Abstract：
BACKGROUND:Myelosuppression has been observed with several multikinase angiogenesis inhibitors in clinical studies, although the frequency and severity varies among the different agents. Inhibitors targeting vascular endothelial growth factor receptor (VEGFR) often inhibit other kinases, which may contribute to their adverse-event profiles. METHODS:Kinase selectivity of pazopanib, sorafenib, and sunitinib was evaluated in a panel of 242 kinases. Cellular potency was measured using autophosphorylation assays. Effect on human bone marrow progenitor growth in the presence of multiple growth factors was evaluated and correlated with the kinase selectivity. RESULTS:Sunitinib inhibited more kinases than pazopanib and sorafenib, at potencies within 10-fold of VEGFR-2. All three compounds potently inhibited VEGFR-2, platelet-derived growth factor receptor-beta and c-Kit, However, pazopanib was less active against Flt-3 in both kinase and cellular assays. The inhibitory properties of pazopanib, sorafenib, and sunitinib were dependent on the growth factor used to initiate bone marrow colony formation. Addition of stem cell factor and/or Flt-3 ligand with granulocyte-macrophage colony stimulating factor resulted in significant shifts in potency for sorafenib and sunitinib but less so for pazopanib. CONCLUSION:Activity against c-kit and Flt-3 by multikinase angiogenesis inhibitors provide a potential explanation for the differences in myelosuppression observed with these agents in patients.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Kumar R,Crouthamel MC,Rominger DH,Gontarek RR,Tummino PJ,Levin RA,King AGdoi
10.1038/sj.bjc.6605366subject
Has Abstractpub_date
2009-11-17 00:00:00pages
1717-23issue
10eissn
0007-0920issn
1532-1827pii
6605366journal_volume
101pub_type
杂志文章abstract：:A representative sample of 4657 adults greater than or equal to 45 years of age from the 5 main ethnic groups in Hawaii (Caucasians, Japanese, Chinese, Filipinos and Hawaiians) were interviewed during 1977-1979 regarding their diets. Quantitative food-consumption histories were obtained, from which average daily intak...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.189
更新日期：1981-09-01 00:00:00
abstract：:Two policies of palliative thoracic radiotherapy for non-small-cell lung cancer have been compared in a randomised multicentre controlled trial. A total of 369 patients with inoperable, histologically or cytologically confirmed disease, too advanced for radical 'curative' radiotherapy, and with their main symptoms rel...
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.1991.62
更新日期：1991-02-01 00:00:00
abstract：:We examined bone marrow aspirates from 100 metastasis-free primary breast cancer patients. In 38/100 patients (38%), tumour cells were detected in the marrow using an immunocytochemical technique with a cocktail of two monoclonal antibodies: anti-EMA and anti-cytokeratin. Median follow-up was 34 months: 15/38 (39%) tu...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.103
更新日期：1994-03-01 00:00:00
abstract：BACKGROUND:The somatic molecular profiles of basal-like breast cancers and high-grade serous ovarian cancers share many similarities, leading to the hypothesis that they have similar aetiologies, in which case they should occur together in the same patient more often than expected. METHODS:We identified 545 women with...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2017.73
更新日期：2017-04-11 00:00:00
abstract：:High experienced continuity of care in patients with cancer is associated with lower needs for care, better quality of life and better psychological outcomes. We developed and evaluated an intervention to improve experienced continuity. The intervention, consisted of (1) a 17-item patient-completed continuity assessme...
