Modulation of mitomycin C-induced multidrug resistance in vitro.

Abstract:

:A series of in vitro cytotoxicity studies were performed to achieve pharmacologic reversal of resistance to the alkylating agent mitomycin (MMC) in L-1210 leukemia cells. A multidrug-resistant (MDR), P-glycoprotein-positive cell line, RL-1210/.1 [11], was exposed to potential MDR modulators in the absence or presence of MMC. The following compounds did not reverse MMC-induced MDR: quinine, quinidine, lidocaine, procaine, dimethylsulfoxide (DMSO), dexamethasone, hydrocortisone, prednisolone, estradiol, and testosterone. Three agents were capable of reversing MMC resistance: progesterone, cyclosporin A, and verapamil. The R- and S-isomers of verapamil were equipotent, although they showed a 10-fold difference in cardiovascular potency (S greater than R). Some agents produced cytotoxic effects in MDR cells in the absence of MMC, including progesterone, quinine, and quinidine. The results suggest that R-verapamil and progesterone may have clinical utility in reversing MMC resistance in human tumors. Progesterone may be uniquely efficacious due to (a) its low toxicity in normal cells, (b) its selective cytotoxicity in MDR cells (in the absence of MMC), and (c) its ability to reverse MMC resistance in vitro. The findings also suggest that the P-glycoprotein induced by MMC differs from that induced by doxorubicin, which is highly sensitive to modulation by lysosomotropic amines such as quinine and quinidine.

authors

Dorr RT,Liddil JD

doi

10.1007/BF00685114

subject

Has Abstract

pub_date

1991-01-01 00:00:00

pages

290-4

issue

4

eissn

0344-5704

issn

1432-0843

journal_volume

27

pub_type

杂志文章
  • Combination of topotecan and etoposide as a salvage treatment for patients with recurrent small cell lung cancer following irinotecan and platinum first-line chemotherapy.

    abstract:PURPOSE:The efficacy and safety of a combined regimen of topotecan and etoposide was tested in patients with relapsed or refractory small-cell lung cancer. PATIENTS AND METHODS:From October 2003 to May 2005, 23 patients who have failed to the previous irinotecan and platinum chemotherapy received intravenous topotecan...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-007-0505-9

    authors: Choi HJ,Cho BC,Shin SJ,Cheon SH,Jung JY,Chang J,Kim SK,Sohn JH,Kim JH

    更新日期:2008-02-01 00:00:00

  • A phase I trial of continuous-infusion cyclophosphamide in refractory cancer patients.

    abstract::Cyclophosphamide demonstrates enhanced tumoricidal activity with decreased bone marrow toxicity when given on a divided-dose schedule in certain animal models. A total of 22 patients presenting with refractory metastatic cancer were treated in a phase I trial of continuous infusion of cyclophosphamide over 96 h. Granu...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00686337

    authors: Eder JP,Elias AD,Ayash L,Wheeler CA,Shea TC,Schnipper LE,Frei E 3rd,Antman KH

    更新日期:1991-01-01 00:00:00

  • Targeting cisplatin-resistant human tumor cells with metabolic inhibitors.

    abstract:PURPOSE:Although cisplatin is the drug of choice in treating lung cancer patients, relapse and resistance is a common drawback to its clinical effectiveness. Based on cisplatin's reported ability to interfere with numerous cellular components, including mitochondria, we probed alterations in metabolism in cisplatin-res...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-013-2366-8

    authors: Sullivan EJ,Kurtoglu M,Brenneman R,Liu H,Lampidis TJ

    更新日期:2014-02-01 00:00:00

  • Combination of fludarabine and arabinosylcytosine for treatment of chronic lymphocytic leukemia: clinical efficacy and modulation of arabinosylcytosine pharmacology.

    abstract::Previous studies have demonstrated that treatment with fludarabine 4 h prior to arabinosylcytosine (ara-C) potentiates the accumulation of the active triphosphate of ara-C (ara-CTP) in leukemic lymphocytes. The clinical efficacy of this combination was evaluated in 15 patients with chronic lymphocytic leukemia (CLL) t...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00686108

    authors: Gandhi V,Robertson LE,Keating MJ,Plunkett W

    更新日期:1994-01-01 00:00:00

  • Randomized phase 2 study of gemcitabine and cisplatin with or without vitamin supplementation in patients with advanced esophagogastric cancer.

    abstract:PURPOSE:Preclinical research and prior clinical observations demonstrated reduced toxicity and suggested enhanced efficacy of cisplatin due to folic acid and vitamin B12 suppletion. In this randomized phase 2 trial, we evaluated the addition of folic acid and vitamin B12 to first-line palliative cisplatin and gemcitabi...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s00280-018-3588-6

    authors: van Zweeden AA,van Groeningen CJ,Honeywell RJ,Giovannetti E,Ruijter R,Smorenburg CH,Giaccone G,Verheul HMW,Peters GJ,van der Vliet HJ

