Abstract：
:A major impediment to the successful use of Taxol in the treatment of cancer is the development of drug resistance. The major cellular target of Taxol is the microtubule that is comprised of alpha- and beta-tubulin heterodimers. Binding sites for Taxol have been delineated on the beta-tubulin subunit that has six isotypes. We have recently described increased expression of the brain-specific human class III beta-tubulin isotype, encoded by the Hbeta4 gene, in both Taxol-resistant ovarian tumours and non-small-cell lung cancer cell lines. To evaluate directly the role of the class III beta-tubulin isotype in mediating Taxol resistance, antisense phosphorothioate oligodeoxynucleotides (ODN) targeted against various regions of the Hbeta4 gene have been designed and examined for their efficacy in reducing Hbeta4 gene and protein expression. Taxol-resistant lung cancer cells, A549-T24, which are 17-fold resistant to Taxol and display a fourfold increase in Hbeta4 expression compared to the parental A549 cells, were treated with 1 microM antisense ODNs. Two ODNs, AS1 and AS3, were found to reduce mRNA expression by 40-50%, as determined by reverse transcription polymerase chain reaction. A concentration-dependent reduction in Hbeta4 mRNA expression was demonstrated with AS1 ODN. Immunofluorescence staining of cells treated with AS1 ODN revealed a decrease in class III protein expression which corresponded to a 39% increase in sensitivity to Taxol (P < 0.005). These findings support an important role for Hbeta4 (class III) beta-tubulin expression in Taxol resistance and have potential implications for the treatment of Taxol-resistant tumours.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Kavallaris M,Burkhart CA,Horwitz SBdoi
10.1038/sj.bjc.6690507subject
Has Abstractpub_date
1999-06-01 00:00:00pages
1020-5issue
7eissn
0007-0920issn
1532-1827journal_volume
80pub_type
杂志文章abstract：:Between 1980 and 1985, 914 patients with head and neck squamous cell carcinoma underwent lymph node dissection in our institution. The prognostic value of clinical factors has already been reported (Mamelle et al, 1994, Am J Surg 168: 494-498). We present here a comparison of biological characteristics of pharyngeal t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.320
更新日期：1998-06-01 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：:In the present study organotypic multicellular spheroids (OMS) were used to study the effects of chemotherapeutic agents on malignant gliomas. Compared with the frequently used cell line models, OMS have several advantages with respect to the preservation of the cellular heterogeneity and the structure of the original...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.336
更新日期：1996-07-01 00:00:00
abstract：:Recent studies indicate that cancer antigen 125 (CA125) response criteria tend to overestimate a tumour reduction measured by standard WHO response criteria in recurrent epithelial ovarian carcinoma. The aim of the study was to validate the recently introduced GCIG (The Gynaecological Cancer Intergroup) CA125 response...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjc.6601501
更新日期：2004-01-26 00:00:00
abstract：:Benzo[b]thiophenesulphonamide 1,1-dioxide (BTS) derivatives are strong cytotoxic agents that induce reactive oxygen species (ROS) overproduction and apoptosis in tumour cells. Although the precise origin of BTS-induced ROS is not known, a clear correlation between their cytotoxic effect and ability to inhibit a tumour...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602383
更新日期：2005-02-28 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：:To study the effect of oral supplemental calcium on colonic epithelial proliferation, 17 adenomatous polyp patients received 1.5 g Ca2+ as calcium carbonate daily during 12 weeks, while on a calcium constant diet, based on the patients' habitual diet. Seven subsequently continued calcium supplementation for 9 months w...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.93
更新日期：1993-03-01 00:00:00
abstract：:Decreased accumulation of the fluorescent dye BCECF [2', 7'-bis-(2-carboxyethyl)-5-(6)- carboxyfluorescein] characterized murine and human multidrug-resistant cell lines overexpressing the multidrug resistance protein (MRP). Indomethacin (10 microM), a known cyclo-oxygenase and glutathione-S-transferase inhibitor as w...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.145
更新日期：1997-01-01 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：:Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was repor...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604329
更新日期：2008-05-06 00:00:00
abstract：:Clinico-cytogenetic correlations were assessed in 88 patients with malignant ovarian tumours. Cytogenetic analysis of the primary tumours yielded normal karyotype (N) in 33 patients and abnormal karyotypes (A) in 55 patients. Within the A group, seven tumours had simple abnormalities (AS), i.e., numerical changes only...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.56
更新日期：1992-02-01 00:00:00
abstract：:L-Glutamine is a requirement for many cells in tissue culture, an intermediate in many metabolic pathways, and an alternative substrate to glucose for energy metabolism. These properties suggest that glutamine concentration might be a determinant of cell viability in tumours, especially in regions that are deficient i...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1986.234
更新日期：1986-11-01 00:00:00
abstract：BACKGROUND:Though p53 mutations are rare in ES, there is a strong indication that p53 mutant tumours form a particularly bad prognostic group. As such, novel treatment strategies are warranted that would specifically target and eradicate tumour cells containing mutant p53 in this subset of ES patients. METHODS:PRIMA-1...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.635
更新日期：2013-11-12 00:00:00
abstract：:Protein kinase C (PKC) has a critical role in several signal transduction pathways, and is involved in renal cancer pathogenesis. Bryostatin-1 modulates PKC activity and has antitumour effects in preclinical studies. We conducted a multicentre phase II clinical trial in patients with advanced renal cancer to determine...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1038/sj.bjc.6601321
更新日期：2003-10-20 00:00:00
