HPV16 integration probably contributes to cervical oncogenesis through interrupting tumor suppressor genes and inducing chromosome instability.

BACKGROUND: The integration of human papilloma virus (HPV) into host genome is one of the critical steps that lead to the progression of precancerous lesion into cancer. However, the mechanisms and consequences of such integration events are poorly understood. This study aims to explore those questions by studying high risk HPV16 integration in women with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (SCC). METHODS: Specifically, HPV integration status of 13 HPV16-infected patients were investigated by ligation-mediated PCR (DIPS-PCR) followed by DNA sequencing. RESULTS: In total, 8 HPV16 integration sites were identified inside or around genes associated with cancer development. In particular, the well-studied tumor suppressor genes SCAI was found to be integrated by HPV16, which would likely disrupt its expression and therefore facilitate the migration of tumor. On top of that, we observed several cases of chromosome translocation events coincide with HPV integration, which suggests the existence of chromosome instability. Additionally, short overlapping sequences were observed between viral derived and host derived fragments in viral-cellular junctions, indicating that integration was mediated by micro homology-mediated DNA repair pathway. CONCLUSIONS: Overall, our study suggests a model in which HPV16 might contribute to oncogenesis not only by disrupting tumor suppressor genes, but also by inducing chromosome instability.

[Effect of intensive insulin therapy on the clinical results of postoperative patients with gastric cancer].

OBJECTIVE: To investigate the influence of intensive insulin therapy on the results of postoperative patients with gastric cancer. METHODS: Forty-six patients with gastric cancer underwent radical operation were randomly divided into two groups: intensive group (n=23, to control blood glucose at 4.4 to 6.1 mmol/L) and conventional group (n=23, to control blood glucose at 10.0 to 11.1 mmol/L). Fasting blood glucose( FBG), fasting insulin (FINS), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C reaction protein (CRP) in 46 patients were detected dynamically during perioperative period. Insulin resistance index (HOMA-IR) were calculated using Homeostasis Model Assessment (HOMA) to evaluate insulin sensitivity. Postoperative complications and other clinical data were recorded. RESULTS: No hypoglycemia occurred in the two groups. Compared with conventional group, morbidity and postoperative duration of fever, antibiotic use and the length of hospital stay in intensive group were significantly reduced (P < 0.05). On the day 1 and 3 after surgery, HOMA-IR and serum levels of TNF-alpha, IL-6 and CRP in patients of intensive group were significantly lower than those in conventional group (P < 0.05). CONCLUSIONS: Intensive insulin therapy could counteract the state of high-inflammation and then improve the outcome of postoperative patients.