    更新日期:2018-07-01 00:00:00

  • Pretreatment with 5-FU enhances cisplatin cytotoxicity in head and neck squamous cell carcinoma cells.

    abstract:PURPOSE:In the treatment of head and neck malignancy, cisplatin and 5-FU have been used the most as chemotherapeutic agents. The difference in efficacies of these is unclear and controversial. To investigate more effective schedule, we analyzed the cytotoxicity in different treatment sequence with two agents in vitro a...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-007-0658-6

    authors: Ijichi K,Adachi M,Hasegawa Y,Ogawa T,Nakamura H,Kudoh A,Yasui Y,Murakami S,Ishizaki K

    更新日期:2008-10-01 00:00:00

  • Pharmacokinetic studies of 9-nitrocamptothecin on intermittent and continuous schedules of administration in patients with solid tumors.

    abstract:PURPOSE:Oral administration of 9-nitrocamptothecin (9NC), and the formation of its metabolite 9-aminocamptothecin (9AC), may be associated with high interpatient and intrapatient variability. Therefore, we evaluated the plasma pharmacokinetics and urine recovery of 9NC administered on three different schedules as part ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00280-004-0835-9

    authors: Jung LL,Ramanathan RK,Egorin MJ,Jin R,Belani CP,Potter DM,Strychor S,Trump DL,Walko C,Fakih M,Zamboni WC

    更新日期:2004-12-01 00:00:00

  • Potentiation of antitumor activity of 1-phthalidyl 5-fluorouracil by acetazolamide.

    abstract::The effect of acetazolamide (A.A.) on the antineoplastic activity of 1-phthalidyl 5-fluorouracil (PH-FU) against rat and mouse solid tumors was examined. A.A., an inhibitor of liver PH-FU hydrolase, had no antitumor activity but greatly enhanced the activity of PH-FU when coadministered. The potentiation was evaluated...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00255286

    authors: Kasai H,Tonda K,Hirata M

    更新日期:1986-01-01 00:00:00

  • A clinical study of nafazatrom in advanced human breast cancer.

    abstract::Prostaglandins (PGs) have been shown to inhibit tumour metastases in experimental animal systems. Nafazatrom is a pyrazolinone derivative that increases endogenous prostacyclin (PGI2) and has experimental anti-cancer activity. In the present study, nafazatrom was given to 47 women with advanced breast cancer; objectiv...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00685120

    authors: Jones AL,Powles TJ,Forgeson GV,Coombes RC

    更新日期:1991-01-01 00:00:00

  • Computed determination of the in vitro optimal chemocombinations of sphaeropsidin A with chemotherapeutic agents to combat melanomas.

    abstract:PURPOSE:Evasion to new treatments of advanced melanoma is still associated with a poor prognosis. Choosing the best combination of agents that can bypass resistance mechanisms remains a challenge. Sphaeropsidin A (Sph A) is a fungal bioactive secondary metabolite previously shown to force melanoma cells to undergo apop...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-017-3293-x

    authors: Ingels A,Dinhof C,Garg AD,Maddau L,Masi M,Evidente A,Berger W,Dejaegher B,Mathieu V

    更新日期:2017-05-01 00:00:00

  • IPI-504, a novel and soluble HSP-90 inhibitor, blocks the unfolded protein response in multiple myeloma cells.

    abstract:BACKGROUND:Inhibitors of heat shock protein (Hsp) 90 induce apoptosis in multiple myeloma (MM) cells, but the molecular mechanisms underlying this cytotoxic outcome are not clear. Here, we investigate the effect of IPI-504, a novel and highly soluble inhibitor of the Hsp90 ATPase activity, on the unfolded protein respo...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-007-0546-0

    authors: Patterson J,Palombella VJ,Fritz C,Normant E

    更新日期:2008-05-01 00:00:00

  • Activity of fenretinide plus chemotherapeutic agents in small-cell lung cancer cell lines.

    abstract:PURPOSE:Fenretinide [N-(4-hydroxyphenyl)retinamide, 4HPR], a synthetic retinoid, is a potent inducer of apoptosis in small-cell lung cancer (SCLC) cell lines that may act through the generation of reactive oxygen species, suggesting that it may enhance the activity of other cytotoxic agents. In light of 4HPR's clinical...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050875

    authors: Kalemkerian GP,Ou X

    更新日期:1999-01-01 00:00:00

  • Plasma and cerebrospinal fluid pharmacokinetics of tasidotin (ILX-651) and its metabolites in non-human primates.