abstract：:When assessing the value of a particular treatment, it is important to consider the impact it may have on the quality of life of those being treated. This is particularly so for cancer patients, whose life expectancy may be short. Patients with advanced colorectal cancer who participated in two international comparati...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1038/bjc.1998.420
更新日期：1998-01-01 00:00:00
abstract：:Covalent modifications of histones, such as acetylation, methylation, and phosphorylation, and other epigenetic modulations of the chromatin, such as methylation of DNA and ATP-dependent chromatin reorganisation, can play a major part in the multistep process of carcinogenesis, with far-reaching implications for human...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6601575
更新日期：2004-02-23 00:00:00
abstract：:The aim of the study is to evaluate the pattern and level of expression of glucose transporter-1 (GLUT-1) in rectal carcinoma in relation to outcome as a potential surrogate marker of tumour hypoxia. Formalin-fixed tumour sections from 43 patients with rectal carcinoma, who had undergone radical resection with curativ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601202
更新日期：2003-09-01 00:00:00
abstract：BACKGROUND:Alternative treatments are needed for elderly patients with acute myeloid leukaemia, as the disease prognosis is poor and the current treatment is unsuitable for many patients. METHODS:In this study, we investigated whether combining the nucleoside analogue sapacitabine with histone deacetylase (HDAC) inhib...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605922
更新日期：2010-10-26 00:00:00
abstract：:Three hundred and nineteen patients with primary adenocarcinoma of the ovary were studied to define those factors, many of them histopathological, which influence survival. The paper considers the stage of spread at the time of operation, the histological type of the tumour, its grade and in particular its mitotic act...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1971.30
更新日期：1971-06-01 00:00:00
abstract：:Cellular adhesion molecules have been implicated in tumour progression and metastasis. This study examines for the first time the serum concentrations of circulating VCAM-1 and E-selectin in a consecutive series of 110 cancer patients seen in a general medical oncology clinic, and confirms and extends previous studies...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.298
更新日期：1993-07-01 00:00:00
abstract：:The prognostic weight of histological and biological factors was compared with that of known clinical prognostic factors in a population of 108 consecutive previously untreated patients with head and neck squamous cell carcinoma. Parameters studied were: tumour vascularisation, mitotic index, histological differentiat...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.92
更新日期：1996-02-01 00:00:00
abstract：:In the family reported here, a mother and both of her children developed a Wilms tumour, and all three tumours were of the relatively rare monomorphous epithelial histopathological subtype. Using restriction fragment length polymorphism analysis, both sibs were shown to inherit the same maternal allele from the 11p13 ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.210
更新日期：1994-06-01 00:00:00
abstract：:Thirty-three patients with squamous cell carcinoma of the head and neck region were studied concerning p53 protein expression and mutations in exons 4-9 of the p53 gene using immunohistochemistry, polymerase chain reaction (PCR)-single strand conformation polymorphism analysis and DNA sequencing. Immunoreactivity was ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.159
更新日期：1995-04-01 00:00:00
abstract：:The genetic basis for the majority of early onset or non-syndromic "familial" colorectal cancer (CRC) is unknown. Attenuated APC phenotype is characterized by relatively few colonic polyps, early age at onset of colon cancer compared with the general population, and inactivating germline mutations within specific regi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.1959
更新日期：2001-08-17 00:00:00
abstract：:Epidemiological, animal, and cell culture studies have identified boron as a chemopreventative agent in prostate cancer. The present objective was to identify boron-induced changes in the DU-145 human prostate cancer cell line. We show that prolonged exposure to pharmacologically-relevant levels of boric acid, the nat...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603009
更新日期：2006-03-27 00:00:00
abstract：:The lability of cell surface histocompatibility antigens of 2 murine lymphomata was examined. These 2 tumours differ greatly in their capacity to metastasize in syngeneic hosts. Cells of the metastatic lymphoma released histocompatibility antigens in vivo and in vitro at a greater rate than cells of the non-metastasiz...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1976.2
更新日期：1976-01-01 00:00:00
abstract：:The in vitro deamination, cytotoxicity, cellular drug uptake, distribution and cellular pharmacology in HL-60 cells of N4-hexadecyl-1-beta-D-arabinofuranosylcytosine (NHAC), a lipophilic derivative of arabinofuranosylcytosine (ara-C), were studied. Compared with ara-C, NHAC in liposomal formulations was highly resista...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.185
更新日期：1995-05-01 00:00:00
abstract：:We screened 50 glioblastomas for P53 mutations. Five glioblastomas showed heterozygous mutations, while three were putatively heterozygous. Six of these eight glioblastomas showed elimination of wild-type P53 mRNA. These results strongly suggest that some sort of mechanism(s) favouring mutated over wild-type P53 mRNA ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604258
更新日期：2008-04-22 00:00:00
abstract：BACKGROUND:Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast can...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.44
更新日期：2011-03-15 00:00:00
abstract：BACKGROUND:Cross-talk between receptor tyrosine kinases and the oestrogen receptor (ER) is implicated in resistance to endocrine therapy. We investigated whether AEE788 (a combined inhibitor of EGFR, HER2 and VEGFR) plus tamoxifen or letrozole enhanced the individual anti-tumour effects of these agents. METHODS:Breast...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605641
更新日期：2010-04-13 00:00:00
