• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.295-298
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• 2016

Background: Breast cancer is a very common health problem in Iranian women. The HER2-neu gene is a transmembrane receptor tyrosine kinase with homology to members of the EGF receptor family. The aim of this study was to investigate the association between HER2-neu oncogene status with prognostic factors of breast cancer in Kermanshah province, Iran. Materials and Methods: Relationship between HER2-neu and prognostic factors of 130 cases of breast cancer were evaluated during two years in Imam Reza hospital in Kermanshah, Iran. Data were analyzed using descriptive statistics and the T-test and Mann-Whitney U non-parametric test using SPSS 19. Results: The mean age for the patients was $46.0{\pm}8.0years$, all being female. Among the predictive factors for breast cancer were family history, stage of disease, involvement of the lymphovascular system, number of involved lymph nodes in axillaries, grading and hormone receptor status with HER2-neu oncogene had direct correlation and between factors, tumor location, patient age and histological characteristics and HER2-neu oncogene had no significant relationship. We found significant correlation between HER2 with ER and PR and also HER2 with ER, PR negative. Conclusions: HER2-neu is risk factor that can be a good prognostic and also predictive factor. For these reasons, we recommend that it be evaluated for all types of BC.

• 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.

• Environmental Analysis Health and Toxicology
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• v.21 no.1 s.52
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• pp.27-34
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• 2006

Numerous studies reported the significant association between genetic polymorphisms in the vitamin D receptor (VDR) gene and various bone phenotypes such as bone mineral density (BMD) and bone quality, although conflicting results were produced. The objective of this study was to investigate the association between a TaqI RFLP in the VDR gene and calcaneal BMD in Korean vegetarian men, and its interaction with nutrition status as an environmental factor. BUA (broadband ultrasound attenuation), SOS (sound of speed) and stiffness index of the calcaneus were measured using an ultrasound bone densitometer in 266 Korean men (age: $mean{\pm}SD;\;50.9{\pm}12.0$ year), and a TaqI RFLP in the VDR gene analysed by PCR-RFLP method. In total subjects, the distribution of TT, Tt and tt genotypes occurred with frequencies of 90.8%, 8.8% and 0.4%, respectively. There were no significant associations between this polymorphism and osteopenia-osteoporosis or several bone phenotypes in our subjects irrespectively of nutrition status (P>0.05). Therefore, our results suggest that a TaqI RFLP in the vitamin D receptor gene does not contribute to the susceptibility to the calcaneal BMD in Korean men.

• 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.

• Journal of Life Science
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• v.15 no.3 s.70
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• pp.505-512
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• 2005

Excitotoxicity and epileptogenesis have often been associated with glutamate receptor activation. Accumulating evidences indicates that topiramate (TPM), an antiepileptic drug with multiple mechanisms of action has neuroprotective activity. We explored the neuroprotective effect of TPM on the status epilepticus (SE)-induced hippocampal neuronal death. After development of SE by kainite injection (15 mg/Kg), rats were treated with TPM (10mg/kg) for 1 week. The neuronal death was detected by Apop tag in situ detection kit, and the expression levels of glutamate receptors were semi-quantitatively analyzed by immunoblot. Kainate-induced SE caused a significant neuronal death and cell loss in CAI and CA3 regions of hippocampus at 1 week. However, treatment of TPM for 1 week after SE markedly reduced hippocampal neuronal death. The expression of N-methyl-D-aspartate (NMDA) receptor subunit 1, was increased by SE, but was not affected by 1 week treatment of TPM. The expressions of NMDA receptor subunit 2a and 2b were not changed by either SE or TPM. As for ${\alpha}-amino-3-hydroxy-5-methyl-4-isoxazole-propionate$ (AMPA) glutamate receptors (GluR), kainate-induced SE markedly up-regulated GluR1 expression but down-regulated GluR2 expression, leading to increased formation of $Ca^{2+}$ permeable GluR2- lacking AMPA receptors. TPM administration for 1 week attenuated SE-induced expression of both the up-regulation of GluR1 and down-regulation of GluR2, reversing the ratio of GluR1/GluR2 to the control value. In conclusion, TPM protects neuronal cell death against glutamate induced excitotoxicity in kainate-induced SE model, supporting the potential of TPM as a neuroprotective agent.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3897-3901
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• 2016

