Abstract:
:Mechanisms of resistance to Tomudex include increased thymidylate synthase activity, as well as reduced intracellular drug uptake and polyglutamation. However, little is known about other mechanisms of resistance, such as a possible protection against Tomudex-induced apoptosis mediated by bcl-2. We transfected the MDA-MB-435 human breast cancer cell line, which is characterized by a mutated p53 gene, with cDNA of the bcl-2 gene and generated two clones (MDA-bcl4 and MDA-bcl7) characterized by bcl-2 expression twofold and fourfold that observed in the control cell clone (MDAneo). A concomitant overexpression of p21wafl was also detected in the MDA-bcl7 clone. The MDA-bcl4 clone was three times more resistant to a 24-h Tomudex exposure than the MDAneo clone, whereas the MDA-bcl7 clone was as sensitive to Tomudex as the control cell clone. A lower sensitivity of the MDA-bcl4 clone than MDAneo and MDA-bcl7 clones to 5-fluorouracil and gemcitabine was also observed. No significant difference was noted in the susceptibility of clones to fludarabine and methothrexate. Basal levels of thymidylate synthase activity were superimposable in the three clones. Tomudex induced a marked accumulation of cells in the S phase in all the clones. However, an apoptotic hypodiploid DNA peak and the characteristic nuclear morphology of apoptosis were observed only in the MDA-bcl7 clone after exposure to Tomudex. No difference in the treatment-induced modulation of proteins involved in cell cycle progression (cyclin A, cdk2, pRB, E2F-1) and apoptosis (bcl-2, bax) was observed in the three clones. The only exception was that the expression of p21wafl in the MDA-bcl4 clone was inducible at a Tomudex concentration much higher than that required to induce the protein in the other clones. Overall, the results indicate that bcl-2 and p21wafl proteins concur in determining the cellular profile of sensitivity/resistance to Tomudex.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Orlandi L,Bearzatto A,Abolafio G,De Marco C,Daidone MG,Zaffaroni Ndoi
10.1038/sj.bjc.6690685subject
Has Abstractpub_date
1999-09-01 00:00:00pages
252-60issue
2eissn
0007-0920issn
1532-1827journal_volume
81pub_type
杂志文章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:In neuroblastoma (NB), the most powerful prognostic marker, the MYCN amplification (MNA), occasionally shows intratumoural heterogeneity (ITH), i.e. coexistence of MYCN-amplified and non-MYCN-amplified tumour cell clones, called heterogeneous MNA (hetMNA). Prognostication and therapy allocation are still uns...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/s41416-018-0098-6
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abstract::To assess the precise role of IGF1 in benign and malignant breast diseases, we analysed the tissular localisation, characterised, and quantified specific insulin-like growth factor 1 (IGF1) binding sites in these heterogenous tissues, using histo-autoradiographic analysis (HAA). The 125I-IGF1 binding was performed on ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.252
更新日期:1992-08-01 00:00:00
abstract::Alveolar macrophage (AM) phagocytic activity and glucose metabolism were evaluated during lung tumour growth in adult rats challenged i.v. with 10(5) viable Walker 256 tumour cells. Phagocytosis was estimated by the in vitro uptake of (14)C-labelled Pseudomonas aeruginosa and glucose oxidation was evaluated by (14)CO(...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1977.249
更新日期:1977-12-01 00:00:00
abstract::The purpose of this study was to compare the growth-inhibitory effect of cisplatin-paclitaxel with that obtained with a cisplatin-docetaxel combination and to assess the type of interaction. Concomitant use of taxanes and cisplatin was studied in seven human ovarian carcinoma cell lines, using the 96-well plate clonog...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690046
更新日期:1999-01-01 00:00:00
abstract::Metastatic variant sublines of the murine large-cell lymphoma cell line RAW117 were tested for their growth and migration properties in vitro in medium conditioned by soluble factors released from syngeneic mouse liver-, lung-, and brain-derived microvessel endothelial cells. Medium conditioned with hepatic sinusoidal...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.269
更新日期:1992-08-01 00:00:00
abstract::Imaging has an essential role in the planning and delivery of radiotherapy. Recent advances in imaging have led to the development of advanced radiotherapy techniques-including image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic body radiotherapy and proton beam therapy. The optimal use of imagin...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/s41416-019-0412-y
