this systematic review. For overall HCC,thr XRCC1 polymorphism Arg399Gln was significantly associated with HCC susceptibility in a homozygote model as well as in a dominant model (G/G vs. A/A, OR=1.253, p=0.028; G/G+A/G vs. A/A, OR= 1.281, p=0.047, respectively), but not in a heterozygote model (A/G vs. A/A, OR=1.271, p=0.066) or a recessive model (G/G vs. A/G + A/A, OR= 1.049, p=0.542). Similar results were also observed on stratification analysis by ethnicity (A/G vs. A/A, OR=1.357, p=0.025; G/G vs. A/A, OR=1.310, p=0.011; G/G+A/G vs. A/A, OR= 1.371, p=0.013). However, no potential contribution of XRCC1 Arg399Gln polymorphism to HCC susceptibility in HBV/HCV subgroups was identified. No publication bias was found in this study. In conclusion, the XRCC1 Arg399Gln polymorphism contributes to HCC susceptibility. Due to the lack of studies in Western countries, further large-sample and rigorous studies are needed to validate the findings.

Ozveren, Husna;Cerit, Birgul;Ertop, Nesime Guzel 5769

https://doi.org/10.7314/APJCP.2013.14.10.5769 PDF KSCI

Background: This is a descriptive study to determine whether coursework that is focused on early diagnosis in cancer makes a difference in self-reported health promoting lifestyle behavior of students who study health management. Materials and Methods: The population of the study consisted of a sample of 104 students enrolled in the Department of Health Management at the Faculty of Health in Kirikkale University in Turkey. Forty-eight students enrolled in a course called "Early Diagnosis of Cancer" and fifty-six did not take this course. Demographic information was collected and the "Health Promotion Life-Style Profile (HPLP)" was used to collect health promotion data. Frequency and descriptive statistics including one-way ANOVA, Mann-Whitney U test, Kruskal Wallis tests were used to evaluate data. Results: The HPLP mean score of the students was found to be $127.5{\pm}17.45$. The highest mean score was observed for self-fulfillment and health responsibility, while the lowest was for diet and exercise sub-scales. It was found that certain variables were effective in developing health promoting lifestyle behaviors such as choosing this job voluntarily, working status of father and participation in social activity (p<0.05). In conclusion, it was found that the students had moderate levels of health promoting lifestyle behavior and they should be supported in terms of diet and exercise.

Zeng, Yu-Jie;Liu, Lu;Wu, Heng;Lai, Wei;Cao, Jie-Zhi;Xu, He-Yang;Wang, Jie;Chu, Zhong-Hua 5775

https://doi.org/10.7314/APJCP.2013.14.10.5775 PDF KSCI

Background: The gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine neoplasm. We summarized data in our centre to investigate the clinicopathological features, diagnostic methods, therapeutic approaches and prognosis for this neoplasm to increase knowledge of this disease in Asian populations. Method: A total of 122 patients treated at Sun Yet-san Memorial Hospital of Sun Yat-sen University between January 2000 and December 2011 were analyzed retrospectively. Results: Pancreas was the most common site of involvement (65/122, 53.3%); this disease has no special symptoms; positive rates of chromogranin A (CgA) and synaptophysin (Syn) were 81.1% and 87.7%, respectively. The positive rate of Syn had statistical difference among the three grades, but not CgA. Some 68 patients had G1 tumors, 32 G2 tumors and 22 G3 tumors, and Chi-square test showed that higher grading was correlated with worse prognosis (${\chi}^2=32.825$, P=0.0001). A total of 32 patients presented with distant metastasis, and 8 cases emerged during following up. Cox proportional hazards regression modeling showed that the tumor grade (P=0.01), lymphatic metastasis (P=0.025) and distant metastasis (P=0.031) were predictors of unfavorable prognosis. The overall 5-year survival rate was 39.6%, the 5-year survival rate of G1 was 55.7%, and the G2 and G3 were 34.2% and 0%, respectively. Conclusions: The incidence of gastroenteropancreatic neuroendocrine tumors has risen over the last 12 years. All grades of these diseases metastasize readily, and further research regarding the treatment of patients after radical surgery is needed to prolong disease-free survival.

Alshatwi, Ali Abdullah;Shafi, Gowhar;Hasan, Tarique Noorul;Syed, Naveed Ahmed;Khoja, Kholoud Khalid 5783

https://doi.org/10.7314/APJCP.2013.14.10.5783 PDF KSCI

Trigonella foenum in graecum (Fenugreek) is a traditional herbal plant used to treat disorders like diabetes, high cholesterol, wounds, inflammation, gastrointestinal ailments, and it is believed to have anti-tumor properties, although the mechanisms for the activity remain to be elucidated. In this study, we prepared a methanol extract from Fenugreek whole plants and investigated the mechanism involved in its growth-inhibitory effect on MCF-7 human breast cancer cells. Apoptosis of MCF-7 cells was evidenced by investigating trypan blue exclusion, TUNEL and Caspase 3, 8, 9, p53, FADD, Bax and Bak by real-time PCR assays inducing activities, in the presence of FME at $65{\mu}g/mL$ for 24 and 48 hours. FME induced apoptosis was mediated by the death receptor pathway as demonstrated by the increased level of Fas receptor expression after FME treatment. However, such change was found to be absent in Caspase 3, 8, 9, p53, FADD, Bax and Bak, which was confirmed by a time-dependent and dose-dependent manner. In summary, these data demonstrate that at least 90% of FME induced apoptosis in breast cell is mediated by Fas receptor-independently of either FADD, Caspase 8 or 3, as well as p53 interdependently.

Wu, Fei;Zhao, Zuo-Hui;Ding, Sen-Tai;Wu, Hai-Hu;Lu, Jia-Ju 5789

https://doi.org/10.7314/APJCP.2013.14.10.5789 PDF KSCI

Background: The high mobility group box 1 (HMGB1) protein is a widespread nuclear protein present in most cell types. It typically locates in the nucleus and functions as a nuclear cofactor in transcription regulation. However, HMGB1 can also localize in the cytoplasm and be released into extracellular matrix, where it plays critical roles in carcinogenesis and inflammation. However, it remains elusive whether HMGB1 is relocated to cytoplasm in clear cell renal cell carcinoma (ccRCC). Methods: Nuclear and cytoplasmic proteins were extracted by different protocols from 20 ccRCC samples and corresponding adjacent renal tissues. Western blotting and immunohistochemistry were used to identify the expression of HMGB1 in ccRCC. To elucidate the potential mechanism of HMGB1 cytoplasmic translocation, HMGB1 proteins were enriched by immunoprecipitation and analyzed by mass spectrometry (MS). Results: The HMGB1 protein was overexpressed and partially localized in cytoplasm in ccRCC samples (12/20, 60%, p<0.05). Immunohistochemistry results indicated that ccRCC of high nuclear grade possess more HMGB1 relocation than those with low grade (p<0.05). Methylation of HMGB1 at lysine 112 in ccRCC was detected by MS. Bioinformatics analysis showed that post-translational modification might affect the binding ability to DNA and mediate its translocation. Conclusion: Relocation of HMGB1 to cytoplasm was confirmed in ccRCC. Methylation of HMGB1 at lysine 112 might the redistribution of this cofactor protein.

Singh, Durg Vijay;Agarwal, Shikha;Singh, Preeti;Godbole, Madan Madhav;Misra, Krishna 5797

https://doi.org/10.7314/APJCP.2013.14.10.5797 PDF KSCI

In order to enhance the bioavailability of curcumin its conjugates with piperic acid and glycine were synthesized by esterifying the 4 and 4' phenolic hydroxyls, the sites of metabolic conjugation. Antiproliferative and apoptotic efficacy of synthesized conjugates was investigated in MCF-7 and MDA-MB-231 cell lines. $IC_{50}$ values of di-O-glycinoyl (CDG) and di-O-piperoyl (CDP) esters of curcumin were found to be comparable with that of curcumin. Both conjugates induced chromatin condensation fragmentation and apoptotic body formation. CDP exposure to MCF-7 cells induced apoptosis initiating loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) followed by inhibition of translocation of transcription factor NF-${\kappa}B$ and release of Cytochrome-C. Reactive oxygen species (ROS) production was evaluated by fluorescent activated cell sorter. Change in ratio of Bcl2/Bclxl was observed, suggesting permeablization of mitochondrial membrane leading to the release of AIF, Smac and other apoptogenic molecules. DNA fragmentation as a hallmark for apoptosis was monitored by TUNEL as well as agrose gel electrophoresis. Thus, it was proven that conjugation does not affect the therapeutic potential of parent molecule in vitro, while these could work in vivo as prodrugs with enhanced pharmacokinetic profile. Pharmacokinetics of these molecules under in vivo conditions is a further scope of this study.

Li, Mei;Jiang, Xiao-Gang;Gu, Zhen-Lun;Zhang, Zu-Bin 5805

https://doi.org/10.7314/APJCP.2013.14.10.5805 PDF KSCI

This study was conducted to analyze the molecular mechanisms responsible for anti-proliferation effects of glaucocalyxin A in cultured MCF-7 and Hs578T breast cancer cells. The concentration that reduced cell viability to 50% (IC50) after 72 h treatment was derived and potential molecular mechanisms of anti-proliferation using the IC50 were investigated as changes in cell cycle arrest and apoptosis. Gene and protein expression changes related to apoptosis were investigated by semi-quantitative RT-PCR and western blotting, respectively. Involvement of phosphorylated mitogen-activated protein kinases and JNK signaling in regulation of these molecules was characterized by western blotting. Cell viability decreased in a concentration-dependent manner and the IC50 was determined as $1{\mu}M$ in MCF-7 and $4{\mu}M$ in Hs578T cell. Subsequently, we demonstrated that the GLA-induced MCF-7 and Hst578T cell death was due to cell cycle arrest at the G2/M transition and was associated with activation of the c-jun N-terminal kinase (JNK) pathway. We conclude that GLA has the potential to inhibit the proliferation of human breast cancer cells through the JNK pathway and suggest its application forthe effective therapy for patients with breast cancer.

Najafi, Behrouz;Anvari, Saeid;Roshan, Zahra Atrkar 5811

https://doi.org/10.7314/APJCP.2013.14.10.5811 PDF KSCI

Background: Breast cancer is the most common cancer among women. Molecular subtypes are important in determining prognosis. This study evaluated five-year disease-free survival among four molecular subtypes in patients with early stages of breast cancer. Materials and Methods: In this retrospective descriptive-analytical study, information on patients with breast cancer between 2001-2010 was evaluated. Five hundred ninety two patients in the early stages of breast cancer (stages 1 and 2) were selected to undergo anthracycline-based chemotherapy. Relapse, death or absence (censor) were considered as the end of the study. Patients based on ER, PR and HER-2 expression were divided into four subtypes (luminal A, luminal B, HER-2 enriched and triple negative). Information based upon questionnaire was analysed. To show the patients survival rate, life table and Kaplan-Meyer methods were used, and for comparing mean survival among different groups, the Log-Rank test was utilized. Results: Mean age at diagnosis was $47.9{\pm}9.6$. Out of the 592 patients, 586 were female (99%) and 6 were male (1%). Considering breast cancer molecular subtypes, 361 patients were in the luminal A group (61%), 49 patients in the luminal B group (8.3%), 48 patients in the HER-2 enriched group (8.1%) and 134 in the triple negative group (22.6%). Mean disease-free survival was 53.7 months overall, 55.4 months for the luminal A group, 48.3 months for the luminal B group, 43 months for the HER-2enriched group and 54.6 months for the triple negatives. Disease free survival differed significantly among the molecular subtypes (p value=0.0001). Conclusions: The best disease-free survival rate was among the luminal A subgroup and the worst disease-free survival rate was among the HER-2 enriched subgroup. Disease free survival rate in the HER-2 positive groups (luminal B and HER-2 enriched) was worse than the HER-2 negative groups (luminal A and triple negative).

Bodapati, Srikanthi Lakshmi;Babu, Giridhara Rathnaiah 5817

https://doi.org/10.7314/APJCP.2013.14.10.5817 PDF KSCI

Background: It is important to understand the perceptions of oncologists to understand the comprehensive picture of clinical presentation of breast cancer. In the absence of clear evidence, clinical practice involving patients of breast cancer in India should provide insights into stages of breast cancer with which women present to their clinics and mode of screening of breast cancer prevalent in Andhra Pradesh. Materials and Methods: A qualitative study was conducted to understand the perceptions of oncologists regarding clinical presentation of breast cancer, stages at which women present to clinics, and mode of screening of breast cancer prevalent in Andhra Pradesh. In-depth interviews (IDI) were conducted with ten practising oncologists from various public and private cancer hospitals in Hyderabad city to understand their perspectives on breast cancer and screening. The data were triangulated to draw inferences suitable for the current public Health scenario. Results: Late presentation was indicated as the most important cause of decreased survival among women. Most women present at Stage 3 and 4 when there is no opportunity for surgical intervention. The results indicate that there is a huge gap in awareness about breast cancer, especially in rural areas and among poor socioeconomic groups. Even despite knowledge, most women delay in reporting due to reasons like fear, embarrassment, cost, ignorance, negligence, and easy going attitude. Conclusions: It is important to improve awareness about breast cancer and screening methods for promoting early screening. The study inferred that it would be beneficial to establish cancer registries in rural areas. Also, the policymakers need to make key decisions which among three methods (breast self examination (BSE), clinical breast examination and mammography) can best be used as a screening tool and how to successfully implement population wide screening program to prevent mortality and morbidity from breast cancer in India.

Rajbhandary, S.;Zhao, Ming-Feng;Zhao, Nan;Lu, Wen-Yi;Zhu, Hai-Bo;Xiao, Xia;Deng, Qi;Li, Yu-Ming 5825

https://doi.org/10.7314/APJCP.2013.14.10.5825 PDF KSCI

Background/Objectives: Maintenance of cellular function in culture is vital for transfer and development following adoptive immunotherapy. Dual properties of IL-21 in activating T cells and reducing activation induced cell death led us to explore the mechanism of action of IL-21 enhanced proliferation and cytotoxic potential of CIK cells. Method: CIK cells cultured from PBMCs of healthy subjects were stimulated with IL-21 and cellular viability and cytotoxicity to K562 cells were measured. To elucidate the mechanism of action of IL-21, mRNA expression of cytotoxic factors was assessed by RT-PCR and protein expression of significantly important cytotoxic factors and cytokine secretion were determined through flow cytometry and ELISA. Western blotting was performed to check the involvement of the JAK/STAT pathway following stimulation. Results: We found that IL-21 did not enhance in vitro proliferation of CIK cells, but did increase the number of cells expressing the CD3+/CD56+ phenotype. Cytotoxic potential was increased with corresponding increase in perforin ($0.9831{\pm}0.1265$ to $0.7592{\pm}0.1457$), granzyme B ($0.4084{\pm}0.1589$ to $0.7319{\pm}0.1639$) and FasL ($0.4015{\pm}0.2842$ to $0.7381{\pm}0.2568$). Interferon gamma and TNF-alpha were noted to increase ($25.8{\pm}6.1ng/L$ to $56.0{\pm}2.3ng/L$; and $5.64{\pm}0.61{\mu}g/L$ to $15.14{\pm}0.93{\mu}g/L$, respectively) while no significant differences were observed in the expression of granzyme A, TNF-alpha and NKG2D, and NKG2D. We further affirmed that IL-21 signals through the STAT-3 and STAT-5b signaling pathway in the CIK cell pool. Conclusion: IL-21 enhances cytotoxic potential of CIK cells through increasing expression of perforin, granzyme B, IFN-gamma and TNF-alpha. The effect is brought about by the activation of STAT-3 and STAT-5b proteins.

