• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3131-3138
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• 2016

Several studies have addressed the possible role of hepatitis C virus genotype-4 (HCV GT4) in apoptosis. However, this still not fully understood. In the current study a re-constructed clone of E1/E2 polyprotein region of the HCV GT4 was transfected into the Huh7 cell line and a human apoptotic PCR array of 84 genes was used to investigate its possible significance for apoptosis. Out of the 84 genes, only 35 showed significant differential expression, 12 genes being up-regulated and 23 down-regulated. The highest-up regulated genes were APAF1 (apoptotic peptidase-activating factor 1), BID (BH3 interacting domain death agonist) and BCL 10 (B-cell CLL/lymphoma protein 10) with fold regulation of 33.2, 30.1 and 18.9, respectively. The most down-regulated were FAS (TNF receptor super family), TNFRSF10B (tumor necrosis factor receptor super-family member 10b) and FADD (FAS-associated death domain) with fold regulation of -30.2, -27.7 and -14.9, respectively. These results suggest that the E1/E2 proteins may be involved in HCV-induced pathogenesis by modulating apoptosis through the induction of the intrinsic apoptosis pathway and disruption of the BCL2 gene family.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3167-3171
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• 2016

Prostate cancer (PCa) is one of the most common diseases in men. It is important to assess prognostic factors and whether high cortisol levels and complex hormonal interactions could be responsible for PCa development. We evaluated the relationship between cortisol, leptin and estrogens in 141 men, 71 with PCa and the remaining 70 constituting a low risk group (LRG). They were recruited for this study from a total of 2906 middle-aged men (ages 45-70 years) who completed an evaluation for prostatic diseases at the Urology Division, Hospital de Clínicas "$Jos{\acute{e}}$ de San $Mart{\acute{i}}n$", University of Buenos Aires, in May 2009. In this cross sectional study, cortisol, PSA, total-testosterone, free-testosterone, bioavailable testosterone, LH and estradiol were measured in serum. We observed increased cortisol levels in PCa patients as compared to LRG cases (p=0.004,). Leptin and estradiol levels were also higher in PCa patients (p=0.048; p<0.0001, respectively). Logistic regression analysis indicated that serum cortisol (OR: 1.110 (95% CI 1.016-1.213), p=0.022), estradiol (OR: 1.044 (95% CI 1.008-1.081), p=0.016) and leptin (OR: 1.248 (95% CI 1.048-1.487), p=0.013) explained 27% of the variance of dependent variables, even after adjusting for age, smoking, BMI and waist circumference. We found increased cortisol levels in PCa patients as compared to LRG, as well as an altered circulating hormonal profile.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3195-3199
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• 2016

Background: Skin cancer is a group of heterogeneous malignancies, in general classified into non-melanoma skin cancer (NMSC) and melanoma skin cancer (MSC). Incidences are high in many parts in the world with considerable geographical and racial variation. In the Yemen, there has been scarce information about skin cancer. The aim of this study was to evaluate the demographic characteristics and histological trend of skin cancer in Southern Governorates of Yemen. Materials and Methods: This retrospective study covered 204 cases of skin cancer at the Modern Histopathology Laboratory and Aden Cancer Registry and Research Center, Faculty of Medicine and Health Sciences, University of Aden, for the period 2006-2013. Data were classified regarding different demographic and tumor related variables and analyzed using CanReg-4 for cancer registry and SPSS (version 21). Results: The commonest encountered skin cancer was NMSC (93.1%). Generally, skin cancer appears slightly more frequently in females than males with a 1:1.06 male: female ratio, with a mean age of 62.9 years. Slightly higher than one-third (36.3%) were from Aden governorate. The head and neck proved to be the most common site in both males and females (58%). Basal cell carcinoma (BCC) is the most common histological type of skin cancer (50.5%). Conclusions: Skin cancer is a common cancer in patients living in southern governorates of Yemen. The pattern appears nearly similar to the international figures with a low incidence of MSC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3223-3228
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• 2016

Reports indicate that 15-deoxy-delta-12,14-prostaglandin-J2 (15d-PGJ2) has anticancer activities, but its mechanisms of action have yet to be fully elucidated. We therefore investigated the effects of 15d-PGJ2 on the human breast cancer cell lines, MCF-7 (estrogen receptor $ER{\alpha}+/ER{\beta}+$) and MDA-MB-231 ($ER{\alpha}-/ER{\beta}+$). Cellular proliferation and cytotoxicity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays while apoptosis was determined by fluorescence microscopy and flow cytometry using annexin V-propidium iodide (PI) staining. ER expression was determined by Western blotting. Intracellular calcium was stained with Fluo-4 AM while intracellular caspase activities were detected with Caspase-$FLICA(R)$ and measured by flow cytometry. We showed that 15d-PGJ2 caused a significant increase in apoptosis in MCF-7 and MDA-MB-231 cells. $ER{\alpha}$ protein expression was reduced in treated MCF-7 cells but pre-incubation with the $ER{\alpha}$ inhibitor' ICI 182 780' did not affect the percentage of apoptotic cells. The expression of $ER{\beta}$ was unchanged in both cell lines. In addition, 15d-PGJ2 increased intracellular calcium ($Ca^{2+}$) staining and caspase 8, 9 and 3/7 activities. We therefore conclude that 15d-PGJ2 induces caspase-dependent apoptosis that is associated with an influx of intracellular $Ca^{2+}$ with no involvement of ER signaling.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3243-3248
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• 2016

