Abstract:
:Patients with refractory metastatic renal cell carcinoma (RCC) were enrolled in a phase II study with teniposide (VM26) and cyclosporin A (CSA) to investigate (1) the effect of CSA on the response rate to VM26; and (2) the effect of CSA on the pharmacokinetics and pharmacodynamics of VM26. Sixteen patients initially received VM26 alone (200 mg m(-2) day(-1) i.v.). No objective responses were observed and all patients crossed over to receive at least an additional two courses (range 2-5) of VM26 plus CSA (5 mg kg(-1) 2h(-1) followed by 30 mg kg(-1) 48h(-1) i.v.). At the end of the 2-h loading dose of CSA, whole-blood CSA levels ranged from 2250 to 3830 ng ml(-1), whereas at the end of the 48-h CSA infusion, CSA ranged from 1830 to 4501 ng ml(-1). CSA significantly (P<0.01) increased the area under the curve (AUC) of VM26. The variation in the paired AUC of VM26 was 50%. Terminal half-life of VM26 was significantly (P<0.01) increased (1.72-fold) after CSA administration, whereas the systemic clearance of VM26 was decreased by 1.4-fold (P<0.01). The nadir neutrophil count after VM26 plus CSA (median 700 microl(-1), range <100 to 2860 microl(-1)) was lower than after VM26 alone (median 1900 microl(-1), range 200 to 6000 microl(-1)). Increased haematological toxicity after CSA could be explained by the increase in the VM26 AUC and by inhibition of P-glycoprotein (P-gp) activity in haematopoietic precursor cells. Bilirubin concentrations in the serum were increased after VM26 plus CSA compared with VM26 alone (P<0.01). Among the 15 patients evaluable for response, one had a minor response, eight had stable disease, and six had progressive disease. In conclusion, the dose of CSA we used achieved plasma concentrations within the effective range for P-gp inhibition. CSA affected both the pharmacokinetics and pharmacodynamics of VM26 in the patients, principally by increasing the plasma concentrations of the antineoplastic drug and VM26 haemopoietic toxicity.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Toffoli G,Sorio R,Gigante M,Corona G,Galligioni E,Boiocchi Mdoi
10.1038/bjc.1997.127subject
Has Abstractpub_date
1997-01-01 00:00:00pages
715-21issue
5eissn
0007-0920issn
1532-1827journal_volume
75pub_type
临床试验,杂志文章abstract::A chelating derivative of alpha-melanocyte stimulating hormone (MSH) has been synthesised, in which two molecules of the hormone are cross-linked by diethylenetriamine pentaacetic acid (DTPA). This compound, bisMSH-DTPA, was equipotent with MSH in an in vitro tyrosinase assay with Cloudman S91 melanoma cells. When DBA...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.409
更新日期:1990-12-01 00:00:00
abstract::Identification of a biomarker of prognosis and response to therapy that can be assessed preoperatively would significantly improve overall outcomes for patients with pancreatic cancer. In this study, patients whose tumours exhibited high LMO4 expression had a significant survival advantage following operative resectio...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604177
更新日期:2008-02-12 00:00:00
abstract:BACKGROUND:Human polypyrimidine tract binding protein 3 (PTBP3) was first discovered in 1999 and has been well characterised as a differentiation regulator. However, its role in human cancer has rarely been reported. Our previous study revealed increased PTBP3 protein level in gastric cancer tissues. Downregulation of ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.32
更新日期:2017-03-28 00:00:00
abstract::ERBB2 is frequently amplified in breast tumours as part of a wide region of amplification on chromosome 17q21. This amplicon contains many candidate genes for breast cancer susceptibility. We used a genetic association study design to determine if common genetic variation (frequency>or=5%) in a 400-kb region surroundi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603473
更新日期:2006-12-18 00:00:00
abstract:BACKGROUND:Metastasis is associated with poor prognosis for melanoma. The formation of metastases is a multi-step process, in which cancer cells can subsequently acquire the potential to intravasate into the blood or lymph vessels, disseminate through the circulation, extravasate through the endothelium and invade the ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6606056
更新日期:2011-02-01 00:00:00
abstract::This study evaluates the overall survival and disease free survival of melanoma patients that were treated with an autologous melanoma cell vaccine, administered as a post-operative adjuvant. Included are 43 patients with totally resected metastatic melanoma (28-AJCC stage III, 15-AJCC stage IV), with a median follow ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6600251
