• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1707-1713
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• 2015

Eighty six cases of invasive ductal breast carcinomas were utilized to investigate GSTP1 polymorphisms in certain immunohistochemistry (IHC) subtypes of breast cancer with respect to ER, PR and HER2 expression. The frequency of wild allele homozygote, heterozygote and variant allele homozygote genotypes were 46.5%, 52.3% and 1.16% respectively; Whereas 54.3% of the control subjects were GSTP1 wild type allele homozygous, 40.0% were heterozygous and 5.71% mutant allele homozygous. There was dramatic inverted relation between positive IHC ER staining and increasing grade of tumors in general (100%, 88.6%, 40.4%) and especially among tumors with heterozygote genotype of GSTP1 (70%, 35.4%, 22.7). There was increase in positive IHC HER2 staining consistent with higher grades in general (20%, 29.6%, 50.0%), especially among tumors with GSTP1 wild allele homozygote genotype (5.0%, 9.1%, 31.8%). A remarkable reverse relation was also observed between the fraction of IHC hormone receptor phenotype ER+/PR+/ HER2- and increased grade of tumors (60.0%, 45.5%, and 27.3%) especially among tumors with GSTP1 heterozygote genotype, and a similar link was noted regarding ER+/PR-/ HER2- and tumor grade. There was increase in frequency of ER-/PR-/ HER2- (0.0%, 6.8%, and 18.2%) and ER-/PR-/ HER2+ (0.0%, 4.54%, and 40.9%) consistent with the higher grades of tumors in general and especially GSTP1 heterozygote genotype tumors. As a conclusion, there is no correlation between GSTP1 polymorphism and increased risk of breast cancer i.e. the mutant allele is randomly distributed in cancer and control cases. However, there is a link between GSTP1 genotypes and hormone receptor expression status and certain phenotypes of breast cancer, which may have clinical importance.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.807-812
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• 2014

Background: The clinical course of the neoplasm may vary due to both patient and tumor cell characteristics. Aim: The aim of this study was to research the influence of certain clinical and pathological features on the prognosis of early stage breast cancer. Materials and Methods: This study included 117 women that were treated and followed-up in between the years 2001-2011. The demographic, clinical and histopathological features of the cases were reviewed retrospectively. Statistical analysis: In categorical comparisons between groups, cross-tab statistics were provided and significance levels were estimated using chi-square test. Cox regression analysis, Pearson and Spearman correlation tests, and the Kaplan-Meier test were also used. Results: With an average of 35-months follow-up, the mean disease-free survival of patients was 91 months and the mean overall survival time was 132 months. In the whole study group, the disease-free survival rates were 88, 84, 83 and 52%, while the overall survival rates 95, 94, 83, and 83% within the first, third, fifth and tenth years, respectively. The disease-free and overall survival rates were decreased with increasing tumor grades, though this was not statistically significant. The presence of lymphovascular invasion, positive staining with Ki67 and postmenopausal status were associated with shorter disease-free and overall survival times. In multivariate analysis, only age and Her2/neu receptor status influenced the prognosis significantly. Conclusions: In parallel to clinical, histopathological, and immunohistochemical prognostic features in breast cancer, in this study positive Her2/neu receptor status, a previously accepted poor prognostic factor, was found to have positive influence after trastuzumab treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6311-6318
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• 2012

Background: HER2/neu overexpression due to gene amplification is an important factor in breast cancer, modifying the sensitivity to anti-HER2 monoclonal antibody therapy. The clinical significance of HER2 expression in non small cell lung carcinoma (NSCLC) is currently under evaluation. The tumor suppressor gene PTEN negatively regulates the HER2/PI3K/Akt signalling pathway. The purpose of this study was to evaluate the role of simultaneous alteration in HER2 and PTEN protein expression in relation to biological behaviour of NSCLCs. Materials and Methods: Protein expression was determined by immunohistochemistry in sixty-one (n=61) NSCLC cases along with CISH for HER2 gene analysis and detection of chromosome 17 aneuploidy. Patients were followed-up for a period of 34 to 41 months after surgery. Results: HER2 overexpression (2+/3+score) was detected in 17 (27.9%) patients while loss of PTEN expression was observed in 24 (39.3%) cases, low expression in 29 (47.6%) and overexpression in 8 (13.1%). Simultaneous HER2 overexpression and PTEN low/loss of expression were correlated with metastasis (71.4% vs 36.2% p=0.03). Analysis in the subgroup of 22 patients of pTNM stage III with lymph node status N1 or N2 revealed that there was a relationship between the number of positive regional lymph node groups and simultaneous deregulation of the two genes (p=0.04). Multivariate analysis determined that HER2 overexpression was associated with an increasing risk of developing metastases (OR: 4.3; 95%CI: 1.2-15.9; p: 0.03) while PTEN overexpression was associated with lower risk (OR: 0.1; 95%CI: 0.1, 1.0; p: 0.05). Conclusions: Simultaneous HER2/PTEN deregulation is a significant genetic event that leads to a more aggressive phenotype of NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7671-7674
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• 2015

