Asian Pacific Journal of Cancer Prevention

Li, Gang;Chang, Hong;Zhai, Yun-Peng;Xu, Wei 4943

https://doi.org/10.7314/APJCP.2013.14.9.4943 PDF KSCI

Hepatocellular carcinoma (HCC) is one of the most common malignancies, with a very poor prognosis. Despite significant improvements in diagnosis and treatment in recent years, the long-term therapeutic efficacy is poor, partially due to tumor metastasis, tecurrence, and resistance to chemo-or radio-therapy. Recently, it was found that a major feature of tumors is a combination of unrestrained cell proliferation and impaired apoptosis. There are now 8 recogized members of the IAP-family: NAIP, c-IAP1, c-IAP2, XIAP, Survivin, Bruce, Livin and ILP-2. There proteins all contribute to ingibition of apoptosis, and provide new potential avenues of cancer treatment. As a powerful tool to suppress gene expression in mammalian cells, RNAi species for inhibiting IAP genes cab be directed against cancers. This review will provide a brief introduction to recent developments of the application IAP-siRNA in tumor studies, with the aim of inspiring future treatment of HCC.

Su, Cheng-Hao;Lin, Yong;Cai, Lin 4953

https://doi.org/10.7314/APJCP.2013.14.9.4953 PDF KSCI

Primary liver cancer is one of the most common cancers at the global level, accounting for half of all cancers in some undeveloped countries. This disease tends to occur in livers damaged through alcohol abuse, or chronic infection with hepatitis B and C, on a background of cirrhosis. Various cancer-causing substances are associated with primary liver cancer, including certain pesticides and such chemicals as vinyl chloride and arsenic. The strong association between HBV infection and liver cancer is well documented in epidemiological studies. It is generally acknowledged that the virus is involved through long term chronic infection, frequently associated with cirrhosis, suggesting a nonspecific mechanism triggered by the immune response. Chronic inflammation of liver, continuous cell death, abnormal cell growth, would increase the occurrence rate of genetic alterations and risk of disease. However, the statistics indicated that only about one fifth of HBV carries would develop HCC in lifetime, suggesting that individual variation in genome would also influence the susceptibility of HCC. The goal of this review is to highlight present level of knowledge on the role of viral infection and genetic variation in the development of liver cancer.

Mohammadzadeh, Niloofar;Safdari, Reza;Rahimi, Azin 4961

https://doi.org/10.7314/APJCP.2013.14.9.4961 PDF KSCI

Greater use of mobile phone devices seems inevitable because the health industry and cancer care are facing challenges such as resource constraints, rising care costs, the need for immediate access to healthcare data of types such as audio video texts for early detection and treatment of patients and increasing remote aids in telemedicine. Physicians, in order to study the causes of cancer, detect cancer earlier, act in prevention measures, determine the effectiveness of treatment and specify the reasons for the treatment ineffectiveness, need to access accurate, comprehensive and timely cancer data. Mobile devices provide opportunities and can play an important role in consulting, diagnosis, treatment, and quick access to health information. There easy carriage make them perfect tools for healthcare providers in cancer care management. Key factors in cancer care management systems through a mobile phone health approach must be considered such as human resources, confidentiality and privacy, legal and ethical issues, appropriate ICT and provider infrastructure and costs in general aspects and interoperability, human relationships, types of mobile devices and telecommunication related points in specific aspects. The successful implementation of mobile-based systems in cancer care management will constantly face many challenges. Hence, in applying mobile cancer care, involvement of users and considering their needs in all phases of project, providing adequate bandwidth, preparation of standard tools that provide maximum mobility and flexibility for users, decreasing obstacles to interrupt network communications, and using suitable communication protocols are essential. It is obvious that identifying and reducing barriers and strengthening the positive points will have a significant role in appropriate planning and promoting the achievements of mobile cancer care systems. The aim of this article is to explain key points which should be considered in designing appropriate mobile health systems in cancer care as an approach for improving cancer care management.

de Menezes, Raquel Ferreira;Bergmann, Anke;Thuler, Luiz Claudio Santos 4965

https://doi.org/10.7314/APJCP.2013.14.9.4965 PDF KSCI

This study aimed to discuss the consumption of alcohol as a risk factor for major cancers. We performed a search in the PubMed database, using the following inclusion criteria: meta-analysis published in English in the last 10 years that addressed the relationship between alcohol and the risk of developing cancer. The results indicate that moderate to heavy consumption of alcohol increases the risk of developing cancer of the oral cavity and pharynx, esophagus, stomach, larynx, colorectum, central nervous system, pancreas, breast and prostate. This review did not find any association between alcohol consumption and an increased risk of cancers of the lung, bladder, endometrium and ovary. It was also observed that alcohol consumption may be inversely related to thyroid cancer. Our systematic review has confirmed consumption of alcohol as a risk factor for the development of several types of cancer.

Sanjaya, I. Putu Gde;Mochtar, Chaidir Arief;Umbas, Rainy 4973

https://doi.org/10.7314/APJCP.2013.14.9.4973 PDF KSCI

Background: To identify correlation and incidence of bone metastases in prostate cancer patient with low Gleason scores (GS) and prostate specific antigen (PSA) levels. Materials and Methods: This descriptive restrospective study covered patients with prostate cancer in Cipto Mangunkusumo Hospital in 2006-2011. Of a total of 478, those who had PSA values, histological examination, and bone scan were included, resulting in 358 eligible cases. PSA values were measured using the sandwich electrochemiluminescent immunoassay. Histological examination was graded according to Gleason's grading system and divided into 3 categories: well differentiated ($GS{\leq}6$), moderately differentiated (GS 7) and poorly differentiated (GS 8-10). Bone scans were performed using a radiopharmaceutical agent ($T_c$ 99m methylenen diphosphonate) with images captured by gamma camera. Results: The mean age was $67.5{\pm}7.8$, mean GS was $7.7{\pm}1.3$ and median PSA was 56.9 (range: 0.48-17000 ng/mL). There were 11 patients (3.0%) with positive bone scan with PSA<20 ng/mL and GS<8. Furthermore, there were 2 patients (0.6%) with $GS{\leq}6$ and PSA<10 ng/mL showing bone metastasis. Conclusions: In our study, there were still small percentage of patients with bone metastasis even when low values of PSA (PSA<10 ng/mL) and GS ($GS{\leq}6$) were applied.

Ersin, Fatma;Bahar, Zuhal 4977

https://doi.org/10.7314/APJCP.2013.14.9.4977 PDF KSCI

Background: The aim of the present study was to investigate perceived inhibiting and facilitating factors concerning cervical cancer early diagnosis behavior in Turkish women over the age of 40. Materials and Methods: The study was carried out by qualitative focus group interview with 35 participating women, in the period between April-June 2010. A semi-structured interview questionnaire based on the Health Belief Model and the Health Promotion Model was used. Content analysis was applied to the study data. Results: Barriers such as lack of knowledge of women as regards to the cervical cancer and early detection, lack of sensitivity-negligence, forgetting, fear, inadequacy of health insurance and transportation, financial problems, inability to get an appointment, lack of female doctors, embarassment, fatalist approach were frequently addressed. As for facilitating factors, these included provision of information, health professionals showing interest and tolerance, free services, provision of transportation means and reminding telephone calls. Conclusions: Focus group interviews were found to be effective in determining inhibiting and facilitating factors concerning cervical cancer early diagnosis behavior. In line with the results of the study, preparation of structured national and regional education programs and their addition to curriculum programs may be effective in realizing and maintaining positive early detection behavior.

Wang, Ning-Ning;Zhao, Li-Jun;Wu, Li-Nan;He, Ming-Feng;Qu, Jun-Wei;Zhao, Yi-Bing;Zhao, Wan-Zhou;Li, Jie-Shou;Wang, Jin-Hua 4983

https://doi.org/10.7314/APJCP.2013.14.9.4983 PDF KSCI

Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.

Indarti, Junita;Fernando, Darrell 4989

https://doi.org/10.7314/APJCP.2013.14.9.4989 PDF KSCI

Aim: To compare p16INK4a immunocytochemistry with the HPV polymerase chain reaction in predicting high grade cervical squamous intraepithelial lesions. Materials and Methods: This diagnostic case-control study was conducted from January 2010 until December 2010. We obtained 30 samples, classified according to the degree of cervical intraepithelial neoplasia (CIN): 11 samples for CIN 1, 9 samples for CIN 2, and 10 samples for CIN 3. HPV PCR, p16INK4a immunocytochemistry, and histopathological examination were performed on all samples. Statistical analysis was conducted using SPSS 20.0. Results: In predicting CIN 2-3, we found p16INK4a to have similar specificity and positive predictive value as HPV PCR (95%, 97.2% vs 96.7%), but better sensitivity (87.5% vs 72.5%) and negative predictive value (82.1% vs 67.6%). The most prevalent types of high-risk HPV in our study were HPV 33, 35, 58, 52, and 16. Conclusions: p16INK4a has better diagnostic values than HPV PCR and may be incorporated in the triage of ASCUS and LSIL to replace HPV PCR. Genotype distribution of HPV differs in each region, providing a challenge to develop HPV vaccines based on the epidemiology of HPV in that particular region.

Nandi, Moujhuri;Mandal, Abhijit;Asthana, Anupam Kumar 4993

https://doi.org/10.7314/APJCP.2013.14.9.4993 PDF KSCI

Background: A retrospective analysis of all cancer patients attending the radiotherapy outpatient department (OPD) of a single unit during the period of January 2005 till December 2006 was conducted to know the geographical distribution and incidence of the most common cancers, their stage of presentation, treatment compliance among the patients and follow-up. Materials and Methods: A total of 4,484 patients were registered in the Institute of Medical Sciences, Banaras Hindu University during the period of January 2005-December 2006; of which 1,975 registered in an individual unit were included for the retrospective analysis. Results: Most of the patients hailed from the various districts of UP and Bihar. Females outnumbered males with a ratio of 1.33:1. Females mostly belonged to the age group of 40-59 years; whilst males were a decade older. Major cancer sites in females were cervix and breast followed by head and neck. Leading cancer sites in males were head and neck, brain, bone, soft tissue and lung. Most of the cases presented in advanced stage of disease (74%). Squamous cell carcinoma was the most common histopathology (56%). A significant proportion of patients defaulted after undergoing preliminary investigations (16%). Only 53.9% of females and 58.5% of males took treatment out of which 68% and 63% completed the prescribed treatment. Compliance with follow-up was poor. Conclusions: The outcome of this study will significantly help us to define region specific strategies needed for cancer management in eastern Uttar Pradesh.

Zhao, Gan-Ting;Yang, Li-Juan;Li, Xi-Xia;Cui, Hui-Lin;Guo, Rui 4999

https://doi.org/10.7314/APJCP.2013.14.9.4999 PDF KSCI

Objective: This study aimed to investigate expression of the proto-oncogene POK erythroid myeloid ontogenic factor (Pokemon) in colorectal cancer (CRC), and assess inhibitory effects of a small interference RNA (siRNA) expression vector in SW480 and SW620 cells. Methods: Semi-quantitative reverse transcription-polymerase chain reaction (PCR) and immunohistochemistry were performed to determine mRNA and protein expression levels of Pokemon in CRC tissues. Indirect immunofluorescence staining was applied to investigate the location of Pokemon in SW480 and SW620 cells. The siRNA expression vectors that were constructed to express a short hairpin RNA against Pokemon were transfected to the SW480 and SW620 cells with a liposome. Expression levels of Pokemon mRNA and protein were examined by real-time quantitative-fluorescent PCR and western blot analysis. The effects of Pokemon silencing on proliferation of SW480 and SW620 cells were evaluated with reference to growth curves with MTT assays. Results: The mRNA expression level of Pokemon in tumor tissues ($0.845{\pm}0.344$) was significantly higher than that in adjacent tumor specimens ($0.321{\pm}0.197$). The positive expression ratio of Pokemon protein in CRC (87.0%) was significantly higher than that in the adjacent tissues (19.6%). Strong fluorescence staining of Pokemon protein was observed in the cytoplasm of the SW480 and SW620 cells. The inhibition ratios of Pokemon mRNA and protein in the SW480 cells were 83.1% and 73.5% at 48 and 72 h, respectively, compared with those of the negative control cells with the siRNA. In the SW620 cells, the inhibition ratios of Pokemon mRNA and protein were 76.3% and 68.7% at 48 and 72 h, respectively. MTT showed that Pokemon gene silencing inhibited the proliferation of SW480 and SW620 cells. Conclusion: Overexpression of Pokemon in CRC may have a function in carcinogenesis and progression. siRNA expression vectors could effectively inhibit mRNA and protein expression of Pokemon in SW480 and SW620 cells, thereby reducing malignant cell proliferation.

Dobo, Cristine;Stavale, Joao Norberto;Lima, Flavio De Oliveira;Ribeiro, Daniel Araki;Arias, Vitor;Gomes, Thiago Simao;Oshima, Celina Tizuko Fujiyama 5007

https://doi.org/10.7314/APJCP.2013.14.9.5007 PDF KSCI

Heat shock proteins are molecular chaperones that may be constitutively present in cells protecting them from various stresses, such as extreme temperature, anoxia or chemical agents. Cervical cancer is the second most prevalent malignancy of women. In this study, we analyzed the expression of Hsp27 by immunohistochemistry in cervical intraepithelial lesions of Brazilian women, along with samples from non neoplasic lesions (NN). Cervical intraepithelial neoplasia I (CIN I), II (CIN II) and III (CIN III)/in situ carcinoma and squamous cell carcinoma (SCC) were included. Immunostaining was observed in 30 (100%) samples of NN, 46 (92%) in CIN I, 50 (100%) in CIN II, 52 (98.11%) in CIN III/CIS, and 46 (98.11%) in SCC. In group NN Hsp27 immunostaining was heterogeneous, more intense in basal and parabasal layers of the epithelium and less or absent in the intermediate and superficial layer. The majority of the samples of CIS and SCC presented strong staining in all epithelial layers. Metaplasic cells, when present, were strongly stained. In this study, Hsp27 protein was found to be commonly expressed in cervical epithelial cells.

Karimi, Khatoon;Mahmoudi, Touraj;Karimi, Negar;Dolatmoradi, Hesamodin;Arkani, Maral;Farahani, Hamid;Vahedi, Mohsen;Parsimehr, Elham;Dabiri, Reza;Nobakht, Hossein;Asadi, Asadollah;Zali, Mohammad Reza 5011

https://doi.org/10.7314/APJCP.2013.14.9.5011 PDF KSCI

Background: Several epidemiological studies have shown associations between colorectal cancer (CRC) risk and type 2 diabetes and obesity. Any effects would be expected to be mediated through the insulin pathway. Therefore it is possible that variants of genes encoding components of the insulin pathway play roles in CRC susceptibility. In this study, we hypothesized that polymorphisms in the genes involving the insulin pathway are associated with risk of CRC. Materials and Methods: The associations of four single nucleotide polymorphisms (SNPs) in IGF-I (rs6214), IGFBP-3 (rs3110697), INSR (rs1052371), and IRS2 (rs2289046) genes with the risk of CRC were evaluated using a case-control design with 167 CRC cases and 277 controls by the PCR-RFLP method. Results: Overall, we observed no significant difference in genotype and allele frequencies between the cases and controls for the IGF-I, IGFBP-3, INSR, IRS2 gene variants and CRC before or after adjusting for confounders (age, BMI, sex, and smoking status). However, we observed that the IRS2 (rs2289046) GG genotype compared with AA+AG genotypes has a protective effect for CRC in normal weight subjects (p=0.035, OR=0.259, 95%CI= 0.074-0.907). Conclusions: These findings do not support plausible associations between polymorphic variations in IGF-I, IGFBP-3, INSR, IRS2 genes and risk of CRC. However, the evidence for a link between the IRS2 (rs2289046) variant and risk of CRC dependent on the BMI of the subjects, requires confirmation in subsequent studies with greater sample size.

Lian, Ji-Hu;Wang, Wei-Hua;Wang, Jia-Qiang;Zhang, Yu-Hong;Li, Yi 5017

https://doi.org/10.7314/APJCP.2013.14.9.5017 PDF KSCI

Objective: MicroRNAs (miRNAs) are a small class of non-coding, single-stranded RNAs with a critical role in genesis and maintenance of renal cancer mainly through binding to 3'-untranslated regions (3'UTR) of target mRNAs, which causes a block of translation and/or mRNA degradation. The aim of the present study was to investigate the potential effects of miR-122 in human renal cell carcinomas. Methods: The expression level of miR-122 was quantified by qRT-PCR. MTT, colony formation, invasion and migration assays were used to explore the potential functions of miR-122 in human renal cell carcinoma cells. Results: Cellular growth, invasion and migration in two A498 and 786-O cells were significantly increased after miR-122 transfection. Further experiments demonstrated that overexpression of miR-122 resulted in the increase of phospho-Akt (Ser473) and phospho-mTOR (Ser2448), then activation of mTOR targets, p70S6K and 4E-BP1. Conclusions: The up-regulation of miR-122 may play an important role in the progress of renal cancer through activating PI3K/Akt signal pathway and could be a potential molecular target for anti-cancer therapeutics.

Domeyer, Philip John;Sergentanis, Theodoros Nikolaos;Katsari, Vasiliki;Souliotis, Kyriakos;Mariolis, Anargiros;Zagouri, Flora;Zografos, George Constantine 5023

https://doi.org/10.7314/APJCP.2013.14.9.5023 PDF KSCI

Background: To evaluate knowledge about screening tests and tests without proven screening value in a Greek Breast Unit population undergoing benign vacuum-assisted breast biopsy (VABB). Materials and Methods: This study included 81 patients. Three knowledge-oriented items (recommended or not, screening frequency, age of onset) were assessed. Regarding screening tests two levels of knowledge were evaluated: i). crude knowledge (CK), i.e. knowledge that the test is recommended and ii). advanced knowledge (AK), i.e. correct response to all three knowledge-oriented items. Solely CK was evaluated for tests without proven screening value. Risk factors for lack of knowledge were assessed with multivariate logistic regression. A second questionnaire was administered 18 months after VABB to assess its impact on the performance of tests. Results: Concerning screening tests considerable lack of AK was noted (mammogram, 60.5%; Pap smear, 59.3%; fecal occult blood testing, 93.8%; sigmoidoscopy, 95.1%). Similarly lack of CK was documented regarding tests without proven screening value (breast self-examination, 92.6%; breast MRI, 60.5%; abdominal ultrasound, 71.6%; barium meal, 48.1%; urine analysis, 90.1%; chest X-Ray, 69.1%; electrocardiogram, 74.1%; cardiac ultrasound, 75.3%). Risk factors for lack of AK were: place of residence (mammogram), age (Pap smear), personal income (sigmoidoscopy); risk factors for lack of CK included number of offspring (breast MRI, chest X-Ray), BMI (abdominal ultrasound), marital status (urine analysis), current smoking status (electrocardiogram). VABB's only effect was improvement in mammogram rates. Conclusions: A considerable lack of knowledge concerning screening tests and misperceptions regarding those without proven value was documented.

