Abstract:
:The antiproliferative effect of simvastatin on tumor cells has been speculated to be by intracellular signal inhibition through 3-hydroxy-3-methylglutaryl acetyl coenzyme A reductase. We examined the killing effect of simvastatin on imatinib-sensitive and resistant chronic myelogenous leukemia (CML) cells (three kinds of CML cell lines representative of each hematopoietic lineage: K562, KCL22, and LAMA84) and T315I and E255K site-directed mutant cells (Ba/F3). The in-vivo effect of simvastatin was determined in K562-xenografted nude mice. Cotreatment with imatinib and simvastatin in imatinib-resistant CML cells showed a synergistic killing effect in K562-R, KCL22-R, LAMA84-R, and E255K mutant cells, but only an additive effect in the T315I mutant cell, although a single treatment of simvastatin strongly inhibited T315I mutant cells. Mechanisms of killing were an induction of apoptosis and cell cycle arrest, through inhibition of tyrosine phosphorylation, and activated STAT5 and STAT3. Simvastatin suppressed the growth of K562-transplanted tumors, and cotreatment with imatinib was more effective in reducing tumor size. Simvastatin also killed primary CD34 cells from patients with CML more efficiently, compared with CD34 CML cells. Our study shows a synergic effect of imatinib and simvastatin both in imatinib-sensitive and imatinib-resistant cells, but more effective synergism in resistant cells. On the basis of these findings, we suggest that a combination of simvastatin and imatinib may be a potential candidate for the treatment of imatinib-resistant CML.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Oh B,Kim TY,Min HJ,Kim M,Kang MS,Huh JY,Kim Y,Lee DSdoi
10.1097/CAD.0b013e32835a0fbdsubject
Has Abstractpub_date
2013-01-01 00:00:00pages
20-31issue
1eissn
0959-4973issn
1473-5741journal_volume
24pub_type
杂志文章abstract::The standard therapy for patients with aggressive lymphoma is cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, which achieves a complete response in more than 60% of patients but is curative in only about 40-50%. More aggressive and/or dose-intensified chemotherapy regimens have failed to...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200211002-00007
更新日期:2002-11-01 00:00:00
abstract::5-Fluorouracil (5-FU) is the most widely used agent for the management of colorectal cancer. Capecitabine is metabolized by three enzymatic actions, the last of which is mediated by thymidine phosphorylase, to produce 5-FU. Given the oral bioavailability of capecitabine as well as in-vitro and in-vivo findings showing...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0b013e3283441a63
更新日期:2011-04-01 00:00:00
abstract::Based on observations of a discrepancy between 'hypersensitivity' reactions to docetaxel (DT) and the clinical features of allergic reactions, we explored the hypothesis that DT-induced acute hypersensitivity reactions (AHRs) have a non-allergic origin. Forty cancer patients receiving DT and 16 patients receiving othe...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000131685.06390.b7
更新日期:2004-07-01 00:00:00
abstract::The efficacy of trastuzumab beyond metastatic disease progression (PD) is controversial. We retrospectively analyzed 213 patients with HER2-positive metastatic breast cancer treated with trastuzumab-based therapies between November 1998 and December 2010. Out of 213 patients, 134 (58%) had received trastuzumab consecu...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32835679d3
更新日期:2012-11-01 00:00:00
abstract::DNA has been one of the major targets of cancer chemotherapy. A variety of anti-neoplastic agents can cause different types of DNA lesions, including base alterations, single- or double-strand DNA breaks, DNA-DNA cross-links and DNA-protein cross-links. The exact processes by which these DNA lesions lead to cell death...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199112000-00003
更新日期:1991-12-01 00:00:00
abstract::Patients with advanced gastric cancer unresponsive or progressing after PELF chemotherapy (5-fluorouracil, leucovorin, cisplatin and epidoxorubicin) received paclitaxel at the dose of 225 mg/m2 every 3 weeks, over 3 h infusion. Thirty-six patients entered the study, and all of them were evaluable for response and toxi...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-199804000-00003
更新日期:1998-04-01 00:00:00
abstract::Patients with metastatic squamous cell cancer of the head and neck (SCCHN) have a poor prognosis, with most patients surviving less than a year. Immunotherapy (IO) is changing the natural history of the disease and programmed death-ligand 1 (PD-L1) inhibitors are showing notable improvements in survival with a more fa...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000706
