• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4209-4214
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• 2013

Background: Breast cancer is among the five most common cancers and ranks first among cancers diagnosed in Iranian women. Screening and treatment of this disease with molecular methods, especially regarding high incidences at early age and advanced stage, is essential. Several genes with altered expression have been identified by cDNA microarray studies in breast cancer, with the Bcl-2 gene indicated as a likely candidate. In this study, we studied Bcl-2 gene expression levels in parallel tumor and non-tumor breast tissues. Materials and Methods: Forty samples including 21 tumor, 16 non tumor (marginal) and 3 benign breast tissues which were all pathologically diagnosed, were subjected to RNA extraction and polyA RT-PCR with the expression level of Bcl-2 quantified using real-time PCR. Results: There is higher expression levels of the Bcl-2 gene in tumor samples compared with marginal samples, but not attaining significance(p>0.05). Bcl-2 expression in 14 (66.7%) of the cases of tumor samples and 9 (56.3%) cases of the marginal samples were positive. Comparison of the expression of the Bcl-2 gene in histological grade showed that a high expression of Bcl-2 was associated with a high histological grade (p<0.41). Conclusions: Our data suggests that dysregulated Bcl-2 gene expression is potentially involved in the pathogenesis of breast cancer. Using gene expression analysis may significantly improve our ability for screening cancer patients and will prove a powerful tool in the diagnosis and prognostic evaluation of the disease whilst aiding the cooperative group trials in the Bcl-2 based therapy project.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4527-4531
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• 2016

Background: PTEN protein is one of the most important tumour suppressor factors which is detectable by immunohistochemistry. The goal of the present study was to investigate the prognostic role of PTEN gene expression in breast cancer patients. Materials and Methods: This descriptive-analytical study was conducted on 100 breast cancer patients referred to Sabzevar hospitals in the north-east of Iran between 2010 and 2011, who were followed up to 2015. PTEN gene expression in tissue samples was determined using specific monoclonal antibodies and data were analyzed using Chi-square test and Fisher's exact test. Patient survival was analyzed after 4 years of follow-up using the Cox regression model. Results: PTEN gene expression was evident in 70 of 100 cnacer samples but was found at high levels in all non-cancer samples. There was an inverse significant relationship between PTEN gene expression and tumour stage or tumour grade (p<0.001). The expression of PTEN in invasive ductal tumours was lower than in non-invasive tumours. There was also an inverse significant relationship between the hazard of death and PTEN gene expression (p<0.001). In addition, there was an inverse significant relationship between tumour stage and hazard of death (p<0.001). Conclusion: These findings indicate that lack of PTEN gene expression can be a sign of a worse prognosis and poor survival in breast cancer cases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5241-5243
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• 2012

Background: Prostate cancer (Pca) is one of the most common complex and polygenic diseases in men. The X-ray repair complementing group 1 gene (XRCC1) is an important candidate in the pathogenesis of Pca. The purpose of this study was to evaluate the association between single nucleotide polymorphisms in the XRCC1 gene and susceptibility to Pca. Materials and Methods: XRCC1 gene polymorphisms and associations with susceptibility to Pca were investigated in 193 prostate patients and 188 cancer-free Chinese men. Results: The c.910A>G variant in the exon9 of XRCC1 gene could be detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods. Significantly increased susceptibility to prostate cancer was noted in the homozygote comparison (GG versus AA: OR=2.95, 95% CI 1.46-5.42, ${\chi}^2$=12.36, P=0.001), heterozygote comparison (AG versus AA: OR=1.76, 95% CI 1.12-2.51, ${\chi}^2$=4.04, P=0.045), dominant model (GG/AG versus AA: OR=1.93, 95% CI 1.19-2.97, ${\chi}^2$=9.12, P=0.003), recessive model (GG versus AG+AA: OR=2.17, 95% CI 1.33-4.06, ${\chi}^2$=8.86, P=0.003) and with allele contrast (G versus A: OR=1.89, 95% CI 1.56-2.42, ${\chi}^2$=14.67, P<0.000). Conclusions: These findings suggest that the c.910A>G polymorphism of the XRCC1 gene is associated with susceptibility to Pca in Chinese men, the G-allele conferring higher risk.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.7.1-7.12
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• 2018