    abstract:PURPOSE:To evaluate the plasma and cerebrospinal fluid (CSF) pharmacokinetics and CSF penetration of tasidotin and metabolites in a nonhuman primate model. METHODS:Tasidotin 0.75 mg/kg was administered intravenously. The plasma and CSF concentrations of tasidotin and its metabolites were determined. Pharmacokinetic pa...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-008-0875-7

    authors: Kilburn LB,Bonate PL,Blaney SM,McGuffey L,Nuchtern JG,Dauser R,Thompson P,Gibson BW,Berg SL

    更新日期:2009-07-01 00:00:00

  • Mechanism-based modeling of the clinical effects of bevacizumab and everolimus on vestibular schwannomas of patients with neurofibromatosis type 2.

    abstract:PURPOSE:To describe the natural growth of vestibular schwannoma in patients with neurofibromatosis type 2 and to predict tumor volume evolution in patients treated with bevacizumab and everolimus. METHODS:Clinical data, including longitudinal tumor volumes in patients treated by bevacizumab (n = 13), everolimus (n = 7...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-016-3046-2

    authors: Ouerdani A,Goutagny S,Kalamarides M,Trocóniz IF,Ribba B

    更新日期:2016-06-01 00:00:00

  • The effect of transcatheter arterial chemoembolization on phase II drug metabolism enzymes in patients with hepatocellular carcinoma.

    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

    authors: Zhang Y,Jia Y,Liu X,Liu L,Wang Q,Wen A

    更新日期:2010-01-01 00:00:00

  • Platinum drug effects on the expression of genes in the polyamine pathway: time-course and concentration-effect analysis based on Affymetrix gene expression profiling of A2780 ovarian carcinoma cells.

    abstract:PURPOSE:As a follow-up to our previous findings that platinum drugs induce a key enzyme in polyamine catabolism, gene expression profiling and mathematical modeling were used to define the effects of cisplatin and oxaliplatin on the expression of polyamine metabolic pathway genes in A2780 human ovarian carcinoma cells....

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-006-0325-3

    authors: Varma R,Hector S,Greco WR,Clark K,Hawthorn L,Porter C,Pendyala L

    更新日期:2007-05-01 00:00:00

  • Effect of nitrosoureas on calmodulin activity in vitro and in mouse intestine in vivo.

    abstract::The effects of BCNU, CCNU, methyl-CCNU, streptozotocin, and chlorozotocin on calmodulin activity were studied in vitro and in vivo. Preincubation of BCNU, CCNU, and methyl-CCNU with calmodulin produced a concentration-dependent inhibition of in vitro calmodulin activity expressed as stimulation of cyclic nucleotide ph...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00434354

    authors: Harrison SD Jr,Mann DM,Giles RC Jr

    更新日期:1985-01-01 00:00:00

  • Phase I trial of indicine-N-oxide in children with leukemia and solid tumors: a Pediatric Oncology Group study.

    abstract::A phase I trial of indicine-N-oxide was carried out in 12 children with solid tumors and in 16 with leukemia. Doses of 5, 6, and 7.5 g/m2 were given parenterally as a 15-min infusion every 3 weeks. The maximum tolerated dose in patients with solid tumors was 7.5 g/m2 and the dose-limiting toxicity was myelosuppression...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02897298

    authors: Whitehead VM,Bernstein ML,Vega R,Vats T,Dyment P,Vietti TJ,Krischer J

    更新日期:1990-01-01 00:00:00

  • Pharmacokinetic study of doxifluridine given by 5-day stepped-dose infusion.

    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

    authors: Reece PA,Olver IN,Morris RG,Bishop JF,Guentert TW,Hill HS,Hillcoat BL

    更新日期:1990-01-01 00:00:00

  • Inhibition of intracellular Ca2+ signalling, cytotoxicity and antitumor activity of the herbicide oryzalin and its analogues.

    abstract:PURPOSE:Studies were conducted on oryzalin (3,5-dinitro-N,N-di(n-propyl)sulfanilamide), a widely used dinitroaniline sulfonamide herbicide, which was identified from plant extracts as an inhibitor of mitogen- and growth factor-mediated intracellular free Ca2+ ([Ca2+]i) signalling in mammalian cells. METHODS AND RESULT...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050703

    authors: Powis G,Gallegos A,Abraham RT,Ashendel CL,Zalkow LH,Dorr R,Dvorakova K,Salmon S,Harrison S,Worzalla J

    更新日期:1997-01-01 00:00:00

  • New natural products of interest under development at the National Cancer Institute.

    abstract::Fourteen new agents of natural products origin which are under development as antitumor agents at the National Cancer Institute are discussed with reference to their sources, structures, antitumor activity, current status, and future prospects as clinically effective agents. ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00254042

    authors: Douros J,Suffness M

    更新日期:1978-01-01 00:00:00

  • Plasma and cerebrospinal fluid pharmacokinetics of ABT-888 after oral administration in non-human primates.

