Abstract：
BACKGROUND:Activating mutations of Fms-like tyrosine kinase 3 (FLT3) constitute a major driver in the pathogenesis of acute myeloid leukaemia (AML). Hence, pharmacological inhibitors of FLT3 are of therapeutic interest for AML. METHODS:The effects of inhibition of FLT3 activity by a novel potent FLT3 inhibitor, BPR1J-097, were investigated using in vitro and in vivo assays. RESULTS:The 50% inhibitory concentration (IC(50)) of BPR1J-097 required to inhibit FLT3 kinase activity ranged from 1 to 10 nM, and the 50% growth inhibition concentrations (GC(50)s) were 21±7 and 46±14 nM for MOLM-13 and MV4-11 cells, respectively. BPR1J-097 inhibited FLT3/signal transducer and activator of transcription 5 phosphorylation and triggered apoptosis in FLT3-driven AML cells. BPR1J-097 also showed favourable pharmacokinetic property and pronounced dose-dependent tumour growth inhibition and regression in FLT3-driven AML murine xenograft models. CONCLUSION:These results indicate that BPR1J-097 is a novel small molecule FLT-3 inhibitor with promising in vivo anti-tumour activities and suggest that BPR1J-097 may be further developed in preclinical and clinical studies as therapeutics in AML treatments.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Lin WH,Jiaang WT,Chen CW,Yen KJ,Hsieh SY,Yen SC,Chen CP,Chang KY,Chang CY,Chang TY,Huang YL,Yeh TK,Chao YS,Chen CT,Hsu JTdoi
10.1038/bjc.2011.564subject
Has Abstractpub_date
2012-01-31 00:00:00pages
475-81issue
3eissn
0007-0920issn
1532-1827pii
bjc2011564journal_volume
106pub_type
杂志文章abstract：:Mutation of c-K-ras oncogene is an important step in progression of colon cancer. We used a hammerhead ribozyme (KrasRz) against mutated K-ras gene transcripts (codon 12, GTT) to inactivate mutant K-ras function in the colon cancer cell line SW480, harbouring a mutant K-ras gene. The beta-actin promoter-driven KrasRz ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1363
更新日期：2000-09-01 00:00:00
abstract：:We have studied the ability of cyclosporin A (CsA) and a non-immunosuppressive analogue, O-acetyl cyclosporin A (OACsA, B3-243) to inhibit the growth of human lung cancer cells in vitro. Using continuous drug exposure and the MTT colorimetric assay to determine cell growth we found that CsA produced partial growth inh...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.68
更新日期：1992-03-01 00:00:00
abstract：:We compared the long-term impact of 1- and 2-year screening mammography intervals using prognostic, screening, and outcome information for women aged 50-74 years obtained from the Screening Mammography Program of British Columbia in two time periods, prior to 1997 (policy of annual mammography) and after 1997 (biennia...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602393
更新日期：2005-03-14 00:00:00
abstract：:The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G(2) assay was used to measure chromosomal radiosensitivity. The results d...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604345
更新日期：2008-05-20 00:00:00
abstract：BACKGROUND:We modified and evaluated an advance care planning (ACP) intervention, which had been shown to improve compliance with patient's end of life (EoL) wishes, in a different patient population. METHODS:Patients with incurable cancer, and a Family Member (FM), were randomised one-to-one to usual care or usual ca...
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/s41416-018-0303-7
更新日期：2018-11-01 00:00:00
abstract：BACKGROUND:While current chemotherapy has increased cure rates for children with acute lymphoblastic leukaemia (ALL), the largest number of relapsing patients are still stratified as medium risk (MR) at diagnosis (50-60%). This highlights an opportunity to develop improved relapse-prediction models for MR patients. We ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-0933-4
更新日期：2020-09-01 00:00:00
abstract：:The reactivation of U.V.-irradiated adenovirus 2 in HeLa cells is enhanced 8-9 fold if the cells are given a brief hyperthermic shock before infection. Maximum reactivation is achieved by heating for 10 min at 45.5 degrees C and with a delay of 36 h between heating and infection. The induction process requires protein...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1984.32
更新日期：1984-02-01 00:00:00
abstract：BACKGROUND:To date, there are few reports on gene products contributing to colon cancer progression. METHODS:We used a gene trap comprised of an enhanced retroviral mutagen (ERM) cassette that includes a tetracycline-responsive promoter upstream of a haemagglutinin (HA) tag and a splice donor site. Integration of the ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605536
更新日期：2010-02-16 00:00:00
abstract：BACKGROUND:Dichloroacetate (DCA), through the inhibition of aerobic glycolysis (the 'Warburg effect') and promotion of pyruvate oxidation, induces growth reduction in many tumours and is now undergoing several clinical trials. If aerobic glycolysis is active in multiple myeloma (MM) cells, it can be potentially targete...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.120
更新日期：2013-04-30 00:00:00
abstract：:We used data from a prospective cohort study of twins to investigate the influence of unmeasured genetic and measured and unmeasured environmental factors on the smoking behaviour of adolescents and young adults. Twins were surveyed in 1988 (aged 11-18 years), 1991, 1996 and 2004 with data from 1409, 1121, 732 and 758...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604250
更新日期：2008-04-22 00:00:00
abstract：:Cancer Research UK has recently sponsored a meeting, organized by the UK Medical Research Council, on cancer drug resistance. Several of the molecular mechanisms responsible for this clinical outcome, such as DNA interstrand crosslink repair, apoptosis evasion, cytochrome P450 and P-glycoprotein, were discussed. There...
