The acquisition of the capacity to invade surrounding tissues confers a more malignant phenotype to tumor cells and is necessary for the establishment of metastases. The understanding of the molecular mechanisms underlying cell invasion in human solid tumors such as colorectal cancers could provide not only more sensitive prognostic analyses but also novel molecular targets for cancer therapy.We report in this article that K ؉ ion channels belonging to the HERG family are important determinants for the acquisition of an invasive phenotype in colorectal cancers. The herg1 gene and HERG1 protein are expressed in many colon cancer cell lines, and the activity of HERG channels modulates colon cancer cell invasiveness. Moreover, the amount of HERG1 protein expressed on the plasma membrane is directly related to the invasive phenotype of colon cancer cells.Finally, both the herg1 gene and HERG1 protein were expressed in a high percentage of primary human colorectal cancers, with the highest incidence occurring in metastatic cancers, whereas no expression could be detected either in normal colonic mucosa or in adenomas.
Helicobacter pylori infection is characterized by an inflammatory infiltrate, consisting mainly of neutrophils and T cells. This study was undertaken to evaluate the type of gastric T cell response elicited by the secreted peptidyl prolyl cis, trans-isomerase of H. pylori (HP0175) in patients with distal gastric adenocarcinoma. The cytokine profile and the effector functions of gastric tumor-infiltrating lymphocytes (TILs) specific for HP0175 was investigated in 20 patients with distal gastric adenocarcinoma and H. pylori infection. The helper function of HP0175-specific TILs for monocyte MMP-2, MMP-9, and VEGF production was also investigated. TILs cells from H. pylori infected patients with distal gastric adenocarcinoma produced Interleukin (IL)-17 and IL-21 in response to HP0175. HP0175-specific TILs showed poor cytolytic activity while expressing helper activity for monocyte MMP-2, MMP-9 and VEGF production. These findings indicate that HP0175 is able to drive gastric Th17 response. Thus, HP0175, by promoting pro-inflammatory low cytotoxic TIL response, matrix degradation and pro-angiogenic pathways, may provide a link between H. pylori and gastric cancer.
Pancreatic cancer (PC) is an aggressive disease with dismal prognosis. Surgical resection is the recommended treatment for long-term survival, but patients with resectable PC are in the minority (with a 5-year survival rate of 20 %). Therefore, development of novel therapeutic strategies, such as anti-PC immunotherapy, is crucial. α-Enolase (ENO1) is an enzyme expressed on the surface of pancreatic cancer cells and is able to promote cell migration and cancer metastasis. The capacity of ENO1 to induce an immune response in PC patients renders it a true tumor-associated antigen. In this study, we characterized the effector functions of ENO1-specific T cells isolated from PC patients, and we specifically evaluated the successful role of intra-tumoral T helper 17 (Th17) cells and the inhibitory role of regulatory T (Tregs) cells in respectively promoting or reducing the cancer-specific immune response. In this ex vivo study, we have demonstrated, for the first time, that ENO1-specific Th17 cells have a specific anti-cancer effector function in PC patients, and that there are decreased levels of these cells in cancer compared to healthy mucosa. Conversely, there are elevated levels of ENO1-specific Tregs in PC patients which lead to inhibition of the antigen-specific effector T cells, thus highlighting a possible role in promoting PC progression. These results may be relevant for the design of novel immunotherapeutic strategies in pancreatic cancer.
BackgroundImmediate implant reconstruction after a conservative mastectomy is an attractive option made easier by prosthetic devices. Titanized polypropylene meshes are used as a hammock to cover the lower lateral implant pole. We conducted a prospective nonrandomized single-institution study of reconstructions using titanium-coated meshes either in a standard muscular mesh pocket or in a complete subcutaneous approach. The complete subcutaneous approach means to wrap an implant with titanized mesh in order to position the implant subcutaneously and spare muscles.MethodsBetween November 2011 and January 2014, we performed immediate implant breast reconstructions after conservative mastectomies using TiLoop® Bra, either with the standard retropectoral or with a prepectoral approach. Selection criteria included only women with normal Body Mass Index (BMI), no large and very ptotic breasts, no history of smoking, no diabetes, and no previous radiotherapy. We analyzed short-term outcomes of such procedures and compared the outcomes to evaluate implant losses and surgical complications.ResultsA total of 73 mastectomies were performed. Group 1 comprised 29 women, 5 bilateral procedures, 34 reconstructions, using the standard muscular mesh pocket. Group 2 comprised 34 women, 5 bilateral procedures, 39 reconstructions with the prepectoral subcutaneous technique. Baseline and oncologic characteristics were homogeneous between the two groups. After a median follow-up period of 13 and 12 months, respectively, no implant losses were recorded in group 1, and one implant loss was recorded in group 2. We registered three surgical complications in group 1 and two surgical complications in group 2.ConclusionsTitanium-coated polypropylene meshes, as a tool for immediate definitive implant breast reconstruction, resulted as safe and effective in a short-term analysis, both for a retropectoral and a totally subcutaneous implant placement. Long-term results are forthcoming. A strict selection is mandatory to achieve optimal results.Level of Evidence: Level II, therapeutic study.
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