Abstract:
PURPOSE:Chemosensitizers such as cyclosporin A can increase intracellular accumulation of chemotherapeutic agents such as Adriamycin in certain multidrug-resistant (MDR) cell lines with overexpression of P-glycoprotein. It is likely that, when combined with cyclosporin A, hyperthermia could increase membrane permeability to Adriamycin and enhance its cytotoxic effects. The ability of both hyperthermia and cyclosporin A to modulate the cytotoxicity, transport and subcellular distribution pattern of Adriamycin was studied in a pleiotropic MDR Chinese hamster ovary cell line (CH(R)C5) and in the drug-sensitive parent line (AuxB1). METHODS:Adriamycin cytotoxicity was evaluated by clonogenic cell survival, drug transport using [(14)C]-labeled Adriamycin and intracellular drug distribution by fluorescence microscopy. RESULTS:Adriamycin cytotoxicity was increased in both drug-sensitive and MDR cells by cyclosporin A (5 microM) alone, and by hyperthermia alone (41-43 degrees C) only in sensitive cells. However, when cyclosporin A and 42 degrees C hyperthermia were used in combination, a large increase in drug cytotoxicity occurred in both cell lines. This effect increased with time and was temperature-dependent. The increase in Adriamycin cytotoxicity caused by cyclosporin A and hyperthermia was accompanied by alterations in membrane permeability to the drug. Cyclosporin A increased [(14)C]Adriamycin uptake, while drug efflux decreased, for both AuxB1 and CH(R)C5 cells and nuclei. For AuxB1 cells only, drug distribution studies showed that cyclosporin A promoted an increase in both nuclear and cytoplasmic drug accumulation. Hyperthermia, combined with cyclosporin A, increased [(14)C]Adriamycin uptake. This effect was seen as an increase in intensity of nuclear and cytosolic drug fluorescence in both cell lines. Cyclosporin A alone diminished drug efflux and caused Adriamycin to remain firmly bound in the nucleus of AuxB1 cells, while it remained primarily in the cytoplasm of CH(R)C5 cells. CONCLUSIONS:Hyperthermia alone had little effect on Adriamycin cytotoxicity and transport in MDR cells, in contrast to drug-sensitive cells. This suggests that P-glycoprotein is fully functional in these MDR cells. Our findings suggest that cyclosporin A and hyperthermia could be beneficial by increasing intracellular drug accumulation, thus improving the effectiveness of Adriamycin against both drug-sensitive and MDR cells within a localized target region.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Larrivée B,Averill DAdoi
10.1007/s002800050033keywords:
subject
Has Abstractpub_date
2000-01-01 00:00:00pages
219-30issue
3eissn
0344-5704issn
1432-0843pii
00450219.280journal_volume
45pub_type
杂志文章abstract::Carmustine (BCNU) has proved to be of value against a variety of primary brain tumors. This agent exhibits a steep dose-response curve in in vitro and animal tumor models and has been proposed for use in high-dose chemotherapy as a single agent or in combination. We conducted a phase II study to assess high-dose BCNU ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050586
更新日期:1997-01-01 00:00:00
abstract::Leucovorin requirements for protection of the T cell line CCRF-CEM and the B cell line LAZ-007 against the cytotoxic effects of a variety of antifolates were studied. Differential leucovorin protection for DDMP-induced growth suppression occurred in the opposite direction to that for MTX, with CCRF-CEM requiring less ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257519
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:The platinum agent oxaliplatin could be useful in treatment of cancer in pregnant women, but it is fetotoxic in rats and its effect on the human fetus is unknown. METHODS:Oxaliplatin was administered to a 25-year-old pregnant woman with metastatic rectal cancer from 20 to 30 weeks gestational age as part of th...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0731-9
更新日期:2009-01-01 00:00:00
abstract::DON (6-diazo-5-oxo-L-norleucine), a glutamine antagonist, has been subjected to limited clinical trials since 1957. Use of the drug in adults has been curtailed due to sparse reports of effectiveness as well as its dose-limiting toxicities, i.e., severe nausea, vomiting and mucositis. In earlier studies, children give...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00262746
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:This study was performed to determine whether or not in cervical, ovarian and lung cancer cell lines, free radicals (ROS) play a role in cisplatin cytotoxicity and activation of the mitochondrial and JNK/p38 pathways. The role of the enzyme, dihydrodiol dehydrogenase (DDH1), in the activation/deactivation of th...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2739-2
更新日期:2015-06-01 00:00:00
