Abstract:
:Treatment failure in AML is often attributed to P-glycoprotein-associated multidrug resistance. However, the importance of increased DNA repair in resistant cells is becoming more apparent. In order to investigate the ability of the DNA repair inhibitor aphidicolin to modulate drug resistance, we continually exposed blasts cells, isolated from 22 patients with AML, to a variety of agents +/- 15 microM aphidicolin for 48 hours. Cell survival was measured using the MTT assay. Overall, there was no significant effect of aphidicolin on sensitivity to daunorubicin, doxorubicin, etoposide or fludarabine. However, there was a marked increase in sensitivity to ara-C with a median 4.75-fold increase overall (range 0.8-80-fold;P< 0.005). The effect of aphidicolin was significantly greater in blast cells found resistant in vitro to ara-C (8.9-fold compared to 2.12-fold, P< 0.01). This observation was further validated by the correlation between ara-C LC(50)and extent of modulation effect (P< 0.05). Cells isolated from 10 cord blood samples were also tested in order to establish the haematological toxicity of combining ara-C and aphidicolin. The therapeutic index (LC(50)normal cells/tumour cells) for ara-C + aphidicolin was higher than that for ara-C alone suggesting no increased myelotoxicity for the combination. Increased cytotoxicity without increased haematotoxicity makes the combination of ara-C plus aphidicolin ideal for inclusion in future clinical trials.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Sargent JM,Elgie AW,Williamson CJ,Lewandowicz GM,Taylor CGdoi
10.1054/bjoc.2000.1639subject
Has Abstractpub_date
2001-03-02 00:00:00pages
680-5issue
5eissn
0007-0920issn
1532-1827pii
S0007092000916392journal_volume
84pub_type
杂志文章abstract::The vaso-active drug hydralazine causes a considerable increase in the cytotoxic effect of melphalan towards the KHT tumour in mice. The enhancement in response, measured as the concentration of melphalan required to achieve a given tumour response, is 3.0 and 2.35 when determined using the regrowth delay assay and th...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.177
更新日期:1988-08-01 00:00:00
abstract::On the basis of preclinical data suggesting the possibility of maximising the efficacy of 5-fluorouracil and cisplatin by interferon, a pilot clinical trial was initiated in recurrent and/or metastatic head and neck cancer. Thirty-four patients were treated with cisplatin at 100 mg m-2, followed by 5-fluorouracil at 1...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1994.72
更新日期:1994-02-01 00:00:00
abstract::This phase II study was designed to evaluate the activity and safety of a combination of irinotecan, docetaxel and oxaliplatin in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Forty patients with measurable distant metastasis received irinotecan 150 mg m(-2) and docetaxel 60 mg m(-2) on day 1, ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603917
更新日期:2007-09-03 00:00:00
abstract::Immunofluorescent assessment of hormone receptors in melanocytic tumours is quite feasible without loss of diagnostic material, in contrast to the impracticability of quantitative biochemical assays. Using this method, oestrogen receptors were demonstrated in 4/6, and progesterone receptors in 3/5 patients with metast...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1981.95
更新日期:1981-05-01 00:00:00
abstract::Resistance to cytotoxic agents may be encountered during the treatment of acute myeloblastic leukaemia (AML). P-glycoprotein encoded by the MDR-1 gene has been implicated as a potential drug resistance mechanism in leukaemic cells. In recent years, many data have been accrued concerning the expression of P-glycoprotei...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/bjc.1994.70
更新日期:1994-02-01 00:00:00
abstract::The association between body height and the incidence rate of breast cancer has been examined in 236 cases of breast cancer that occurred among 23,831 Norwegian women during 11-14 years of follow-up. At the time of height measurement they were 35-51 years of age. The age-adjusted incidence rate ratio (IRR) of breast c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.197
更新日期:1990-06-01 00:00:00
abstract:BACKGROUND:Progression-free survival (PFS) is a surrogate endpoint widely used for overall survival (OS) in oncology. Validation of PFS as a surrogate must be done for each indication and each intervention. We aimed to identify all studies evaluating the validity of PFS as a surrogate for OS in oncology, and to describ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0805-y
更新日期:2020-05-01 00:00:00
