Abstract：
BACKGROUND:We previously reported that chaetocin has potent and selective anti-myeloma activity attributable to reactive oxygen species (ROS) induction imposed by inhibition of the redox enzyme thioredoxin reductase; we now detail its effects in solid tumours. METHODS:Cellular assays, transcriptional profiling and the NCI60 screen were used to assess the effects of chaetocin in solid tumour and endothelial cells. RESULTS:NCI-60 screening demonstrated chaetocin to even more potently inhibit proliferation in solid tumour than in haematological cell lines; transcriptional profiling revealed a signature consistent with induction of inflammatory response and cell death pathways. Chaetocin induced ROS, oxidative damage to cellular proteins and apoptosis, with 2-10 nM IC(50)s (24 h exposures) in all tested solid tumour cell lines. The pan-caspase inhibitor zVAD-fmk did not block chaetocin-induced cell death despite inhibiting mitochondrial membrane depolarisation and apoptosis. Further, Molt-4 rho(0) cells lacking metabolically functional mitochondria were readily killed by chaetocin; in addition chaetocin-induced cytotoxicity was unaffected by autophagy inhibitors or hypoxia and consequent HIF-1α upregulation. Moreover, chaetocin inhibited SKOV3 ovarian cancer xenografts producing less vascular tumours, and inhibited human umbilical vein endothelial cell proliferation. CONCLUSION:Chaetocin has intriguing and wide-ranging in vitro and in vivo anticancer effects, and is an attractive candidate for further preclinical and clinical development.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Isham CR,Tibodeau JD,Bossou AR,Merchan JR,Bible KCdoi
10.1038/bjc.2011.522subject
Has Abstractpub_date
2012-01-17 00:00:00pages
314-23issue
2eissn
0007-0920issn
1532-1827pii
bjc2011522journal_volume
106pub_type
杂志文章abstract：:The aim of this study was to find a procedure allowing estimation of individual pharmacokinetic parameters for adriamycin with minimal cost and disturbance for the patient. Twenty-five patients with breast cancer were treated by short infusion of adriamycin at a dose of 12 mg m-2 week-1 (41 courses). Population charac...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.226
更新日期：1989-07-01 00:00:00
abstract：:Recent studies indicate that cancer antigen 125 (CA125) response criteria tend to overestimate a tumour reduction measured by standard WHO response criteria in recurrent epithelial ovarian carcinoma. The aim of the study was to validate the recently introduced GCIG (The Gynaecological Cancer Intergroup) CA125 response...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjc.6601501
更新日期：2004-01-26 00:00:00
abstract：:The aims of this study were to identify prognostic variables for toxicity and survival in patients with cancer participating in phase I clinical trials and compare characteristics of those treated with cytotoxic chemotherapy (CT) and non-cytotoxic drugs (non-CT). Data were collected from 420 (114 CT, 306 non-CT) patie...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601218
更新日期：2003-10-06 00:00:00
abstract：BACKGROUND:There are currently two million cancer survivors in the United Kingdom, and in recent years this number has grown by 3% per annum. The aim of this paper is to provide long-term projections of cancer prevalence in the United Kingdom. METHODS:National cancer registry data for England were used to estimate can...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.366
更新日期：2012-09-25 00:00:00
abstract：:A phase I study of the bispecific antibody MDX-H210 in combination with granulocyte colony-stimulating factor (G-CSF) was performed in stage IV breast carcinoma patients, overexpressing HER-2/neu. MDX-H210, constructed by crosslinking antigen binding fragments (F(ab') fragments) of monoclonal antibody (mAb) H22 to Fc ...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjc.6601367
更新日期：2003-12-15 00:00:00
abstract：:Cancer-associated fibroblasts (CAFs) were originally presumed to represent a homogeneous population uniformly driving tumorigenesis, united by their morphology and peritumoural location. Our understanding of CAFs has since been shaped by sophisticated in vitro and in vivo experiments, pathological association and, mor...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/s41416-019-0509-3
更新日期：2019-08-01 00:00:00
abstract：:We have recently reported the activation of a new oncogene in human papillary thyroid carcinomas. This oncogene, named PTC, is a novel rearranged version of the ret proto-oncogene. In fact PTC is the product of the fusion of the tyrosine kinase domain of the ret proto-oncogene with the 5'-terminal region of another ge...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.416
更新日期：1992-12-01 00:00:00
