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排序方式: 共有1296条查询结果,搜索用时 31 毫秒
51.
Xi-wei JI Run-tao LI Zai-quan LI Liang LI Xue-yan SHAO Si-yuan WANG Yin YUAN Tian-yan ZHOU Wei LU 《Acta pharmacologica Sinica》2014,35(2):239-247
Aim: To investigate the effects of a novel dithiocarbamate derivative TM208 on human breast cancer cells as well as the pharmacoki- netic characteristics of TM208 in human breast cancer xenograft mice. Methods: Human breast cancer MCF-7 and MDA-MB-231 cells were treated with TM208 or a positive control drug tamoxifen. Cell pro- liferation was examined using SRB and colony formation assays. Cell apoptosis was analyzed with Annexin V-FITC/PI staining assay. Protein expression was examined with Western blot, ELISA and immunohistochemical analyses. MCF-7 breast cancer xenograft nude mice were orally administered TM208 (50 or 150 mg.k$1〈1-1) or tamoxifen (50 mg.kgl〈t-~) for 18 d. On d 19, the tumors were collected for analyses. Blood samples were collected from the mice treated with the high dose of TM208, and plasma concentrations of TM208 were measured using LC-MS/MS. Results: Treatment of MCF-7 and MDA-MB-231 cells with TM208 dose-dependently inhibited the cell proliferation and colony formation in vitro (the IC~o values were 36.38+3.77 and 18.13+0.76 pmol/L, respectively). TM208 (20-150pmol/L) dose-dependently induced apoptosis of both the breast cancer cells in vitro. In MCF-7 breast cancer xenograft nude mice, TM208 administration dose-depend- ently reduced the tumor growth, but did not result in the accumulation of TM208 or weight loss. TM208 dose-dependently inhibited the phosphorylation of EGFR and ERK1/2 in both the breast cancer cells in vitro as well as in the MCF-7 xenograft tumor. Conclusion: Inhibition of EGFR autophosphorylation plays an important role in the anticancer effect of TM208 against human breast cancer. 相似文献
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54.
Naohisa Ogo Yoshinobu Ishikawa Jun-ichi Sawada Kenji Matsuno Akihiro Hashimoto Akira Asai 《ACS medicinal chemistry letters》2015,6(9):1004-1009
l-cysteine derivatives as selective KSP inhibitors. Here, we
report further optimizations using docking modeling in the L5 allosteric
binding site, which led to the discovery of several high affinity
derivatives with two fused phenyl rings in the trityl group giving
low nanomolar range KSP ATPase inhibition. The representative derivatives
potently inhibited cell growth of HCT116 cells in correlation with
KSP inhibitory activities and significantly suppressed tumor growth
in the xenograft model in vivo. 相似文献
55.
John E. Campbell Kevin W. Kuntz Sarah K. Knutson Natalie M. Warholic Heike Keilhack Tim J. Wigle Alejandra Raimondi Christine R. Klaus Nathalie Rioux Akira Yokoi Satoshi Kawano Yukinori Minoshima Hyeong-Wook Choi Margaret PorterScott Nigel J. Waters Jesse J. Smith Richard Chesworth Mikel P. Moyer RobertA. Copeland 《ACS medicinal chemistry letters》2015,6(5):491-495
56.
