Genetics and Molecular Biology Research Unit UPGEM

São José do Rio Preto, Brazil

Genetics and Molecular Biology Research Unit UPGEM

São José do Rio Preto, Brazil

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Ruiz M.T.,Genetics and Molecular Biology Research Unit UPGEM | Ruiz M.T.,Federal University of Triângulo Mineiro | Galbiatti A.L.S.,Genetics and Molecular Biology Research Unit UPGEM | Pavarino E.C.,Genetics and Molecular Biology Research Unit UPGEM | Goloni-Bertollo E.M.,Genetics and Molecular Biology Research Unit UPGEM
Molecular Biology Reports | Year: 2012

The KiSS-1 metastasis-suppressor gene (KiSS-1) product (metastin, kisspeptin) is reported to act after binding with the natural ligand of aG-protein coupled receptor and this gene product inhibits chemotaxis, invasion, and metastasis of cells. The aim of this study was to evaluate the Q36R polymorphism of KiSS-1 in patients with head and neck cancer and to compare the results with healthy individuals and its association with clinicopathological parameters. Gender, age, smoking and alcohol consumption were analyzed for 744 individual (252 head and neck cancer patients and in 522 control individuals). The molecular analysis of these individuals was made after extraction of genomic DNA using the SSCP-PCR technique. This study did not reveal any significant differences in genotype frequencies between healthy individuals and patients with head and neck cancer orwith the clinical parameters. This study showed an increase frequency of the Q36R polymorphism in pharyngeal cancer. © Springer Science+Business Media B.V. 2011.


Galbiatti A.L.S.,Genetics and Molecular Biology Research Unit UPGEM | Ruiz M.T.,Genetics and Molecular Biology Research Unit UPGEM | Rezende Pinto D.,Genetics and Molecular Biology Research Unit UPGEM | Pavarino-Bertelli E.C.,Genetics and Molecular Biology Research Unit UPGEM | Goloni-Bertollo E.M.,Genetics and Molecular Biology Research Unit UPGEM
Molecular Biology Reports | Year: 2011

Reduced folate carrier is an essential folate transporter and the A80G polymorphism in reduced folate carrier 1 gene (rs1051266) has been shown to be associated with alterations in folate metabolism and consequently cancer development. We evaluated the association of this polymorphism with head and neck squamous cell carcinoma risk in a case-control study of 322 head and neck carcinoma patients and 531 individuals without cancer in a Brazilian population and association of this polymorphism with clinical histopathological parameters, and gender and lifestyle factors. The PCR-RFLP technique was used to genotype the polymorphism and multiple logistic regression was used for comparation between the groups and for interaction between the polymorphism and risk factors and clinical histopathological parameters. We observed association between the RFC1 A80G polymorphism and the risk of this disease. Male gender, tobacco habit and RFC1 AG or GG genotypes may be predictors of this disease (P < 0.05). The genotype, 80AG or GG was associated with for >50 years, male gender and non alcohol consumption (P ≤ 0.05). The polymorphism did not show any association with the primary site, aggressiveness, lymph node involvement or extension of the tumor. In conclusion tobacco and male gender are associated with etiology of this disease and our data provide evidence that supports an association between the RFC1 A80G polymorphism and head and neck squamous cell carcinoma risk, male gender, alcohol non consumption and age over 50 years. However, further studies of folate and plasma concentrations may contribute to the better understanding of the factors involved in the head and neck squamous cell carcinoma etiology. © 2010 Springer Science+Business Media B.V.


Galbiatti A.L.S.,Genetics and Molecular Biology Research Unit UPGEM | Ruiz M.T.,Genetics and Molecular Biology Research Unit UPGEM | Pavarino-Bertelli E.C.,Genetics and Molecular Biology Research Unit UPGEM | Goloni-Bertollo E.M.,Genetics and Molecular Biology Research Unit UPGEM
Archives of Medical Science | Year: 2010

