Abstract：
:Cytochrome P450 3A is a drug-metabolising enzyme activity due to CYP3A4 and CYP3A5 gene products, that is involved in the inactivation of anticancer drugs. This study analyses the potential of cytochrome P450 3A enzyme in human colorectal cancer to impact anticancer therapy with drugs that are cytochrome P450 3A substrates. Enzyme activity, variability and properties, and the ability to inactivate paclitaxel (taxol) were analysed in human colorectal cancer and healthy colorectal epithelium. Cytochrome P450 3A enzyme activity is present in healthy and tumoral samples, with a nearly 10-fold interindividual variability. Nifedipine oxidation activity+/-s.d. for colorectal cancer microsomes was 67.8+/-36.6 pmol min(-1) mg(-1). The K(m) of the tumoral enzyme (42+/-8 microM) is similar to that in healthy colorectal epithelium (36+/-8 microM) and the human liver enzyme. Colorectal cancer microsomes metabolised the anticancer drug paclitaxel with a mean activity was 3.1+/-1.2 pmol min(-1) mg(-1). The main metabolic pathway is carried out by cytochrome P450 3A, and it is inhibited by the cytochrome P450 3A-specific inhibitor ketoconazole with a K(I) value of 31 nM. This study demonstrates the occurrence of cytochrome P450 3A-dependent metabolism in colorectal cancer tissue. The metabolic activity confers to cancer cells the ability to inactivate cytochrome P450 3A substrates and may modulate tumour sensitivity to anticancer drugs.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Martínez C,García-Martín E,Pizarro RM,García-Gamito FJ,Agúndez JAdoi
10.1038/sj.bjc.6600494subject
Has Abstractpub_date
2002-09-09 00:00:00pages
681-6issue
6eissn
0007-0920issn
1532-1827journal_volume
87pub_type
杂志文章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：BACKGROUND:Malignancy alters cellular complex lipid metabolism and membrane lipid composition and turnover. Here, we investigated whether tumorigenesis in cancer-derived prostate epithelial cell lines influences protein kinase C-linked turnover of ethanolamine phosphoglycerides (EtnPGs) and alters the pattern of ethano...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.457
更新日期：2014-10-14 00:00:00
abstract：BACKGROUND:Identification of promising biomarkers that predict the prognosis of patients with breast cancer is needed. In this study, we hypothesised that the expression of the epithelial-mesenchymal transition-related biomarker plastin3 (PLS3) in peripheral blood could be a prognostic factor in breast cancer. METHODS...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2015.132
更新日期：2015-04-28 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：:Lung cancer is the primary cause of cancer mortality in developed countries. First diagnosis only when disease has already reached the metastatic phase is the main reason for failure in treatment. To this regard, although low-dose spiral computed tomography (CT) has proven to be effective in the early detection of lun...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6605660
更新日期：2010-06-08 00:00:00
abstract：:Two hundred and twenty-two patients with advanced breast cancer were randomised in two separate trials of similar design to either concomitant combination treatment or sequential use of the same drugs given as single agents changed only at disease progression. Both trials used cyclophosphamide, methotrexate, 5-fluorou...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/bjc.1989.46
更新日期：1989-02-01 00:00:00
abstract：:Many kallikrein genes were found to be differentially expressed in various malignancies, and prostate specific antigen (encoded by the KLK3 gene) is the best tumour marker for prostate cancer. Prostate specific antigen has recently been shown to be an independent favourable prognostic marker for breast cancer. KLK15 i...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600590
更新日期：2002-11-18 00:00:00
abstract：BACKGROUND:Oestrogen (E2) induces apoptosis in long-term E2-deprived MCF7 cells (MCF7:5C). Taxanes have been used extensively in the treatment of early and advanced breast cancer. We have interrogated the sequence of events that involve the apoptotic signalling pathway induced by E2 in comparison with paclitaxel. METH...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.50
更新日期：2014-03-18 00:00:00
abstract：:Oesophageal adenocarcinoma is believed to arise from metaplastic mucosa in the distal oesophagus, a condition also known as Barrett's oesophagus (BE). BE develops as a result of injury caused by refluxing gastric and duodenal contents and is associated with increased risk of malignant transformation. Matrix metallopro...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.1929
更新日期：2001-08-03 00:00:00
abstract：:Oestrogen (RE) and progesterone (RP) cytosolic receptors have been studied in 59 clinically inflammatory tumours of the human breast. The results were compared to those obtained in a series of 496 operable tumours. A single saturating dose of oestradiol for RE and R 5020 for RP was used and the cut-off between negativ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.291
更新日期：1981-12-01 00:00:00
abstract：BACKGROUND:The Nottinghamshire Lymphoma Registry contains the details of all the patients diagnosed with lymphoma (since 1 January 1973) within a defined geographical area with a population of 1.1 million. It was therefore possible to study the outcome of treatment for Hodgkin's disease for three 10-year cohorts (1973-...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.228
更新日期：2012-07-24 00:00:00
abstract：BACKGROUND:In the coBRIM study, cobimetinib plus vemurafenib (C+V) significantly improved survival outcomes vs placebo and vemurafenib (P+V) in patients with advanced/metastatic BRAFV600-mutated melanoma. An analysis of health-related quality of life (HRQOL) from coBRIM is reported. METHODS:Patients completing the Eur...