Guizani, Nejib;Waly, Mostafa Ibrahim;Singh, Vandita;Rahman, Mohammad Shafiur 5031

https://doi.org/10.7314/APJCP.2013.14.9.5031 PDF KSCI

Zizyphus spina-christi (ZSC) fruit is a rich source of bioactive compounds but any medicinal properties in chemoprevention of colon cancer have hitherto not been studied. The aim of the present study was to examine in vivo protective effects of ZSC water extract on colon carcinogenesis in azoxymethane (AOM)-treated rats. Our results showed that ZSC significantly reduced AOM-induced colonic aberrant crypt foci development and AOM-induced oxidative stress as indicated by restoration of endogenous glutathione depletion and abrogating the impairment of total antioxidant capacity. Caspase-3 cleavage, which has been considered as an apoptotic index, was almost undetectable in AOM-treated rats and ZSC exhibited pro-apoptotic effects evidenced by increased levels of cleaved caspase-3. In the studied model, our findings provide the first in vivo evidence that ZSC extract could inhibit the early stage of colon carcinogenesis by preventing oxidative stress and inducing apoptosis.

Mao, Ying-Ying;Jing, Fang-Yuan;Jin, Ming-Juan;Li, Ying-Jun;Ding, Ye;Guo, Jing;Wang, Fen-Juan;Jiang, Long-Fang;Chen, Kun 5037

https://doi.org/10.7314/APJCP.2013.14.9.5037 PDF KSCI

Accumulated evidence has indicated that Ephrin A1 (EFNA1) is associated with angiogenesis and tumorigenesis in various types of malignancies, including colorectal cancer (CRC). In the current study, we performed an online search using the public microarray database to investigate whether EFNA1 expression might be altered in CRC tissues. We then conducted a case-control study including 306 subjects (102 cases and 204 well-matched controls) in Xiaoshan County to assess any association between genetic polymorphisms in EFNA1 and CRC susceptibility. Searches in the Oncomine expression profiling database revealed EFNA1 to be overexpressed in CRC tissue compared with adjacent normal tissue. The rs12904 G-A variant located in the 3' untranslated region (UTR) of EFNA1 was observed to be associated with CRC susceptibility. Compared with the AA homozygous genotype, those carrying GA genotype had a decreased risk of developing CRC (odds ratio (OR)=0.469, 95% confidence interval (CI): 0.225-0.977, and P=0.043). The association was stronger among smokers and tea drinkers, however, no statistical evidence of interaction between rs12904 polymorphism and smoking or tea drinking on CRC risk was found. Our results suggest that EFNA1 is involved in colorectal tumorigenesis, and rs12904 A>G polymorphism in the 3' UTR of EFNA1 is associated with CRC susceptibility. Larger studies and further mechanistic investigations are warranted to confirm our findings.

Cheung, Min Rex 5043

https://doi.org/10.7314/APJCP.2013.14.9.5043 PDF KSCI

Background: This is a part of a larger effort to characterize the effects on socio-economic factors (SEFs) on cancer outcome. Surveillance, Epidemiology and End Result (SEER) bone and joint sarcoma (BJS) data were used to identify potential disparities in cause specific survival (CSS). Materials and Methods: This study analyzed SEFs in conjunction with biologic and treatment factors. Absolute BJS specific risks were calculated and the areas under the receiver operating characteristic (ROC) curve were computed for predictors. Actuarial survival analysis was performed with Kaplan-Meier method. Kolmogorov-Smirnov's 2-sample test was used to for comparing two survival curves. Cox proportional hazard model was used for multivariate analysis. Results: There were 13501 patients diagnosed BJS from 1973 to 2009. The mean follow up time (SD) was 75.6 (90.1) months. Staging was the highest predictive factor of outcome (ROC area of 0.68). SEER stage, histology, primary site and sex were highly significant pre-treatment predictors of CSS. Under multivariate analysis, patients living in low income neighborhoods and rural areas had a 2% and 5% disadvantage in cause specific survival respectively. Conclusions: This study has found 2-5% decrement of CSS of BJS due to SEFs. These data may be used to generate testable hypothesis for future clinical trials to eliminate BJS outcome disparities.

Nair, Kesavan Sreekantan;Raj, Sherin;Tiwari, Vijay Kumar;Piang, Lam Khan 5049

https://doi.org/10.7314/APJCP.2013.14.9.5049 PDF KSCI

Background: To assess the treatment pattern and expenditure incurred by cancer patients undergoing treatment at government tertiary hospitals in India. Materials and Methods: A cross-sectional study of 508 cancer patients randomly selected from tertiary cancer hospitals funded by central/state governments located in major cities of five states in India, namely Kerala, Maharashtra, Rajasthan, West Bengal and Mizoram, during March - May 2011 was conducted. Information related to direct costs, indirect costs and opportunity costs incurred on investigations and treatment, major source of payment and difficulties faced by patients during the course of treatment was collected. Results: About 45% of the patients used private health facilities as the first point of contact for cancer related diseases as against 32% in public hospitals. About 47% sought private health facilities for cancer investigations, 21% at district/sub-district hospitals, and about 4% contacted primary health care facilities. A majority of the patients (76%) faced financial problems while undergoing treatment. Conclusions: The results highlight the importance of involving the primary health care system in the cancer prevention activities.

Gao, Xing-Hui;Yang, Xue-Qin;Wang, Bi-Cheng;Liu, Shao-Ping;Wang, Fu-Bing 5055

https://doi.org/10.7314/APJCP.2013.14.9.5055 PDF KSCI

Objective: Twist, a basic helix-loop-helix transcription factor, plays a key role in the metastatic progression of human cancer. Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type IV collagen, therefore being possibly related to tumor progression. It has been reported that Twist and matrix metalloproteinase-9 (MMP-9) are expressed in gastric cancers. However, the exact roles of Twist and MMP-9 in tumor metastasis and prognosis remain unclear. The aim of this study was to casts light on this question. Methods:Twist and MMP-9 expression in tissue sections of 37 gastric carcinomas was evaluated with immunohistochemistry. The staining results were compared with clinicopatholgic features and to patients' outcome. Results: Twist positive expression was significantly increased in gastric cancer cases with lymph node metastasis (P=0.023). But no correlations were found between MMP-9 overexpression and clinicopathologic features, such as recurrence, TNM stage, and lymph node metastasis. Overall survival (OS) was significantly correlated with recurrence, serosa invasion, TNM stages, distant metastasis, and MMP-9 (P=0.027, 0.021, 0.000, 0.024 and 0.036, respectively). Disease-free survival (DFS) was prominently related to recurrence location, serosa invasion and TNM stages (P=0.000, 0.038 and 0.003, respectively). In the Cox regression multivariate analysis, TNM stage, distant metastasis and MMP-9 were significantly associated with prognosis of gastric cancer (P=0.002, 0.019, and 0.032, respectively). Conclusions: This study showed Twist positive expression to be significantly correlated with lymph node metastasis in gastric cancer. MMP-9 overexpression is associated with OS, suggesting that MMP-9 is a prognostic indicator for survival in patients with gastric cancer.

Krishnamurthy, Arvind;Ramshankar, Vijayalakshmi 5061

https://doi.org/10.7314/APJCP.2013.14.9.5061 PDF KSCI

Background: Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer diagnosed within the oral cavity worldwide. Many studies in India report OTSCC ranking among the top two most common subsites within the oral cavity. India is often labeled the oral cancer capital of the world. The incidence of tongue cancers in the population-based cancer registry (PBCR) of Chennai is showing an increasing trend. A majority of the oral cavity cancers (85%) in our cancer center present in advanced stages (III and IV). In contrast, early tongue cancers (stages I and II) constitute nearly 45% of all OTSCCs. Aim: The aim of this study was to analyze the clinical profile and epidemiological trends in our early stage tongue cancer patients with an emphasis on tobacco and alcohol habits. Materials and Methods: This retrospective analysis was based on a prospectively collected database of 458 consecutive early stage OTSCC in-patients at a tertiary care oncology centre in Chennai between 1995 and 2008. Results: Our study suggests that the earlier trends have clearly changed whereby nearly half of our patients are now never-tobacco users. The findings of the study indicate that a majority of the patients were never alcohol users (86.4%) and nearly half of them were never tobacco users (49.3%), and they had the best survival outcomes. This increasing trend of OTSCC among non-tobacco users is in contrast to our earlier experience of tongue cancer more than five decades ago.The median age of patients in our study was 53.3 years; the male to female ratio was approximately 2:1. The median follow up for the 458 patients was 53 months. Conclusions: Our study importantly as well as interestingly shows a conspicuous absence of association with the traditional risk factors, tobacco and alcohol.

Kandula, Mahesh;Chennaboina, Kalyan Kumar;Ammi Raju, Y.S.;Raju, Suryanarayana 5067

https://doi.org/10.7314/APJCP.2013.14.9.5067 PDF KSCI

Background: The phosphatidylinositol 3-kinase (PI3K) pathway plays a significant role in apoptosis, cellular proliferation and motility. The aim of the present study was to analyze mutations and gene expression profiles of the PI3KCA gene to determine any role in breast carcinomas. Materials and Methods: We analyzed 38 breast cancers for mutations in the two PIK3CA hotspots in exons 9 and 20 by direct sequencing of DNA obtained from biopsy samples. We have also analyzed expression of the PI3KCA gene in 38 breast carcinoma tumor and corresponding control tissue samples at the mRNA level by RT-PCR. The Fisher's exact test ($2{\times}2$ only) was performed using MedCalc software for to examine associations with mRNA levels. Results: In the present study a total of 13 cases demonstrated somatic mutations. In 9/13 cases 1633 G>A (E545K) were found in exon 9, whereas in exon 20, 4/13 cases had 3140A>G mutation. Our combined analysis showed PI3KCA mutations present in 34% of human breast cancer patients. In our study, we have also clearly found significantly higher expression in breast cancer tissues in comparison with control tissues (p=0.001). Conclusions: PIK3CA mutation is an emerging tumor marker that, in the future, might be used in the process of choosing a treatment. The detection of PI3KCA mutation might have important clinical implications for diagnosis, progression and therapy.

Qi, Bo;Yao, Wen-Jian;Zhao, Bao-Sheng;Qin, Xiu-Guang;Wang, Yi;Wang, Wen-Ju;Wang, Tian-Yun;Liu, Shang-Guo;Li, Han-Chen 5073

https://doi.org/10.7314/APJCP.2013.14.9.5073 PDF KSCI

Objective: This study aimed to investigate whether the miR-198 expression level is related to clinicopathological factors and prognosis of esophageal cancer. Methods: MicroRNA was extracted from esophageal cancer patients who underwent surgery for assessment using the Taqman@ MicroRNA assay. The correlation between miR-198 expression and clinicopathological features was analyzed, and the significance of miR-198 as a prognostic factor and its relationship with survival was determined. Results: MicroRNA-198 (miR-198) expression was higher in patients with poor prognosis than those with good prognosis (P<0.05). Kaplan-Meier analysis results showed that the miR-198 expression level had a significant correlation with survival time (P=0.030) and that patients with a higher expression of miR-198 had a shorter survival time. Cox multi-factor model analysis showed that patient prognosis (P=0.014), tumor length (P=0.040) and expression (P=0.012), and survival time had a significant correlation; the corresponding risks were 7.268, 1.246, and 3.524, respectively. Conclusion: miR-198 overexpression is involved in the poor prognosis of esophageal cancer and can be used as a biomarker for selection of cases requiring especial attention.

Babu, Giridhara Rathnaiah;Lakshmi, Srikanthi Bodapati;Thiyagarajan, Jotheeswaran Amuthavalli 5077

https://doi.org/10.7314/APJCP.2013.14.9.5077 PDF KSCI

Background: Breast cancer is the most frequent cancer in women globally and represents the second leading cause of cancer death among women (after lung cancer). India is going through epidemiologic transition. It is reported that the incidence of breast cancer is rising rapidly as a result of changes in reproductive risk factors, dietary habits and increasing life expectancy, acting in concert with genetic factors. Materials and Methods: In order to understand the existing epidemiological correlates of breast cancer in South India, a systematic review of evidence available on epidemiologic correlates of breast cancer addressing incidence, prevalence, and associated factors like age, reproductive factors, cultural and religious factors was performed with specific focus on screening procedures in southern India. Results: An increase in breast cancer incidence due to various modifiable risk factors was noted, especially in women over 40 years of age, with late stage of presentation, lack of awareness about screening, costs, fear and stigma associated with the disease serving as major barriers for early presentation. Conclusions: Educational strategies should be aimed at modifying the life style, early planning of pregnancy, promoting breast feeding and physical activity. It is very important to obtain reliable data for planning policies, decision-making and setting up the priorities.

Tang, Li;Xu, Fenglian;Zhang, Taotao;Lei, Jun;Binns, Colin William;Lee, Andy Ho-Won 5085

https://doi.org/10.7314/APJCP.2013.14.9.5085 PDF KSCI

Background: The north-western region of China has a high incidence of oesophageal cancer. This study aimed to investigate whether the intake of food and beverage at high temperature is associated with the risk of oesophageal cancer among adults residing in this remote part of China. Materials and Methods: A case-control study was undertaken in Urumqi and Shihezi, Xinjiang Uyghur Autonomous Region of China, between 2008 and 2009. Participants were 359 incident oesophageal cancer patients and 380 hospital-based controls. Information on temperature of food and beverage intake was obtained by face-to-face interview. Logistic regression analyses were performed to ascertain the association between intake temperature and the risk of oesophageal cancer. Results: The oesophageal cancer patients consumed foods and beverages at higher temperatures than controls, p<0.001. High temperature of tea, water and food intake appeared to increase the risk of oesophageal cancer by more than two-fold, with adjusted odds ratio (95% confidence intervals) of 2.86 (1.73-4.72), 2.82 (1.78-4.47) and 2.26 (1.49-3.45), respectively. Conclusions: Intake of food and beverage at high temperature was positively associated with the incidence of oesophageal cancer in north-western China.

Li, Cai-Xia;Zhang, Kai;Xie, Fu-Bo 5089

https://doi.org/10.7314/APJCP.2013.14.9.5089 PDF KSCI

Objective: This study aimed to investigate the effects of BCRP expression on tumor recurrence, metastasis and treatment tolerability. Methods: A VX2 rabbit liver tumor model was established. Division was randomly into 4 groups: namely saline control group; A group, given hydration lipiodol; B group, Ad-p53; and C group, Ad-p53+hydration lipiodol. After the intervention, samples were collected to detect the BCRP, MMP-2, VEGF and PCNA. Results: The expression of BCRP, MMP-2, PCNA and VEGF in tumors in Group A had no significant difference when compared with the control group, while in B and C group, the values were significantly lower (P<0.05). BCRP positive expression in metastatic lesions significantly increased (P<0.05), and was correlated with MMP-2 ($X^2=6.172$, P=0.0131). Conclusions: BCRP may play an important role in mediating liver cancer multidrug resistance to chemotherapy, and may be correlated with tumor recurrence and metastasis, which leads to weakened treatment effect. Ad-P53 can down-regulate the expression of related genes, playing a role in multidrug resistance reversal and increased sensitivity in liver cancer treatment.

Thapa, Bibhusal;Singh, Yogendra;Sayami, Prakash;Shrestha, Uttam Krishna;Sapkota, Ranjan;Sayami, Gita 5095

https://doi.org/10.7314/APJCP.2013.14.9.5095 PDF KSCI

Background: The overall incidence of breast cancer in South Asian countries, including Nepal, is low compared to Western countries. However, the incidence of breast cancer among young women is relatively high. Breast cancer in such cases is characterized by a relatively unfavorable prognosis and unusual pathological features. The aim of this study was to investigate clinico-pathological and biological characteristics in younger breast cancer patients (<40 years) and compare these with their older counterparts. Materials and Methods: Nine hundred and forty four consecutive female breast cancer patients, admitted to the Department of Surgery, Tribhuvan University Teaching Hospital, Kathmandu, Nepal between November 1997 and October 2012, were retrospectively analyzed. Results: Out of the 944 female breast cancer patients, 263 (27.9%) were <40 years. The mean age was $34.6{\pm}5.0$ years among younger patients compared to $54.1{\pm}9.9$ for those ${\geq}40$ years. The mean age at menarche was also significantly lower ($13.5{\pm}1.5$ vs $14.2{\pm}1.5$ years p=0.001) while the mean duration of symptoms was significantly longer (7.6 vs 6.5 months p=0.004). Family history of breast cancer was evident in 3.0% of the young women versus 0.3% in the older one. Mammography was performed less frequently in younger patients (59.7%), compared to older (74.4%), and was of diagnostic benefit in only 20% of younger patients compared to 85% of older ones. At diagnosis, the mean tumor diameter was significantly larger in young women ($5.0{\pm}2.5$ vs $4.5{\pm}2.4cm$, p=0.005). Axillary lymph nodes were positive in 73% of younger patients and 59% of older patients. In the younger group, the proportion of stage III or IV disease was higher (55.1% vs 47.1%, $p{\leq}0.05$). The proportion of breast conserving surgery was higher in young patients (25.1% vs 8.7%) and a higher proportion of younger patients receive neoadjuvant chemotherapy (9.9% vs 2.8%). The most common histological type was ductal carcinoma (93.1% vs 86%). The proportion of histological grade II or III was higher in younger patients (55.9% vs 24.5%). Similarly, in the younger group, lymphatic and vascular invasion was more common (63.2% vs 34.3% and 39.8% vs 25.4%, respectively). Patients in the younger age group exhibited lower estrogen and/or progesterone receptor positivity (34.7% vs 49.8%). Although statistically not significant, the proportion of triple negative tumors in younger age group was higher (22.4% vs 13.6%). Conclusions: Breast cancer in young Nepalese women represents over one quarter of all female breast cancers, many being diagnosed at an advanced stage. Tumors in young women exhibit more aggressive biological features. Hence, breast cancer in young women is worth special attention for earlier detection.

