Abstract:
:6-Mercaptopurine (MP)-sensitive and -resistant cell culture lines were used to further characterize the apparent ability of MP nucleotide derivatives to overcome resistance to the parent drug. 6-Mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [MPRP], bis(6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(MPR)P], bis(O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside)-5', 5"'-monophosphate [bis(dibut.MPR)P], and O2',O3'-dibutyryl-6-mercaptopurine-9-beta-D-ribofuranoside 5'-monophosphate [dibut.MPRP] were tested for cytotoxic and/or growth inhibitory effects against MP-resistant sublines of V79 Chinese hamster lung fibroblasts (CH/TG) and L1210 mouse leukaemia cells (L1210/MPR) in which deficiencies of hypoxanthine-guanine phosphoribosyltransferase, and hence drug nucleotide forming capacity were the basis of resistance. L1210/MPR cells were totally resistant to 1 mM 6-mercaptopurine-9-beta-D-ribofuranoside [MPR] and 2 mM MPRP, but were inhibited by high concentrations (greater than 0.25 mM) of bis(MPR)P. These results suggested that bis(MPR)P was taken up by cells as the intact molecule since MPR and MPRP were its extracellular breakdown products. L1210/MPR cells were much more sensitive to the lipophilic bis(dibut.MPR)P derivative which had a predominantly cytotoxic action as judged by trypan blue staining and the ability of treated cells to produce macroscopic colonies in soft agar medium. However, cells killed by bis(dibut.MPR)P did not disintegrate appreciably over periods of up to 10 days. The effects of bis(dibut.MPR)P were probably the result of cellular uptake of the intact molecule. Dibut.MPRP showed minimal ability to inhibit L1210/MPR cells although this compound was a possible breakdown product of bis(dibut.MPR)P and a source of the same extracellular degradation products. The median cell size decreased in L1210/MPR cultures during exposure to both bis(MPR)P and bis(dibut.MPR)P. This effect was elicited more rapidly and at lower concentration by bis(dibut.MPR)P than by bis(MPR)P. In contrast, sodium butyrate, a breakdown product of bis(dibut.MPR)P induced increases in cell size at high concentration. Bis (dibut.MPR)P was also cytotoxic to MP-resistant CH/TG cells and was approximately 300 times more effective than bis(MRP)P and MPR which exhibited similar activity against this cell line. Bis(dibut.MPR)P and dibut.MPRP were equivalent and less active than MPR in their effects on MP-sensitive L1210/0 cells where their predominant mechanism of action was via degradation to release MPR.(ABSTRACT TRUNCATED AT 400 WORDS)
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Johnston HP,Hawley P,White SE,Gibson I,Tidd DMdoi
10.1038/bjc.1985.73subject
Has Abstractpub_date
1985-04-01 00:00:00pages
505-14issue
4eissn
0007-0920issn
1532-1827journal_volume
51pub_type
杂志文章abstract::The relationship between breast self examination (BSE) and breast cancer stage at diagnosis was examined in 616 women aged 15-59 years. Differences in tumour characteristics between those not practising BSE and those practising but not taught were small and inconstant. However, women who had both practised and had bee...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.39
更新日期:1987-02-01 00:00:00
abstract::The factors affecting long-term survival following oesophagectomy for oesophageal cancer are poorly understood. We examined the significance of microscopic tumour involvement at the circumferential resection margin (CRM) on postoperative survival following oesophagectomy. The case notes of 329 patients who underwent a...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600931
更新日期:2003-05-19 00:00:00
abstract:BACKGROUND:Type 2 diabetes mellitus and high total cholesterol and triglycerides are known to be associated with increased colorectal cancer risk for the general population. These associations are unknown for people with a germline DNA mismatch repair gene mutation (Lynch syndrome), who are at high risk of colorectal c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0580-9
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND:Epidermal growth factor receptor (EGFR) is highly expressed in adenoid cystic carcinoma (ACC). The efficacy and toxicity of cetuximab with concomitant platinum-based chemoradio- or chemotherapy in patients with locally advanced or metastatic ACC, respectively, was evaluated. METHODS:Eligible patients (9 wit...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.468
更新日期:2013-09-03 00:00:00
abstract::The relationship between circulating C-reactive protein concentrations and potential cytokine and receptor mediators (interleukin-6, leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), soluble IL-6 receptor, soluble gp130, soluble TNF receptor, interleukin-1 receptor antagonist and interleukin-8 (IL...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602248
更新日期:2004-12-13 00:00:00
abstract::Cultured cells maintained in very low oxygen levels alter their structure, metabolism and genetic expression. Culture conditions for cells were modified to minimise variation of nutrients and to allow normal survival levels after 24 h of hypoxic exposure. Under these hypoxic conditions, glucose consumption and lactate...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.264
更新日期:1990-08-01 00:00:00
