In vivo antitumor activity of S16020, a topoisomerase II inhibitor, and doxorubicin against human brain tumor xenografts.

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 glioblastoma (IGRG88, 93, 121) xenografts treated at an advanced stage of tumor growth in comparison with that of doxorubicin. Animals were randomly assigned to receive i.v. S16020 or doxorubicin weekly for three consecutive weeks. The optimal dose was 80 mg/kg per week. S16020 demonstrated a significant antitumor activity in two out of three medulloblastoma xenografts. IGRM57 xenografts were highly sensitive with 100% tumor regressions and a tumor growth delay (TGD) of 102 days, while one of eight IGRM34 xenografts showed a partial regression with a TGD of 16 days. Doxorubicin was significantly more active than S16020 in these two models. IGRM33, a model established from a tumor in relapse after chemotherapy and radiotherapy, was refractory to both drugs. S16020 demonstrated a significant antitumor activity in the three glioblastoma xenografts evaluated. The wild-type p53 IGRG93 xenograft was highly sensitive with 100% tumor regressions and a TGD of 54 days. IGRG121 (wt p53) and IGRG88 (mutant p53) were moderately sensitive with TGDs of 33 and 23 days, respectively. Doxorubicin showed greater activity in two of these models. All six xenografts exhibited low expression of mdr1 as quantitated by RT-PCR, and no correlation was found with the activity of either drug. Conversely, a low activity of the two drugs was significantly associated with a high expression of MRP1 in medulloblastomas. Finally, no relationship was observed between drug sensitivity to either drug and expression of their target, topoisomerase IIalpha. In conclusion, S16020 and doxorubicin showed significant antitumor activity in brain tumor xenografts treated at an advanced stage of tumor growth. Their activity was related to MRP1 expression in medulloblastomas.

authors

Vassal G,Merlin JL,Terrier-Lacombe MJ,Grill J,Parker F,Sainte-Rose C,Aubert G,Morizet J,Sévenet N,Poullain MG,Lucas C,Kalifa C

doi

10.1007/s00280-003-0584-1

keywords:

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

385-94

issue

5

eissn

0344-5704

issn

1432-0843

journal_volume

51

pub_type

杂志文章
  • In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents.

    abstract:PURPOSE:Artemisinins are now established drugs for treatment of malaria. These agents have been shown to possess impressive anti-cancer properties. We have investigated the role of artemisone (ATM), a novel derivative of artemisinin (ART) in a cancer setting both alone and in combination with established chemotherapeut...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-010-1355-4

    authors: Gravett AM,Liu WM,Krishna S,Chan WC,Haynes RK,Wilson NL,Dalgleish AG

    更新日期:2011-03-01 00:00:00

  • Potentiation of etoposide-induced cytotoxicity and DNA damage in CCRF-CEM cells by pretreatment with non-cytotoxic concentrations of arabinosyl cytosine.

    abstract::Pretreatment of the human lymphoblastoid cell line CCRF-CEM with 0.02 microM arabinosyl cytosine (ara C) enhances both the cytotoxic and the DNA-damaging effects of etoposide. This concentration of ara C is itself non-cytotoxic and results in no detectable DNA damage as measured by alkaline elution. Ara C pretreatment...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00685101

    authors: Chresta CM,Hicks R,Hartley JA,Souhami RL

    更新日期:1992-01-01 00:00:00

  • Serum microRNA-21 predicted treatment outcome and survival in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy combined with trastuzumab.

    abstract:PURPOSE:The purpose of this study was to evaluate the expression of ser-miRNAs at different periods during treatment and analyze their relationship with therapeutic response and prognosis in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy combined with trastuzumab (NCCT). METHODS:Venous blood w...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-019-03937-9

    authors: Liu B,Su F,Lv X,Zhang W,Shang X,Zhang Y,Zhang J

    更新日期:2019-11-01 00:00:00

  • Carboplatin-based combination chemotherapy for advanced carcinoma of the cervix.

    abstract::A combination of carboplatin, vincristine, methotrexate and bleomycin (COMB) was given to 29 patients with locally advanced, metastatic or recurrent cervical carcinoma. A total of 85 cycles of chemotherapy were given, with half of the patients receiving greater than 3 cycles. Both the response rate (32.1%) and the med...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00685165

    authors: Junor E,Davies J,Habeshaw T,Kaye S,Paul J,Rankin E,Reed N,Symonds RP

    更新日期:1991-01-01 00:00:00

  • New approaches to drug discovery and development: a mechanism-based approach to pharmaceutical research and its application to BNP7787, a novel chemoprotective agent.