更新日期:2002-05-20 00:00:00
abstract::Fifteen human glioma cell lines were examined for their sensitivity to 1,3-bis(chloroethyl)-nitrosourea (BCNU, carmustine) and cis-dichlorodiamminoplatinum (cisplatin), the induction of DNA interstrand cross-linking (DNA-ISC) induced by the two agents and cellular O6-alkylguanine alkyltransferase (ATase) activity. Cel...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.87
更新日期:1997-01-01 00:00:00
abstract::Dormant and regressing implants of C3H mammary carcinoma MC2 were always found to be surrounded by a cellular fibrous capsule where macrophages and T cells predominated as the cellular elements. Macrophages were always closely associated with the collagen deposition, and stained with anti-collagen type I immuno-peroxi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.169
更新日期:1991-05-01 00:00:00
abstract:BACKGROUND:Limited literature on the role of intraarterial chemotherapy as first-line therapy for penile squamous cell carcinoma is available. METHODS:From 2005 to 2013, a total of 12 patients with various stages of penile squamous cell carcinoma received intraarterial chemotherapy. The chemotherapeutic agents used we...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.394
更新日期:2014-09-09 00:00:00
abstract::Eighteen consecutive patients with measurable locally advanced or metastatic pancreatic adenocarcinoma were treated with goserelin (Zoladex) 3.6 mg subcutaneously every 4 weeks. Hydrocortisone 20 milligrams twice daily was commenced with the second injection of goserelin. Objective tumour response was monitored by com...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1993.69
更新日期:1993-02-01 00:00:00
abstract::In a population-based prospective study of 19,998 Japanese individuals, consumption of vegetables, green-yellow and green leafy vegetables was inversely associated with the risk of hepatocellular carcinoma (101 cases), with multivariable hazard ratios for the highest vs lowest tertile of 0.61 (95% confidence interval ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604843
更新日期:2009-01-13 00:00:00
abstract::Immunohistochemical localization of chondroitin sulphate and dermatan sulphate proteoglycans (PGs) was observed in 70 tumour tissues, using monoclonal antibodies 9A-2 and 3B-3 raised against core molecules obtained from chondroitin sulphate PG by chondroitinase ABC-treatment. They recognize a stub of delta Di-4S and d...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.12
更新日期:1988-01-01 00:00:00
abstract::The pharmacokinetics and pharmacodynamics of oral S-1, a dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine, were compared with those of protracted venous infusion (PVI) of 5-fluorouracil (5-FU). In all, 10 patients with gastric cancer received PVI of 5-FU at a dose of 250 mg m(-2) day(-1) for 5 days. A...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601224
更新日期:2003-09-01 00:00:00
abstract::To investigate the usefulness of thyroglobulin mRNA (Tg-mRNA) detection in peripheral blood in the follow-up of papillary and follicular (differentiated) thyroid cancer, a literature study was performed. Both evidence for and evidence against the usefulness of Tg-mRNA detection were found. Also, evidence for the expre...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6601991
更新日期:2004-07-19 00:00:00
abstract:BACKGROUND:A major molecular pathway of genetic instability in cancer is DNA mismatch repair deficiency. High-level microsatellite instability (MSI-H) is currently the best predictor of responsiveness towards immune checkpoint blockade. Data about the prevalence of high-level microsatellite instability in cholangiocarc...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0199-2
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:The need to unfold the underlying mechanisms of lung cancer aggressiveness, the deadliest cancer in the world, is of prime importance. Because Fas-associated death domain protein (FADD) is the key adaptor molecule transmitting the apoptotic signal delivered by death receptors, we studied the presence and cor...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.196
更新日期:2012-06-05 00:00:00
abstract:BACKGROUND:The Sloane audit compares screen-detected ductal carcinoma in situ (DCIS) pathology with subsequent management and outcomes. METHODS:This was a national, prospective cohort study of DCIS diagnosed during 2003-2012. RESULTS:Among 11,337 patients, 7204 (64%) had high-grade DCIS. Over time, the proportion of ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-01152-5
更新日期:2020-11-17 00:00:00
