Pharmacokinetic, biochemical and clinical effects of dimethyltriazenoimidazole-4-carboxamide-bischloroethylnitrosourea combination therapy in patients with advanced breast cancer.

Abstract:

:We assessed whether split dosing with the methylating agent DTIC is an effective strategy for inactivating the DNA repair protein O6-alkylguanine DNA-ATase in order to decrease tumour resistance to BCNU. ATase levels in PBMCs were used as a surrogate for tumour ATase depletion to determine whether this correlated with either the pharmacokinetics of DTIC and its major metabolite AIC or other clinical sequelae. Two 1 hr infusions of DTIC (400 mg/m(2)) 4 hr apart followed another 4 hr later by BCNU (75 mg/m(2)) were administered every 6 weeks in 7 patients with heavily pretreated advanced breast cancer. The extent and kinetics of ATase depletion and recovery in PBMCs varied not only between patients but also between cycles in the same patient. Serial FNAs showed heterogeneity in tumour ATase expression but no clear pattern of change in ATase activity. DTIC and AIC exhibited biphasic clearance from the blood, consistent with a 2-compartment pharmacokinetic model. The AUC of AIC was strongly correlated with the percentage decrease in PBMC ATase levels. There were no clinical responses, and toxicity in neutrophils and platelets was marked. Split-dose DTIC therefore does not appear to be a clinically effective approach to overcome O(6)-alkylating agent resistance in advanced breast cancer.

journal_name

Int J Cancer

authors

Clemons M,Ranson M,Margison JM,El Teraifi H,Griffiths A,Kelly J,Morris CQ,Howell A,Margison GP

doi

10.1002/ijc.10849

keywords:

subject

Has Abstract

pub_date

2003-02-20 00:00:00

pages

686-92

issue

5

eissn

0020-7136

issn

1097-0215

journal_volume

103

pub_type

杂志文章
  • Beta-galactoside alpha2,6 sialyltransferase in human colon cancer: contribution of multiple transcripts to regulation of enzyme activity and reactivity with Sambucus nigra agglutinin.

    abstract::Colon cancer tissues display an increased activity of beta-galactoside alpha2,6 sialyltransferase (ST6Gal.I) and an increased reactivity with the lectin from Sambucus nigra (SNA), specific for alpha2,6-sialyl-linkages. Experimental and clinical studies indicate a contribution of these alterations to tumor progression,...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0215(20001001)88:1<58::aid-ijc9>3.0.c

    authors: Dall'Olio F,Chiricolo M,Ceccarelli C,Minni F,Marrano D,Santini D

    更新日期:2000-10-01 00:00:00

  • Treatment de-escalation in HPV-positive oropharyngeal carcinoma: ongoing trials, critical issues and perspectives.

    abstract::Due to the generally poor prognosis of head and neck squamous cell carcinoma (HNSCC), treatment has been intensified, these last decades, leading to an increase of serious side effects. High-risk human papillomavirus (HR-HPV) infection has been recently etiologically linked to a subset of oropharyngeal squamous cell c...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1002/ijc.28847

    authors: Mirghani H,Amen F,Blanchard P,Moreau F,Guigay J,Hartl DM,Lacau St Guily J

    更新日期:2015-04-01 00:00:00

  • Pharmacokinetics, pharmacodynamics and efficacy on pediatric tumors of the glioma radiosensitizer KU60019.

    abstract::We have recently reported that glioblastoma (GB)-initiating cells (GIC) with low expression and/or mutation of TP53 and high expression of PI3K ("responder" genetic profile) can be effectively and safely radiosensitized by the ATM inhibitor KU60019. We report here on drug's diffusion and elimination from the animal bo...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29121

    authors: Vecchio D,Daga A,Carra E,Marubbi D,Raso A,Mascelli S,Nozza P,Garrè ML,Pitto F,Ravetti JL,Vagge S,Corvò R,Profumo A,Baio G,Marcello D,Frosina G

    更新日期:2015-03-15 00:00:00

  • Telomere homolog oligonucleotides induce apoptosis in malignant but not in normal lymphoid cells: mechanism and therapeutic potential.