Recent findings from The Cancer Genome Atlas project have provided a comprehensive map of genomic alterations that occur in hepatocellular carcinoma (HCC), including unexpected mutations in apolipoprotein B (APOB). We aimed to determine the clinical significance of this non-oncogenetic mutation in HCC. An Apob gene signature was derived from genes that differed between control mice and mice treated with siRNA specific for Apob (1.5-fold difference; P < 0.005). Human gene expression data were collected from four independent HCC cohorts (n = 941). A prediction model was constructed using Bayesian compound covariate prediction, and the robustness of the APOB gene signature was validated in HCC cohorts. The correlation of the APOB signature with previously validated gene signatures was performed, and network analysis was conducted using ingenuity pathway analysis. APOB inactivation was associated with poor prognosis when the APOB gene signature was applied in all human HCC cohorts. Poor prognosis with APOB inactivation was consistently observed through cross-validation with previously reported gene signatures (NCIP A, HS, high-recurrence SNUR, and high RS subtypes). Knowledge-based gene network analysis using genes that differed between low-APOB and high-APOB groups in all four cohorts revealed that low-APOB activity was associated with upregulation of oncogenic and metastatic regulators, such as HGF, MTIF, ERBB2, FOXM1, and CD44, and inhibition of tumor suppressors, such as TP53 and PTEN. In conclusion, APOB inactivation is associated with poor outcome in patients with HCC, and APOB may play a role in regulating multiple genes involved in HCC development.

• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.280-288
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• 2024

The fusogenic membrane glycoprotein (FMG) derived from the human endogenous retrovirus-W (HERV-W) exhibits fusogenic properties, making it a promising candidate for cancer gene therapy. When cells are transfected with HERV-W FMG, they can fuse with neighboring cells expressing the receptor, resulting in the formation of syncytia. These syncytia eventually undergo cell death within a few days. In addition, it has been observed that an HERV-W env mutant, which is truncated after amino acid 483, displays increased fusogenicity compared to the wild-type HERV-W env. In this study, we observed syncytium formation upon transfection of HeLa and TE671 human cancer cells with plasmids containing the HERV-W 483 gene. To explore the potential of a semi-replication-competent retroviral (s-RCR) vector encoding HERV-W 483 for FMG-mediated cancer gene therapy, we developed two replication-defective retroviral vectors: a gag-pol vector encoding HERV-W 483 (MoMLV-HERV-W 483) and an env vector encoding VSV-G (pCLXSN-VSV-G-EGFP). When MoMLV-HERV-W 483 and pCLXSN-VSV-G-EGFP were co-transfected into HEK293T cells to produce the s-RCR vector, gradual syncytium formation was observed. However, the titers of the s-RCR virus remained consistently low. To enhance gene transfer efficiency, we constructed an RCR vector encoding HERV-W 483 (MoMLV-10A1-HERV-W 483), which demonstrated replication ability in HEK293T cells. Infection of A549 and HT1080 human cancer cell lines with this RCR vector induced syncytium formation and subsequent cell death. Consequently, both the s-RCR vector and RCR encoding HERV-W 483 hold promise as valuable tools for cancer gene therapy.

• Toxicological Research
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• v.19 no.3
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• pp.247-257
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• 2003

Medicine is undergoing a revolution in the understanding of the mechanisms through which disease processes develop. The advent of genetics and molecular biology to oncology not only is providing surrogate predictors of therapy response and survival which are forming the basis for selection among established treatment options, but is providing targets for new directions in therapy as well. Molecular modification of somatic cells for the purposes of protecting the normal cells from the toxicity of cancer chemotherapy, for the sensitization of the tumor cells to therapy and use of conditionally replicating viral vector have been new directions of cancer treatment which have reached the clinical arena. Advances in molecular pharmacology and vector design summarized in this paper may provide solutions to some of the existing problems in the technology of gene transfer therapy. Continued basic research into the biological basis of human disease, systemic studies of the application of these discoveries to therapy and the improvement of vector for gene delivery all combined may result in advances in this important field of therapy over the next few years.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3539-3548
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• 2012