abstract::Ultrafiltrates from spleen inhibited both DNA synthesis and the proliferation of normal lymphocytes stimulated inculture from both mouse and man without apparent cytotoxicity. However, the same doses of this spleen ultrafiltrate will kill up to two-thirds of the leukaemic lymphoblasts from both mouse and man after 24 ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.280
更新日期:1975-12-01 00:00:00
abstract::The aim of this study was to ascertain whether assessing the growth fraction of cervical carcinoma of 28 patients, using antibody Ki-67, would be of value in clinical practice. The results showed no relationship between growth fraction and age, clinical stage, lymph node involvement or short term (3-5 years) survival....
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.167
更新日期:1992-05-01 00:00:00
abstract::The relationship between skin tumours in man and exposure to polyaromatic hydrocarbons has been studied in lathe operators exposed to cutting oils. Seven cases of scrotal cancer and 13 cases of senile keratosis and keratoacanthoma were observed. The risk varied as the 1.6th power of duration of exposure for cancer on ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.435
更新日期:1990-12-01 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:Pancreaticoduodenectomy remains a major undertaking. A preoperative blood test, which could confidently predict the benefits of surgery would improve the selection of pancreatic cancer patients for surgery. This study aimed to identify protein biomarkers prognostic for long-term survival and to validate them...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.458
更新日期:2012-11-20 00:00:00
abstract::Data obtained from multiple sources indicate that no single mechanism can explain the resistance to chemotherapy exhibited by non-small cell lung carcinomas. The multi-factorial nature of drug resistance implies that the analysis of comprising expression profiles may predict drug resistance with higher accuracy than s...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600463
更新日期:2002-07-29 00:00:00
abstract:BACKGROUND:Operable non-small cell lung cancer (NSCLC) patients whose tumours have spread to regional or central lymph nodes at the time of diagnosis have dismal prognoses compared with those who have limited disease. The current TNM staging system for NSCLC poorly distinguishes patients with lymph-node metastases who ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.92
更新日期:2016-05-10 00:00:00
abstract::The effect of acute carbon monoxide (CO) breathing on blood oxygenation and tumour hypoxia was related to the radiation response of the C3H/Tif mammary carcinoma. Blood gas analysis showed that CO breathing caused a time- and dose-dependent formation of carboxyhaemoglobin (HbCO), a significant left shift of the oxygen...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.8
更新日期:1994-01-01 00:00:00
abstract::The sera from patients with advanced cancer were tested for their specific inhibitory effects on the cytotoxicity of autologous lymphocytes on tumour cells in a microculture assay. By adding a standard volume of the sera to suspensions of well-washed lymphocytes the inhibitory effect was quantitated by comparison with...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1973.67
更新日期:1973-07-01 00:00:00
abstract::Development of thermotolerance is an important phenomenon that must be considered when thermochemotherapy with multiple heat treatments is used clinically. To study the effect of thermotolerance on cellular cisplatin (cDDP) sensitivity at 37 degrees C and 43 degrees C in cell lines with different cDDP sensitivities, t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.100
更新日期:1995-03-01 00:00:00
abstract::Oestrogen receptor (ER) is used routinely to predict endocrine responsiveness in patients with breast cancer. A second ER, ERbeta has been described but its significance remains undefined; most studies have described mRNA levels rather than protein expression. Here, we demonstrate for the first time, immunohistochemic...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.1721
更新日期:2001-04-20 00:00:00
abstract::We assessed the feasibility and pharmacokinetics of high-dose infusional paclitaxel in combination with doxorubicin, cyclophosphamide, and peripheral blood progenitor cell rescue. Between October 1995 and June 1998, 63 patients with high-risk primary [stage II with >or= 10 axillary nodes involved, stage IIIA or stage ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1054/bjoc.2001.1835
更新日期:2001-06-15 00:00:00
abstract::Serial transplantation of an HCG-producing human testicular teratoma in immune-deprived mice is described. The xenografted tumour was compared to the tumour of origin in histology, immunohistochemistry (using an immune peroxidase technique to localize HCG) autoradiography, marker production and growth rate. It is conc...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1979.104
更新日期:1979-05-01 00:00:00
abstract::In vitro cloned lines derived from a primary nickel-induced rat rhabdomyosarcoma exhibited diverse levels of susceptibility to spontaneous NK activity. The presence of NK target structures was revealed by competition assays on all cloned cell lines, and the NK susceptibility of the tumour lines varied according to the...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.159
更新日期:1983-07-01 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:BACKGROUND:Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern ...
