Abstract：
BACKGROUND:Panobinostat, a pan-deacetylase inhibitor, overcomes imatinib resistance in preclinical models of gastrointestinal stromal tumours (GIST). Here we determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of panobinostat in combination with imatinib (IM) for treatment of patients with refractory GIST. METHODS:Following a 7-day run-in phase of IM (400 mg per day), escalating doses of panobinostat were added following a '3 plus 3' design. Twelve heavily pretreated GIST patients were enrolled in two dose levels. RESULTS:Most common adverse events were thrombocytopenia, anaemia, fatigue, creatinine elevation, nausea, emesis and diarrhoea. Twenty micrograms of panobinostat and 400 mg IM were declared the MTD. Pharmacologically active concentrations of panobinostat and IM were achieved as evidenced by histone H3 acetylation in blood mononuclear cells in vivo and inhibition of the IM-resistant KIT (D816) mutation in vitro. In FDG-PET-CT scans after IM run-in and following 3 weeks panobinostat treatment, 1 out of 11 evaluable patients showed a metabolic partial response, 7 patients were metabolically stable and 3 patients progressed. Longest treatment duration was 17 weeks (median 6). CONCLUSION:Panobinostat and IM can be administered at doses achieving target inhibition in vivo. Further clinical exploration of patients with treatment-refractory GIST is warranted. Correlative studies in this trial may help to optimise dosing schedules in GIST.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Bauer S,Hilger RA,Mühlenberg T,Grabellus F,Nagarajah J,Hoiczyk M,Reichardt A,Ahrens M,Reichardt P,Grunewald S,Scheulen ME,Pustowka A,Bock E,Schuler M,Pink Ddoi
10.1038/bjc.2013.826subject
Has Abstractpub_date
2014-03-04 00:00:00pages
1155-62issue
5eissn
0007-0920issn
1532-1827pii
bjc2013826journal_volume
110pub_type
杂志文章abstract：:Question prompt lists (QPLs) have been shown to be an inexpensive and effective communication tool for patients in oncology consultations. We aimed to develop and pilot a QPL for palliative care (PC) patients. In order to identify suitable questions for inclusion in the QPL, we conducted focus groups and individual in...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601380
更新日期：2003-12-01 00:00:00
abstract：BACKGROUND:Tumour heterogeneity is documented for many characters, including the production of growth factors, one of the hallmarks of cancer. What maintains heterogeneity remains an open question that has implications for diagnosis and treatment, as drugs that target growth factors are susceptible to the evolution of ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.336
更新日期：2013-08-20 00:00:00
abstract：:In a population-based, matched, case-control study from southern Sweden of 571 patients with a first diagnosis of cutaneous malignant melanoma and 913 healthy controls aged 16-80 years, the association between sunbed use and malignant melanoma was evaluated. A total of 250 (44%) cases and 372 (41%) controls reported e...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.1999.1181
更新日期：2000-05-01 00:00:00
abstract：:A previous publication (Leith et al., 1992) showed that administration of basic fibroblast growth factor (FGF-2, 0.25 mg kg-1, q.i.d. x 7) to mice bearing xenografted DLD-2 human colon cancers would increase treated tumour growth rates as compared to control neoplasms. Additionally, at the end of the 7 day treatment p...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.418
更新日期：1993-10-01 00:00:00
abstract：BACKGROUND:Oestrogen (E2) induces apoptosis in long-term E2-deprived MCF7 cells (MCF7:5C). Taxanes have been used extensively in the treatment of early and advanced breast cancer. We have interrogated the sequence of events that involve the apoptotic signalling pathway induced by E2 in comparison with paclitaxel. METH...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.50
更新日期：2014-03-18 00:00:00
abstract：BACKGROUND:Cellular Dissociation Grade (CDG) composed of tumour budding and cell nest size has been shown to independently predict prognosis in pre-therapeutic biopsies and primary resections of oesophageal squamous cell carcinoma (ESCC). Here, we aimed to evaluate the prognostic impact of CDG in ESCC after neoadjuvant...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0623-2
更新日期：2019-12-01 00:00:00
abstract：:Metastatic variant sublines of the murine large-cell lymphoma cell line RAW117 were tested for their growth and migration properties in vitro in medium conditioned by soluble factors released from syngeneic mouse liver-, lung-, and brain-derived microvessel endothelial cells. Medium conditioned with hepatic sinusoidal...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.269
更新日期：1992-08-01 00:00:00
abstract：:DBA/2J mice bearing a clonal isolate of the transplantable murine lymphocytic leukaemia line P388 were used to examine the effects of L-histidinol on the antitumour activity of three alkalyating agents (bis-chloroethylnitrosourea (BCNU), cis-diamminedichloroplatinum (II) (cisDDP) and cyclophosphamide) and the antitumo...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.333
更新日期：1989-11-01 00:00:00
abstract：BACKGROUND:Abiraterone and enzalutamide are novel endocrine treatments that abrogate androgen receptor (AR) signalling in castration-resistant prostate cancer (CRPC). Here, we developed a circulating tumour cells (CTCs)-based assay to evaluate AR expression in real-time in CRPC and investigated nuclear AR expression in...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2015.63
更新日期：2015-03-31 00:00:00
abstract：:We assessed incidence and mortality of colorectal cancer (CRC) at various ages among women and men in 38 European countries. The ages at which defined levels of incidence and mortality were reached varied between 9 and 17 years between countries. This variation requires consideration in the definition of screening gui...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604488
更新日期：2008-08-05 00:00:00
abstract：BACKGROUND:Cervical cancer screening coverage remains insufficient in most countries. Our objective was to assess whether in-home vaginal self-sampling with a dry swab for high-risk human papillomavirus (HR-HPV) testing is effective and cost-effective in increasing participation in cervical cancer screening. METHODS:I...
