Abstract:
:Valinomycin is a depsipeptide antibiotic that selectively translocates potassium ion across biologic membranes. This drug has been reported to display antitumor effects, but its use has been limited by its extreme toxicity. However, its incorporation into lipid vesicles (liposomes) has resulted in a reduction in toxicity and in the enhancement of the drug's therapeutic index. As a preliminary investigation of the mechanistic basis for this enhancement, the in vitro response of normal 3T3 and ras-transformed cells to free (VM) and liposomal valinomycin (VM-MLV) was examined. The incorporation of [3H]-leucine and [methyl-3H]-thymidine was used to assess macromolecular synthesis, and the MTT vital dye assay was used to measure cell survival and growth. Pretreatment of exponentially growing NIH/3T3 cells with 20 nM VM for 1 h decreased [3H]-leucine and [methyl-3H]-thymidine incorporation by 90% and 80%, respectively. However, Ha-ras 3T3 cells showed resistance to VM treatment with inhibitory doses in the range of 200 nM. At equimolar VM concentrations, VM-MLV was found to be less inhibitory than VM for protein and DNA synthesis. Specifically, marked protective activity was apparent with normal 3T3 cells. In this report we also demonstrate that VM selectively killed normal cells compared with ras-transformed cells grown in vitro. However, VM-MLV displayed a modest cytotoxic selectivity (3- to 4-fold) to ras-transformed cells. Our data suggests that first, there is good correlation between growth inhibition and inhibition of DNA and protein synthesis by VM, and second, VM-MLV exhibits a modest, selective toxicity to the ras-transformed 3T3 cell line as compared with nontransformed 3T3 cells, whereas free VM has the opposite selectivity.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Daoud SS,Juliano RLdoi
10.1007/BF00267946subject
Has Abstractpub_date
1989-01-01 00:00:00pages
151-5issue
3eissn
0344-5704issn
1432-0843journal_volume
23pub_type
杂志文章abstract::Cyclophosphamide (Cy) is widely used as an effective cytotoxic drug, but its use is limited because of its toxicity. In this report, we describe for the first time the ability of purified protein A (P) of Staphylococcus aureus to reduce Cy-induced toxicity in rats. Protein A-treated animals recover quickly from the to...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00552727
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:Trifluorothymidine (TFT) is a fluoropyrimidine that is part of the novel combination metabolite TAS-102, in which TFT is combined with a potent thymidine phosphorylase inhibitor (TPI). TAS-102 is currently tested as an orally chemotherapeutic agent in different schedules in a phase I study. In its monophosphate...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0033-4
更新日期:2006-01-01 00:00:00
abstract:PURPOSE:This study evaluated mechanistic differences of pralatrexate, methotrexate, and pemetrexed. METHODS:Inhibition of dihydrofolate reductase (DHFR) was quantified using recombinant human DHFR. Cellular uptake and folylpolyglutamate synthetase (FPGS) activity were determined using radiolabeled pralatrexate, methot...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-0954-4
更新日期:2009-10-01 00:00:00
abstract:PURPOSE:BMS-310705, a novel semisynthetic derivative of epothilone B, is a tubulin-polymerization agent currently in phase I clinical trials for anticancer therapy. The in vitro and in vivo pharmacokinetics and oral bioavailability of BMS-310705 were investigated in mice, rats, and dogs. In addition, comparison of the ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0928-5
更新日期:2005-08-01 00:00:00
abstract::The purpose of this study was to evaluate the response rate, methotrexate plasma levels, and toxicity of a three-drug regimen in patients with gastric carcinoma. A total of 37 patients with advanced measurable adenocarcinoma of the stomach were treated with Adriamycin, methotrexate, and 5-fluorouracil (AMF). Adriamyci...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254103
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:Bevacizumab (BV) prolongs the survival of colorectal cancer patients when combined with irinotecan (CPT-11)-based regimens. In the AVF2107g study, the area under the curve (AUC) ratio for bolus CPT-11/5-fluorouracil (5-FU)/leucovorin (LV) (IFL) with the BV arm to bolus IFL with placebo indicated that SN-38 conc...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-009-1051-4
更新日期:2010-02-01 00:00:00
abstract::We have recently demonstrated that continuous-infusion (CI) 5-fluorouracil (FU) eradicates human colon carcinoma cells made resistant to bolus FU in vitro. In addition, in the same experimental system, the mechanisms of resistance to pulse and CI FU were found to be different. These observations led us to test the cli...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685339