abstract::To: (1) estimate the prevalence of clinically significant emotional distress in patients attending a cancer outpatient department and (2) determine the associations between distress and demographic and clinical variables, we conducted a survey of outpatients attending selected clinics of a regional cancer centre in Ed...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603626
更新日期:2007-03-26 00:00:00
abstract:BACKGROUND:The aim of this study was to investigate the safety of neoadjuvant chemoradiation using radiotherapy (RT) combined with concurrent capecitabine and irinotecan for locally advanced rectal cancer before surgery. METHODS:Forty-six patients were recruited and treated on the basis that MRI scanning had shown poo...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605258
更新日期:2009-09-15 00:00:00
abstract::One hundred and seventy-eight patients with non metastatic inflammatory breast cancer (IBC) have been treated at the Centre H. Becquerel. Median follow up is 67 months (6-178). Every patient received neoadjuvant chemotherapy (mean number of cycles = 4; range: 2-8), followed by a loco regional treatment (radiotherapy =...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.109
更新日期:1993-03-01 00:00:00
abstract::The clearance of an intradermally-injected solution of 133Xenon in 0.9% saline has been used to study the impairment and recovery of blood flow in mouse tail for 5 days following photodynamic therapy (PDT) with 2mg TPPS i.v. per mouse and a range of doses of white light. Impairment of blood flow was observed within 10...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.105
更新日期:1988-05-01 00:00:00
abstract::The cytotoxicity of three platinum complexes, cis-diamminedichloroplatinum(II) (cis-platin), cis-dichloro-trans-dihydroxy-cis-bis (isopropylamine) platinum(IV), (CHIP) and diammine (1, 1-cyclobutane-dicarboxylato) platinum(II) (carboplatin) on Chinese Hamster ovary (CHO) and mouse sarcoma RIF-1 cells cultured in vitro...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.126
更新日期:1988-06-01 00:00:00
abstract::Cancer of the colon and rectum is one of the most frequent malignancies both in the US and Europe. Standard palliative therapy is based on 5-fluorouracil/folinic acid combinations, with or without oxaliplatin or irinotecan, given intravenously. Oral medication has the advantage of greater patient convenience and accep...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6600781
更新日期:2003-03-10 00:00:00
abstract::Protein kinase B/Akt has been described as a central mediator of anti-apoptotic signals transduced by the PI3 kinase. Although the role of Akt in the suppression of apoptosis is well elucidated, a potential function of Akt in tumorigenesis and chemoresistance is less intensively documented. In this study, we describe ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600566
更新日期:2002-10-07 00:00:00
abstract::BW12C (5-[2-formyl-3-hydroxypenoxyl] pentanoic acid) is an agent which stabilises oxyhaemoglobin and thus reduces oxygen delivery to tissues. It is of interest as a possible potentiator of bioreductive agents and/or hyperthermia. The increases in radiobiological hypoxic fraction of RIF-1 and KHT tumours 30 min after 7...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.387
更新日期:1991-10-01 00:00:00
abstract::Minisatellite DNA probes which can detect a large number of autosomal loci dispersed throughout the human genome were used to examine the constitutional and tumour DNA of 35 patients with a variety of cancers of which eight were of gastrointestinal origin. Somatic changes were seen in the tumour DNA in ten of the 35 c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.71
更新日期:1987-04-01 00:00:00
abstract::In the present study we have used flow cytometric DNA measurements on synchronised human NHIK 3025 cells to measure cell cycle progression under various conditions of reduced oxygenation. Our data indicate that addition of 0.1 mM deoxycytidine or uridine has no effect on the oxygen-dependent arrest in late G1 or on th...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.411
更新日期:1994-11-01 00:00:00
abstract::The reactivation of U.V.-irradiated adenovirus 2 in HeLa cells is enhanced 8-9 fold if the cells are given a brief hyperthermic shock before infection. Maximum reactivation is achieved by heating for 10 min at 45.5 degrees C and with a delay of 36 h between heating and infection. The induction process requires protein...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1984.32
更新日期:1984-02-01 00:00:00
abstract:BACKGROUND:Combined-modality therapy is a promising approach to improve the therapeutic index of radiotherapy. However, these improvements could come at the cost of increased toxicities. Clinical trials evaluating anti-tumour efficacy of bevacizumab combined with radiotherapy have encountered unexpected side effects. T...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.236