journal_title：British journal of cancer
pub_type：
doi：10.1038/sj.bjc.6602821
更新日期：2005-10-31 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
abstract：:The effect of LiCl on melanoma cell growth and differentiation was studied in mouse and human melanoma cell lines. LiCl markedly inhibited B16 and HT-144 melanoma cell growth in vitro. Clonogenicity in soft agar of the melanoma cells was also markedly inhibited by LiCl. Pretreatment of B16 mouse melanoma cells with Li...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1987.9
更新日期：1987-01-01 00:00:00
abstract：:Eleven groups of workers submitted a total of 21 bronchial tumour-associated antigen preparations and 19 antisera for comparative studies. Many of the antisera proved to be polyspecific despite absorption procedures. Most of the antigen preparations contained some material reactive towards a reference antiserum to nor...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.216
更新日期：1981-10-01 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:Tumour microenvironments can differ according to intratumoural locations. We investigated the immune status at different locations in primary tumours and its clinical significance in oesophageal squamous cell carcinoma (ESCC). METHODS:The number of CD8+ tumour-infiltrating immune cells (TIICs) and PD-1+ TII...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0622-3
更新日期：2020-02-01 00:00:00
abstract：BACKGROUND:There is clinical evidence to suggest that tumour necrosis factor-α (TNF-α) may be a therapeutic target in renal cell carcinoma (RCC). Multi-targeted kinase inhibitors, such as sorafenib and sunitinib, have become standard of care in advanced RCC. The anti-TNF-α monoclonal antibody infliximab and sorafenib h...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605889
更新日期：2010-10-12 00:00:00
abstract：:Following an i.p. dose of 150 mg x kg(-1) 5-fluorouracil (5-FU), drug uptake and metabolism over a 2-h period were studied by in vivo (19)F magnetic resonance spectroscopy (MRS) for the murine colon carcinoma lines C26-B (5-FU-insensitive; n=11) and C26-10 (5-FU-sensitive; n=15) implanted s.c. in Balb/C mice. Time cou...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601162
更新日期：2003-08-18 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：:Monoclonal antibodies 19-9 and C-50 were used to assay the cancer associated tumour antigens CA 19-9 and CA-50 in plasma from patients with confirmed pancreatic cancer, and related to the blood group and Lewis blood cell status. The plasma expressions of CA 19-9 or CA-50 were similar, including cases where the patient...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.241
更新日期：1990-07-01 00:00:00
abstract：:To design hybrid tumour necrosis factor-alpha (TNF-alpha) applicable to systemic anti-tumour therapeutic use, we assessed the relationships among the molecular size of hybrid TNF-alpha, in vitro bioactivity and in vivo anti-tumour potency. Natural human TNF-alpha was covalently modified with polyethylene glycol (PEG) ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.495
更新日期：1996-10-01 00:00:00
abstract：:The level of Gross cell-surface antigen (GCSAa) expression at the surface of murine retrovirus-infected fibroblasts was determined by quantitative absorption of the anti-GCSAa activity of a serum produced in syngeneic W/Fu rats immunized against (C58NT)D lymphoma, and tested in a cytotoxicity assay against E male G2 l...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.97
更新日期：1981-05-01 00:00:00
abstract：BACKGROUND:Gram-negative bacteria mediated gemcitabine resistance in pre-clinical models. We determined if intratumoural lipopolysaccharide (LPS) detection by immunohistochemistry is associated with outcome in advanced pancreatic ductal adenocarcinoma (PDAC) treated with gemcitabine and non-gemcitabine containing 1st-l...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-01029-7
更新日期：2020-10-01 00:00:00
abstract：:To evaluate current guidelines criteria for inclusion of women in special 'breast cancer family history' surveillance programmes, records were reviewed of women referred to Scottish breast cancer family clinics between January 1994 and December 2003 but discharged as at 'less than 'moderate' familial risk'. The Scotti...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究
doi：10.1038/sj.bjc.6604155
更新日期：2008-02-26 00:00:00
abstract：:Colorectal tumours from MYH polyposis patients display an excess of somatic G : C --> T : A transversions in the adenomatous polyposis coli gene. Here, we identify k-ras mutations in nine out of 54 (16.7%) MYH polyposis tumours. Their presence was associated with increased dysplasia and tubulovillous morphology (P=0.0...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601747
更新日期：2004-04-19 00:00:00
abstract：:To evaluate whether green tea consumption provides protection against stomach cancer, the relative risks (RRs) were calculated in the Japan Collaborative Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was based on 157 incident cases and 285 controls aged 40...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601512
更新日期：2004-01-12 00:00:00
abstract：:EWS-Fli-1, a fusion gene found in Ewing's sarcoma and primitive neuro-ectodermal tumour (PNET), encodes a transcriptional activator and promotes cellular transformation. We have made stable Ewing's sarcoma cells expressing antisense EWS-Fli-1 transcripts by transfecting the antisense EWS-Fli-1 expression plasmid. Thes...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.1998.0870
更新日期：2000-01-01 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:Placental-site trophoblastic (PSTT) and epithelioid trophoblastic tumours (ETT) are the rarest malignant forms of gestational trophoblastic disease (GTD). Our prior work demonstrated that an interval of ≥48 months from the antecedent pregnancy was associated with 100% death rate, independent of the stage. He...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0402-0
更新日期：2019-03-01 00:00:00
abstract：:Increases of individual beta tubulin isotypes in antimicrotubule drug resistant cell lines have been reported by several laboratories. We have previously described elevations in beta(III)and beta(IVa)isotypes in estramustine and paclitaxel resistant human prostate carcinoma cells. To investigate further the function o...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.1956
更新日期：2001-09-01 00:00:00
