Abstract:
:The novel compound 7(-)[4'-(2-nitroimidazol-l-yl)-butyl]-theophylline (NITP) can be used as an immunologically detectable probe for hypoxic cells. Because of the limited water solubility of NITP, it has been administered dissolved in peanut oil with 10% dimethylsulphoxide (DMSO). A new aqueous formulation has been devised, based on a 50% solution of a modified beta-cyclodextrin (Molecusol HPB), which increases the water solubility of NITP 10-fold. The pharmacokinetics of NITP in plasma and tumours have been compared following oral and intraperitoneal (i.p.) administration of the NITP in Molecusol, i.p. administration of NITP dissolved in peanut oil + 10% DMSO and injection of a near-saturated aqueous solution of the drug intravenously via the tail vein or i.p. or directly into the tumours. Binding of the marker to hypoxic cells within tumours was also measured after the different routes of administration. The Molecusol vehicle was unexpectedly toxic when administered i.p., but there was no toxicity from NITP dissolved in Molecusol when administered orally. Binding of the drug within tumours was seen for both the peanut oil + 10% DMSO and Molecusol formulations and for both oral and intraperitoneal routes. Binding of NITP within tumours has also been observed following direct injection of the drug, with minimal whole-body exposure to NITP. However, the bound metabolites of NITP within tumours were localised to the injection site, suggesting that direct injection is unlikely to be a useful method of administering bioreductive hypoxia markers. The data in this paper demonstrate that bound metabolites of the hypoxia marker NITP can be detected in tumours following oral administration of an aqueous formulation of NITP, and suggest that oral administration could be a satisfactory administration route for clinical studies with NITP.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Hodgkiss RJ,Stratford MR,Dennis MF,Hill SAdoi
10.1038/bjc.1995.530subject
Has Abstractpub_date
1995-12-01 00:00:00pages
1462-8issue
6eissn
0007-0920issn
1532-1827journal_volume
72pub_type
杂志文章abstract::To determine whether resistance to chemoimmunotherapy is acquired during therapy, we investigated the effects of chemotherapeutic agents and anti-tumour polysaccharide, lentinan, on the progression of Rous sarcoma virus-induced S908.D2 fibrosarcomas. The chemoimmunotherapy was effective against the parental S908.D2-be...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.82
更新日期:1996-02-01 00:00:00
abstract:BACKGROUND:We evaluated the association between smoking status and thyroid cancer risk and whether this association is mediated by body mass index (BMI) and thyroid-stimulating hormone (TSH). METHODS:We performed a cohort study of 96,855 Korean adults who were followed annually or biennially for a median of 5.9 years....
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0224-5
更新日期:2018-08-01 00:00:00
abstract::Tumorigenic mouse lung-derived type 2 cell lines have large reductions in both beta-adrenergic-stimulated cAMP production and ligand binding to beta-adrenergic receptors. These tumorigenic cells are also relatively insensitive to glucocorticoids. Because glucocorticoids regulate both beta-adrenergic receptor expressio...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.377
更新日期:1996-08-01 00:00:00
abstract::Identification of a biomarker of prognosis and response to therapy that can be assessed preoperatively would significantly improve overall outcomes for patients with pancreatic cancer. In this study, patients whose tumours exhibited high LMO4 expression had a significant survival advantage following operative resectio...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604177
更新日期:2008-02-12 00:00:00
abstract::I.p. administration at several dose levels over periods of up to 12 weeks, or continuous i.v. infusion of high doses of misonidazole (MISO) for 15 h, produced no significant change in peripheral nerve conduction velocity (NCV) and did not prevent the normal increase in NCV as the animals matured from 12 to 24 weeks of...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1980.94
更新日期:1980-04-01 00:00:00
abstract::I have studied the effects on growth of two tumours in mice and on host toxicity, of combining Misonidazole (MISO) or Metronidazole (METRO) with Methotrexate (MTX)-5-fluorouracil (FU) or Adriamycin (ADR). The nitroimidazoles alone had no effect on the growth of either tumour, but MISO (1 mg/g) led to a small increase ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1980.334
更新日期:1980-12-01 00:00:00
abstract:BACKGROUND:Tumours are made up of a mixed population of different types of cells that include normal structures as well as ones associated with the malignancy, and there are multiple interactions between the malignant cells and the local microenvironment. These intercellular interactions, modulated by the microenvironm...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.517