更新日期:2012-07-10 00:00:00
abstract::Extramammary Paget's disease is a particular form of skin cancer of unknown histogenesis. To look for the genetic defects underlying the pathogenesis of this tumour, we have examined loss of heterozygosity (LOH), p53 and human papillomavirus (HPV) status, and the expression of c-erbB-2 and bcl-2 proteins in 14 cases. ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.482
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND:Dulanermin (rhApo2L/TRAIL) induces apoptosis by binding to death receptors DR4 and DR5, leading to caspase activation and subsequent cell death. A Phase1a trial evaluated the safety and tolerability of dulanermin in patients with advanced tumours. One aim was to develop and validate pharmacodynamic biomarker...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.456
更新日期:2011-12-06 00:00:00
abstract::There is considerable interest in immunohistochemical markers of proliferation which are suitable for use on routinely fixed clinical material. The novel proliferation-associated antibody Ki-S1 shows promise in this respect. In this study we have: (i) defined the pattern of Ki-S1 labelling relative to the cell cycle p...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.122
更新日期:1993-04-01 00:00:00
abstract:BACKGROUND:Random error in the numbers of avoidable deaths among cancer patients has not been considered in earlier studies. METHODS:Methods to obtain valid confidence intervals (CIs) for numbers of avoidable deaths were developed. The excess mortality rates were estimated for patients diagnosed with colon cancer in f...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.169
更新日期:2012-05-22 00:00:00
abstract::Preoperative radiotherapy (PRT) in resectable rectal cancer improves local control but increases probability of faecal incontinence and sexual dysfunction. Consensus was reached in 2001 in the Netherlands on a guideline advising PRT to new patients. Purpose was to assess at what benefit oncologists and rectal cancer p...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603954
更新日期:2007-09-17 00:00:00
abstract::Astrocytomas develop intense vascular proliferation, essential for tumour growth and invasiveness. Angiotensin II (ANGII) was initially described as a vasoconstrictor; recent studies have shown its participation in cellular proliferation, vascularisation, and apoptosis. We conducted a prospective study to evaluate the...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604431
更新日期:2008-07-08 00:00:00
abstract::In this study, we have investigated the expression of inhibin subunits and activin receptors (ActRs) in normal and malignant ovarian cells. Each product of the inhibin subunits (alpha, betaa, betab) and activin receptors (ActRs) amplified by reverse transcription polymerase chain reaction were detected as a single ban...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.1999.1127
更新日期:2000-04-01 00:00:00
abstract::Pulmonary metastasectomy is widely and increasingly practiced in the belief that this intervention can cure patients with colorectal cancer, and that without it few survive 5 years. No good evidence exists supporting such convictions, indeed recent trial results challenge them. What evidence underpins this acceptance ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0927-2
更新日期:2020-08-01 00:00:00
abstract::This paper illustrates the efficacy of DNA vaccination through electroporation in the prevention of oral transplantable carcinoma in Syrian hamsters. At 21 and 7 days before tumour challenge, 19 hamsters were vaccinated with plasmids coding for the extracellular and transmembrane domains of rat HER-2 receptor (EC-TM p...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602853
更新日期:2005-11-28 00:00:00
abstract:BACKGROUND:Cisplatin-radiotherapy is a preferred standard for locally advanced, head and neck squamous cell carcinoma (HNSCC). However, the cisplatin-attributable survival benefit is small and toxicity substantial. A biomarker of cisplatin resistance could guide treatment selection and spare morbidity. The ERCC1-XPF nu...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/bjc.2013.576
更新日期:2013-10-15 00:00:00
abstract:BACKGROUND:Combined oral contraceptive (COC) use reduces epithelial ovarian cancer (EOC) risk. However, little is known about risk with COC use before the first full-term pregnancy (FFTP). METHODS:This Canadian population-based case-control study (2001-2012) included 854 invasive cases/2139 controls aged ⩾40 years who...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.400
更新日期:2017-01-17 00:00:00