Abstract:
:The acute toxicity, pharmacokinetics and hypoxic cytotoxicity of RSU-1069 were investigated using the subcutaneous (sc) rat 9L tumour model. The pharmacokinetics were studied after i.p. injection of RSU-1069 (20 mg kg-1 or 100 mg kg-1). For both doses, the elimination of RSU-1069 followed first-order kinetics in both plasma and unclamped tumours. After 100 mg kg-1, the peak plasma concentration of RSU-1069 was 40 micrograms ml-1; the elimination t1/2 was 39.3 +/- 11.1 min. After 20 mg kg-1, the peak plasma concentration was 3 micrograms ml-1; the elimination t1/2 was 47.8 +/- 6.3 min. In unclamped tumours, the peak concentration was 50 micrograms g-1 with an elimination t1/2 of 36.1 +/- 9.6 min for the 100 mg kg-1 dose, and 4 micrograms g-1 with an elimination t1/2 of 41.9 +/- 6.1 min for the 20 mg kg-1 dose. The tumour and plasma elimination half-times were not significantly different (P greater than 0.2) for the two doses. Clamping the tumour 30 min after administration of 100 mg kg-1 of RSU-1069 decreased the tumour elimination t1/2 to 10.9 +/- 1.4 min. After releasing the clamp, RSU-1069 returned rapidly to the unclamped tumour concentration. The unclamped tumour/plasma ratio reached a maximum of 4-6, then decreased to a constant value of about 2 for both doses, indicating that RSU-1069 accumulates in these 9L tumours. RSU-1069 kills hypoxic sc 9L cells more efficiently than oxic sc 9L cells; at a surviving fraction of 0.5, the SER was 4.8. For in vitro 9L cells, the SER was approximately 50 when the comparison was between those treated in 2.1% 0(2) and those treated in less than 7.5 x 10(-3)% 0(2); it was approximately 100 when the comparison was between those treated in 21% 0(2) and those treated in less than 7.5 x 10(-3)% 0(3). Tumours treated with RSU-1069 and clamped for various times exhibited biphasic cell-kill kinetics; at 50 mg kg-1, little additional cell kill was achieved after 40 min of clamping. Our data also indicate that RSU-1069 is 300-1000 fold more efficient than misonidazole or SR2508 for killing hypoxic sc 9L tumour cells in situ.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Wong KH,Koch CJ,Wallen CA,Wheeler KTdoi
10.1038/bjc.1991.116subject
Has Abstractpub_date
1991-04-01 00:00:00pages
484-8issue
4eissn
0007-0920issn
1532-1827journal_volume
63pub_type
杂志文章abstract::This is the first study to investigate the associations of IGF-1, IGF-2 and IGFBP-3 concentrations with the risk of colorectal cancer in prospectively collected blood samples from an Oriental population. Between 1986 and 1989 serum samples were collected at baseline from 18 244 men, aged 45-65 years, without a history...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.2172
更新日期:2001-11-30 00:00:00
abstract::We evaluated animal food intake and cooking methods in relation to endometrial cancer risk in a population-based case-control study in Shanghai, China. A validated food frequency questionnaire was used to collect the usual dietary habits of 1204 cases and 1212 controls aged 30-69 years between 1997 and 2003. Statistic...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603458
更新日期:2006-12-04 00:00:00
abstract:BACKGROUND:Novel treatment strategies in Ewing sarcoma include targeted cellular therapies. Preclinical in vivo models are needed that reflect their activity against systemic (micro)metastatic disease. METHODS:Whole-body magnetic resonance imaging (WB-MRI) was used to monitor the engraftment and dissemination of human...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.356
更新日期:2013-08-06 00:00:00
abstract::Circulating serum factors have been said to abrogate the effects of immune response in cancer, i.e. "blocking" and "antigenic inhibition". The aim of this investigation was to isolate such specific factors in a purified and native state. F(ab)2 fragments isolated from hypernephroma were insolubilized on the surfaces o...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.279
更新日期:1975-12-01 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:BACKGROUND:New therapeutic options for metastatic pancreatic cancer are urgently needed. In pancreatic cancer, overexpression of the epidermal growth factor receptor 2 (HER2) has been reported in up to 45%. This multicentre phase II study investigated the efficacy and toxicity of the HER2 antibody trastuzumab combined ...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2012.18