更新日期:2012-01-03 00:00:00
abstract::A case-control study of lung cancer involving interviews with 965 female patients and 959 controls in Shenyang and Harbin, two industrial cities which have among the highest rates of lung cancer in China, revealed that cigarette smoking is the main causal factor and accounted for about 35% of the tumours among women. ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.421
更新日期:1990-12-01 00:00:00
abstract:BACKGROUND:Progression-free survival (PFS) is a surrogate endpoint widely used for overall survival (OS) in oncology. Validation of PFS as a surrogate must be done for each indication and each intervention. We aimed to identify all studies evaluating the validity of PFS as a surrogate for OS in oncology, and to describ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0805-y
更新日期:2020-05-01 00:00:00
abstract::Monoclonal and polyclonal antibodies against placental alkaline phosphatase (PLAP) were evaluated for tumour immunolocalization of human PLAP-producing Hep 2 tumours in nude mice. The antibodies were labelled with 125I and injected i.p. in mice with developing Hep 2 tumours. The distribution of 125I-anti PLAP in vario...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1984.23
更新日期:1984-02-01 00:00:00
abstract:BACKGROUND:The immune system has a central role in controlling cancer, and factors that influence protective antitumour immunity could therefore have a significant impact on the course of malignant disease. Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the p...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/bjc.2014.384
更新日期:2014-08-26 00:00:00
abstract::The clinical formulation of the anti-tumour agent Taxol involves the use of a mixture of ethanol and Cremophor EL. Gel electrophoresis and density-gradient ultracentrifugation were used to detect effects of Taxol infusions on serum lipoproteins. Use of the Cremophor vehicle results in a decrease in the electrophoretic...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.317
更新日期:1994-09-01 00:00:00
abstract::Virus-directed enzyme prodrug therapy (VDEPT) utilising the bacterial enzyme nitroreductase delivered by a replication-defective adenovirus vector to activate the prodrug CB1954 is a promising strategy currently undergoing clinical trials in patients with a range of cancers. An understanding of the mechanism of tumour...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601211
更新日期:2003-09-01 00:00:00
abstract::Monocyte-macrophage series have an important role in host surveillance against cancer. The cytotoxic/cytostatic activity of macrophages is, to a great extent, attributed to the up-regulation of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO). Here, in 28 patients with primary lung cancer and...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.528
更新日期:1998-08-01 00:00:00
abstract::Benzo[b]thiophenesulphonamide 1,1-dioxide (BTS) derivatives are strong cytotoxic agents that induce reactive oxygen species (ROS) overproduction and apoptosis in tumour cells. Although the precise origin of BTS-induced ROS is not known, a clear correlation between their cytotoxic effect and ability to inhibit a tumour...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602383
更新日期:2005-02-28 00:00:00
abstract:BACKGROUND:Laboratory studies suggest a possible role of magnesium intake in colorectal carcinogenesis but epidemiological evidence is inconclusive. METHOD:We tested magnesium-colorectal cancer hypothesis in the Nurses' Health Study, in which 85 924 women free of cancer in 1980 were followed until June 2008. Cox propo...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.76
更新日期:2012-03-27 00:00:00
abstract::Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. Using reversed-phase and size-fractionation ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.91
更新日期:1993-03-01 00:00:00
abstract::A substantial excess risk of lymphomas and nonmelanoma skin cancer has been demonstrated following organ transplantation. Large sample size and long follow-up time may, however, allow more accurate risk estimates and detailed understanding of long-term cancer risk. The objective of the study was to assess the risk of ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601219
更新日期:2003-10-06 00:00:00
abstract::Patients with recurrent or refractory head and neck squamous cell carcinoma received cisplatin/epinephrine injectable gel or placebo gel injected directly into the clinically dominant tumour. The double-blind phase III trial comprised of up to 6 weekly treatments over 8 weeks, 4 weekly evaluation visits, and then mont...