更新日期:2019-04-01 00:00:00
abstract::Monoclonal and polyclonal antibodies against placental alkaline phosphatase (PLAP) were evaluated for tumour immunolocalization of human PLAP-producing Hep 2 tumours in nude mice. The antibodies were labelled with 125I and injected i.p. in mice with developing Hep 2 tumours. The distribution of 125I-anti PLAP in vario...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1984.23
更新日期:1984-02-01 00:00:00
abstract::In a previous study we found that aromatic amines, particularly 4-aminobiphenyl, formed haemoglobin adducts at higher concentrations in the blood of smokers compared to non-smokers. We re-analyse here data on haemoglobin adducts of 14 aromatic amines in order to ascertain if the inter-individual variability left unexp...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.120
更新日期:1990-04-01 00:00:00
abstract::The sequential histological changes and neoplastic response occurring in the subcutaneous tissue of rats after injection of surfactants or carcinogens were compared. Twice weekly subcutaneous injections of the surfactants Blue VRS and Light Green SF elicited a deranged connective tissue repair with continued prolifera...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1973.28
更新日期:1973-03-01 00:00:00
abstract::To assist in the description of the cellular heterogeneity present in normal and neoplastic urothelium, a panel of monoclonal antibodies (MoAbs) was raised against human transitional cell carcinoma (TCC) of the urinary bladder. All immunizations were carried out using whole cells and membrane preparations from well di...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.220
更新日期:1987-10-01 00:00:00
abstract::Time trends in therapeutic approaches and in the prognosis of colon cancer for patients aged 75 years and above have been investigated in comparison with corresponding trends for younger patients using a population-based series of 2089 colon cancer patients diagnosed between 1976 and 1990 in the Côte-d'Or area (478,00...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.492
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND:Mesothelin is expressed in various types of malignant tumour, and we recently reported that expression of mesothelin was related to an unfavourable patient outcome in pancreatic ductal adenocarcinoma. In this study, we examined the clinicopathological significance of the mesothelin expression in gastric canc...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.235
更新日期:2012-06-26 00:00:00
abstract::Cells from V79 multicell spheroids must be exposed to approximately 50 times more etoposide than exponentially growing monolayers in order to produce the same amount of cell killing. A part of this difference in sensitivity is readily explained by the decrease in growth fraction of large spheroids, and by the protecti...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.97
更新日期:1993-03-01 00:00:00
abstract::Photoradiation therapy of cancer in the presence of haematoporphyrin derivative is based on a retention of porphyrin in malignant tissue. After long term incubation of NHIK 3025 cells in the presence of 25 microgram ml-1 haematoporphyrin derivative, one fraction is easily removed from the cells by washing with a serum...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.154
更新日期:1983-07-01 00:00:00
abstract:BACKGROUND:Kaposi's Sarcoma Herpesvirus (KSHV) is a gammaherpesvirus strongly linked to human cancer. The virus is also able to induce immune suppression, effect that contributes to onset/progression of the viral-associated malignancies. As KSHV may infect macrophages and these cells abundantly infiltrate Kaposi's sarc...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0872-0
更新日期:2020-07-01 00:00:00
abstract::A study is presented of all cases of primary sarcoma of bone registered during the period 1946 to 1974 for a specified population resident in south-western England. Ninety-six per cent of the 365 cases were histologically and radiologically verified and are separated into 8 categories of sarcoma. The number of tumours...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1977.221
更新日期:1977-10-01 00:00:00
abstract:BACKGROUND:Tumours are made up of a mixed population of different types of cells that include normal structures as well as ones associated with the malignancy, and there are multiple interactions between the malignant cells and the local microenvironment. These intercellular interactions, modulated by the microenvironm...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.517
更新日期:2012-01-03 00:00:00