Background: Stomach cancer is the fourth most common cancer and the second leading cause of death from cancer in the world. In Iran, this type of cancer has high rates of incidence and mortality. This study aimed to assess the survival rate of patients with stomach cancer and its determinants in Kurdistan, a province with one of the highest incidence rates of stomach cancer in the country. Materials and Methods: We studied a total of 202 patients with stomach cancer who were admitted to Tohid Hospital in Sanandaj from 2009 to 2013. Using Kaplan-Meier nonparametric methods the survival rate of patients was calculated in terms of different levels of age at diagnosis, gender, education, residential area, occupation, underweight, and clinical variables including tumor histology, site of tumor, disease stage, and type of treatment. In addition, we compared the survival rates using the log-rank test. Finally, Cox proportional hazards regression was applied using Stata 12 and R 3.1.0 software. The significance level was set at 0.05. Results: The mean age at diagnosis was $64.7{\pm}12.0$ years. The survival rate of patients with stomach cancer was 43.9% and 7% at the first and the fifth year after diagnosis, respectively. The results of log-rank test showed significant relationships between survival and age at diagnosis, education, disease stage, type of treatment, and degree of being underweight (P<0.05). Moreover, according to the results of Cox proportional hazards regression model, the variables of education, disease stage, and type of treatment were associated with patient survival (P<0.05). Conclusions: The survival rate of patients with stomach cancer is low and the prognosis is very poor. Given the poor prognosis of the patients, it is critical to find ways for early diagnosis and facilitating timely access to effective treatment methods.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3265-3269
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• 2016

Background: Around half of input data in the global burden of disease cancer collaboration (GBD-CC) and GLOBOCAN projects come from low quality sources, mainly from developing countries. This may lead to loss of precision in estimates. Our question was: Are the absolute values and trends of the GBD-CC and GLOBOCAN estimates for lung cancer (LC) in Iran consistent with available statistics?. Materials and Methods: Incidence and mortality statistics were extracted from national reports (N.IRs & N.MRs) and GBD-CC (GBD-incidence & mortality) and GLOBOCAN databases for 1990-2013 where available. Trends were analyzed and absolute values and annual percentage changes (APCs) were estimated and compared. Incompleteness of case ascertainment at the Iranian national cancer registry and Iranian national civil registration was assessed for better understanding. Results: Trends of N.IRs were significantly rising for males (APC: 19.4; 95% CI: 12.5-26.7) and females (23.2; 16.0-30.8). Trends of GBD-incidence were stable for males (-0.2; -1.5-1.1) and females (-1.0; -2.3-0.4). Absolute N.IRs were less than GBD-incidence steadily except for 2009. Trend of N.MRs was increasing up to 2004, but stable thereafter. Trends of GBD-mortality were also stable. Absolute N.MRs were less than GBD-mortality for years up to 2003 and more than GBD-mortality since 2005. The estimates of GLOBOCAN were more than N.IRs and N.MRs. Conclusions: The GBD-CC and GLOBOCAN values for LC in Iran are underestimates. Generation of data quality indices to present along with country specific estimates is highly recommended.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3289-3294
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• 2016

Naringin, a bioflavonoid found in Citrus seeds, inhibits proliferation of cancer cells. The objectives of this study were to investigate the mode and mechanism(s) of hepatocellular carcinoma HepG2 cell death induced by naringin. The cytotoxicity of naringin towards HepG2 cells proved dose-dependent, measured by MTT assay. Naringin-treated HepG2 cells underwent apoptosis also in a concentration related manner, determined by annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) employing flow cytometry. Mitochondrial transmembrane potential (MTP) measured using 3,3'-dihexyloxacarbocyanine iodide ($DiOC_6$) and flow cytometer was reduced concentration-dependently, which indicated influence on the mitochondrial signaling pathway. Caspase-3, -8 and -9 activities were enhanced as evidenced by colorimetric detection of para-nitroaniline tagged with a substrate for each caspase. Thus, the extrinsic and intrinsic pathways were linked in human naringin-treated HepG2 cell apoptosis. The expression levels of pro-apoptotic Bax and Bak proteins were increased whereas that of the anti-apoptotic Bcl-xL protein was decreased, confirming the involvement of the mitochondrial pathway by immunoblotting. There was an increased expression of truncated Bid (tBid), which indicated caspase-8 proteolysis activity in Bid cleavage as its substrate in the extrinsic pathway. In conclusion, naringin induces human hepatocellular carcinoma HepG2 cell apoptosis via mitochondria-mediated activation of caspase-9 and caspase-8-mediated proteolysis of Bid. Naringin anticancer activity warrants further investigation for application in medical treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3325-3328
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• 2016