Orsolic N Giles FJ Gourdeau H Golemovic M Beran M Cortes J Freireich EJ Kantarjian H Verstovsek S 《British journal of haematology》2004,124(6):727-738
The in vitro and in vivo activity of a deoxycytidine analogue, troxacitabine, alone or in combination with imatinib mesylate (IM), was evaluated against human chronic myeloid leukaemia (CML) cell lines both sensitive (KBM5 and KBM7) and resistant (KBM5-R and KBM7-R) to IM. These cell lines differ in their sensitivity to IM but all showed similar sensitivity to treatment with troxacitabine (IC50 = 0.5-1 micromol/l). Combined treatment with troxacitabine and IM revealed additive or synergistic effects. Greater apoptotic response was seen with combined treatment than with either agent alone in KBM7-R cells. In clonogenic assays, troxacitabine showed activity against mononuclear cells from CML patients (IC50 = 0.01 micromol/l) with either IM-sensitive or resistant disease. In vivo efficacy studies were carried out in severe combined immunodeficient mice bearing KBM5 or KBM5-R cells. Troxacitabine was administered i.p. daily for 5 d starting on day 20, at doses of 5, 10, 20, or 25 mg/kg. IM was administered i.p. twice a day for 10 d at a dose of 50 mg/kg starting on day 25. In this setting of late stage disease, troxacitabine led to a significant increase in life span, while IM did not. When IM was combined with troxacitabine at 10 and 25 mg/kg in the KBM5 xenograft model, a further increase in life span was observed and some mice achieved long-term survival. These data indicate that the combination of troxacitabine and IM has significant preclinical activity in advanced CML and that clinical evaluation of this combination is warranted. 相似文献
57.
Bertrand Vabres Yan Chérel David Minault Jérémy Hervouet Yvette Ducournau Anne Moreau Véronique Daguin Flora Coulon Annaïck Pallier Sophie Brouard Simon C. Robson Mark B. Nottle Peter J. Cowan Eric Venturi Pascal Mermillod Philippe Brachet Cesare Galli Irina Lagutina Roberto Duchi Jean‐Marie Bach Bernard Vanhove 《Xenotransplantation》2014,21(5):431-443
58.
《Journal of pediatric urology》2014,10(1):123-129
ObjectiveLack of appropriate approaches that reliably predict response of Wilms' tumor (WT) to anticancer agents remains a major deficiency in clinical practice of individualized cancer therapy. The aim of this study was to establish a patient-derived tumor tissue (PDTT) xenograft model of WT for individualized chemotherapeutic regimen selection in accordance with the patient's tumor nature.Material and methodsTumor specimens of a primary WT were orthotopically implanted into three nude mice, and after 4 weeks xenografts were harvested for serial heterotopic transplantation in 20 nude mice that were divided into three experimental groups and one control group. In vitro and in vivo chemosensitivity to doxorubicin, actinomycin-D, and vincristine were evaluated. Hematoxylin and eosin (H&E) staining and immunohistochemical examination with desmin, vimentin, myogenin, and neuron-specific enolase (NSE) were also applied to determine histological stability of the xenograft during serial transplantation compared with the original tumor tissue.ResultsThe xenograft model was successfully established. Histopathologic characteristics of the xenograft tumors were similar to the patient's tumor. Early passage of the PDTT showed a similar chemosensitivity pattern to the original tumor tissue.ConclusionsPDTT xenograft of WT provides an appropriate model for individualized cancer therapeutic regimen selection by means of its biological stability compared with original patient's tumor. 相似文献
59.
Ryan M. O'Connell Aadel A. Chaudhuri Dinesh S. Rao William S. J. Gibson Alejandro B. Balazs David Baltimore 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(32):14235-14240
The production of blood cells depends on a rare hematopoietic stem-cell (HSC) population, but the molecular mechanisms underlying HSC biology remain incompletely understood. Here, we identify a subset of microRNAs (miRNAs) that is enriched in HSCs compared with other bone-marrow cells. An in vivo gain-of-function screen found that three of these miRNAs conferred a competitive advantage to engrafting hematopoietic cells, whereas other HSC miRNAs attenuated production of blood cells. Overexpression of the most advantageous miRNA, miR-125b, caused a dose-dependent myeloproliferative disorder that progressed to a lethal myeloid leukemia in mice and also enhanced hematopoietic engraftment in human immune system mice. Our study identifies an evolutionarily conserved subset of miRNAs that is expressed in HSCs and functions to modulate hematopoietic output. 相似文献
60.