journal_title：British journal of cancer
pub_type： 杂志文章,随机对照试验
doi：10.1038/sj.bjc.6604836
更新日期：2009-01-27 00:00:00
abstract：:Currently the only tumour marker to have a well-defined and validated role in the management of ovarian cancer is CA125. Changes in the level of CA125 can be used as a reliable indication of response or progression according to various criteria, but it does not yet have a clear place in diagnosis or prognosis. Its val...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1054/bjoc.2000.1174
更新日期：2000-05-01 00:00:00
abstract：BACKGROUND:PI3K/Akt (PKB) pathway has been shown in several cell types to be activated by ligands to cell surface integrins, leading to the metastasis of tumour cells. The signalling pathways involved in the metastatic spread of human scirrhous gastric carcinoma cells have not been defined. METHODS:The role of the PI3...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.107
更新日期：2012-04-24 00:00:00
abstract：:When purified fibre and hexon proteins of adenovirus 12 were given intramuscularly to 4-week-old BALB/c mice (250-300 mug/mouse) 2 h prior to inoculation with mouse sarcoma virus (0.05 ml of 10(4) FFU/ml) at the same site, significant suppression of tumour growth (P less than 0.001), and rapid regression in tumour siz...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1976.63
更新日期：1976-04-01 00:00:00
abstract：:Combretastatin-A4 phosphate (cis-CA-4) is a tubulin-binding agent currently undergoing clinical trials as an anti-tumour drug. We have investigated whether CA-4 functions as a tumour-specific anti-vascular agent using the hyperplastic thyroid as a novel in vivo model of neovascularization. CA-4 elicited pathological c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1653
更新日期：2001-03-23 00:00:00
abstract：BACKGROUND:Patients with high-grade gliomas are treated with surgery followed by chemoradiation. The risk factors and implications of neurological side effects are not known. METHODS:Acute and late ≥ grade 3 neurological toxicities (NTs) were analysed among 2761 patients from 14 RTOG trials accrued from 1983 to 2003. ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.123
更新日期：2011-04-26 00:00:00
abstract：:The purpose of this study was to determine the maximum-tolerated dose of gemcitabine plus mitoxantrone in women with metastatic breast cancer (MBC) and to evaluate activity and toxicity of this combination in a phase II trial. Sixty-three patients with MBC, previously treated with chemotherapy including anthracycline ...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjc.6600780
更新日期：2003-02-24 00:00:00
abstract：:When L2C leukaemic B lymphocytes from guinea-pigs were incubated in vitro with antibody directed to their surface immunoglobulin (Ig), a rapid rise in intracellular adenosine 3':5'-phosphate (cyclic adenosine monophosphate, cAMP) was observed. Estimation of cAMP was by a protein-binding assay using bovine adrenal prot...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.77
更新日期：1979-04-01 00:00:00
abstract：:To examine the hypothesis that colorectal carcinomas with and without TP53 mutations may be characterised by aetiological heterogeneity, we analysed a group of 107 patients with primary Dukes' C colorectal cancer seen at the Memorial Sloan-Kettering Cancer Center (MSKCC) from 1986 to 1990. We assessed p53 overexpressi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.171
更新日期：1995-04-01 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：BACKGROUND:The pathogenesis of lymph node metastases in preinvasive breast cancer – ductal carcinoma in situ (DCIS) – remains controversial. The one-step nucleic acid amplification (OSNA) assay is a novel molecular method that can assess a whole node and detect clinically relevant metastases. In this retrospective coho...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.168
更新日期：2012-05-08 00:00:00
abstract：:High-mol.-wt levan injected locally inhibits the growth of Lewis lung carcinoma in C57BL mice. The inhibition is dependent on the number of tumour cells injected and on the dose of levan. The inhibition decreases tumour incidence and size as well as prolonging survival. The polysaccharide is most effective when inject...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.225
更新日期：1979-10-01 00:00:00
abstract：:Loss of the short arm of chromosome 1 is a hallmark of oligodendroglial tumours (OTs). Deletion mapping studies in OTs have revealed multiple commonly deleted regions on chromosome 1p, suggesting that there are more than one tumour suppressor gene. To map critical deletion regions on 1p, a series of 25 OTs were examin...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602093
更新日期：2004-09-13 00:00:00