Rasool, Sabha;Kadla, Showkat Ahmad;Khan, Tanzeela;Qazi, Falak;Shah, Nisar Ahmad;Basu, Javed;Khan, Bilal Ahmad;Ahktar, Qulsum;Sameer, Aga Syed;Ganai, Bashir Ahmad 5833

https://doi.org/10.7314/APJCP.2013.14.10.5833 PDF KSCI

Roles of the vitamin D receptor in etiology of cancers, including colorectal cancer, have been repeatedly stressed in different parts of the world. A case control study aimed to evaluate the relationship between the two was therefore initiated in Kashmir, known both for its increasing incidence of gastrointestinal cancers and deficiency of micro-nutrients especially vitamin D. The study included a total of 617 subjects (312 colorectal cancer cases and 305 controls), with sampling carried out over a period of 5 years. DNA samples from the blood of the subjects were analyzed for start codon Fok I VDR polymorphism. We obtained a 1.3 fold increased risk among individuals homozygous for f variants as compared to subjects homozygous for F allele (odds ratio OR 1.3, 95%CI, 0.861-1.65). Our study also showed statistically significant results when dwelling and tumor location characteristics were stratified with Fok I polymorphism, all of which suggests a possible role of Fok I polymorphism in the etiology of CRC in Kashmir.

Yang, Bo;Chen, Wei-Hua;Wen, Xiao-Fei;Liu, Hui;Liu, Feng 5839

https://doi.org/10.7314/APJCP.2013.14.10.5839 PDF KSCI

Aim: We assessed the association between genetic variants of XPG, XPA, XPD, CSB, XPC and CCNH in the nucleotide excision repair (NER) pathway and risk of prostate cancer. Methods: We genotyped the XPG, XPA, XPD, CSB, XPC and CCNH polymorphisms by a 384-well plate format on the MassARRAY(R) platform. Multivariate logistical regression analysis was used to assess the associations between the six gene polymorphisms and risk of prostate cancer. Results: Individuals carrying the XPG rs229614 TT (OR=2.01, 95%CI=1.35-3.27) genotype and T allele (OR=1.73, 95%CI=1.37-2.57) were moderately significantly associated with a higher risk of prostate cancer. Subjects with XPD rs13181 G allele had a marginally increased risk of prostate cancer, with adjusted OR(95%CI) of 1.53 (1.04-2.37). Moreover, individuals carrying with CSB rs2228526 GG genotype (OR=2.05, 95% CI=1.23-3.52) and G allele (OR=1.56, 95%CI=1.17-2.05) were associated with a higher increased risk of prostate cancer. The combination genotype of XPG rs2296147 T and CSB rs2228526 G allele had accumulative effect on the risk of this cancer, with an OR (95% CI) of 2.23(1.37-3.59). Conclusions: Our study indicates that XPG rs2296147 and CSB rs2228526 polymorphisms are significantly associated with increased risk of prostate cancer, and that combination of XPG rs2296147 T allele and CSB rs2228526 G allele is strongly associated with an increased risk.

Panigoro, Ramdan;Susanto, Herman;Novel, Sinta Sasika;Hartini, Sri;Sahiratmadja, Edhyana 5843

https://doi.org/10.7314/APJCP.2013.14.10.5843 PDF KSCI

Background: Persistent infection with high risk human papillomavirus (hrHPV) is strongly associated with cervical cancer. Normal cervical cells may also harbor hrHPV, and detection of early hrHPV infection may minimize risk of cervical cancer development. This study aimed to compare two commercial HPV genotyping assays that may affordable for early screening in a limited-resource setting in Bandung, Indonesia. Materials and Methods: DNA from cervical biopsies with histologically confirmed as squamous cell cervical cacinoma were HPV genotyped by Linear Assay 1 (Roche Diagnostics, Mannheim, Germany) or Linear Assay 2 (Digene HPV Genotyping RH Test, Qiagen Gaithersburg, MD). In a subset of samples of each group, HPV genotype results were then compared. Results: Of 28 samples genotyped by linear assay 1, 22 (78.6%) demonstrated multiple infections with HPV-16 and other hrHPV types 18, 45 and/or 52. In another set of 38 samples genotyped by linear assay 2, 28 (68.4%) were mostly single infections by hrHPV type 16 or 18. Interestingly, 4 samples that had been tested by both kits showed discordant results. Conclusions: In a limited-resource area such as in Indonesia, country with a high prevalence of HPV infection a reliable cervical screening test in general population for early hrHPV detection is needed. Geographical variation in HPV genotyping result might have impacts for HPV prevalence and molecular epidemiology as the distribution in HPV genotypes should give clear information to assess the impact of HPV prophylactic vaccines.

Du, Peng;Cao, Hua;Wu, Hao-Rong;Zhu, Bao-Song;Wang, Hao-Wei;Gu, Chun-Wei;Xing, Chun-Gen;Chen, Wei 5849

https://doi.org/10.7314/APJCP.2013.14.10.5849 PDF KSCI

Background: Apoptosis may be induced after Bcl-2 expression is inhibited in proliferative cancer cells. This study focused on the effect of autophagy activation by ABT737 on anti-tumor effects of epirubicin. Methods: Cytotoxic effects of ABT737 on the HepG2 liver cancer cell line were assessed by MTT assay and cell apoptosis through flow cytometry. Mitochondrial membrane potential was measured by fluorescence microscopy. Monodansylcadaverin (MDC) staining was used to detect activation of autophagy. Expression of p53, p62, LC3, and Beclin1, apoptotic or autophagy related proteins, was detected by Western blotting. Results: ABT737 and epirubicin induced growth inhibition in HepG2 cells in a dose- and time-dependent manner. Both ABT737 and epirubicin alone could induce cell apoptosis with a reduction in mitochondrial membrane potential as well as increased apoptotic protein expression. Further increase of apoptosis was detected when HepG2 cells were co-treated with ABT373 and epirubicin. Furthermore, our results demonstrated that ABT373 or epirubicin ccould activate cell autophagy with elevated autophagosome formation, increased expression of autophagy related proteins and LC3 fluorescent puncta. Conclusions: ABT737 influences cancer cells through both apoptotic and autophagic mechanisms, and ABT737 may enhance the effects of epirubicin on HepG2 cells by activating autophagy and inducing apoptosis.

Hussain, Arif;Mohsin, Javeria;Prabhu, Sathyen Alwin;Begum, Salema;Nusri, Qurrat El-Ain;Harish, Geetganga;Javed, Elham;Khan, Munawwar Ali;Sharma, Chhavi 5855

https://doi.org/10.7314/APJCP.2013.14.10.5855 PDF KSCI

Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking or reversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer related death. One such promising chemopreventive agent which has attracted considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. The present study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent, gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the results by nuclear morphological examination. Further we analyzed the modulation of expression of Bcl-2 and COX-2 on treatment of these cells with SFN by RT-PCR. SFN showed cytotoxic effects on MCF-7 cells in a dose- and time-dependent manner via an apoptotic mode of cell death. In addition, a combinational treatment of SFN and gemcitabine on MCF-7 cells resulted in growth inhibition in a synergistic manner with a combination index (CI)<1. Notably, SFN was found to significantly downregulate the expression of Bcl-2, an anti-apoptotic gene, and COX-2, a gene involved in inflammation, in a time-dependent manner. These results indicate that SFN induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 and COX-2 respectively. The combination of SFN and gemcitabine may potentiate the efficacy of gemcitabine and minimize the toxicity to normal cells. Taken together, SFN may be a potent anti-cancer agent for breast cancer treatment.

Sui, Shuang;Jiao, Zhen;Niyazi, Mayinuer;Sulaiya, Sulaiya;Lu, Ping;Qiao, You-Lin 5861

https://doi.org/10.7314/APJCP.2013.14.10.5861 PDF KSCI

We investigated the distribution of HPV genotypes in Uyghur women in Xinjiang region of China, and behavioral factors which could predispose them to HPV infection. In this cross-sectional study, women aged 15-59 years were recruited by cluster sampling method in Yutian region in 2009. Liquid-based cytology samples were analyzed centrally for HPV genotype with a linear array detector. Univariate and multivariate logistic regression analyses were performed to identify behavioral risk factors for HPV infection. A total of 883 Uyghur women were recruited successfully. The prevalence of high-risk HPV and low-risk HPV were 7.25% and 1.58%, respectively; the most common HPVs were HPV16, 51, 31, 39 and 58. We found that age of first sexual intercourse was a strong predictor for HPV infection (odds ratio of 4.01 for ${\leq}15$ years versus ${\geq}25$). Having sexual partners ${\geq}3$ was the second predictor (OR 3.69, 95% CI 2.24-7.16). Cleaning the vagina after sex showed an increased risk of HPV infection (OR 2.72; 95% CI 1.98-5.13); Using the condom showed protective factors for HPV infection (OR 0.36; 95%CI0.12-0.53). HPV16, 51, 31, 39 and 58 were the priority types; the age of first sexual intercourse was identified as a major risk factor for HPV infection. Other notable risks were number of sexual partners and cleaning the vagina after sex. Changing these behavioral risk factors could help to reduce the occurrence of cervical cancer in this population.

Rashid, Rima Marhayu Abdul;Dahlui, Maznah 5867

https://doi.org/10.7314/APJCP.2013.14.10.5867 PDF KSCI

Background: Cervical cancer is the second most common cancer among Malaysian women with an ASR of 17.9 and a mortality rate of 5.6 per 100,000 population in 2008 (GLOBOCAN, 2008). The 5 year prevalence was estimated to be 14.5 per 100,000 population. As the second most common cancer affecting productive females, cervical cancer imposes an impact to the socioeconomic aspect of the country. However, the poor uptake of cervical cancer screening is a major problem in detecting early pre-cancerous lesions and thus, delay in initiating treatment for cervical cancer. Realizing the urgency to increase the uptake of PAP smear, besides enhancing the promotion of PAP smear screening for women above 35 years old, the call-recall system for pap smear screening had been piloted in one of the suburban districts which aimed to improve regular participation of women for cervical and breast cancer screening. This is of public health importance as identifying the best feasible option to increase patient's respond to participate in the screening program effectively in our setting will be helpful in implementing an organized regular population based screening program tailored to our setting. The pilot program of cervical cancer screening in Klang was an opportunity to assess different options in recalling patients for a repeat pap smear to increase their participation and adherence to the program. Methods and Results: This was a population based randomized control trial. Women aged 20-65 years in the population that matched the inclusion and exclusion criteria were re-called for a repeat smear. There are four different intervention groups; letter, registered letters, short messages services (SMS) and phone calls where 250 subjects were recruited into each group. Samples were generated randomly from the same population in Klang into four different groups. The first group received a recall letter for a repeat smear similar to the one that has been given during the first invitation. The intervention groups were either be given a registered letter, an SMS or a phone call to re-call them. The socio-demographic data of the patients who came for uptake were collected for further analysis. All the groups were followed up after 8 weeks to assess their compliance to the recall. Conclusions: The study will provide recommendations about the most effective methods for recall in a population based pap smear screening program on two outcomes: i) patients response; ii) uptake for repeat pap smear.

Yang, Xin;Wang, Xiao-Xiao;Qiu, Man-Tang;Hu, Jing-Wen;Yin, Rong;Xu, Lin;Zhang, Qin 5871

https://doi.org/10.7314/APJCP.2013.14.10.5871 PDF KSCI

Background: Single nucleotide polymorphisms (SNPs) occurring in Toll-like receptors (TLRs) may contribute to cancer risk. Many polymorphisms of TLR2 have been studied for associations, but the findings are conflicting. Methodology/Principal Findings: We performed a meta-analysis of 14 studies to confirm the association between TLR2+597T>C (rs3804099), +1350C>T (rs3804100) and Arg753Gln (rs5743708) polymorphisms and cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of associations. There was no significant association between TLR2+597T>C and cancer risk in the codominant models (CC vs. TT: OR = 1.01, 95%CI = 0.86-1.17, $P_{heterogeneity}=0.148$; CT vs. TT: OR = 0.92, 95%CI = 0.69-1.23, $P_{heterogeneity}$ < 0.001), the recessive model (CC vs. CT+TT: OR = 0.86, 95%CI = 0.67-1.10, $P_{heterogeneity}=0.007$), the dominant model (CC+CT vs. TT: OR = 0.93, 95%CI = 0.76-1.15, $P_{heterogeneity}=0.001$) and the allele model (C vs. T: OR =0.93, 95%CI = 0.81-1.08, $P_{heterogeneity}=0.019$). Similarly, no significant associations between TLR2+1350C>T, Arg753Gln polymorphisms and cancer risk were found. However, in the sub-group analysis of ethnicities, the trend of pooled ORs in Asians was opposite to Caucasians. Conclusions: The present meta-analysis suggests that TLR2+597T>C (rs3804099), +1350C>T (rs3804100) and Arg753Gln (rs5743708) polymorphisms are not associated with cancer risk.