abstract::Sixty-seven patients with acute nonlymphoblastic leukemia (ANLL) and above the age of 60 years were randomly allocated to treatment with either prednimustine + vincristine or cycles with cytosine arabinoside and thioguanine. Of the 67 patients, 13 (19%) entered a complete remission and four a partial remission. Of 33 ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00265385
更新日期:1982-01-01 00:00:00
abstract:PURPOSE:The purpose of this investigation was to evaluate the effectiveness of oral 5-(phenylthio)acyclouridine (PTAU) in reducing 5-fluorouracil (FUra) host-toxicity and enhancing its chemotherapeutic efficacy against human colon tumors. PTAU is a potent and specific inhibitor of uridine phosphorylase (UrdPase, EC 2.4...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0213-x
更新日期:2006-11-01 00:00:00
abstract:PURPOSE:Ibrutinib is an orally administered, irreversible Bruton's tyrosine kinase inhibitor for treatment of B-cell malignancy. This study evaluated the effects of single-dose ibrutinib at therapeutic and supratherapeutic exposures on cardiac repolarization in healthy subjects. METHODS:Part 1 used an open-label, two-...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3471-x
更新日期:2017-12-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/BF00685041
更新日期:1993-01-01 00:00:00
abstract::A 44-year-old man who had achieved a complete remission of malignant peritoneal mesothelioma after the intraperitoneal administration of 25 mg/m2 mitoxantrone presented with clinical and radiological signs of intestinal obstruction suggestive of recurrent disease at about 2 years following the initial treatment. Howev...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686012
更新日期:1992-01-01 00:00:00
abstract::We evaluated the antiproliferative and the proapoptotic ability of gemcitabine in three non-small-cell lung cancer (NSCLC) cell lines. NCI-H292 (mucoepidermoid carcinoma), NCI-CorL23 (large-cell carcinoma) and NCI-Colo699 (adenocarcinoma) cells were cultured with and without 0.5, 0.05 and 0.005 microM gemcitabine for ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800000183
更新日期:2000-01-01 00:00:00
abstract:PURPOSE:The dolastatins are a class of naturally occurring cytotoxic peptides which function by inhibiting microtubule assembly and tubulin polymerization. Cemadotin is a synthetic analogue of dolastatin 15 with potent antiproliferative and preclinical antitumor activity. This report describes a phase I study to evalua...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800000152
更新日期:2000-01-01 00:00:00
abstract::Irinotecan-induced mucositis is a major oncological problem. Goblet cells secrete mucus, protecting the intestinal mucosa, with secretion altered during mucositis. The enteric nervous system is involved in regulating gut motility and secretion. The aim of this study was to determine whether enteric neural cells and go...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03787-5
更新日期:2019-05-01 00:00:00
abstract::New active drugs are needed for the treatment of primary brain tumors in both children and adults. S16020 is a cytotoxic olivacine derivative that inhibits topoisomerase II. The aim of the study was to determine its antitumor activity in athymic mice bearing subcutaneous medulloblastoma (IGRM33, 34, 57) and glioblasto...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0584-1
更新日期:2003-05-01 00:00:00
abstract:PURPOSE:To evaluate the efficacy and safety of irinotecan as second-line treatment in patients with advanced colorectal cancer (ACC) failing or relapsing after 5-fluorouracil (5-FU) plus leucovorin (LV) standard chemotherapy. PATIENTS AND METHODS:Irinotecan was randomly administered in two different schedules (once ev...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00280-003-0659-z
更新日期:2003-12-01 00:00:00
abstract::Forty-three previously untreated patients, all of whom had poor-prognosis small cell lung cancer and/or were greater than 65 years old, received treatment with vindesine and VP16-213. Thirteen patients had limited disease and 30 extensive disease. Response rates (CR + PR) of 86% (CR 29%) and 66% (CR 17%) were seen in ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257124
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:Transcatheter arterial chemoembolization (TACE) causes damage to liver function and decreases the activity of cytochrome P450 in patients with hepatocellular carcinoma (HCC). But there was no report on whether the activity of Phase II conjugating enzymes was affected in HCC patients after TACE treatment. The pu...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-009-1040-7
更新日期:2010-01-01 00:00:00
abstract::S-1 is an oral formulation of ftorafur (FT), oxonic acid and 5-chloro-2,4-dihydroxypyridine (CDHP) at a molar ratio of 1:0.4:1. FT is a 5-fluorouracil (5-FU) prodrug, CDHP is a dihydropyrimidine dehydrogenase (DPD) inhibitor and oxonic acid is an inhibitor of 5-FU phosphoribosylation in the gastrointestinal mucosa and...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-003-0617-9
更新日期:2003-07-01 00:00:00