更新日期:2019-02-01 00:00:00
abstract::Preoperative chemoradiotherapy (CRT) is generally performed for locally advanced rectal cancer (LARC, cStage 2 or 3) to improve local disease control and patient survival. The pathological tumor response to CRT is a surrogate marker that is associated with oncological outcome. Thus, markers that predict the response t...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000391
更新日期:2016-09-01 00:00:00
abstract::The in-vitro growth inhibition of cancer and normal cell lines caused by mixed or covalently linked antimetabolites should clarify whether the conjugation of antimetabolites influences cell sensitivity and growth inhibition in a manner that differs from an equimolar mixture of the same antimetabolites or not. Growth i...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32835e5996
更新日期:2013-04-01 00:00:00
abstract::Cantharidin is a natural toxin that possesses potent anti-tumor properties. Its clinical application, however, is limited due to severe side-effects. Its cytotoxicity is believed to be mediated by the inhibition of serine/threonine protein phosphatase 2A. In order to identify new compounds with potential clinical ther...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000217428.90325.35
更新日期:2006-09-01 00:00:00
abstract::Hemolytic uremic syndrome (HUS) is a rare clinical and biological entity. HUS has been reported after several anticancer chemotherapies and most often after mitomycin C-based chemotherapy regimens. Little information is available concerning the occurrence and outcome of this syndrome after administration of more recen...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199907000-00004
更新日期:1999-07-01 00:00:00
abstract::In this study, we tried to define in vitro interactions of two antitumor agents that have different sites and different mechanisms of action. Vinblastine (VLB) in combination with human recombinant interferon-alpha A/D (rHuIFN-alpha A/D) and in combination with murine recombinant interferon-gamma (rMuIFN-gamma) was st...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199402000-00008
更新日期:1994-02-01 00:00:00
abstract::Low doses of drugs delivered at close, regular intervals are increasingly being used to manage patients with different neoplasms. Despite the good tolerability, treatment-related adverse events still occur following metronomic protocols. The aim of this study was to retrospectively investigate whether polymorphisms of...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000429
更新日期:2016-11-01 00:00:00
abstract::The antitumor effect and tumor levels of 5-fluoro-2'-deoxyuridylate (FdUMP) following oral administration of tetradecyl 2'-deoxy-5-fluoro-5'-uridylate (TT-62) were compared with those attained following intravenous (i.v.) or intraperitoneal (i.p.) administration of 5-fluorouracil (5-FU) or 5-fluoro-2'-deoxyuridine (FU...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199206000-00013
更新日期:1992-06-01 00:00:00
abstract::Our objectives were to study the biological activity of a novel gemcitabine-cardiolipin conjugate (NEO6002) and compare that with gemcitabine. Cytotoxicity in vitro was determined against several gemcitabine-sensitive parental and gemcitabine-resistant cancer cell lines using the sulforhodamine B assay. The in vivo to...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000185182.80227.48
更新日期:2006-01-01 00:00:00
abstract::The objective of this study was to determine the safety and efficacy of intravesical novantrone in refractory superficial bladder cancer. The eligibility criteria included proven carcinoma in situ or superficial transitional cell carcinoma of the bladder at stage Ta or T1 that was proven refractory to or in relapse af...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-199104000-00005
更新日期:1991-04-01 00:00:00
abstract::The combination of platinum and paclitaxel is the standard treatment of advanced ovarian carcinoma; however, recent studies have questioned the actual role of the combination as compared to either of the two agents alone. We report an open-label, two-center, phase II study of upfront paclitaxel for patients with histo...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-200306000-00004
更新日期:2003-06-01 00:00:00
abstract::We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small-cell lung cancer. Chemotherapy-naive patients with advanced non-small-cell lung cancer were treated with S-1 ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32801265eb
更新日期:2007-04-01 00:00:00
abstract::The aim of this study was to study the effect of the homologous series of 1-alkylpyrrolidine N-oxides on ATP-producing processes in Ehrlich ascites and L1210 murine leukemia cells. 1-Decylpiperidine N-oxide (deP-NO), one of the active compounds, significantly stimulated the course of aerobic glycolysis of Ehrlich cell...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199308000-00008