The Nm23 gene is a metastatic suppressor identified in a melanoma cell line and expressed in different tumors where their levels of expression are associated with reduced or increased metastatic potential. Nm23 is one of the over 20 metastasis suppressor genes (MSGs) confirmed in vivo. It is highly conserved from yeast to human, implying a critical developmental function. Tumors with alteration of the p53 gene and reduced expression of the Nm23 gene are more prone to metastasis. Nm23-H1 has 3'-5' exonuclease activity. This review focuses on the role of Nm23 in cancer progression and also a potential novel target for cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4689-4693
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• 2012

Lung cancer is the most common type of cancer and one of the leading causes of death in the world. Genetic factors play an important role in its development. PDCD6, the encoding gene for programmed cell death protein 6, may function as a tumor suppressor gene. Non-small cell lung cancer (NSCLC) contributes about 80% to newly histologically diagnosed lung cancer patients. To explore the relationship between PDCD6 and NSCLC, we examined two single nucleotide polymorphisms(rs3756712 G/T andrs4957014 G/T, both in the intron region) of the PDCD6gene.A hospital-based case-control study was carried out including 302 unrelated NSCLC patients and 306 healthy unrelated subjects. Significantly increased NSCLC risk was found to be associated with the T allele of rs4957014 (P=0.027, OR=0.760, 95%CI=0.596-0.970). The genotype and allele frequencies of rs3756712 did not shown any significant difference between NSCLC group and controls (P=0.327, OR=0.879, 95%CI=0.679-1.137). In conclusion, we firstly demonstrated the association between the PDCD6 gene and risk of NSCLC in a Chinese Han population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2833-2836
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• 2012

Aim: Gastric cancer is the third most frequent cause of cancer mortality worldwide. In Iran, it is one of the leading causes at the national level. Localized at chromosome 8q22, the human MTDH gene has been reported to be over-expressed in a spectrum of malignancies. However, since there is a lack of data concerning with expression in gastric cancer at the transcriptional level, in this study we evaluated MTDH expression in Iranian cases. Methods: Totally, thirty paired gastric samples were examined by quantitative real-time RT-PCR. Results: Although the mRNA expression was significantly elevated in 46.6% of the examined tumor tissues; its expression was low in others (36.6%). Moreover, there was only a marginal statistical difference between the MTDH gene expression of all tumor specimens compared to their paired non-tumor ones and no statistically significant association with the grades and types of the tumors. Conclusion: Taken together, our results demonstrated that expression of MTDH at the transcriptional level may be increased in gastric cancer tissue samples but with considerable heterogeneity. Due to this, it may have the potential to be used as a target for diagnostic/therapeutic purposes only in a subset of patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.10009-10013
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• 2014

Background: Vitamin D receptor (VDR) gene has been a subject of extensive pharmacogenetic research recently. Association studies between different types of cancers including prostate cancer (PCa) and VDR gene polymorphism have also been conducted. The objective of this study was to find possible associations between PCa and VDR gene polymorphisms in the Pakistani population. Materials and Methods: A total of 162 subjects, including prostate cancer patients and controls, were genotyped for Apa I, Taq I and Fok I polymorphisms in the VDR gene using allele specific PCR, PCR-RFLP and direct DNA sequencing. Allelic frequencies were tested for Hardy-Weinberg equilibrium and associations between the genetic markers and PCa were calculated using logistic regression. Results: Apa I CC genotype was found to have strongest association with PCa risk, and "A" genotype was found to have protective effect. Fok I and Taq I did not have appreciable levels of association with PCa, although Taq I "TC" heterozygotes seemed to have some protective effect. Similarly the "C" allele of Fok I also seemed to have protective effect. Conclusions: To our knowledge, this is the first report showing association between VDR gene polymorphisms and PCa in Pakistan. Our findings may be somewhat skewed because of small sample size and tendency of consanguineous marriages in Pakistani society; nevertheless, it shows the trend of association and protective effects of certain VDR gene polymorphisms against PCa.