更新日期:1993-01-01 00:00:00
abstract::6-[Bis-(2-chloroethyl)-amino]-6-deoxy-D-glucose (C-6) is a new glucose-containing nitrogen mustard that has significant activity for murine P388 leukemia with relative sparing of bone marrow in mice. The in vitro myelotoxicity of C-6 compared with that of melphalan, a clinically active, myelosuppressive nitrogen musta...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00256165
更新日期:1986-01-01 00:00:00
abstract::Antibodies can be used to target cancer therapies to malignant tissue; the approach is attractive because conventional treatments such as chemo- and radiotherapy are dose limited due to toxicity in normal tissues. Effective targeting relies on appropriate pharmacokinetics of antibody-based therapeutics, ideally showin...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/pl00014055
更新日期:2000-01-01 00:00:00
abstract:PURPOSE:We reported the first case of phenytoin intoxication due to the concomitant use of phenytoin and TS-1, together with a review of the literature regarding the occurrence of phenytoin intoxication due to the concomitant use of phenytoin and fluoropyrimidine antitumor drugs such as fluorouracil (5-FU) and tegafur ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0621-6
更新日期:2008-08-01 00:00:00
abstract::Imatinib is the treatment of choice for FIP1L1-PDGFRalpha (F/P+) positive myeloproliferative neoplasms, but little is known about optimal dose and duration of treatment to maintain complete molecular remission once achieved. We describe a case of F/P+ patients who started imatinib and reached a molecular remission, bu...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0858-8
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:The presence of hepatic portal venous gas (HPVG) is a rare finding. It is most commonly caused by bowel necrosis and typically carries a grave prognosis. Bevacizumab has emerged as an effective standard therapy in the frontline management of advanced non-small cell lung cancer (NSCLC). Although bevacizumab i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1104-8
更新日期:2009-12-01 00:00:00
abstract::Dihydroartemisinin, a more water-soluble metabolite of artemisinin derivatives, is a safe and most effective antimalarial analog of artemisinin. In the present study, we investigated the antiangiogenic activity of dihydroartemisinin in vitro and in vivo, and investigated dihydroartemisinin-induced apoptosis in human u...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0751-4
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:In a phase I clinical trial of oxaliplatin (OPT) in combination with paclitaxel (PXL), a pharmacokinetic interaction was observed when OPT was given as a 2-h i.v. infusion followed by a 1-h i.v. infusion of PXL. The purpose of this study was to use a rat model to evaluate whether the pharmacokinetic interact...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-002-0531-6
更新日期:2002-12-01 00:00:00
abstract::Thirty-eight patients with small cell carcinoma of the bronchus resistant to initial chemotherapy with cyclophosphamide methotrexate and CCNU, were treated with VP16-213 alone in a dose of 120 mg/m2 i.v. on days 1, 3, and 5 every 3 weeks. Twelve patients died before three courses of treatment. In 26 patients who recei...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254544
更新日期:1982-01-01 00:00:00
abstract:PURPOSE:The objectives of this phase I dose-finding study of erlotinib were to investigate the toxicity profile, to confirm the acceptable toxicity of doses up to 150 mg/day, and to assess the pharmacokinetic (PK) profile and antitumor activity in Japanese patients with solid tumors. PATIENTS AND METHODS:Patients with...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0494-8
更新日期:2008-03-01 00:00:00
abstract::Doxifluridine (5'-deoxy-5-fluorouridine, 5'-dFUR) metabolism has been reported to be saturable and associated with a fall in clearance of the drug as the dose is increased. The aim of the present study was to determine the disposition of 5'-dFUR and 5-fluorouracil (5-FU) when 5'-dFUR was given as a 5-day infusion, wit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00684885
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Multidrug resistance (MDR) is known as a problem limiting the success of therapy in patients treated long term with chemotherapeutic drugs. The drug resistance is mainly due to the overexpression of the 170 kDa P-glycoprotein (Pgp), which causes a reduction in drug accumulation in the cancer cells. In this stud...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0848-4
更新日期:2004-12-01 00:00:00
