Abstract：
BACKGROUND:There is growing evidence that spleen tyrosine kinase (SYK) is critical for acute myeloid leukaemia (AML) transformation and maintenance of the leukemic clone in AML patients. It has also been found to be over-expressed in AML patients, with activating mutations in foetal liver tyrosine kinase 3 (FLT3), particularly those with internal tandem duplications (FLT3-ITD), where it transactivates FLT3-ITD and confers resistance to treatment with FLT3 tyrosine kinase inhibitors (TKIs). METHODS:We have previously described a pharmacological approach to treating FLT3-ITD-positive AML that relies on proteasome-mediated FLT3 degradation via inhibition of USP10, the deubiquitinating enzyme (DUB) responsible for cleaving ubiquitin from FLT3. RESULTS:Here, we show that USP10 is also a major DUB required for stabilisation of SYK. We further demonstrate that degradation of SYK can be induced by USP10-targeting inhibitors. USP10 inhibition leads to death of cells driven by active SYK or oncogenic FLT3 and potentiates the anti-leukemic effects of FLT3 inhibition in these cells. CONCLUSIONS:We suggest that USP10 inhibition is a novel approach to inhibiting SYK and impeding its role in the pathology of AML, including oncogenic FLT3-positive AML. Also, given the significant transforming role SYK in other tumours, targeting USP10 may have broader applications in cancer.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Yang J,Meng C,Weisberg E,Case A,Lamberto I,Magin RS,Adamia S,Wang J,Gray N,Liu S,Stone R,Sattler M,Buhrlage S,Griffin JDdoi
10.1038/s41416-020-0731-zsubject
Has Abstractpub_date
2020-04-01 00:00:00pages
1175-1184issue
8eissn
0007-0920issn
1532-1827pii
10.1038/s41416-020-0731-zjournal_volume
122pub_type
杂志文章abstract：:Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. We report lymphocytic DPD data concerning a group of 53 patients (23 men, 30 women, mean age 58, range 36-73), treated by 5-FU-based chemotherapy in different French institutions and who developed unantic...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690098
更新日期：1999-02-01 00:00:00
abstract：BACKGROUND:Evasion of apoptosis contributes to the pathogenesis of solid tumours including non-small cell lung cancer (NSCLC). Malignant cells resist apoptosis through over-expression of inhibitor of apoptosis proteins (IAPs), such as X-linked IAP (XIAP). METHODS:A phenylurea-based small molecule inhibitor of XIAP, XI...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605418
更新日期：2010-01-05 00:00:00
abstract：:The aim of this study was to assess the cost-effectiveness of combination chemotherapy with paclitaxel/cisplatin, compared with standard etoposide/cisplatin in patients with advanced non-small cell lung cancer (NSCLC). We obtained the primary survival and resource utilization data from a large three-arm randomized tri...
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/sj.bjc.6690426
更新日期：1999-05-01 00:00:00
abstract：:With recent development in molecular biology, reverse transcriptase polymerase chain reaction (RT-PCR) has been applied to detect occult lymph node metastasis, but there have been few reports concerning oesophageal cancer. The objective of this study is to investigate the usefulness of the squamous cell carcinoma (SCC...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.1999.0938
更新日期：2000-01-01 00:00:00
abstract：BACKGROUND:Current evidence indicates that a stem cell-like sub-population within malignant glioblastomas, that overexpress members of the adenosine triphosphate-binding cassette (ABC) family transporters, is responsible for multidrug resistance and tumour relapse. Eradication of the brain tumour stem cell (BTSC) compa...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.188
更新日期：2013-05-28 00:00:00
abstract：:Oestrogen receptor protein (ER) was detected in 9 of 11 samples of malignant breast tissue and 8 of 9 samples of normal breast tissue. Levels of cytosolic ER (ERc) in malignant breast were 21-1102 fmol mg-1 soluble protein (Kd 1.8 X 10(-9)-3.1 X 10(-8) mol l-1) and those of nucleosolic ER (ERn), 13-526 fmol mg-1 solub...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1986.196
更新日期：1986-09-01 00:00:00