更新日期:2012-03-13 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:BACKGROUND:Previous epidemiologic studies have shown inconsistent results for the association between alcohol intake and endometrial cancer risk. Most of the studies, however, assessed alcohol intake after cancer diagnosis, or measured alcohol intake at baseline only. METHODS:We prospectively examined the association ...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2014.257
更新日期:2014-07-08 00:00:00
abstract:BACKGROUND:Systemic inflammation measured by the neutrophil-to-lymphocyte ratio (NLR), leucocyte-to-lymphocyte ratio (LLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and CRP/albumin ratio (CRP/Alb) was shown to impact the survival prognosis in patients with extracranial solid cancer. METHO...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-01254-0
更新日期:2021-01-21 00:00:00
abstract::It has been reported that the rho genes, which consist of a ras-related small GTPase protein family, regulate cytoskeletal structures and have the potential to transform cultured cells. To investigate the biological relevance of the rho genes in pancreatic carcinogenesis, we examined expressions of the rhoA, B and C g...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.23
更新日期:1998-01-01 00:00:00
abstract::In addition to the direct targeting effects on HER2-positive cells, trastuzumab may have a therapeutic role modulating the activity of the cellular immune system in patients with breast cancer. To investigate this further, the balance of T-regulatory (T(reg)), Th17, natural killer (NK) and NK T (NKT) cells before, dur...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604963
更新日期:2009-04-07 00:00:00
abstract:BACKGROUND:There is a need for sensitive and specific blood-borne markers for the detection of gastric cancer. Raised serum macrophage inhibitory factor (MIF) levels have been proposed as a marker for gastric cancer diagnosis but, to date, studies have only encompassed patients from high-incidence areas. METHODS:We ha...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.405
更新日期:2012-10-23 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:BACKGROUND:A Population-Based Cancer Registry (PBCR) was set up in Sikkim (a state in the North Eastern India) in 2003. We examined incidence rates by ethnic groups from 2003-2008. METHODS:Age-adjusted incidence rates (AARs) per 100,000 person-years were calculated by direct method using the world standard population,...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.598
更新日期:2012-02-28 00:00:00
abstract::Exploring the fundamental mechanisms behind the low tumour uptake of labelled monoclonal antibodies (MoAbs) during in vivo immunotargeting, experiments were performed to estimate the in vivo value of the association constant (Ka) in an experimental targeting reaction. An artificial tumour model was utilised, based on ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.219
更新日期:1992-07-01 00:00:00
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 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:BACKGROUND:Congenital anomalies have been found more often in children with cancer than in those without. Rib abnormalities (RAs) have been associated with childhood cancer; however, studies have differed in the type of RAs and cancers implicated. METHODS:Rib abnormalities were assessed predominantly by X-ray in a hos...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.366
更新日期:2011-10-25 00:00:00
abstract:BACKGROUND:Thyroid function has been suggested to interfere with tumour biology and prognosis in different cancers. The present study was performed to investigate the impact of pre-therapeutic serum thyroid-stimulating hormone (TSH) levels on the prognosis of patients with endometrial cancer. METHODS:Pre-therapeutic s...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2013.282
更新日期:2013-07-09 00:00:00
abstract:BACKGROUND:We previously showed that activation of the nuclear factor of activated T cells (NFAT)1/Fas ligand (FasL) pathway induces glioma cell death. Lithium (Li) is an inhibitor of glycogen synthase kinase (GSK)-3 that activates NFAT1/FasL signalling. Temozolomide (TMZ) inhibits GSK-3 and activates Fas in tumour pro...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.89
