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INTRODUCTION: Epidemiological studies indicate that diet rich in fruits and vegetables is associated with decreased cancer risk thereby indicating that dietary polyphenols can be potential chemo-preventive agents. The reversible nature of epigenetic modifications makes them a favorable target for cancer prevention. Polyphenols have been shown to reverse aberrant epigenetic patterns by targeting the regulatory enzymes, DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). In vitro and in silico studies of DNMTs and HDACs were planned to examine genistein's role as a natural epigenetic modifier in human cervical cancer cells, HeLa. METHODS: Expression of the tumour suppressor genes (TSGs) [MGMT, RARß, p21, E-cadherin, DAPK1] as well the methylation status of their promoters were examined alongwith the activity levels of DNMT and HDAC enzymes after treatment with genistein. Expression of DNMTs and HDACs was also studied. In-silico studies were performed to determine the interaction of genistein with DNMTs and HDACs. RESULTS: Genistein treatment significantly reduced the expression and enzymatic activity of both DNMTs and HDACs in a time-dependent way. Molecular modeling data suggest that genistein can interact with various members of DNMT and HDAC families and support genistein mediated inhibition of their activity. Timedependent exposure of genistein reversed the promoter region methylation of the TSGs and re-established their expression. CONCLUSIONS: In this study, we find that genistein is able to reinstate the expression of the TSGs studied by inhibiting the action of DNMTs and HDACs. This shows that genistein could be an important arsenal in the development of epigenetic based cancer therapy.

Asunto(s)

Antineoplásicos/farmacología , Epigénesis Genética/efectos de los fármacos , Genisteína/farmacología , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genisteína/síntesis química , Genisteína/química , Células HeLa , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/química , Humanos , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología

RESUMEN

INTRODUCTION: Lymph nodes are normal structures distributed throughout the human body and are enlarged in various disease entities. Identifying the relevant lymph nodes is important in treating these patients. High resolution sonography (HRSG) and fine needle aspiration cytology (FNAC) play crucial role in planning the treatment. OBJECTIVE: To assess the diagnostic accuracy of HRSG differentiate neoplastic and non neoplastic causes of enlarged cervical lymph nodes. MATERIALS AND METHODS: HRSG evaluation of enlarged cervical lymph nodes were performed to differentiate neoplastic from non neoplastic lymph nodes followed by FNAC correlation and the accuracy of HRSG was studied. RESULTS: One hundred and fourteen lymph nodes of 106 patients were analysed to accomplish the study objective. In our study, HRSG had 96% sensitivity and 90.6% specificity for differentiating between neoplatic and non-neoplastic cervical lymphadenopathy. Similarly positive and negative predictive values were 88.9% and 96.7% respectively. Overall accuracy of HRSG was 93%. CONCLUSION: Owing to high sensitivity and negative predictive value, HRSG with Doppler is an excellent first line investigating tool for enlarged lymph nodes and avoids invasive procedures like FNAC in cases of reactive/ inflammatory (non-neoplastic) lymph nodes. However, neoplastic diagnosis of HRSG needs further confirmation by FNAC.

RESUMEN

BACKGROUND: Children with adenoid hypertrophy have been shown to harbor pathogenic bacteria in the nasopharynx despite antibiotics. Removal of the adenoid is associated with a reduction in the bacterial count. AIMS: The study was done to determine the bacteriology of the adenoid tissue in chronic adenotonsillitis and adenoid hypertrophy, and determine the antibiotic sensitivity of potential pathogens. MATERIALS AND METHODS: This is a descriptive study conducted on 100 patients aged between three and twelve years who underwent adenotonsillectomy/adenoidectomy. After adenoidectomy, the specimen along with the swab taken from the surface of the adenoid was sent for microbiological examination. After 48 and 96 hours, the microbial growth was identified and the antibiotic-sensitivity pattern of the isolate was studied. RESULTS: Aerobic organisms grew in 93% of the specimens and anaerobic organisms in 68%, whereas 7% had no growth. The surface was predominated by commensals and the pathogens were mainly found in the core. The predominant pathogens were Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus species. The organisms were resistant to penicillin but showed sensitivity to co-amoxiclav and ciprofloxacin. Co-amoxiclav and ciprofloxacin should be considered as the first line of medical treatment for adenotonsillar diseases. CONCLUSIONS: Infection is the main cause of adenoid hypertrophy. Amoxicillin with potassium clavulanate and ciprofloxacin should be considered as the drugs of choice for all adenotonsillar diseases. Early and prompt treatment of adenoid hypertrophy with appropriate antibiotics will avoid unnecessary exposure to repeated antimicrobial therapy, thereby maintaining the beneficial effects of the normal adenoid flora.