abstract：:Tumour angiogenesis is a complex multistep process regulated by a number of angiogenic factors. One such factor, platelet-derived endothelial cell growth factor has recently been shown to be thymidine phosphorylase (TP). TP catalyses the reversible phosphorylation of thymidine to deoxyribose-1-phosphate and thymine. A...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.49
更新日期：1996-02-01 00:00:00
abstract：:Immunofluorescent assessment of hormone receptors in melanocytic tumours is quite feasible without loss of diagnostic material, in contrast to the impracticability of quantitative biochemical assays. Using this method, oestrogen receptors were demonstrated in 4/6, and progesterone receptors in 3/5 patients with metast...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.95
更新日期：1981-05-01 00:00:00
abstract：BACKGROUND:Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias. METHODS:We pooled data from 39 Ovarian Cancer Association Con...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析
doi：10.1038/s41416-018-0011-3
更新日期：2018-04-01 00:00:00
abstract：:Photodynamic therapy (PDT) for cancer in the oesophagus and bronchi with red (630 nm) light may occasionally lead to wall perforation and fistula. Therefore, we investigated the clinical use of a less penetrating wavelength (514 nm) for the curative treatment of nine superficial carcinomas in the oesophagus and bronch...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.330
更新日期：1998-06-01 00:00:00
abstract：BACKGROUND:CA-125 as a tumour progression criterion in relapsing ovarian cancer (ROC) trials remains controversial. CALYPSO is a large randomised trial incorporating CA-125 (GCIG criteria) and symptomatic deterioration in addition to Response Evaluation Criteria in Solid Tumours (RECIST) criteria (radiological) to dete...
journal_title：British journal of cancer
pub_type： 杂志文章,随机对照试验
doi：10.1038/bjc.2011.593
更新日期：2012-02-14 00:00:00
abstract：:Eighty-two patients were randomly allocated to receive intravenous acyclovir 5 mg kg-1 t.d.s. for 23 days followed by oral acyclovir 800 mg 6-hourly for 6 months or matching placebos after allogeneic bone marrow transplantation. Herpes simplex and varicella zoster virus infections were significantly reduced during the...
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.1989.88
更新日期：1989-03-01 00:00:00
abstract：:In several phase II-trials encouraging tumour responses rates in advanced metastatic melanoma (stage IV; AJCC-classification) have been reported for the application of biochemotherapy containing interleukin 2. This study was designed to compare the efficacy of therapy with dacarbazine (DTIC) and interferon alpha (IFN-...
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：10.1054/bjoc.2001.1731
更新日期：2001-04-20 00:00:00
abstract：BACKGROUND:Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents. Patients who respond poorly to chemotherapy have a higher risk of metastatic disease and 5-year survival rates of only 10-20%. Therefore, identifying molecular targets that are specific for OS, or more specifically, metasta...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605723
更新日期：2010-06-29 00:00:00
abstract：:Id protein family consists of four members namely Id-1 to Id-4. Different from other basic helix-loop-helix transcription factors, they lack the DNA binding domain. Id proteins have been shown to be dysregulated in many different cancer types and their prognostic value has also been demonstrated. Recently, Id-1 has be...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604035
更新日期：2007-11-19 00:00:00
abstract：:Isomerisation to all-trans-retinoic acid (ATRA) is widely accepted as the key mechanism underlying the favourable clinical properties of 13-cis-retinoic acid (13cisRA). As intracellular metabolism of ATRA by CYP26 may result in clinical resistance to 13cisRA, an increase in efficacy may be achieved through modulation ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603779
更新日期：2007-06-04 00:00:00
abstract：:Following relapse on endocrine therapy for advanced, hormone receptor-positive breast cancer, it is common for patients to experience responses to alternative endocrine agents. Fulvestrant ('Faslodex') is a new type of endocrine treatment--an oestrogen receptor (ER) antagonist with no agonist effects. Fulvestrant down...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6601632
更新日期：2004-03-01 00:00:00