Background: Overexpression of HER2-neu has been reported in many epithelial malignancies, including cancers of the breast, ovaries, lungs, prostate, bladder, pancreas, colorectum and stomach as well as osteosarcomas. The aim of this study was evaluation of expression of HER2-neu immunohistochemistry (IHC) status and clinicopathologic features in a series of colonic adenocarcinomas. Materials and Methods: In this descriptive and analytical study, we surveyed 211 samples of colon adenocarcinoma from 182 patients (86.3%) undergoing total or partial colectomy and 29 (7.13%) with biopsies by colonoscopy. A sufficient sample size was obtained from all cases and the slides were stained with hematoxylin and eosin and also by IHC (HER2) staining. Results: The mean age for the patients at diagnosis was 57.9 years (range, 15-88 years). One hundred and twenty one patients (57.3%) were male. Of all patients, 201 samples (95.3%) were conventional adenocarcinomas (159, 29 and 13 cases were well, moderately and poorly differentiated, respectively) and 10 (4.7%) were mucinous type. Out of 211 cases, 171 were checked for lymph nodes metastasis and 64 were positive. There is a correlation between HER2 scores and differentiation, most score 3 cases being well differentiated (P<0.05). Conclusions: In patients with advanced colon cancer, surgery alone is not curative and other forms of therapy may be required to prolong patient survival. HER2 overexpression was found in some cases and this could be a guideline to new adjuvant therapy for these patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6397-6401
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• 2012

Background: No factor has thus far been identified to predict the efficacy of bevacizumab therapy for colorectal cancer. We here therefore studied PTEN, VEGF, HER2 and p53 by immunohistochemistry as possible prognostic and predictive factors. Materials and Methods: A total of 34 retrospectively collected tumor samples were evaluated, all from patients receiving bevacizumab-based regimens. VEGF-A, PTEN, HER2, p53 were assessed and data was compared with clinicopathologic characteristics of patients and the bevacizumab response rate. Results: In this study, the median age of the 34 metastatic colorectal cancer patients was 55.5 (24-75), twelve (35.3%) being women and 22 (64.7%) men. PTEN, VEGF, HER2, p53 expressions were compared with bevacizumab response and other chacteristics of disease. Statistical significant differences were not found between bevacizumab response rates and different expression levels of VEGF, PTEN, HER2 and p53 (respectively p=0.256, p=0.832, p=0.189, p=0.131). However, a survival difference was noted in the VEGF expression negative group (median OS:55 months; 95%CI, 22-88 months) (p=0.01). There was no statistically significant OS difference in other groups (PTEN p=0.6, HER2 p=0.189, p53 p=0.13). Conclusions: We did not find any predictive factor for BV therapy in our study. VEGF negative expression could be an important prognostic factor in metastatic colorectal carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7651-7656
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• 2013

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

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1261-1264
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• 2016

Background: In breast cancer (BC), it has been suggested that nuclear overexpression of p53 protein might be an indicator of poor prognosis. The aim of the current study was to evaluate the expression of p53 BC in Kurdish women from the West of Iran and its correlation with other clinicopathology figures. Materials and Methods: In the present retrospective study, 231 patients were investigated for estrogen receptor (ER) and progesterone receptor (PR) positivity, defined as ${\geq}10%$ positive tumor cells with nuclear staining. A binary logistic regression model was selected using Akaike Information Criteria (AIC) in stepwise selection for determination of important factors. Results: ER, PR, the human epidermal growth factor receptor 2 (HER2) and p53 were positive in 58.4%, 55.4%, 59.7% and 45% of cases, respectively. Ki67 index was divided into two groups: 54.5% had Ki67<20% and 45.5% had Ki67 ${\geq}20%$. Of 214 patients, 137(64%) had lymph node metastasis and of 186 patients, 122(65.6%) had vascular invasion. Binary logistic regression analysis showed that there was inverse significant correlation between lymph node metastasis (P=0.008, OR 0.120 and 95%CI 0.025-0.574), ER status (P=0.006, OR 0.080, 95%CI 0.014-0.477) and a direct correlation between HER2 (P=005, OR 3.047, 95%CI 1.407-6.599) with the expression of p53. Conclusions: As in a number of studies, expression of p53 had a inverse correlation with lymph node metastasis and ER status and also a direct correlation with HER2 status. Also, p53-positivity is more likely in triple negative BC compared to other subtypes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4959-4964
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• 2015