    abstract:PURPOSE:ABT-888 inhibits poly(ADP-ribose) polymerase (PARP) and may enhance the efficacy of chemotherapy and radiation in CNS tumors. We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics (PK) of ABT-888 in a non-human primate (NHP) model that is highly predictive of human CSF penetration. METHODS:ABT-8...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-009-1044-3

    authors: Muscal JA,Thompson PA,Giranda VL,Dayton BD,Bauch J,Horton T,McGuffey L,Nuchtern JG,Dauser RC,Gibson BW,Blaney SM,Su JM

    更新日期:2010-02-01 00:00:00

  • Studies on the mechanism of 3-deazaguanine cytotoxicity in L1210-sensitive and -resistant cell lines.

    abstract::3-Deazaguanine (3-DG), a purine analogue, has unusual antitumor activity against experimental mammary tumor models and a number of other solid tumors. Others have shown that mutant CHO cells deficient in hypoxanthine guanine phosphoribosyl transferase (HGPRTase) or adenine phosphoribosyl transferase (APRTase) are resi...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00273409

    authors: Singh G,Luna MK,Ardalan B

    更新日期:1988-01-01 00:00:00

  • In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human ovarian cancers.

    abstract:PURPOSE:To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of the standard platinum agents, cisplatin and carboplatin, against fresh human, epithelial ovarian cancers. METHODS:The Hamburger-Salmon human tumor colony-forming assay (HTCA) was used to measure the chemosensit...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050604

    authors: Alberts DS,Fanta PT,Running KL,Adair LP Jr,Garcia DJ,Liu-Stevens R,Salmon SE

    更新日期:1997-01-01 00:00:00

  • A phase I trial of flavopiridol in relapsed multiple myeloma.

    abstract:PURPOSE:Flavopiridol is primarily a cyclin-dependent kinase-9 inhibitor, and we performed a dose escalation trial to determine the maximum tolerated dose and safety and generate a pharmacokinetic (PK) profile. METHODS:Patients with a diagnosis of relapsed myeloma after at least two prior treatments were included. Flav...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-013-2347-y

    authors: Hofmeister CC,Poi M,Bowers MA,Zhao W,Phelps MA,Benson DM,Kraut EH,Farag S,Efebera YA,Sexton J,Lin TS,Grever M,Byrd JC

    更新日期:2014-02-01 00:00:00

  • Phase 1 dose-escalation study of the PARP inhibitor CEP-9722 as monotherapy or in combination with temozolomide in patients with solid tumors.

    abstract:PURPOSE:Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme important in DNA repair. PARP-1 activation at points of DNA strand break results in poly(ADP-ribose) polymer formation, opening the DNA structure, and allowing access of other repair enzymes. CEP-9722 inhibits PARP-1 and PARP-2 and is designed to potent...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00280-014-2486-9

    authors: Plummer R,Stephens P,Aissat-Daudigny L,Cambois A,Moachon G,Brown PD,Campone M

    更新日期:2014-08-01 00:00:00

  • Preclinical pharmacokinetics and oral bioavailability of BMS-310705, a novel epothilone B analog.

    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

    authors: Kamath AV,Chang M,Lee FY,Zhang Y,Marathe PH

    更新日期:2005-08-01 00:00:00

  • Intracellular activation and cytotoxic action of RS-1541 against cultured human tumor cells.

    abstract::RS-1541, an acyl-derivative of rhizoxin (Fig. 1), is a potent antitumor compound. This agent showed cytotoxicity in vitro on some cultured human tumor cells, although it was less potent than rhizoxin. Rhizoxin exhibited antitumor effects by inhibiting the polymerization of tubulin, whereas RS-1541 did not inhibit tubu...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00689446

    authors: Takatori T,Koizumi T,Tokui T,Mitsuhashi Y,Shiraishi A,Tsuruo T

    更新日期:1995-01-01 00:00:00

  • Chemotherapy for the carcinoid syndrome.

    abstract::Patients with carcinoid syndrome usually die from carcinomatosis, rather than the pharmacological effects of the tumour. Functioning carcinoid tumours are resistant to radiotherapy. Twenty-four different cytotoxic drugs or combinations have been used to treat the carcinoid syndrome, but only actinomycin D, cyclophosph...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00258469

    authors: Harris AL

    更新日期:1981-01-01 00:00:00

  • High-dose carmustine for high-grade gliomas in childhood.

    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

    authors: Bouffet E,Khelfaoui F,Philip I,Biron P,Brunat-Mentigny M,Philip T

    更新日期:1997-01-01 00:00:00