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Phosphatase and tensin homolog (PTEN) and p16INK4a (p16) genes are tumor suppressor genes, associated with epigenetic alterations. PTEN and p16 promoter hypermethylation is a major epigenetic silencing mechanism leading to cancer. The cooperation between PTEN and p16 in pathogenesis of cancers suggest that their combination might be considered as potential molecular marker for specific subgroups of patients. Hence, the present study aimed to investigate whether PTEN and p16 promoter methylations were involved in oral squamous cell carcinoma (OSCC) in south Indian subjects. DNA methylation quantitative analyses of the two candidate tumor suppressor genes PTEN and p16 were performed by methylation-specific polymerase chain reaction (MSP). Fifty OSCC biopsy samples and their corresponding non-malignant portions as controls were studied comparatively. The methylation status was correlated with the clinical manifestations. Twelve out of 50 patients (24 %) were found to be methylated for PTEN gene, whereas methylation of the p16 gene occurred in 19 out of 50 cases (38 %). A statistically significant result was obtained (P = <0.0001 and 0.017) for both PTEN and p16 genes. PTEN and p16 promoter methylation may be the main mechanism leading to the low expression of PTEN and p16 genes indicating the progress of tumor development. Our data suggest that a low PTEN and p16 expression due to methylation may contribute to the cancer progression and could be useful for prognosis of OSCC. Therefore, analysis of promoter methylation in such genes may provide a biomarker valuable for early detection of oral cancer.
Assuntos
Carcinoma de Células Escamosas/genética , Metilação de DNA , DNA de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica , Genes p16 , Neoplasias Bucais/genética , PTEN Fosfo-Hidrolase/genética , Adulto , Idoso , Biomarcadores Tumorais , Biópsia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/fisiologia , DNA de Neoplasias/química , Detecção Precoce de Câncer , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/patologia , PTEN Fosfo-Hidrolase/análise , PTEN Fosfo-Hidrolase/fisiologia , Regiões Promotoras Genéticas/genética , Fatores de RiscoRESUMO
BCL2 (B-cell leukemia/lymphoma 2) gene functions as antiapoptotic regulatory element and known to be associated with tumorigenesis. The SNP-938 (C>A) (rs2279115), located in the inhibitory P2 promoter of the BCL2 gene, influences differential binding affinities of transcriptional factors thereby affecting BCL2 expression. The present study is an attempt to evaluate the association between BCL2(-938C>A) polymorphism and clinical characteristics of breast cancer patients as well as to analyze BCL2 expression and Ki67 proliferation index with respect to the genotypes. One hundred ten primary breast cancer tumor tissues were genotyped for -938 C>A polymorphism through PCR-RFLP method as well as evaluated for BCL2 expression and ki67 proliferation index by immunohistochemistry. Evaluation of apoptosis level was performed by flowcytometry. The results revealed that AA genotype was associated with an increased risk (AA Vs AC + CC) by 2.86-fold (p = 0.07) for breast cancer development which reflected in elevated A allele frequency also. AA genotype was found to be predominant among BCL2 positive tumors as compared to BCL2 negative tumors. Further, AA genotype was found to be associated with advanced stage tumors, node positive status, and high Ki67 proliferation index compared to CA and CC genotypes indicating that elevated expression of BCL2 gene in the presence of A allele might be associated with decreased apoptosis and enhanced proliferation rate. AA genotype of BCL2-938C>A polymorphism might influence BCL2 gene expression there by associated with elevated risk for breast cancer progression. Probably, failure of apoptosis due to enhanced expression and antiapoptotic protein BCL2 might promote malignant growth.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Expressão Gênica , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-bcl-2/genética , Adulto , Alelos , Apoptose , Biomarcadores Tumorais , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Frequência do Gene , Genótipo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Adulto JovemRESUMO
INTRODUCTION: Breast cancer (BC) is the most common cancer among Indian women and invasive duct cell carcinoma (IDCC) the most common histology (80-90%) followed by noninvasive duct cell carcinoma (non-IDCC) subtypes (about 10%). Most of the non-IDCC are rare (<1-2%), and literature on this topic is sparse. Age is an important prognostic factor and varies with ethnicity. The aim of our study is to evaluate the incidence and age at presentation of different types of BC. MATERIAL AND METHODS: This is a single institute retrospective observational study evaluating BC over the last 7 years at our institute. We evaluated the demographic and pathological features. RESULTS: There were a total of 2725 patients, of these 89.7% had IDCC and 10.2% had non-IDCC. There were 13 subtypes of non-IDCC, the most common being sarcoma/phyllodes (2.4%) and lobular (2.3%). The other subtypes were very rare (<1.5% each). The non-IDCC male BC was very rare (0.07%). The median age at presentation was similar for IDCC and non-IDCC types (50 years). The p value for age at presentation was significant for mucinous (0.0001), phyllodes (<0.0001), and sarcoma breast (0.009) when compared with IDCC. CONCLUSION: The incidence of IDCC, non-IDCC, and rare subtypes of non-IDCC are comparable to literature except lobular (lower) and phyllodes/sarcoma (higher). Indian patients presented a decade earlier for both IDCC and non-IDCC types. Tubular and papillary presented at an age comparable to IDCC, in contrast to the West. Given these differences, the prognosis of non-IDCC needs to be evaluated in future studies on Indian BC patients.