Ceber, Esin;Mermer, Gulengul;Okcin, Figen;Sari, Dilek;Demireloz, Mahide;Eksioglu, Aysun;Ogce, Filiz;Cakır, Dilek;Ozenturk, Gulsun 5877

https://doi.org/10.7314/APJCP.2013.14.10.5877 PDF KSCI

Background: The aim of the study was to determine breast cancer risk and early diagnosis applications in women aged ${\geq}50$. Materials and Methods: This cross-sectional, descriptive field study focused on a population of 4,815 in Mansuro$\breve{g}$lu with a 55.1% participation rate in screening. In the study, body mass index (BMI) was also evaluated in the calculation of breast cancer risk by the Breast Cancer Risk Assessment Tool (BCRA) (also called the "Gail Risk Assessment Tool"). The interviewers had a three-hour training provided by the researchers, during which interactive training methods were used and applications were supported with role-plays. Results: The mean age of the women participating in the study was $60.1{\pm}8.80$. Of these women, 57.3% were in the 50-59 age group, 71.7% were married, 57.3% were primary school graduates and 61.7% were housewives. Breast-cancer development rate was 7.4% in the women participating in the study. When they were evaluated according to their relationship with those with breast cancer, it was determined that 73.0% of them had firstdegree relatives with breast cancer. According to the assessment based on the Gail method, the women's breast cancer development risk within the next 5 years was 17.6%, whereas their calculated lifetime risk was found to be as low as 0.2%. Statistically significant differences (P=0.000) were determined between performing BSE-CBE and socio-demographic factors. Conclusions: It was determined that 17.6% of the participants had breast cancer risk. There was no statistically significant difference between the women with and without breast cancer risk in terms of early diagnosis practices, which can be regarded as a remarkable finding. It was planned to provide training about the early diagnosis and treatment of breast cancer for people with high-risk scores, and to conduct population-based breast cancer screening programs.

Chen, Ying;Zhang, Lei;Lv, Rui;Zhang, Wen-Qi 5883

https://doi.org/10.7314/APJCP.2013.14.10.5883 PDF KSCI

Previously, we demonstrated overexpression of semaphorin4D (SEMA4D, CD100) to be closely related to tumor angiogenesis in epithelial ovarian cancers (EOCs). However, the function and expression of SEMA4D in the EOC microenvironment has yet to be clarified in detail. In this study, we confirmed that overexpression of SEMA4D in primary tumors and ascites was related to low differentiation, platinum resistance and a refractory status (P<0.05), while high M2 macrophage count and percentage were evident in EOC patients with advanced FIGO stage and platinum resistance (P<0.05), using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and fluorescence-activated cell sorting (FACS), respectively. The data showed correlations of SEMA4D expression and M2 macrophage counts in primary tumors and M2 macrophage percentage in ascites (r=0.281 and 0.355, each P<0.05). In the Cox proportional hazard mode, SEMA4D expression was an independent indicator of overall survival (OS) and progression-free survival (PFS) for EOC patients. Furthermore, higher expression of SEMA4D in ovarian cancer cell lines (SKOV3, A2780, and SW626) and their supernatants were found than that in a human primary cultured ovarian cell and its supernatant by reversed transcript PCR (RT-PCR), Western blotting and ELISA, respectively. Interestingly, peripheral blood monocytes (MOs) tended towards the M2-polarized macrophage phenotype ($CD163^{high}$) in vitro after human recombined soluble SEMA4D protein stimulation. These findings suggest that SEMA4D might possibly serve as a reliable tool for early and accurate prediction of EOC poor prognosis and could playan important role in promoting tumor dissemination and metastasis in the EOC microenvironment. Thus SEMA4D and its role in macrophage polarization in EOC warrants further study.

Okamoto, Etsuji 5891

https://doi.org/10.7314/APJCP.2013.14.10.5891 PDF KSCI

Incidence/mortality of liver cancer follow logistic curves because there is a limit reflecting the prevalence of hepatitis virus carriers in the cohort. The author fitted logistic curves to incidence/mortality data covering the nine five-year cohorts born in 1911-1955 of both sexes. Goodness-of-fit of logistic curves was sufficiently precise to be used for future predictions. Younger cohorts born in 1936 or later were predicted to show constant decline in incidence/mortality in the future. The male cohort born in 1931-35 showed an elevated incidence/mortality of liver cancer early in their lives supporting the previous claim that this particular cohort had suffered massive HCV infection due to nation-wide drug abuse in the 1950s. Declining case-fatality observed in younger cohorts suggested improved treatment of liver cancer. This study demonstrated that incidence/mortality of liver cancer follow logistic curves and fitted logistic formulae can be used for future prediction. Given the predicted decline of incidence/mortality in younger cohorts, liver cancer is likely to be lost to history in the not-so-distant future.

An, Fu-Fei;Liu, Yuan-Chong;Zhang, Wei-Wei;Liang, Lei 5895

https://doi.org/10.7314/APJCP.2013.14.10.5895 PDF KSCI

Dictamnine (Dic) has the ability to exert cytotoxicity in human cervix, colon, and oral carcinoma cells and dihydroartemisinin (DHA) also has potent anticancer activity on various tumour cell lines. This report explores the molecular mechanisms by which Dic treatment and combination treatment with DHA and Dic cause apoptosis in human lung adenocarcinoma A549 cells. Dic treatment induced concentration- and time-dependent cell death. FCM analysis showed that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) was not involved. In addition, inhibition of caspase-3 using the specific inhibitor, z-DQMD-fmk, did not attenuate Dic-induced apoptosis, implying that Dic-induced caspase-3-independent apoptosis. Combination treatment with DHA and Dic dramatically increased the apoptotic cell death compared to Dic alone. Interestingly, pretreatment with z-DQMD-fmk significantly attenuated DHA and Dic co-induced apoptosis, implying that caspase-3 plays an important role in Dic and DHA co-induced cell apoptosis. Collectively, we found that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which mitochondria and caspase were not involved and DHA enhanced Dic induced A549 cell apoptosis via a caspase-dependent pathway.

Rashid, Rima Marhayu Abdul;Mohamed, Majdah;Hamid, Zaleha Abdul;Dahlui, Maznah 5901

https://doi.org/10.7314/APJCP.2013.14.10.5901 PDF KSCI

Objective: To compare the effectiveness of different methods of recall for repeat Pap smear among women who had normal smears in the previous screening. Design: Prospective randomized controlled study. Setting: All community clinics in Klang under the Ministry of Health Malaysia. Participants: Women of Klang who attended cervical screening and had a normal Pap smear in the previous year, and were due for a repeat smear were recruited and randomly assigned to four different methods of recall for repeat smear. Intervention: The recall methods given to the women to remind them for a repeat smear were either by postal letter, registered letter, short message by phone (SMS) or phone call. Main Outcome Measures: Number and percentage of women who responded to the recall within 8 weeks after they had received the recall, irrespective whether they had Pap test conducted. Also the numbers of women in each recall method that came for repeat Pap smear. Results: The rates of recall messages reaching the women when using letter, registered letter, SMS and phone calls were 79%, 87%, 66% and 68%, respectively. However, the positive responses to recall by letter, registered letter, phone messages and telephone call were 23.9%, 23.0%, 32.9% and 50.9%, respectively (p<0.05). Furthermore, more women who received recall by phone call had been screened (p<0.05) compared to those who received recall by postal letter (OR=2.38, CI=1.56-3.62). Conclusion: Both the usual way of sending letters and registered letters had higher chances of reaching patients compared to using phone either for sending messages or calling. The response to the recall method and uptake of repeat smear, however, were highest via phone call, indicating the importance of direct communication.

Lan, X.Y.;Sun, H.Y.;Liu, J.J.;Lin, Y.;Zhu, Z.Y.;Han, X.;Sun, X.;Li, X.R.;Zhang, H.C.;Tang, Z.Y. 5905

https://doi.org/10.7314/APJCP.2013.14.10.5905 PDF KSCI

Background: To investigate the preventive and therapeutic potential of garlic oil on human pancreatic carcinoma cells. Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was performed to study the effects of garlic oil on three human pancreatic cancer cell lines, AsPC-1, Mia PaCa-2 and PANC-1. Cell cycle progression and apoptosis were detected by flow cytometry (FCM), staining with PI and annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI), respectively. Morphologic changes of pancreatic cancer cells were observed under transmission electron microscopy (TEM) after treatment with garlic oil at low inhibitory concentrations ($2.5{\mu}M$ and $10{\mu}M$) for 24 hours. Results: Proliferation of the AsPC-1, PANC-1, and Mia PaCa-2 cells was obviously inhibited in the first 24 hours with the MTT assay. The inhibition effect was more significant after 48 hours. When cells were exposed to garlic oil at higher concentrations, an early change of the apoptotic tendency was detected by FCM and TEM. Conclusion: Garlic oil could inhibit the proliferation of AsPC-1, PANC-1, and Mia PaCa-2 cells in this study. Moreover, due to programmed cell death, cell cycle arrest, or both, pro-apoptosis effects on AsPC-1 cells were induced by garlic oil in a dose and time dependent manner in vitro.

Yildiz, Mustafa;Bozcu, Hakan;Tokgun, Onur;Karagur, Ege Riza;Akyurt, Oktay;Akca, Hakan 5911

https://doi.org/10.7314/APJCP.2013.14.10.5911 PDF KSCI

Cyclamen coum is a traditional medicinal plant in the Turkey. Its anticancer properties and whether cyclamen extract induces any cytotoxicity in solid cancer cell lines have not been thoroughly investigated previously. Therefore we examined cytotoxic effects on cervical cells; HeLa and non small cell lung cancer cell, H1299, lines; Cyclamen extract induced cellular death of both HeLa and H1299 cells in a dose dependent manner. We also analyzed the capacity of cyclamen extract to induce apoptosis by the TUNEL method. Here, for the first time we report that the extract of Cyclamen coum, an endemic plant for Turkey, Bulgaria, Georgia and the Middle East can induce cytotoxicity via apoptosis in HeLa and H1299 cells. These results imply that cyclamen extract can be further analyzed to potentially find novel anticancer compounds.

Huang, Fei;Lin, Chen;Shi, Yong-Hua;Kuerban, Gulinar 5915

https://doi.org/10.7314/APJCP.2013.14.10.5915 PDF KSCI

Aim: Although aberrant miRNA expression has been documented, altered miR-101 expression in cervical cancer and its carcinogenic effects and mechanisms remain unexplored. The aim of our study was to investigate the role of miR-101 alteration in cervical carcinogenesis. Methods: Expression of miR-101 was examined by quantitative real-time reverse transcriptase PCR (qRT-PCR) in Hela cells. After modulating miR-101 expression using miR-101 mimics, cell growth, apoptosis and proliferation, and migration were tested separately by MTT or flow cytometry and cell wound healing assay and protein expression was detected by qRT-PCR. The expression of COX-2 in Hela cell was also examined by immunohistochemical staining and the correlation with miR-101 expression was analysed. Results: The miR-101 demonstrated significantly low expression in Hela cell. When we transfected miR-101 mimics into Hela cells, the modulation of miR-101 expression remarkably influenced cell proliferation, cycling and apoptosis: 1) The expression of microRNA-101 tended to increase after transfection; 2) Overexpression of miR-101 was able to promote cell apoptosis, the apoptosis rate being markedly higher (97.6%) than that seen pre-transfection (12.2%) (P<0.05); 3) The miR-101 negatively regulates cell migration and invasion, scratch results being lower ($42.7um{\pm}2um$) than that observed pre-transfection ($181.4um{\pm}2um$); 4) miRNA-101 inhibits the proliferation of Hela cells as well as the level of COX-2 protein, which was negatively correlated with miR-101 expression. Conclusions: Overexpression of miR-101 has obvious inhibitory effects on cell proliferation, migration and invasion. Thus reduced miR-101 expression could participate in the development of cervical cancer at least partly through loss of inhibition of target gene COX-2, which probably occurs in a relative late phase of carcinogenesis. Our data suggest an important role of miR-101 in the molecular etiology of cancer and indicate potential application of miR-101 in cancer therapy.

Perez-Santos, Jose Luis Martin;Anaya-Ruiz, Maricruz 5921

https://doi.org/10.7314/APJCP.2013.14.10.5921 PDF KSCI

The objetive of this study was to explore a bibliometric approach to quantitatively assess current research trends with regard to breast cancer in Mexico. Articles were analyzed by scientific output and research performances of individuals, institutes, and collaborative countries with Mexico. Data were retrieved from the Web of Science database from 2003 to 2012; this was searched using different terms related to breast cancer, including "breast cancer", "mammary ductal carcinoma" and "breast tumour". Data were then extracted from each file, transferred to Excel charts and visualised as diagrams. A total of 256 articles were retrieved. The institutions with the majority of publications were the National Autonomous University of Mexico (22.3%), the National Institute of Cancerology (21.9%), and Social Security Mexican Institute (20.3%); clinical observation studies were the dominant investigation type (64%), and the main types of research were metabolics (24.2%) and pathology (21.5%). This article demonstrates the usefulness of bibliometrics to address key evaluation questions and to establish priorities, define future areas of research, and develop breast cancer control strategies in Mexico.

Li, Jun-Chuan;Zhu, Hong-Yu;Chen, Ting-Xuan;Zou, Lan-Ying;Wang, Xiao-Yan;Zhao, Hui-Chuan;Xu, Jun 5925

https://doi.org/10.7314/APJCP.2013.14.10.5925 PDF KSCI

Objective: This study aimed to examine the relationship between expression of mammal target of rapamycin (mTOR) and phosphorylation of mTOR (p-mTOR) protein in the PI3K/Akt/mTOR signaling pathways in gastrointestinal stromal tumors and relatiuonships with clinical factors. Methods: Immunohistochemistry was used to detect the expression of the associated proteins mTOR, p-mTOR, and phosphorylation of the tumor suppressor genes PTEN, P27, VEGF, and EGFR in 40 cases of gastrointestinal stromal tumors, with division into a very low and low risk group as well as a moderate and high risk group. Results: The positive rate of mTOR and p-mTOR was significantly increased in the moderate and high risk group compared with the very low and low risk group. The difference was statistically significant (P<0.05). When grouped according to size, the positive mTOR expression rate exhibited a statistical difference (P<0.05), which was significantly increased in the group of tumors larger than 5 cm. The difference in the positive mTOR and p-mTOR expression rate exhibit no statistical significance among the PTEN, P27, VEGF, and EGFR expression subgroups (P>0.05). Conclusion: The different expressions of mTOR and p-mTOR in the signal transduction pathway of gastrointestinal stromal tumor in the different degree-of-risk groups suggested that the mTOR and p-mTOR of the signal transduction pathway serve an important function in the occurrence and development of gastrointestinal stromal tumors.