abstract：:Human papillomavirus (HPV) is thought to cause some vulval squamous cell carcinomas (VSCC) by degrading p53 product. Evidence on whether HPV-negative VSCC results from p53 mutation is conflicting. We performed immunohistochemistry for p53 product on 52 cases of lone vulval intraepithelial neoplasia (VIN), 21 cases of ...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析,多中心研究
doi：10.1038/sj.bjc.6600677
更新日期：2003-01-27 00:00:00
abstract：:Antibody drug conjugates (ADCs) employ the exquisite specificity of tumour-specific monoclonal antibodies (mAb) for the targeted delivery of highly potent cytotoxic drugs to the tumour site. The chemistry of the linker, which connects the drug to the mAb, determines how and when the drug is released from the mAb. This...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/bjc.2017.367
更新日期：2017-12-05 00:00:00
abstract：:The frequency of M-components was studied by agar gel electrophoresis in sera from 807 patients, 467 (57%) females and 340 (43%) males with histologically proven solid malignant neoplasms.M-components were found in the sera of 40 male and 20 female patients. Apart from two known cases of multiple myeloma and one case ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1973.34
更新日期：1973-04-01 00:00:00
abstract：:Initial studies revealed that proline-directed protein kinase F(A) (PDPK F(A)) was overexpressed in various cancerous tissues relative to normal controls. However, the functional role of overexpressed PDPK F(A) in cancer remains to be established. In this report, we explore the potential role of PDPK F(A) in leukaemia...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.1999.1133
更新日期：2000-04-01 00:00:00
abstract：:The clearance of an intradermally-injected solution of 133Xenon in 0.9% saline has been used to study the impairment and recovery of blood flow in mouse tail for 5 days following photodynamic therapy (PDT) with 2mg TPPS i.v. per mouse and a range of doses of white light. Impairment of blood flow was observed within 10...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.105
更新日期：1988-05-01 00:00:00
abstract：:Over a wide range of pH, the semiquinone free radicals formed by reduction of adriamycin exist as a form which is strongly stabilised by internal hydrogen bonding and resonance. They protonate with pKa = 2.9. Below this pH they exhibit absorption maxima at 430 nm (Emax = 13,200 dm3 mol-1 cm-1) and approximately 720 nm...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1985.74
更新日期：1985-04-01 00:00:00
abstract：:We have established a highly sensitive and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method to detect axillary lymph node metastases of breast cancer. Amplifying cytokeratin 19 (CK19) mRNA transcripts using real-time TaqMan PCR made it possible to quantify axillary metastatic burden. Metast...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601248
更新日期：2003-11-03 00:00:00
abstract：:NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit an efficient accumulation in solid tumours in mice. The purpose of this study was to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjc.6602204
更新日期：2004-11-15 00:00:00
abstract：:Ovarian cancer is the fifth leading cause of female cancer deaths in the Western world. Significant progress has been made in the treatment of patients with ovarian cancer, however, the majority of patients experience disease recurrence and new therapies are being sought for such patients. Clinical investigation of po...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/bjc.2015.395
更新日期：2015-12-15 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：BACKGROUND:The arachidonic acid metabolite 12(S)-HETE is suspected to enhance metastatic spread by inducing cancer cell- and lymph endothelial cell (LEC) motility. However, the molecular mechanisms leading to 12(S)-HETE-triggered cell migration are still elusive. METHODS:To delineate the signalling pathways involved i...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.201
更新日期：2016-07-26 00:00:00
abstract：:Incidence and mortality data, stage of disease and treatment information for female breast cancer were obtained for the years 1975-1999 for the former Yorkshire Regional Health Authority area, from the Northern and Yorkshire Cancer Registry and Information Service. Deaths by age group and 3-year calendar period were s...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601614
更新日期：2004-02-09 00:00:00
abstract：BACKGROUND:The addition of breast magnetic resonance imaging (MRI) to screening mammography for women with BRCA mutations significantly increases sensitivity, but there is little data on clinical outcomes. We report screening performance, cancer stage, distant recurrence rate, and breast cancer-specific mortality in ou...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.204
更新日期：2012-06-26 00:00:00