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Paratesticular rhabdomyosarcoma is a very rare mesenchymal tumor. It is an intrascrotal tumor that is localized in paratesticular structures such as the epididymis or spermatic cord. Rhabdomyosarcoma is most often observed in children and adolescents, presenting as a painless scrotal mass. An 18-year-old man presented with a painless left scrotal mass and lump abdomen that had evolved over four months. A histological examination of the lesion revealed rhabdomyosarcoma. Chemotherapy with alternative cycles of Vincristine, Adriamycin, Cyclophosphamide followed by Ifosphamide, Etoposide was given. Paratesticular rhabdomyosarcoma is a rare aggressive tumor manifesting in children and very young adults. Localized forms have a good prognosis whereas metastatic tumors show very poor results. A well-defined treatment based on surgery and chemotherapy yields good results.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfadenopatia/diagnóstico , Orquiectomia , Rabdomiossarcoma/diagnóstico , Neoplasias Testiculares/diagnóstico , Adolescente , Quimioterapia Adjuvante/métodos , Humanos , Linfadenopatia/etiologia , Linfadenopatia/terapia , Masculino , Rabdomiossarcoma/complicações , Rabdomiossarcoma/patologia , Rabdomiossarcoma/terapia , Neoplasias Testiculares/complicações , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapia , Resultado do TratamentoRESUMO
OBJECTIVE: To determine interest in and barriers to video visits in safety-net patients with diverse age, racial/ethnic, or linguistic background. MATERIALS AND METHODS: We surveyed patients in an urban safety-net system to assess: interest in video visits; ability to successfully complete test video visits; and barriers to successful completion of test video visits. RESULTS: Among 202 participants, of which 177 (87.6%) were persons of color and 113 (55.9%) preferred non-English languages, 132 (65.3%) were interested in and 109 (54.0%) successfully completed a test video visit. Younger age, non-English preference, and prior smartphone application use were associated with interest. Over half (n = 112) reported barriers to video visits; Internet/data access was the most common barrier (n = 50, 24.8%). CONCLUSION: Safety-net patients are interested in video visits and able to successfully complete test visits. Internet or mobile data access is a common barrier in even urban safety-net settings and may impact equitable telemedicine access.
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Atitude Frente a Saúde , Multilinguismo , Provedores de Redes de Segurança , Telemedicina , Adolescente , Adulto , Fatores Etários , Idoso , Atitude Frente a Saúde/etnologia , California , Estudos Transversais , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Serviços Urbanos de Saúde , Adulto JovemRESUMO
Here we report a 60 year aged male presented with complaints of right neck swelling of 3 months duration, swelling was initially small in size and gradually increasing. On examination right level II, hard mobile lymph node was palpable measuring 4 × 4 cm in size, oral cavity and oropharynx was normal. Computed tomography of face neck showed moderately enhancing soft tissue mass of 2 × 3 cm in the supra glottis and left level II cervical lymphadenopathy of size 5 × 5 cm with infiltrating into left sternomastoid muscle. Direct laryngoscopy revealed an ulcero proliferative growth in the supra glottis extending into vallaculla biopsy from the growth showed small round cells with scant amount of cytoplasm with hyperchromatic nucleus, atypical mitosis and at places rosettoid arrangement was seen. Immunohistochemistry with pancytokeratin, CD 56 and synaptophysin were positive, LCA was negative and Ki 67 was >70 %, features consisted with neuroendocrine carcinoma small cell type. Computed tomography of chest, abdomen and pelvis was normal. Finally it was labeled as localized neuro endocrine carcinoma small cell type of larynx (supraglottis). This patient treated with external beam radiotherapy 70 Gy in 35 fractions @ 2 Gy per fraction over 7 weeks along with concurrent chemotherapy with weekly cisplatin followed by adjuvant chemotherapy with Cisplatin and Etoposide for six cycles.