    abstract::Human B- or T-cell lymphoma lines and primary murine lymphomas were treated with DNA oligonucleotides homologous to the telomere (TTAGGG repeat; "T-oligo"), either alone or in combination with standard, widely-used anticancer chemotherapeutic agents. T-oligo induces cell cycle arrest and apoptosis in cultured human or...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23946

    authors: Longe HO,Romesser PB,Rankin AM,Faller DV,Eller MS,Gilchrest BA,Denis GV

    更新日期:2009-01-15 00:00:00

  • Co-expression of heparin-binding EGF-like growth factor and related peptides in human gastric carcinoma.

    abstract::Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a member of the EGF family of polypeptide growth factors, which includes EGF, transforming growth factor alpha(TGF-alpha), amphiregulin (AR) and betacellulin (BTC). To assess the potential role of HB-EGF in human gastric carcinomas, the expre...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-0215(19960503)66:3<315::AID-IJC

    authors: Naef M,Yokoyama M,Friess H,Büchler MW,Korc M

    更新日期:1996-05-03 00:00:00

  • Development and validation of a cycle-specific risk score for febrile neutropenia during chemotherapy cycles 2-6 in patients with solid cancers: The CSR FENCE score.

    abstract::The absolute risk reduction by prophylaxis in chemotherapy-induced febrile neutropenia (FN) is largest in patients at highest underlying risk. Therefore, reliable predictive models are needed. Here, we develop and validate such a model for risk of FN during chemotherapy cycles 2-6. A prediction score for risk of FN du...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32249

    authors: Aagaard T,Reekie J,Roen A,Daugaard G,Specht L,Sengeløv H,Mocroft A,Lundgren J,Helleberg M

    更新日期:2020-01-15 00:00:00

  • NK- and T-cell subsets in malignant mesothelioma patients: Baseline pattern and changes in the context of anti-CTLA-4 therapy.

    abstract::Malignant mesothelioma (MM) is a highly aggressive form of cancer with limited treatment options. Although the role of NK cells has been studied in many solid tumors, the pattern of NK-cell subsets and their recognition of mesothelioma cells remain to be explored. We used RNA expression data of MM biopsies derived fro...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32363

    authors: Sottile R,Tannazi M,Johansson MH,Cristiani CM,Calabró L,Ventura V,Cutaia O,Chiarucci C,Covre A,Garofalo C,Pontén V,Tallerico R,Frumento P,Micke P,Maio M,Kärre K,Carbone E

    更新日期:2019-10-15 00:00:00

  • Human melanoma-specific oncofetal antigen defined by a mouse monoclonal antibody.

    abstract::140.240, an IgG2a mouse monoclonal antibody raised against a cultured human melanoma cell line, was highly specific for melanoma cells as determined by direct and absorption analyses in a mixed hemadsorption assay. Supernatants of doubly cloned hybridomas producing antibody 140.240 reacted with all cultured and fresh ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910300507

    authors: Liao SK,Clarke BJ,Khosravi M,Kwong PC,Brickenden A,Dent PB

    更新日期:1982-11-15 00:00:00

  • Food-frequency questionnaire-based estimates of total antioxidant capacity and risk of non-Hodgkin lymphoma.

    abstract::Antioxidants, primarily from fruits and vegetables, have been hypothesized to protect against non-Hodgkin lymphoma (NHL). The oxygen radical absorbance capacity (ORAC) assay, which measures total antioxidant capacity of individual foods and accounts for synergism, can be estimated using a food-frequency questionnaire ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.26491

    authors: Holtan SG,O'Connor HM,Fredericksen ZS,Liebow M,Thompson CA,Macon WR,Micallef IN,Wang AH,Slager SL,Habermann TM,Call TG,Cerhan JR

    更新日期:2012-09-01 00:00:00

  • Prevalence of antibody to adult T-cell leukemia virus-associated antigens (ATLA) in Japanese monkeys and other non-human primates.

    abstract::The prevalence of adult T-cell-leukemia virus (ATLV) infection was examined in Japanese monkeys living naturally in various parts of Japan and in other species of non-human primates imported into and kept in Japan. Sera of 2,650 Japanese monkeys from 41 troops throughout Japan were tested. High incidences of anti-ATLV...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910330205

    authors: Hayami M,Komuro A,Nozawa K,Shotake T,Ishikawa K,Yamamoto K,Ishida T,Honjo S,Hinuma Y