Kulkarni, Padmaja Ramesh;Rani, Hephzibah;Vimalambike, Manjunath Gubbanna;Ravishankar, Sunila 5101

https://doi.org/10.7314/APJCP.2013.14.9.5101 PDF KSCI

The incidence and mortality of cervical cancer remains high in India even after sixty years of introduction of the Pap smear (cervical cytology) which is an effective means of identifying preinvasive lesions of carcinoma cervix. The morbidity and mortality due to cervical cancer has come down drastically in countries with well established screening programmes at national level. This study aims at screening women for cervical cancer opportunistically during their visit to hospital and to study various types of neoplastic and non-neoplastic lesions of the cervix by cervical smear study (Pap smear study). In the present study, a total of 350 cervical smears were studied. The age of patients ranged from 19 years to 80 years with mean age being 37.5 years. Out of 350 cases, the diagnosis of neoplasia was given in 43 cases and 258 cases were diagnosed as inflammatory smears. Forty-cases were normal and 9 cases were inadequate to evaluate. Forty-three patients who were found to have neoplastic lesions on cytology were referred for further investigations like colposcopy and biopsy to confirm the diagnosis and avail proper treatment. Limitation of the present study was small sample size as all female patients aged between 20 and 60 years visiting hospital were not included in the screening, other screening tests like VIA (visual inspection with acetic acid test) and HPV DNA (human papilloma virus) tests were not done. Until the time centrally organised screening programmes for cervical cancer are established in India, arrangements should be made for hospital based opportunistic screening for all women attending hospital. The cost effectiveness of different screening tests for cervical cancer should be evaluated.

Yavuzcan, Ali;Caglar, Mete;Kayikci, Muhammet Ali;Basaran, Ekrem;Tekin, Ali;Ozdemir, Enver;Dilbaz, Serdar;Ustun, Yusuf;Cam, Haydar Kamil 5107

https://doi.org/10.7314/APJCP.2013.14.9.5107 PDF KSCI

Background: Among women with haematuria, defining individuals under high risk for bladder cancer based on reproductive factors prior to cystoscopy would be of great benefit in the management of this condition. The aim of this study was to compare age and reproductive factors such as menopausal status, parity, age at first delivery and age at the last delivery between women who have haematuria with or without bladder cancer. Materials and Methods: A total of 463 patients underwent diagnostic cystoscopy in D$\ddot{u}$zce University Faculty of Medicine between 1 June 2008 and 1 June 2013. Female patients who presented with persistent microscopic or macroscopic haematuria and underwent standard evaluation for haematuria including urinalysis, urine culture, urine cytology, urinary tract imaging with excretory urography or computerized tomography with contrast enhancement and endoscopic evaluation of the urethra and bladder were included in this study. Exclusion criteria were tobacco use and high risk occupations for bladder cancer such as textile, dry cleaning, painting and etc. Forteen women had hematuria due to benign conditions, and 18 due to bladder cancer. Data were retrospectively retrieved from the medical records of Duzce University Hospital. Results: Patients with haematuria due to benign reasons did not significantly differ from patients who were found to have bladder cancer in terms of age (p=0.28), menopausal status (p=0.29), mean parity (p=0.38), being nulliparous (p=0.57), parity ${\geq}3$ (p=0.22), age ${\leq}18$ years at first delivery (p=1.00), age ${\geq}30$ years at last delivery (p=0.26), age ${\geq}35$ years at last delivery (p=0.23) and percentage of the patients with advanced age (${\geq}65$ years) (p=0.18). Conclusions: It is difficult to predict a high risk for developing bladder cancer in women with haematuria based solely on reproductive factors.

Heidarnia, Mohammad Ali;Monfared, Esmat Davoudi;Akbari, Mohammad Esmail;Yavari, Parvin;Amanpour, Farzaneh;Mohseni, Maryam 5111

https://doi.org/10.7314/APJCP.2013.14.9.5111 PDF KSCI

Background: Early in the 21st century, cancers are the second cause of death worldwide. Colon cancer is third most common cancer and one of the few amenable to early diagnosis and treatment. Evaluation of factors affecting this cancer is important to increase survival time. Some of these factors affecting all diseases including cancer are social determinants of health. According to the importance of this disease and relation with these factors, this study was conducted to assess the relationship between social determinants of health and colon cancer survival. Materials and Methods: This was a cross-sectional, descriptive study for patients with colon cancer registered in the Cancer Research Center of Shahid Beheshti University of Medical Science, from April 2005 to November 2006, performed using questionnaires filled by telephone interview with patients (if patients had died, with family members). Data was analyzed with SPSS software (version 19) for descriptive analysis and STATA software for survival analysis including log rank test and three step Cox Proportional Hazard regression. Results: Five hundred fifty nine patients with ages ranging from 23 to 88 years with mean${\pm}$standard deviation of $63{\pm}11.8$ years were included in the study. The five year survival was 68.3%( 387 patients were alive and 172 patients were dead by the end of the study). The Cox proportional hazard regression showed 5-year survival was related to age (HR=0.53, p=0.042 for>50 years versus<50 years old) in first step, gender (HR=0.60, p=0.006 for female versus male) in second step, job (HR=1.7, p=0.001 for manual versus non manual jobs), region of residency (HR=3.49, p=0.018 for west versus south regions), parents in childhood (HR=2.87, p=0.012 for having both parents versus not having), anatomical cancer location (HR=2.16, p<0.033 for colon versus rectal cancer) and complete treatment (HR=5.96, p<0.001 for incomplete versus complete treatment). Conclusions: Social determinants of health such as job, city region residency and having parents during childhood have significant effects in 5-year survival of colon cancer and it may be better to consider these factors in addition to developing cancer treatment and to focus on these determinants of health in long-time planning.

He, Mao-Lin;Wu, Yang;Zhao, Jin-Min;Wang, Zhe;Chen, Ying-Bin 5117

https://doi.org/10.7314/APJCP.2013.14.9.5117 PDF KSCI

Purpose: To explore the association between PIK3CA and AKT single nucleotide polymorphisms(SNP) and osteosarcoma susceptibility. Methods: TaqMan polymerase chain reaction(PCR) was used to detect the genotypes of SNPs (rs7646409, rs6973569 and rs9866361) in peripheral blood samples from 59 patients with osteosarcoma and from 63 healthy controls. Unconditional logistic regression was used to analyze the correlation between SNPs and osteosarcoma risk. Results: No statistically significant difference was found between osteosarcoma patients and healthy controls in the genotype of AKT rs6973569 (P=0.7). However, after stratified analysis, the genotype AA of AKT rs6973569 carried a higher risk of osteosarcoma metastasis (OR:2.94, 95%CL:1.00-8.59); the difference of rs7646409 genotype distributions between the case and control groups was statistically significant (P=0.032). Taking genotype TT as a reference, the risk of osteosarcoma increased three fold in patients with genotype CC (OR:3.47, 95%CL:1.26-9.56). A statistically significant difference was found between the alleles C and T (P=0.005). Further analysis showed that the risk factor was more pronounced in male patients with Enneking's stage IIB and osteoblastic osteosarcoma. PIK3CA rs9866361 did not fit Hardy-Weinberg equilibrium (P<0.05). Conclusions: Genotype CC in locus PIK3CA rs7646409 may increase the risk of osteosarcoma in the Chinese population.

Abbastabar, Hedayat;Hamidifard, Parvin;Roustazadeh, Abazar;Mousavi, Seyyed Hamid;Mohseni, Shokrallah;Sepandi, Mojtaba;Barouni, Mohsen;Alizadeh, Ali 5123

https://doi.org/10.7314/APJCP.2013.14.9.5123 PDF KSCI

Background: Breast cancer is one the most common cause of cancer-related deaths among women worldwide. The aims of this study were to investigate the impact of dietary factors and health status indicators on breast cancer (BC) incidence. Materials and Methods: Risk factor data (RFD) of 89,404 individuals (15-64 years old) were gathered by questionnaire and laboratory examinations through a cross sectional study from the Non-Communicable Disease Surveillance Centre (NCDSC) of Iran. BC incidences of all provinces through 2001-2006 segregated by age and gender were obtained from the Cancer Registry Ministry of Health (CRMH). Results: a significant positive relationship was seen between diabetes mellitus, fish comsupmption, percent of academic education and non-consumption of fruit, and breast cancer in women. However, non fish consumption, percent age illiteracy and taking fruit showed a significant negative relationship with the incidence of breast cancer. In addition, multiple linear regression analysis showed associations among percentage with academic education, fruit consumption and diabetes. Conclusions: We conclude that dietary factors such as fish and furit consumption, dairy products, health status indicators, academic education, and some diseases like diabetes mellitus can affect the BC incidence, although the results of ecologic studies like this must naturally be interpreted with caution.

Yoney, Adnan;Isikli, Levent 5127

https://doi.org/10.7314/APJCP.2013.14.9.5127 PDF KSCI

Background: 5-fluoro-uracil (FU) is a common agent in postoperative chemoradiation in gastric adenocarcinoma. However, FU is not well tolerated in a significant proportion of patients. Capecitabine (CA) is an orally administered fluoropyrimidine carbamate which is preferentially converted to active 5-FU and is one of the agents used instead of FU in such cases. We compared the toxicity, local and distant control and survival rates with FU or oral CA during the course of concurrent radiotherapy to assess the role of CA used instead of FU. Materials and Methods: We conducted an analysis of survival, disease control and toxicity data in 46 patients treated with postoperative chemoradiation following total or subtotal gastrectomy for gastric adenocarcinoma with either FU or CA between January 2008 and December 2012. Results: Median follow-up was 19 months (range: 3-59), median survival time was 23 ({\pm}6.08) months and 1-3 years overall survival (OS) rates were 64.9-39% for all patients. Compared with the CA regimen, the incidence of treatment interruption was higher with FU (p=0.023), but no significant differences were seen in local control (p=0.510), distant recurrences (p=0.721) and survival rates (p=0.866) among patients. Conclusions: Concurrent CA with radiotherapy seems to be a more tolerable and an equally effective regimen for the postoperative treatment of gastric adenocarcinoma when compared to FU.

Zhang, Jun-Feng;Hua, Rong;Sun, Yong-Wei;Liu, Wei;Huo, Yan-Miao;Liu, De-Jun;Li, Jiao 5133

https://doi.org/10.7314/APJCP.2013.14.9.5133 PDF KSCI

Background: Perineural invasion (PNI) has been reported as one of the sources of locoregional recurrence in resected pancreatic cancer (PC). However the impact of PNI in resected pancreatic cancer remains controversial. The purpose of this study was to determine the association between PNI status and clinical outcomes. Methods: Publications were identified which assessed prognostic significance of PNI status in resected pancreatic cancer up to February 2013. A meta-analysis was performed to clarify the association between PNI status and clinical outcomes. Results: A total of 21 studies met the inclusion criteria, covering 4,459 cases. Analysis of these data showed that intrapancreatic PNI was correlated with reduced overall survival only in resected pancreatic ductal adenocarcinoma (PDAC) patients (HR=1.982, 95%CI: 1.526-2.574, p=0.000). Extrapancreatic PNI was correlated with reduced overall survival in all resected pancreatic cancer patients (HR=1.748, 95%CI: 1.372-2.228, p=0.000). Moreover, intrapancreatic PNI status may be associated with tumor recurrence in all resected pancreatic cancer patients (HR=2.714, 95%CI: 1.885-3.906, p=0.000). Conclusion: PNI was an independent and poor prognostic factor in resected PDAC patients. Moreover, intrapancreatic PNI status may be associated with tumor recurrence.

Lohsiriwat, Varut;Anubhonganant, Worabhong;Prapasrivorakul, Siriluck;Iramaneerat, Cherdsak;Riansuwan, Woramin;Boonnuch, Wiroon;Lohsiriwat, Darin 5141

https://doi.org/10.7314/APJCP.2013.14.9.5141 PDF KSCI

Background: This study aimed to determine clinical outcomes of local excision for early rectal cancer from a University Hospital in Thailand. Materials and Methods: We performed a retrospective review of 22 consecutive patients undergoing local excision for early rectal cancer (clinical and radiological T1/T2) from 2005-2010 at the Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok. Data were collected from patients' medical records, including demographic and clinical characteristics, pathological report and surgical outcomes. Results: This study included 10 males and 12 females, with average age of 68 years. Nineteen patients (86%) underwent transanal excision and the others had trans-sacral excision. Median operative time was 45 minutes. Postoperative complications occurred in 2 patients (9%); 1 fecal fistula and 1 wound infection following trans-sacral excision. There was no 30-day postoperative mortality. Median hospital stay was 5 days. Pathological reports revealed T1 lesion in 12 cases (55%), T2 lesion in 8 cases (36%) and T3 lesion in 2 cases (9%). Eight patients received additional treatment; one re-do transanal excision, two proctectomies, and five adjuvant chemoradiation. During the median follow-up period of 25 months, local recurrence was detected in 4 patients (18%); two cases of T2 lesions with close or positive margins, and two cases of T3 lesions. Three patients with local recurrence underwent salvage abdominoperineal resection. No local recurrence was found in T1/T2 lesions with free surgical margins. Conclusions: Local excision is a feasible and acceptable alternative to radical resection only in early rectal cancer with free resection margins and favorable histopathology.

Li, Qing;Wang, Jian-Min;Peng, Yu;Zhang, Shi-Heng;Ren, Tao;Luo, Hao;Cheng, Yi;Wang, Dong 5145

https://doi.org/10.7314/APJCP.2013.14.9.5145 PDF KSCI

Background: Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles. Aims: To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma. Materials and Methods: We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models. Results: After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02-3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1-141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants, was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004). Conclusion: This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1-141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.

Sungwalee, Wararat;Vatanasapt, Patravoot;Kamsa-ard, Siriporn;Suwanrungruang, Krittika;Promthet, Supannee 5153

https://doi.org/10.7314/APJCP.2013.14.9.5153 PDF KSCI

Background: Because of the gender disparity in the incidence of thyroid cancer, this study aimed to determine the association between reproductive factors and thyroid cancer. Methods: A total of 10,767 eligible women from the Khon Kaen Cohort, recruited and interviewed between 1990 and 2001, were followed up until 2011. The data were linked to the Khon Kaen Population-Based Cancer Registry to detect thyroid cancer cases. Results: There was 17 thyroid cancer cases detected, an incidence of 11.2 per 100,000 person-years, of which 70.6 % were papillary tumors. The incidence was apparently greater among those with an early age of menarche, nulligravida women, and oral contraceptive users. Conlusions: There was a trend for thyroid cancer to develop in relation to longer estrogen exposure. This evidence is inconclusive but warrants further investigation.

Tastan, Sevinc;Andsoy, Isil Isik;Iyigun, Emine 5157

https://doi.org/10.7314/APJCP.2013.14.9.5157 PDF KSCI

The aim of the study was to evaluate of the knowledge, behavior and health beliefs of individuals over 50 regarding colorectal cancer screening, with a descriptive and cross-sectional design at Karabuk Life and Health Center in Turkey. A total of 160 people meeting set criteria were included in the study. The questionnaire consisted of two parts. The first part was composed of questions on characteristics of participants and the second part of questions derived from the Champion's Health Belief Model Scale. Only 15.0% of participants (n=24) had undergone a fecal occult blood test (FOBT), 11.3% (n=18) had had colonoscopy and 4.4% (n=7) had had sigmoidoscopy. Some 90.6% of the participants had low levels of risk awareness about the colorectal cancer. It was found that the average point of severity subscale of participants over 65 is higher than that of participants under 65 (p<0.05). In conclusion, because of the many barriers and health beliefs for the colorectal cancer screening program, the rate of participation in screening programs is not sufficient. Healthcare providers have important responsibilities for increasing rate of attendance in colorectal cancer screening programs.

Khunamornpong, Surapan;Settakorn, Jongkolnee;Sukpan, Kornkanok;Suprasert, Prapaporn;Lekawanvijit, Suree;Siriaunkgul, Sumalee 5165

https://doi.org/10.7314/APJCP.2013.14.9.5165 PDF KSCI

Background: To evaluate the pathological characteristics of invasive margins in early-stage cervical squamous cell carcinomas and their association with other clinicopathological features including clinical outcomes. Materials and Methods: Patients with FIGO stage IB-IIA cervical squamous cell carcinomas who received surgical treatment and had available follow-up information were identified. Their histological slides were reviewed for prognostic variables including tumor size, grade, extent of invasion, lymphovascular invasion, involvement of vaginal margin or parametrium, and lymph node metastasis. The characteristics of invasive margins including invasive pattern (closed, finger-like, or spray-like type), degree of stromal desmoplasia, and degree of peritumoral inflammatory reaction were evaluated along the entire invasive fronts of tumours. Associations between the characteristics of invasive margins and other clinicopathological variables and disease-free survival were assessed. Results: A total of 190 patients were included in the study with a median follow-up duration of 73 months. Tumour recurrence was observed in 18 patients (9%). Spray-like invasive pattern was significantly more associated as compared with closed or finger-like invasive pattern (p=0.005), whereas the degree of stromal desmoplasia or peritumoral inflammatory reaction was not. Low degree of peritumoral inflammatory reaction appeared linked with lymph node metastasis (p=0.021). In multivariate analysis, a spray-like invasive pattern was independently associated with marked stromal desmoplasia (p=0.013), whilst marked desmoplasia was also independently associated with low inflammatory reactions (p=0.009). Furthermore, low inflammatory reactions were independently associated with positive margins (p=0.022) and lymphovascular invasion (p=0.034). The patients with spray-like invasive pattern had a significantly lower disease-free survival compared with those with closed or finger-like pattern (p=0.004). Conclusions: There is a complex interaction between cancer tissue at the invasive margin and changes in surrounding stroma. A spray-like invasive pattern has a prognostic value in patients with early-stage cervical squamous cell carcinoma.

Sun, Yan;Zhang, Yong-Jun;Kong, Xiang-Ming 5171

https://doi.org/10.7314/APJCP.2013.14.9.5171 PDF KSCI

Background: This study aimed to explore potential associations between single nucleotide polymorphisms (SNPs) of the x-ray repair cross-complementing group 1 (XRCC1) and cleft lip and palate transmembrane protein 1-like (CLPTM1L) and non-small cell lung cancer (NSCLC) susceptibility in non-smoker Chinese patients. Methods: A total of 200 NSCLC patients and 200 healthy controls with matched age and gender were recruited for genotyping of XRCC1 SNPs (rs2256507 and rs1001581) and CLPTM1L SNPs (rs401681 and rs4975616). Association of these SNPs with NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses with adjustment for gender and age. Results: The frequencies of genotype and allele in these four loci (rs2256507, rs1001581, rs401681, and rs4975616) were not significantly different between the cases and controls, or between either of the histological subgroups (adenocarcinoma and squamous cell carcinoma) and controls. Conclusions: Although these SNPs are associated with NSCLC risk in patients with a tobacco-smoking habit, this study demonstrated that XRCC1 and CLPTM1L gene SPNs are not linked with NSCLC risk in non-smoking patients, indicating that molecular mechanisms of NSCLC betwee tobacco smokers and non-smokers may be different. Future studies are needed to uncover the underlying molecular mechanisms for NSCLC in non-smokers.