Background: To assess the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor-2 (HER2) neu receptor in breast cancer and their associations with various clinicopathological characteristics. Materials and Methods: This is a retrospective analysis of women who presented with primary, unilateral breast cancer in the Department of Medical Oncology at Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India during the period from January 2008 to December 2011. Data were retrieved from the medical records of the hospital including both early and locally advanced cancer cases. ER, PgR and HER2neu expression in these patients was assessed and triple negative patients were identified. Associations of triple negative and non-triple negative groups with clinicopathological characteristics were also evaluated. Results: A total of 1,284 women (mean age 52.1 years, 41.9% premenopausal) were included in the analysis. Hormone receptor positivity (ER and/or PgR) was seen in 63.4% patients, while 23.8% of tumors were triple negative. Only 23.0% were HER2 positive. Around 10.0% of tumors were both ER and HER2 positive. ER and PgR positivity was significantly associated with negative HER2 status (p-value <0.0001). Younger age, premenopausal status, higher tumor grade, lymph node negativity, advanced cancer stage, and type of tumor were strongly associated with triple negativity. Significantly, a smaller proportion of women had ductal carcinoma in situ in the triple negative group compared with the non-triple negative group (35.6% versus 60.8%, p-value<0.01). Conclusions: The present analysis is one of the largest studies from India. The majority of the Indian breast cancer patients seen in our hospital present with ER and PgR positive tumors. The triple negative patients tended to be younger, premenopausal, and were associated with higher tumor grades, negative lymph nodes status and lower frequency of ductal carcinoma in situ.

• Science of Emotion and Sensibility
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• v.21 no.2
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• pp.43-60
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• 2018

The primary goal of this study is to investigate the effects of individual's subjective social status on meaning of work. We hypothesized that individual's subjective social status, defined as the respect and influence an individual has at her/his workplace, would promote meaning of work. Further, we hypothesized that individual's subjective social status would be more highly associated with meaning of work based on her/his occupation's subjective social status. Using two experimental studies, we found that individual's subjective social status increased meaning of work in American (Experiment 1) and South Korean working adults (Experiment 2). Participant's meaning of work was more influenced by individual subjective social status than occupation subjective social status (Experiment 1). Also, the results from Experiment 2 indicated that objective social status within an organization (i.e., rank) moderated the effects of individual subjective social status on meaning of work, such that the beneficial effects of individual subjective social status on meaning of work were found only for participants with low objective social status. In contrast, meaning of work in participants with high objective social status did not vary depending on subjective social status. We discussed the implications of these results, study limitations, and directions for future research.

• Journal of Nutrition and Health
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• v.26 no.7
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• pp.867-886
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• 1993

Vitamin B-6 status parameters of mothers were assessed in relation to th condition of the infant at birth and during the neonatal period. Parameters were assessed at birth and then weekly in 18 mother-infant pairs during the neonatal period ; mothers were supplemented postnatally with 2 or 27 mg PN-HCI/d. Vitamin B-6 inadequacy in the 2mg supplemented group was suggested by the vitamin status parameters. Mothers whose infants had unsatisfactory Apgar scores at 5min after birth(<7) had lower vitamin B-6 status parameters than mothers whose infants were scored satisfactory. Also, infants who scored unsatisfactory at birth and whose mothers were supplemented with the low level of PN had significantly lower vitamin B-6 status parameters at 7 days of age than infants who scored satisfactory. Infants scored unsatisfactory showed some beneficial effects in both vitamin B-6 status and growth associated with the higher level of maternal postnatal vitamin B-6 supplement. In summary, the mother's prenatal and postnatal vitamin B-6 intake were significantly related to the condition of her infant at birth and during the neonatal period, respectively.