Abstract:
:We evaluated the myelotoxicity and the anti-tumor potential of tallimustine, three of its analogues and carzelesin, with melphalan as reference substance. Tallimustine was tested by clonogenic assays on both human bone marrow (BM) and cord blood (hCB) cells, the other compounds on hCB only. The degree of inhibition of the haemopoietic progenitors GM-CFC, CFC-E and BFU-E was evaluated after exposure to different concentrations. The same schedules were tested on five tumour cell lines. We found that the dose-response curves for tallimustine on BM and hCB cells were similar. Carzelesin was shown to be the most potent of the substances tested and to be the one with the best in vitro therapeutic index; of the distamycin analogues, the one bearing an alpha-bromoacrylic group (FCE 25450) had the best index. For melphalan, tallimustine and carzelesin, the concentration inhibiting the growth of 70% of progenitor cells in vitro (ID70) was similar to the concentrations found in the serum of patients treated at the maximum tolerated dose (MTD). We conclude that hCB cells may be used instead of BM cells for in vitro myelotoxicity tests. Therapeutic indexes can be extrapolated from this model and could help in selecting the most promising analogue for further clinical development. The in vitro-active concentrations are similar to myelotoxic concentrations in patients, suggesting a predictive value for the assay.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Ghielmini M,Bosshard G,Capolongo L,Geroni MC,Pesenti E,Torri V,D'Incalci M,Cavalli F,Sessa Cdoi
10.1038/bjc.1997.155subject
Has Abstractpub_date
1997-01-01 00:00:00pages
878-83issue
6eissn
0007-0920issn
1532-1827journal_volume
75pub_type
杂志文章abstract::The mechanisms underlying sperm protein 17 (Sp17) gene expression in myeloma cells remained unclear. Using reverse transcription-polymerase chain reaction (RT-PCR), Sp17 transcripts were detected in ARK-B, ARP-1, RPMI-8226 and KMS-11 but not in H929, IM-9, MM1-R and U266 cells. Using a panel of primer pairs in methyla...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602160
更新日期:2004-10-18 00:00:00
abstract::We have investigated the influence of tumour cell DNA content (ploidy) on survival of 416 patients undergoing excisional surgery for colorectal cancer. Two hundred and eleven (51%) tumours had an abnormal DNA content (aneuploid or tetraploid). There was no correlation between ploidy status, sex, age and pathological s...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.393
更新日期:1990-11-01 00:00:00
abstract::The cytochrome P450 CYP1B1 is consistently overexpressed in tumour cells as compared to their normal counterparts, but its precise role in drug resistance is yet to be defined. It has been reported that transfection of CYP1B1 results in increased resistance to docetaxel in V79 cells (McFadyen et al, 2001). In this stu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604195
更新日期:2008-02-12 00:00:00
abstract::Expression of vascular endothelial growth factor (VEGF), an important angiogenic factor in colon cancer, is tightly regulated by factors in the microenvironment. However, specific factors indigenous to the organ microenvironment of colon cancer growth that regulate VEGF expression in human colon cancer are not well de...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690553
更新日期:1999-07-01 00:00:00
abstract::1-5% of cancer patients treated with cytotoxic chemotherapy die within a month after the administration of chemotherapy. Risk factors for these early deaths (ED) are not well known. The purpose of this study was to establish a risk model for ED after chemotherapy applicable to all tumour types. The model was delineate...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.2011
更新日期:2001-09-14 00:00:00
abstract::Fibroblast growth factor receptor 3 (FGFR3) is one of four high-affinity tyrosine kinase receptors for the FGF family of ligands, frequently associated with growth arrest and induction of differentiation. The extracellular immunoglobulin (IgG)-like domains II and III are responsible for ligand binding; alternative usa...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601249
更新日期:2003-10-06 00:00:00
abstract::This single-centre phase I trial was designed to determine the maximum tolerated dose of irinotecan and the recommended dose to use in combination with a fixed dose of 5-fluorouracil (5-FU) administered as a protracted venous infusion, for the first-line treatment of metastatic colorectal cancer (CRC). Tolerability an...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6602173
更新日期:2004-10-18 00:00:00
abstract::The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of livin may present a novel tumour-specific ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604028
更新日期:2007-11-05 00:00:00
abstract::Several substances mark the course of lung cancer and may reliably help the clinician in decision-making. This is the first clinical study specifically designed to compare tissue polypeptide antigen and CA 125 tumour associated antigen. Three hundred and eighty-four new lung cancer patients (309 males) were studied at...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600577
更新日期:2002-11-04 00:00:00
abstract::In the years 1979-1982, 83 patients with malignant teratoma of the testis who had retroperitoneal adenopathy at presentation or after a period of surveillance were treated. Complete radiological resolution of disease was obtained in 34 patients and a residual mass remained in 26, the remainder having progression of th...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1986.105
更新日期:1986-05-01 00:00:00
abstract::Both host carbogen (95% oxygen/5% carbon dioxide) breathing and nicotinamide administration enhance tumour radiotherapeutic response and are being re-evaluated in the clinic. Non-invasive magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) methods have been used to give information on the ef...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1144
更新日期:2000-06-01 00:00:00
abstract::The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case-control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690008
更新日期:1999-01-01 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::Basal cell carcinoma (BCC) is a common malignancy with a good prognosis in the majority of cases. However, some BCC patients develop a more advanced disease that poses significant management challenges. Such cases include locally advanced, recurrent or metastatic BCC, or tumours that occur in anatomical sites where su...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.270