Introduction: Susceptibility to head and neck squamous cell carcinoma may be modified by functional polymorphisms in genes involved in the folate pathway, such as cystathionine beta-synthase (CBS). The CBS 844ins68 polymorphism is associated with DNA methylation changes and cancer development. Material and methods: A case-control retrospective study was conducted in 322 patients with head and neck squamous cell carcinoma and in 531 control subjects without cancer. The polymerase chain reaction-restriction fragment length polymorphism technique was used to genotype the polymorphism. For statistical analysis, χ2 test was conducted to examine whether the genotypic frequency of CBS 844ins68 was in Hardy-Weinberg equilibrium and multiple logistic regression was used for comparisons between groups, and for interactions between the polymorphism and risk factors and clinical histopathological parameters. Results: No significant difference in CBS 844ins68 genotypic distribution was observed between the groups. Age > 50 years, male gender and tobacco consumption were predictors of the disease with increased risk of 7.89 (95% CI: 5.56-11.21), 2.49 (95% CI: 1.72-3.62), 6.44 (95% CI: 4.63-8.96) and 2.29 times (95% CI: 1.71-3.06) respectively. There was no association between the distribution of the CBS 844ins68 genotype and risk factors for this disease. According to clinical histopathological parameters, CBS 884ins68 polymorphism presented high frequency in oral cavity (p < 0.05) and patients with the polymorphism presented less survival time (p < 0.05). Conclusions: We concluded that the CBS 844ins68 polymorphism is not associated with HNSCC risk and there is increased risk of this disease in male gender individuals smokers aged over 50 years. In adittion, the polymorphism is more frequent in patients with oral cavity as primary site and in patients with less survival time. Copyright © 2010 Termedia & Banach.


Biselli P.M.,Genetics and Molecular Biology Research Unit UPGEM | Guerzoni A.R.,Genetics and Molecular Biology Research Unit UPGEM | Eberlin M.N.,University of Campinas | Haddad R.,University of Campinas | And 4 more authors.
Journal of Thrombosis and Thrombolysis | Year: 2010

Objectives Alterations in the enzymes involved in homocysteine (Hcy) metabolism or vitamin deficiency could play a role in coronary artery disease (CAD) development. This study investigated the influence of MTHFR and MTR gene polymorphisms, plasma folate and MMA on Hcy concentrations and CAD development. MMA and folate concentrations were also investigated according to the polymorphisms. Methods Two hundred and eighty-three unrelated Caucasian individuals undergoing coronary angiography (175 with CAD and 108 non-CAD) were assessed in a case-control study. Plasma Hcy and MMA were measured by liquid chromatography/tandem mass spectrometry. Plasma folate was measured by competitive immunoassay. Dietary intake was evaluated using a nutritional questionnaire. Polymorphisms MTHFR and MTR were investigated by polymerase chain reaction (PCR) followed by enzyme digestion or allele-specific PCR. Results Hcy mean concentrations were higher in CAD patients compared to controls, but below statistical significance (P = 0.246). Increased MMA mean concentrations were frequently observed in the CAD group (P = 0.048). Individuals with MMA concentrations >0.5 μmol/l (vitamin B12 deficiency) were found only in the CAD group (P = 0.004). A positive correlation between MMA and Hcy mean concentrations was observed in both groups, CAD (P = 0.001) and non-CAD (P = 0.020). MMA mean concentrations were significantly higher in patients with hyperhomocysteinemia in both groups, CAD and non-CAD (P = 0.0063 and P = 0.013, respectively). Folate mean concentration was significantly lower in carriers of the wild-type MTHFR 1298AA genotype (P = 0.010). Conclusion Our results suggest a correlation between the MTHFR A1298C polymorphism and plasma folate concentration. Vitamin B12 deficiency, reflected by increased MMA concentration, is an important risk factor for the development both of hyperhomocysteinemia and CAD. © 2009 Springer Science+Business Media, LLC.


Galbiatti-Dias A.L.S.,Genetics and Molecular Biology Research Unit UPGEM | Pavarino E.C.,Genetics and Molecular Biology Research Unit UPGEM | Kawasaki-Oyama R.S.,Genetics and Molecular Biology Research Unit UPGEM | Maniglia J.V.,Genetics and Molecular Biology Research Unit UPGEM | And 2 more authors.
Cellular and Molecular Biology | Year: 2015

Head and neck cancer (HNC) is a multifaceted and genomically complex disease and rapidly emerging preclinical and clinical studies have provided a broader landscape of signaling. It is being realized that Intra-Tumor heterogeneity, genetic and epigenetic mutations considerably challenge wide ranging therapeutics and patients frequently develop locoregional recurrences, second primary tumours and distant metastases. Using High-Throughput technologies, it has been revealed that existence of different subpopulations of cells within tumor mass with different phenotypic and functional properties with distinct Tumour-Initiating potential is responsible to HNC resistance. In light of accumulating evidence reported in recent years, it is now known that different intracellular proteins and cell surface markers have been used to study CSCs. This review provides an overview of CSC biomarkers in HNC treatment and their potential as therapeutic targets in improving the diagnosis, prognosis and treatment of HNC patients for new therapeutic strategies with information about estimation of prognosis and treatment decision. Further studies regarding biomarkers are necessary to determine the specific role of CSCs in HNC which could be useful in development of new therapeutic strategies to eliminate CSCs and maximize clinical outcome. Furthermore, CD44 still need more research in HNC once the studies show contradictions. Studies using lineage tracing and deep sequencing will provide a comprehensive understanding of CSC model and extent to which it is accountable for resistance against therapeutics and carcinogenesis. © 2015.


