Abstract：
:Flunarizine is a class IV calcium channel blocker which increases oxygen delivery to hypoxic regions in solid tumours, exerting a radiosensitising effect in vivo in animal tumour models. Precisely how the drug improves oxygenation is not well understood. We hypothesised that metabolic conditions present within solid tumours reduce red blood cell (RBC) deformability and that flunarizine exerts its in vivo effect by preventing this loss of RBC deformability. A microrheometer was used to compare the viscosity of rat and human RBC suspensions in conditions of hypoxia (pO2 < 10 mmHg), acidic environment (pH 6.8), and elevated lactate concentration (lactate 5 mMol l-1), without or with flunarizine at concentrations of 5, 10, and 50 mg l-1. The effects of flunarizine on RBC density and morphology were also recorded. Hypoxia, low pH, and lactate exposure together increased both human and rat RBC suspension viscosity. Flunarizine at concentrations of 5 and 10 mg l-1 prevented the increases in viscosity. The drug caused dose-dependent shifts toward lower cell density while inducing a characteristic cupped shape (stomatcytic morphology), suggesting a mechanism involving calmodulin inhibition. The results support the hypothesis that flunarizine improves tumour blood flow and oxygenation by enhancing flow properties of RBC's in solid tumours.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Kavanagh BD,Coffey BE,Needham D,Hochmuth RM,Dewhirst MWdoi
10.1038/bjc.1993.134subject
Has Abstractpub_date
1993-04-01 00:00:00pages
734-41issue
4eissn
0007-0920issn
1532-1827journal_volume
67pub_type
杂志文章abstract：:The relationship between melanoma incidence and latitude was investigated in North American and Europe, using the data collected by 43 population-based cancer registries. In North America melanoma incidence increased with decreasing latitude, supporting the role of UV light in the induction of melanoma. Within England...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.260
更新日期：1979-11-01 00:00:00
abstract：:The effect of acute carbon monoxide (CO) breathing on blood oxygenation and tumour hypoxia was related to the radiation response of the C3H/Tif mammary carcinoma. Blood gas analysis showed that CO breathing caused a time- and dose-dependent formation of carboxyhaemoglobin (HbCO), a significant left shift of the oxygen...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.8
更新日期：1994-01-01 00:00:00
abstract：:Cell viability following short (1 h) contact with paclitaxel or docetaxel was assayed using synchronised HeLa cells. Docetaxel proved almost totally lethal against S-phase cells. Its toxicity was only partial against cells in mitosis, and declined to a minimum with progression to G1. For paclitaxel, cytotoxicity incre...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.232
更新日期：1995-06-01 00:00:00
abstract：:The results of treating two series of patients with Burkitt's lymphoma are presented in the form of survival curves. The second series shows an improved survival rate which seems to be due to a potentiating effect by potassium iodide on oral cyclophosphamide. So far no reason for this effect has been found. ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1971.6
更新日期：1971-03-01 00:00:00
abstract：:The effects of cis-dichlorodiammine platinum II (DDP) on the intestinal mucosa and the kidney were studied after single and multiple treatments with intervals of 7-45 days. After a single treatment, the jejunal epithelium underwent a transient interruption of cell proliferation followed by a hyperplastic recovery and ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1982.45
更新日期：1982-02-01 00:00:00
abstract：:The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603685
更新日期：2007-04-23 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：:In the UK there are standardized surveillance procedures for gestational trophoblastic disease. However, there are differences in practice between the two treatment centres in terms of definition of persistent gestational trophoblastic disease, prognostic risk assessment and chemotherapeutic regimens. The role of prop...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690203
更新日期：1999-03-01 00:00:00
abstract：:Bilateral kidney ligation of mice immediately before injection of misonidazole (MIS) prolongs the plasma half-life of this radiosensitizer from about 2 h (in normal mice) to 10-11 h, similar to that in man. Kidney ligation does not, however, change the relative proportions of MIS and its O-demethylated metabolite, Ro-...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.55
更新日期：1979-03-01 00:00:00
abstract：BACKGROUND:Melanoma is highly resistant to current modalities of therapy, with the extent of pigmentation playing an important role in therapeutic resistance. Nuclear factor-κB (NF-κB) is constitutively activated in melanoma and can serve as a molecular target for cancer therapy and steroid/secosteroid action. METHODS...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.458
更新日期：2011-12-06 00:00:00
abstract：:During the development of indazolylpyrimidines as novel and potent inhibitors of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2) tyrosine kinase, we observed that some human tumour xenografts are more sensitive to VEGFR2 kinase inhibitors than others. A better understanding of the basis for this differen...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602109
更新日期：2004-10-04 00:00:00
abstract：:Multiple primary tumours occurring in a three-year population-based series of patients with histopathologically peer-reviewed sarcomas from North West England were ascertained in order to look at the patterns of neoplasms seen. A total of 30 out of the 310 patients entered in the study had additional primary tumours. ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.512
更新日期：1993-12-01 00:00:00
abstract：:A method for testing organic chemicals for their carcinogenic potential is described. Baby hamster kidney cells (BHK-21/C1 13) were exposed to different doses of test compound in liquid tissue culture medium containing rat liver post-mitochondrial supernatant and cofactors (S-9 mix) to aid metabolism, but without seru...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1977.231