Background: There are limited studies on oncoplastic breast conserving surgery in Asian women. We aimed to determine the applicability and safety of oncoplastic surgery, highlighting the specific circumstances when it will be most useful and compare our preferred technique with the worldwide practice of oncoplastic approaches. Materials and Methods: Breast cancer patients who underwent oncoplastic breast conserving surgery at a single institution from 1st May 2014-31st March 2015 were included. Data on patient demographics, tumor characteristics and the type of oncoplastic surgery performed were collected. Results: Nineteen breast cancer patients were identified. 42.1% of patients had grade I ptosis. The indications for surgery included a large tumor to breast size ratio (52.6%), multifocal/multicentric lesions (36.8%) and asymmetric breasts (10.6%), averting a mastectomy in 89.4%. Round block was the commonest technique in 63% of patients, in contrast to the inverted T pattern most frequently used in renowned institutions in the West. Mean and median tumor size and weight of specimen were 29.4/25mm (11 - 75mm) and 77g/64g (10 - 246g) respectively. Re-excision rate was 10.5%. Complete mastectomy was performed for one patient. One patient developed wound dehiscence which was treated conservatively. Cosmetic outcome was rated as excellent/good by 94.7% of patients. The patients remained clinically well after a median 16 months follow up. Conclusions: Oncoplastic breast conserving surgery is useful in a specific subgroup of Asian patients with a relatively small breast volume and minimal ptosis. Round block was the commonest technique in our series, in contrast to the worldwide utility of oncoplastic techniques. It is oncologically safe and has good cosmetic outcomes.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3385-3390
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• 2016

Background: Sequential use of circulating prostate cell (CPC) detection has been reported to potentially decrease the number of unnecessary prostate biopsies in men suspected of prostate cancer. In order to determine the real world effectiveness of the test, we present a prospective study of men referred to two hospitals from primary care physicians, one using CPC detection to determine the necessity of prostate biopsy the other not doing so. Materials and Methods: Men with a suspicion of prostate cancer because of elevated PSA >4.0ng/ml or abnormal DRE were referred to Hospitals A or B. In Hospital A all underwent 12 core TRUS biopsy, in Hospital B only men CPC (+), with mononuclear cells obtained by differential gel centrifugation identified using double immunomarking with anti-PSA and anti-P504S, were recommended to undergo TRUS biopsy. Biopsies were classifed as cancer or no-cancer. Diagnostic yields were calculated, including the number of posible biopsies that could be avoided and the number of clinically significant cancers that would be missed. Results: Totals of 649 men attended Hospital A, and 552 men attended Hospital B; there were no significant differences in age or serum PSA levels. In Hospital A, 228 (35.1%) men had prostate cancer detected, CPC detection had a sensitivity of 80.7%, a specificity of 88.6%, and a negative predictive value of 89.5%. Some 39/44 men CPC negative with a positive biopsy had low grade small volume tumors. In Hospital B, 316 (57.2%) underwent biopsy. There were no significant differences between populations in terms of CPC and biopsy results. The reduction in the number of biopsies was 40%. Conclusions: The use of sequential CPC testing in the real world gives a clear decision structure for patient management and can reduce the number of biopsies considerably.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3505-3510
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• 2016

Cervical cancer is a major public health problem in Thailand, being ranked second only to breast cancer. Thai women have been reported to have a low rate of cervical cancer screening (27.7% of the 80% goal of WHO). We therefore aimed to apply the social marketing theory and health belief model in promoting cervical cancer screening in Kanthararom District, Sisaket Province. A total of 92 from 974 targeted women aged 30-60 years were randomly divided into two groups. The experimental group underwent application of social marketing theory and a health belief model program promoting cervical cancer screening while the control group received normal services. Two research tools were used: (1) application of social marketing theory and health belief model program and (2) questionnaire used to evaluate perceptions of cervical cancer. Descriptive and inferential statistics including paired sample t-test and independent t-test were used to analyze the data. After the program had been used, the mean score of perception of cervical cancer of experimental group was at a higher level (${\bar{x}}=4.09$; S.D.=0.30), than in the control group (${\bar{x}}=3.82$; S.D.=0.20) with statistical significance (p<0.001). This research demonstrated an appropriate communication process in behavioral modification to prevent cervical cancer. It can be recommended that this program featuring social marketing and the health belief model be used to promote cervical cancer screening in targeted women and it can be promoted as a guideline for other health services, especially in health promotion and disease prevention.