Abstract:
:We have investigated the effects of 50 min whole-body hyperthermia (WBH; 15 min equilibration followed by 41 degrees C for 35 min) on the toxicity and pharmacokinetics of the radiosensitizer Ro 03-8799 in mice. WBH markedly reduced Ro 03-8799 LD50/7d from 779 to 259 micrograms g-1 (P less than 0.001). Pharmacokinetics were studied at 175 micrograms g-1 (approximately 0.6 WBH LD50/7d) with and without heat and 437 micrograms g-1 (approximately 0.6 control LD50/7d) without heat. WBH increased Ro 03-8799 plasma concentrations and prolonged its elimination t1/2 by 26% (P less than 0.01). Total plasma area under the curve (AUC0-infinity) was increased by 22%, but was still less than 50% of the unheated high-dose value. Ro 03-8799 concentrated 300-400% in tumour and brain relative to plasma. Absolute tumour and brain levels were unaltered by WBH, giving reduced tissue/plasma ratios. WBH greatly inhibited glomerular filtration (51Cr EDTA clearance) during heating, contributing to the increased plasma Ro 03-8799 concentrations. WBH increased peak plasma concentrations of the Ro 03-8799 N-oxide metabolite Ro 31-0313 by 61% and the beta-phase AUC of i.v. administered Ro 31-0313 by 36%. Since Ro 31-0313 levels were increased to a greater extent after Ro 03-8799 and WBH than Ro 31-0313 and WBH, WBH must both increase metabolite production and decrease its plasma clearance. WBH had no effect on Ro 31-0313 tumour concentrations or its exclusion from brain. These complex effects of WBH on Ro 03-8799 pharmacokinetics may contribute to the enhanced toxicity, possibly through hyperthermia-stimulated bioreductive drug activation, but do not wholly explain it.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Walton MI,Bleehen NM,Workman Pdoi
10.1038/bjc.1987.96subject
Has Abstractpub_date
1987-05-01 00:00:00pages
469-76issue
5eissn
0007-0920issn
1532-1827journal_volume
55pub_type
杂志文章abstract::A multicentre phase 2 trial (single-stage design) was undertaken to test the efficacy and toxicity of carboplatin (AUC 6 according to Calvert) plus paclitaxel (175 mg/m(2)3-h infusion) every 4 weeks in the first line treatment of patients affected by extensive small cell lung cancer. The primary end-point of the trial...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1054/bjoc.2000.1541
更新日期:2001-01-05 00:00:00
abstract::In adults, the haemolytic-uraemic syndrome (HUS) is associated with probable causative factors in the minority of all cases. Cytotoxic drugs are one of these potential causative agents. Although metastatic cancer by itself is a recognized risk-factor for the development of HUS, therapy with mitomycin-C, with cis-plati...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690242
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND:Earlier studies have shown raised risks of leukaemia and non-Hodgkin lymphoma in children, teenagers and young adults resident either at birth or diagnosis in Seascale. Some increases in cancer risk in these age groups have also been noted among those living around Dounreay. We aimed to update previous analy...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.357
更新日期:2014-10-28 00:00:00
abstract:PURPOSE:To determine the feasibility of induction chemotherapy and chemo-IMRT in head and neck squamous cell cancers at risk of bilateral nodal spread (midline tumours) and to evaluate whether bilateral superficial lobe parotid-sparing IMRT can reduce the incidence of ⩾G2 subjective xerostomia. METHODS:Patients with m...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.553
更新日期:2015-01-06 00:00:00
abstract::Ordinary lipomas are cytogenetically characterized by a variety of balanced rearrangements involving chromosome segment 12q13-15, whereas well differentiated liposarcomas (WDL) show supernumerary ring and giant marker chromosomes, known to contain amplified 12q sequences. The tight correlation between the presence of ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.1999.1090
更新日期:2000-04-01 00:00:00
abstract:BACKGROUND:We modified and evaluated an advance care planning (ACP) intervention, which had been shown to improve compliance with patient's end of life (EoL) wishes, in a different patient population. METHODS:Patients with incurable cancer, and a Family Member (FM), were randomised one-to-one to usual care or usual ca...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/s41416-018-0303-7
更新日期:2018-11-01 00:00:00
abstract::The tumour-suppressor gene TP53 is frequently mutated in breast tumours, and the majority of the mutations are clustered within the core domain, the region involved in DNA binding. We searched for alterations in this central domain of the TP53gene in 222 human breast cancer specimens using polymerase chain reaction-si...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.187