Biselli-Chicote P.M.,Genetics and Molecular Biology Research Unit UPGEM | Oliveira A.R.C.P.,Genetics and Molecular Biology Research Unit UPGEM | Pavarino E.C.,Genetics and Molecular Biology Research Unit UPGEM | Goloni-Bertollo E.M.,Genetics and Molecular Biology Research Unit UPGEM
Journal of Cancer Research and Clinical Oncology | Year: 2012

Tumor growth and progression depend on angiogenesis, a process of new blood vessels formation from a preexisting vascular endothelium. Tumors promote angiogenesis by secreting or activating angiogenic factors that stimulate endothelial proliferation and migration and capillary morphogenesis. The newly formed blood vessels provide nutrients and oxygen to the tumor, increasing its growth. Thus, angiogenesis plays a key role in cancer progression and development of metastases. An important growth factor that promotes angiogenesis and participates in a variety of physiological and pathological processes is the vascular endothelial growth factor (VEGF-A or VEGF). Overexpression of VEGF results in increased angiogenesis in normal and pathological conditions. The existence of an alternative site of splicing at the 30 untranslated region of the mRNA results in the expression of isoforms with a C-terminal region which are downregulated in tumors and may have differential inhibitory effects. This suggests that control of splicing can be an important regulatory mechanism of angiogenesis in cancer. © Springer-Verlag 2011.


Galbiatti A.L.S.,Genetics and Molecular Biology Research Unit UPGEM | Castro R.,Genetics and Molecular Biology Research Unit UPGEM | Caldas H.C.,Laboratory of Experimental Immunology and Transplantation LITEX | Padovani J.A.,Sao Jose Do Rio Preto Medical School FAMERP | And 2 more authors.
Tumor Biology | Year: 2013

Inter-individual variations to methotrexate (MTX) outcome have been attributed to different expression profiles of genes related to folate metabolism. To elucidate the mechanisms of variations to MTX outcome, we investigated MTHFR, DHFR, TYMS, and SLC19A1 gene expression profiles by quantifying the mRNA level of the genes involved in folate metabolism to MTX response in laryngeal cancer cell line (HEP-2). For this, three different concentrations of MTX (0.25, 25, and 75 μmol) were added separately in HEP-2 cell line for 24 h at 37 C. Apoptotis quantification was evaluated with fluorescein isothiocyanate-labeled Bcl-2 by flow cytometry. Real-time quantitative PCR technique was performed by quantification of gene expression with TaqMan® Gene Expression Assay. ANOVA and Bonferroni's post hoc tests were utilized for statistical analysis. The results showed that the numbers of apoptotic HEP-2 cells with 0.25, 25.0, and 75.0 μmol of MTX were 14.57, 77.54, and 91.58 %, respectively. We found that the expression levels for MTHFR, DHFR, TYMS, and SLC19A1 genes were increased in cells with 75.0 μmol of MTX (p < 0.05). Moreover, SLC19A1 gene presented lower expression in cells treated with 0.25 μmol of MTX (p < 0.05). In conclusion, our data suggest that MTHFR, DHFR, TYMS, and SLC19A1 genes present increased expression after the highest application of MTX dose in laryngeal cancer cell line. Furthermore, SLC19A1 gene also presents decreased expression after the lowest application of MTX dose in laryngeal cancer cell line. Significant alterations of expression of these studied genes in cell culture model may give support for studies in clinical practice and predict interesting and often novel mechanisms of resistance of MTX chemotherapy. © 2013 International Society of Oncology and BioMarkers (ISOBM).


Cury N.M.,Genetics and Molecular Biology Research Unit UPGEM | Russo A.,Genetics and Molecular Biology Research Unit UPGEM | Galbiatti A.L.S.,Genetics and Molecular Biology Research Unit UPGEM | Ruiz M.T.,Genetics and Molecular Biology Research Unit UPGEM | And 4 more authors.
Molecular Biology Reports | Year: 2012