更新日期:2017-05-09 00:00:00
abstract:BACKGROUND:Ewing sarcoma is a paradigm of solid tumour -bearing chromosomal translocations resulting in fusion proteins that act as deregulated transcription factors. Ewing sarcoma translocations fuse the EWS gene with an ETS transcription factor, mainly FLI1. Most of the EWS-FLI1 target genes still remain unknown and ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605104
更新日期:2009-07-07 00:00:00
abstract::Ductal carcinoma in situ (DCIS) now represents 20-25% of all 'breast cancers' consequent upon detection by population-based breast cancer screening programmes. Currently, all DCIS lesions are treated, and treatment comprises either mastectomy or breast-conserving surgery supplemented with radiotherapy. However, most D...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/s41416-019-0478-6
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:Based on the microRNA (miRNA) signature of bladder cancer (BC) by deep sequencing, we recently found that several double-stranded mature miRNAs derived from the same pre-miRNAs were sufficiently expressed and acted as tumour suppressors by regulating common target genes in BC. Our deep-sequencing signature o...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.43
更新日期:2017-04-11 00:00:00
abstract:BACKGROUND:The germline BRCA2 mutation is associated with increased prostate cancer (PrCa) risk. We have assessed survival in young PrCa cases with a germline mutation in BRCA2 and investigated loss of heterozygosity at BRCA2 in their tumours. METHODS:Two cohorts were compared: one was a group with young-onset PrCa, t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605822
更新日期:2010-09-07 00:00:00
abstract::Seventy three children with rhabdomyosarcoma were treated by members of the Children's Solid Tumour Group during the period, 1974-1981. The extent of disease at diagnosis was found to be the major influence affecting outcome. Children with tumours confined to the tissue of origin with no evidence of nodal or metastati...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.175
更新日期:1983-08-01 00:00:00
abstract::Broad-spectrum neuropeptide growth factor antagonists, such as [D-Arg1, D-Phe5, D-Trp7,9, Leu11]substance P (antagonist D) and [Arg6, D-Trp7,9, NmePhe8]substance P(6-11) (antagonist G), are currently being investigated as possible anti-tumour agents. These compounds are hoped to be effective against neuropeptide-drive...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.126
更新日期:1996-03-01 00:00:00
abstract:BACKGROUND:Regulator of cullins-1 (ROC1) is a key subunit in the cullin-RING ligase (CRL) protein complex. Our previous study indicated that ROC1 was essential for bladder cancer cell survival and that ROC1 knockdown inhibited CRL activity, triggering G2 phase arrest and senescence. However, the role of ROC1 in the mal...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.444
更新日期:2016-02-02 00:00:00
abstract:BACKGROUND:Stromal-tumour interactions facilitate pancreatic cancer (PC) progression. The hepatocyte growth factor (HGF)/c-MET pathway is upregulated in PC and mediates the interaction between cancer cells and stromal pancreatic stellate cells (PSCs). This study assessed the effect of HGF/c-MET inhibition plus gemcitab...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0782-1
更新日期:2020-05-01 00:00:00
abstract:BACKGROUND:A major molecular pathway of genetic instability in cancer is DNA mismatch repair deficiency. High-level microsatellite instability (MSI-H) is currently the best predictor of responsiveness towards immune checkpoint blockade. Data about the prevalence of high-level microsatellite instability in cholangiocarc...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0199-2
更新日期:2019-01-01 00:00:00
abstract::Between 1971 and 1988, 20 patients with previously undiagnosed non-Hodgkin's lymphoma (NHL), of intermediate or high grade histology presented with extradural spinal cord compression. All had decompressive surgery. The first treatment after surgery was chemotherapy in nine and radiotherapy in 11 patients. At presentat...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.25
更新日期:1991-01-01 00:00:00