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/bjc.2017.488
更新日期：2018-03-20 00:00:00
abstract：:We analysed 29 consecutive cases of primary gastric lymphoma (20 men and 9 women) treated in our unit between January 1977 and May 1983. Median age was 55 years. Abdominal pain and weight loss were the main presenting symptoms while there was no palpable disease in the majority of cases. Upper gastrointestinal radiolo...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1985.206
更新日期：1985-09-01 00:00:00
abstract：:In the present multicentre randomized phase II trial, the activity and toxicity of three platinum-based combination regimens for the treatment of advanced non-small-cell lung cancer (NSCLC) were evaluated. The three regimens were: MVP (mitomycin-C 6 mg m(-2) on day 1, vindesine 3 mg m(-2) on days 1 and 15, and cisplat...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/bjc.1998.393
更新日期：1998-06-01 00:00:00
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：:A bispecific monoclonal antibody recognising both carcinoembryonic antigen (CEA) and ricin toxin A chain (RTA) was tested for its ability to target recombinant RTA (r-RTA) to CEA-expressing tumour cells, alone and in combination with ricin B chain (RTB). The antibody, 636 (Robins et al., 1990), induced significant RTA...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.153
更新日期：1991-05-01 00:00:00
abstract：BACKGROUND:Pancreatic cancer is highly malignant and characterised by rapid and uncontrolled growth. While some of the important regulatory networks involved in pancreatic cancer have been determined, the cancer relevant genes have not been fully identified. METHODS:We screened genes that may control proliferation in ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2017.165
更新日期：2017-07-11 00:00:00
abstract：:Cytogenetic investigation was performed on direct preparations of 15 endometrial cancers showing different histotypes. Clonal abnormalities were found in 11 out of 13 analysable cases. The modal chromosome number was near diploid in all cases. The abnormal karyotypes contained relatively simple numerical or structural...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.312
更新日期：1997-01-01 00:00:00
abstract：:Oestrogen receptor alpha (ER-alpha) gene has two specific promoters, distal (P0) and proximal (P1), which induce almost identical transcripts in size due to different splicing. We examined the methylation at both promoter regions of the ER-alpha gene using HpaII, a methylation-sensitive restriction enzyme, prior to po...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690631
更新日期：1999-08-01 00:00:00
abstract：:The relationship between hepatic arterial albumin microsphere distribution and hepatic arterial blood flow and the effects of regional angiotensin II were studied in a rat liver metastases model. Hooded-Lister rats were inoculated subcapsularly with 2 x 10(6) HSN sarcoma cells. At 20 days, hepatic arterial blood flow ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.258
更新日期：1992-08-01 00:00:00
abstract：:Even though the majority of patients with bladder malignancies initially present with low stage disease, the clinical epidemiology of these so-called superficial bladder tumours is not well known. In this paper, disease characteristics at initial presentation and during follow-up are described in 1,745 primary cases d...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究
doi：10.1038/bjc.1993.147
更新日期：1993-04-01 00:00:00
abstract：:We followed 353 women referred with abnormal cervical cytology in a non-intervention cohort study. In 91 pregnant women we compared high-risk human papilloma virus rates in the subsequent trimesters and postpartum in comparison to 262 non-pregnant women. High-risk human papilloma virus clearance was compared with 179 ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600367
更新日期：2002-07-01 00:00:00
abstract：:The retinoblastoma gene product (RB) contributes to normal cell growth control. One of its functions is manifest as a block to exit from G1, which is carried out by an RB subspecies which is un- or underphosphorylated. After RB phosphorylation, a process which occurs towards the end of G1 in cycling cells, the block i...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/bjc.1993.325
更新日期：1993-08-01 00:00:00
abstract：BACKGROUND:Multiple early gastric cancers (EGCs) may develop in 6-14% of patients even after achieving curative endoscopic submucosal dissection (ESD); however, a useful biomarker for predicting recurrence is not available. The present study investigated whether the expression of CD44 variant 9 (CD44v9), a functional c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.314
更新日期：2013-07-23 00:00:00
abstract：:An increasing body of evidence indicates that glutathione S-transferases play a role in the intrinsic and acquired resistance of tumours to anticancer drugs. In view of the wide use of tumour cell lines to understand the factors which confer either sensitivity or resistance to chemotherapeutic agents we have determine...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.280
更新日期：1989-09-01 00:00:00
abstract：:Wistar rats were sensitized to rat embryonic tissue by immunization with irradiated (5000 rad) rat embryo cells (2 X 10(6) s.c. + 1 X 10(6) i.p.) derived from embryos aged 14-15 days, or by implantation of irradiated (5000 rad) tissue grafts from these embryos. Three to five immunizations were given at weekly interval...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1976.94
更新日期：1976-06-01 00:00:00
abstract：:Carcinomas of unknown primary (CUP) represent between 3 and 10% of malignancies. Treatment with nonspecific chemotherapy is commonly unhelpful and the median survival is between 3 and 6 months. Gene expression microarray (GEM) analysis has demonstrated that molecular signatures can aid in tumour classification and pro...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604315
更新日期：2008-04-22 00:00:00
abstract：:Geographical correlations between standardized, mortality ratios (SMRs) of cancers and consumption of different types of alcoholic beverages (saké synthetic saké, shochu, beer, wine, and whisky), of cigarettes, and urbanization were examined for all 46 prefectures in Japan. Suggestive correlations were observed betwee...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.200
更新日期：1979-09-01 00:00:00
abstract：:Eighteen patients with inoperable hepatocellular carcinoma (HCC) were treated with intrahepatic arterial yttrium-90 microspheres. All these patients showed a lung shunting below 15% and a tumour-to-normal ratio higher than 2 as determined by diagnostic technetium-99m macroaggregated albumin (Tc-MAA) gamma scintigraphy...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1994.436
更新日期：1994-11-01 00:00:00
abstract：BACKGROUND:Metabolomics has shown promise in gastric cancer (GC) detection. This research sought to identify whether GC has a unique urinary metabolomic profile compared with benign gastric disease (BN) and healthy (HE) patients. METHODS:Urine from 43 GC, 40 BN, and 40 matched HE patients was analysed using (1)H nucle...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2015.414
更新日期：2016-01-12 00:00:00