更新日期:1998-04-01 00:00:00
abstract::The importance of tumour angiogenesis in the process of tumour growth and progression in solid tumours has been widely accepted. Among many angiogenic factors, vascular endothelial growth factor (VEGF) has been shown to play a major role in the development and dissemination of the malignant tumours. Nitric oxide (NO) ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690573
更新日期:1999-07-01 00:00:00
abstract::Cellular adhesion molecules have been implicated in tumour progression and metastasis. This study examines for the first time the serum concentrations of circulating VCAM-1 and E-selectin in a consecutive series of 110 cancer patients seen in a general medical oncology clinic, and confirms and extends previous studies...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.298
更新日期:1993-07-01 00:00:00
abstract::In the search for effective chemotherapy regimens which can be used in multimodality treatment programmes for patients with cancer of the oesophagus, we conducted a phase II trial to determine the activity and toxicity of the combination of cisplatin and etoposide in patients with advanced squamous cell carcinoma of t...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1996.469
更新日期:1996-09-01 00:00:00
abstract::The pp125 focal adhesion kinase (FAK) is involved in integrin-mediated cell signalling and overexpressed in a variety of solid tumours. Focal adhesion kinase expression has been correlated to invasion and metastasis, but the data on breast cancer are inconclusive. We analysed FAK mRNA, protein levels and expression pa...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602744
更新日期:2005-09-19 00:00:00
abstract:BACKGROUND:Health-related quality of life (HRQoL) comprises different domains of physical, mental, and social well-being. In this analysis, we focus on sexual quality of life in Hodgkin Lymphoma (HL) patients. METHODS:Four-thousand one-hundred and sixty patients enroled in the HD10-HD12 trials underwent HRQoL assessme...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.550
更新日期:2013-01-15 00:00:00
abstract::While statins have been highly effective for lowering serum cholesterol and reducing the incidence of coronary events, they have multiple other effects. Certain statins block the interaction of adhesion molecules that are important for cell-cell interactions including those between EBV-transformed B cells. These same ...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6602561
更新日期:2005-05-09 00:00:00
abstract:BACKGROUND:In neuroblastoma (NB), the most powerful prognostic marker, the MYCN amplification (MNA), occasionally shows intratumoural heterogeneity (ITH), i.e. coexistence of MYCN-amplified and non-MYCN-amplified tumour cell clones, called heterogeneous MNA (hetMNA). Prognostication and therapy allocation are still uns...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/s41416-018-0098-6
更新日期:2018-05-01 00:00:00
abstract::Hypoxic cells in KHT sarcomas were characterized using fluorescence activated cell sorting based on the diffusion properties of the fluorochrome Hoechst 33342. Tumour-bearing female C3H/HeJ mice were injected i.v. with 10 micrograms g-1 Hoechst 33342 and the cells derived from the tumours sorted on the basis of their ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.207
更新日期:1988-09-01 00:00:00
abstract::A case-control study of lung cancer involving interviews with 965 female patients and 959 controls in Shenyang and Harbin, two industrial cities which have among the highest rates of lung cancer in China, revealed that cigarette smoking is the main causal factor and accounted for about 35% of the tumours among women. ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.421
更新日期:1990-12-01 00:00:00
abstract::Prostate cancer is the second leading cause of male death from malignant disease in Europe and in the USA. Failure to prevent or eliminate metastatic dissemination is a fundamental problem underlying the current inadequate treatment of prostate cancer, and novel therapeutic strategies are required if this disease is t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.45
更新日期:1998-01-01 00:00:00
abstract::O6-benzylguanine (O6-BG) and 3-aminobenzamide (3-AB) inhibit the DNA repair proteins O6-alkylguanine-DNA alkyltransferase (AGT) and poly(ADP-ribose) polymerase (PARP) respectively. The effect of O6-BG and/or 3-AB on temozolomide and 1,3-bis(2-chloroethyl)-nitrosourea (BCNU) cytotoxicity, was assessed in seven human tu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.485
更新日期:1996-10-01 00:00:00