Etiz, Durmus;Ataizi, Fulya Colak;Bayman, Evrim;Akcay, Melek;Acikalin, Mustafa Fuat;Colak, Ertugrul;Ciftci, Evrim 5175

https://doi.org/10.7314/APJCP.2013.14.9.5175 PDF KSCI

Background: The prognostic value of tumor osteopontin (OPN) in patients with squamous-cell head and neck cancer (SCHNC) was investigated. Materials and Methods: OPN expression was assessed by immunohistochemical methods in 50 patients, who were treated with primary radiotherapy (RT) for locally advanced SCHNC. The effects of OPN on clinical parameters, local-regional control after RT and metastasis-free survival, was assessed. Results: The rate of OPN expression in tumor tissue was 76%. OPN positive cases had lower Hb levels (p=0.088). Mean time to local recurrence was 53.8 months (SE 3.9) in OPN-negative cases and 39.1 months (SE 4.7) in OPN-positive cases (p=0.047). OPN increased the risk of local recurrence 5.9 times (p=0.085). It had no effect on metastasis-free (p=0.116) or overall survival (p=0.123). OPN was positive in 12 of 19 cases that developed grade 3-4 acute radiation dermatitis (p=0.096). Conclusions: OPN expression is associated with an increase in local recurrence in patients who were treated with primary RT for locally advanced SCHNC.

Liu, Ai-Hua;Peng, Tang-Ming;Wu, Zhen;Xiao, Xin-Ru;Jiang, Chu-Han;Wu, Zhong-Xue;Li, You-Xiang 5179

https://doi.org/10.7314/APJCP.2013.14.9.5179 PDF KSCI

The cerebellar hemangioblastoma (CHB) has an abundant blood supply and deep anatomical location. Complete surgical resection is generally very difficult. This study investigated the safety and effectiveness of preoperative embolization followed by surgical resection of CHB in a large cohort of patients. A database of 125 CHB patients with surgical resection in Beijing Tiantan Hospital between July 2006 and July 2012 was reviewed. Of those, 46 cases (experimental group) received preoperative embolization, 79 cases (control group) underwent surgery without embolization. Patient demographics, tumor size, duration of surgery, blood loss, blood transfusion, complications and follow-up results were collected and analyzed retrospectively. In the experimental group, the Kamofsky score (KS) was 80-100 in 40 cases (86.9%), 40-70 in 4 cases (8.7%), and below 40 in 2 cases (4.3%). Among 31 cases with follow-up, KS was 80-100 in 27 cases (87.1%), 40-70 in 2 cases (6.5%), and 0 in 2 cases (6.5%). In control group, KS was 80 -100 in 65 cases (82.2%), 40-70 in 6 cases (7.6%), 10-30 in 3 cases (3.8%), and 0 in 3 cases (3.8%). Among 53 cases with follow-up, KS was 80-100 in 44 cases (83.0%), 40-70 in 4 cases (7.5%), 10-30 in 1 case (1.9%), and 0 in 4 cases (7.5%). There were statistically significant differences between the experimental and control groups in tumor size, duration of surgery, amount of intraoperative blood loss and transfusion (p<0.01). However, complications (p=0.31) and follow-up results (p=0.76) showed no significant differences between groups. Selective preoperative embolization of those CHB patients with richer blood supply, higher hemorrhage risk, is safe and effective, and is a reliable adjuvant therapy for complete surgical resection of CHB.

Yetisyigit, Tarkan;Arpaci, Erkan;Seber, Erdogan Selcuk;Kucukoner, Mehmet;Kos, Fatma Tugba;Sonmez, Ozlem Uysal;Alici, Suleyman;Akman, Tulay;Aktas, Bilge;Yildiz, Ramazan;Gunaydin, Yusuf;Inanc, Mevlude;Demirci, Umut;Alkis, Necati;Gumus, Mahmut 5185

https://doi.org/10.7314/APJCP.2013.14.9.5185 PDF KSCI

Background: We aimed to evaluate prognostic factors and response rates to various treatment approaches to patients with synovial sarcoma in an advanced setting. Materials and Methods: We retrospectively reviewed the medical records of 55 patients (18 pts; 32.7% women) diagnosed with synovial sarcomas. Twenty had metastatic disease at the time of diagnosis while the remainder of the study group consisted of patients who developed metastatic or inoperable locally advanced disease during follow up. Results: The median follow up time was 15 months (range: 1-53). Regarding outcomes for the 55 patients, 3 and 5 year overall survival rates were 26% and 14%, respectively. In univariate analyses among demographic factors female gender was associated with a better outcome (p=0.030). Patients with early progressing disease (<2 years) had a worse prognosis when compared to patient group with late relapse, but this difference did not reach statistical significance (p=0.056). According to multivariate Cox regression analysis patients who had undergone metastasectomy had a significant survival advantage (p=0.044). The overall response rate to different salvage chemotherapy regimens given as second line treatment was around 42.9-53.9% for all regimes. There were no statistically significant differences between chemotherapy regimens given in either second or third line settings in terms of overall survival. Conclusions: We observed no major differences in terms of response rate and survival between different salvage chemotherapy regimens. Although metastatic disease still carries a poor prognosis, metastasectomy was found to be associated with improved survival.

Liu, Ying;Zhou, Long-Shu;Xu, Xiao-Ming;Deng, Liang-Qing;Xiao, Qian-Kun 5189

https://doi.org/10.7314/APJCP.2013.14.9.5189 PDF KSCI

Aim: We aimed to investigate the associations of dietary intake of folate, vitamin $B_6$ and $B_{12}$ and MTHFR genotype with breast cancer in a Chinese population. Methods: A matched case-control study was conducted, and 435 patients with newly diagnosed and histologically confirmed breast cancer and 435 controls were collected. The folate intake, vitamin $B_6$ and vitamin $B_{12}$ were calculated, and MTHFR C665T, C677T and A1298C were analyzed by PCR-RFLP. Results: We found vitamin $B_{12}$ was likely to reduce the risk of breast cancer, and MTHFR 665TT was associated with increased risk of breast cancer. Folate intake, vitamin $B_{12}$ intake and variants of MTHFR C677T and MTHFR A1298C demonstrated no association with risk of breast cancer. However, we found patients with low intake of vitamin $B_6$ and MTHFR 665TT genotype had a higher risk of breast cancer (OR=1.87, 95% CI=1.29-2.77), the association being less pronounced among subjects with a moderate intake of vitamin $B_6$ and MTHFR 665TT genotype (OR=1.58, 95% CI=1.03-2.49, P=0.03). Conclusion: Our study indicated that the MTHFR C665T polymorphism and vitamin $B_6$ are associated with risk of breast cancer, which indicated roles for nutrients in developing breast cancer.

Woo, Hae Dong;Park, Ki-Soon;Shin, Aesun;Ro, Jungsil;Kim, Jeongseon 5193

https://doi.org/10.7314/APJCP.2013.14.9.5193 PDF KSCI

The glycemic index (GI) and glycemic load (GL) have been considered risk factors for breast cancer, but association studies of breast cancer risk using simple GI and GL might be affected by confounding effects of the overall diet. A total of 357 cases and 357 age-matched controls were enrolled, and dietary intake was assessed using a validated food frequency questionnaire (FFQ) with 103 food items. GI and GL dietary patterns were derived by reduced rank regression (RRR) method. The GI and GL pattern scores were positively associated with breast cancer risk among postmenopausal women [OR (95%CI): 3.31 (1.06-10.39), p for trend=0.031; 9.24 (2.93-29.14), p for trend<0.001, respectively], while the GI pattern showed no statistically significant effects on breast cancer risk, and the GL pattern was only marginally significant, among premenopausal women (p for trend=0.043). The GI and GL pattern scores were positively associated with the risk of breast cancer in subgroups defined by hormone receptor status in postmenopausal women. The GI and GL patterns based on all food items consumed were positively associated with breast cancer.

Zhou, Guang-Xi;Li, Xiao-Yu;Zhang, Qi;Zhao, Kun;Zhang, Cui-Ping;Xue, Chang-Hu;Yang, Kun;Tian, Zi-Bin 5199

https://doi.org/10.7314/APJCP.2013.14.9.5199 PDF KSCI

Background/Aim: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. Methods: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. Results: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1, YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). Conclusion: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer.

Tayyem, Reema Fayez;Shehadeh, Ihab Numan;AbuMweis, Suhad Sameer;Bawadi, Hiba Ahmad;Hammad, Shatha Sabri;Bani-Hani, Kamal Eddin;Al-Jaberi, Tareq Mohammad;Alnusai, Majed Mohammed 5207

https://doi.org/10.7314/APJCP.2013.14.9.5207 PDF KSCI

Background: Physical activity has been found to play a role in cancer prevention. The purpose of this matched case-control study was to investigate the association between physical activity levels, water intake, constipation and colorectal cancer (CRC). Materials and Methods: Two hundred and thirty-two patients diagnosed with CRC (125 male, 107 female) were enrolled in this case-control study. Cases were matched to 271 population controls (137 male, 134 female). Results: Drinking more than 4 cups of water daily decreased the risk of CRC by 33-42%; however, this effect was non-significant. Having constipation was found to be a significant risk factor for developing CRC with an OR=6.284 (95%CI=2.741-14.40). With reference to sedentary behavior, minimum activity (600-3000 Metabolic Equivalents Task (MET)) had 43% protection against CRC and the level of Health Enhancing Physical Activity OR was 0.58 (at 95%CI; 0.37-0.92). A significant negative association was found between CRC and physical activity levels expressed as both METs and MET-hours/week (p for trend=0.017 and 0.03, respectively). Among females, a significant trend of reduction in CRC by 62% was observed with increasing the level of physical activity expressed in MET (p for trend=0.04). Conclusions: The risk of CRC may be reduced by adopting a healthy lifestyle and practicing physically activity regularly, especially among females. Consuming adequate amounts of water and healthy bowel motility could also reduce the risk of CRC.

Ozbas-Gerceker, Filiz;Bozman, Nazli;Gezici, Sevgi;Pehlivan, Mustafa;Yilmaz, Mehmet;Pehlivan, Sacide;Oguzkan-Balci, Sibel 5213

https://doi.org/10.7314/APJCP.2013.14.9.5213 PDF KSCI

Transporter associated with antigen presenting (TAP) 1 and TAP2 genes are localized in the major histocompatability complex (MHC) class II region and form a heterodimer playing a key role in endogenous pathways for antigen presentation. Defects of these genes have been reported to be common in different types of cancer. Polymorphisms identified in these loci have also been investigated and reported to be associated with several autoimmune disorders, viral infections and neoplasms. In the present study, for the first time, the allele and genotype frequencies of TAP1-333, TAP2-565, TAP2-651 and TAP2-665 were determined in patients with hematological malignancies (HM) using a PCR-RFLP method and compared with the frequencies in the control group. Our results suggested an association of TAP1-333 polymorphism with multiple myeloma-MM and TAP2-565 polymorphism with chronic lymphoid leukemia-CLL. In addition, it could be concluded that the TAP2-665 GG genotype might be a risk factor for all types of hematological malignancies included in this study.

Xiao, Xiang-Sheng;Tang, Hai-Lin;Xie, Xin-Hua;Li, Lai-Sheng;Kong, Ya-Nan;Wu, Min-Qing;Yang, Lu;Gao, Jie;Wei, Wei-Dong;Xie, Xiaoming 5219

https://doi.org/10.7314/APJCP.2013.14.9.5219 PDF KSCI

The number of axillary lymph nodes involved and retrieved are important prognostic factors in breast cancer. The purpose of our study was to investigate whether the lymph node ratio (LNR) is a better prognostic factor in predicting disease-free survival (DFS) for breast cancer patients as compared with pN staging. The analysis was based on 804 breast cancer patients who had underwent axillary lymph node dissection between 1999 and 2008 in Sun Yat-Sen University Cancer Center. Optimal cutoff points of LNR were calculated using X-tile software and validated by bootstrapping. Patients were then divided into three groups (low-, intermediate-, and high-risk) according to the cutoff points. Predicting risk factors for relapse were performed according to Cox proportional hazards analysis. DFS was estimated using the Kaplan-Meier method and compared by the log-rank test. The 5-year DFS rate decreased significantly with increasing LNRs and pN. Univariate analysis found that the pT, pN, LNR, molecule type, HER2, pTNM stage and radiotherapy well classified patients with significantly different prognosis. By multivariate analysis, only LNR classification was retained as an independent prognostic factor. Furthermore, there was a significant prognostic difference among different LNR categories for pN2 category, but no apparent prognostic difference was seen between different pN categories in any LNR category. Therefore, LNR rather than pN staging is preferable in predicting DFS in node positive breast cancer patients, and routine clinical decision-making should take the LNR into consideration.

Doroudchi, Mehrnoosh;Pishe, Zahra Ghanaat;Malekzadeh, Mahyar;Golmoghaddam, Hossein;Taghipour, Mousa;Ghaderi, Abbas 5225

https://doi.org/10.7314/APJCP.2013.14.9.5225 PDF KSCI

Background: There is a Th1/Th2 cytokine imbalance and expression of IL-17 in patients with brain tumours. We aimed to compare the levels of IL-17A and IL-6 in sera of glioma, meningioma and schwannoma patients as well as in healthy individuals. Materials and Methods: IL-17A and IL-6 levels were measured in sera of 38 glioma, 24 meningioma and 18 schwannoma patients for comparison with 26 healthy controls by commercial ELISA assays. Results: We observed an increase in the IL-17A in 30% of glioma patients while only 4% and 5.5% of meningioma and schwannoma patients and none of the healthy controls showed elevated IL-17A in their sera ($0.29{\pm}0.54$, $0.03{\pm}0.15$ and $0.16{\pm}0.68$ vs. $0.00{\pm}0.00pg/ml$; p=0.01, p=0.01 and p=0.001, respectively). There was also a significant decrease in the level of IL-6 in glioma patients compared to healthy controls ($2.34{\pm}4.35$ vs. $4.67{\pm}4.32pg/ml$; p=0.01). There was a direct correlation between the level of IL-17A and age in glioma patients (p=0.005). Glioma patients over 30 years of age had higher IL-17A and lower IL-6 in their sera compared to the young patients. In addition, a non-significant grade-specific inverse trend between IL-17A and IL-6 was observed in glioma patients, where high-grade gliomas had higher IL-17A and lower IL-6. Conclusions: Our data suggest a Th17 mediated inflammatory response in the pathogenesis of glioma. Moreover, tuning of IL-6 and IL-17A inflammatory cytokines occurs during progression of glioma. IL-17A may be a potential biomarker and/or immunotherapeutic target in glioma cases.

Hu, Xiu-Feng;Yao, Jun;Gao, She-Gan;Wang, Xin-Shuai;Peng, Xiu-Qing;Yang, Yan-Tong;Feng, Xiao-Shan 5231

https://doi.org/10.7314/APJCP.2013.14.9.5231 PDF KSCI

Objective: NF-E2-related factor 2 (Nrf2) is activated in several human malignancies. However, the role of Nrf2 in gastric cancer (GC) remains incompletely understood. In this study, we therefore analyzed associations of Nrf2 expression status with clinical features and chemotherapeutic resistance in GC. Materials and Methods: A total of 186 samples from GC patients who underwent gastrectomy were used for prognostic assessment. A further 142 samples from GC cases who received first-line combination chemotherapy were applied for investigation of chemoresistance. The Nrf2 expression was evaluated by immunohistochemistry in GC samples, and its relationship with clinicopathological parameters and chemotherapy sensitivity was analyzed. The effect of Nrf2 gene silencing on chemotherapy resistance was also examined by cell viability assay in vivo. Results: Of the 186 patients with GC, 104/186 (55.9%) showed high expression for Nrf2. The overexpression of Nrf2 was an independent predictor of overall survival [OS, hazard ratio (HR) 3.9; P=0.011] and disease-free survival (DFS, HR 4.3; P=0.002). The gene silencing of Nrf2 reduced resistance to cell death induced by 5-FU in GC cell lines. Conclusion: Our data show that Nrf2 is an independent prognostic factor in GC. Furthermore, Nrf2 confers resistance to chemotherapeutic drug 5-FU in GC cells. Taken together, Nrf2 is a potential prognostic marker and predictive for 5-FU resistance in GC.

Unal, Dilek;Eroglu, Celalettin;Kurtul, Neslihan;Oguz, Arzu;Tasdemir, Arzu 5237

https://doi.org/10.7314/APJCP.2013.14.9.5237 PDF KSCI

Background: Inflammation is a critical component of tumor progression. Many cancers arise from sites of infection, chronic irritation, and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an essential participant in the neoplastic process, promoting proliferation, survival and migration. Platelets can release some growth factors such as platelet-derived growth factor, platelet factor 4, and thrombospondin. Such factors have been shown to promote hematogenous tumour spread, tumor cell adhesion and invasion, and angiogenesis and to play an important role in tumor progression. In this study, we aimed to investigate effects of the pretreatment neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) on survival and response to chemoradiotherapy in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: Ninety-four patients with non-metastatic NSCLC were included and separated into two groups according to median valuse of NLR and PLR (low:<3.44 or high:${\geq}3.44$ and low:<194 or high${\geq}194$, respectively). Results: Pretreatment high NLR and PLR were associated with significantly shorter disease-free and overall survival rates. Multivariate analysis revealed that the overall survival rates were significantly linked with PLR (OR: 1.87, CI: 1.20-2.91, p: 0.006) and response to chemoradiotherapy (OR: 1.80, CI: 1.14-2.81, p: 0.012) and the disease-free survival rates were significantly associated with NLR (OR: 1.81, CI: 1.16-2.82, p: 0.009) and response to chemoradiotherapy (OR: 2.30, CI: 1.45-3.66, p: 0.001). There was no significant difference between patients with high and low NLR in terms of response to chemoradiotherapy. Similarly, there was no significant influence of the PLR. Conclusions: Pretreatment NLR and PLR measurements can provide important prognostic results in patients with NSCLC and assessment of the two parameters together appears to better predict the prognosis in patients with NSCLC. The effect of inflammation, indicators of NLR and PLR, on survival seems independent of the response to chemoradiotherapy.

