Résumé
The interactions between the tumor microenvironment and tumor cells determine the behavior of the primary tumors. Whether cancer-associated fibroblasts (CAF) have a tumor progressive or a protective role likely depends on the type of tumor cells and the CAF subpopulation. In the present study, we analyzed the prognostic significance of CAF subpopulations in colorectal cancer (CRC). CAF phenotypes were analyzed in 302 CRC patients by using antibodies against podoplanin (PDPN), alpha-smooth muscle actin (alpha-SMA), and S100A4. The relationship between the CAF phenotypes and 11 clinicopathological parameters were evaluated and their prognostic significance was analyzed from the disease-free and overall survival times. We observed that at the tumor invasive front, PDPN CAFs were present in 40% of the cases, and S100A4 or alpha-SMA CAFs were detected in all the cases. PDPN/S100A4 and alpha-SMA/S100A4 dual-stained CAFs were observed in 10% and 40% of the cases, respectively. The PDPN+ CAFs were associated with 6 favorable clinicopathological parameters and prolonged disease-free survival time. The PDPN-/alpha-SMA(high) CAFs were associated with 6 aggressive clinicopathological parameters and tended to exhibit shorter disease-free survival time. On the other hand, the PDPN-/S100A4(high) CAFs were associated with 2 tumor progression parameters, but not with disease prognosis. The PDPN+ CAF phenotype is distinct from the alpha-SMA or S100A4 CAFs in that it is associated with less aggressive tumors and a favorable prognosis, whereas the PDPN-/alpha-SMA(high) or PDPN-/S100A4(high) CAFs are associated with tumor progression in CRC. These findings suggest that CAFs can be a useful prognostic biomarker or potential targets of anti-cancer therapy in CRC.
Sujets)
Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Actines/immunologie , Anticorps/immunologie , Antigène carcinoembryonnaire/sang , Tumeurs colorectales/diagnostic , Survie sans rechute , Fibroblastes/cytologie , Immunohistochimie , Métastase lymphatique , Glycoprotéines membranaires/immunologie , Stadification tumorale , Phénotype , Pronostic , Protéines S100/immunologie , Marqueurs biologiques tumoraux/métabolismeRésumé
PURPOSE: The purpose of management of the donor is to maintain a moist condition that promotes healing process and prevents pain, infection. We have performed a prospective study to compare the usefulness between Aquacel Ag(R) and Mepitel(R). METHODS: 36 consecutive patients, in whom STSG was performed, were included into the study. STSG are harvested as a usual manner and the donor site are dressed with Aquacel Ag(R) or Mepitel(R), alternatively. The usefulness are compared with re-epithelialization, pain, frequency to change the second dressing, and ease of application. RESULTS: There are no differences in the days of re-epithelialization, pain perception of patients, but significantly differences in frequency to change the second dressing, and ease of application. Aquacel Ag(R) is better than Mepitel(R). CONCLUSION: We concluded that Aquacel Ag(R) dressing is better than Mepitel(R) for STSG donor site just in the frequency to change the second dressing and ease of application.
Sujets)
Humains , Bandages , Carboxyméthylcellulose de sodium , Perception de la douleur , Études prospectives , Réépithélialisation , Peau , Donneurs de tissus , TransplantsRésumé
Fe65 has been characterized as an adaptor protein, originally identified as an expressed sequence tag (EST) corresponding to an mRNA expressed at high levels in the rat brain. It contains one WW domain and two phosphotyrosine interaction/phosphotyrosine binding domains (PID1/PID2). As the neuronal precursor cell expressed developmentally down regulated 4-2 (Nedd4-2) has a putative WW domain binding motif (72PPLP75) in the N-terminal domain, we hypothesized that Fe65 associates with Nedd4-2 through a WW domain interaction, which has the characteristics of E3 ubiquitin-protein ligase. In this paper, we present evidence for the interaction between Fe65 WW domain and Nedd4-2 through its specific motif, using a pull down approach and co-immunoprecipitation. Additionally, the co-localization of Fe65 and Nedd4-2 were observed via confocal microscopy. Co-localization of Fe65 and Nedd4-2 was disrupted by either the mutation of Fe65 WW domain or its putative binding motif of Nedd4-2. When the ubiquitin assay was performed, the interaction of Nedd4-2 (wt) with Fe65 is required for the cell apoptosis and the ubiquitylation of Fe65. We also observed that the ubiquitylation of Fe65 (wt) was augmented depending on Nedd4-2 expression levels, whereas the Fe65 WW domain mutant (W243KP245K) or the Nedd4-2 AL mutant (72PPLP75 was changed to 72APLA75) was under-ubiquitinated significantly. Thus, our observations implicated that the protein-protein interaction between the WW domain of Fe65 and the putative binding motif of Nedd4-2 down-regulates Fe65 protein stability and subcellular localization through its ubiquitylation, to contribute cell apoptosis.