RESUMO
INTRODUCTION: TP53 gene is the most frequently altered tumor suppressor gene in breast cancer. It has been observed that MDM2 plays a central role in regulating the TP53 pathway. This study aimed to investigate the role of TP53 Arg72Pro and MDM2 T309G polymorphisms in breast cancer patients. MATERIAL AND METHOD: The TP53 (Arg72Pro) and MDM2 (T309G) polymorphisms were studied in a hospital-based case control study by AS-PCR in 100 breast cancer patients and 100 healthy control subjects. RESULTS: It was observed that TP53 Arg72Pro polymorphism was significantly associated with breast cancer (χ (2) = 9.92, p = 0.007). A significantly increased breast cancer risk was associated with the Proline allele [odds ratio 1.84 (95 % CI: 1.22-2.77), risk ratio 1.34 (95 % CI: 1.11-1.63), p value 0.003], HER2/neu status (p = 0.01) and distant metastasis (p = 0.05). On the other hand, we have found a significant correlation between MDM2 (T309G) polymorphism with HER2/neu status (χ (2) = 11.14, p = 0.003) and distant metastasis (p value = 0.04). CONCLUSION: Our finding suggests that TP53 (Arg72Pro) polymorphism may play a significant role as risk factor for breast cancer in north Indian breast cancer patients. While MDM2 (T309G) polymorphism may not be directly associated with the risk of breast cancer occurrence in the same population, but it may play role in disease progression by triggering TP53.
Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Genes p53/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-mdm2/genética , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: In India, Epithelial ovarian cancer has emerged as one of the most common malignancies affecting women. Tumor protein 53 (TP53) induces expression of the B cell lymphoma 2-associated X protein (BAX) gene by directly binding to the TP53-binding element in the BAX promoter. Therefore, we hypothesized that single-nucleotide polymorphism of BAX promoter -248G>A and TP53 72Arg>Pro gene may jointly contribute to ovarian cancer risk. OBJECTIVES: This study aimed at exploring the association of BAX promoter -248G>A and TP53 72Arg>Pro gene polymorphism with risk of developing EOC and its clinicopathological features and to evaluate gene-gene interaction of these two polymorphisms with risk of developing EOC. MATERIALS: The study was conducted on 70 Epithelial ovarian cancer patients and 70 healthy controls. Genotyping of p53 codon 72 and BAX promoter gene was examined by ASO-PCR and PICA-PCR, respectively. Odds ratios and 95 % confidence intervals were calculated. RESULTS: We found an increased cancer risk associated with the BAX AA (ORs = 4.1, 95 %, CI = 1.23-13.97) genotype. An increased risk was also associated with the TP53 Pro/Pro (OR = 4.4, 95 % CI = 1.40-13.99) and Arg/Pro genotype (OR = 2.3, 95 % CI = 1.13-4.86). The gene-gene interaction of these polymorphisms increased EOC risk in a more than additive manner (ORs for the presence of both BAX AA and TP53 Arg/Pro genotypes = 8.7, 95 % CI = 1.66-45.48). BAX GG genotype was associated with adverse staging of cancer (P = 0.01). CONCLUSIONS: The findings suggest that polymorphism of BAX and TP53 genes may be potential genetic modifiers for developing ovarian cancer.