Liu, Yao;Cui, Yun-Fu 5243

https://doi.org/10.7314/APJCP.2013.14.9.5243 PDF KSCI

Background: Triptolide, extracted from the herb Tripteryglum wilfordii Hook.f that has long been used as a natural medicine in China, has attracted much interest for its anti-cancer effects against some kinds of tumours in recent years. Artesunate, extracted from the Chinese herb Artemisia annua, has proven to be effective and safe as an anti-malarial drug that possesses anticancer potential. The present study attempted to clarify if triptolide enhances artesunate-induced cytotoxicity in pancreatic cancer cell lines in vitro and in vivo. Methods: In vitro, to test synergic actions, cell viability and apoptosis were analyzed after treatment of pancreatic cancer cell lines with the two agents singly or in combination. The molecular mechanisms of apoptotic effects were also explored using qRT-PCR and Western blotting. In vivo, a tumor xenograft model was established in nude mice, for assessment of inhibitory effects of triptolide and artesunate. Results: We could show that the combination of triptolide and artesunate could inhibit pancreatic cancer cell line growth, and induce apoptosis, accompanied by expression of HSP 20 and HSP 27, indicating important roles in the synergic effects. Moreover, tumor growth was decreased with triptolide and artesunate synergy. Conclusion: Our result indicated that triptolide and artesunate in combination at low concentrations can exert synergistic anti-tumor effects in pancreatic cancer cells with potential clinical applications.

Cho, Kyoung-Hee;Park, Sohee;Lee, Kwang-Sig;Jang, Sung-In;Yoo, Ki-Bong;Kim, Jae-Hyun;Park, Eun-Cheol 5249

https://doi.org/10.7314/APJCP.2013.14.9.5249 PDF KSCI

Background: The purpose of this study was to develop a single measure of cancer burden (SMCB), which can prioritize cancer sites by considering incidence and mortality. Materials and Methods: Incidence data from 1999 to 2010 were obtained from the Korea Central Cancer Registry. Mortality data from 1999 to 2010 were obtained from Statistics Korea. The SMCB was developed by adding incidence and mortality scores. The respective scores were given such that incidence and mortality were classified by ten ranges of equal intervals. Results: According to the SMCB in 2010, stomach cancer ranked $1^{st}$ in males with 20 points, and colorectal cancer was $2^{nd}$ with 11 points. Breast cancer and thyroid cancer were joint $1^{st}$ with 11 points for females. The SMCB for females was less than that for males. The burden of stomach cancer was $1^{st}$ in males from 1999-2010. The incidences of lung cancer and liver cancer decreased, whereas thyroid cancer and colon cancer increased during the period. Breast cancer and thyroid cancer burden showed tendencies to increase in females. Comparison of SMCB with disability-adjusted life years (DALY) and socioeconomic costs in 2005 showed that the top five cancer sites were similar, but there were differences in the size of the cancer burden. Conclusions: The SMCB indicated that the burdens of stomach cancer in males and thyroid and breast cancers in females were large. The single measure showed an advantage, reflected as the equivalent dimensions of incidence and mortality, whereas DALY and economic costs showed tendencies to reflect premature death.

Wang, Run-Chao;Yang, Lei;Tang, Yang;Bai, Ou 5257

https://doi.org/10.7314/APJCP.2013.14.9.5257 PDF KSCI

The micronucleus frequency (MNF) in peripheral blood lymphocytes (PBL) is a biomarker of chromosomal damage and genome instability in human populations.The relationship of micronucleus frequency with prognosis of patients with acute leukemia is not clear. We therefore investigated MNF in mitogen-activated peripheral blood lymphocytes from patients with hematologic diseases and solid tumours. Patients included 50 with acute leukemia, 49 diagnosed with myelodysplastic syndrome (MDS), 54 with benign blood diseases, and 45 with solid tumours, examined with 50 healthy controls. The mean MNF was significantly higher in cases of hematologic diseases and solid tumor patients than in healthy controls (P<0.001). There was no evident difference between MNF in the acute leukemia ($7.15{\pm}2.18$) and solid tumor groups ($7.11{\pm}1.47$), but both were higher than in the MDS group ($5.12{\pm}1.29$) and benign blood diseases group ($3.08{\pm}1.08$). Taking 7.15‰, the average MNF of the acute leukemia group as standard, and dividing 50 cases of acute leukemia patients into high MNF group ($MNF{\geq}7.15$‰) and low MNF group (MNF<7.15‰). The overall response (complete remission + partial remission) rates of the low MNF group were significantly higher than in the high MNF group (P=0.001). The high MNF group further showed lower overall survival rates than the low MNF group. MNF expression and progression-free survival seemed to have a opposite relationship, with a correlation coefficient of -0.702. These data indicate that MNF in peripheral blood lymphocytes is important for evaluation of prognosis of acute leukemia patients, and it can reflect progression of disease to a certain degree.

Unal, Olcun Umit;Oztop, Ilhan;Unek, Ilkay Tugba;Yilmaz, Ahmet Ugur 5263

https://doi.org/10.7314/APJCP.2013.14.9.5263 PDF KSCI

Background: The aim of this study was to evaluate the efficacy and tolerability of a gemcitabine, 5-fluorouracil and leucovorin (GEMFUFOL) chemotherapy regimen as first line treatment of metastatic biliary tract cancer. Materials and Methods: All patients received folinic acid $400mg/m^2$ on day 1, 5-fluorouracil bolus $400mg/m^2$ on day 1, IV infusion of 5-fluorouracil $2400mg/m^2$ over 46 hours, and gemcitabine $1250mg/m^2$ on day 1. Results: A total of 29 patients with metastatic biliary tract cancer received GEMFUFOL regimen as the firstline treatment. The mean follow-up was 22.1 months (95%CI, 12.5-31.8). One patient (3.4%) achieved complete response, 5 (17.2%) had partial response, and 4 (13.8%) had stable disease. The median progression-free survival was 3.3 months (95%CI, 2.9-3.7), and the median overall survival was 8.8 months (95%CI, 3.5-14). The 1-year and 2-year survival rates were 58.6% and 30%, respectively. Grade 3 and 4 toxicity included neutropenia in 4 patients (13.7%), thrombocytopenia in 2 (6.8%), anemia2 (6.8%), and alopecia in 1 (3.4%). Two patients (6.8%) developed febrile neutropenia. A dose reduction was achieved in 8 patients (27.6%) while 5 patients had extended-interval dosage (17.2%) for toxicity. Conclusions: The GEMFUFOL chemotherapy regimen was generally efficacious and tolerable as a first-line treatment of metastatic biliary tract cancer.

Zhang, Tao;Wang, Hui 5269

https://doi.org/10.7314/APJCP.2013.14.9.5269 PDF KSCI

Aim: We conducted a case-control matched study to investigate the role of IL-16 gene polymorphisms, rs4072111, rs1131445, rs4778889 and rs11556218, in the risk of gastric cancer in a Chinese population, also performing subgroup analysis by subsites. Methods: To test the hypothesis of involvement, we analyzed the four SNPs of IL16 in 347 cancer patients and 368 controls. Demographic data and other information were collected using a newly designed questionnaire. Genotyping of IL16 (rs4072111, rs1131445, rs4778889 and rs11556218) was performed in a 384-well plate format on the MassARRAY(R) platform. Results: In our study, we found the gastric cancer patients were more likely to be male and have a family history of cancer (P<0.05). We found the rs4778889 CC and rs11556218 GG genotype was significantly associated with 1.97 and 1.84-fold increased risk of non-cardia gastric cancer, while we did not find significant association between the four IL-16 SNPs and cardia gastric cancer. Conclusions: In conclusion, our study indicated that IL-16 rs4778889 CC and rs11556218 GG genotypes are associated with an increased risk of non-cardia gastric cancer in a Chinese population. Our results offer insights into the influence of IL-16 on development of gastric cancer.

Natukula, Kirmani;Jamil, Kaiser;Pingali, Usha Rani;Attili, Venkata Satya Suresh;Madireddy, Umamaheshwar Rao Naidu 5275

https://doi.org/10.7314/APJCP.2013.14.9.5275 PDF KSCI

Background: The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair) pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repair efficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene (at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity and increased genomic instability in multiple studies. Hence our investigation focused on genotyping these variants to correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that these variants of the XRCC1 gene might influence disease susceptibility. Materials and Methods: We examined the frequency of the polymorphism in one hundred cases and an almost equal number of controls after recording their demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCR studies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed. Results: The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%), and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln to show association with lung cancer. Correlating these genotypes with several parameters, we also found that these two variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Gln genotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenario where Arg399Gln genotypes were found to be associated with stage of the disease in females. Conclusions: It is concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients with smoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lung cancer for diagnosis and prognosis.

Li, Jian;Xu, Ya-Hong;Lu, Yi;Ma, Xiao-Ping;Chen, Ping;Luo, Shun-Wen;Jia, Zhi-Gang;Liu, Yang;Guo, Yu 5281

https://doi.org/10.7314/APJCP.2013.14.9.5281 PDF KSCI

Purpose: Prostate cancer caused by the abnormal disorderly growth of prostatic acinar cells is the most prevalent cancer of men in western countries. We aimed to screen out differentially expressed genes (DEGs) and explore small molecule drugs for prostate cancer. Materials and Methods: The GSE3824 gene expression profile of prostate cancer was downloaded from Gene Expression Omnibus database which including 21 normal samples and 18 prostate cancer cells. The DEGs were identified by Limma package in R language and gene ontology and pathway enrichment analyses were performed. In addition, potential regulatory microRNAs and the target sites of the transcription factors were screened out based on the molecular signature database. In addition, the DEGs were mapped to the connectivity map database to identify potential small molecule drugs. Results: A total of 6,588 genes were filtered as DEGs between normal and prostate cancer samples. Examples such as ITGB6, ITGB3, ITGAV and ITGA2 may induce prostate cancer through actions on the focal adhesion pathway. Furthermore, the transcription factor, SP1, and its target genes ARHGAP26 and USF1 were identified. The most significant microRNA, MIR-506, was screened and found to regulate genes including ITGB1 and ITGB3. Additionally, small molecules MS-275, 8-azaguanine and pyrvinium were discovered to have the potential to repair the disordered metabolic pathways, abd furthermore to remedy prostate cancer. Conclusions: The results of our analysis bear on the mechanism of prostate cancer and allow screening for small molecular drugs for this cancer. The findings have the potential for future use in the clinic for treatment of prostate cancer.

Afshar, Reza Malekpour;Mollaie, Hamid Reza;Fazlalipour, Mehdi;Arabzadeh, Seyad Alimohammad 5287

https://doi.org/10.7314/APJCP.2013.14.9.5287 PDF KSCI

The human papilloma virus (HPV) causes skin and mucous membrane infections. It crosses from one person to another by skin-to-skin contact, such as sexual contact. There are more than 100 types of HPV that can influence different parts of the body. Some types of HPV can cause cancer (such as cervical or anal cancer) and others can cause warts (such as genital or plantar warts). HPV infection is one of the most common sexually transmitted infections (STIs) in Iran and around the world. Considerable molecular evidence suggests a role for human papilloma virus (HPV) in the pathogenesis of carcinoma. Epidemiological studies on human papilloma viruses (HPVs) infections in general population are critical for the performing of health policy guidelines for developing the strategies to hinder the primary and secondary different cancer. In different parts of Iran, there is a lack of population-based studies to determine the prevalence of HPV in the general population. The aim of this population-based study was therefore to report the prevalence ratse of HPV types among Iranian patients. To study the risk of human papilloma virus (HPV) infection, we managed a retrospective study in Kerman province, southeast of Iran. For this purpose, 410 patients tested for the presence of HPV DNA using PCR and INNo-Lipa assays. HPV DNA was detected in 108 out of 410 patients (26.34%), while it was not detected in any of the control group samples. Patients included 23 (21.1%) males and 86 (78.8%) females. HPV type 6 was the most common (49%) followed by HPV type 16 (10.1%), and also HPV type11 (9.2%). The prevalence of HPV in Iran is comparable to those reported in other regions of the world. In a similar manner, it seems that HPV types 6, 16 and11 are the most common types in Kerman. Additional studies on larger group of patients, particularly in those with pre-invasive forms of disease, are needed to explain the roles of different HPV types in this location of Iran.

Fei, Zheng-Hua;Yao, Cheng-Yun;Yang, Xiao-Lei;Huang, Xin-En;Ma, Sheng-Lin 5293

https://doi.org/10.7314/APJCP.2013.14.9.5293 PDF KSCI

Purpose: High levels of bone morphogenetic protein (BMPs) have been reported in patients with lung cancer. This study was conducted to assess correlations between serum BMP-2 levels and prognostic outcome in patients with non-small-cell lung cancer (NSCLC). Methods: Blood samples from 84 patients with advanced NSCLC and 42 healthy controls were analyzed and quantitated for serum BMP-2 levels before and after two cycles of chemotherapy using a commercially available ELISA kit. Results: The median level of BMP-2 was 146.9 pg/ml in patients with NSCLC vs. 87.7 pg/ml in healthy controls (P<0.01). A significant correlation was observed between pretreatment serum BMP-2 level and ECOG PS, disease stage and number of organs with metastases (P<0.05). Serum BMP-2 level decreased significantly in patients who achieved objective response after two cycles of chemotherapy. Multivariate analysis showed that increased BMP-2 level and advanced clinical stage were significantly correlated with poor prognosis. Conclusion: Thes erum BMP-2 level is positively correlated with clinical stage, ECOG PS and metastatic burden and may serve as an independent negative predictor for prognosis. Decreased BMP-2 after chemotherapy could be a reliable marker for efficacy of treatment.

Akdeniz, Onder;Akduman, Davut;Haksever, Mehmet;Ozkarakas, Haluk;Muezzinoglu, Bahar 5301

https://doi.org/10.7314/APJCP.2013.14.9.5301 PDF KSCI

The biological mechanisms of cancer and associations with behavior of tumours need to be studied to understand progression and determine appropriate treatments. Here we investigated expression of VEGF, MMP-9 and E-cadherin in laryngeal SCCs and their relations with clinical behavior. This prospective study was based on 38 surgical specimens from patients with primary laryngeal SCC and data recorded in their cards. Expression of the three factors in tumor tissue was examined using immunohistochemistry and correlations with clinical parameters of primary tumors, regional lymph node metastases, stage of disease, histopathologic differentiation, and vascular/cartilage invasion were investigated. Regarding the cases with positive MMP-9 expression, the difference between well and moderately/poorly differentiated tumors was statistically significant. However, differences between early stage (stage I and II) and late-stage (stage III and IV) tumours, and between positive and negative for pLN metastasis were not. No significant relationship between positive VEGF and tumor differentiation or stage was apparent, but E-cadherin levels significantly differed between well and moderately/poorly differentiated tumours and with the presence of pLN metastasis. E-cadherin staining did not vary between MMP-9 positive and negative cases. In conclusion, MMP-9 may be a negative predictor of differentiation in laryngeal SCC, while E-cadherin is a predictor of differentiation and nodal metastases. Even if the difference between VEGF expression and tumor stage was not statistically significant, it seems that there exists some relationship, which might be clarified with a greater number of cases.

Han, Fei-Fei;Guo, Chang-Long;Gong, Li-Li;Jin, Zhu;Liu, Li-Hong 5311

https://doi.org/10.7314/APJCP.2013.14.9.5311 PDF KSCI

A functional polymorphism in the NQO1 gene, featuring a 609C>T substitution,leading to proline to serine amino-acid and enzyme activity changes, has been implicated in cancer risk. However, individually published investigations showed inconclusive results, especially for leukemia. In this study, we therefore performed a meta-analysis of 21 publications with a total of 3,634 cases and 4,827controls, mainly for leukemia. We summarized the data on the association between the NQO1 609C>T polymorphism and risk of leukemia and performed subgroup analyses by ethnicity and leukemia type. We found that the variant TT homozygous genotype o was associated with a modestly increased risk of leukemia (TT versus CT/CC: OR=1.23, 95%CI=1.00-1.51, heterogeneity=0.76; $I^2$=0%). Following further stratified analyses, increased risk was only observed in subgroups of Caucasians. This meta-analysis suggests that the NQO1 609T allele is a high-penetrance risk factor for leukemia in Caucasians. The effect on leukemia may be modified by ethnicity and leukemia type, and the small sample sizes of the subgroup analyses suggest that further larger studies are needed.

Fattahi, Sadegh;Ardekani, Ali Motevalizadeh;Zabihi, Ebrahim;Abedian, Zeinab;Mostafazadeh, Amrollah;Pourbagher, Roghayeh;Akhavan-Niaki, Haleh 5317

https://doi.org/10.7314/APJCP.2013.14.9.5317 PDF KSCI

Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of $r^2$=0.997. Dose-dependent and anti-proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an $IC_{50}$ value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer.

Pan, Lei;Han, Li-Li;Tao, Li-Xin;Zhou, Tao;Li, Xia;Gao, Qi;Wu, Li-Juan;Luo, Yan-Xia;Ding, Hui;Guo, Xiu-Hua 5325

https://doi.org/10.7314/APJCP.2013.14.9.5325 PDF KSCI

Objectives: Although there are many reports about the risk of breast cancer, few have reported clinical factors including history of breast-related or other diseases that affect the prevalence of breast cancer. This study explores these risk factors for breast cancer cases reported in Beijing in 2009. Materials and Methods: Data were derived from a Beijing breast cancer screening performed in 2009, of 568,000 women, from 16 districts of Beijing, all aged between 40 and 60 years. In this study, multilevel statistical modeling was used to identify clinical factors that affect the prevalence of breast cancer and to provide more reliable evidence for clinical diagnostics by using screening data. Results and Conclusion: Those women who had organ transplants, compared with those with none, were associated with breast cancer with an odds ratio (OR)=65.352 [95% confidence interval (CI): 8.488-503.165] and those with solid breast mass compared with none had OR=1.384 (95% CI: 1.022-1.873). Malignant tendency was strongly associated with increased risk of breast cancer, OR=207.999(95% CI: 151.950-284.721). The risk of breast cancer increased with age, $OR_1$=2.759 (95% CI: 1.837-4.144, 56-60 vs. 40-45), $OR_2$=2.047 (95% CI: 1.394-3.077, 51-55 vs. 40-45), $OR_3$=1.668 (95% CI: 1.145-2.431). Normal results of B ultrasonic examination show a lower risk among participants, OR= 0.136 (95% CI: 0.085-0.218). Those women with ductal papilloma compared with none were associated with breast cancer, OR=6.524 (95% CI: 1.871-22.746). Therefore, this study suggests that clinical doctors should pay attention to these high-risk factors.