Polymorphisms in genes that encode P450 cytochrome enzymes may increase carcinogen activation or decrease their inactivation and consequently, promote the development of cancer. The aims of this study were to identify the MspI-CYP1A1, PstI-CYP2E1 and DraI-CYP2E1 polymorphisms in patients with head and neck cancer and to compare with individuals without cancer; to evaluate the association of these polymorphisms with risk factors and clinical histopathological parameters. In the study group, 313 patients were evaluated for CYP1A1, 217 for CYP2E1 (PstI) and 211 for CYP2E1 (DraI) and in the control group 417, 334 and 374 individuals, respectively. Molecular analysis was performed by PCR-RFLP technique, and chi-square and multiple logistic regression tests were used for statistical analysis. The result of analysis regarding individuals evaluated for CYP1A1 (MspI) showed that age (OR: 8.15; 95% CI 5.57-11.92) and smoking (OR: 5.37; 95% CI 3.52-8.21) were predictors for the disease; for the CYP2E1 (PstI and DraI), there were associations with age (PstI-OR: 9.10; 95% CI 5.86-14.14/ DraI-OR: 8.07; 95% CI 5.12-12.72), smoking (PstI-OR: 4.10; 95% CI 2.44-6.89/DraI-OR: 5.73; 95% CI 3.34-9.82), alcohol (PstI-OR: 1.93; 95% CI 1.18-3.16/ DraI-OR: 1.69; 95% CI 1.02-2.81), respectively, with disease development. CYP2E1 (PstI) was less frequent in patient group (OR: 0.48; 95% CI 0.23-0.98). Regarding clinical histopathological parameters, CYP1A1 polymorphism was less frequent in the larynx primary anatomic site (OR = 0.45; 95% CI = 0.28-0.73; P = 0.014). In conclusion, we confirm that age, smoking and alcohol consumption are risk factors for this disease and the polymorphisms investigated have no association with the development of head and neck cancer. © 2011 Springer Science+Business Media B.V.


Batista Da Silva L.M.R.,Genetics and Molecular Biology Research Unit UPGEM | Silva Galbiatti A.L.,Genetics and Molecular Biology Research Unit UPGEM | Ruiz M.T.,Genetics and Molecular Biology Research Unit UPGEM | Raposo L.S.,Sao Jose Do Rio Preto Medical School FAMERP | And 3 more authors.
Molecular Biology Reports | Year: 2012

Alterations in folate metabolism may contribute to the process of carcinogenesis by influencing DNA methylation and genomic stability. Polymorphisms in genes encoding enzymes involved in this pathway may alter enzyme activity and consequently interfere in concentrations of homocysteine and S-adenosylmethionine that are important for DNA synthesis and cellular meth-ylation reactions. The objectives were to investigate MTHFD1 G1958A, BHMT G742A, TC2 C776G and TC2 A67G polymorphisms involved in folate metabolism on head and neck cancer risk and the association between these polymorphisms with risk factors. Polymorphisms were investigated in 762 individuals (272 patients and 490 controls) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Real Time-PCR. Chi-square and Multiple logistic regression were used for the statistical analysis. Multiple logistic regression showed that tobacco and male gender were predictors for the disease (P < 0.05). Hardy-Weinberg equilibrium showed that the genotypic distributions were in equilibrium for both groups in all polymorphisms studied. The BHMT 742GA or AA genotypes associated with tobacco consumption (P = 0.016) increase the risk for head and neck squamous cell carcinoma (HNSCC). The present study suggests that BHMT 742GA polymorphism associated to tobacco modulate HNSCC risk. However, further investigation of gene-gene interactions in folate metabolism and studies in different populations are needed to investigate polymorphisms and HNSCC risk. © 2011 Springer Science+Business Media B.V.


PubMed | Genetics and Molecular Biology Research Unit UPGEM
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2013

Inter-individual variations to methotrexate (MTX) outcome have been attributed to different expression profiles of genes related to folate metabolism. To elucidate the mechanisms of variations to MTX outcome, we investigated MTHFR, DHFR, TYMS, and SLC19A1 gene expression profiles by quantifying the mRNA level of the genes involved in folate metabolism to MTX response in laryngeal cancer cell line (HEP-2). For this, three different concentrations of MTX (0.25, 25, and 75 mol) were added separately in HEP-2 cell line for 24 h at 37 C. Apoptotis quantification was evaluated with fluorescein isothiocyanate-labeled Bcl-2 by flow cytometry. Real-time quantitative PCR technique was performed by quantification of gene expression with TaqMan Gene Expression Assay. ANOVA and Bonferronis post hoc tests were utilized for statistical analysis. The results showed that the numbers of apoptotic HEP-2 cells with 0.25, 25.0, and 75.0 mol of MTX were 14.57, 77.54, and 91.58%, respectively. We found that the expression levels for MTHFR, DHFR, TYMS, and SLC19A1 genes were increased in cells with 75.0 mol of MTX (p < 0.05). Moreover, SLC19A1 gene presented lower expression in cells treated with 0.25 mol of MTX (p < 0.05). In conclusion, our data suggest that MTHFR, DHFR, TYMS, and SLC19A1 genes present increased expression after the highest application of MTX dose in laryngeal cancer cell line. Furthermore, SLC19A1 gene also presents decreased expression after the lowest application of MTX dose in laryngeal cancer cell line. Significant alterations of expression of these studied genes in cell culture model may give support for studies in clinical practice and predict interesting and often novel mechanisms of resistance of MTX chemotherapy.

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