Yilmaz, Umit;Zeybek, Umit;Kahraman, Ozlem Timirci;Kafadar, Ali Metin;Toptas, Bahar;Yamak, Nesibe;Celik, Faruk;Yaylim, Ilhan 5929

https://doi.org/10.7314/APJCP.2013.14.10.5929 PDF KSCI

Background: Primary brain tumors constitute a small percent of all malignant cancers, but their etiology remains poorly understood. ${\beta}3$ integrin (ITGB3) has been recognized to play influential roles in angiogenesis, tumor growth and metastasis. Intercellular adhesion molecule-1 (ICAM-1) is a surface glycoprotein important for tumor invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and ITGB3 could be associated with brain cancer development and progression in a Turkish population. Our study is the first to our knowledge to investigate the relationship between brain tumor risk and ICAM-1 and ${\beta}3$ integrin gene polymorphisms. Materials and Methods: The study covered 92 patients with primary brain tumors and 92 age-matched healthy control subjects. Evaluation of ${\beta}3$ integrin (Leu33Pro (rs5918)) and ICAM-1 (R241G (rs1799969) and K469E (rs5498)) gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: According to results of our research, the A allele of the ICAM-1 R241G gene polymorphism appeared to be a risk factor for primary brain tumors (p<0.001). Similarly, the frequency of the A mutant allele of ICAM-1 R241G was statistically significant in patients with brain tumors classified as glioma (p<0.001). When allele and genotype distributions of ICAM-1 K469E, ICAM-1 R241G and ${\beta}3$ integrin Leu33Pro gene polymorphisms were evaluated with age, sex, and smoking, there were no statistically significant differences. Haplotype analysis revealed that the frequencies of GAC (rs1799969-rs5498-rs5918) and GAT (rs1799969-rs5498-rs5918) haplotypes were significantly lower in patients as compared with controls (p=0.001; p=0.036 respectively). Conclusions: This study provides the first evidence that ICAM-1 R241G SNP significantly contributes to the risk of primary brain tumors in a Turkish population. In addition, our results suggest that ICAM-1 R241G in combination ICAM-1 K469E may have protective effects against the development of brain cancer.

Li, Xiao-Chao;Song, Wen-Jing 5935

https://doi.org/10.7314/APJCP.2013.14.10.5935 PDF KSCI

Our study is to determine the presence of endometrial intraepithelial neoplasia (EIN) in endometrial biopsy specimens classified by the 1994 World Health Organization (WHO) criteria for endometrial hyperplasia. Endometrial biopsy specimens that were stained with hematoxylin and eosin (HE) were examined and categorized by the WHO 1994 criteria and for the presence of EIN as defined by the International Endometrial Collaborative Group. ${\beta}$-catenin expression was examined by immunohistochemistry. A total of 474 cases of HE stained endometrial biopsy tissues were reviewed. There were 379 cases of simple endometrial hyperplasia, 16 with simple atypical endometrial hyperplasia, 48 with complex endometrial hyperplasia, and 31 with complex atypical endometrial hyperplasia. Among the 474 endometrial hyperplasia cases, there were 46 (9.7%) that were classified as EIN. Of these 46 cases, 11(2.9%) were classified as simple endometrial hyperplasia, 1 (6.3%) as simple atypical endometrial hyperplasia, 6 (12.5%) as complex endometrial hyperplasia, and 28 (90.3%) as complex atypical endometrial hyperplasia. EIN was associated with a higher rate of ${\beta}$-catenin positivity than endometrium classified as benign hyperplasia (72% vs. 22.5%, respectively, P<0.001), but a lower rate than endometrial adenocarcinoma (72% vs. 96.2%, respectively, P<0.001). In benign endometrial hyperplasia, high ${\beta}$-catenin expression was noted in the cell membranes, whereas in EIN and endometrial adenocarcinoma high expression was noted in the cytoplasm. In conclusion, EIN is more accurate than the WHO classification for the diagnosis of precancerous lesions of the endometrium.

de Camargo, Elaine Aparecida;da Silva, Glenda Nicioli;Gobette, Camila Pereira;de Castro Marcondes, Joao Paulo;Salvadori, Daisy Maria Favero 5941

https://doi.org/10.7314/APJCP.2013.14.10.5941 PDF KSCI

Tumor response to antineoplastic drugs is not always predictable. This is also true for bladder carcinoma, a highly recurrent neoplasia. Currently, the combination of cisplatin and gemcitabine is well accepted as a standard protocol for treating bladder carcinoma. However, in some cases, this treatment protocol causes harmful side effects. Therefore, we investigated the roles of the genes TP53, RASSF1A (a tumor suppressor gene) and hMLH1 (a gene involved in the mismatch repair pathway) in cell susceptibility to cisplatin/gemcitabine treatment. Two bladder transitional carcinoma cell (TCC) lines, RT4 (wild-type TP53) and 5637 (mutated TP53), were used in this study. First, we evaluated whether the genotoxic potential of cisplatin/gemcitabine was dependent on TP53 status. Then, we evaluated whether the two antineoplastic drugs modulated RASSF1A and hMLH1 expression in the two cell lines. Increased DNA damage was observed in both cell lines after treatment with cisplatin or gemcitabine and with the two drugs simultaneously, as depicted by the comet assay. A lack of RASSF1A expression and hypermethylation of its promoter were observed before and after treatment in both cell lines. On the other hand, hMLH1 downregulation, unrelated to methylation status, was observed in RT4 cells after treatment with cisplatin or with cisplatin and gemcitabine simultaneously (wild-type TP53); in 5637 cells, hMLH1 was upregulated only after treatment with gemcitabine. In conclusion, the three treatment protocols were genotoxic, independent of TP53 status. However, cisplatin was the most effective, causing the highest level of DNA damage in both wild-type and mutated TP53 cells. Gemcitabine was the least genotoxic agent in both cell lines. Furthermore, no relationship was observed between the amount of DNA damage and the level of hMLH1 and RASSF1A expression. Therefore, other alternative pathways might be involved in cisplatin and gemcitabine genotoxicity in these two bladder cancer cell lines.

Wei, Xue-Qing;Li, Xing;Xin, Xiao-Jie;Tong, Zhong-Sheng;Zhang, Sheng 5949

https://doi.org/10.7314/APJCP.2013.14.10.5949 PDF KSCI

Objectives: To compare the clinicalpathological features and prognosis between premenopausal breast cancer patients aged of <35 and ${\geq}35$ years old. Methods: The clinical data and survival status of 1498 cases premenopausal operable breast cancer treated in our hospital from 2002.1 to 2004. 12 were collected, 118 cases were aged <35. They were divided into 4 groups: Luminal A, Luminal B, HER2-positive, Triple-negative. The disease free survival (DFS) and overall survival (OS) were identified. Results: The 5-year DFS and OS rates were significantly lower in age<35 than in $age{\geq}35$ patients. In the Luminal B, HER2-positive, Triple-negative group, the 5-year recurrence risk was higher in age<35 than in $age{\geq}35$ patients, and age<35 patients' 5-year death risk was higher only in Luminal B, Triple-negative group. Regardless of whether lymph node involved, age<35 patients had a bad prognosis in both DFS and OS. Conclusions: Compared with premenopausal age ${\geq}35$ breast cancer, age<35 patients had a worse outcome.

Manwong, Mereerat;Songserm, Nopparat;Promthet, Supannee;Matsuo4, Keitaro 5953

https://doi.org/10.7314/APJCP.2013.14.10.5953 PDF KSCI

Background: Cholangiocarcinoma (CCA) is the most common cancer in Northeast Thailand. It is also a crucial health problem for Thai people. Various risk factors for CCA have been identified in the upper part of Northeast Thailand, but no similar studies of risk factors have been conducted in the lower parts of the region. This study aimed to investigate factors associated with CCA in the resident population. Materials and Methods: A hospital-based case-control study was conducted during 2009-2012 with the recruitment of 123 CCA cases and 123 non-CCA patient controls, matched for sex, age and residential area. Information was collected by interview with a structured questionnaire. Blood samples were collected for assays of anti-OV antibodies. Associations between various personal factors, dietary habits, family history, the presence of anti-OV antibodies and CCA were analyzed using multiple conditional logistic regression. Results: Patients who consumed raw meat (beef, pork) and alcoholic beverages ${\geq}3$ times per week had a higher risk of CCA than non-consumers ($OR_{adj}$=4.33; 95%CI=1.14-16.35 and $OR_{adj}$=2.13; 95%CI=1.00-4.55, respectively). Patients who had a family history of cancer had a higher risk than those who did not ($OR_{adj}$=4.34; 95%CI=1.80-10.43). Also, patients who had anti-OV antibodies (AU>23.337) had a higher risk than those whose anti-OV antibodies were below the cut-off ($AU{\leq}23.34$) ($OR_{adj}$=3.09; 95%CI=1.04-9.16). Conclusions: As is the case in the upper part of Northeast Thailand, OV infection is a crucial risk factor for CCA in people who live in lower part of the region. Similarly, a family history of cancer and the consumption of alcohol are risk factors for CCA.

Wang, Ying-Xin;Fan, Kai;Tao, Ding-Bo;Dong, Xiang 5957

https://doi.org/10.7314/APJCP.2013.14.10.5957 PDF KSCI

Background: Gliomas are the most common type of primary brain tumor in adults, and the X-ray repair complementing group 1 gene (XRCC1) is an important candidate gene influencing its risk. The objective of this study was to detect the influence of XRCC1 genetic polymorphisms on glioma risk. Materials and Methods: A total of 629 glioma patients and 641 cancer-free subjects were enrolled in this case-control study. The genotypes of the c.1471G>A genetic polymorphism were determined by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. The influence of the XRCC1 genetic polymorphism on glioma risk was evaluated by association analysis. Results: Our data indicated that the alleles/genotype of this genetic variant was statistically associated with glioma risk. The AA genotype was statistically associated with the increased risk of glioma compared to the GG wild genotype (odds ratios (OR) = 1.89, 95% CI 1.25-2.87, P = 0.003). The allele-A may contribute to increased the susceptibility to glioma (OR = 1.23, 95% CI 1.04-1.46, P = 0.017). Conclusions: These preliminary findings indicate that the c.1471G>A genetic polymorphism of XRCC1 has the potential to influence glioma susceptibility, and might be used as molecular marker for assessing glioma risk.

Toleutay, Ulpan;Reznik, Vitaly;Kalmatayeva, Zhanna;Smigelskas, Kastytis 5961

https://doi.org/10.7314/APJCP.2013.14.10.5961 PDF KSCI

Background: Breast cancer in Kazakhstan and its Kyzylorda oblast is the most prevalent cancer in women and features increasing trends of incidence. The aim of study was to reveal risk factors for breast cancer among women of Kyzylorda oblast of Kazakhstan. Materials and Methods: A hospital-based case-control study was conducted at Kyzylorda oblast Oncology Center, including 114 cases of breast cancer and 196 controls. Binary logistic regression analysis was performed. Results: Social and behavioral risk factors for breast cancer were evaluated, among which unfavorable living conditions, chronic stress, unilateral breastfeeding, breastfeeding less than 3 months and over 2 years, abortions, and hereditary predisposition were found to be related with increased breast cancer risk. Breastfeeding for 6-24 months was found to be protective. Conclusions: The findings may have significant impact on activity planning aimed towards breast cancer reduction among women in Kazakhstan.

Zhu, Yan-Mei;Liu, Jing-Wei;Xu, Qian;Yuan, Yuan 5965

https://doi.org/10.7314/APJCP.2013.14.10.5965 PDF KSCI

PIN1 is one member of the parvulin PPIase family. By controlling Pro-directed phosphorylation, PIN1 plays an important role in cell transformation and oncogenesis. There are many polymorphisms in the PIN1 gene, including rs2233678 and rs2233679 affecting the PIN1 promoter. Recently, a number of case-control studies were conducted to investigate the association between PIN1 gene rs2233678 and rs2233679 polymorphism and cancer risk. However, published data are still conflicting. In this paper, we summarized data for 5,427 cancer cases and 5,469 controls from 9 studies and attempted to assess the susceptibility of PIN1 gene polymorphism to cancers by a synthetic meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. All analyses were performed using Stata software. Our results suggested that rs2233678 represented a protective factor in overall analysis (CC vs GG: OR= 0.697, 95%CI: 0.498-0.976; CG vs GG: OR=0.701, 95%CI: 0.572-0.858; Dominant model: OR= 0.707, 95%CI: 0.590-0.847; C allele vs G allele: OR=0.734, 95%CI: 0.623-0.867) and especially for squamous cell carcinoma of the head and neck, lung cancer and breast cancer in Asians and Caucasians. The rs2233679 polymorphism was significantly associated with decreased cancer risk in overall analysis (CT vs CC: OR=0.893, 95%CI=0.812-0.981; Dominant model: OR=0.893, 95%CI=0.816-0.976; T allele vs C allele; OR=0.947, 95%CI=0.896-1.000) and especially in Asians. In conclusion, our meta-analysis suggested that -842G>C (rs2233678) and -667C>T (rs2233679) may contribute to genetic susceptibility for cancer risks. Further prospective research with larger numbers of worldwide participants is warranted to draw comprehensive and firm conclusions.

Manijeh, Mahdavi;Mehrnaz, Keyhanfar;Violaine, Moreau;Hassan, Mohabatkar;Abbas, Jafarian;Mohammad, Rabbani 5973

https://doi.org/10.7314/APJCP.2013.14.10.5973 PDF KSCI

At present, the most common cause of cancer-related death in women is breast cancer. In a large proportion of breast cancers, there is the overexpression of human epidermal growth factor receptor 2 (HER2). This receptor is a 185 KDa growth factor glycoprotein, also known as the first tumor-associated antigen for different types of breast cancers. Moreover, HER2 is an appropriate cell-surface specific antigen for passive immunotherapy, which relies on the repeated application of monoclonal antibodies that are transferred to the patient. However, vaccination is preferable because it would stimulate a patient's own immune system to actively respond to a disease. In the current study, several bioinformatics tools were used for designing synthetic peptide vaccines. PEPOP was used to predict peptides from HER2 ECD subdomain III in the form of discontinuous-continuous B-cell epitopes. Then, T-cell epitope prediction web servers MHCPred, SYFPEITHI, HLA peptide motif search, Propred, and SVMHC were used to identify class-I and II MHC peptides. In this way, PEPOP selected 12 discontinuous peptides from the 3D structure of the HER2 ECD subdomain III. Furthermore, T-cell epitope prediction analyses identified four peptides containing the segments 77 (384-391) and 99 (495-503) for both B and T-cell epitopes. This work is the only study to our knowledge focusing on design of in silico potential novel cancer peptide vaccines of the HER2 ECD subdomain III that contain epitopes for both B and T-cells. These findings based on bioinformatics analyses may be used in vaccine design and cancer therapy; saving time and minimizing the number of tests needed to select the best possible epitopes.