journal_title:British journal of cancer
pub_type: 杂志文章,实务指引
doi:10.1038/bjc.2017.334
更新日期:2017-11-07 00:00:00
abstract:BACKGROUND:Ewing sarcoma is a paradigm of solid tumour -bearing chromosomal translocations resulting in fusion proteins that act as deregulated transcription factors. Ewing sarcoma translocations fuse the EWS gene with an ETS transcription factor, mainly FLI1. Most of the EWS-FLI1 target genes still remain unknown and ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605104
更新日期:2009-07-07 00:00:00
abstract::Piwi proteins and their interaction with piRNAs have rapidly emerged as important contributors to gene regulation, indicating their crucial function in germline and stem cell development. However, data on the Hiwi 1 (Hiwi) gene, one of the four human Piwi homologues, are still scarce. Therefore, we investigated the Hi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604653
更新日期:2008-10-07 00:00:00
abstract::The aim of this study was to evaluate serum midkine (S-MK) concentrations as a prognostic tumour marker in oral squamous cell carcinoma (OSCC). We measured S-MK concentrations in patients with OSCC and healthy volunteers. In addition, we performed real-time quantitative reverse transcription-PCR analysis and immunohis...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604539
更新日期:2008-08-19 00:00:00
abstract::The objective of this paper is to compare the hospital costs of treating patients with colorectal cancers detected as a result of a faecal occult blood screening programme with those of patients whose cancers present symptomatically (control group). Patient-specific cost estimates are made, using case records and hosp...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.462
更新日期:1993-11-01 00:00:00
abstract:BACKGROUND:Cancer survival statistics are typically reported by using measures discounting the impact of other-cause mortality, such as net survival. This is a hypothetical measure and is interpreted as excluding the possibility of cancer patients dying from other causes. Crude probability of death partitions the all-c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0597-0
更新日期:2019-11-01 00:00:00
abstract::HER-2/neu is a tumour antigen that is overexpressed in human breast tumours. Among the vaccine strategies developed to overcome immune tolerance to self-proteins, vaccination with anti-idiotypic (anti-Id) antibodies has been described as a promising approach for treatment of several malignant diseases. To develop an a...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601825
更新日期:2004-05-17 00:00:00
abstract::Immunotoxins that carry two toxin molecules to the target cell should in theory have a greater anti-tumour effect than those that carry just one. We have investigated the therapeutic efficacy of two anti-CD7-saporin immunotoxins constructed with one saporin (HB2-Sap 1-mer) or two saporin molecules (HB2-Sap 2-mer) per ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.177
更新日期:1997-01-01 00:00:00
abstract::Detailed data and statistics per each morphological site of various digestive neoplasms were obtained for the period 1976-87 from the Vaud Cancer Registry datafile, a population-based cancer registration scheme covering about 530,000 inhabitants from the French-speaking part of Switzerland. Tabulations presented inclu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.132
更新日期:1991-04-01 00:00:00