Abstract：
BACKGROUND:Here, we explore the therapeutic potential of dasatinib, a small-molecule inhibitor that targets multiple cytosolic and membrane-bound tyrosine kinases, including members of the Src kinase family, EphA2, and focal adhesion kinase for the treatment of ovarian cancer. METHODS:We examined the effects of dasatinib on proliferation, invasion, apoptosis, cell-cycle arrest, and kinase activity using a panel of 34 established human ovarian cancer cell lines. Molecular markers for response prediction were studied using gene expression profiling. Multiple drug effect/combination index (CI) isobologram analysis was used to study the interactions with chemotherapeutic drugs. RESULTS:Concentration-dependent anti-proliferative effects of dasatinib were seen in all ovarian cancer cell lines tested, but varied significantly between individual cell lines with up to a 3 log-fold difference in the IC(50) values (IC(50) range: 0.001-11.3 micromol l(-1)). Dasatinib significantly inhibited invasion, and induced cell apoptosis, but less cell-cycle arrest. At a wide range of clinically achievable drug concentrations, additive and synergistic interactions were observed for dasatinib plus carboplatin (mean CI values, range: 0.73-1.11) or paclitaxel (mean CI values, range: 0.76-1.05). In this study, 24 out of 34 (71%) representative ovarian cancer cell lines were highly sensitive to dasatinib, compared with only 8 out of 39 (21%) representative breast cancer cell lines previously reported. Cell lines with high expression of Yes, Lyn, Eph2A, caveolin-1 and 2, moesin, annexin-1, and uPA were particularly sensitive to dasatinib. CONCLUSIONS:These data provide a clear biological rationale to test dasatinib as a single agent or in combination with chemotherapy in patients with ovarian cancer.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Konecny GE,Glas R,Dering J,Manivong K,Qi J,Finn RS,Yang GR,Hong KL,Ginther C,Winterhoff B,Gao G,Brugge J,Slamon DJdoi
10.1038/sj.bjc.6605381subject
Has Abstractpub_date
2009-11-17 00:00:00pages
1699-708issue
10eissn
0007-0920issn
1532-1827pii
6605381journal_volume
101pub_type
杂志文章abstract：:A clinical trial conducted according to a schedule of interim analyses written into the protocol, and stopped according to a predetermined rule, is known to statisticians as a sequential clinical trial. This methodology is becoming more widely used in trials concerning life-threatening diseases because of its ability ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.500
更新日期：1993-12-01 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：:We conducted a case-control study to investigate the role of early infections in the aetiology of childhood acute leukaemias. The study included 280 incident cases (240 acute lymphoblastic leukaemia and 40 acute non-lymphoblastic leukaemia) and 288 hospital controls, frequency matched by age, gender, hospital, catchme...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600091
更新日期：2002-04-08 00:00:00
abstract：BACKGROUND:A dose-dense strategy has been considered to improve results of adjuvant chemotherapy for breast cancer. This randomised phase II trial investigated the feasibility of this approach with sequential anthracyclines and taxanes-based chemotherapy. METHODS:Patients with high-risk node-positive breast cancer wer...