abstract:PURPOSE:Evodiamine is one of active alkaloids isolated from the traditional Chinese medicine Evodia rutaecarpa Bentham and has various pharmacological properties. In this study, we investigated its effects on the migration, invasion, and associated mechanism in human nasopharyngeal carcinoma (NPC) cells. METHODS:Cell ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2902-9
更新日期:2015-12-01 00:00:00
abstract:PURPOSE:The intra-tumour distribution of anticancer drugs remains an important, but often under-estimated, influence on drug efficacy. Tumour acidity and the presence of efflux pumps were examined for their influence on the distribution of doxorubicin in a solid tumour model. METHODS:Anticancer drug distribution and o...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1598-8
更新日期:2011-11-01 00:00:00
abstract::In early studies of the antitumor drug 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1nitrosourea (methyl-CCNU), animal models consistently predicted that the compound would be nephrotoxic in humans. Nephrotoxicity in cancer patients who had received methyl-CCNU was not confirmed until about 6 years after clinical trials b...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257241
更新日期:1982-12-01 00:00:00
abstract::The pharmacokinetics of mitomycin (MMC) was studied in Wistar rats. Up to five half-lives, the plasma concentration-time curve was biphasic. The AUC changed linearly with increasing doses between 0.5 and 7.5 mg/kg, which corresponds to 0.2 and 3 times the LD50 value in rats. Most of the drug was metabolized, and only ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257305
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:The safety and tolerability of vandetanib (ZACTIMA; ZD6474) plus FOLFIRI was investigated in patients with advanced colorectal cancer (CRC). METHODS:Patients eligible for first- or second-line chemotherapy received once-daily oral doses of vandetanib (100 or 300 mg) plus 14-day treatment cycles of FOLFIRI. RE...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-008-0914-4
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:We evaluated the influence of serum cystatin C (CysC) with respect to other glomerular filtration rate (GFR) markers on the treatment effect of everolimus in a phase II study in patients with metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS:Outcomes were from the study's primary analysis. GFR w...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3084-9
更新日期:2016-08-01 00:00:00
abstract::The purpose of the present study was to determine the maximally tolerated dose of thioTEPA given with fixed high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous bone marrow (ABM) with or without granulocyte colony-stimulating factor (G-CSF)-primed peripheral-blood progenitor cells (PBPCs) in pa...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050429
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:To evaluate whether celecoxib alters the conversion of gemcitabine into its active metabolite, difluorodeoxycytidine triphosphate (dFdCTP), in peripheral blood mononuclear cells (PBMCs). METHODS:Patients with advanced pancreatic cancer who had not received chemotherapy and had acceptable organ function were el...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-004-0916-9
更新日期:2005-06-01 00:00:00
abstract::The cellular metabolism of 3'-amino-2',3'-dideoxycytidine (3'-NH2-dCyd), a cytotoxic agent previously reported to be a poor substrate for purified Cyd/dCyd deaminase (dCydD), was compared with that of cytosine arabinoside (ara-C) in cells that displayed dCydD activity (HeLa) and in cells that did not (L1210). Growth i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686406
更新日期:1992-01-01 00:00:00
abstract:BACKGROUND:As tumors evolve, they upregulate glucose metabolism while also encountering intermittent periods of glucose deprivation. Here, we investigate mechanisms by which pancreatic cancer cells respond to therapeutic (2-deoxy-D-glucose, 2-DG) and physiologic (glucose starvation, GS) forms of glucose restriction. M...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2358-8
更新日期:2014-02-01 00:00:00
abstract:PURPOSE:Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, l...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2176-z
更新日期:2013-07-01 00:00:00
abstract::Cancer is a major health issue worldwide and the global burden of cancer is expected to reduce the costs of treatment as well as prolong the survival time. One of the promising approaches is drug repurposing, because it reduces costs and shortens the production cycle of research and development. Disulfiram (DSF), whic...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-020-04216-8
更新日期:2021-01-10 00:00:00