abstract：:Nuclear polyploidization in the livers of CF-1 mice, exposed to dieldrin (0, 1, 5 and 10 ppm in the diet), was studied up to the median time of liver tumour development (ranging from 15 to 27 months) in the respective treatment groups. In untreated controls nuclear polyploidization is characterized by a linear increas...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.160
更新日期：1988-07-01 00:00:00
abstract：:Serum levels of cell-free interleukin-2 receptors were elevated above normal in mice bearing the IL-2R positive T-cell lymphoma Eb or its highly metastatic variant ESb. Although ESb cells expressed less IL-2R molecules than Eb cells on their cell surface, serum receptor levels were raised more quickly in ESb than in E...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1987.119
更新日期：1987-06-01 00:00:00
abstract：:O6-benzylguanine (O6-BG) and 3-aminobenzamide (3-AB) inhibit the DNA repair proteins O6-alkylguanine-DNA alkyltransferase (AGT) and poly(ADP-ribose) polymerase (PARP) respectively. The effect of O6-BG and/or 3-AB on temozolomide and 1,3-bis(2-chloroethyl)-nitrosourea (BCNU) cytotoxicity, was assessed in seven human tu...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.485
更新日期：1996-10-01 00:00:00
abstract：:High-level microsatellite instability (MSI-H) in colorectal cancer accounts for about 12% of colorectal cancers and is typically associated with a dense infiltration with cytotoxic CD8-positive lymphocytes. The role of regulatory T cells that may interfere with the host's antitumoural immune response in MSI-H colorect...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604756
更新日期：2008-12-02 00:00:00
abstract：BACKGROUND:Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensives. Recently, these drugs have been associated with a protective effect against pancreatic cancer, but data on this putative association remain limited. Thus, the objective of this study...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.375
更新日期：2017-01-03 00:00:00
abstract：:The incidence of Kaposi's sarcoma (KS) in 1976-90 was assessed in Italy, taking advantage of a network of nine population-based cancer registries covering, at its maximum, approximately 5.6 million subjects. The first examined period (1976-84) substantially reflects the epidemiology of KS prior to the AIDS epidemic in...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.60
更新日期：1994-02-01 00:00:00
abstract：:Endosialin is a transmembrane glycoprotein selectively expressed in blood vessels and stromal fibroblasts of various human tumours. It has been functionally implicated in angiogenesis, but the factors that control its expression have remained unclear. As insufficient delivery of oxygen is a driving force of angiogenes...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604685
更新日期：2008-10-21 00:00:00
abstract：BACKGROUND:Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast can...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.44
更新日期：2011-03-15 00:00:00
abstract：BACKGROUND:There are phase 3 clinical trials underway evaluating anti-PD-L1 antibodies as adjuvant (postoperative) monotherapies for resectable renal cell carcinoma (RCC) and triple-negative breast cancer (TNBC); in combination with antiangiogenic VEGF/VEGFR2 inhibitors (e.g., bevacizumab and sunitinib) for metastatic ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-018-0297-1
更新日期：2019-01-01 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：BACKGROUND:Evidence suggests that dysregulation of energy-sensing pathways closely associates with renal cell carcinoma (RCC) development. The metabolic regulation is largely controlled by 5'-AMP activated protein kinase (AMPK) which is activated through phosphorylation by LKB1. METHODS:The expression of LKB1 was dete...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.574
更新日期：2013-02-05 00:00:00
abstract：OBJECTIVE:Detection of lymph node involvement in women with IB2-IIB cervical cancer could have a positive effect on survival. We set out to evaluate the incidence of pelvic and/or para-aortic lymph node involvement using the sentinel node (SN) biopsy and its impact on survival. METHODS:From 2002 to 2010, 66 women with...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.541
更新日期：2012-01-03 00:00:00
abstract：:Human topoisomerase II enzymes are targets for a number of widely used anticancer agents. We have analysed a lung adenocarcinoma cell line CALU3, which has co-amplified topoisomerase II alpha and ERBB2 sequences, for the structure of the amplicon and for expression of both topoisomerase II alpha and beta. The region o...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.430
更新日期：1993-10-01 00:00:00
abstract：:There is evidence that patients living in outlying areas have poorer survival from cancer. This study set out to investigate whether they have more advanced disease at diagnosis. Case notes of 1323 patients in north and northeast Scotland who were diagnosed with lung or colorectal cancer in 1995 or 1996 were reviewed....