journal_title：British journal of cancer
pub_type： 杂志文章,随机对照试验
doi：10.1038/bjc.2011.414
更新日期：2011-11-08 00:00:00
abstract：:Twenty patients with non-Hodgkin's lymphoma were treated with a combination of cyclophosphamide (750 mg m(-2), day 1), epidoxorubicin (60 mg m(-2), day 1), vincristine (1.4 mg m(-2), day 1) and prednisone (100 mg m(-2), days 1-5) every 14 days. Shortening of intervals was associated with the prophylactic employment of...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1998.578
更新日期：1998-09-01 00:00:00
abstract：:Information on exposure and reaction to sunlight, together with the history of exposure to fluorescent lighting, was elicited by postal questionnaire. Case-control analysis from 58 patients with malignant melanoma, 182 matched controls and 151 unmatched controls showed associations between malignant melanoma and (i) b...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1985.255
更新日期：1985-11-01 00:00:00
abstract：:The presence of specific and high affinity epidermal growth factor receptors (EGF-R) has been demonstrated in human prostate cancer (CaP). Scatchard analysis of the binding data revealed a linear plot consistent with a single class of binding sites with a mean dissociation constant (Kd) +/- s.d. = 1.6 +/- 0.4 nmol 1-1...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.216
更新日期：1989-07-01 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:On the base of the microRNA (miRNA) expression signature of bladder cancer (BC), we found that miR-1 and miR-133a were significantly downregulated in BC. In this study, we focussed on the functional significance of miR-1 and miR-133a in BC cell lines and identified a molecular network of these miRNAs. METHO...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.23
更新日期：2011-03-01 00:00:00
abstract：BACKGROUND:Lynch syndrome (LS) is associated with a significant lifetime risk of endometrial cancer (EC). There are limited data on factors modifying the EC risk in LS patients. METHODS:The study cohort included 136 LS mutation-positive women. Exposure data were collected by postal questionnaires. Cox regression model...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.193
更新日期：2016-07-26 00:00:00
abstract：:The chick embryo was used to study the relationship between the onset of tumour neovascularization and tumour growth. Walker 256 carcinosarcoma was implanted on the chrioallantoic membrane (CAM) of about 600 embryos aged 5-16 days. Tumour diameter and changes in the CAM vasculature in response to the implants were rec...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1977.49
更新日期：1977-03-01 00:00:00
abstract：:HMGI-C belongs to the high-mobility-group-protein (HMG) family of architectural transcription factors and considerable interest has recently been shown in its expression in neoplastic tissues and apparent involvement in tumorigenesis. We could previously demonstrate an expression of HMGI-C mRNA in the peripheral blood...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600935
更新日期：2003-05-06 00:00:00
abstract：:NIH3T3 cells transfected with c-H-ras and/or c-myc genes were examined for differences in drug sensitivity. The five transfectants used were N8, NIH3T3-nm-1, pT22-3-nm-2, pP1-4 and pT22-3. They were transfected with pKOneo alone, pKOneo and c-myc, pKOneo and c-myc plus activated c-H-ras, normal c-H-ras and activated c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.56
更新日期：1991-02-01 00:00:00
abstract：:Photodynamic therapy (PDT) is a form of cancer treatment based on the destruction of cells by the interaction of light, oxygen and a photosensitizer. Aminolaevulinic acid (ALA) is the prodrug of the photosensitizer protoporphyrin IX (PpIX). ALA-induced PDT depends on the rate of cellular synthesis of PpIX, which may v...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.441
更新日期：1998-07-01 00:00:00
abstract：:Killing of autologous melanoma (auto-Me) was obtained with pooled allostimulated peripheral blood lymphocytes (PBL) in 34/42 cases and found not to be due to a cross-reactivity between melanoma and allogeneic normal antigens. To see whether generation of tumour cytotoxic PBL by allostimulation was due to release of IL...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1985.151
更新日期：1985-07-01 00:00:00
abstract：:In spite of the wide range of tumours successfully treated with 5-aminolevulinic acid mediated photodynamic therapy, the fact that 5-aminolevulinic acid has low lipid solubility, limits its clinical application. More lipophilic 5-aminolevulinic acid prodrugs and the use of liposomal carriers are two approaches aimed a...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600144
更新日期：2002-03-04 00:00:00
abstract：BACKGROUND:Metastasis is associated with poor prognosis for melanoma. The formation of metastases is a multi-step process, in which cancer cells can subsequently acquire the potential to intravasate into the blood or lymph vessels, disseminate through the circulation, extravasate through the endothelium and invade the ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6606056
更新日期：2011-02-01 00:00:00