    abstract::Any approach applied to drug discovery and development by the medical community and pharmaceutical industry has a direct impact on the future availability of improved, novel, and curative therapies for patients with cancer. By definition, drug discovery is a complex learning process whereby research efforts are direct...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/s00280-003-0653-5

    authors: Hausheer FH,Kochat H,Parker AR,Ding D,Yao S,Hamilton SE,Petluru PN,Leverett BD,Bain SH,Saxe JD

    更新日期:2003-07-01 00:00:00

  • Pegylated liposomal doxorubicin in combination with vinorelbine as salvage treatment in pretreated patients with advanced breast cancer: a multicentre phase II study.

    abstract:PURPOSE:To investigate the activity and tolerance of pegylated liposomal doxorubicin in combination with vinorelbine in pretreated patients with metastatic breast cancer. PATIENTS AND TREATMENT:Thirty-six women with metastatic breast cancer were enrolled. The median age was 64 years, 80% of the patients had a performa...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00280-006-0236-3

    authors: Ardavanis A,Mavroudis D,Kalbakis K,Malamos N,Syrigos K,Vamvakas L,Kotsakis A,Kentepozidis N,Kouroussis C,Agelaki S,Georgoulias V,Breast Cancer Committee of the Hellenic Oncology Research Group.

    更新日期:2006-12-01 00:00:00

  • Effective combination therapy of metastatic murine solid tumors with edatrexate and the vinca alkaloids, vinblastine, navelbine and vindesine.

    abstract::Studies are described in which a new folate analogue, edatrexate (EDX), in combination with the vinca alkaloids, vinblastine (VBL), navelbine (NVB) or vindesine (DVA) was evaluated against E0771 mammary adenocarcinoma, T241 fibrosarcoma and the Lewis lung tumor. Each of the four agents when given individually to anima...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00685901

    authors: Otter GM,Sirotnak FM

    更新日期:1994-01-01 00:00:00

  • Disposition of conjugate-bound and free doxorubicin in tumor-bearing mice following administration of a BR96-doxorubicin immunoconjugate (BMS 182248).

    abstract:PURPOSE:The chimeric BR96-doxorubicin (DOX) immunoconjugate, BMS 182248, has induced remissions and cures of human lung adenocarcinoma (L2987) implanted in athymic mice. The purpose of this study was to evaluate the biodistribution of DOX after BMS 182248 administration to tumor-bearing mice and to evaluate the ability...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050655

    authors: Mosure KW,Henderson AJ,Klunk LJ,Knipe JO

    更新日期:1997-01-01 00:00:00

  • Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model.

    abstract:PURPOSE:Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excis...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-008-0703-0

    authors: Kelner MJ,McMorris TC,Rojas RJ,Estes LA,Suthipinijtham P

    更新日期:2008-12-01 00:00:00

  • Comparison of 5-FU versus FUDR activity in human colorectal cancer using an in vitro clonogenic assay (HTCA).

    abstract::Comparative in vitro drug testing was performed in 72 of 183 surgically removed human colorectal cancer specimens (34 primary lesions, 38 metastases). In 10 of these tumors, comparative dose-response curves were obtained. Given a greater than or equal to 70% ICF (inhibition of colony formation) as threshold for in vit...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00273390

    authors: Flentje M,Flentje D,Schlag P

    更新日期:1986-01-01 00:00:00

  • Treatment of resistant metastatic melanoma using sequential epigenetic therapy (decitabine and panobinostat) combined with chemotherapy (temozolomide).

    abstract:PURPOSE:To explore the safety and tolerability of combining two epigenetic drugs: decitabine (a DNA methyltransferase inhibitor) and panobinostat (a histone deacetylase inhibitor), with chemotherapy with temozolomide (an alkylating agent). The purpose of such combination is to evaluate the use of epigenetic priming to ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-014-2501-1

    authors: Xia C,Leon-Ferre R,Laux D,Deutsch J,Smith BJ,Frees M,Milhem M

    更新日期:2014-10-01 00:00:00

  • Effect of front-line chemotherapy on circulating CK-19 mRNA-positive cells in patients with metastatic breast cancer.

    abstract:PURPOSE:To evaluate the effect of front-line chemotherapy on CK-19mRNA+ circulating tumor cells (CTCs) and their relevance in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS:The presence of CK-19mRNA+ CTCs was assessed using a real-time RT-PCR assay in 298 previously untreated patients with MBC befo...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00280-014-2598-2

    authors: Georgoulias V,Apostolaki S,Bozionelou V,Politaki E,Perraki M,Georgoulia N,Kalbakis K,Kotsakis A,Xyrafas A,Agelaki S,Mavroudis D

    更新日期:2014-12-01 00:00:00

  • Polymorphic tandem repeat sequences of the thymidylate synthase gene correlates with cellular-based sensitivity to fluoropyrimidine antitumor agents.