Ansil, Puthuparampil Nazarudeen;Prabha, Santhibhavan Prabhakaran;Nitha, Anand;Latha, Mukalel Sankunni 5331

https://doi.org/10.7314/APJCP.2013.14.9.5331 PDF KSCI

Colorectal cancer is one of the leading causes of cancer death, both in men and women. This study investigated the effects of Amorphophallus campanulatus tuber methanolic extract (ACME) on aberrant crypt foci (ACF) formation, colonic cell proliferation, lipid peroxidative damage and the antioxidant status in a long term preclinical model of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rats. Male Wistar rats were divided into six groups, viz., group I rats served as controls; group II rats treated as drug controls receiving 250 mg/kg body weight of ACME orally; group III rats received DMH (20 mg/kg body weight) subcutaneously once a week for the first 15 weeks; groups IV, V and VI rats received ACME along with DMH during the initiation, post-initiation stages and the entire period of the study, respectively. All the rats were sacrificed at the end of 30 weeks and the intestinal and colonic tissues from different groups were subjected to biochemical and histological studies. Administration of DMH resulted in significant ($p{\leq}0.05$) intestinal and colonic lipid peroxidation (MDA) and reduction of antioxidants such as catalase, glutathione peroxidase, glutathione reductase, glutathione-Stransferase and reduced glutathione. Whereas the supplementation of ACME significantly ($p{\leq}0.05$) improved the intestinal and colonic MDA and reduced glutathione levels and the activities of antioxidant enzymes in DMH intoxicated rats. ACME administration also significantly suppressed the formation and multiplicity of ACF. In addition, the DMH administered rats showed amplified expression of PCNA in the colon and decreased expression of this proliferative marker was clearly noted with initiation, post-initiation and entire period of ACME treatment regimens. These results indicate that ACME could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.

Su, Long;Gao, Su-Jun;Tan, Ye-Hui;Han, Wei;Li, Wei 5341

https://doi.org/10.7314/APJCP.2013.14.9.5341 PDF KSCI

Objectives: To explore the relationships between age, cytogenetic subgroups, molecular markers, and cells with leukemic aberrant immunophenotype in patients with acute myeloid leukemia (AML). Methods: In this study, we evaluated the correlations between age, cytogenetic subgroups (normal, balanced and unbalance karyotype), molecular mutations (NPM1, FLT3-ITD, and CEBPA mutations) and marrow leukemia cells (LC) identified by flow cytometry in 256 patients with de novo AML. Results: From age group 10-19 years to age group ${\geq}60$ years, the percentage of LC decreased from $67.0{\pm}18.4%$ to $49.0{\pm}25.1%$ (F=2.353, P=0.041). LC percentage was higher in patients with balanced karyotypes ($65.7{\pm}22.4%$), than those with unbalanced karyotypes ($46.0{\pm}26.6%$) (u=3.444, P=0.001) or a normal karyotype ($49.9{\pm}22.1%$) (u=5.093, P<0.001). Patients with FLT3-ITD ($64.3{\pm}19.5%$) had higher LC percentages compared with those without ($54.2{\pm}24.3%$) (u=2.794, P=0.007). Conclusions: Associations between age, cytogenetics, molecular markers, and marrow leukemia cells may offer beneficial information to understand the biology and pathogenesis of AML.

Choi, So Young 5345

https://doi.org/10.7314/APJCP.2013.14.9.5345 PDF KSCI

Background: This study developed and measured the effects of a cervical cancer prevention program for married women immigrants. Materials and Methods: A nonequivalent control group pre-test/post-test design was used with a group of married women immigrants registered at the multi-cultural center in the city of "J." Data on for 30 participants in the intervention group and 27 participants in the control group (N=57) were used for analysis. The intervention group attended a 4-session cervical cancer prevention program. Results: The knowledge of the intervention and control groups about cervical cancer post-intervention was significantly different (F=12.55, p<0.001). The perceived susceptibility score before and after the experiment, for the intervention group, and 29.4 and 28 for the control group, was significantly different (t=2.063, p=0.043). After the program, cancer prevention behavior was significantly different in the intervention group (t=2.646, p=0.010). Conclusions: The results obtained in this study indicate that the cervical cancer preventive program was effective in increasing cervical cancer knowledge, perceived susceptibility, and cancer prevention behavior.

Leung, Doris Y.P.;Au, Doreen W.H.;Lam, Tai-Hing;Chan, Sophia S.C. 5351

https://doi.org/10.7314/APJCP.2013.14.9.5351 PDF KSCI

Four hundred and thirty-five Chinese smokers who had attended the first smoking cessation clinic and received stage-matched individualized cessation counseling in Hong Kong during the period of August 2000 to January 2002 were successfully followed-up between February and August 2008. Some 38% of the participants (165/495) had stopped smoking during the 12-month follow-up after treatment. Participants with higher conscientiousness score (OR = 1.65, 95% CI: 1.09 - 2.48) and lower openness to experience score (OR = 0.64, 95% CI: 0.45 - 0.92) showed a greater likelihood of quitting smoking after controlling the effect of daily cigarettes smoked and stage of readiness at baseline. The study suggests an important role of conscientiousness and openness to experience on long-term quitting behaviors following treatment, and provides useful information for the development of matched intervention for smoking cessation among Chinese smokers.

Intaraphet, Suthida;Kasatpibal, Nongyao;Siriaunkgul, Sumalee;Sogaard, Mette;Patumanond, Jayanton;Khunamornpong, Surapan;Chandacham, Anchalee;Suprasert, Prapaporn 5355

https://doi.org/10.7314/APJCP.2013.14.9.5355 PDF KSCI

Background: Clarifying the prognostic impact of histological type is an essential issue that may influence the treatment and follow-up planning of newly diagnosed cervical cancer cases. This study aimed to evaluate the prognostic impact of histological type on survival and mortality in patients with cervical squamous cell carcinoma (SCC), adenocarcinoma (ADC) and small cell neuroendocrine carcinoma (SNEC). Materials and Methods: All patients with cervical cancer diagnosed and treated at Chiang Mai University Hospital between January 1995 and October 2011 were eligible. We included all patients with SNEC and a random weighted sample of patients with SCC and ADC. We used competing-risks regression analysis to evaluate the association between histological type and cancer-specific survival and mortality. Results: Of all 2,108 patients, 1,632 (77.4%) had SCC, 346 (16.4%) had ADC and 130 (6.2%) had SNEC. Overall, five-year cancer-specific survival was 60.0%, 54.7%, and 48.4% in patients with SCC, ADC and SNEC, respectively. After adjusting for other clinical and pathological factors, patients with SNEC and ADC had higher risk of cancer-related death compared with SCC patients (hazard ratio [HR] 2.6; 95% CI, 1.9-3.5 and HR 1.3; 95% CI, 1.1-1.5, respectively). Patients with SNEC were younger and had higher risk of cancer-related death in both early and advanced stages compared with SCC patients (HR 4.9; 95% CI, 2.7-9.1 and HR 2.5; 95% CI, 1.7-3.5, respectively). Those with advanced-stage ADC had a greater risk of cancer-related death (HR 1.4; 95% CI, 1.2-1.7) compared with those with advanced-stage SCC, while no significant difference was observed in patients with early stage lesions. Conclusion: Histological type is an important prognostic factor among patients with cervical cancer in Thailand. Though patients with SNEC were younger and more often had a diagnosis of early stage compared with ADC and SCC, SNEC was associated with poorest survival. ADC was associated with poorer survival compared with SCC in advanced stages, while no difference was observed at early stages. Further tailored treatment-strategies and follow-up planning among patients with different histological types should be considered.

Li, Xiao-Fei;He, Hua-Bin;Zhu, Yan-Shuang;He, Jin-Ke;Ye, Wei-Wei;Chen, Yong-Xin;Lou, Lian-Qing 5361

https://doi.org/10.7314/APJCP.2013.14.9.5361 PDF KSCI

The objective of this study was to evaluate the influence of a genetic variant in the multidrug resistance 1 gene (MDR1) on hepatocellular carcinoma (HCC) risk. This case-control study was conducted in a Chinese population of 645 HCC cases and 658 cancer-free controls. The genotype of the c.3751G>A genetic variant in the MDR1 gene was investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Our data demonstrated significantly differences detected in the allelic and genotypic frequencies between HCC cases and those of cancer-free controls. Association analyses indicated that there were statistically increased risk of HCC in the homozygote comparison (AA versus (vs.) GG: OR=2.22, 95% CI 1.51-3.27, ${\chi}^2$=16.90, P<0.001), dominant model (AA/GA vs. GG: OR=1.25, 95% CI 1.00-1.55, ${\chi}^2$=3.98, P=0.046), recessive model (AA vs. GA/GG: OR=2.14, 95% CI 1.47-3.09, ${\chi}^2$=16.68, P<0.001) and allele comparison (A vs. G: OR=1.33, 95% CI 1.13-1.57, ${\chi}^2$=11.66, P=0.001). The allele-A and genotype-AA may contribute to HCC susceptibility. These preliminary findings suggest that the c.3751G>A genetic variant in the MDR1 gene is potentially related to HCC susceptibility in a Chinese Han population, and might be used as a molecular marker for evaluating HCC susceptibility.

Mosavi-Jarrahi, Alireza;Ahmadi-Jouibari, Toraj;Najafi, Farid;Mehrabi, Yadollah;Aghaei, Abbas 5367

https://doi.org/10.7314/APJCP.2013.14.9.5367 PDF KSCI

Background: Having knowledge or estimation of cancer incidence is necessary for planning and implementation of any cancer prevention and control programs. Population-based registries provide valuable information to achieve these objectives but require extra techniques to estimate the incidence rate. The present study aimed to estimate the esophageal cancer incidence using a log-linear method based on Tehran population-based cancer registry data. Materials and Methods: New cases of esophageal cancer reported by three sources of pathology reports, medical records, and death certificates to Tehran Metropolitan Area Cancer Registry Center during 2002-2006 were entered into the study and the incidence rate was estimated based on log-linear models. We used Akaike statistics to select the best-fit model. Results: During 2002-2006, 1,458 new cases of esophageal cancer were reported by the mentioned sources to the population-based cancer registry. Based on the reported cases, cancer incidence was 4.5 per 100,000 population and this was estimated to be 10.5 per 100,000 by the log-linear method. Conclusions: Based on the obtained results, it can be concluded that an estimated incidence for 2004 of 8.3 per 100,000 population could be a good benchmark for the incidence of esophageal cancer in the population of Tehran metropolis.

Liu, Ai-Hong;Sun, Xuan;Wei, Xiao-Qiang;Zhang, You-Zhong 5371

https://doi.org/10.7314/APJCP.2013.14.9.5371 PDF KSCI

Objective: Photodynamic therapy (PDT) is an emerging therapeutic procedure suitable for the treatment of cervical cancer. However, the side effects of PDT are severe, including skin ulceration, so we designed an experiment to examine the effects of multiple low-dose photodynamic therapy of 5, 10, 15, 20-tetrakis(1-methylpyridinium-4-yl) porphyrin (Tmpyp4) on tumour growth by utilizing a model in nude mice implanted with Hela cervical cancer cells. Materials and Methods: Female BALB/c nude mice (aged 5-6 weeks, weighing 18-20 g) were used. Hela cervical cancer cells were injected subcutaneously ($1{\times}10^7cells/200{\mu}L$). Ten days after injection, the mice were divided into three groups (n=6), the A group of controls without any treatment, the B group receiving a single-treatment with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation (blue laser, $108J/cm^2$), and the C group given three-treatments with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation at intervals of two days. After starting treatment, tumours were measured every two days, to assess growth. At 2 weeks after the last treatment of C group, tumour tissue and organs were collected from each mouse to evaluate tumor histology and organ damage. Results: Tumour growth in C group was significantly inhibited compared with A and B groups (P<0.05), without any injury to the skin and internal organs. Conclusion: Our novel findings demonstrated that multiple low-dose photodynamic therapy of Tmpyp4 could inhibit cervical cancer growth significantly with no apparent side effects.

Mahawerawat, Sukanda;Charoenkwan, Kittipat;Srisomboon, Jatupol;Khunamornpong, Surapan;Suprasert, Prapaporn;Sae-Teng, Charuwan Tantipalakorn 5375

https://doi.org/10.7314/APJCP.2013.14.9.5375 PDF KSCI

Background: This study was undertaken to evaluate the surgical outcomes of patients with stage IA2 cervical cancer treated with radical hysterectomy. Data for 58 patients who underwent modified radical hysterectomy or radical hysterectomy with pelvic lymphadenectomy between January 2003 and December 2012 at Chiang Mai University Hospital were retrospectively reviewed. The analysis included clinico-pathological risk factors (nodal metastasis, parametrial involvement), adjuvant treatment, 5-year disease-free survival and 5-year overall survival. All pathologic slides were reviewed by a gynecologic pathologist. Follow-up methods included at least cervical cytology and colposcopy with directed biopsy if indicated. Univariate analysis was performed to identify factors associated with median survival. At the median follow up time of 73 months, the 5-year disease-free survival and the 5-year overall survival were 97.4% and 97.4%, respectively. Two (3.4%) patients had pelvic lymph node metastases. In a univariate analysis, there was no statistically significant association between survival and prognostic factors such as age, histological cell type, lymph-vascular space invasion, vaginal margin status and lymph node status. Surgical and survival outcomes of women with stage IA2 cervical cancer are excellent. No parametrial involvement was detected in our study. Patients with stage IA2 cervical cancer may be treated with simple or less radical hysterectomy with pelvic lymphadenectomy.

Yang, Tao;Zheng, Xiao-Fei;Li, Mei;Lin, Xi;Yin, Qing-Shui 5379

https://doi.org/10.7314/APJCP.2013.14.9.5379 PDF KSCI

Therapeutic effects of zoledronic acid (ZOL) on giant cell tumour of bone (GCT) have been proven. Apoptosis induction was considered to be one of the mechanisms of ZOL tumour inhibition. In this study, we presented the possibility of an osteogenic differentiation stimulation mechanism of ZOL and further investigated dosage and time effects. We treated stromal cells of GCT (GCTSC) with ZOL for 48 hours at different concentrations ($0{\mu}M$, $0.01{\mu}M$, $0.1{\mu}M$, $1{\mu}M$, 5${\mu}M$, $30{\mu}M$) and assessed apoptotic and osteogenic differentiation markers with immunohistochemical techniques and real-time quantitative RT-PCR. Our results suggested that ZOL enhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at $1{\mu}M$ in GCTSC. Time course experiments indicated a time dependent osteogenic differentiation effect. In conclusion, ZOL may be considered as an adjuvant in the treatment of GCT not only by inducing apoptosis but also by stimulating osteogenic differentiation of remaining tumor stromal cells after surgery.

Hashemi, Farnaz Amouzegar;Akbari, Ehsan Hamed;Kalaghchi, Bita;Esmati, Ebrahim 5385

https://doi.org/10.7314/APJCP.2013.14.9.5385 PDF KSCI

Background: For more than 80 years, the standard treatment of locally advanced cervical cancer was radiotherapy. However, based on several phase III randomized clinical trials in the past decade, concurrent cisplatin-based chemoradiotherapy is the current standard for this disease. Gemcitabine has potent radiosensitizing properties in preclinical and clinical trials, so it can be utilized simultanously with radiation. Materials and Methods: Thirty women with untreated invasive squamous cell carcinoma of the cervix of stage IIB to stage IVA were enrolled in the study in the Radiation Oncology Department of Imam Khomeini Hospital in Tehran from September 2009 to September 2010. Sixty $mg/m^2$ gemcitabine followed by $35mg/m^2$ cisplatin were concurrently administered with radiotherapy to the whole pelvic region on day one of each treatment week for five weeks. One and three months after treatment, patients underwent a complete physical examination and MRI to determine the response to treatment. Results: The mean age of patients was $58.1{\pm}11.8$ (29-78) years. After 3 months of treatment, 73.3%had complete and 26.7% demonstrated partial response to treatment. Grade 3 anemia was seen in 10%, grade 3 thrombocytopenia in 3.3% and grade 3 leukopenia in 10% of the patients. Conclusions: According to the positive results of this study in stage IIB, further phase II and III clinical trials are suggested to evaluate the role of chemoradiation using Gemcitabine for advanced cervical cancers.

Wang, Qiang;Wang, Xian;Zhang, Can-Bin 5391

https://doi.org/10.7314/APJCP.2013.14.9.5391 PDF KSCI

Aim: To investigate the role of Golgi phosphoprotein 3 (GOLPH3) in tumour growth and metastasis of esophageal squamous cancer. Methods: A lentiviral shRNA-vector was utilized to stably knockdown GOLPH3 in Eca-109 esophageal squamous cancer cells. mRNA transcription and protein expression of GOLPH3 were examined by real-time quantitative PCR and Western blotting, respectively. Cell proliferation activity was assessed by MTT assay and invasion and migration potentials by matrigel invasion and transwell motility assays. Results: Stable knockdown in the GOLPH3 cell line was established. PD-A gene expression was significantly suppressed by lentivirus-mediated RNAi, which resulted in reducing the capacity for cell proliferation, migration, invasion and adhesion in vitro. In vivo, GOLPH3 depletion resulted in inhibition of tumour growth, with stable decrease in the expression of GOLPH3 in tumor xenografts. Conclusions: Our findings suggest that lentivirus mediated silencing of the GOLPH3 gene has a significant anti-tumour effect on esophageal squamous cancer in vitro and in vivo. In addition, the results indicate that GOLPH3 might be an effective molecular target for gene therapy in esophageal squamous cancer.

Byambaragchaa, Munkhzaya;de la Cruz, Joseph;Yang, Seung Hak;Hwang, Seong-Gu 5397

https://doi.org/10.7314/APJCP.2013.14.9.5397 PDF KSCI

The rates of morbidity and mortality of hepatocellular carcinoma (HCC) have not lessened because of difficulty in treating tumor metastasis. Mongolian Saussurea involucrata (SIE) possesses various anticancer activities, including apoptosis and cell cycle arrest. However, detailed effects and molecular mechanisms of SIE on metastasis are unclear. Thus, the present study was undertaken to investigate antimetastatic effects on HCC cells as well as possible mechanisms. Effects of SIE on the growth, adhesion, migration, aggregation and invasion of the SK-Hep1 human HCC cell line were investigated. SIE inhibited cell growth of metastatic cells in dose- and time-dependent manners. Incubation of SK-Hep1 cells with $200-400{\mu}g/mL$ of SIE significantly inhibited cell adhesion to gelatin-coated substrate. In the migration (wound healing) and aggregation assays, SIE treated cells showed lower levels than untreated cells. Invasion assays revealed that SIE treatment inhibited cell invasion capacity of HCC cells substantially. Quantitative real time PCR showed inhibitory effects of SIE on MMP-2/-9 and MT1-MMP mRNA levels, and stimulatory effects on TIMP-1, an inhibitor of MMPs. The present study not only demonstrated that invasion and motility of cancer cells were inhibited by SIE, but also indicated that such effects were likely associated with the decrease in MMP-2/-9 expression of SK-Hep1 cells. From these results, it was suggested that SIE could be used as potential anti-tumor agent.

