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Zygogianni A.,Kapodistrian University of Athens | Kyrgias G.,University of Thessaly | Kouvaris J.,Kapodistrian University of Athens | Mystakidou K.,Kapodistrian University of Athens | And 2 more authors.
Reviews on Recent Clinical Trials | Year: 2011

Surgery remains the mainstay of melanoma therapy at all sites. Melanoma is widely believed to be a radioresistant tumor, a misconception that has historically led to the limited use of RT for its treatment. We searched pubmed from 1978 until 2010 by means of prospective randomized trials. The aim was to assess the potential impact of radiotherapy (RT) on local control, quality of life and overall survival. Radiotherapy should be considered in lentigo maligna, especially in elderly patients with extensive or unresectable disease in difficult areas on the face, with adequate tumor control with good cosmetic and functional results. In addition, radiation therapy provides effective palliation in patients with metastatic malignant melanoma. Doses up to 30 Gy or BED > 39.0Gy were found to be associated with prolonged palliation. These findings should be viewed with caution because the lack of data regarding performance status as well as other unknown confounding factors limits the applicability of retrospectives studies. We recommend that higher doses of RT be considered when using RT for the palliation of patients with metastatic melanoma and a performance status that could tolerate such therapy. In the futute, the combination of radiation therapy with hyperthermia may be a reasonable therapeutic option. © 2011 Bentham Science Publishers Ltd.

PubMed | Kapodistrian University of Athens, Biogen Idec, Case Western Reserve University and University of Cardiff
Type: Journal Article | Journal: Journal of immunology (Baltimore, Md. : 1950) | Year: 2016

TNF-like cytokine 1A (TL1A) is expressed on APCs and provides costimulatory signals to activated lymphocytes that bear its functional receptor, death receptor 3 (DR3). TL1A/DR3 signaling is involved in the pathogenesis of human and experimental inflammatory bowel disease. In the current study, we investigated the role of this cytokine/receptor pair in acute intestinal injury/repair pathways. We demonstrate that intact DR3 signaling protected mice from acute dextran sodium sulfate colitis because DR3(-/-) mice showed more severe mucosal inflammation and increased mortality. DR3(-/-) mice were compromised in their ability to maintain adequate numbers of CD4(+)CD25(+)Foxp3(+) regulatory T cells in response to acute mucosal damage. This defect in immune regulation led to a nonspecific upregulation of effector proinflammatory pathways, which was most prominent for the Th17 immunophenotype. TL1A(-/-) mice were similarly more susceptible to dextran sodium sulfate colitis, although without mortality and with delayed kinetics compared with DR3(-/-) mice, and also displayed significantly reduced numbers of regulatory T cells. Infection of DR3(-/-) mice with Salmonella typhimurium was associated with defective microbial clearance and elevated bacterial load. Taken together, our findings indicate a novel protective role for the TL1A/DR3 axis in the regulation of mucosal homeostasis during acute intestinal injury/repair, which contrasts with its known pathogenic function during chronic intestinal inflammation.

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