    abstract:PURPOSE:Thymidylate synthase (TS) is one of the target molecules for the antitumor effects of fluoropyrimidine drugs. The cellular thymidylate synthase level is one of the determining factors for the antitumor activity of fluoropyrimidines. TYMS, which encodes TS, has been reported to possess 28-bp tandem repeat sequen...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-005-1018-z

    authors: Yawata A,Kim SR,Miyajima A,Kubo T,Ishida S,Saito Y,Nakajima Y,Katori N,Matsumoto Y,Fukuoka M,Ohno Y,Ozawa S,Sawada J

    更新日期:2005-11-01 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

  • Enhancing the anticancer efficacy of camptothecin using biotinylated poly(ethylene glycol) conjugates in sensitive and multidrug-resistant human ovarian carcinoma cells.

    abstract:BACKGROUND:Camptothecin (CPT) is an anticancer agent that kills cells by converting DNA topoisomerase I into a DNA-damaging agent. Although CPT and its derivatives are now being used to treat tumors in a variety of clinical protocols, the low water solubility of the drug and its unique pharmacodynamics and reactivity i...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-002-0463-1

    authors: Minko T,Paranjpe PV,Qiu B,Lalloo A,Won R,Stein S,Sinko PJ

    更新日期:2002-08-01 00:00:00

  • Pharmacokinetic and phase I study of intravenous DON (6-diazo-5-oxo-L-norleucine) in children.

    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

    authors: Sullivan MP,Nelson JA,Feldman S,Van Nguyen B

    更新日期:1988-01-01 00:00:00

  • Quantification of 4-hydroxyifosfamide in plasma of ifosfamide-treated mice.

    abstract:PURPOSE:Ifosfamide is becoming an important clinical anticancer drug. Meaningful pharmacology studies require quantification of its activated and active metabolites, 4-hydroxyifosfamide (HOIfos) and isophosphoramide mustard (IPM), respectively. METHODS:Current methodology for quantifying the unstable HOIfos in biologi...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050625

    authors: Struck RF,McCain DM,Tendian SW,Tillery KH

    更新日期:1997-01-01 00:00:00

  • High-dose VP16 cisplatinum in soft tissue sarcoma of children.

    abstract::Nine children with soft tissue sarcomas, five of them rhabdomyosarcomas with initial metastatic disease, (one patient, partial response, one patient), refractory primary, (two patients, relapse, five patients) were treated with a combination of high-dose VP16 (100 mg/m2 daily for 5 days) and cisplatin (40 mg/m2 daily ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00685912

    authors: Grabois M,Frappaz D,Bouffet E,Carrie C,Bouhour D,Philip T,Brunat-Mentigny M

    更新日期:1994-01-01 00:00:00

  • A phase I study of 5-fluorouracil, leucovorin and levamisole.

    abstract:PURPOSE:The activity of 5-fluorouracil (5-FU) against colon cancer is enhanced by leucovorin and the combination of 5-FU and levamisole has activity in the adjuvant treatment of colonic malignancies. The combination of 5-FU with both leucovorin and levamisole may provide additional benefit in the treatment of colon can...

    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/s002800050576

    authors: Cleary JF,Arzoomanian R,Alberti D,Feierabend C,Storer B,Witt P,Carbone P,Wilding G

    更新日期:1997-01-01 00:00:00

  • ABCC4 functional SNP in the 3' splice acceptor site of exon 8 (G912T) is associated with unfavorable clinical outcome in children with acute lymphoblastic leukemia.

    abstract:OBJECTIVES:ATP-binding cassette subfamily C member 4 (ABCC4) encoding MRP4 protein is involved in pediatric acute lymphoblastic leukemia (ALL) drug resistance. The nonsynonymous single nucleotide polymorphism (SNP) rs2274407 (G912T; K304N) is located in the 3' splice acceptor site of exon 8 of ABCC4 pre-mRNA. The aim o...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-017-3340-7

    authors: Mesrian Tanha H,Rahgozar S,Mojtabavi Naeini M

    更新日期:2017-07-01 00:00:00

  • Clinical pharmacology of intracarotid etoposide.

    abstract::Pharmacokinetics studies were performed in ten patients who received VP-16 by intracarotid infusion at 100-300 mg/m2. VP-16 was analyzed by high-pressure liquid chromatography. ESTRIP and NONLIN were used to characterize VP-16 pharmacokinetics. VP-16 disappeared biphasically, with a t1/2 beta of 6.1 +/- 1.4 h; the tot...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00293995

    authors: Savaraj N,Feun LG,Lu K,Wallace S,Fields WS,Loo TL

    更新日期:1986-01-01 00:00:00

  • Fixed-dose rate infusion and standard rate infusion of gemcitabine in patients with advanced non-small-cell lung cancer: a meta-analysis of six trials.