journal_title：British journal of cancer
pub_type： 杂志文章,随机对照试验
doi：10.1038/bjc.2014.510
更新日期：2014-11-25 00:00:00
abstract：:Mechanisms of resistance to Tomudex include increased thymidylate synthase activity, as well as reduced intracellular drug uptake and polyglutamation. However, little is known about other mechanisms of resistance, such as a possible protection against Tomudex-induced apoptosis mediated by bcl-2. We transfected the MDA...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690685
更新日期：1999-09-01 00:00:00
abstract：:Diffuse invasion of the brain, an intrinsic property of gliomas, renders these tumours incurable, and is a principal determinant of their spatial and temporal growth. Knowledge of the invasive potential of gliomas is highly desired in order to understand their behaviour in vivo. Comprehensive ex vivo invasion studies ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602048
更新日期：2004-08-16 00:00:00
abstract：:Tumour angiogenesis is essential for progression of solid tumours and constitutes an interesting target for therapy. However, impaired tumour blood supply may also be an important obstacle for treatment by radiotherapy and chemotherapy. Estramustine has been shown to increase tumour blood flow and potentiate the effec...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690333
更新日期：1999-04-01 00:00:00
abstract：:Collagen breakdown, and thus bone resorption, can now be assessed by measuring the urinary excretion of the collagen crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd). In a pilot study we measured Pyd and Dpd in 20 patients with breast cancer, ten with known bone metastases and ten with no recognised metastas...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.419
更新日期：1991-11-01 00:00:00
abstract：:Findings in humans and animal models suggest that in utero hormonal and dietary exposures increase later breast cancer risk. Since alcohol intake by adult women consistently increases their breast cancer risk, we wondered whether maternal alcohol consumption during pregnancy increases female offspring's mammary tumori...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601793
更新日期：2004-06-01 00:00:00
abstract：BACKGROUND:We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy. ME...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.306
更新日期：2014-08-26 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：:Anti-vascular effects of the novel Vinca alkaloid, vinflunine have been investigated in the MAC 15A transplantable murine colon adenocarcinoma model and compared with those induced by the most recently identified clinically useful third generation Vinca. Administration of the maximum tolerated dose of either vinflunin...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1587
更新日期：2001-01-01 00:00:00
abstract：:This single-centre phase I trial was designed to determine the maximum tolerated dose of irinotecan and the recommended dose to use in combination with a fixed dose of 5-fluorouracil (5-FU) administered as a protracted venous infusion, for the first-line treatment of metastatic colorectal cancer (CRC). Tolerability an...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjc.6602173
更新日期：2004-10-18 00:00:00
abstract：:The association between Ki-ras mutations and proliferation activity was investigated in a comprehensive series of biliary tract carcinomas (BTCs). We precisely microdissected samples of tissue from paraffin-embedded sections of 77 BTCs including 22 intrahepatic cholangiocarcinomas (ICCs), 36 extrahepatic cholangiocarc...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.459
更新日期：1996-09-01 00:00:00
abstract：BACKGROUND:Lignans - oestrogenic substances present in various foods - are associated with postmenopausal breast cancer risk, but not much is known regarding their effects on survival. METHODS:In a follow-up study of 2653 postmenopausal breast cancer patients diagnosed between 2001 and 2005, vital status and causes of...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.374
更新日期：2011-10-11 00:00:00
abstract：BACKGROUND:We performed a retrospective nationwide study to explore age as a prognostic factor in synovial sarcoma patients. METHODS:Data on 613 synovial sarcoma patients were obtained from the Netherlands Cancer Registry. The prognostic relevance of age groups (children, adolescent and young adults (AYAs), adults, an...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2015.375
更新日期：2015-12-01 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：:An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602040
更新日期：2004-08-31 00:00:00
abstract：BACKGROUND:Four-and-a-half LIM domains protein 2 (FHL2) is a component of the focal adhesion structures and has been suggested to have a role in cancer progression. It has been shown to be overexpressed in the colorectal cancer (CRC). METHODS:Here, we examined a possible prognostic value of FHL2 in CRC. Immunohistoche...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.290
更新日期：2013-07-09 00:00:00
abstract：:We retrospectively analysed neuromuscular toxicity associated with paclitaxel 210 mg m(-2) given by 3-h infusion in 247 patients. The severity correlated significantly with total cumulative dose, but could not be predicted by the pretreatment clinical variables or by pharmacokinetic parameters. The toxicity tended to ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.278
更新日期：1998-05-01 00:00:00
abstract：:To investigate whether parents of children with congenital malformations more often developed cancer after birth of the child, a population-based case-control study in Denmark was undertaken. By linking the Cancer Registry with the Central Population Registry, we identified 8783 cancer patients having their first chil...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600488
更新日期：2002-08-27 00:00:00
abstract：:Birth size of a woman has been positively associated with her breast cancer risk, particularly before menopause, but no study has investigated neonatal growth in relation to this risk. We conducted a case-control study nested within a population-based cohort of women, born in Sweden between 1901 and 1961, covering all...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604702
更新日期：2008-11-04 00:00:00
abstract：:A urinary gonadotrophin peptide (UGP) was isolated and purified from semi-purified human chorionic gonadotrophin (hCG), prepared from pregnancy urine. The peptide showed hCG-B subunit activity and no hCG-alpha subunit activity as demonstrated by binding studies with the relevant antibodies. It had a molecular weight s...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.204
更新日期：1988-09-01 00:00:00