    更新日期:1984-02-15 00:00:00

  • Efficacy of intra-hepatectomy 5-FU on recurrence and metastasis of human hepatocellular carcinoma in nude mice.

    abstract::A novel intra-operative chemotherapy nude mouse model for human hepatocellular carcinoma (HCC) has been developed. Intra-peritoneal (i.p.) administration of 5-fluorouracil (5-FU) was begun 2 hr before hepatic resection of HCC and then continued post-operatively for 4 consecutive days. This regime, termed intra-hepatec...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0215(200002)9999:9999<::aid-ijc1042>3

    authors: Rashidi B,An Z,Sun FX,Li X,Tang ZY,Moossa AR,Hoffman RM

    更新日期:2001-01-15 00:00:00

  • Identification of HLA class I dependent immunogenic peptides from clonotypic TCRbeta expressed in cutaneous T-cell lymphoma.

    abstract::The clonotypic T-cell receptor (TCR) is a potential target antigen for specific immunotherapy of cutaneous T-cell lymphoma (CTCL). We identified T-cell epitopes from the rearranged TCR beta chain of the malignant T-cell population by the "reverse immunology" approach. Peptide-specific T-cell lines were generated again...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22113

    authors: Zeng J,Müller-Berghaus J,Nguyen XD,Klüter H,Schönhaber H,Song M,Schwinn N,Schadendorf D,Goerdt S,Eichmüller S,Dippel E

    更新日期:2006-11-15 00:00:00

  • Comorbidities, age and period of diagnosis influence treatment and outcomes in early breast cancer.

    abstract::Survival for breast cancer (BC) is lower in eastern than northern/central Europe, and in older than younger women. We analysed how comorbidities at diagnosis affected whether selected standard treatments (STs) were given, across Europe and over time, also assessing consequences for survival/relapse. We analysed 7581 s...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31974

    authors: Minicozzi P,Van Eycken L,Molinie F,Innos K,Guevara M,Marcos-Gragera R,Castro C,Rapiti E,Katalinic A,Torrella A,Žagar T,Bielska-Lasota M,Giorgi Rossi P,Larrañaga N,Bastos J,Sánchez MJ,Sant M,European HR Working Group on

    更新日期:2019-05-01 00:00:00

  • Oncogenicity of Friend-virus-infected cells: determination of origin of spleen colonies by the H-2 antigens as genetic markers.

    abstract::Spleen cells from mice infected with Friend leukemia virus (FLV) inoculated by the intravenous route give rise to macroscopically visible colonies in the spleens of normal F1 histocompatible hybrid hosts. A study of H-2 antigens as generic markers for identification of strains of origin of cells constituting the splee...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910220418

    authors: Wendling F,Tambourin PE

    更新日期:1978-10-15 00:00:00

  • Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study.

    abstract::Acrylamide, a probable human carcinogen, is formed during the cooking of many commonly consumed foods. Data are scant on whether dietary acrylamide represents an important cancer risk in humans. We studied the association between acrylamide and prostate cancer risk using 2 measures of acrylamide exposure: intake from ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.24175

    authors: Wilson KM,Bälter K,Adami HO,Grönberg H,Vikström AC,Paulsson B,Törnqvist M,Mucci LA

    更新日期:2009-05-15 00:00:00

  • Cytomatrix reorganization in dimethyl sulfoxide-induced "Qi" substate murine hepatic tumor cells.

    abstract::Cultured murine hepatic tumor (HT) cells respond to the polar solvent dimethylsulfoxide (DMSO) with specific alterations in morphology, proliferative kinetics, and biochemical properties. These include entrance into a quiescent "Qi" substate (characterized by accumulation of cells in G1 phase and lowered cellular RNA ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910420222

    authors: Ryan MP,Higgins PJ

    更新日期:1988-08-15 00:00:00

  • COX-2 and p53 in human sinonasal cancer: COX-2 expression is associated with adenocarcinoma histology and wood-dust exposure.