abstract::Capecitabine is an oral prodrug of 5-fluorouracil (FU). Since FU concentrations achieved in malignant lesions are an important determinant of efficacy, we investigated the intratumoral transcapillary transfer of capecitabine and its metabolites in vivo. A total of 10 patients with skin metastases from breast cancer re...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600809
更新日期:2003-03-10 00:00:00
abstract::High expression of thymidylate synthase (TS) and inactivation of p53 are allegedly associated with chemoresistance. The authors evaluated TS and p53 expression in gastric cancer treated with neoadjuvant S-1/cisplatin chemotherapy. Paraffin sections of pretreatment biopsy and surgical specimens from 41 gastric cancers ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603546
更新日期:2007-01-29 00:00:00
abstract:BACKGROUND:Emergence of drug-resistant cancer phenotypes is a challenge for anti-cancer therapy. Cancer stem cells are identified as one of the ways by which chemoresistance develops. METHOD:We investigated the anti-inflammatory combinatorial treatment (DA) of doxorubicin and aspirin using a preclinical microfluidic m...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0301-9
更新日期:2019-02-01 00:00:00
abstract::We have recently established a cancer-reactive human monoclonal antibody, GAH, with a positive ratio of over 90% against stomach cancer. GAH was formulated as polyethyleneglycol (PEG)-modified immunoliposomal doxorubicin (DXR) (ILD) and its efficacy was examined against gastrointestinal human cancers. In in vitro stud...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601341
更新日期:2003-10-20 00:00:00
abstract:BACKGROUND:Cancer/testis-antigens (CTAs) are specifically expressed in human malignancies and testis tissue, but their molecular functions are poorly understood. CTAs serve as regulators of gene expression, cell cycle and spermatogenesis, as well as targets for immune-based therapies. The CTA PRAME is expressed in vari...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.187
更新日期:2016-08-09 00:00:00
abstract::An analysis of the occurrence of breast cancer in this long-term prospective cohort study shows a significant relative risk (RR) in women who have ever used oral contraceptives (OC) of 3.33 in women age 30 to 34 years at diagnosis and an RR of 5.88 (P = 0.0011) in women who were parity 1 at the time of diagnosis. In w...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.285
更新日期:1988-11-01 00:00:00
abstract::In addition to cobalt, metallic nickel, cadmium and other metals (e.g. zinc and copper) dissolve when incubated with horse serum at 37°. The dissolving property of copper in serum resembles that of cobalt, its solubility being increased greatly in the presence of oxygen, whereas the solubilities of cadmium, zinc and m...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1972.38
更新日期:1972-08-01 00:00:00
abstract::The present study was designed to examine whether different p53 haplotypes of exon 4-intron 3-intron 6 affect the frequency of mutations and loss of heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had significantly high...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602271
更新日期:2005-01-17 00:00:00
abstract::Male and female Swiss strain mice were put on a 0.03% thioacetamide diet at the age of 2 months. Control mice were kept on a stock diet. Control and treated mice were killed at the ages of 6, 9, 13 and 17 months. Progressive morphological, histological and biochemical alterations in the liver and tumour tissue of the ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1970.60
更新日期:1970-09-01 00:00:00
abstract::Using bivariate flow cytofluorometry, we have determined the nuclear DNA distribution and the expression of the p21 protein (coded by the Ha-ras oncogene) in the bone marrow (BM) cells of five solid tumour patients having histologically normal BM and in those of 57 patients with plasma cell dyscrasia (28 with monoclon...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.379
更新日期:1990-11-01 00:00:00
abstract::One hundred resected cases of squamous cell carcinomas of the oesophagus were reviewed and a series of histological criteria related to the survival time. Two histological features were important in the assessment of survival. Good prognostic factors were a marked lymphocytic response to the tumour and a lack of intra...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.87
更新日期:1989-03-01 00:00:00
abstract::The prognostic value of tissue-type plasminogen activator (tPA) measured in samples derived from 865 patients with primary breast cancer using a recently developed enzyme-linked immunosorbent assay (ELISA) was evaluated. Since the assay could easily be adapted to the assessment of the complex of tPA with its type-1 in...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690353
更新日期:1999-04-01 00:00:00