abstract::Human monocytes can be induced to synthesize a cytotoxin which affects certain tumour cell lines. The interaction of monocyte cytotoxin with a susceptible cell line (L929) has been studied to obtain clues to the mode of action of the cytotoxin. The cytotoxin acts directly on the cells rather than on the culture medium...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.205
更新日期:1983-09-01 00:00:00
abstract:BACKGROUND:Gamma-glutamyltransferase (GGT) - a membrane-bound enzyme crucially involved in the cell's detoxification pathway and apoptotic balance - is involved in tumour development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosi...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2013.323
更新日期:2013-08-06 00:00:00
abstract::No numerical aberration of chromosomes that might be specific for prostate cancer has so far been established. We used fluorescence in situ hybridisation (FISH) with centromere-specific probes for chromosomes 7, 8, 17, X and Y to establish the distribution of centromere copy numbers in frozen-stored or freshly prepare...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.617
更新日期:1996-12-01 00:00:00
abstract:BACKGROUND:This study had two aims: (a) to test the hypothesis that advanced age is associated with lower levels of tolerability and clinical benefit to experimental Phase I trial agents; (b) to assess the validity of the Royal Marsden Hospital (RMH) prognostic score as a patient selection tool in older patients. METH...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.477
更新日期:2016-02-02 00:00:00
abstract::The aim of the present study was to evaluate the occult lymph node carcinomatous diffusion in head and neck squamous cell carcinoma (HNSCC). A total of 1328 lymph nodes from 31 patients treated between 2004 and 2005 were prospectively evaluated by routine haematoxylin-eosin-safran (HES) staining, immunohistochemistry ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603073
更新日期:2006-04-24 00:00:00
abstract::Cancer incidence in the Falkland Islands, 1989-2000, was compared with rates in England and Wales, from which most Islanders originate. Colon and rectum cancer incidence was significantly raised 1989-93 but greatly reduced after 1994, when colonoscopic screening in high-risk families and sigmoidoscopic screening in th...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.2099
更新日期:2001-11-02 00:00:00
abstract:BACKGROUND:Gestational trophoblastic diseases (GTDs) are related to trophoblasts, and human chorionic gonadotropin (hCG) is secreted by GTDs as well as normal placentas. However, the asparagine-linked sugar chains on hCG contain abnormal biantennary structures in invasive mole and choriocarcinoma, but not normal pregna...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.496
更新日期:2012-12-04 00:00:00
abstract::We used the nation-wide Swedish Family-Cancer Database to examine the risk for testicular cancer in offspring through parental and sibling probands. Among 0-68-year-old offspring, 4082 patients had testicular cancer in years 1961-2000, among whom 68 (1.67%) had an affected father/brother. Standardized incidence ratios...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601714
更新日期:2004-05-04 00:00:00
abstract::Trastuzumab has significantly improved the overall survival of patients with HER2+ metastatic breast cancer (MBC). However, outcomes can vary, with patients progressing within 1 year of treatment or exceptional cases of complete response to trastuzumab for ≥10 years. Identification of the underlying genomic aberration...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0999-z
更新日期:2020-10-01 00:00:00
abstract::A study was conducted on the effects of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on peroxisomal enzyme activities in mouse embryo fibroblasts C3H/10T1/2 C18 cells and chemically transformed C3H/10T1/2 MCA16 cells. TPA is a potent tumour promoter and treatment with this compound of the two cell lines induced peroxis...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1986.17
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:This study was done to investigate the long-term event free and overall survival of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT), compared to maintenance chemotherapy (MT). Patterns of recurrences and late sequelae of both arms were analysed. METHODS:A randomised open label...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/s41416-018-0169-8
更新日期:2018-08-01 00:00:00
abstract::A human prostate tumour cell line, LNCaP C4-2, when injected into athymic male nude mice, produced tumours containing: (1) only human cancer cells similar to those injected; (2) only murine stromal cells containing abnormal chromosome constitutions; or (3) both human prostate cancer cells similar to those injected and...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.524
更新日期:1997-01-01 00:00:00