These observations in cultured epithelial cells are consistent with the observation that post-IRI kidney epithelial tubules have autophagosomes detected by reorganization selleck chemical of native LC3 to vesicles in sections stained with anti-LC3 antibodies (Supplemental Fig. S2A) as well as detection of increased transcripts for the autophagy proteins Atg5 and Atg7 (Supplemental Fig. S2B). Gpnmb is recruited to the phagocytic cup and promotes phagosomal acidification in epithelial cells Macroautophagy is a bulk degradation pathway involved in the disposal of used macromolecular structures within the cell via lysosomal degradation (33). Since Gpnmb colocalizes with autophagy prot
Colorectal cancer (CRC) is one of the most frequent cancers in the world with a very high mortality rate even after surgical resection, radio- and chemotherapy (Cancer Research Campaign, 1999).
It seems evident that CRC frequently follows and develops from adenomatous polyps (Leslie et al, 2002). Several studies suggest that non-steroidal anti-inflammatory drugs (NSAIDS) such as selective cyclooxygenase-2 (COX2) inhibitors have an anti-neoplastic effect (Giercksky, 2001; Cho et al, 2007; Saini et al, 2009). Cyclooxygenase-2, one of the key enzymes of arachidone acid metabolism and prostaglandin synthesis, is described to be involved in the early stage of colorectal carcinogenesis. Cyclooxygenase-2 overexpression was shown in 85% of CRCs in proportion to normal tissue, and this expression alteration occurs in 50% of adenomas (Eberhart et al, 1994).
Cyclooxygenase-2 can be activated through several cancer-associated biological pathways, such as Wnt- and Ras-related ones (Brown and DuBois, 2005). Pre-clinical studies suggest that the treatment of colorectal adenomas with selective COX2 inhibitors can contribute to the chemoprevention of CRC (Brown and DuBois, 2005). The lack of COX2 expression characterises most normal tissues, but its level rapidly increases under mitogens and cytokines, which results in the accumulation of prostanoids (such as PGE2) in neoplastic and inflamed tissues (Eisinger et al, 2007). Elevated COX2 levels may lead to tumour development and expansion through activation of EGFR- and Tcf/Lef signal transduction pathways. Inhibition GSK-3 of apoptosis, interference with the immune system and facilitation of angiogenesis (vascular endothelial growth factor (VEGF) activation) and tumour invasion may also result from elevated PGE2 levels (Gr?sch et al, 2006). Selective COX2 inhibitors seem to reduce the risk of developing colon cancer through COX2-dependent and -independent mechanisms.