Zhong, Liang-Rui;Chen, Xian;Wei, Ke-Min 5983

https://doi.org/10.7314/APJCP.2013.14.10.5983 PDF KSCI

Radix Tetrastigma Hemsleyani Flavone (RTHF) is widely used as a traditional herb for its detoxification and anti-inflammation activity. Recently, several studies have shown that RTHF can inhibit growth and induce apoptosis in human cancer cell lines. However, the mechanisms are not completely understood yet. In this study we investigated the potential effects of RTHF on growth and apoptosis in human lung adenocarcinoma A549 cells as well as its mechanisms. A549 cells were treated with RTHF at various concentrations for different times. In vitro the MTT assay showed that RTHF had obvious anti-proliferation effects on A549 cells in a dose- and time-dependent manner. Cell morphological changes observed by inverted microscope and Hoechst33258 methods were compared with apoptotic changes observed by fluorescence microscope. Cell apoptosis inspected by flow cytometry showed significant increase in the treatment group over the control group (P<0.01). Expression of apoptosis related Bax/Bcl-2, caspases and MAPK pathway proteins were detected by Western blotting. The results showed that RTHF up-regulated the Bax/Bcl-2 ratio and cle-caspase3/9, cle-PARP expression in a dose-dependent manner. Expression of p-p38 increased, p-ERK decreased significantly and that of p-JNK was little changed in the RTHF group when compared with the control group. These results suggest that RTHF might exert anti-growth and apoptosis activity against lung cancer A549 cells through activation of caspases and Bcl-2 family proteins and the MAPK pathway, therefore presenting as a promising therapeutic agent for the treatment of lung cancer.

Abbasi, Ahmed Nadeem;Hafiz, Asim;Ali, Nasir;Khan, Khurshid Ahmed 5989

https://doi.org/10.7314/APJCP.2013.14.10.5989 PDF KSCI

Background: Radiation therapy is the mainstay of treatment for nasopharyngeal carcinoma. Importance of tumor coverage and challenges posed by its unique and critical location are well evident. Therefore we aimed to evaluate our radiation treatment plan through dose volume histograms (DVHs) to find planning target volume (PTV) dose coverage and factors affecting it. Materials and Methods: This retrospective study covered 45 histologically proven nasopharyngeal cancer patients who were treated with definitive 3D-CRT and chemotherapy between Feb 2006 to March 2013 at the Department of Oncology, Section Radiation Oncology, Aga Khan University Hospital, Karachi, Pakistan. DVH was evaluated to find numbers of shrinking field (phases), PTV volume in different phases and its coverage by the 95% isodose lines, along with influencing factors. Results: There were 36 males (80%) and 9 females (20%) in the age range of 12-84 years. Stage IVA (46.7%) was the most common stage followed by stage III (31.1). Eighty six point six-percent received induction, 95.5% received concurrent and 22.2% received adjuvant chemotherapy. The prescribed median radiation dose was 70Gy to primary, 60Gy to clinically positive neck nodes and 50Gy to clinically negative neck regions. Mean dose to spinal cord was 44.2Gy and to optic chiasma was 52Gy. Thirty seven point eight-percent patients completed their treatment in three phases while 62.2% required four to five phases. Mean volume for PTV3 was $247.8cm^3$ (50-644.3), PTV4 $173.8cm^3$ (26.5-345.1) and PTV5 $119.6cm^3$ (18.9-246.1) and PTV volume coverage by 95% isodose lines were 74.4%, 85.7% and 100% respectively. Advanced T stage, intracranial extension and tumor volume > $200cm^3$ were found to be important factors associated with decreased PTV coverage by 95% isodose line. Conclusions: 3D CRT results in adequate PTV dose coverage by 95% isodose line. However advanced T stage, intracranial extension and large target volume require more advanced techniques like IMRT for appropriate PTV coverage.

Wang, Shi-Ying;Zhu, Wen-Hao;Vargulick, Sonya;Lin, Sam Bill;Meng, Zhi-Qiang 5995

https://doi.org/10.7314/APJCP.2013.14.10.5995 PDF KSCI

Background: Nausea and vomiting after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) are common in clinical practice, but few studies have reported the incidence and risk factors of such events. Objective: The purpose of this study was to analyze the incidence and risk factors of nausea and vomiting after TACE for HCC. Methods: This study was a single-center retrospective analysis of a prospectively maintained database. Between May 2010 and October 2012, 150 patients with HCC were analyzed for incidence and preprocedural risk factors. Results: The incidence of postembolization nausea and vomiting was 38.8% and 20.9%, respectively, in patients with HCC. Patients who developed nausea had lower levels (<100 IU/L) of serum alkaline phosphatase (ALP) compared to those without nausea ($123.04{\pm}69.38$ vs. $167.41{\pm}138.95$, respectively, p=0.044). Female gender correlated to a higher incidence of nausea as well (p=0.024). Patients who developed vomiting, compared to those who did not, also had lower levels (<100 IU/L) of serum ALP ($112.52{\pm}62.63$ vs. $160.10{\pm}127.80$, respectively, p=0.010), and serum alanine transferase (ALT) ($35.61{\pm}22.87$ vs. $4.97{\pm}29.62$, respectively, p=0.045). There were no statistical significances in the incidences of nausea and vomiting between male patients over 50 years old and female patients who have entered menopause (p=0.051 and p=0.409, respectively). Multivariate analysis by logistic regression analysis demonstrated that female gender and ALP>100 IU/L were the most independent predictive factors of postembolization nausea (odds ratio (OR): 3.271, 95% CI: 1.176-9.103, p=0.023 and OR: 0.447, 95% CI: 0.216-0.927, p=0.030, respectively). ALP>100 IU/L was also the most independent predictive risk factor of postembolization vomiting (OR: 0.389, 95% CI: 0.159-0.952, p=0.039). Conclusions: Postembolizaiton nausea and vomiting are common in patients with HCC. Recognition of the risk factors presented above before TACE is important for early detection and proper management of postembolization nausea and vomiting. Nevertheless, future studies are required.

Singh, Arjun Kumar;Manoharan, Shanmugam;Vasudevan, Krishnamurthy;Rajasekaran, Duraisamy;Manimaran, Asokan;Suresh, Kathiresan 6001

https://doi.org/10.7314/APJCP.2013.14.10.6001 PDF KSCI

Our aim was to explore anti-cell proliferative and anti-angiogenic potential of andrographolide by analyzing the expression pattern of cell proliferative (PCNA, Cyclin D1) and angiogenic (VEGF) markers during 7, 12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. DMBA painting three times a week for 14 weeks in the buccal pouch of golden Syrian hamsters resulted in oral tumors which were histopathologically diagnosed as well differentiated squamous cell carcinoma. Immunohistochemical (PCNA, VEGF) and RT-PCR (Cyclin D1) studies revealed over expression of PCNA, VEGF and Cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/kg bw to hamsters treated with DMBA not only suppressed the histological abnormalities but also down regulated the expression of PCNA, VEGF and Cyclin D1. The results of the present study suggest that andrographolide suppressed tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative and anti-angiogenic potential.

Sun, Meng-Yao;Xing, Rui-Huan;Gao, Xiao-Jie;Yu, Xiang;He, Hui-Min;Gao, Ning;Shi, Hong-Yan;Hu, Yan-Yan;Wang, Qi-Xuan;Xu, Jin-Hui;Hou, Ying-Chun 6007

https://doi.org/10.7314/APJCP.2013.14.10.6007 PDF KSCI

ANXA2, a member of the annexin family, is overexpressed and plays important roles in tumor development. However, the significance of ANXA2 expression in gastric carcinoma has not been clarified.To elucidate its roles in growth of gastric cancer, ANXA2 expression in SGC-7901 cells was inhibited with a designated siRNA, then cell proliferation, cell cycling, apoptosis and motility were determined by MTT assay, flow cytometry, Hoechst 33342 staining and wound healing assay, respectively. To further assess the behavior of ANXA2 deleted SGC-7901 cells, changes of microstructures were observed under fluorescence microscopy, laser scanning confocal microscopy and electron microscopy. We found that inhibition of ANXA2 expression caused cell proliferation to decrease significantly with G1 arrest, motility to be reduced with changes in pseudopodia/filopodia structure and F-actin and ${\beta}$-tubulin expression, and apoptosis to be enhanced albeit without significance. At the same time, ANXA2 deletion resulted in fewer pseudopodia/filopodia, non-stained areas were increased, contact inhibition among cells reappeared, and expression of F-actin and ${\beta}$-tubulin was decreased, with induction of polymerized disassembled forms. Taken together, these data suggest that ANXA2 overexpression is important to maintain the malignancy of cancer cells, and this member of the annexin family has potential to be considered as a target for the gene therapy of gastric carcinoma.

Somali, Isil;Ustaoglu, Bahar Yakut;Tarhan, Mustafa Oktay;Yigit, Seyran Ceri;Demir, Lutfiye;Ellidokuz, Hulya;Erten, Cigdem;Alacacioglu, Ahmet 6013

https://doi.org/10.7314/APJCP.2013.14.10.6013 PDF KSCI

Background: To evaluate the clinicopathologic and demographic characteristics of triple-negative breast cancer (TNBC) patients and to determine differences from non-triple-negative cases. Materials and Methods: A detailed review of the medical records of 882 breast cancer (BC) patients was conducted to obtain information regarding age, menopausal status, height and weight at the time of diagnosis, presence of diabetes or hypertension, and pathologic characteristics of the tumor (tumor size, lymph node status, histologic grade, ER status, PR status, HER2 status, p53 mutation). Body mass index (BMI) was calculated and a value of ${\geq}30$ was considered as indicative of obesity. Results: 14.9% (n=132) of the patients had TNBC. There was no difference among the patients in terms of median age, comorbid conditions and menopausal status. The proportion of medullary, tubular and mucinous carcinomas was significantly higher (15.9%) in the triple-negative (TN) group, while invasive lobular histology was more frequent (8.2%) among non-triple negative (NTN) cases (p<0.001). Grade 3 (G3) tumors were more frequent in the triple-negative group (p<0.001). The rate of p53 mutation was 44.3% in TN tumors versus 28.2% in the NTN group (p<0.001). The two groups were similar in terms of LN metastasis. In the NTN group, the rate of patients with BMI ${\geq}30$ was 53% among postmenopausal patients, while it was 36% among premenopausal women, and the difference was statistically significant (p<0.001). No significant difference was observed in terms of BMI between postmenopausal and premenopausal patients in the TN group (p=0.08). Conclusions: TNBC rates and clinicopathologic characteristics of the Turkish patient population were consistent with the data from Europe and America. However, no relationship between obesity and TNBC was observed in our study. The association between TNBC and obesity needs to be evaluated in a larger patient population.

Wang, Jing-Jing;Wu, Hai-Feng;Sun, Tao;Li, Xia;Wang, Wei;Tao, Li-Xin;Huo, Da;Lv, Ping-Xin;He, Wen;Guo, Xiu-Hua 6019

https://doi.org/10.7314/APJCP.2013.14.10.6019 PDF KSCI

Lung cancer, one of the leading causes of cancer-related deaths, usually appears as solitary pulmonary nodules (SPNs) which are hard to diagnose using the naked eye. In this paper, curvelet-based textural features and clinical parameters are used with three prediction models [a multilevel model, a least absolute shrinkage and selection operator (LASSO) regression method, and a support vector machine (SVM)] to improve the diagnosis of benign and malignant SPNs. Dimensionality reduction of the original curvelet-based textural features was achieved using principal component analysis. In addition, non-conditional logistical regression was used to find clinical predictors among demographic parameters and morphological features. The results showed that, combined with 11 clinical predictors, the accuracy rates using 12 principal components were higher than those using the original curvelet-based textural features. To evaluate the models, 10-fold cross validation and back substitution were applied. The results obtained, respectively, were 0.8549 and 0.9221 for the LASSO method, 0.9443 and 0.9831 for SVM, and 0.8722 and 0.9722 for the multilevel model. All in all, it was found that using curvelet-based textural features after dimensionality reduction and using clinical predictors, the highest accuracy rate was achieved with SVM. The method may be used as an auxiliary tool to differentiate between benign and malignant SPNs in CT images.

Saeed, Hesham Mahmoud;Alanazi, Mohammad Saud;Parine, Narasimha Reddy;Shaik, Jilani;Semlali, Abdelhabib;Alharbi, Othman;Azzam, Nahla;Aljebreen, Abdulrahman;Almadi, Majid;Shalaby, Manal Aly 6025

https://doi.org/10.7314/APJCP.2013.14.10.6025 PDF KSCI

Background: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism (SNP) at -1306, which disrupts a Sp1-type promoter site (CCACC box), results in strikingly lower promoter activity with the T allele. In the present study, we investigated whether this MMP-2 genetic polymorphism might be associated with susceptibility to colorectal cancer (CRC) in the Saudi population. We also analyzed MMP-2 gene expression level sin CRC patients and 4 different cancer cell lines. Materials and Methods: TaqMan allele discrimination assays and DNA sequencing techniques were used to investigate the $C^{-1306}T$ SNP in the MMP-2 gene of Saudi colorectal cancer patients and controls. The MMP-2 gene expression level was also determined in 12 colon cancer tissue samples collected from unrelated patients and histologically normal tissues distant from tumor margins. Results and Conclusions: The MMP-2 $C^{-1306}T$ SNP in the promoter region was associated with CRC in our Saudi population and the MMP-2 gene expression level was found to be 10 times higher in CRC patients. The MMP-2 $C^{-1306}T$ SNP is significantly associated with CRC in the Saudi population and this finding suggested that MMP-2 variants might help predict CRC progression risk among Saudis. We propose that analysis of this gene polymorphism could assist in identification of patient subgroups at risk of a poor disease outcome.

Liu, Shu-Zheng;Wang, Bing;Zhang, Fang;Chen, Qiong;Yu, Liang;Cheng, Lan-Ping;Sun, Xi-Bin;Duan, Guang-Cai 6031

https://doi.org/10.7314/APJCP.2013.14.10.6031 PDF KSCI

This study describes recent trends in incidence, survival and prevalence of subgroups of esophageal and gastric cancer in Linzhou city between 2003 and 2009. Data of esophageal and gastric cancer for the period of interest were extracted from the Linzhou Cancer Registry. Using information on tumor morphology or anatomical site, data were divided into six groups; esophageal squamous cell carcinoma, esophageal adenocarcinoma, other and unspecified types of esophageal cancer, and cardia, non-cardia, and unspecified anatomical site of stomach cancer. Incidence, survival and prevalence rates for each of the six cancer groups were calculated. The majority of esophageal cancers were squamous cell carcinomas (82%). Cardiac cancer was the major gastric cancer group (64%). The incidence of esophageal squamous cell carcinoma and gastric cardiac cancer increased between 2003 and 2009. Both esophageal and gastric cancer had a higher incidence in males compared with females. Overall survival was poor in all sub-groups with 1 year survival ranging from 45.9 to 65.6% and 5 year survival ranging from 14.7 to 30.5%. Prevalence of esophageal squamous cell carcinoma and gastric cardiac cancer was high (accounting for 80% overall). An increased focus on prevention and early diagnosis, especially in esophageal squamous cell carcinoma and gastric cardiac cancer, is required.