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.6600588
更新日期:2002-10-21 00:00:00
abstract::Ovarian cancer is the fifth leading cause of female cancer deaths in the Western world. Significant progress has been made in the treatment of patients with ovarian cancer, however, the majority of patients experience disease recurrence and new therapies are being sought for such patients. Clinical investigation of po...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/bjc.2015.395
更新日期:2015-12-15 00:00:00
abstract::The cisplatin analogue 1R,2R-diaminocyclohexane(trans-diacetato)(dichloro)platinum(IV) (DAP) is a DNA-damaging agent that will be entering clinical trials for its potent cytotoxic effects against cisplatin-resistant tumour cells. This cytotoxicity may reside in its ability to selectively activate G1-phase checkpoint r...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603448
更新日期:2006-12-04 00:00:00
abstract:BACKGROUND:Locally advanced oesophageal cancer (LAEC) is associated with poor survival and more effective treatments are needed. The aim of this phase I trial was to assess the maximum tolerated dose (MTD) of a novel weekly docetaxel and cisplatin regimen concurrent with radical radiotherapy. METHODS:Patients with unr...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/sj.bjc.6606051
更新日期:2011-01-18 00:00:00
abstract::The origin of metastatic adenocarcinoma lesions can sometimes be difficult to diagnose. The objectives of our study were to establish the cytokeratin staining pattern of primary and metastatic lung and colorectal adenocarcinomas, and to determine if this helps to identify the site of origin of metastatic lesions. We r...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600326
更新日期:2002-06-17 00:00:00
abstract::This study explored the relationships of serum insulin-like growth factors, IGF-I and IGF-II, and their binding proteins (IGFBP)-2 and IGFBP-3, with key clinicopathological parameters in 92 patients with colorectal cancer (cases). Comparisons were made with 57 individuals who had a normal colonoscopy (controls). Seria...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1462
更新日期:2000-11-01 00:00:00
abstract:BACKGROUND:Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse. METHOD:The aim of this study was to compare tumour stage and survival of IBD patients...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605359
更新日期:2009-11-17 00:00:00
abstract::The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers overexpressing the c-erbB-2 gene. In vitro and in vivo anti-tumour effects of a humanised antibody against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 was less effective than its mu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.259
更新日期:1996-06-01 00:00:00
abstract::In rapidly frozen livers from chickens affected with myeloblastosis and Marek's disease and from unaffected control birds there exists a strong correlation between catalase activity and catalase Electron Paramagnetic Resonance (EPR) signal intensities. The diseased chickens had activities and signals reduced to as lit...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1984.189
更新日期:1984-09-01 00:00:00
abstract::Small cell bronchial carcinoma (SCC) xenografts with differing sensitivity to cyclophosphamide (CY) were investigated using a variety of techniques. Two xenografts (HX78 and HX88) were relatively sensitive to CY, one xenograft (HX72) was inherently resistant to CY and a fourth xenograft (HX78Cy) was a CY induced resis...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1985.98
更新日期:1985-05-01 00:00:00
abstract::We used a nested case-control design on data from men in four prospective studies (from the UK, Maryland in the USA, and two from Finland) with available stored serum samples to determine whether there was an advantage in measuring both free prostate-specific antigen (PSA) and total PSA as a potential screening test f...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.1999.0988
更新日期:2000-02-01 00:00:00
abstract::NIH3T3 cells transfected with c-H-ras and/or c-myc genes were examined for differences in drug sensitivity. The five transfectants used were N8, NIH3T3-nm-1, pT22-3-nm-2, pP1-4 and pT22-3. They were transfected with pKOneo alone, pKOneo and c-myc, pKOneo and c-myc plus activated c-H-ras, normal c-H-ras and activated c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.56
更新日期:1991-02-01 00:00:00