更新日期:2014-10-14 00:00:00
abstract:BACKGROUND:While lung adenocarcinoma patients can somewhat benefit from anti-angiogenic therapies, patients with squamous cell lung carcinoma (SQLC) cannot. The reasons for this discrepancy remain largely unknown. Soluble VEGF receptor-1, namely sVEGFR1-i13, is a truncated splice variant of the cell membrane-spanning V...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0128-4
更新日期:2018-06-01 00:00:00
abstract::To design hybrid tumour necrosis factor-alpha (TNF-alpha) applicable to systemic anti-tumour therapeutic use, we assessed the relationships among the molecular size of hybrid TNF-alpha, in vitro bioactivity and in vivo anti-tumour potency. Natural human TNF-alpha was covalently modified with polyethylene glycol (PEG) ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.495
更新日期:1996-10-01 00:00:00
abstract::Up to 60% of gastro-oesophageal junction (GEJ) adenocarcinomas show nuclear beta-catenin expression, pointing to activated T-cell factor (TCF)/beta-catenin-driven gene transcription. We demonstrate in five human GEJ adenocarcinoma cell lines that nuclear beta-catenin expression indeed correlates with enhanced TCF-medi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601589
更新日期:2004-02-23 00:00:00
abstract::Window of opportunity trials exploit the 'window' of time after cancer diagnosis, typically prior to initiation of cancer therapy. In recent years this study design has become a more regular feature of drug development, as this 'window' provides an opportunity to carry out a thorough pharmacodynamic assessment of a th...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/s41416-019-0621-4
更新日期:2020-01-01 00:00:00
abstract::Relationships between incidence of Wilms' tumour and information recorded at birth were investigated in a prospective study of the 1,489,297 children born in Norway between 1967 and 1992. A total of 119 individuals were diagnosed with Wilms' tumour in the age interval 0-14 years. A high length at birth was significant...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.505
更新日期:1996-10-01 00:00:00
abstract::For the first time in a clinical study oral Ifosfamide was used: 65 elderly or unfit patients with small cell lung cancer (SCLC) were treated as outpatients with fractionated oral Ifosfamide and Etoposide. Forty patients (62%) had extensive stage (ED) disease. The median age of the patients was 66 years. In the 60 pat...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.265
更新日期:1989-08-01 00:00:00
abstract:BACKGROUND:The Obermair nomogram was recently developed to predict the risk of relapse in patients with borderline ovarian tumours (BOTs) based on five readily available clinical, biological, and pathological characteristics. We set out to externally validate and assess its robustness using a multi-institutional BOT da...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2013.678
更新日期:2013-11-26 00:00:00
abstract:BACKGROUND:Regulator of cullins-1 (ROC1) is a key subunit in the cullin-RING ligase (CRL) protein complex. Our previous study indicated that ROC1 was essential for bladder cancer cell survival and that ROC1 knockdown inhibited CRL activity, triggering G2 phase arrest and senescence. However, the role of ROC1 in the mal...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.444
更新日期:2016-02-02 00:00:00
abstract::The UK National Case-Control Study Group has examined the relationship between smoking (both own smoking and passive), alcohol consumption and caffeine consumption and the risk of breast cancer. A total of 755 women with breast cancer diagnosed before the age of 36, each with an age-matched general population control,...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.258
更新日期:1994-07-01 00:00:00
abstract:BACKGROUND:The community-based incidence of cancer treatment-related long-term consequences is uncertain. We sought to establish the burden of health outcomes that have been associated with treatment among British long-term cancer survivors. METHODS:We identified 26,213 adults from the General Practice Research Databa...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.420
更新日期:2011-11-08 00:00:00
abstract::One hundred cancer patients undergoing active treatment were interviewed to determine how they perceived their illness and how their perceptions compared with those of their attending physicians. Ninety-eight patients recognized that they had cancer and 87 correctly identified the tumour type. Sixty-four of 67 patient...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.218
更新日期:1988-09-01 00:00:00
abstract::Bleomycin is a chemotherapuetic drug used primarily in the treatment of squamous-cell carcinoma, while misonidazole is an effective radiosensitizer and potent cytotoxic agent selectively affecting hypoxic cells. V79 Chinese hamster cells were used to investigate the cytotoxicity of bleomycin (BLM) under aerated and hy...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1978.34
更新日期:1978-02-01 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::The important role of the p53 gene in tumour progression and cellular response to DNA damage has prompted investigation of the clinical significance of alterations to this gene. We examined both p53 overexpression and mutation of the gene in endometrial carcinoma in order to evaluate the prognostic significance of the...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.401
更新日期:1996-08-01 00:00:00
abstract:BACKGROUND:Prescribing anti-programmed death-1 (PD-1) immunotherapy for advanced melanoma is currently not restricted by any biomarker assessment. Determination of programmed death-ligand-1 (PD-L1)-expression status is technically challenging and is not mandatory, because negative tumours also achieve therapeutic respo...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0168-9
更新日期:2018-07-01 00:00:00
abstract::We screened 145 HIV-infected non-pregnant women at a tertiary care centre in Lusaka, Zambia. Liquid-based cytology and human papillomavirus (HPV) genotyping with PGMY09/11 biotinylated primers (Roche Linear Array HPV genotyping test) maximised sensitivity of cytology and HPV assessments. Among high-risk (HR) types, HP...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603737
更新日期:2007-05-07 00:00:00