Fathallah, Raja Mohd-Talal;Dajani, Rana 6035

https://doi.org/10.7314/APJCP.2013.14.10.6035 PDF KSCI

Background: Cancer is a complex disease caused by multiple factors, both genetic and environmental. It is a major health concern worldwide, in the Middle East and in Jordan specifically and the fourth most common killer in the Middle East. Hypothesis: The relative genetic homogeneity of the Circassian and Chechan populations in Jordan results in incidences of cancer that differ from the general Jordanian population, who are mostly Arabs. Materials and Methods: National Cancer Registry data were obtained for the years 1996-2005 The Chechen and Circassian cancer cases were identified and cancer registry data were divided into three populations. Crude rates were calculated based on the number of cancer cases and estimated populations. Results: Breast cancer is the most common cancer type constituting about one third of female cancers in all three populations. Higher crude rates are observed in the Circassian and Chechen populations than in the Arab Jordanian population. The rate ratios (95%CI) in Circassians and Chechens with respect to the Arab Jordanian population are 2.1 (1.48, 2.72) and 1.81 (1.16, 2.85), respectively. Lung cancer is the most common cancer in male Arab Jordanians and Chechens with crude rates of 4.2 and 8.0 per 100,000 respectively. The male to female ratio in these two populations in respective order are 5:1 and 7:1. The lung cancer crude rate in Circassians is 6.5 per 100,000 with a male to female ratio of only 1.6:1. The colorectal cancer crude rates in Arab Jordanians and Chechens are similar at 6.2 and 6.0 per 100,000, respectively, while that in Circassians is twice as high. Conclusions: Considerable ethnic variation exists for cancer incidence rates in Jordan. The included inbred and selected populations offer an ideal situation for investigating genetic factors involved in various cancer types.

Tsunematsu, Miwako;Kawasaki, Hiromi;Masuoka, Yuko;Kakehashi, Masayuki 6041

https://doi.org/10.7314/APJCP.2013.14.10.6041 PDF KSCI

Background: Japanese women in their 40s or older have been encouraged to attend breast cancer screening. However, the breast cancer screening rate in Japan is not as high as in Europe and the United States. The aim of this study was to identify psychological and personal characteristics of women concerning their participation in breast cancer screening using the Health Belief Model (HBM). In addition, the attributes of screening more easily accepted by participants were analyzed by conjoint analysis. Materials and Methods: In this cross sectional study of 3,200 age 20-69 women, data were collected by an anonymous questionnaire. Questions were based on HBM and personal characteristics, and included attitudes on hypothetical screening attributes. Data of women aged 40-69 were analyzed by logistic regression and conjoint analysis to clarify the factors affecting their participation in breast cancer screening. Results: Among responses collected from 1,280 women of age 20-69, the replies of 993 women of age 40-69 were used in the analysis. Regarding the psychological characteristics based on HBM, the odds ratios were significantly higher in "importance of cancer screening" (95%CI: 1.21-2.47) and "benefits of cancer screening" (95%CI: 1.09-2.49), whereas the odds ratio was significantly lower in "barriers to participation before cancer screening" (95%CI: 0.27-0.51). Conjoint analysis revealed that the respondents, overall, preferred screening to be low cost and by female staff members. Furthermore, it was also clarified that attributes of screening dominant in decision-making were influenced by the employment status and the type of medical insurance of the women. Conclusions: In order to increase participation in breast cancer screening, it is necessary to disseminate accurate knowledge on cancer screening and to reduce barriers to participation. In addition, the attributes of screening more easily accepted were inexpensive, provided by female staff, executed in a hospital and finished in a short time.

Barchana, Micha;Liphshitz, Irena 6049

https://doi.org/10.7314/APJCP.2013.14.10.6049 PDF KSCI

Background: Following research demonstrating an increased risk for meningiomas in the Jewish population of Shiraz (Iran) we conducted a cohort analysis of meningiomas among Jews originating in Iran and residing in Israel. Materials and Methods: We use the population-based registry data of the Israeli National Cancer Registry (INCR) for the main analysis. All benign meningioma cases diagnosed in Israel from January 2000 to the end of 2009 were included. Patients that were born in Iran, Iraq, Turkey, Bulgaria and Greece were used for the analysis, whereby we calculated adjusted incidence rates per 100,000 people and computed standardized incidence ratios (SIRs) comparing the Iranian-born to each of the three other groups. Results: Iranian-born Jews had statistically significant higher meningioma rates rates compared to other Jews originating in Balkan states: 1.46 fold compared to Turkish Jews and 1.86 fold compared to the Bulgaria-Greece group. There was a small increase in risk for the Iranian born group compared to those who were born in Iraq (1.06, not significant). Conclusions: Higher rates of meningiomas were seen in Jews originating in Iran that are living in Israel as compared to rates in neighboring countries of origin. These differences can be in part attributed to early life environmental exposures in Iran but probably in larger amount are due to genetic and hereditary factors in a closed community like the Iranian Jews. Some support for this conclusion was also found in other published research.

Bekar, Mine;Guler, Handan;Evcili, Funda;Demirel, Gulbahtiyar;Duran, Ozlem 6055

https://doi.org/10.7314/APJCP.2013.14.10.6055 PDF KSCI

The current study determines the knowledge of female course attendees of the "Municipality Cultural Center for Women", located in the city center of Sivas, Turkey, and their attitudes regarding gynecological cancer prevention. The participants of the study include 497 women attending one of the two Municipality Cultural Centers situated in the city center of Sivas. In this study, the sample was not selected; all participants were encompassed within the scope of our research. A total of 418 female course attendees who volunteered to participate in the research were identified as the sample. The data were collected during the months March-June 2011, by a questionnaire developed by the researchers. To compare the distribution of the collected data "Anova", "two independent t test examples" and "chi square test" were used. The research indicates that 45.1% of the women had had gynecological examination as a consequence of a physical disorder. The reason for 54.9% of the women to have gynecological examination is to have been scanned to check for gynecological cancer, 51.2% had a pap smear test. Some 34.9% of them had obtained information about cervical cancer, 39.7% via radio, television or internet and 36.3% from a doctor. Age, education level and marital status of the women participating in this study demonstrated statistically significant correlations (p<0.05) with gynecological examination and undergoing a pap smear test.

Yu, Da-Ping;Han, Yi;Zhao, Qiu-Yue;Liu, Zhi-Dong 6061

https://doi.org/10.7314/APJCP.2013.14.10.6061 PDF KSCI

Objective: To explore the feasibility of pulmonary lobectomy combined with pulmonary arterioplasty by complete video-assisted thoracic surgery (VATS) in patients with lung cancer, and summarize its surgical methods. Materials and Methods: Twenty-one patients with lung cancer in Beijing Chest Hospital Affiliated to Capital Medical University from Feb., 2010 to Jun., 2013 were selected, males and females accounting for 15 and 6 cases, respectively. Ten underwent right upper lobectomy, 5 right lower lobectomy, 4 left upper lobectomy (in which left upper sleeve lobectomy was conducted for 2) and 2 left lower lobectomy. At the same time, local resection of pulmonary arterioplasty was performed for 12 patients, and sleeve resection of pulmonary arterioplasty for 9. Results: Twenty-one patients recovered well after surgery. Thoracic drainage tube was maintained for 3-8 days, with an average of 4.9 days, and hospital stays were 8-15 days, with an average of 11 days. There were no deaths in the perioperative period, and the complications like pulmonary embolism, bronchopleural fistula, chest infection and pulmonary atelectasis did not occur after surgery. Conclusions: Performance of pulmonary lobectomy and pulmonary arterioplasty together by complete VATS is a safe and effective surgical method, which can expand the indications of patients with lung cancer undergoing thoracoscopic pulmonary lobectomy, and make more patients profit from such minimally invasive treatment.

Tural, Deniz;Elicin, Olgun;Batur, Sebnem;Arslan, Deniz;Oz, Buge;Serdengecti, Suheyla;Uzel, Omer 6065

https://doi.org/10.7314/APJCP.2013.14.10.6065 PDF KSCI

Background: Primary aim of this study is to assess whether or not there is an increase at rate of HPV positive oropharyngeal cancers during 1996-2011 in Turkey, for comparison with prior reports from Western countries. Materials and Methods: A total of 138 newly diagnosed patients with oropharyngeal cancer were identified, 39 of which had no primary tumor specimen available and 18 patients with invalid HPV status, therefore HPV status for remaining 81 patients was evaluated. The presence and type of HPV DNA were determined with formalin-fixed paraffin embedded specimens, using an HPV DNA-based multiplex PCR assay. Associations between HPV status and clinicopathological characteristics were evaluated using a two-sample t-test for the continuous variables and the categorical variables were compared by chi-square test. Overall survival (OS) periods were calculated with Kaplan-Meier method. Results: The proportion of HPV-positive cancer has continued to increase during 2004-2011 as compared with 1996-2003. Notably, 33% (6/18) of the cases were HPV-positive in 1996-1999, 43% (9/21) in 2000-2003, 55% (11/20) in 2004-2007 and 70% (16/23) in 2008-2011. Thus, when we compared the results obtained during the 2004-2011with results of 1996-2003 period, we found that increase at HPV-positivity ratio was statistically significant (38% vs 64% p=0.012). Conclusions: This study demonstrated that HPV positive oropharyngeal cancers are increasing in Turkish patients as in the Western world.

Deng, Bao-Guo;Yao, Jin-Hua;Liu, Qing-Yin;Feng, Xian-Jun;Liu, Dong;Zhao, Li;Tu, Bin;Yang, Fan 6069

https://doi.org/10.7314/APJCP.2013.14.10.6069 PDF KSCI

Background: At present, the diagnosis of colorectal cancer (CRC) requires a colorectal biopsy which is an invasive procedure. We undertook this pilot study to develop an alternative method and potential new biomarkers for diagnosis, and validated a set of well-integrated tools called ClinProt to investigate the serum peptidome in CRC patients. Methods: Fasting blood samples from 67 patients diagnosed with CRC by histological diagnosis, 55 patients diagnosed with colorectal adenoma by biopsy, and 65 healthy volunteers were collected. Division was into a model construction group and an external validation group randomly. The present work focused on serum proteomic analysis of model construction group by ClinProt Kit combined with mass spectrometry. This approach allowed construction of a peptide pattern able to differentiate the studied populations. An external validation group was used to verify the diagnostic capability of the peptidome pattern blindly. An immunoassay method was used to determine serum CEA of CRC and controls. Results: The results showed 59 differential peptide peaks in CRC, colorectal adenoma and health volunteers. A genetic algorithm was used to set up the classification models. Four of the identified peaks at m/z 797, 810, 4078 and 5343 were used to construct peptidome patterns, achieving an accuracy of 100% (> CEA, P<0.05). Furthermore, the peptidome patterns could differentiate the validation group with high accuracy close to 100%. Conclusions: Our results showed that proteomic analysis of serum with MALDI-TOF MS is a fast and reproducible approach, which may provide a novel approach to screening for CRC.

Ortashi, Osman;Raheel, Hina;Shalal, Musa;Osman, Nawal 6077

https://doi.org/10.7314/APJCP.2013.14.10.6077 PDF KSCI

Background: Cervical cancer is the second commonest female cancer worldwide. The 50-55 cases of cervical cancer are reported annually in the UAE. There is a scarcity of data from Middle Eastern region regarding knowledge and attitude of women towards HPV infection, cervical cancer prevention and HPV vaccine. The aim of our study was to assess the knowledge of women regarding HPV infection and vaccine in UAE. Materials and Methods: A cross-sectional survey of 640 women aged 18-50 years was conducted in Al-Ain district in UAE using convenience sampling. Women with previous diagnosis of cervical cancer, non-residents of UAE, younger than 18 or older than 50 years of age and those unable to speak Arabic or English were excluded from the study. Logistic regression analysis was performed to assess the association of HPV knowledge with independent factors like age, education etc. Results: Only 29% of our sampled women have ever heard of HPV infection. Only 15.3% women recognized it as STI. Only about 22% women have also heard of the HPV vaccine. Three quarter of the women in our study thought that cervical cancer can be prevented. About 28% recognized vaccine as a preventive measure against cervical cancer. Age (AOR 1.049, 95%CI 1.02-1.08) and husband's level of education were found to be significant (p value 0.015) after adjusting for women's age. Conclusions: The knowledge of HPV infection and vaccine is low in the UAE. Few women recognized HPV as sexually transmitted infection. Increasing age and husband's education are associated with better knowledge of HPV infection.

Han, Shu-Jing;Guo, Qing-Qing;Wang, Ting;Wang, You-Xin;Zhang, Yu-Xiang;Liu, Fen;Luo, Yan-Xia;Zhang, Jie;Wang, You-Li;Yan, Yu-Xiang;Peng, Xiao-Xia;Ling, Rui;He, Yan 6081

https://doi.org/10.7314/APJCP.2013.14.10.6081 PDF KSCI

Objective: Both estrogen receptors, ER alpha ($ER{\alpha}$) and ER beta ($ER{\beta}$), are expressed in 50-70% of breast cancer cases. The role of $ER{\alpha}$ as a prognostic marker in breast cancer has been well established as its expression is negative correlated with tumor size and lymph node metastasis. $ER{\beta}$ is also a favorable prognostic predictor although this is less well documented than for $ER{\alpha}$. Materials and Methods: To explore whether ERs independently or together might influence clinical outcome in breast cancer, the correlation between the ERs with the clinicopathological features was analyzed in 84 patients. Results: $ER{\alpha}$ expression negatively correlated with tumor stage (r=-0.246, p=0.028) and tended to be negatively correlated with lymph node status (r=-0.156, p=0.168) and tumor size (r=-0.246, p=0.099). Also, $ER{\beta}$ was negatively correlated with nodal status (r=-0.243, p=0.028), as was coexpression of $ER{\alpha}$ and $ER{\beta}$ (p=0.043, OR=0.194, 95% CI= 0.040-0.953). Conclusion: Coexpression of ERs might serve as an indicator of good prognosis in breast cancer patients.

