Characterization of global transcription profile of normal and HPV-immortalized keratinocytes and their response to TNF treatment

<p>Abstract</p> <p>Background</p> <p>Persistent infection by high risk HPV types (e.g. HPV-16, -18, -31, and -45) is the main risk factor for development of cervical intraepithelial neoplasia and cervical cancer. Tumor necrosis factor (TNF) is a key mediator of epithelial cell inflammatory response and exerts a potent cytostatic effect on normal or HPV16, but not on HPV18 immortalized keratinocytes. Moreover, several cervical carcinoma-derived cell lines are resistant to TNF anti-proliferative effect suggesting that the acquisition of TNF-resistance may constitute an important step in HPV-mediated carcinogenesis. In the present study, we compared the gene expression profiles of normal and HPV16 or 18 immortalized human keratinocytes before and after treatment with TNF for 3 or 60 hours.</p> <p>Methods</p> <p>In this study, we determined the transcriptional changes 3 and 60 hours after TNF treatment of normal, HPV16 and HPV18 immortalized keratinocytes by microarray analysis. The expression pattern of two genes observed by microarray was confirmed by Northern Blot. NF-κB activation was also determined by electrophoretic mobility shift assay (EMSA) using specific oligonucleotides and nuclear protein extracts.</p> <p>Results</p> <p>We observed the differential expression of a common set of genes in two TNF-sensitive cell lines that differs from those modulated in TNF-resistant ones. This information was used to define genes whose differential expression could be associated with the differential response to TNF, such as: <it>KLK7 </it>(<it>kallikrein 7</it>), <it>SOD2 </it>(<it>superoxide dismutase 2</it>), <it>100P </it>(<it>S100 calcium binding protein P</it>), <it>PI3 </it>(<it>protease inhibitor 3, skin-derived</it>), <it>CSTA </it>(<it>cystatin A</it>), <it>RARRES1 </it>(<it>retinoic acid receptor responder 1</it>), and <it>LXN </it>(<it>latexin</it>). The differential expression of the <it>KLK7 </it>and <it>SOD2 </it>transcripts was confirmed by Northern blot. Moreover, we observed that <it>SOD2 </it>expression correlates with the differential NF-κB activation exhibited by TNF-sensitive and TNF-resistant cells.</p> <p>Conclusion</p> <p>This is the first in depth analysis of the differential effect of TNF on normal and HPV16 or HPV18 immortalized keratinocytes. Our findings may be useful for the identification of genes involved in TNF resistance acquisition and candidate genes which deregulated expression may be associated with cervical disease establishment and/or progression.</p

Determinantes nutricionais e sóciodemográficos da variação de peso no pós-parto: uma revisão da literatura Nutritional and socio-demographic determinants of post-partum weight change: a literature review

Trata-se de um estudo de revisão sobre os fatores nutricionais e sócio-demográficos da variação de peso no pós-parto. Foi realizada uma busca bibliográfica nas bases de dados eletrônicas Scientific Eletronic Library On-line (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Medical Literature Analysis and Retrieval System Online (MEDLINE) referente a literatura publicada na última década (1997-2008). Treze artigos, um informe técnico e dois livros considerados relevantes sobre o assunto e publicados anteriormente ao ano 1997 foram citados na revisão. A revisão priorizou estudos de ensaios clínicos randomizados e de seguimento realizados com gestantes e mulheres no pós-parto. Os resultados obtidos mostram como principais fatores associados com a variação de peso no pós-parto o ganho de peso gestacional acima das recomendações do Institute of Medicine, Índice de Massa Corporal Pré-Gestacional > 25 kg/m2, dieta, tempo e intensidade do aleitamento materno e os fatores sócio-demográficos: raça negra, primiparidade, idade materna, baixa renda e baixa escolaridade. A prática regular de atividade física é recomendada como uma estratégia para evitar o ganho de peso excessivo e melhorar a perda de peso durante o pós-parto. No Brasil não existe uma estratégia nacional para prevenir o ganho de peso excessivo e garantir a adequada perda de peso nesse período. Durante o pós-parto, a maioria das ações de saúde visa basicamente garantir o aleitamento materno.<br>This study is a review of nutritional and sociodemographic factors determining post-partum weight variation. A bibliographical search was carried out on the electronic databases Scientific Eletronic Library On-line (SciELO), Latin-American and Caribbean Literature on Health Sciences (LILACS) and Medical Literature Analysis and Retrieval System Online (MEDLINE) for titles published in the past decade (1997-2008). Thirteen articles, one technical note and two books considered relevant to the subject and published prior to 1997 are also cited in the review. The review prioritized studies involving randomized clinical trials and follow-up carried out among pregnant and post-partum women. The results show that the following are the main factors associated with post-partum weight variation: gestational weight gain above the recommendations of the Institute of Medicine, Pregestational Body Mass > 25 kg/m2, diet, duration and intensity of breast-feeding and socio-demographic factors, such as being black, having given birth only once, the age of the mother, low income and low schooling. Regular physical activity is recommended as a strategy for avoiding excessive weight gain and improving weight loss during post partum. In Brazil, there is no national strategy for preventing excessive weight gain and ensuring adequate weight loss during this period. During post-partum, most health service actions are restricted to ensuring that mothers breastfeed

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AimThe SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery.MethodsThis was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin.ResultsOverall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P ConclusionOne in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease