The Experts below are selected from a list of 359358 Experts worldwide ranked by ideXlab platform
Senitiroh Hakomori - One of the best experts on this subject based on the ideXlab platform.
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functional role of glycosphingolipids in contact Inhibition of Growth in a human mammary epithelial cell line
FEBS Letters, 2017Co-Authors: Xiaohua Huang, Nathan Schurman, Kazuko Handa, Senitiroh HakomoriAbstract:We have demonstrated previously the involvement of certain glycosphingolipids (GSLs) in “contact Inhibition” (dependent on cell-to-cell contact) of cell Growth. Here, we examined the roles of specific GSLs in contact Inhibition of the human epithelial cell line MCF10A. Contact-inhibited cells show increased expression of the ganglioside GD3 and the globo-series GSL Gb3, and of the mRNAs for the corresponding sialyltransferases ST8SIA1 (GD3 synthase) and galactosyltransferase A4GALT (Gb3 synthase). siRNA knockdown of ST8SIA1 and/or A4GALT significantly suppress contact Inhibition. Exogenous addition of GD3 or Gb3 inhibits proliferation of low-density cells. Our findings suggest that GSLs play functional roles in contact Inhibition of these cells and that Merlin/NF2, a tumor suppressor protein, is involved in the GSL function. This article is protected by copyright. All rights reserved.
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functional role of glycosphingolipids in contact Inhibition of Growth in a human mammary epithelial cell line
FEBS Letters, 2017Co-Authors: Xiaohua Huang, Nathan Schurman, Kazuko Handa, Senitiroh HakomoriAbstract:We have demonstrated previously the involvement of certain glycosphingolipids (GSLs) in 'contact Inhibition' (dependent on cell-to-cell contact) of cell Growth. Here, we examined the roles of specific GSLs in contact Inhibition of the human epithelial cell line MCF10A. Contact-inhibited cells show increased expression of the ganglioside GD3 and the globo-series GSL Gb3, and of the mRNAs for the corresponding sialyltransferases ST8SIA1 (GD3 synthase) and galactosyltransferase A4GALT (Gb3 synthase). siRNA knockdown (KD) of ST8SIA1 and/or A4GALT significantly suppresses contact Inhibition. Exogenous addition of GD3 or Gb3 inhibits proliferation of low-density cells. Our findings suggest that GSLs play functional roles in contact Inhibition of these cells and that Merlin/NF2, a tumor suppressor protein, is involved in the GSL function.
Chung S Yang - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of Growth and induction of apoptosis in human cancer cell lines by tea polyphenols
Carcinogenesis, 1998Co-Authors: Guangyu Yang, Jie Liao, Edward J Yurkow, Chung S YangAbstract:In order to study the biological activities of tea preparations and purified tea polyphenols, their Growth inhibitory effects were investigated using four human cancer cell lines. Growth Inhibition was measured by [ 3 H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) displayed strong Growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC 50 values of 22 μM, but were less effective against lung cancer cell line H441 and colon cancer cell line HT-29 with IC 50 values 2- to 3-fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)-epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the Growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols. Exposure of H661 cells to 30 μM EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 μM of these compounds, the apoptosis indices were 82, 76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose-dependent formation of H 2 O 2 . Addition of H 2 O 2 to H661 cells caused apoptosis in a manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H 2 O 2 may mediate apoptosis and that this may contribute to the Growth inhibitory activities of tea polyphenols in vitro.
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Inhibition of Growth and induction of apoptosis in human cancer cell lines by tea polyphenols
Carcinogenesis, 1998Co-Authors: Guangyu Yang, Jie Liao, Edward J Yurkow, Kyounghyun Kim, Chung S YangAbstract:In order to study the biological activities of tea preparations and purified tea polyphenols, their Growth inhibitory effects were investigated using four human cancer cell lines. Growth Inhibition was measured by [3H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) displayed strong Growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC50 values of 22 microM, but were less effective against lung cancer cell line H441 and colon cancer cell line HT-29 with IC50 values 2- to 3-fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)-epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the Growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols. Exposure of H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microM of these compounds, the apoptosis indices were 82, 76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose-dependent formation of H2O2. Addition of H2O2 to H661 cells caused apoptosis in a manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H2O2 may mediate apoptosis and that this may contribute to the Growth inhibitory activities of tea polyphenols in vitro.
Robert J Smith - One of the best experts on this subject based on the ideXlab platform.
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endotoxin induced Inhibition of Growth hormone receptor signaling in rat liver in vivo
Endocrinology, 1999Co-Authors: Yilei Mao, Peira Ling, Timothy P Fitzgibbons, Karen C Mccowen, Peter G Frick, Bruce R Bistrian, Robert J SmithAbstract:The bacterial lipopolysaccharide endotoxin induces a catabolic response characterized by resistance to multiple anabolic hormones. The objective of this study was to determine the effects of endotoxin on the GH signaling pathway in rat liver in vivo. After the iv injection of Escherichia coli endotoxin (1 mg/kg), there was a progressive decrease in liver STAT5 (signal transducer and activator of transcription-5) tyrosine phosphorylation in response to GH (40% decrease 6 h after endotoxin), which occurred in the absence of a change in abundance of the STAT5 protein. Endotoxin resulted in a rapid 40-fold increase in liver Janus family kinase-2 (JAK2) messenger RNA, followed by a 2-fold increase in JAK2 protein abundance. This was associated with a 50% decrease in phosphorylated/total JAK2 after GH stimulation. GH receptor abundance was unchanged, suggesting a postreceptor site of endotoxin-induced GH resistance. Rat complementary DNAs for three members of the suppressor of cytokine signaling gene family were cloned [cytokine-inducible sequence (CIS), suppressor of cytokine signaling-2 (SOCS-2), and SOCS-3] and, using these probes, messenger RNAs for SOCS-3 and CIS were shown to be increased 10- and 4-fold above control values, respectively, 2 h after endotoxin infusion. The finding of endotoxin Inhibition of in vivo STAT5 tyrosine phosphorylation in response to a supramaximal dose of GH in the absence of a change in GH receptor abundance or total GH-stimulated JAK2 tyrosine phosphorylation provides the first demonstration of acquired postreceptor GH resistance. We hypothesize that this may occur through a specificity-spillover mechanism involving the induction of SOCS genes by cytokines released in response to endotoxin and subsequent SOCS Inhibition of GH signaling.
Guangyu Yang - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of Growth and induction of apoptosis in human cancer cell lines by tea polyphenols
Carcinogenesis, 1998Co-Authors: Guangyu Yang, Jie Liao, Edward J Yurkow, Chung S YangAbstract:In order to study the biological activities of tea preparations and purified tea polyphenols, their Growth inhibitory effects were investigated using four human cancer cell lines. Growth Inhibition was measured by [ 3 H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) displayed strong Growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC 50 values of 22 μM, but were less effective against lung cancer cell line H441 and colon cancer cell line HT-29 with IC 50 values 2- to 3-fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)-epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the Growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols. Exposure of H661 cells to 30 μM EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 μM of these compounds, the apoptosis indices were 82, 76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose-dependent formation of H 2 O 2 . Addition of H 2 O 2 to H661 cells caused apoptosis in a manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H 2 O 2 may mediate apoptosis and that this may contribute to the Growth inhibitory activities of tea polyphenols in vitro.
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Inhibition of Growth and induction of apoptosis in human cancer cell lines by tea polyphenols
Carcinogenesis, 1998Co-Authors: Guangyu Yang, Jie Liao, Edward J Yurkow, Kyounghyun Kim, Chung S YangAbstract:In order to study the biological activities of tea preparations and purified tea polyphenols, their Growth inhibitory effects were investigated using four human cancer cell lines. Growth Inhibition was measured by [3H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) displayed strong Growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC50 values of 22 microM, but were less effective against lung cancer cell line H441 and colon cancer cell line HT-29 with IC50 values 2- to 3-fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)-epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the Growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols. Exposure of H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microM of these compounds, the apoptosis indices were 82, 76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose-dependent formation of H2O2. Addition of H2O2 to H661 cells caused apoptosis in a manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H2O2 may mediate apoptosis and that this may contribute to the Growth inhibitory activities of tea polyphenols in vitro.