abstract：:We have analysed DNA extracted from the serum and peritoneal fluid of 20 ovarian cancer patients for the presence of tumour-specific genetic alterations. The 20 patients included six with stage Ia disease. Using six polymorphic microsatellite loci we were able to detect novel alleles or loss of heterozygosity in 17/20...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690601
更新日期：1999-08-01 00:00:00
abstract：:Insulin-like growth factor-1 (IGF-1) has been described as an important factor in proliferation, cell survival and migration of multiple myeloma (MM) cells. Angiogenesis correlates with development and prognosis of the MM disease. Vascular endothelial growth factor (VEGF) is one of the prominent factors involved in th...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601613
更新日期：2004-03-08 00:00:00
abstract：:Histochemical studies on the cell surface and intercellular matrix of normal cervical epithelium, and squamous cell carcinomata have shown the mucosubstances present may be symbolized by the descriptive formula:C(G) mucosubstance; B 3.5; A 2.5 (0.6m MgCl(2)); T; S.This indicates that sulphate groups are absent and tha...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1970.88
更新日期：1970-12-01 00:00:00
abstract：:To evaluate the impact of prior adjuvant chemotherapy on response rate (RR), progression-free (PFS) and overall survival (OS) of metastatic breast cancer patients treated with epirubicin/paclitaxel (ET) regimens. In all, 291 patients enrolled in five studies in metastatic breast cancer were analysed: 101 (35%) were ch...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601634
更新日期：2004-03-08 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600340
更新日期：2002-06-05 00:00:00
abstract：:Neuroendocrine tumours (NETs) comprise a heterogenous group of malignancies with an often unpredictable course, and with limited treatment options. Thus, new diagnostic, prognostic, and therapeutic markers are needed. To shed new lights into the biology of NETs, we have by cDNA transcript profiling, sought to identify...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604565
更新日期：2008-10-21 00:00:00
abstract：:The author Sara Lonardi was incorrectly listed as Sara Leonardi. The correct name is listed above. ...
journal_title：British journal of cancer
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41416-018-0067-0
更新日期：2018-06-01 00:00:00
abstract：BACKGROUND:Metastatic clear cell renal cell carcinoma (ccRCC) patients have <9% 5-year survival rate, do not respond well to targeted therapy and eventually develop resistance. A better understanding of molecular pathways of RCC metastasis is the basis for the discovery of novel prognostic markers and targeted therapie...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.828
更新日期：2014-03-04 00:00:00
abstract：:The evolution and structure of adenomatous polyps and adenocarcinomata of the colon in NMRI mice induced by dimethylhydrazine are described. Severe toxic reactions in the liver and other organs are produced by dimethylhydrazine (DMH), but tumours are induced only in the colon and around the anus. The 100% incidence an...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1973.183
更新日期：1973-12-01 00:00:00
abstract：BACKGROUND:Lapatinib, a dual EGFR and HER2 inhibitor has shown disappointing results in clinical trials of metastatic oesophago-gastric adenocarcinomas (OGAs), and in vitro studies suggest that MET, IGFR, and HER3 confer resistance. This trial applied Lapatinib in the curative neoadjuvant setting and investigated the f...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1038/bjc.2015.342
更新日期：2015-11-03 00:00:00
abstract：:The levels of CA 242, a new tumour marker of carbohydrate nature, were measured in sera of 185 patients with malignancies of the digestive tract and of 123 patients with benign digestive tract diseases. High percentages of elevated CA 242 levels (greater than 20 U ml-1) were recorded in patients with pancreatic and bi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.146
更新日期：1991-04-01 00:00:00
abstract：BACKGROUND:A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting. METHODS:Patients with unresectable and/or r...
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/bjc.2012.222
更新日期：2012-06-26 00:00:00
abstract：:This corrects the article DOI: 10.1038/bjc.2017.85. ...
journal_title：British journal of cancer
pub_type： 杂志文章,已发布勘误
doi：10.1038/bjc.2017.437
更新日期：2018-03-20 00:00:00