    abstract::The causal role of wood-dust exposure in sinonasal cancer (SNC) has been established in epidemiological studies, but the mechanisms of SNC carcinogenesis are still largely unknown. Increased amounts of COX-2 are found in both premalignant and malignant tissues, and experimental evidence link COX-2 to development of ca...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23360

    authors: Holmila R,Cyr D,Luce D,Heikkilä P,Dictor M,Steiniche T,Stjernvall T,Bornholdt J,Wallin H,Wolff H,Husgafvel-Pursiainen K

    更新日期:2008-05-01 00:00:00

  • Resident macrophages specifically inhibit DNA synthesis in the nuclei of transformed cells in heterokaryons.

    abstract::DNA synthesis in heterokaryons of mouse peritoneal macrophages and various proliferating cultured cells was analyzed. Macrophages did not inhibit replication in the nuclei of non-immortalized and spontaneously immortalized cells (rat fibroblasts and macrophages, mouse pre-macrophages, NIH3T3 cells). On the contrary, t...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910440611

    authors: Prudovsky IA,Gumeniuk RR,Yegorov YE,Zelenin AV

    更新日期:1989-12-15 00:00:00

  • Cost of decentralized CAR T-cell production in an academic nonprofit setting.

    abstract::Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy with high acquisition costs, and it has raised concerns about affordability and sustainability in many countries. Furthermore, the current centralized production paradigm for the T cells is less than satisfactory. Therefore, several countries ...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1002/ijc.33156

    authors: Ran T,Eichmüller SB,Schmidt P,Schlander M

    更新日期:2020-12-15 00:00:00

  • Synchronous multiple primary gastrointestinal cancer exhibits frequent microsatellite instability.

    abstract::Colorectal (CRC) and gastric cancers (GC), the most common gastrointestinal malignancies, have been known to develop occasionally in a same patient. Previous studies have focused on the etiology of patients with multiple primary gastric and colorectal cancer (MPGCC); however, the carcinogenic process of MPGCC remains ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(20000601)86:5<678::aid-ijc

    authors: Ohtani H,Yashiro M,Onoda N,Nishioka N,Kato Y,Yamamoto S,Fukushima S,Hirakawa-Ys Chung K

    更新日期:2000-06-01 00:00:00

  • Novel melanoma antigen, FCRL/FREB, identified by cDNA profile comparison using DNA chip are immunogenic in multiple melanoma patients.

    abstract::We applied a strategy that utilized a combination of systematic gene expression analysis with various tissues and immunological detection with sera from melanoma patients to identify melanoma antigens expressed preferentially in melanoma and melanocytes. We selected 101 genes by comparing cDNA profiles obtained by Gen...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20735

    authors: Inozume T,Matsuzaki Y,Kurihara S,Fujita T,Yamamoto A,Aburatani H,Shimada S,Kawakami Y

    更新日期:2005-03-20 00:00:00

  • Comparative expression of the psoriasin (S100A7) and S100C genes in breast carcinoma and co-localization to human chromosome 1q21-q22.

    abstract::Using differential screening of a breast cancer cDNA library, we isolated a cDNA encoding the psoriasin (S100A7) protein, previously identified in psoriatic epidermis. In the present study, we demonstrate that the psoriasin gene is expressed in breast cancer cell lines and in cancer cells of some breast carcinomas but...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910630225

    authors: Moog-Lutz C,Bouillet P,Régnier CH,Tomasetto C,Mattei MG,Chenard MP,Anglard P,Rio MC,Basset P

    更新日期:1995-10-09 00:00:00

  • Key signaling pathways in the muscle-invasive bladder carcinoma: Clinical markers for disease modeling and optimized treatment.

    abstract::In this review, we evaluate key molecular pathways and markers of muscle-invasive bladder cancer (MIBC). Overexpression and activation of EGFR, p63, and EMT genes are suggestive of basal MIBC subtype generally responsive to chemotherapy. Alterations in PPARγ, ERBB2/3, and FGFR3 gene products and their signaling along ...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1002/ijc.29918

    authors: Kiselyov A,Bunimovich-Mendrazitsky S,Startsev V

    更新日期:2016-06-01 00:00:00

  • Esophagin and proliferating cell nuclear antigen (PCNA) are biomarkers of human esophageal neoplastic progression.