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BACKGROUND: Few prospective studies have investigated the relationship between spousal cigarette smoking and the risk of incident stroke. METHODS: Stroke-free participants in the U.S.-based Health and Retirement Study (HRS) aged >or=50 years and married at baseline (n=16,225) were followed, on average, 9.1 years between 1992 and 2006) for proxy or self-report of first stroke (1,130 events). Participants were stratified by gender and own smoking status (never-smokers, former smokers, or current smokers), and the relationship assessed between the spouse's smoking status and the risk of incident stroke. Analyses were conducted in 2007 with Cox proportional hazards models. All models were adjusted for age; race; Hispanic ethnicity; Southern birthstate; parental education; paternal occupation class; years of education; baseline income; baseline wealth; obesity; overweight; alcohol use; and diagnosed hypertension, diabetes, or heart disease. RESULTS: Having a spouse who currently smoked was associated with an increased risk of first stroke among never-smokers (hazard ratio=1.42, 95% CI=1.05, 1.93) and former smokers (hazard ratio=1.72, 95% CI=1.33, 2.22). Former smokers married to current smokers had a stroke risk similar to respondents who themselves smoked. CONCLUSIONS: Spousal smoking poses important stroke risks for never-smokers and former smokers. The health benefits of quitting smoking likely extend to both the individual smoker and his or her spouse.
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Fumar/efeitos adversos , Cônjuges , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Fatores Etários , Intervalos de Confiança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fumar/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
The incidence of breast cancer in India is on the rise and is rapidly becoming the primary cancer in Indian women. The aldoketo reductase (AKR) family has more than 190 proteins including aldose reductase (AKR1B1) and aldose reductase like protein (AKR1B10). Apart from liver cancer, the status of AKR1B1 and AKR1B10 with respect to their expression and activity has not been reported in other human cancers. We studied the specific activity and expression of AKR1B1 and AKR1B10 in breast non tumor and tumor tissues and in the blood. Fresh post-surgical breast cancer and non-cancer tissues and blood were collected from the subjects who were admitted for surgical therapy. Malignant, benign and pre-surgical chemotherapy samples were evaluated by histopathology scoring. Expression of AKR1B1 and AKR1B10 was carried out by immunoblotting and immunohistochemistry (IHC) while specific activity was determined spectrophotometrically. The specific activity of AKR1B1 was significantly higher in red blood cells (RBC) in all three grades of primary surgical and post-chemotherapy samples. Specific activity of both AKR1B1 and AKR1B10 increased in tumor samples compared to their corresponding non tumor samples (primary surgical and post-chemotherapy). Immunoblotting and IHC data also indicated overexpression of AKR1B1 in all grades of tumors compared to their corresponding non tumor samples. There was no change in the specific activity of AKR1B1 in benign samples compared to all grades of tumor and non-tumors.
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Aldeído Redutase/metabolismo , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Mama/enzimologia , Eritrócitos/enzimologia , Adolescente , Adulto , Idoso , Aldeído Redutase/análise , Aldo-Ceto Redutases , Mama/química , Neoplasias da Mama/química , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/análise , Gradação de Tumores , Período Pós-Operatório , Período Pré-Operatório , Fator de Transcrição RelA/análise , Fator de Transcrição RelB/análise , Adulto JovemRESUMO
BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules, implicated in several activities like initiation, progression and prognosis of various cancers. Single nucleotide polymorphisms (SNPs) in miRNA genes can lead to alteration in mRNA expression, resulting in diverse functional consequences. The aim of our study was to investigate the association of miR-149C>T and miR-196a2C>T SNPs with susceptibility to development of oral squamous cell carcinoma (OSCC) in South Indian subjects. MATERIALS AND METHODS: 100 OSCC patients and 102 healthy controls from the general population were recruited for the study. Genetic analysis was performed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) as per a standard protocol. RESULTS: The genotype frequencies in miR-196a2 polymorphism, of TT, CT and CC in the OSCC patients were 69%,10% and 22% respectively while for control group it was 80%, 15% and 5% respectively. The CC genotype of miR196a2 polymorphism was significantly associated with oral squamous cell carcinoma. The genotype frequencies in miR-149 polymorphisms of CC, CT and TT in the oral squamous cell carcinoma (OSCC) patients were 72%, 22% and 6% respectively and for control group 88%, 12% and 0% respectively. CT and TT genotypes of miR149 polymorphism were found to be significantly associated with OSCC (p = 0.05 and 0.07). CONCLUSIONS: Our study suggests that miR-196a2C>T and miR-149C>T polymorphisms may play crucial roles in the development of OSCC in South Indian subjects.
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Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/genética , MicroRNAs/genética , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/genética , Adulto , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Adulto JovemRESUMO
A prospective study was undertaken on suspected lymph node TB (LNTB) patients, to evaluate the diagnostic utility of mycobacterial culture of fine needle aspirate (FNA), in comparison with the cytological examination and acid fast staining. Eighty percent of 157 aspirates studied were positive by cytological examination; 18% by ZN smear and 45% were positive by culture. Twelve aspirates which were negative by cytological features yielded positive mycobacterial cultures; four out of these were from HIV positive patients. Our observations suggest that supplementing FNA cytology with mycobacterial culture would increase the sensitivity of diagnosing LNTB; in addition to giving a highly specific diagnosis.