更新日期:1993-08-01 00:00:00
abstract::Long lasting occupational exposure to asbestos dust may cause skin corns, benign pleural effusion, hyaline plaques of the parietal pleura, diffuse thickening of the pulmonary pleura, and asbestosis, i.e. diffuse interstitial pulmonary fibrosis. Malignant disorders include lung cancer and mesothelioma of the pleura, pe...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199012000-00012
更新日期:1990-12-01 00:00:00
abstract::Schlafen-11 (SLFN11) showed a highly significant positive correlation with the response of topoisomerase inhibitors in cancer cell lines derived from prostate, lung, etc. However, this finding has not been validated in colorectal cancers (CRCs). Although irinotecan (CPT-11), a topoisomerase inhibitor, is one of the mo...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000151
更新日期:2014-11-01 00:00:00
abstract::Desmoid tumour/aggressive fibromatosis (DT/AF) is a rare soft-tissue neoplasm that is locally aggressive but does not metastasize. There is no standard systemic treatment for symptomatic patients, although a number of agents are used. Tyrosine kinase inhibitors have recently been reported to show useful activity. We r...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000474
更新日期:2017-04-01 00:00:00
abstract::Chemotherapy is the only option of treatment for most patients presenting with a recurrent and/or metastatic head and neck squamous cell carcinoma. The triple association of cisplatin, 5-fluorouracile, and cetuximab is still the current standard for fit patients. Other schemes are currently being compared with this pr...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0000000000000473
更新日期:2017-04-01 00:00:00
abstract::The current reference treatment of hormone-refractory prostate cancer consists mainly of chemotherapy with docetaxel. To improve the management of advanced prostate cancer, one should examine the benefits of adding other agents to docetaxel. We examined the growth inhibitory effects of a triple combination, including ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000224444.23953.90
更新日期:2006-08-01 00:00:00
abstract::Five hundred and fifty thousand new head and neck cancer cases are diagnosed each year worldwide. They are mostly locally advanced squamous cell carcinoma with a poor prognosis in terms of locoregional and distant failure. A major challenge for patients with locally advanced squamous cell carcinoma is to achieve a hig...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0b013e3283425871
更新日期:2011-08-01 00:00:00
abstract::Studies have shown that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells. However, breast cancer cells are generally resistant to TRAIL. In the present study, we explored the effect of bufalin on TRAIL-induced breast cancer cell apoptosis. The results showed...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000095
更新日期:2014-07-01 00:00:00
abstract::An international meeting on 'New Drugs in Cancer Therapy' was held at the National Tumor Institute of Naples, on 17-18 June 2004. The first session of the meeting focused on analogs of conventional anti-cancer drugs, such as taxanes, platinum compounds, anthracyclines and topoisomerase I inhibitors. The data of a phas...
journal_title:Anti-cancer drugs
pub_type:
doi:10.1097/00001813-200502000-00014
更新日期:2005-02-01 00:00:00
abstract::A toxicology study of DENSPM was carried out in rats by multiple (once daily for 5 days) intravenous injection. Doses of 12.5, 25 and 50 mg DENSPM/kg were well tolerated. Infusion of 100 mg DENSPM resulted in distressing physical signs, including labored breathing, convulsive movements and acute death. There were no e...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199408000-00010
更新日期:1994-08-01 00:00:00
abstract::Lung cancer is considered the number one killer among all cancers. Recent observations have altered the treatment paradigm for non-small-cell lung cancer (NSCLC). The discovery of activating mutations in the epidermal growth factor receptor and anaplastic lymphoma kinase positivity has made personalized treatment for ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0b013e3283585149
更新日期:2012-11-01 00:00:00
abstract::Gossypol [(2,2'-binaphthalene)-8,8'-dicarboxaldehyde-1,1',6,6',7,7'-hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl] 1a is a naturally occurring compound extracted from the cotton plant and has been extensively studied as an oral male contraceptive. Its favorable toxicity profile, and the more recent demonstration of anti-...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200003000-00009
更新日期:2000-03-01 00:00:00