Assuntos
Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Proteína Supressora de Tumor p53/genética , Proteína X Associada a bcl-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Carcinoma Epitelial do Ovário , Estudos de Casos e Controles , Epistasia Genética , Feminino , Estudos de Associação Genética , Humanos , Índia/epidemiologia , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Ovarianas/epidemiologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras GenéticasRESUMO
BACKGROUND: MicroRNAs (miRs) have been implicated in the etiology of various human cancers. The aim of this study was to investigate the association of the expression of three members--miR 200a, miR 200b, and miR 200c belonging to the miR-200 family with clinicopathological characteristics and their impact on the progression of epithelial ovarian cancer (EOC). MATERIALS AND METHODS: Total RNA from serum was isolated by Trizol method, polyadenylated, and reverse transcribed into cDNA. Expression levels of miR-200a, miR-200b, and miR-200c were detected by using miRNA qRT-PCR. We measured miR expression in 70 serum samples of EOC patients with matched controls using U6 snRNA as a reference. Levels of miR expression was compared with distinct clinicopathological features. RESULTS: Expression of miR-200a was found to be greater than six-fold (p = 0.01), miR-200b and miR-200c greater than three-fold (p = 0.01) in comparison with matched normal controls. Association of miRNA expression with clinicopathological factors and progression was statistically evaluated. The expression levels of miR-200a and miR-200c were found to be significantly associated with disease progression (p = 0.04 and p < 0.001, respectively). miR-200a overexpression was found be associated with tumor histology and stage. Patients with lymph node metastasis showed significant elevation of miR-200c (p = 0.006). The AUC in ROC curve also indicated that serum levels of miR-200a and miR-200c might be worthwhile as a diagnostic tool in the near future. CONCLUSION: Our findings suggest that miR-200a, miR-200b, and miR-200c overexpressions are associated with the aggressive tumor progression and be recognized as reliable markers to predict the prognosis and survival in EOC patients.
Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Linfonodos/patologia , MicroRNAs/genética , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Adenocarcinoma de Células Claras/sangue , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/sangue , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Papilar/sangue , Adenocarcinoma Papilar/genética , Adenocarcinoma Papilar/patologia , Adulto , Área Sob a Curva , Biomarcadores Tumorais/sangue , Carcinoma Endometrioide/sangue , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , Carcinoma Epitelial do Ovário , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Metástase Linfática , MicroRNAs/sangue , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Císticas, Mucinosas e Serosas/sangue , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Carga Tumoral , Regulação para CimaRESUMO
OBJECTIVE: Vitamin D deficiency is reported to be involved in pathogenesis of ovarian cancer. But the mechanism is yet to be explored. An imbalance between Th1 and Th2 activity play a crucial role in pathogenesis of many cancers. The purpose of the study is to find out the Th1/Th2 status by estimating TNF-α (Th1 marker) and IL-4 (Th2 marker) in ovarian cancer cases and controls and to correlate these with serum vitamin D levels. MATERIALS AND METHODS: A case-control study with 50 ovarian cancer cases and 50 healthy controls was conducted. The cytokines TNF-α and IL-4 were estimated by ELISA. Serum vitamin D was measured by electro-chemiluminescence immunoassay method. RESULTS: Median TNF-α levels (12.2 vs 6.2 pg/ml; p value <0.001) were significantly higher in ovarian cancer patients and mean IL-4 levels (2.22 ± 0.51 vs 2.99 ± 0.68 pg/ml; p value <0.05) were significantly lower as compared to those of controls. Levels of TNF-α and IL-4 did not vary significantly with clinical staging, and histological grading. Vitamin D levels were negatively correlated with TNF-α and positively correlated with IL-4. CONCLUSIONS: Low vitamin D levels promotes Th1 activity increasing TNF-α levels and inhibits Th2 activity decreasing IL-4 levels in ovarian cancer. These low levels of vitamin D may induce pro-inflammatory micro ambience which might contribute to pathogenesis of ovarian cancer.