Shen, Bo;Zheng, Ma-Qing;Lu, Jian-Wei;Jiang, Qian;Wang, Tai-Hong;Huang, Xin-En 5403

https://doi.org/10.7314/APJCP.2013.14.9.5403 PDF KSCI

Objective: CXCL12 exerts a wide variety of chemotactic effects on cells. Evidence indicates that CXCL12, in conjunction with its receptor, CXCR4, promotes invasion and metastasis of tumor cells. Our objective was to explore whether the CXCL12-CXCR4 biological axis might influence biological behavior of pancreatic cancer cells. Methods: Miapaca-2 human pancreatic cancer cells were cultured under three different conditions: normal medium (control), medium + recombinant CXCL12 (CXCL12 group), or medium + CXCR4-inhibitor AMD3100 (AMD3100 group). RT-PCR was applied to detect mRNA expression levels of CXCL12, CXCR4, matrix metalloproteinase 2 (MMP-2), MMP-9, and human urokinase plasminogen activator (uPA). Additionally, cell proliferation and invasion were performed using CCK-8 colorimetry and transwell invasion assays, respectively. Results: CXCL12 was not expressed in Miapaca-2 cells, but CXCR4 was detected, indicating that these cells are capable of receiving signals from CXCL12. Expression of extracellular matrix-degrading enzymes MMP-2, MMP-9, and uPA was upregulated in cells exposed to exogenous CXCL12 (P<0.05). Additionally, both proliferation and invasion of pancreatic cancer cells were enhanced in the presence of exogenous CXCL12, but AMD3100 intervention effectively inhibited these processes (P<0.05). Conclusions: The CXCL12-CXCR4 biological axis plays an important role in promoting proliferation and invasion of pancreatic cancer cells.

Saeng-Anan, Ubol;Pantasri, Tawiwan;Neeyalavira, Vithida;Tongsong, Theera 5409

https://doi.org/10.7314/APJCP.2013.14.9.5409 PDF KSCI

Background: To assess the accuracy of ultrasound in differentiating endometrioma from ovarian cancer and to describe pattern recognition for atypical endometriomas mimicking ovarian cancers. Materials and Methods: Patients scheduled for elective surgery for adnexal masses were sonographically evaluated for endometrioma within 24 hours of surgery. All examinations were performed by the same experienced sonographer, who had no any information of the patients, to differentiate between endometriomas and non-endometriomas using a simple rule (classic ground-glass appearance) and subjective impression (pattern recognition). The final diagnosis as a gold standard relied on either pathological or post-operative findings. Results: Of 638 patients available for analysis, 146 were proven to be endometriomas. Of them, the simple rule and subjective impression could sonographically detect endometriomas with sensitivities of 64.4% (94/146) and 89.7% (131/146), respectively. Of 52 endometriomas with false negative tests by the simple rule, 13 were predicted as benign masses and 39 were mistaken for malignancy. Solid masses and papillary projections were the most common forms mimicking ovarian cancer, consisting of 38.5% of the missed diagnoses. However, with pattern recognition (subjective impression), 32 from 39 cases mimicking ovarian cancer were correctly predicted for endometriomas. All endometriomas subjectively predicted for ovarian malignancy were associated with high vascularization in the solid masses. Conclusions: Pattern recognition of endometriomas by subjective assessment had a higher sensitivity than the simple rule in characterization of endometriomas. Most endometriomas mimicking ovarian malignancy could be correctly predicted by subjective impression based on familiarity of pattern recognition.

Ren, Yang-Wu;Yin, Zhi-Hua;Wan, Yan;Guan, Peng;Wu, Wei;Li, Xue-Lian;Zhou, Bao-Sen 5415

https://doi.org/10.7314/APJCP.2013.14.9.5415 PDF KSCI

Background: Cell cycle deregulation is a major component of carcinogenesis. The p53 tumor suppressor gene plays an important role in regulating cell cycle arrest, and mouse double minute 2 (MDM2) is a key regulator of p53 activity and degradation. Abnormal expression of p53 and MDM2 occurs in various cancers including lung cancer. Methods: We investigated the distribution of the p53 Arg72Pro (rs1042522) and MDM2 SNP309 (rs2279744) genotypes in patients and healthy control subjects to assess whether these single nucleotide polymorphisms (SNPs) are associated with an increased risk of lung adenocarcinomas in Chinese female non-smokers. Genotypes of 764 patients and 983 healthy controls were determined using the TaqMan SNP genotyping assay. Results: The p53 Pro/Pro genotype (adjusted OR = 1.55, 95% CI = 1.17-2.06) significantly correlated with an increased risk of lung adenocarcinoma, compared with the Arg/Arg genotype. An increased risk was also noted for MDM2 GG genotype (adjusted OR = 1.68, 95% CI = 1.27-2.21) compared with the TT genotype. Combined p53 Pro/Pro and MDM2 GG genotypes (adjusted OR = 2.66, 95% CI = 1.54-4.60) had a supermultiplicative interaction with respect to lung adenocarcinoma risk. We also found that cooking oil fumes, fuel smoke, and passive smoking may increase the risk of lung adenocarcinomas in Chinese female non-smokers who carry p53 or MDM2 mutant alleles. Conclusions: P53 Arg72Pro and MDM2 SNP309 polymorphisms, either alone or in combination, are associated with an increased lung adenocarcinoma risk in Chinese female non-smokers.

Klongpityapong, Papavadee;Supabphol, Roongtawan;Supabphol, Athikom 5421

https://doi.org/10.7314/APJCP.2013.14.9.5421 PDF KSCI

Background: To assess the antioxidant effects of gamma-oryzanol on human prostate cancer cells. Materials and Methods: Cytotoxic activity of gamma-oryzanol on human DU145 and PC3 prostate cancer cells was determined by proliferation assay using 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) reagent. mRNA levels of genes involved in the intracellular antioxidant system, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GSR) were determined by reverse transcription-polymerase chain reaction (RT-PCR). Cancer cell lysates were used to measure lipid peroxidation using thiobarbituric acid reactive substance (TBARS). Glutathione contents of the cell lysates were estimated by the reaction between sulfhydryl group of 5, 5'-dithio (bis) nitrobenzoic acid (DTNB) to produce a yellow-color of 5-thio-2-nitrobenzoic acid using colorimetric assay. Catalase activity was also analysed by examining peroxidative function. Protein concentration was estimated by Bradford's assay. Results: All concentrations of gamma-oryzanol, 0.1-2.0mg/ml, significantly inhibited cell growth in a dose- and time-dependent fashion in both prostate cancer cell lines, DU145 and PC3. Gene expression of catalase in DU145 and PC3 exposed to gamma-orizanol at 0.5mg/ml for 14 days was down regulated, while mRNA of GPX was also down regulated in PC3. The MDA and glutathione levels including catalase activity in the cell lysates of DU145 and PC3 treated with gamma-oryzanol 0.1 and 0.5mg/ml were generally decreased. Conclusions: This study highlighted effects of gamma-oryzanol via the down-regulation of antioxidant genes, catalase and GPX, not cytotoxic roles. This might be interesting for adjuvant chemotherapy to make prostate cancer cells more sensitive to free radicals. It might be useful for the reduction of cytotoxic agents and cancer chemoprevention.

Wang, Shuai;Liu, Hong;Akhtar, Javed;Chen, Hua-Xia;Wang, Zhou 5427

https://doi.org/10.7314/APJCP.2013.14.9.5427 PDF KSCI

5-Azacytidine (5-azaC) was originally identified as an anticancer drug (NSC102876) which can cause hypomethylation of tumor suppressor genes. To assess its effects on runt-related transcription factor 3 (RUNX3), expression levels and the promoter methylation status of the RUNX3 gene were assessed. We also investigated alteration of biologic behavior of esophageal carcinoma TE-1 cells. MTT assays showed 5-azaC inhibited the proliferation of TE-1 cells in a time and dose-dependent way. Although other genes could be demethylated after 5-azaC intervention, we focused on RUNX3 gene in this study. The expression level of RUNX3 mRNA increased significantly in TE-1 cells after treatment with 5-azaC at hypotoxic levels. RT-PCR showed 5-azaC at $50{\mu}M$ had the highest RUNX3-induction activity. Methylation-specific PCR indicated that 5-azaC induced RUNX3 expression through demethylation. Migration and invasion of TE-1 cells were inhibited by 5-azaC, along with growth of Eca109 xenografts in nude mice. In conclusion, we demonstrate that the RUNX3 gene can be reactivated by the demethylation reagent 5-azaC, which inhibits the proliferation, migration and invasion of esophageal carcinoma TE-1 cells.

Chaleunvong, Kongmany;Kamsa-ard, Supot;Suwanrungruang, Krittika;Wiangnon, Surapon;Sychareun, Vanphanom;Alounlangsy, Phetsamone;Durham, Jo;Promthet, Supannee 5435

https://doi.org/10.7314/APJCP.2013.14.9.5435 PDF KSCI

Background: Recent estimates suggest that in the Lao People's Democratic Republic (Lao PDR) the burden of cancer in terms of DALYs lost is amongst the highest in South East Asia. As such, increasingly cancer is becoming an important public health concern in the country. Lao PDR however has no population-based cancer registry and only one hospital-based registry. Cancer treatment within the country is extremely limited. Patients who can, may travel to neighboring countries for treatment, but little information about this is available in the country. The aim of this study was to estimate some of the otherwise largely unknown parameters of the cancer burden in Lao PDR. Materials and Methods: This is a retrospective, descriptive study based on the records of 847 Lao cancer cases treated with surgery, radiation and chemotherapy at Srinagarind Hospital, Khon Kaen University, in Thailand between 1988 and 2010. Results: The annual rate of registration of Lao cancer cases fluctuated, but showed an increasing trend. Most cancers were diagnosed by histology (65.2%), and a combination of endoscopy and radiology (15.6%). In most cases (70.2%) the stage of cancer at diagnosis could not be determined. In those whose stage could be identified, 54.0% were at the final stage (Stage IV). Among males, the commonest cancer sites were the liver (16.1%), blood (12.3%) and nasopharynx (10.6%). Those in female patients were the cervix (22.2%), breast (14.6%) and blood (8.1%). Conclusions: This study indicates that despite some fluctuations, the number of Lao cancer patients presenting at Srinagarind Hospital, Khon Kaen, gradually increased between 1988 and 2010. The unfavorable pattern of late-stage cancer diagnosis among male and female patients suggests a need for cancer control interventions and the establishment of cancer registration and treatment facilities within Lao PDR.

Yang, Liu;Huang, Xin-En;Xu, Lin;Zhou, Xin;Zhou, Jian-Nong;Yu, Dong-Sheng;Li, Dong-Zheng;Guan, Xin 5441

https://doi.org/10.7314/APJCP.2013.14.9.5441 PDF KSCI

Purpose: To demonstrate the value of sequential determinations of pelvic drainage in the identification of increased risk of anastomotic leakage (AL) after anterior resection for rectal cancer with a double stapling technique. Patients and Methods: Between January 2004 and December 2011, data for the daily postoperative pH of pelvic drainage fluid in 753 consecutive patients with rectal cancer who initially underwent anterior resection with a double stapling technique were reviewed. All patients experienced a total mesorectal excision. Patients with anastomotic leakage (Group AL, n=57) were compared to patients without leakage (Group nAL, n=696). Patients with perioperatively abdominopelvic implants that were likely to affect pH value (determined at $25^{\circ}C$) other than leakage were excluded. Mean postoperative values were compared. Results: Anastomotic leakage was noted in 57 (7.6%) of 753 patients with rectal cancer. The diagnosis of AL was made between the $6^{th}$ and $12^{th}$ postoperative day (POD; mean $8^{th}$ POD). There was no significance of the daily average values of pH on POD1 & 2 in group AL while a significantly sharp declining mean pH value reached its diagnostic point of AL (p<0.001) on POD3. A cut-off value of 6.978 on the $3^{rd}$ POD maximized the sensitivity (98.7.0%) and specificity (94.7%) in assessing the risk of leakage. Conclusion: According to these results, an early and persistent declining of pH value of pelvic drainage fluid after rectal surgery with anastomosis, is a marker of AL. A cut-off value of 6.798 determined at $25^{\circ}C$ on POD3 maximizes sensitivity and specificity.

Ozen, Filiz;Polat, Fikriye;Arslan, Sulhattin;Ozdemir, Ozturk 5449

https://doi.org/10.7314/APJCP.2013.14.9.5449 PDF KSCI

Background: A large variety of familiar and non-familiar lung carcinomas (LC) are caused by long term exposure to chemical carcinogens that are present in tobacco smoke. We aimed to investigate the prevalence of 5 thrombophilic germ-line mutations in patients with lung carcinomas. Materials and Methods:A total of 52 LC patients and 212 healthy controls from same population were analyzed for FV Leiden, factor V H1299R (R2), PAI-1, MTHFR C677T, MTHFR A1298C, ACE I/D, and Apo E genes and compared. Results: Overall, heterozygous and/or homozygous point mutations in FV Leiden Apo E2, PAI-1 and MTHFR C677T genes were associated with LC in the current cohort. There was no meaningful association between LC and ACE I/D gene markers. Conclusions: The current results showed that LC is related to combined thrombophilic gene mutations and individuals with homozygosity of 4G in PAI-1 and MTHFR C677T genes and heterozygosity of FV Leiden, Apo E4 genes have a germ-line risk for LC tumorigenesis.

Yavuzcan, Ali;Caglar, Mete;Ozgu, Emre;Ustun, Yusuf;Dilbaz, Serdar;Ozdemir, Ismail;Yildiz, Elif;Gungor, Tayfun;Kumru, Selahattin 5455

https://doi.org/10.7314/APJCP.2013.14.9.5455 PDF KSCI

Background: The risk of malignancy index (RMI) for the evaluation of adnexal masses is a sensitive tool in certain populations. The best cut off value for RMI 1, 2 and 3 is 200. The cut off value of RMI-4 to differentiate benign from malignant lesions is 450. Our aim was to evaluate the efficiency of four different malignancy indexes (RMI1-4) in a homogeneous population. Materials and Methods: We evaluated a total of 153 non-pregnant women with adnexal masses who did not have a history of malignancy and who were above 18 years of age. Results: A cut-off value of 250 for RMI-1 provided 95.9% inter-observer agreement, yielding 95.9% specificity, 93.5% negative predictive value, 75.0% sensitivity and 82.8% positive predictive value. A cut-off value of 250 for RMI-1 showed high performance in preoperative diagnosis of invasive malignant lesions than cut-off value of 200 in our population. A cut-off value of 350 for RMI-2 provided 94.5% inter-observed agreement, yielding 94.2% specificity, 93.4% negative predictive value, 75.0% sensitivity and 77.4% positive predictive value. RMI-2 showed the higher performance when the cut-off value was set at 350 in our population. A cut-off value of 250 provided 95.2% inter-observer agreement, yielding 95.0% specificity, 93.2% negative predictive value, 75.0% sensitivity, and 88.0% positive predictive value. RMI-3 showed the highest performance to diagnose malignant adnexal masses when the cut-off value was set at 250. In our study, RMI-4 showed similar statistical performance when the cut-off value was set at 400 [(Kappa: 0.684/p=0.000), yielding 93.8% inter-observer agreement, 93.4% specificity, 93.4% negative predictive value, 75.0% sensitivity, and 75.0% negative predictive value]. Conclusions: We showed successful utilization of RMIs in preoperative differentiation of benign from malignant masses. Many studies conducted in Asian and Pacific countries have reported different cut-off values as was the case in our study. We think that it is difficult to determine universally accepted cut-off values for RMIs for common use around the globe.

Suresh, Shruthy;Raghu, Dinesh;Karunagaran, Devarajan 5461

https://doi.org/10.7314/APJCP.2013.14.9.5461 PDF KSCI

Oral cancer is one of the most commonly occurring cancers worldwide, decreasing the patient's survival rate due to tumor recurrence and metastasis. Menadione (Vitamin K3) is known to exhibit cytotoxicity in various cancer cells but the present study focused on its effects on viability, apoptosis, epithelial to mesenchymal transition (EMT), anchorage independent growth and migration of oral cancer cells. The results show that menadione is more cytotoxic to SAS (oral squamous carcinoma) cells but not to non-tumorigenic HEK293 and HaCaT cells. Menadione treatment increased the expression of pro-apoptotic proteins, Bax and p53, with a concurrent decrease in anti-apoptotic proteins, Bcl-2 and p65. Menadione induced the expression of E-cadherin but reduced the expression of EMT markers, vimentin and fibronectin. Menadione also inhibited anchorage independent growth and migration in SAS cells. These findings reveal and confirm that menadione is a potential candidate in oral cancer therapy as it exhibits cytotoxic, antineoplastic and antimigratory effects besides effectively blocking EMT in oral cancer cells.

Xu, Wei;Chang, Hong;Qin, Cheng-Kun;Zhai, Yun-Peng 5467

https://doi.org/10.7314/APJCP.2013.14.9.5467 PDF KSCI

Objective: To construct short hairpin RNA (shRNA) eukaryotic expression vectors targeting Livin and Survivin genes, and to explore the impact of co-transfection of Livin and Survivin shRNA expression vectors on the biological behavior of HepG2 cells. Methods: shRNA eukaryotic expression vectors pSD11-Livin and pSD11-Survivin were designed and constructed then transfected into HepG2 cells separately or in combination. mRNA and protein expression in transfected cells was assessed by quantitative fluorescence PCR and Western blotting, respectively. Cell proliferation was measured by MTT assay and cell apoptosis by TUNEL assay. Results: The Livin and Survivin shRNA eukaryotic expression vectors were successfully constructed and transfected into HepG2 cells. The relative mRNA expression levels of Livin and Survivin in HepG2 cells co-transfected with pSD11-Livin and pSD11-Survivin were $0.12{\pm}0.02$ and $0.33{\pm}0.13$, respectively, which was significantly lower than levels in cells transfected with either pSD11-Livin or pSD11-Survivin (P<0.05). The relative protein expression levels of Livin and Survivin in the co-transfected cells were also significantly decreased compared to single-transfection (P<0.05). The inhibition rate of cell growth in the co-transfection group was higher than that in the single-transfection groups at 48 h, 60 h, or 72 h after transfection (P<0.01). The apoptotic rate increased to the greatest extent in the co-transfection group relative to any other group (P<0.05). Conclusions: Co-transfection with pSD11-Livin and pSD11-Survivin was more efficient than transfection with either vector alone in reducing the mRNA and protein expression of Livin and Survivin genes in HepG2 cells. Co-transfection also inhibited the proliferation of transfected cells more than the other groups, and induced cellular apoptosis more effectively.