abstract::Tumor angiogenesis is essential for tumor growth and metastasis formation. Luminex methodology was used to measure the levels of four angiogenic cytokines in cell culture medium and in the plasma of mice bearing human tumors. We obtained plasma and conditioned culture medium from 12 different human tumor cell lines. T...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0572-5
更新日期:2003-04-01 00:00:00
abstract::We have previously reported that multidrug (MDR)-reversal activity can be exerted by compounds in which two ring structures of certain types are connected by one alkyl bridge to a secondary or tertiary amine group. In the present investigation we studied the MDR-reversal activity of compounds in which the two ring str...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685568
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:To investigate the effects of genetic polymorphisms on morphine-induced adverse events in cancer patients. METHODS:We examined the relation of morphine-related adverse events to polymorphisms in UDP-glucuronosyltransferase (UGT) 2B7, ATP-binding cassette, sub-family B, number 1 (ABCB1), and μ-opioid receptor 1...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1029-2
更新日期:2010-01-01 00:00:00
abstract:PURPOSE:Phosphatidylinositol (PtdIns) 3-kinase is an important mediator of many cellular functions. The study of PtdIns 3-kinase has been facilitated by the existence of the potent irreversible inhibitor of p110 PtdIns 3-kinase, wortmannin. The purpose of the study was to investigate the relationship between the cell g...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800051123
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND:Ovarian cancer is one of the most frequently fatal gynecological cancers because most cases are diagnosed at an advanced stage. Loss of growth control and a marked resistance to apoptosis are considered major mechanisms driving tumor progression. Little is known about the effect of various treatment regimens...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00280-004-0993-9
更新日期:2005-10-01 00:00:00
abstract::Using flow cytometry and conventional spectrofluorimetry we have previously shown that chloroethylnitrosoureas (CNUs) can exhibit marked inhibition of cellular enzymes catalysing hydrolysis of fluorescein diacetate (FDA). More potent inhibition was seen for the carbamoylating CNUs, whereas alkylating agents were large...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689574
更新日期:1989-01-01 00:00:00
abstract:BACKGROUND:Fenretinide is a synthetic retinoid that can induce cytotoxicity by several mechanisms. Achieving effective systemic exposure with oral formulations has been challenging. An intravenous lipid emulsion fenretinide formulation was developed to overcome this barrier. We conducted a study to establish the maximu...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04224-8
更新日期:2021-01-10 00:00:00
abstract::In the 1981 cooperative soft-tissue sarcoma (CWS-81) study, a clear correlation between the degree of response to initial chemotherapy comprising vincristine, actinomycin D, cyclophosphamide, and Adriamycin (VACA) and the survival of patients with rhabdomyosarcoma was found. In the subsequent CWS-86 study, cyclophosph...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00253241
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:To evaluate the plasma protein binding and pharmacokinetics of prednisolone during therapeutic use in children with acute lymphoblastic leukemia (ALL) using the population approach. METHODS:A two-compartment pharmacokinetic model was used to describe data from 23 children with ALL (aged 2-15 years). Prednisolo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-003-0602-3
更新日期:2003-06-01 00:00:00
abstract:BACKGROUND:TAP chemotherapy (paclitaxel, doxorubicin, and cisplatin) is effective for advanced and recurrent endometrial carcinoma, but has occasional severe toxicity. TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) has been suggested to have less toxicity; however, the optimal dosage has yet to be determine...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1638-4
更新日期:2011-12-01 00:00:00
abstract::To evaluate the antiemetic efficacy of high-dose methylprednisolone (MP) in previously untreated cancer patients receiving cisplatin (CPDD) for the first time, we performed a randomized double blind study. MP or a placebo (PLB) was administered six times during each course of chemotherapy. The first dose was 500 mg an...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00258123
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:Several studies have identified amino acid residues located on the hydrophobic side of the helix that forms transmembrane domain 6 (TM6) of the ABC transporter P-glycoprotein (Pgp) as being important for function. The purpose of this study was to determine if alterations to residues on the hydrophilic side coul...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800100354
更新日期:2001-11-01 00:00:00