更新日期：1977-11-01 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：:Meningiomas are tumours derived from the arachnoid and pia mater. During embryogenesis, these membranes develop from the migrating craniofacial neural crest. We have previously demonstrated that meningiomas have characteristic features of embryonic meninges. Craniofacial neural crest derivatives are affected during no...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690705
更新日期：1999-10-01 00:00:00
abstract：:An increasing body of evidence indicates that glutathione S-transferases play a role in the intrinsic and acquired resistance of tumours to anticancer drugs. In view of the wide use of tumour cell lines to understand the factors which confer either sensitivity or resistance to chemotherapeutic agents we have determine...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.280
更新日期：1989-09-01 00:00:00
abstract：:Previous studies have characterized the enzymatic properties and inhibition of a trypsin-like neutral protease on the surface of Ehrlich ascites cells by means of kinetic analysis. The present study links these kinetic studies with the recently reported role of a tumour-cell membrane-bound serine protease in tumour-in...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1982.304
更新日期：1982-12-01 00:00:00
abstract：:Pulmonary metastasectomy is widely and increasingly practiced in the belief that this intervention can cure patients with colorectal cancer, and that without it few survive 5 years. No good evidence exists supporting such convictions, indeed recent trial results challenge them. What evidence underpins this acceptance ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-0927-2
更新日期：2020-08-01 00:00:00
abstract：BACKGROUND:There have been controversies in prognostic impact of mucinous histology on colorectal cancer, and its implication in patients treated with adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is unclear. METHODS:Stage II and III colorectal cancer patients who underwent curative resection followed ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.232
更新日期：2013-05-28 00:00:00
abstract：:The structural characteristics of mesoionic compounds, which contain distinct regions of positive and negative charges associated with a poly-heteroatomic system, enable them to cross cellular membranes and interact strongly with biomolecules. Potential biological applications have been described for mesoionic compoun...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601946
更新日期：2004-07-19 00:00:00
abstract：:Forty-three children with malignant soft tissue sarcomas (IRS Groups II-IV) were treated with rapid dose delivery chemotherapy protocol comprising six courses of vincristine, adriamycin and cyclophosphamide, given in most cases within 8 weeks (Rapid VAC). This was followed in 36 patients by high dose melphalan with au...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.313
更新日期：1991-08-01 00:00:00
abstract：:In this study, we have investigated the expression of inhibin subunits and activin receptors (ActRs) in normal and malignant ovarian cells. Each product of the inhibin subunits (alpha, betaa, betab) and activin receptors (ActRs) amplified by reverse transcription polymerase chain reaction were detected as a single ban...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.1999.1127
更新日期：2000-04-01 00:00:00
abstract：:To understand the role of p53 tumour suppressor gene in the carcinogenesis of arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan, we collected tumour samples from 23 patients with Bowen's disease, seven patients with basal cell carcinomas (BCC) and nine patients with squamous cell carcinoma...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690467
更新日期：1999-06-01 00:00:00
abstract：:The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case-control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690008
更新日期：1999-01-01 00:00:00
abstract：:Sodium polyanethol sulphonate (SPS) when incorporated into rat erythrocyte lysate (REL) containing semi-solid agar medium at 1 mg ml-1. markedly enhanced colony formation by a number of anchorage-independent cell lines. REL usually needed to be included for the expression of SPS induced potentiation as in its absence ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1984.230
更新日期：1984-11-01 00:00:00
abstract：:The 62 kDa protein product of the c-myc oncogene (p62 c-myc) is thought to be involved in the control of normal cellular proliferation and differentiation. We have measured oncoprotein levels using a flow cytometric assay in 141 operable breast cancers and have correlated levels with prognostic variables, patient surv...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.337
更新日期：1989-11-01 00:00:00
abstract：:Germline mutations in genes encoding proteins involved in DNA mismatch repair are responsible for the autosomal dominantly inherited cancer predisposition syndrome hereditary nonpolyposis colorectal cancer (HNPCC). We describe here analysis of hMLH1 and hMSH2 in nine Greek families referred to our centre for HNPCC. A ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602260
更新日期：2005-01-31 00:00:00
abstract：:Detailed data and statistics per each morphological site of various digestive neoplasms were obtained for the period 1976-87 from the Vaud Cancer Registry datafile, a population-based cancer registration scheme covering about 530,000 inhabitants from the French-speaking part of Switzerland. Tabulations presented inclu...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.132
更新日期：1991-04-01 00:00:00
abstract：:Male inbred Fischer rats were fed phenobarbitone-Na at a level of 500 parts/10(6) in the diet for 1 week, followed by 1000 parts 10(6) for 103 weeks at which time the survivors were killed. Thirty-three treated rats survived to 80 weeks. Before 80 weeks, no animals showed hyperplastic lesions. Of the 33 rats surviving...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1978.62
更新日期：1978-03-01 00:00:00
abstract：BACKGROUND:Combined oral contraceptive (COC) use reduces epithelial ovarian cancer (EOC) risk. However, little is known about risk with COC use before the first full-term pregnancy (FFTP). METHODS:This Canadian population-based case-control study (2001-2012) included 854 invasive cases/2139 controls aged ⩾40 years who...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.400
更新日期：2017-01-17 00:00:00
