17 research outputs found

    Apoptotic HPV Positive Cancer Cells Exhibit Transforming Properties

    Get PDF
    Previous studies have shown that DNA can be transferred from dying engineered cells to neighboring cells through the phagocytosis of apoptotic bodies, which leads to cellular transformation. Here, we provide evidence of an uptake of apoptotic-derived cervical cancer cells by human mesenchymal cells. Interestingly, HeLa (HPV 18+) or Ca Ski (HPV16+) cells, harboring integrated high-risk HPV DNA but not C-33 A cells (HPV-), were able to transform the recipient cells. Human primary fibroblasts engulfed the apoptotic bodies effectively within 30 minutes after co-cultivation. This mechanism is active and involves the actin cytoskeleton. In situ hybridization of transformed fibroblasts revealed the presence of HPV DNA in the nucleus of a subset of phagocytosing cells. These cells expressed the HPV16/18 E6 gene, which contributes to the disruption of the p53/p21 pathway, and the cells exhibited a tumorigenic phenotype, including an increased proliferation rate, polyploidy and anchorage independence growth. Such horizontal transfer of viral oncogenes to surrounding cells that lack receptors for HPV could facilitate the persistence of the virus, the main risk factor for cervical cancer development. This process might contribute to HPV-associated disease progression in vivo

    PRODIG (Prevention of new onset diabetes after transplantation by a short term treatment of Vildagliptin in the early renal post-transplant period) study: study protocol for a randomized controlled study

    No full text
    International audienceBACKGROUND: Post-transplant diabetes is a frequent and serious complication of kidney transplantation. There is currently no treatment to prevent or delay the disease. Nevertheless, identification of risk factors make it possible to target a population at risk of developing de novo diabetes. We hypothesized that a short-term treatment with vildagliptin may prevent new onset diabetes after transplantation (NODAT) in high-risk patients.METHODS/DESIGN: This is a multicenter, double-blind, placebo-controlled randomized clinical trial. Patients undergoing first kidney transplantation will be included from ten French transplant centers. Included patients will be randomized (1:1) to receive either vildagliptin 100 or 50 mg/day (depending on glomerular filtration rate) during 2 months (the first dose being administered before entering the operating theatres) or placebo. Additional antidiabetic therapy could be administered according to glycemic control. The primary outcome is the proportion of diabetic patients 1 year after transplantation, defined as patients receiving a diabetic treatment, or having a fasting glucose above 7 mmol/l, and/or with an abnormal oral glucose tolerance test. Secondary outcomes include glycated hemoglobin, the occurrence of acute rejection, infection, graft loss and patient death at 3 months, 6 months, and 12 months after transplantation. Outcomes will be correlated to clinical and general characteristics of the patient, cardiovascular history, nephropathy, dialysis history, transplantation data, biological data, health-related quality of life, and the cost-effectiveness of prevention of diabetes with vildagliptin.DISCUSSION: We have scarce data on the pharmacological prevention of post-transplant diabetes. If our hypothesis is verified, our results will have a direct application in clinical practice and could limit diabetes-associated morbidity, reduce cardiovascular complications, increase quality of life of renal transplant patients, and consequently promote graft and patient survival. Our results may possibly serve for non-transplant patients carrying a high-risk of diabetes associated with other co-morbidities

    Ice caves as an indicator of winter climate evolution: a case study from the Jura Mountains

    No full text
    Subsurface ice fillings were first described in the Jura Mountains at the end of the sixteenth century. In order to assess the impact of climate change on low-altitude cave ice a detailed inventory has been drawn up and more than 50 objects have been identified. Comparisons between older cave maps, photographic documents and present-day observations outline a negative trend in ice mass balances, a trend that increased at the end of the 1980s. As most of these ice caves act as cold air traps, this negative mass balance is mainly attributed to higher winter temperatures and to reduced snow precipitation at low altitudes. The equilibrium line altitude of ice caves is believed to have increased several hundred metres between AD 1978 and 2004. Photographic comparisons and proxy records in some of the caves studied provide evidence of a rapid mass turnover. Ice ages range between less than a few decades and a millennium. Climatic records in these ice fillings will therefore present only short time series compared with other cave sediments. However, indications of former ice fillings have been found in different caves of the Jura Mountains and outline their potential role as palaeoclimatic markers
    corecore