Kaya, Vildan;Yildirim, Mustafa;Demirpence, Ozlem;Yildiz, Mustafa;Yalcin, Aysen Yesim 5473

https://doi.org/10.7314/APJCP.2013.14.9.5473 PDF KSCI

Background: In our study, the LDH, albumin, hemoglobin, neutrophile, thrombocyte, lymphocyte counts and prognostic significance of neutrophile-lymphocyte and thrombocyte-lymphocyte ratios in NSCLC derived from these counts obtained during regular examinations of patients were examined. Materials and Methods: Histopathologically diagnosed non-small-cell-lung cancer patients between 2008 and 2010 were included in the study. Before the treatment, full blood count including routine lymphocyte count, blood biochemistry examinations including liver (AST, ALT, total protein, Albumin), LDH and kidney (BUN, Cre) function tests were performed. Results: A total of 156 patients, 76 of whom (48.7%) were female and 80 of whom (51.3%) were male were included. Mean hemoglobin level was determined as 12. Overall survival was found to be significantly dependent on whether patients were anemic or not (p: 0.005). Mean LDH level was determined as 233.4. There was nosurvival difference between patients with and without high LDH (p: 0.532). In patients where NLR showed systemic inflammatory response, overall survival was 10.8 months whereas this duration was 19.6 months in patients where the systemic inflammatory response was negative (p: 0.012). In patients where TLR showed systemic inflammatory response, overall survival was 13.6 months whereas this duration was 21.9 months in patients where the systemic inflammatory response was negative (p: 0.04). Conclusions: Molecular methods have been changing rapidly in today's world and they manage the treatment besides defining the prognosis of patients. However, easily accessible and cheap laboratory parameters should be considered in the prognosis of patients besides these new methods.

Citak, Ebru Akgun;Toruner, Ebru Kilicarslan;Gunes, Nebahat Bora 5477

https://doi.org/10.7314/APJCP.2013.14.9.5477 PDF KSCI

Background: Communication plays an important role for the well being of patients, families and also health care professionals in cancer care. Conversely, ineffective communication may cause depression, increased anxiety, hopelessness and decreased of quality life for patients, families and also nurses. Objective: This study aimed to explore communication difficulties of pediatric hematology/oncology nurses with patients and their families, as well as their suggestions about communication difficulties. Materials and Methods: It was conducted in a pediatric hematology/oncology hospital in Ankara, Turkey. Qualitative data were collected by focus groups, with 21 pediatric hematology/oncology nursing staff from three groups. Content analysis was used for data analysis. Results: Findings were grouped in three main categories. The first category concerned communication difficulties, assessing problems in responding to questions, ineffective communication and conflicts with the patient's families. The second was about the effects of communication difficulties on nurses and the last main category involved suggestions for empowering nurses with communication difficulties, the theme being related to institutional issues. Conclusions: Nurses experience communication difficulties with children and their families during long hospital stays. Communication difficulties particularly increase during crisis periods, like at the time of first diagnosis, relapse, the terminal stage or on days with special meaning such as holidays. The results obtained indicate that pediatric nurses and the child/family need to be supported, especially during crisis periods. Feeling of empowerment in communication will improve the quality of care by reducing the feelings of exhaustion and incompetence in nurses.

Du, Yang;Han, Li-Yuan;Li, Dan-Dan;Liu, Hui;Gao, Yan-Hui;Sun, Dian-Jun 5483

https://doi.org/10.7314/APJCP.2013.14.9.5483 PDF KSCI

Background: Associations between Arg399Gln, Arg194Trp and Arg280His polymorphisms of the XRCC1 gene and risk of differentiated thyroid carcinoma (DTC) have been widely studied but the findings are contradictory. Methods: We performed a meta-analysis in the present study using STATA 11.0 software to clarify any associations. Electronic literature databases and reference lists of relevant articles revealed a total of 10, 6 and 6 published studies for the Arg399Gln, Arg194Trp and Arg280His polymorphisms, respectively. Results: No significant associations were observed between Arg399Gln and DTC risk in all genetic models within the overall and subgroup meta-analyses, while the Trp/Trp vs Arg/Arg and recessive model of the Arg194Trp polymorphism was associated with DTC susceptibility, and the dominant model of Arg280His polymorphism contributed to DTC susceptibility in Caucasians. Conclusions: Our meta-analysis suggests that XRCC1 Arg194Trp may be a risk factor for DTC development.

Alagozlu, Hakan;Ozdemir, Ozturk;Koksal, Binnur;Yilmaz, Abdulkerim;Coskun, Mahmut 5489

https://doi.org/10.7314/APJCP.2013.14.9.5489 PDF KSCI

In the current study we aimed to show the common YMDD motif mutations in viral polymerase gene in chronic hepatitis B patients during lamivudine and adefovir therapy. Forty-one serum samples obtained from chronic hepatitis B patients (24 male, 17 female; age range: 34-68 years) were included in the study. HBV-DNA was extracted from the peripheral blood of the patients using an extraction kit (Invisorb, Instant Spin DNA/RNA Virus Mini Kit, Germany). A line probe assay and direct sequencing analyses (INNO-LIPA HBV DR v2; INNOGENETICS N.V, Ghent, Belgium) were applied to determine target mutations of the viral polymerase gene in positive HBV-DNA samples. A total of 41 mutations located in 21 different codons were detected in the current results. In 17 (41.5%) patients various point mutations were detected leading to lamivudin, adefovir and/or combined drug resistance. Wild polymerase gene profiles were detected in 24 (58.5%) HBV positive patients of the current cohort. Eight of the 17 samples (19.5%) having rtM204V/I/A missense transition and/or transversion point mutations and resistance to lamivudin. Six of the the mutated samples (14.6%) having rtL180M missense transversion mutation and resistance to combined adefovir and lamivudin. Three of the mutated samples (7.5%) having rtG215H by the double base substituation and resistance to adefovir. Three of the mutated samples (7.5%) having codon rtL181W due to the missense transversion point mutations and showed resistance to combined adefovir and lamivudin. Unreported novel point mutations were detected in the different codons of polymerase gene region in the current HBV positive cohort fromTurkish population. The current results provide evidence that rtL180M and rtM204V/I/A mutations of HBV-DNA may be associated with a poor antiviral response and HBV chronicity during conventional therapy in Turkish patients.

Puttipanyalears, Charoenchai;Subbalekha, Keskanya;Mutirangura, Apiwat;Kitkumthorn, Nakarin 5495

https://doi.org/10.7314/APJCP.2013.14.9.5495 PDF KSCI

Background: Alu elements are one of the most common repetitive sequences that now constitute more than 10% of the human genome and potential targets for epigenetic alterations. Correspondingly, methylation of these elements can result in a genome-wide event that may have an impact in cancer. However, studies investigating the genome-wide status of Alu methylation in cancer remain limited. Objectives: Oral squamous cell carcinoma (OSCC) presents with high incidence in South-East Asia and thus the aim of this study was to evaluate the Alu methylation status in OSCCs and explore with the possibility of using this information for diagnostic screening. We evaluated Alu methylation status in a) normal oral mucosa compared to OSCC; b) peripheral blood mononuclear cells (PBMCs) of normal controls comparing to oral cancer patients; c) among oral epithelium of normal controls, smokers and oral cancer patients. Materials and Methods: Alu methylation was detected by combined bisulfite restriction analysis (COBRA) at 2 CpG sites. The amplified products were classified into three patterns; hypermethylation ($^mC^mC$), partial methylation ($^uC^mC+^mC^uC$), and hypomethylation ($^uC^uC$). Results: The results demonstrate that the $%^mC^mC$ value is suitable for differentiating normal and cancer in oral tissues (p=0.0002), but is not significantly observe in PBMCs. In addition, a stepwise decrease in this value was observed in the oral epithelium from normal, light smoker, heavy smoker, low stage and high stage OSCC (p=0.0003). Furthermore, receiver operating characteristic (ROC) curve analyses demonstrated the potential of combined $%^mC$ or $%^mC^mC$ values as markers for oral cancer detection with sensitivity and specificity of 86.7% and 56.7%, respectively. Conclusions: Alu hypomethylation is likely to be associated with multistep oral carcinogenesis, and might be developed as a screening tool for oral cancer detection.

Prompakay, Russameekae;Promthet, Supannee;Kamsa-ard, Siriporn;Suwanrungruang, Krittika;Wiangnon, Surapon;Bradshaw, Peter 5503

https://doi.org/10.7314/APJCP.2013.14.9.5503 PDF KSCI

This cross-sectional analytic study aimed to investigate any relationship between the body mass index (BMI) and an abnormal Pap smear. The subjects were 7,720 women aged 30-69 years who lived in Khon Kaen Province, Thailand, and had been recruited as participants in the Khon Kaen Cohort Study during 1990-2001. All had received Pap smear screening for cervical cancer. The data were analyzed using descriptive and inferential statistics. Multiple logistic regression was used to determine the relationship between body mass index and an abnormal Pap smear. The mean BMI was $24.53kg/m^2$ (SD=3.98), and 2.14% had abnormal Pap smears. Compared with the reference group of women with a BMI ${\leq}22.9kg/m^2$, those with a body mass index of $23.0-24.9kg/m^2$ had a reduced risk of an abnormal smear (ORadj=0.92, 95%CI: 0.57-1.47), but women with a BMI $25.0-29.9kg/m^2$ were found to have an approximately 1.24 times higher risk ($OR_{adj}=1.24$, 95%CI: 0.86-1.80), and those with a BMI ${\geq}30.0kg/m^2$ had an approximately 1.63 times higher risk ($OR_{adj}=1.63$, 95%CI: 0.98-2.69). The results indicated that the risk of Pap smear abnormalities is increased in women who have a higher than normal body mass index, but this finding was not statistically significant. Nevertheless, public health personnel should encourage women to maintain their BMI in the normal range to reduce the possible future risk of cervical cancer.

Zhang, Yi-Yin;Gu, Kang-Sheng 5507

https://doi.org/10.7314/APJCP.2013.14.9.5507 PDF KSCI

Objective: To investigate the correlation between ERCC1 expression levels in tumor tissue and peripheral blood lymphocytes (PBL) from patients with gastric cancer and assess the relationship between PBL DNA repair rate (DRR) and the efficacy of platinum chemotherapy. Methods: A total of 53 patients with gastric cancer receiving surgery and 20 controls were studied. ERCC1 protein expression in tumour tissue and PBL were determined by immunohistochemical staining. The PBL DRRs of 47 advanced patients and 20 controls were estimated by comet assay. Results: The positive expression rates of ERCC1 were 67. 9%, 56. 6% and 10.0% in tumour tissues, PBLs of gastric cancer patients, and PBLs of the control group. PBL ERCC1 expression correlated with that in tissue (${\chi}^2$=15. 463, p=0.000). Pearson contingency coefficient=0.475). DRRs of cancer patients by tail length (TL) (Z=4. 662, p=0.000) and tail moment (TM) (Z=3. 827, p=0.000) were significantly lower than that of control group. When TL was applied as an indicator, the correlation between DRR and chemotherapy efficacy was significant (Spearman rank correlation r=0.327, p=0.032). Patients with low levels of DRR in PBL presented better short-term efficacy of chemotherapy than those with high levels of DRR. Conclusions: The ERCC1 expression in PBLs may indirectly reflect ERCC1 expression in gastric cancer tissues. Compared with non-cancer populations, patients with gastric cancer may have lower DNA repair capacity. DRR in PBL may predict the short-term efficacy of platinum-based chemotherapy for patients with advanced gastric cancer.

Zhao, Ying-Hui;Wang, Tao;Yu, Guang-Fu;Zhuang, Dong-Ming;Zhang, Zhong;Zhang, Hong-Xin;Zhao, Da-Peng;Yu, Ai-Lian 5513

https://doi.org/10.7314/APJCP.2013.14.9.5513 PDF KSCI

IFN-${\gamma}$ plays an indirect anti-cancer role through the immune system but may have direct negative effects on cancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferation and how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-${\gamma}$ and found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-${\gamma}$ on apoptosis of cell lines and no effect on cell aging as assessed by ${\beta}$-gal staining. Microarray assay revealed that IFN-${\gamma}$ changed the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well as chemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-${\gamma}$ arrested the cells in the G1/S phase. IFN-${\gamma}$ may slow proliferation of some gastric cancer cells by affecting the cell cycle to play a negative role in the development of gastric cancer.

Nilyanimit, Pornjarim;Wanlapakorn, Nasamon;Niruthisard, Somchai;Pohthipornthawat, Natkrita;Karalak, Anant;Laowahutanont, Piyawat;Phanuphak, Nittaya;Gemma, Nobuhiro;Poovorawan, Yong 5519

https://doi.org/10.7314/APJCP.2013.14.9.5519 PDF KSCI

Background: Cervical cancer is the second most common cancer in Thai women after breast cancer. Currently, the Papanicolaou (Pap) smear is the recommended procedure for cervical cancer screening in Thailand, but only a relatively small percentage of women follow this screening program. An alternative method to detect HPV genotypes associated with cervical cancer is self-sampling of urine, which is a more widely accepted method. Our study aimed to evaluate the prevalence of HPV in Thai women using urine and cervical swabs and prevalence of HPV in Thai men using urine samples. Materials and Methods: Tumorigenic HPV detection was accomplished by electrochemical DNA chip and PCR/direct sequencing. In addition to HPV prevalence, we report the concordance between different methods and sample types. One-hundred and sixteen women and 100 men were recruited. Histological examination revealed normal cytology in 52 women, atypical squamous cells of undetermined significance (ASCUS) in 9, low-grade squamous intraepithelial lesions (LSIL) in 24, and high-grade squamous intraepithelial lesions (HSIL) in 31. One-hundred men were classified as heterosexuals (n=45) and homosexuals (n=55). Results: The most prevalent HPV genotype in our study was HPV16. The HPV detection rate was generally lower in urine samples compared with cervical samples. Overall, there was good agreement for the detection of carcinogenic HPV from female cervical samples between the DNA chip and PCR/sequencing, with 88.8% total agreement and a kappa value of 0.76. In male urine samples, the level of agreement was higher in heterosexuals compared with homosexuals. Conclusions: Further improvement is required to increase an overall yield of HPV DNA detection in urine samples before clinical application of a urine-based HPV screening program. The electrochemical DNA chip test is a promising technique for carcinogenic HPV detection.

Zheng, You-Bing;Zhao, Wei;Liu, Bing;Lu, Li-Gong;He, Xu;Huang, Jian-Wen;Li, Yong;Hu, Bao-Shan 5527

https://doi.org/10.7314/APJCP.2013.14.9.5527 PDF KSCI

Background and Aim: Increasing evidence correlates the presence of systemic inflammation with poor survival in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the prognostic significance of the blood neutrophil-to-lymphocyte ratio (NLR) in patients with advanced HCC who received sorafenib monotherapy. Methods: A total of sixty-five patients with advanced HCC, not eligible for locoregional therapy, treated with sorafenib were enrolled. Potential prognostic factors such as age, gender, tumoral characteristics, performance status and NLR were analyzed. Results: Median OS and TTP for the entire cohort were 10.0 months (95%CI, 7.6-12.3 months) and 4.5 months (95% CI, 4.0-4.9 months). The mean NLR at baseline was 2.89. The median OS of patients with a high NLR (>4) was 6.5 months (95%CI, 5.2-7.7 months) compared with 12.5 months (95%CI, 9.9-15.0) for patients with a normal NLR (${\leq}4$) (P=0.01). Age ${\leq}65$, NLR>4, extrahepatic metastases and vascular invasion were all predictors of poorer overall survival. Multivariate analysis showed that NLR > 4, vascular invasion and extrahepatic metastases were independent predictors of poorer overall survival. The median TTP of patients with a high NLR was 2.5 months (95%CI, 1.4-3.6 months) compared with 4.5 months (95%CI, 3.9-5.1 months) for patients with a normal NLR (P=0.012). Conclusions: High baseline NLR was associated with worse OS and TTP for patients with advanced HCC treated with sorafenib.

Sun, Xiao-Jin;Liu, Hao;Zhang, Pei;Zhang, Xu-Dong;Jiang, Zhi-Wen;Jiang, Chen-Chen 5533

https://doi.org/10.7314/APJCP.2013.14.9.5533 PDF KSCI

MicroRNA-10b (miR-10b) has been reported to play an important role in some types of cancer, but the effects and possible mechanisms of action of miR-10b in the metastasis of nasopharyngeal carcinoma cells (NPC) have not been explored. The aim of the present study was to investigate the function of miR-10b in nasopharyngeal carcinoma and to determine the molecular mechanisms underlying its action. The MTT assay was used to assess proliferation of CNE-2Z cells. Wound healing and transwell migration assays were applied to assess cell migration and invasion, while and expression of E-cadherin and MMP-9 were detected using Western blot analysis. Real-time PCR was employed to detect the expression of genes related to migration and invasion and the $2^{-{\Delta}{\Delta}Ct}$ method was used to calculate the degree of expression. MTT assay showed the expression of miR-10b to have no effect on the proliferation of NPC cell lines. The wound healing assay showed that miR-10b mimics promoted the mobility and invasion of NPC cell lines. Inhibitors of miR-10b reduced the ability of NPC cell lines to migrate and invade. In addition, the expression of genes related to migration and invasion, such as E-cadherin, vimentin, and MMP-9, were confirmed to be different in the CNE-2Z NPC cell line transfected with miR-10b mimics and with miR-10b inhibitors. In the present study, miR-10b was found to upregulate the expression of MMP-9 and knockdown of miR-10b was found to significantly downregulate the expression of E-cadherin. On the whole, these results showed that miR-10b plays an important role in the invasion and metastasis of NPC cells.

Khokhar, Anita 5539

https://doi.org/10.7314/APJCP.2013.14.9.5539 PDF KSCI

There is a consensus among researchers about the fact that women should be familiar with their breasts but there is a lot of argument as to how to make them aware of what is normal for them. For over decades breast self examination (BSE) was advocated for the same but as an outcome of work conducted by researchers in various countires a controversy has been raised in the West. In a country like India, where breast cancer screening is not popular and limited resources are available we should question what would be the best strategy to make women familiar with their breasts to facilitate best use of BSE.

Asian Pacific Journal of Cancer Prevention

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2017

2016

2015

2014

2013

2012

Volume 14 Issue 9

Asian Pacific Journal of Cancer Prevention

Domain

Aim & Scope

2017

2016

2015

2014

2013

2012

Volume 14 Issue 9

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