Verim, Levent;Yildirim, Asif;Basok, Erem Kaan;Peltekoglu, Erol;Pelit, Eyup Sabri;Zemheri, Ebru;Tokuc, Resit 6085

https://doi.org/10.7314/APJCP.2013.14.10.6085 PDF KSCI

Prostate specidic antigen (PSA) and digital rectal examination (DRE) are the known predictive factors for positive prostate biopsies differing according to the age, region and race. There have been only very limited studies about the impact of PSA on histological findings at prostate biopsy in Turkey. The aim of this study was to evaluate the impact of PSA and clinical stage on histologic findings of prostate biopsy in men older than 75 years of age as a first study in the Turkish population. A total of 1,645 consecutive prostate biopsies were included, with 194 men aged 75 or older. Cancer was identified in 104 patients (53.6%). Of the 104 positive biopsies, Gleason scores were less than 7 in 53 (49%) patients, 7 or greater in 51 (51%) patients. Positive prostate biopsies were significantly correlated with advanced age (p=0.0001), abnormal DRE (p=0.0001) and raised PSA (p=0.0001). The prostate volume was significantly correlated with advanced age especially in prostate cancer patients over 75 years, compared with those under 75 (p=0.0001). These results are useful for counseling men older than 75 years for prostate cancer detection. However, PCa screening decisions are currently based on urologist judgment and detection of latent asymptomatic disease is an important concern regarding costs, overdiagnosis, overtreatment and quality of life (QOL) for men aged 75 years and older. Healthy old patients with a long life expectancy need to be carefully evaluated for eligibility for PCa screening.

Wen, Chun-Jie;Wu, Lan-Xiang;Fu, Li-Juan;Yu, Jing;Zhang, Yi-Wen;Zhang, Xue;Zhou, Hong-Hao 6089

https://doi.org/10.7314/APJCP.2013.14.10.6089 PDF KSCI

Berberine, a common isoquinoline alkaloid, has been shown to possess anti-cancer activities. However, the underlying molecular mechanisms are still not completely understood. In the current study, we investigated the effects of berberine on cell growth, colony formation, cell cycle distribution, and whether it improved the anticancer efficiency of cisplatin and doxorubicin in human breast cancer estrogen receptor positive (ER+) MCF-7 cells and estrogen receptor negative (ER-) MDA-MB-231 cells. Notably, berberine treatment significantly inhibited cell growth and colony formation in the two cell lines, berberine in combination with cisplatin exerting synergistic growth inhibitory effects. Accompanied by decreased growth, berberine induced G1 phase arrest in MCF-7 but not MDA-MB-231 cells. To provide a more detailed understanding of the mechanisms of action of berberine, we performed genome-wide expression profiling of berberine-treated cells using cDNA microarrays. This revealed that there were 3,397 and 2,706 genes regulated by berberine in MCF-7 and MDA-MB-231 cells, respectively. Fene oncology (GO) analysis identified that many of the target genes were involved in regulation of the cell cycle, cell migration, apoptosis, and drug responses. To confirm the microarray data, qPCR analysis was conducted for 10 selected genes based on previously reported associations with breast cancer and GO analysis. In conclusion, berberine exhibits inhibitory effects on breast cancer cells proliferation, which is likely mediated by alteration of gene expression profiles.

Lee, Myung Ha;Choi, Kui Son;Lee, Yoon Young;Suh, Mina;Jun, Jae Kwan 6095

https://doi.org/10.7314/APJCP.2013.14.10.6095 PDF KSCI

Few studies have examined the relationship between social support and stages of adoption of cancer screening. Here we investigated associations between both structural and functional aspects of social support and stages of adoption of gastric cancer screening in the general population of Korea. The study population was derived from the 2011 Korean National Cancer Screening Survey (KNCSS), an annual cross-sectional survey that uses nationally representative random sampling to investigate cancer screening rates. Data were analyzed from 3,477 randomly selected respondents aged 40-74 years. Respondents were classified according to their stage of adoption of gastric cancer screening: precontemplation (13.2%), contemplation (18.0%), action/maintenance (56.1%), relapse risk (8.5%), and relapse stage (4.1%). Respondents with larger social networks were more likely to be in the contemplation/action/maintenance, or the relapse risk/relapse stages versus the precontemplation stage (OR=1.91, 95%CI: 1.52-2.91; p for tend=0.025). Emotional and instrumental supports were not associated with any stage of adoption of gastric cancer screening. However, respondents who reported receiving sufficient informational support were more likely to be in the relapse risk/relapse stages versus the precontemplation, or the contemplation/action/maintenance stage (p for trend=0.016). Interventions involving interactions between social network members could play an important role in increasing participation in gastric cancer screening.

Liu, Jing-Wei;He, Cai-Yun;Sun, Li-Ping;Xu, Qian;Xing, Cheng-Zhong;Yuan, Yuan 6103

https://doi.org/10.7314/APJCP.2013.14.10.6103 PDF KSCI

Objective: Excision repair cross-complementing group 6 (ERCC6) is a major component of the nucleotide excision repair pathway that plays an important role in maintaining genomic stability and integrity. Several recent studies suggested a link of ERCC6 polymorphisms with susceptibility to various cancers. However, the relation of ERCC6 polymorphism with gastric cancer (GC) risk remains elusive. In this sex- and age-matched case-control study including 402 GC cases and 804 cancer-free controls, we aimed to investigate the association between a potentially functional polymorphism (rs1917799 T>G) in the ERCC6 regulatory region and GC risk. Methods: The genotypes of rs1917799 were determined by Sequenom MassARRAY platform and the status of Helicobacter pylori infection was detected by enzyme-linked immunosorbent assay. Odd ratios (ORs) and 95% confidential interval (CI) were calculated by logistic regression analysis. Results: Compared with the common TT genotype, the ERCC6 rs1917799 GG genotype was associated with increased GC risk (adjusted OR=1.46, 95%CI: 1.03-2.08, P=0.035). When compared with (GT+TT) genotypes, the GG genotype also demonstrated a statistical association with increased GC risk (adjusted OR=1.38, 95%CI: 1.01-1.89, P=0.044). This was also observed for the male subpopulation (GG vs. TT: adjusted OR=1.71, 95%CI: 1.12-2.62, P=0.013; G allele vs. T allele: adjusted OR=1.32, 95%CI: 1.07-1.62, P=0.009). Genetic effects on increased GC risk tended to be enhanced by H. pylori infection, smoking and drinking, but their interaction effects on GC risk did not reach statistical significance. Conclusions: ERCC6 rs1917799 GG genotype might be associated with increased GC risk in Chinese, especially in males.

Aydiner, Adnan;Ciftci, Rumeysa;Karabulut, Senem;Kilic, Leyla 6109

https://doi.org/10.7314/APJCP.2013.14.10.6109 PDF KSCI

Aim: To determine whether beta-blockers (BBs) improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC). Materials and Methods: The medical charts of 107 patients with metastatic NSCLC were retrospectively assessed. Thirty-five patients (BB group) using BBs during chemotherapy (CT) were compared with 72 controls [control=(C) group] who did not use BBs following the diagnosis of NSCLC. The histological tumor subtype, performance status (ECOG), age, gender, smoking status, comorbidities, other medications and chemotherapeutics that were received in any line of treatment were recorded. We compared the overall survival (OS) of the patients in the BB and C groups. Results: The mean age of the patients was 61 years (range 42-81 years) and all patients were administered CT. The BB group was more likely to have HT and IHD and was more likely to use RAS blockers (p<0.01 for all) compared with the C group, as expected. The mean follow-up time was 17.8 months (range 1-102 months) for the entire group. The most commonly prescribed BB agent was metoprolol (80% of cases). At the time of the analysis, 74 (69%) of all patients had died. In the univariate analysis the median overall survival (OS) was 19.25 (${\pm}2.87$) months (95%CI: 13.62-24.88) in the BB group and 13.20 (${\pm}2.37$) months (95%CI: 8.55-17.85) in the C group (p=0.017). However, the benefit of BBs on survival disappeared in the multivariate analysis. Conclusions: The use of BBs during CT may be associated with an improved OS for patients with metastatic NSCLC.

Jiang, Lei;Hao, Jin-Li;Jin, Mu-Lan;Zhang, Yun-Gang;Wei, Ping 6115

https://doi.org/10.7314/APJCP.2013.14.10.6115 PDF KSCI

Introduction: Some non-small cell lung cancer (NSCLC) tumor cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) -based therapy. This study was conducted to examine the effect of embelin on the sensitivity of the A549 NSCLC cell line to TRAIL receptor2 (TRAILR2) monoclonal antibodies and to investigate the potential mechanisms. Materials and Methods: A549 cells were treated with embelin, TRAILR2 mAb or a combination of both. Cell viability was measured using ATPlite assay and apoptosis rates were determined by flow cytometry with AnnexinV-FITC and propidium iodide staining, with the expression levels of proteins analyzed by Western blotting. Results: The cell survival rate of separate treatments with 100 ng/ml TRAILR2 antibody or 25 uM embelin were $81.5{\pm}1.57%$ and $61.7{\pm}2.84%$, respectively. Their combined use markedly decreased cell viability in A549 cells to $28.1{\pm}1.97%$ (P<0.05). The general caspase inhibitor Z-VAD-FMK could inhibit the embelin-enhanced sensitivity of A549 cells to TRAILR2 mAb ($75.97{\pm}3.17%$)(P<0.05). Both flow cytometry and cell morphological analysis showed that embelin was able to increase TRAIL-induced apoptosis in A549 cells. Combined treatment with embelin and TRAILR2 mAb augmented the activation of initiator caspases and effector caspase. In addition, A549 cells showed increasing levels of TRAILR2 protein and decreasing levels of Bcl-2, survivin and c-FLIP following the treatment with embelin+TRAILR2 mAb. Conclusions: Embelin could enhance TRAIL-induced apoptosis in A549 cells. The synergistic effect of the combination treatment might be due to modulation of multiple components in the TRAIL receptor-mediated apoptotic signaling pathway, including TRAILR2, XIAP, survivin, Bcl-2 and c-FLIP.

Balik, Gulsah;Kagitci, Mehmet;Ustuner, Isik;Akpinar, Funda;Guven, Emine Seda Guvendag 6121

https://doi.org/10.7314/APJCP.2013.14.10.6121 PDF KSCI

Background: Endometrial cancers are the most common gynecologic cancers. Endometrial sampling is a preferred procedure for diagnosis of the endometrial pathology. It is performed routinely in many clinics prior to surgery in order to exclude an endometrial malignancy. We aimed to investigate the accuracy of endometrial sampling in the diagnosis of endometrial pathologies and which findings need intra-operative frozen sections. Materials and Methods: Three hundred nine women applying to a university hospital and undergoing endometrial sampling and hysterectomy between 2010 and 2012 were included to this retrospective study. Data were retrieved from patient files and pathology archives. Results: There was 17 patients with malignancy but endometrial sampling could detect this in only 10 of them. The endometrial sampling sensitivity and specificity of detecting cancer were 58.8% and 100%, with negative and positive predictive values of 97.6%, and 100%, respectively. In 7 patients, the endometrial sampling failed to detect malignancy; 4 of these patients had a preoperative diagnosis of complex atypical endometrial hyperplasia and 2 patients had a post-menopausal endometrial polyps and 1 with simple endometrial hyperplasia. Conclusions: There is an increased risk of malignancy in post-menopausal women especially with endometrial polyps and complex atypia hyperplasia. Endometrial sampling is a good choice for the diagnosis of endometrial pathologies. However, the diagnosis should be confirmed by frozen section in patients with post-menopausal endometrial polyps and complex atypia hyperplasia.

Xia, Ling-Yun;Zeng, Xian-Tao;Li, Cheng;Leng, Wei-Dong;Fan, Ming-Wen 6127

https://doi.org/10.7314/APJCP.2013.14.10.6127 PDF KSCI

This study aimed to investigate the association between p53 Arg72Pro polymorphism and the risk of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) by conducting meta-analysis. The PubMed database was searched for relevant studies until May 30, 2013. Relevant studies were selected and data were extracted by two independent authors. Overall, subgroup, and sensitivity analyses were then conducted using the Comprehensive Meta-Analysis v2.2 software. Wild-genotype ArgArg was considered as reference [odds ratio (OR) = 1.00]. Nine studies involving 1071 HNSCC cases were obtained. Meta-analysis results indicated no association between p53 Arg72Pro polymorphism and the risk of HPV-related HNSCC: for Pro/Pro vs. Arg/Arg, OR = 1.17, 95% confidence interval (CI) = 0.70-1.98; for Arg/Pro vs. Arg/Arg, OR = 1.25, 95% CI = 0.97-1.72; and for (Pro/Pro + Arg/Pro) vs. Arg/Arg, OR = 1.28, 95% CI = 0.95-1.70. These meta-analysis results were supported by subgroup and sensitivity analysis results. In conclusions, p53 Arg72Pro polymorphism is a potential marker of HP infection-related HNSCC rather than a susceptibility gene polymorphism.

Unal, Betul;Karaveli, Fatma Seyda;Pestereli, Hadice Elif;Erdogan, Gulgun 6131

https://doi.org/10.7314/APJCP.2013.14.10.6131 PDF KSCI

Background: The two basic methods that are currently accepted to identify the HER2 status are immunohistochemistry and flyorescence in situ hybridization (FISH). The aim of this study was to perform the dual-color silver in situ hybridization (dc-SISH) technique as an alternative to FISH. Materials and Methods: A total of 40 invasive breast carcinoma cases were assessed for HER2 gene amplification by FISH and dual-color SISH. Results: Significant correlation was found in the HER2 expression results obtained with the two approaches (p=0.001, p<0.05). The concordance rate was 92.3%. Conclusions: Foutine practical use of the dc-SISH method, which is much easier to apply, score, and evaluate, has many advantages. HER2 and CEN17 status can be evaluated simultaneously with the newly developed "Dual-Color Probe". All these specifications and the reliable results obtained support the widespread use of SISH technique in clinical practice.