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1708
更新日期：2001-04-06 00:00:00
abstract：:Palliative chemotherapy for inoperable/metastatic oesophageal cancer has limited activity. This study assesses the feasibility and activity of gemcitabine and cisplatin in this group of patients. In total, 42 patients with locally advanced/metastatic squamous or adenocarcinoma of the oesophagus were treated with gemci...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602842
更新日期：2005-11-14 00:00:00
abstract：:The tolerability, anti-tumour activity and pharmacokinetic interaction of high-dose intravenous cyclosporin combined with intravenous etoposide was evaluated in children. Eighteen patients with recurrent or refractory tumours, all of whom had previously received etoposide, were treated with a combination of high-dose ...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1998.383
更新日期：1998-06-01 00:00:00
abstract：BACKGROUND:The need to unfold the underlying mechanisms of lung cancer aggressiveness, the deadliest cancer in the world, is of prime importance. Because Fas-associated death domain protein (FADD) is the key adaptor molecule transmitting the apoptotic signal delivered by death receptors, we studied the presence and cor...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.196
更新日期：2012-06-05 00:00:00
abstract：:The present study was designed in order to evaluate the response rate and the toxicity of continuous infusion of Interleukin 2 (IL2) in patients over 65 with metastatic renal cell carcinoma. Twenty-five patients, median age 69 (range 65-77), without any prior systemic anticancer therapy received a continuous infusion ...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1992.152
更新日期：1992-05-01 00:00:00
abstract：:Increased fibre intake has been shown to reduce serum oestrogen concentrations. We hypothesized that fibre exerts this effect by decreasing the time available for reabsorption of oestrogens in the colon. We tested this in volunteers by measuring changes in serum oestrogen levels in response to manipulation of intestin...
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.1997.397
更新日期：1997-01-01 00:00:00
abstract：BACKGROUND:Transarterial chemo-embolisation (TACE) is recommended for patients with BCLC intermediate stage hepatocellular carcinoma (stage B), particularly in patients with good underlying liver function and minimal symptoms. The hepatoma arterial embolisation prognostic (HAP) score combines measures of liver function...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.423
更新日期：2017-02-14 00:00:00
abstract：:Primary liver cancer (PLC) incidence trends from Africa are unknown. Using Kampala Cancer Registry data from 1960 to 1980 and 1991 to 2005, we identified 771 PLCs. Although rates were stable among men, PLC incidence among women increased >50%. Investigations of viral hepatitis, aflatoxin, obesity, and human immunodefi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604893
更新日期：2009-03-10 00:00:00
abstract：:Neurofilaments (NFs) are specific intermediate filaments to neural cells. Mammalian NFs are protein triplets composed of three major subunits with respective molecular weights of approximately 70, 150 and 200 kD. Using an immunohistochemical method, 13 carcinoid tumours from different sites were examined for the prese...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.161
更新日期：1991-05-01 00:00:00
abstract：:The presence of a mononuclear cell reaction to 41 gestational choriocarcinomata, 10 invasive moles and 13 malignant trophoblastic teratomata has been investigated. The intensity of the reaction was graded; there was a significantly better response to therapy and survival rate in those with a "severe" cellular reaction...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1973.144
更新日期：1973-09-01 00:00:00