Assuntos
Biomarcadores Tumorais/sangue , Interleucina-4/sangue , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Epiteliais e Glandulares/prevenção & controle , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/prevenção & controle , Fator de Necrose Tumoral alfa/sangue , Vitamina D/sangue , Vitaminas/sangue , Carcinoma Epitelial do Ovário , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/imunologia , Neoplasias Ovarianas/imunologia , Prognóstico , Células Th1/imunologia , Células Th2/imunologiaRESUMO
BACKGROUND: B cell lymphoma 2 (BCL-2) gene is a well-known regulator of apoptosis and a key element in cancer development and progression. A regulatory (-938C>A, rs2279115) single-nucleotide polymorphism in the inhibitory P2 BCL-2 gene promoter generates significantly different BCL-2 promoter activities and has been associated with different clinical outcomes in various malignancies. The aim of the present study was to analyze the possible influence of the (-938C>A) SNP on the risk and survival of Indian patients suffering from NSCLC. MATERIALS AND METHODS: A hospital-based case-control study of 155 age- and sex-matched patients diagnosed with NSCLC and 155 cancer-free controls was conducted and genotyped by performing PIRA-PCR to elucidate the putative association between clinical outcome and genotypes of BCL-2 (-938C>A, rs2279115). The association of the polymorphism with the survival of NSCLC patients was analyzed by Kaplan-Meier curves. RESULTS: In Indian NSCLC, patients increased risk of developing NSCLC was found to be associated with BCL-2 (-938) CC genotype, [OR 3.68 (1.92-6.79), RR 1.87 (1.35-2.57) and RD 31.03 (16.79-45.27) p 0.00006 for CC and OR 2.08 (1.18-3.66), RR 1.36 (1.08-1.71) and RD 17.74 (4.68-30.81) p 0.01 for AC genotype]. Patients homozygous for C allele exhibited a significant poor overall survival compared with patients displaying AC + CC or AC or AA genotype [median survival (months) 8 vs. 11 vs. 14 vs. 35.5 (p < 0.0001)]. In addition, significant associations were observed between TNM stage, histological type, distant metastases status, family history of any cancer, gender and age group of NSCLC patients with BCL-2 (-938C>A) polymorphism. CONCLUSION: Genetic polymorphism in the inhibitory P2 promoter region of anti-apoptotic BCL-2 genes contributes to the risk of developing non-small-cell lung cancer in Indian population. BCL-2 (-938CC) genotype was an independent adverse prognostic factor for patients with NSCLC.
Assuntos
Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Genes bcl-2/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Genótipo , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Regiões Promotoras Genéticas/genéticaRESUMO
Anencephaly and myelomeningocele are the 2 most common forms of neural tube defects (NTDs). During embryogenesis large numbers of extrinsic and intrinsic factors are responsible for the closing of the neural tube. "Stem cells" maintain the pluripotency during differentiation of 3 germ layers, including the neural ectoderm. We examined the role of Oct4, Nanog3, and Sox2 genes in the etiopathology of NTDs in an eastern Indian population using PCR-based DNA analysis. The highest frequency (16%) of complete loss of the Sox2 gene was found in NTDs. The highest frequency (48%) of overexpression (upregulation) was found for Nanog3, while 40% was observed for Oct4 and Sox2. The odds ratio for cases versus controls was from 0.132 at 95% confidence interval = 0.005-1.298 for Nanog3 to 2.316 (0.424-13.812) for Oct4. The highest frequency (77%) of overexpression for Nanog3 and Sox2 was observed in encephalocele and anencephalic patients, while in the comparison of regional variation, i.e., cephalic to caudal regions of NTDs, the highest frequency of downregulation (regression) of Nanog3 and Sox2 was found in lumbosacral myelomeningocele patients. However, cervical myelomeningocele patients had the highest frequency of overexpression in all 3 genes, suggesting that the mutational spectra of stem cells influence the cells of the neural crest in NTDs.
Assuntos
Defeitos do Tubo Neural/genética , População/genética , Células-Tronco/classificação , Biomarcadores/metabolismo , Estudos de Casos e Controles , Frequência do Gene , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Índia , Lactente , Recém-Nascido , Mutação , Proteína Homeobox Nanog , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Células-Tronco/metabolismoRESUMO
Cystathionine beta synthase gene (CßS) catalyzes the condensation of homocysteine with serine, forming cystathionine by the transsulfuration pathway. Disruption of CßS enzyme activity due to defective folic acid metabolism increases the risk factor for neural tube defects. We evaluated the CßS gene mutation in 25 children with neural tube defects (NTDs), including lumbosacral and thoracic myelomeningocele and open NTDs and mothers of cases, along with 25 healthy children and their mothers, serving as controls. Genomic DNA was isolated to assess the polymorphism of 852Ins68 in the CßS gene using PCR-RFLP analysis and nucleotide sequencing techniques. The 68-bp insertion was observed in one of the 25 NTD cases (lumbosacral myelomeningocele), and in two of the mothers of NTD cases. Statistical analysis was carried out using the Fischer exact probability test, which showed a lack of significance (P > 0.05), but the odds ratio of 2.08 with 95% confidence interval of 0.17-24.6 in NTDs mother was quite high because of the small sample size. However, the study was further extended to find out the involvement of specific nucleotide sequences, which again confirmed the 852Ins68 insertion and replacement of nucleotides (TCCAT to GGGG) in lumbosacral myelomeningocele (due to other category of NTDs), suggesting that it could be an independent risk factor for birth defects, including NTDs.