    abstract::PCNA and esophagin have been implicated in the multistep process of carcinogenesis, but simultaneous characterization of these proteins in the early stages of esophageal neoplastic progression has yet to be undertaken. In morphologically normal esophageal epithelium, esophagin stains the granular layer cells, principa...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20267

    authors: Kimos MC,Wang S,Borkowski A,Yang GY,Yang CS,Perry K,Olaru A,Deacu E,Sterian A,Cottrell J,Papadimitriou J,Sisodia L,Selaru FM,Mori Y,Xu Y,Yin J,Abraham JM,Meltzer SJ

    更新日期:2004-09-01 00:00:00

  • Antibody responses to Herpesvirus papio antigens in baboons with lymphoma.

    abstract::An Epstein-Barr virus-related herpesvirus, termed Herpesvirus papio (HVP), was isolated from baboons (Papio hamadryas) at the Institute of Experimental Pathology and Therapy, Sukhumi, USSR, where there is a continuing outbreak of lymphoma. In the present study sera from diseased baboons and from age- and sex-matched c...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910230208

    authors: Neubauer RH,Rabin H,Strnad BC,Lapin BA,Yakovleva LA,Indzie E

    更新日期:1979-02-01 00:00:00

  • Activation of ras oncogenes and expression of tumor-specific transplantation antigens in methylcholanthrene-induced murine fibrosarcomas.

    abstract::The DNA of 22 fibrosarcomas, newly induced in BALB/c mice by subcutaneous doses of 3-methylcholanthrene (3-MCA), was tested in NIH 3T3 transformation assay. Activation of K-ras and N-ras was found in 7 and 3 cases respectively. No H-ras activation was detected. Polymerase chain reaction and oligonucleotide hybridizati...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910470423

    authors: Carbone G,Borrello MG,Molla A,Rizzetti MG,Pierotti MA,Della Porta G,Parmiani G

    更新日期:1991-02-20 00:00:00

  • Suppressor cell activity in melanoma patients. II. Concanavalin A-induced suppressor cells in relation to tumor growth and suppressor T-cell subsets.

    abstract::The relative proportions of T, B and T gamma suppressor cells were determined sequentially in peripheral blood of melanoma patients before and after surgery. Concanavalin A (Con A)-induced suppression against lymphocyte mitogenesis of melanoma patients and age matched controls was measured concurrently. The mean perce...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910280103

    authors: Werkmeister J,Phillips G,McCarthy W,Hersey P

    更新日期:1981-07-15 00:00:00

  • H-Ras selectively up-regulates MMP-9 and COX-2 through activation of ERK1/2 and NF-kappaB: an implication for invasive phenotype in rat liver epithelial cells.

    abstract::One of the most frequent events in carcinogenesis is uncontrolled activation of Ras signaling pathway. A previous study demonstrated that the introduction of H-Ras into the normal WB-F344 rat liver epithelial (WB) cell line and adult male F344 rats resulted in tumorigenicity. The present study investigated whether H-R...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22056

    authors: Lee KW,Kim MS,Kang NJ,Kim DH,Surh YJ,Lee HJ,Moon A

    更新日期:2006-10-15 00:00:00

  • Loss of specific natural cell-mediated cytotoxicity with absorption of natural antibodies from serum.

    abstract::When effector cells from most individuals are tested directly against a number of target cells for cell-mediated cytotoxicity, most of the reactivity is non-selective. This apparent non-selectiveness is a result of specific activity against multiple antigens on target cells by each effector suspension. The specific re...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910190603

    authors: Akira D,Takasugi M

    更新日期:1977-06-15 00:00:00

  • Cancer risk in people infected with human immunodeficiency virus in the United States.

    abstract::Data are limited regarding cancer risk in human immunodeficiency virus (HIV)-infected persons with modest immunosuppression, before the onset of acquired immunodeficiency syndrome (AIDS). For some cancers, risk may be affected by highly active antiretroviral therapy (HAART) widely available since 1996. We linked HIV/A...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23487

    authors: Engels EA,Biggar RJ,Hall HI,Cross H,Crutchfield A,Finch JL,Grigg R,Hylton T,Pawlish KS,McNeel TS,Goedert JJ

    更新日期:2008-07-01 00:00:00