Showing papers by "Rork Kuick published in 2011"
TL;DR: It is shown that TAMs express significantly higher levels of IRAK-M compared with peritoneal macrophages in a syngeneic mouse model of lung cancer, and TGF-β-dependent induction of IRAk-M expression is an important, clinically relevant mechanism by which tumors may circumvent anti-tumor responses ofmacrophages.
Abstract: TGF-β-induced IRAK-M expression in tumor-associated macrophages regulates lung tumor growth
113 citations
TL;DR: In vivo administration of the histone methylation inhibitor 3-deazaneplanocin A (DZNep) arrests ongoing GVHD in mice after allogeneic BM transplantation and preserves the antileukemia activity of donor T cells and did not impair the recovery of hematopoiesis and lymphocytes, leading to significantly improved survival of recipients after allogenicic BM transplation.
63 citations
TL;DR: The data reveal that rapamycin is a novel modulator of TGF-&bgr; signaling, and along with 17-AAG and LY294002, could be used as therapeutic agent for inhibiting EMT.
57 citations
TL;DR: In-depth quantitative proteomics was applied to 40 lung adenocarcinoma cell lines resulting in the identification of the known members of the ALDH family, and a distinct pattern of expression was observed in cells exhibiting epithelial features relative to cells exhibiting mesenchymal features.
Abstract: We have explored the potential of proteomic profiling to contribute to the delineation of the range of expression and subcellular localization of aldehyde dehydrogenases (ALDHs) in lung adenocarcinoma. In-depth quantitative proteomics was applied to 40 lung adenocarcinoma cell lines resulting in the identification of the known members of the ALDH family. Substantial heterogeneity in the level and occurrence of ALDHs in total lysates and on the cell surface and in their release into the culture media was observed based on mass spectrometry counts. A distinct pattern of expression of ALDHs was observed in cells exhibiting epithelial features relative to cells exhibiting mesenchymal features. Strikingly elevated levels of ALDH1A1 were observed in two cell lines. We also report on the occurrence of an immune response to ALDH1A1 in lung cancer.
14 citations
TL;DR: The results suggest that in neuroblastoma, clusterin exerts its anti-apoptotic effects downstream of Ku70 acetylation, likely by directly blocking Bax activation and affecting histone deacetylase-inhibitor-induced Ku70acetylation.
Abstract: Clusterin is a ubiquitously expressed glycoprotein with multiple binding partners including IL-6, Ku70, and Bax. Clusterin blocks apoptosis by binding to activated Bax and sequestering it in the cytoplasm, thereby preventing Bax from entering mitochondria, releasing cytochrome c, and triggering apoptosis. Because increased clusterin expression correlates with aggressive behavior in tumors, clusterin inhibition might be beneficial in cancer treatment. Our recent findings indicated that, in neuroblastoma cells, cytoplasmic Bax also binds to Ku70; when Ku70 is acetylated, Bax is released and can initiate cell death. Therefore, increasing Ku70 acetylation, such as by using histone deacetylase inhibitors, may be therapeutically useful in promoting cell death in neuroblastoma tumors. Since clusterin, Bax, and Ku70 form a complex, it seemed likely that clusterin would mediate its anti-apoptotic effects by inhibiting Ku70 acetylation and blocking Bax release. Our results, however, demonstrate that while clusterin level does indeed determine the sensitivity of neuroblastoma cells to histone deacetylase inhibitor-induced cell death, it does so without affecting histone deacetylase-inhibitor-induced Ku70 acetylation. Our results suggest that in neuroblastoma, clusterin exerts its anti-apoptotic effects downstream of Ku70 acetylation, likely by directly blocking Bax activation.
5 citations