Toll like receptor (TLR) signaling has been suggested to play an important role in the inflammatory microenvironment of solid tumors and through this inflammation-mediated tumor growth. Here, we studied the role of tumor cells in their process of self-maintaining TLR expression independent of inflammatory cells and cytokine milieu for autoregulative tumor growth signaling in pancreatic cancer. We analyzed the expression of TLR2, -4, and -9 in primary human cancers and their impact on tumor growth via induced activation in several established pancreatic cancers. TLR-stimulated pancreatic cancer cells were specifically investigated for activated signaling pathways of VEGF/PDGF and anti-apoptotic Bcl-xL expression as well as tumor cell growth. The primary pancreatic cancers and cell lines expressed TLR2, -4, and -9. TLR-specific stimulation resulted in activated MAP-kinase signaling, most likely via autoregulative stimulation of demonstrated TLR-induced VEGF and PDGF expression. Moreover, TLR activation prompted the expression of Bcl-xL and has been demonstrated for the first time to induce tumor cell proliferation in pancreatic cancer. These findings strongly suggest that pancreatic cancer cells use specific Toll like receptor signaling to promote tumor cell proliferation and emphasize the particular role of TLR2, -4, and -9 in this autoregulative process of tumor cell activation and proliferation in pancreatic cancer.

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In patients with peritoneal carcinomatosis cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) represents a promising treatment strategy. Here, we studied the role of hyperthermic chemotherapy on heat shock protein (HSP) expression and induction of tumor cell death and survival. HSP27, HSP70, and HSP90 combined with effects on tumor cell proliferation and chemosensitivity were analyzed in human colon cancer. Hyperthermic chemotherapy resulted in significant HSP27/HSP70 and HSP90 gene/protein overexpression in analyzed HT-29/SW480/SW620 colon cancer cells and peritoneal metastases from patients displaying amplified expression of proliferation markers, proliferating cell nuclear antigen and antiapoptotic protein Bcl-xL. Moreover, functionally increased chemoresistance against 5-fluorouracil/mitomycin C and oxaliplatin after hyperthermic chemotherapy points to induced survival mechanisms in cancer cells. In conclusion, the results indicate that intracellular HSP-associated antiapoptotic and proliferative effects after hyperthermic chemotherapy negatively influence beneficial effects of hyperthermic chemotherapy-induced cell death. Therefore, blocking HSPs could be a promising strategy to further improve the rate of tumor cell death and outcome of patients undergoing HIPEC therapy.

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showed that the patients treated with the adapted protocol presented similar results to the original protocol in relation to the muscular conditions.

Background: CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). Aim: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. Methods: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. Results: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. Conclusions: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.

OBJECTIVES:The removal of pre-malignant colorectal lesions prevents cancer. Hyoscine has been proposed as a means of improving diagnosis by reducing colonic movements. The aim of this study was to analyze whether this anti-spasmodic enhances the detection of pre-malignant colorectal lesions.METHODS:In a randomized, double-blinded fashion patients received hyoscine or a saline solution in all consecutive colonoscopies in which the cecum was reached. Lesions were analysed with respect to number, size, location, histology and capillary pattern.RESULTS:A total of 440 colonoscopies were randomized. The overall polyp detection rate (PDR) and the adenoma detection rate (ADR) were 65.2% and 49.3%, respectively. In the hyoscine group, non-polypoid lesions were detected significantly more often (p=0.01). In the placebo group 281 lesions were diagnosed (202 adenomas) and in the hyoscine group 282 lesions were detected (189 adenomas) (p=0.23). The PDR and ADR were similar between the placebo and hyoscine groups (64% vs 66% and 50% vs 47%, respectively). No differences were observed between the two groups in the advanced-ADR or advanced neoplasia detection rate, as well the mean numbers of polyps, adenomas, advanced adenomas and advanced neoplasias detected per patient. The administration of hyoscine also did not improve the diagnostic accuracy of digital chromoendoscopy. The presence of adenomatous polyps in the right colon was detected significantly more frequently in the hyoscine group (OR 5.41 95% CI 2.7 - 11; p<0.01 vs OR 2.3 95% CI 1.1 - 4.6; p=0.02).CONCLUSION:The use of hyoscine before beginning the withdrawal of the colonoscope does not seem to enhance the PDR and the ADR.

RESUMOObjetivo: Avaliar os efeitos clínicos da secreção das glândulas salivares labiais como alternativa de lubrificação ocular para alívio do olho seco, em casos moderados, severos e refratários ao tratamento clínico, através da técnica de transposição de glândulas salivares labiais para o fórnice conjuntival pela autoenxertia. Métodos: Foram selecionados 17 cães os quais apresentavam olho seco autoimune sem reposta satisfatória ao tratamento clínico. O teste lacrimal de Schirmer e o tempo de ruptura do filme lacrimal foram realizados no pré-operatório para avaliar a quantidade e a qualidade da lágrima produzida. Os pacientes foram submetidos aos exames oftálmicos completos no pré-operatório, a cada 15 dias por dois meses e a cada 30 dias por mais dois meses, totalizando seis retornos pós-operatórios. No pré-operatório e em todos os pós-operatórios fotografias digitais foram tiradas para o arquivo fotográ-fico. Utilizou-se o programa photoshop para avaliação e marcação dos neovasos corneanos em todos os retornos. Resultados: Houve redução em todos os casos da secreção mucopurulenta, hiperemia conjuntival e blefarospasmo, bem como estabilização de lesões pré-existentes e redução importante do número de neovasos corneanos. A transposição resultou na melhora do tempo de ruptura do filme lacrimal, porém sem alterações significativas no teste de Schirmer. Conclusão: O transplante das glândulas salivares labiais para o fórnice conjuntival é um procedimento de fácil execução, rápido, eficaz, acessível a qualquer cirurgião veterinário oftalmologista e de grande valia para casos moderados e severos de ceratoconjuntivite seca não responsivos às medicações existentes.