Chen, Si-Ying;Hu, Sa-Sa;Dong, Qian;Cai, Jiang-Xia;Zhang, Wei-Peng;Sun, Jin-Yao;Wang, Tao-Tao;Xie, Jiao;He, Hai-Rong;Xing, Jian-Feng;Lu, Jun;Dong, Ya-Lin 6135

https://doi.org/10.7314/APJCP.2013.14.10.6135 PDF KSCI

Background: Breast cancer is a common malignant tumor which affects health of women and multidrug resistance (MDR) is one of the main factors leading to failure of chemotherapy. This study was conducted to establish paclitaxel-resistant breast cancer cell line and nude mice models to explore underlying mechanisms of MDR. Methods: The breast cancer drug-sensitive cell line MCF-7 (MCF-7/S) was exposed in stepwise escalating paclitaxel (TAX) to induce a resistant cell line MCF-7/TAX. Cell sensitivity to drugs and growth curves were measured by MTT assay. Changes of cell morphology and ultrastructure were examined by optical and electron microscopy. The cell cycle distribution was determined by flow cytometry. Furthermore, expression of proteins related to breast cancer occurrence and MDR was tested by immunocytochemistry. In Vivo, nude mice were injected with MCF-7/S and MCF-7/TAX cells and weights and tumor sizes were observed after paclitaxel treatment. In addition, proteins involved breast cancer and MDR were detected by immunohistochemistry. Results: Compared to MCF-7/S, MCF-7/TAX cells had a higher resistance to paclitaxel, cross-resistance and prolonged doubling time. Moreover, MCF-7/TAX showed obvious alterations of ultrastructure. Estrogen receptor (ER) expression was low in drug resistant cells and tumors while expression of human epidermal growth factor receptor 2 (HER2) and Ki-67 was up-regulated. P-glycoprotein (P-gp), lung resistance-related protein (LRP) and glutathione-S-transferase-${\pi}$ (GST-${\pi}$) involved in the MDR phenotype of resistant cells and tumors were all overexpressed. Conclusion: The underlying MDR mechanism of breast cancer may involve increased expression of P-gp, LRP and GST-${\pi}$.

Parakh, Abhinav;Megalamanegowdru, Jayachandra;Agrawal, Rohit;Hathiwala, Siddhi;Chandrakar, Mayank;Tiwari, Ram;Veeranna, Thippeswamy 6141

https://doi.org/10.7314/APJCP.2013.14.10.6141 PDF KSCI

Background: The objective of the study was to determine the knowledge, attitude and behaviors of the practicing dentists regarding tobacco cessation counseling (TCC) in Chhattisgarh state and also the barriers that prevent them from doing so. Materials and Methods: The study was conducted among dental practitioners of Raipur district, Chhattisgarh state (India). The sampling frame was registration with the State Dental Council and practicing in Raipur district. A questionnaire was personally administered and the practitioners were given explanations regarding how to complete it. Only descriptive statistics were calculated (SPSS version 16 for Windows). Results: Based on the responding dentists' self reports, 76% were not confident in TCC, 48% did not assume TCC to be their responsibility, 17% considered that it might have a negative impact on their clinical practice, whereas 24% considered it might take away precious time from their practice, 25% considered TCC by dentists to be effective to a considerable extent and 80% considered TCC activities are not effective due to lack of formal training, 69% considered dental clinics as an appropriate place for TCC but 82% thought there must be separate TCC centre and 100% of the dentists wanted TCC training to be a part of practice and that it should be included in dental curriculum. Some 95% of them were of the view that tobacco products should be banned in India and 86% responded that health professionals must refrain from tobacco habits so to act as role models for society. Conclusions: Dental professionals must expand their armamentarium to include TCC strategies in their clinical practice. The dental institutions should include TCC in the curriculum and the dental professionals at the primary and the community health care level should also be trained in TCC to treat tobacco dependence.

Ghadiri, Fereshteh;Iranpour, Negar;Yunesian, Masud;Shadlou, Zahra;Kaviani, Ahmad 6147

https://doi.org/10.7314/APJCP.2013.14.10.6147 PDF KSCI

Background: Breast feeding is considered to be mutually beneficial for both mothers and infants, though the effect of lactation problems on development of breast lesions (whether benign or malignant) is not clear. Objectives: This study was conducted to identify possible relations between lactation problems and benign and malignant breast disease. Materials and Methods: 308 patients referred to two referral breast clinics in Tehran, the capital city of IR Iran, between January 2008 and January 2011, were recruited. They were interviewed by a standard questionnaire regarding breast feeding problems. The study population was classified in 3 major groups; breast feeding without any problem, unwillingness to breast feed according to whether mothers' preference not to feed or some breast problems like mastitis, and finally insufficient milk that caused the mothers to feed their babies with formula. Results: Recruiting binary logistic regression method, mother's unwillingness to feed her child by breast milk, and also breast problems such as mastitis and abscess during lactation period showed significant relation with both benign and malignant breast diseases (p value<0.01). Surprisingly, inadequate milk was not associated with any of these conditions. Conclusions: We concluded that lactation problems which involve normal milk drainage from the breast may play an important role in whether the mother wll subsequently develope both benign and malignant pathologies. In contrast in the situation that the production of the milk is not sufficient and there are no intentional or unintentional problems in drainage of the produced milk, future problems would not be more common.

Wang, Kai-Feng;Pan, Wei;Wang, Fei;Wang, Gao-Feng;Madhava, Pai;Pan, Hong-Ming;Kong, De-Xing;Liu, Xiang-Guan 6151

https://doi.org/10.7314/APJCP.2013.14.10.6151 PDF KSCI

Radio frequency ablation (RFA) is an effective means of achieving local control of liver cancer. It is a particularly suitable mode of therapy for small and favorably located tumors. However, local progression rates are substantially higher for large tumors (>3.0 cm). In the current study, we report on a mathematical model based on geometric optimization to treat large liver tumors. A database of mathematical models relevant to the configuration of liver cancer was also established. The specific placement of electrodes and the frequency of ablation were also optimized. In addition, three types of liver cancer lesion were simulated by computer guidance incorporating mathematical models. This approach can be expected to provide a more effective and rationale mechanism for employing RFA in the therapy of hepatic carcinoma.

Ulasli, Sevinc Sarinc;Celik, Sefa;Gunay, Ersin;Ozdemir, Mehmet;Hazman, Omer;Ozyurek, Arzu;Koyuncu, Tulay;Unlu, Mehmet 6159

https://doi.org/10.7314/APJCP.2013.14.10.6159 PDF KSCI

Background: Phytochemical compounds are emerging as a new generation of anticancer agents with limited toxicity in cancer patients. The purpose of this study was to investigate the potential effcts of thymoquinone, caffeic acid phenylester (CAPE) and resveratrol on inflammatory markers, oxidative stress parameters, mRNA expression levels of proteins and survival of lung cancer cells in Vitro. Materials and Methods: The A549 cell line was treated with benzo(a)pyrene, benzo(a)pyrene plus caffeic acid phenylester (CAPE), benzo(a)pyrene plus resveratrol (RES), and benzo(a)pyrene plus thymoquinone (TQ). Inflammatory markers, oxidative stress parameters, mRNA expression levels of apoptotic and anti-apoptotic proteins and cell viability were assessed and results were compared among study groups. Results: TQ treatment up-regulated Bax and down-regulated Bcl2 proteins and increased the Bax/Bcl2 ratio. CAPE and TQ also up-regulated Bax expression. RES and TQ down-regulated the expression of Bcl-2. All three agents decreased the expression of cyclin D and increased the expression of p21. However, the most significant up-regulation of p21 expression was observed in TQ treated cells. CAPE, RES and TQ up-regulated TRAIL receptor 1 and 2 expression. RES and TQ down-regulated the expression of NF-kappa B and IKK1. Viability of CAPE, RES and TQ treated cells was found to be significantly decreased when compared with the control group (p=0.004). Conclusions: Our results revealed up-regulation of the key upstream signaling factors, which ultimately cause increase in their regulatory p53 levels affecting the induction of G2/M cell cycle arrest and apoptosis. Overall these results provide mechanistic insights for understanding the molecular basis and utility of the anti-tumor activity of TQ, RES and CAPE.

Li, Wei-Juan;Liu, Ge-Ling;Yu, Fang;Xiang, Xiu-Xiu;Lu, Yi-Fang;Xiao, Hong-Zhen;Shi, Yan-Ping 6165

https://doi.org/10.7314/APJCP.2013.14.10.6165 PDF KSCI

This study aimed to analyze the expression and clinical significance of cyclin G2 (CCNG2) in thyroid carcinoma and the biological effects of CCNG2 overexpression in a cell line. Immunohistochemistry and Western blotting were used to analyze CCNG2 protein expression in 63 cases of thyroid cancer and normal tissues to allow the relationship with clinical factors to be assessed. CCNG2 lentiviral and empty vectors were transfected into the thyroid cancer K1 cell line. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were applied to detect the mRNA and protein levels of CCNG2. MTT assay and cell cycle were also conducted to assess the influence of up-regulated expression of CCNG2 on K1 cell biology. The level of CCNG2 protein expression was found to be significantly lower in thyroid cancer tissue than normal tissues (P<0.05). Western blot: The relative amount of CCNG2 protein in thyroid cancer tissue was respectively found to be significantly lower than in normal tissues (P<0.05), correlating with lymph node metastasis, clinic stage and histological grade (P<0.05), but not gender, age or tumor size (P>0.05). Loss of CCNG2 expression correlated significantly with poor overall survival time on Kaplan-Meier analysis (P<0.05). The results for biological functions showed that K1 cell transfected CCNG2 had a lower survival fraction, a greater percentage in the G0/G1 phases, and lower cyclin-dependent kinase 2 (CDK2) protein expression compared with K1 cells non-transfected with CCNG2 (P<0.05). CCNG2 expression decreased in thyroid cancer and correlated significantly lymph node metastasis, clinic stage, histological grade and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator in thyroid cancer K1 cells by promoting degradation of CDK2.

Budkaew, Jiratha;Chumworathayi, Bandit 6173

https://doi.org/10.7314/APJCP.2013.14.10.6173 PDF KSCI

Background: Our objective was to determine the knowledge and attitudes of Thai generalists (general physicians) toward palliative terminal cancer care (PC) in a primary care setting. Materials and Methods: We performed a cross-sectional descriptive survey using a self-administered questionnaire. The total number of completed and returned questionnaires was 63, giving a 56% response rate. Data analysis was based on these (Cronbach's alpha=0.82) and percentages and mean values were assessed using the Fisher's exact test to determine the correlation of variables. Results: Overall, attitude and knowledge levels were slightly satisfactory. Results indicated that general physicians had moderate scores in both attitudes (84.1%) and knowledge (55.7%) regarding palliative terminal cancer care. However, they had insufficient knowledge regarding truth telling, pain control and management with morphine, emergency management in terminal cancer care and treatment of fluid intake in terminal stages. Attitude and knowledge scores were statistically correlated (p=0.036). Knowledge scores were further positively associated with being taught palliative care in their medical curriculum (p=0.042). Conclusions: Formal education in palliative care and development of palliative care services are very much needed in Thailand to provide holistic care to terminally ill patients.

El-Basmy, Amani;Al-Mohannadi, Shihab;Al-Awadi, Ahmed 6181

https://doi.org/10.7314/APJCP.2013.14.10.6181 PDF KSCI

Background: Lung cancer is the most frequent cancer in males and the fourth most frequent site in females, worldwide. This study is the first to explore the profile of lung cancer in Kuwait. Materials and Methods: Cases of primary lung cancer (Kuwaiti) in Kuwait cancer Registry (KCR) were grouped in 4 periods (10 years each) from 1970-2009. Epidemiological measures; age standardized incidence rate (ASIR) with 95% confidence intervals (CI), Standardized rate ratio (SRR) and Cumulative risk and Forecasting to year 2020-2029 used for analysis. Results: Between years, 2000-2009 lung cancer ranked the 4th and the 9th most frequent cancer in males and females respectively. M:F ratio 1:3. Mean age at diagnosis (95%CI) was 65.2 (63.9-66.4) years. The estimated risk of developing lung cancer before the age of 75 years in males is 1.8% (1/56), and 0.6 (1/167) in females. The ASIR for male cases was 11.7, 17.1, 17.0, 14.0 cases/100,000 population in the seventies, eighties, nineties and in 2000-2009 respectively. Female ASIR was 2.3, 8.4, 5.1, 4.4 cases/100,000 population in the same duration. Lung cancer is the leading cause cancer death in males 168 (14.2%) and the fifth cause of death due to cancer in females accounting for 6.1% of all cancer deaths. The ASMR (95%CI) was 8.1 (6.6-10.0) deaths/100,000 population and 2.8 (1.3-4.3) deaths/100,000 population in males and females respectively. The estimated Mortality to incidence Ratio was 0.6. Conclusions: The incidence of lung cancer between years 2000-2009 is not different from that reported in the seventies. KCR is expecting the number of lung cancer cases to increase.

Pandey, Saumya;Chandravati, Chandravati 6185

https://doi.org/10.7314/APJCP.2013.14.10.6185 PDF KSCI

Cervical cancer has emerged as a major public health problem in Lucknow and New York in the $21^{st}$ century. Cancer genetic studies are essential to identify/stratify disease-susceptible individuals in a population-based cohort. Sample size homogeneity and North Indian caste in female urology genetic-studies are significant issues in meaningful interpretation of data. A review of scientific literature using Pubmed database was conducted, including an assessment of cervical cancer genetic studies conducted as part of the author's doctoral dissertation at a premier Lucknow-based medical research Institute. Sample size numbers and caste criteria in the North Indian cohort ($N{\leq}400$ subjects) were evaluated with homogeneity in the sample cohort data set(s). Subgroup caste-stratification of North Indian cohort is equally essential, for instance, Brahmin (e.g. Pandey), Vaishya (e.g. Mittal), Rajput (e.g. Singh) and Kshudra (e.g. Yadav) during the conception and design of genetics-based studies. Sample size homogeneity in histopathologically confirmed case and control numbers and caste-based stratification in a North Indian cohort is essential in single nucleotide polymorphism (SNP) studies in cervical cancer susceptible populations to draw more definitive conclusions.

Hadji, Maryam;Nahvijou, Azin;Seddighi, Zahra;Beiki, Omid;Mohagheghi, Mohammad Ali;Mosavi-Jarrahi, Alireza;Marnani, Ahmad Barati;Zendehdel, Kazem 6189

https://doi.org/10.7314/APJCP.2013.14.10.6189 PDF KSCI

In December 2011, the Cancer Research Centre of the Cancer Institute of Iran sponsored a 3-day workshop on "Cancer Registration Principle and Challenges in Iran", which convened cancer registry experts. The objectives of the workshop were: to introduce standard cancer registration, to review the policy and procedure of cancer registration in Iran, and to review the best practices in the cancer registries in Iran. Challenges to cancer registration were discussed and recommendations were developed. The workshop was evaluated by participants for better organization of subsequent workshops. The objective of publication of this report is that based on Cancer in 5 Continents, many low- or middle-income countries do not meet the criteria for a standard population-based cancer registry (PBCR); on the other hand cancer is the most important cause of mortality and the essential part of any cancer control program is the cancer registry. Therefore this report focuses on problems and challenges of PBCR and provides recommendations which might help other developing countries to decrease their PBCR defects.

Kumar, Surendra;Kumar, Dinesh;Muniyandi, Malaisamy;Soan, Visheshwar;Pandey, Maya;Mishra, Dinesh Kumar 6195

https://doi.org/10.7314/APJCP.2013.14.10.6195 PDF KSCI

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