Andrew V Schally - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of Growth of experimental human and hamster pancreatic cancers in vivo by a targeted cytotoxic bombesin analog
Pancreas, 2005Co-Authors: Karoly Szepeshazi, Andrew V Schally, Attila Nagy, Gabor HalmosAbstract:OBJECTIVES: Targeting anticancer agents to receptors for peptide hormones such as bombesin/gastrin-releasing peptide (GRP) on tumor cells increases the efficacy and lowers the toxicity of cancer therapy. We studied the expression of bombesin/GRP receptors in 6 experimental pancreatic cancers and evaluated tumor Inhibition in vivo produced by targeted chemotherapy with the cytotoxic bombesin analog AN-215. METHODS: Nude mice with xenografts of Panc-1, CFPAC-1, Capan-1, Capan-2, MiaPaCa-2, and SW-1990 human ductal pancreatic cancers, as well as hamsters with nitrosamine-induced pancreatic cancers, were treated with AN-215 or its cytotoxic radical 2-pyrrolinodoxorubicin (AN-201) for 7 to 12 weeks. Tumor Growth reduction and survival were analyzed, and cell proliferation rate and apoptosis were examined by histologic methods. Bombesin/GRP receptors on the tumors were studied by ligand-binding assays and their mRNA expression was studied by reverse transcriptase-polymerase chain reaction. RESULTS: All tumors expressed mRNA for subtype 1 bombesin/GRP receptor, but MiaPaCa-2, and in one experiment, SW-1990 tumors did not show binding sites for bombesin. AN-215 powerfully inhibited the Growth of all pancreatic cancers that expressed functional receptors for bombesin/GRP. AN-201 was less effective on most tumors and somewhat more toxic than AN-215. CONCLUSIONS: Bombesin/GRP receptors are expressed on most ductal pancreatic carcinoma cell lines and can be used for targeted chemotherapy with the cytotoxic bombesin analog AN-215.
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Inhibition of Growth of ov 1063 human epithelial ovarian cancers and c jun and c fos oncogene expression by bombesin antagonists
British Journal of Cancer, 2000Co-Authors: Ioulia Chatzistamou, Andrew V Schally, Baodong Sun, Patricia Armatis, Karoly SzepeshaziAbstract:Inhibition of Growth of OV-1063 human epithelial ovarian cancers and c- jun and c- fos oncogene expression by bombesin antagonists
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Inhibition of Growth of human ovarian cancer in nude mice by luteinizing hormone releasing hormone antagonist cetrorelix sb 75
Fertility and Sterility, 1995Co-Authors: Alberto Manetta, Gisela Gamboavujicic, Potenciano Paredes, Dennis Emma, Shu Liao, Lily Leong, Barbara Asch, Andrew V SchallyAbstract:Objective To report on the in vitro and in vivo inhibitory effects of LH-releasing hormone (LH-RH) antagonist Cetrorelix (SB-75; Asta Medica, Frankfurt-Main, Germany) against a panel of human ovarian carcinomas. Interventions In vitro studies: the effect of SB-75 was measured using a standardized chemo-sensitivity assay in the following ovarian cancer cell lines: UCI 101; UCI 107; PA-1; NIH: OVCAR 3; UCLA: 222; A2780, parental; A2780-CR, cisplatin resistant; A2780-DR, doxorubicin resistant; and the human breast cancer cell line, MCF-7. Results were expressed as percent Growth Inhibition determined by crystal violet photometric analysis. In vivo studies: the antiproliferative effect of this agent was examined using UCI-107, a primary epithelial ovarian carcinoma cell line, in a nude mouse model. On day 0,10 × 10 6 UCI 107 cells were implanted subcutaneously into 20 intact female athymic nude mice (5 to 6 weeks old). On day 8, the mice were randomly divided into two groups of 10; control mice were implanted with miniosmotic pumps filled with a vehicle solution consisting of 5.2% mannitol in saline; and treated animals received pumps filled to deliver continuous administration of SB-75 at 60 µ g per mouse per day. Results In vitro studies: direct Inhibition of cell proliferation by SB-75 was not observed at concentrations ranging from 1 nM to 100 µ M (exposure lasting three to four cell doublings) with the exception of MCF-7, which demonstrated a 33% Inhibition at the latter concentration. In vivo studies: on day 16, caliper measurements were taken from subcutaneous tumor nodules in SB-75-treated and untreated mice and a significant difference of 270% in mean tumor volume was observed. End point was determined, on day 30, when control tumor volume approached 10,000 mm 3 . At that time the difference in mean tumor volumes increased to 600%, indicating a substantial antiproliferative effect had been achieved in the SB-75-treated group. Conclusion Our in vitro findings show direct Inhibition by SB-75 on proliferation of human breast cancer cells. This direct Inhibition in vitro was not observed in our ovarian cancer cell lines. However, in vivo SB-75 caused a significant Inhibition of Growth of human epithelial ovarian cancer. This may be a result of Inhibition of the pituitary gonadal axis and gonadotropin secretion. Our results warrant further investigation.