Background: Breast cancer is by far the most frequent cancer of women (23% of all cancers), ranking second overall when both sexes are considered together. Since there has been change in clinico-pathological factors and treatment profiles for breast cancer patients over the years, the present study to evaluate the change trends in India. Materials and Methods: A detailed analysis was carried out with respect to age, menopausal status, family history, disease stage, surgery performed, histopathology, hormone receptor status, and use of chemotherapy or hormonal therapy. Change in various clinico-pathological factors and treatments of breast cancer cases was recorded and analysed. Results: Mean age at presentation was found to be earlier in 2005-2006 compared with 1997-98 (p value: 0.046). More premenopausal women were diagnosed with breast cancer in 2005-2006 when this was compared with initial years of assessment (p value ${\leq}0.001$). When change in the receptor status was evaluated, we observed that there was a decrease in cases of ER and PR receptor positivity which was significant (p value: 0.007). Over the period of time, more f patients were not offered surgery initially in view of advanced disease when the two time periods were compared (p value: ${\leq}0.001$). There was a significant increase in patients who were initially offered neo-adjuvant chemotherapy in view of advanced disease at presentation (p value: ${\leq}0.001$). There was increasing number of patients who received palliative treatment for symptoms in 2005-2006 when compared to patients treated in 1997-98((p value: ${\leq}0.001$). Conclusions: Changes in mean age at presentation, premenopausal status, and stage at presentation have occurred over the years. More aggressive patterns of disease have become more common with early age at presentation and aggressive biological behaviour with receptor negative tumours.

• Radiation Oncology Journal
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• v.34 no.1
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• pp.1-9
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• 2016

Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

• Journal of Integrative Natural Science
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• v.16 no.3
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• pp.97-102
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• 2023

The gasdermins are a family of recently identified pore-forming effector proteins that cause membrane permeabilization and pyroptosis, a lytic pro-inflammatory type of cell death. A role in the regulation of cell proliferation and/or differentiation is suggested by the differentiation status-specific expression of gasdermin proteins in epithelial tissues. One of the GSDM protein is Gasdermin A (GSDMA), which decreased in stomach and esophageal cancers, suggesting a tumor suppressor role. GSDMA receptor antagonists have been researched as potential treatments for inflammatory diseases and baldness. GSDMA's significance in a wide range of disorders makes it an important therapeutic target. As a result, homology modelling of the GSDMA receptor was undertaken in the current study using the crystal structures of Mus musculus (GSDMA3), Human gasdermin D (GSDMD), and Murine gasdermin D (murine GSDMD). The best model was chosen based on the validation results after 20 models were developed utilising single template-based approaches. The generated structures can be used for further binding site and docking studies in the future.

• Journal of Gastric Cancer
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• v.13 no.3
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• pp.172-178
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• 2013

Purpose: The aims of this study were as follow: 1) to de scribe the expression status of estrogen receptor-${\alpha}$ and -${\beta}$ mRNAs in five gastric carcinoma cell lines; 2) to evaluate in vitro the effects of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of the cell lines. Materials and Methods: Detection of estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNA in five human gastric cancer cell lines (AGS, KATO III, MKN28, MKN45 and MKN74) was made by the reverse transcription-polymerase chain reaction system. To evaluate the effect of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of gastric cancer cell line, the cell lines which expressed both es trogen receptors were chosen and treated with $17{\beta}$-estradiol and estrogen receptor antagonists (methyl-piperidino-pyrazole and pyrazolo [1,5-a] pyrimidine). Cell proliferation was assessed with the methylthiazol tetrazolium test. Results: Estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNAs were expressed in three (KATO III, MKN28 and MKN45) and all of the five gastric cancer cell lines, respectively. At higher concentrations, $17{\beta}$-estradiol inhibited cell growth of MKN28, MKN45 and KATO III cell lines. Neither estrogen receptor-${\alpha}$ nor estrogen receptor-${\beta}$ antagonist blocked the anti-proliferative effect of $17{\beta}$-estradiol. Conclusions: Our results indicate that estrogen receptor-${\beta}$ mRNAs are preferentially expressed in gastric cancers and also imply that hormone therapy rather than estrogen receptor blockers may be a useful strategy for the treatment of estrogen receptor-${\beta}$ positive gastric cancer. Its therapeutic significance in gastric cancer are, however, limited until more evidence of the roles of estrogen receptors in the gastric cancer are accumulated.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10627-10630
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• 2015

Background: Epidermal growth factor receptor (EGFR) mutations play a vital role in the prognosis of patients with lung adenocarcinoma. Such somatic mutations are more common in women who are non-smokers with adenocarcinoma and are of Asian origin. However, to our knowledge, there are few studies that have focused on men. Materials and Methods: One hundred and eighty-four consecutive patients (90 men and 94 women) of resected lung adenocarcinoma were studied retrospectively. Results: EGFR mutations were positive in 48.9% and negative (wild type) in 51.1%. Overall mutation was significant in women (66.0% vs. 32.2%) compared with men (p<0.001). For overall patients, EGFR mutation status was associated with gender, pStage, pT status, lepidic dominant histologic subtype, pure or mixed ground-glass nodule type on computed tomography and smoking status. However, in men, EGFR mutation status was only associated with lepidic dominant histologic subtype and not the other variables. Interestingly, the Brinkman index of men with mutant EGFR also did not differ from that for the wild type ($680.0{\pm}619.3$ vs. $813.1{\pm}552.1$ p=0.1077). Conclusions: The clinical characteristics of men with lung adenocarcinoma related to EGFR mutation are not always similar to that of overall patients. Especially we failed to find the relationship between EGFR mutations and smoking status in men.