Assuntos
Cistationina beta-Sintase/genética , Meningomielocele/genética , Mutagênese Insercional , Defeitos do Tubo Neural/genética , Polimorfismo de Fragmento de Restrição , Adulto , Pré-Escolar , Cistationina beta-Sintase/metabolismo , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Meningomielocele/enzimologia , Meningomielocele/epidemiologia , Defeitos do Tubo Neural/enzimologia , Reação em Cadeia da Polimerase/métodos , Prevalência , Fatores de RiscoRESUMO
Infertility is a major reproductive health threat; the frequency of male infertility due to Y-chromosome microdeletions is 13-18% in the human population; these microdeletions involve recurrent loss of three non-overlapping regions designated as AZFa, AZFb and AZFc, associated with spermatogenic failure. Several contradictory reports have been published regarding deletion frequency based on sequence-tagged site markers and genotype-phenotype correlation. We examined the prevalence of Yq- deletion in 64 clinically diagnosed infertile male patients. We found a 3% frequency of microdeletion of the AZFc region; hormone profiles (FSH, LH and testosterone) showed significantly (P < 0.001) elevated levels compared to controls. No mutations were observed in the AZFa and AZFb regions, perhaps due to the selective use of sequence-tagged site markers.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Y/genética , Infertilidade Masculina/genética , Proteínas de Plasma Seminal/genética , Adulto , Primers do DNA/genética , Loci Gênicos , Marcadores Genéticos , Humanos , Masculino , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Sitios de Sequências RotuladasRESUMO
Fourteen Azospirillum brasilense strains growing at a sub-optimum temperature were selected based on their ability to grow and carry out plant growth promoting activities at 22 degrees C. The strains were tested for their response to inoculation in wheat (two popular cultivars, HD2285 and WH547, under sterile conditions) crop using sterile and nonsterile rooting medium. Significant increase in plant growth parameters was observed; the overall response to inoculation was better in cultivar HD2285. Based on their performance under sterile conditions, 4 strains were selected and compared under nonsterile conditions with strain sensitive to a sub-optimum temperature in pots using wheat variety HD2285. The strains capable of growing at the sub-optimum temperature can colonize the wheat endorhizosphere efficiently and improve the plant growth and yield as compared to sensitive strain; a 25-27% increase in grain yield was found on inoculating two selected strains compared to NO3- control.
Assuntos
Azospirillum brasilense/crescimento & desenvolvimento , Azospirillum brasilense/isolamento & purificação , Raízes de Plantas/microbiologia , Triticum/crescimento & desenvolvimento , Triticum/microbiologia , Meios de Cultura , Ácidos Indolacéticos/metabolismo , Nitrogenase/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Sideróforos/metabolismo , Microbiologia do Solo , TemperaturaRESUMO
Cephalendra indica (41//v/v alcoholic extract of the wild variety of Cephalendra indica Naud.), on regular administration in doses ranging from 25uml to 75uml/100g of body weight (gbw) by the oral or intraperitoneal (ip) route produced a significant fall in blood sugar level in alloxan-induced diabetic rats. Biochemical studies showed stabilization of blood sugar level in 70//of cases at fourteen to twenty days after withdrawal of the drug. Histopathological studies revealed regeneration of pancreatic B cells. The hypothesis is that the drug acts through the hypothalamo-hypophysial-pancreatic axis, producing selective regeneration of B cells. The drug may indirectly release inhibitory factors from hypothalamic neurons, inhibiting the secretion of growth hormone and triggering insulin secretions from B cells. The therapeutic action of the drug on pancreatic B cells and lack of acute and subacute toxicity may open up new prospects in the treatment of diabetes mellitus