abstract：BACKGROUND:Early detection of non-small-cell lung cancer (NSCLC) and accurate prognostic risk assessment could improve patient outcome. We examined the significance of urinary N(1), N(12)-diacetylspermine (DiAcSpm) in the detection and prognostic stratification of NSCLC patients. METHODS:A DiAcSpm/cutoff ratio (DASr) ...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究
doi：10.1038/bjc.2015.349
更新日期：2015-11-17 00:00:00
abstract：BACKGROUND:First Spanish trial of Ewing sarcoma (ES) including adults and children with the aim to test the efficacy of Gemcitabine and Docetaxel (G/D) in newly diagnosed high-risk (HR) patients. METHODS:This was a prospective, multicentric, non-randomised, open study for patients ⩽40 years with newly diagnosed ES. HR...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究
doi：10.1038/bjc.2017.252
更新日期：2017-09-05 00:00:00
abstract：BACKGROUND:The clinical utility of machine-learning (ML) algorithms for breast cancer risk prediction and screening practices is unknown. We compared classification of lifetime breast cancer risk based on ML and the BOADICEA model. We explored the differences in risk classification and their clinical impact on screenin...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-0937-0
更新日期：2020-09-01 00:00:00
abstract：:The survival of 64 consecutive patients with disseminated midgut carcinoid tumours was compared in a retrospective study with that of 25 consecutive patients with sporadic malignant endocrine pancreatic tumours treated according to similar surgical principles. The presence of hepatic metastases implied a worse prognos...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690494
更新日期：1999-06-01 00:00:00
abstract：:The use of cytotoxic drug vincristine (VCR) is limited by the occurrence of peripheral neuropathy. A neurotrophic ACTH(4-9) analogue, ORG 2766, is being studied for its protective effect. Possible modulatory effects of ORG 2766 on tumour cell growth and interference with the cytotoxic efficacy of VCR were studied in t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.90
更新日期：1994-03-01 00:00:00
abstract：:Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from rHuEPO, due to its increa...
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.2001.1748
更新日期：2001-04-01 00:00:00
abstract：BACKGROUND:Tallness has consistently been associated with an increased risk of breast cancer. We investigated the association further by decomposing height into leg length and sitting height. METHODS:From the prospective Danish cohort 'Diet, Cancer and Health', 23 864 postmenopausal women enrolled during 1993-1997 wer...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.244
更新日期：2012-06-26 00:00:00
abstract：:The reaction patterns of eight antibodies directed against blood group substances A, B and H, respectively, against Lewis B antigen, difucosylated carbohydrate antigens (DFCA), gastrointestinal cancer antigen CA 19-9 (GICA), carcinoma-associated antigen CA-50 and CEA, were studied in 68 rectal carcinomas using the avi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1987.102
更新日期：1987-05-01 00:00:00
abstract：:Malignancy of neoplasms is partly dependent on angiogenesis. Angiotensin II mediates angiogenesis and transcription of growth-related factors through stimulation of the AT1 receptor (AT1R). Losartan, a drug used mostly for treatment of hypertension, binds strongly to this receptor. We found the presence of AT1 recepto...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.2102
更新日期：2001-11-02 00:00:00
abstract：:ApoE single nucleotide polymorphisms (SNPs) Cys112Arg (Epsilon-4), and Arg158Cys (Epsilon-2) have been implicated in cardiovascular and Alzheimer's disease, but their role in colorectal cancer (CRC) has not been extensively studied. We investigated whether ApoE polymorphisms alone or in combination with dietary factor...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605097
更新日期：2009-06-16 00:00:00
abstract：BACKGROUND:BRCAness is defined as shared tumour characteristics between sporadic and BRCA-mutated cancers. However, how to exactly measure BRCAness and its frequency in breast cancer is not known. Assays to establish BRCAness would be extremely valuable for the clinical management of these tumours. We assessed BRCAness...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.144
更新日期：2013-05-28 00:00:00
abstract：BACKGROUND:It is known that cancer stage is affected by comorbidity, but the evidence regarding the magnitude and even direction of this effect is highly inconsistent and poorly understood. The aims of this study were to establish the impact of comorbidity on cancer stage at diagnosis, using both specific individual co...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2015.355
更新日期：2015-11-03 00:00:00
abstract：:Lines of fibroblasts have been established from normal individuals and from patients diagnosed as suffering from one of the mucopolysaccharidoses or mucopolysaccharide-storage diseases. Transformation of these lines with SV40 virus has been found to reduce their capacity to secrete sulphated mucopolysaccharides into t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1977.156
更新日期：1977-07-01 00:00:00