    abstract:PURPOSE:To compare the response, survival, hematological and non-hematological toxicities of gemcitabine administrated at fixed-dose rate infusion (10 mg/m(2)/min, FDR) and standard 30 min infusion in patients with advanced non-small-cell lung cancer (NSCLC). METHODS:Electronic databases of MEDLINE, EMBASE and Cochran...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,meta分析

    doi:10.1007/s00280-012-1974-z

    authors: Qiu MT,Ding XX,Hu JW,Tian HY,Yin R,Xu L

    更新日期:2012-12-01 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

  • Phase II trial of biweekly paclitaxel plus infusional 5-fluorouracil and leucovorin in patients with advanced or recurrent inoperable gastric cancer.

    abstract:PURPOSE:To investigate the efficacy and safety of combination chemotherapy with biweekly paclitaxel plus infusional 5-fluorouracil and leucovorin in the treatment of patients with advanced or metastatic gastric cancer. PATIENTS AND METHODS:Chemonaive patients with histologically confirmed advanced or recurrent inopera...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-008-0752-4

    authors: Lee HJ,Cho DY,Park JC,Bae SB,Lee KT,Cho IS,Han CS,Park SY,Yun HJ,Kim S

    更新日期:2009-02-01 00:00:00

  • NECTIN-4 increased the 5-FU resistance in colon cancer cells by inducing the PI3K-AKT cascade.

    abstract:PURPOSE:5-Fluorouracil is the most commonly used drug for the treatment of colon cancer, yet clinical resistance to this drug is frequently observed in patients making this drug ineffective. Thus, identification of gene responsible for 5-FU resistance is of utmost importance. METHODS:Cellular cytotoxicity and expressi...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-015-2794-8

    authors: Das D,Satapathy SR,Siddharth S,Nayak A,Kundu CN

    更新日期:2015-09-01 00:00:00

  • Translational research of a novel humanized epidermal growth factor receptor-related protein: a putative inhibitor of pan-ErbB.

    abstract:PURPOSE:The ErbB family members are protein tyrosine kinases, which play a crucial role in the signal transduction pathways that regulate key cellular functions. Overexpression of the ErbB family members is associated with oncogenicity, metastatic potential, cell proliferation, apoptosis, angiogenesis, and prognosis in...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/s00280-011-1748-z

    authors: Fu XH,Li J,Huang JJ,Zheng S,Zhang SZ

    更新日期:2011-12-01 00:00:00

  • Nonimmunological release of histamine from rat mast cells elicited by antineoplastic agents: effect of drug combinations.

    abstract::We studied the release of histamine elicited by some antineoplastic drugs in rat pleural and peritoneal mast cells. The drugs tested included the antibiotic mitomycin; the anthracyclines daunorubicin, doxorubicin, and epirubicin; the glycopeptide bleomycin; the chromopeptide dactinomycin; the platinum coordination com...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00685603

    authors: Botana LM,Arnaez E,Vieytes MR,Alfonso A,Louzao MC

    更新日期:1992-01-01 00:00:00

  • A phase I study of sunitinib combined with modified FOLFOX6 in patients with advanced solid tumors.

    abstract:PURPOSE:This phase I study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, and preliminary antitumor effects of sunitinib combined with modified FOLFOX6 (mFOLFOX6). METHODS:Patients with advanced solid malignancies received mFOLFOX6 in 2-week cycles with escalating sunitinib doses (2...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-012-1880-4

    authors: Leong S,Eckhardt SG,Chan E,Messersmith WA,Spratlin J,Camidge DR,Diab S,Khosravan R,Lin X,Chow Maneval E,Lockhart AC

    更新日期:2012-07-01 00:00:00

  • An appraisal of subcutaneous trastuzumab: a new formulation meeting clinical needs.

    abstract::Trastuzumab has deeply and radically changed the course of HER2-positive breast cancer disease. The recent development of a subcutaneous (SC) formulation of trastuzumab is an important step towards improved patients' care. SC trastuzumab at a fixed dose of 600 mg administered every 3 weeks for about 5 min provides a v...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-013-2289-4

    authors: Launay-Vacher V

    更新日期:2013-12-01 00:00:00

  • Pharmacokinetics of lenalidomide during high cut-off dialysis in a patient with multiple myeloma and renal failure.

    abstract:INTRODUCTION:High cut-off dialysis, increasingly used in multiple myeloma patients, is susceptible to influence anticancer drug elimination. We report about lenalidomide disposition in a patient on high cut-off dialysis for renal failure secondary to myeloma cast nephropathy. METHODS:The patient received a higher dosa...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-016-3219-z

    authors: Dao K,Lu Y,Peer CJ,Figg WD,Stadelmann R,Burnier M,Buclin T,Kissling S

    更新日期:2017-01-01 00:00:00