abstract::Hepatic arterial floxuridine (HAI) in 35 patients with systemic fluorouracil/folinic acid-resistant colorectal liver metastases achieved a 14% partial response and 26% disease stabilization rate, with a median response duration of 7 months from onset of HAI. ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1998.627
更新日期:1998-10-01 00:00:00
abstract::Mediastinal masses include a wide variety of tumours and remain an interesting diagnostic challenge for radiologist. We performed positron emission tomography (PET) studies of primary mediastinal tumours in order to predict the malignancy of these tumours preoperatively. Twenty-two patients with primary mediastinal tu...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1996.157
更新日期:1996-04-01 00:00:00
abstract::The association between soya foods and breast cancer risk was investigated in a prospective study of 34759 women in Hiroshima and Nagasaki, Japan. Women completed dietary questionnaires in 1969-1970 and/or in 1979-1981 and were followed for incident breast cancer until 1993. The analysis involved 427 cases of primary ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690837
更新日期:1999-12-01 00:00:00
abstract::The fluorometric microculture cytotoxicity assay (FMCA) was employed for analysing the effect of different chemotherapeutic drug combinations and their single constituents in 44 cases of acute myelocytic leukaemia (AML). A large heterogeneity with respect to cell kill was observed for all combinations tested, the inte...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1993.178
更新日期:1993-05-01 00:00:00
abstract:BACKGROUND:The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. In this study, we validate the prognostic value of a cell cycle progression score (CCP score) independently and in a prespecified linea...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.223
更新日期:2015-07-28 00:00:00
abstract:BACKGROUND:Tumour budding has been reported to reflect invasiveness, metastasis and unfavourable prognosis in colorectal cancer. The aim of the study was to examine the relationship between tumour budding and clinicopathological characteristics, tumour microenvironment and survival in patients with primary operable col...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.173
更新日期:2016-07-12 00:00:00
abstract:BACKGROUND:In this study, we evaluated the possibility that KRAS mutational status might be predictive of oxaliplatin (OXA) efficacy. We also explored the role of excision repair cross complementing group-1 (ERCC-1). METHODS:Ninety anti-epidermal growth factor receptor-naive advanced colorectal cancer patients were re...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.526
更新日期:2013-01-15 00:00:00
abstract::Flavone acetic acid (FAA) was administered at a dose of 4.8 g m-2 over 1 h to patients with advanced malignant disease in combination with Interleukin II. A new high performance liquid chromatography method is described to determine both the parent compound and eight drug-related products, and the conditions required ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.250
更新日期:1993-06-01 00:00:00
abstract::The effect of 10(-6) M tamoxifen on MCF-7 cells adapted to growth in 0.5% foetal calf serum has been studied. The growth inhibitory effect of this tamoxifen concentration was abolished by simultaneous addition of 10(-8) M oestradiol, indicating that tamoxifen may exert its effect via binding to the oestrogen receptor....
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1984.113
更新日期:1984-06-01 00:00:00
abstract::To understand genetic events which play a role in the development and/or progression of human endometrial cancer, we studied allelotypes on all autosomal chromosomes, as well as chromosome X, with 42 microsatellite markers and 56 endometrial cancers. The most frequent loss of heterozygosity (LOH) was observed on the l...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.663
更新日期:1996-12-01 00:00:00
abstract::This article was originally published under a standard license to Publish, but has now been made available under a CC BY license. The PDF and HTML versions of the paper have been modified accordingly.An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:British journal of cancer
pub_type: 已发布勘误
doi:10.1038/s41416-019-0534-2
更新日期:2019-10-01 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::This paper describes the results of a study set up to investigate factors associated with the high proportions of 'death certificate only' registrations (DCOs) for all cancers registered in south-east England between 1987 and 1989 and to identify those which might be subject to registry intervention. DCOs as a proport...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.125
更新日期:1995-03-01 00:00:00