Abstract:
:Cells from V79 multicell spheroids must be exposed to approximately 50 times more etoposide than exponentially growing monolayers in order to produce the same amount of cell killing. A part of this difference in sensitivity is readily explained by the decrease in growth fraction of large spheroids, and by the protection afforded by nutrient deprivation which also reduces cellular ATP. However, cells composing the outer 10% of large (approximately 600 microns diameter) V79 spheroids, although actively cycling, were still ten times more resistant to etoposide than exponentially growing monolayers, regardless of whether cells were exposed in situ in spheroids or dispersed by trypsin immediately prior to exposure to the drug. Four cell doublings (48 h) as monolayers were required before the outer cells of spheroids regained drug sensitivity equivalent to that of exponentially growing monolayers. No differences in uptake/efflux of 3H-etoposide or in levels of p-glycoprotein were observed between monolayers and the outer cells of spheroids. In addition, topoisomerase II protein measured by immunoblotting and topoisomerase II activity measured by decatenation of kinetoplast DNA were not reduced in the outer cells of spheroids compared to monolayers. DNA strand breakage measured in individual cells using the DNA precipitation and comet assays correlated well with cell killing with one exception: DNA damage was not affected when cells were incubated with etoposide in phosphate-buffered saline, although the etoposide concentration required to produce a given amount of cell killing was increased approximately 7-fold compared to cells incubated with the drug in complete medium. These results indicate that etoposide toxicity towards V79 spheroids is influenced not only by proliferative status of the cells but also by factors which may include DNA packaging and the growth environment of the cell prior to and during treatment.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Olive PL,Banáth JP,Evans HHdoi
10.1038/bjc.1993.97subject
Has Abstractpub_date
1993-03-01 00:00:00pages
522-30issue
3eissn
0007-0920issn
1532-1827journal_volume
67pub_type
杂志文章abstract::BNP7787 (disodium 2,2'-dithio-bis-ethane sulphonate; Tavocept) is a novel agent developed to protect against cisplatin (cis-diammine-dichloroplatinum(II))-associated chronic toxicities. In this study, we determined the recommended dose of BNP7787 when preceding a fixed dose of cisplatin, the pharmacokinetics (PKs) and...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6602553
更新日期:2005-05-09 00:00:00
abstract::Both misonidazole (MISO) and hyperthermia are known to enhance the radiation response of hypoxic cells, and to be selectively cytotoxic against cells in a hypoxic and acidic environment. The ability of these conditions to modify the effect of irradiation and their individual relationship was studied in a C3H mammary c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1980.2
更新日期:1980-01-01 00:00:00
abstract::We have examined a series of human colorectal adenomas, carcinomas and cell lines derived from human colorectal cancer for loss of heterozygosity (LOH) on chromosome 11q22-23 by polymerase chain reaction (PCR) amplification of a microsatellite polymorphism of the dopamine D2 receptor (DRD2) locus. LOH was demonstrated...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.315
更新日期:1994-09-01 00:00:00
abstract::Burnet proposed in the 1950's that the immune system is engaged in identifying and destroying abnormal cancerous cells. This process, termed immune surveillance, has been at the centre of intense debate for decades. Results using immunodeficient mice lend support to the immune surveillance hypothesis. We surmised that...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603824
更新日期:2007-06-18 00:00:00
abstract::Chlamydia pneumoniae, Chlamydia trachomatis and Chlamydia psittaci were detected at low frequencies (<20%) among 69 pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas, 30 other lymphoproliferative disorders (LPD) and 44 non-LPD. The incidence of individual Chlamydiae was generally higher in MALT lymphoma tha...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603981
更新日期:2007-10-08 00:00:00
abstract::It has recently been reported that a series of testis cancers shows a temporal cycle in birth dates with a peak in certain months. This observation has been tested by an examination of a larger series covering all testis cancers diagnosed in the years 1971-84 in England and Wales, in men born in 1940 or later. Limited...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.117
更新日期:1987-05-01 00:00:00
abstract::The survival and clonogenic growth (measured in terms of colony forming efficiency (CFE) of intravenously injected (i.v.) Walker (W256) tumour cells in the lungs of rats was greatly enhanced by states of topical and systemic stress induced by the intraperitoneal (i.p.) injection of rats with a single dose of 10(-5)-10...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1976.7
更新日期:1976-01-01 00:00:00
abstract::Survivin is an apoptotic inhibitor that is expressed at high levels in a variety of malignancies. Survivin has four known alternative splice forms (Survivin, Survivin-2B, Survivin-deltaEx3, and Survivin-3B), and the recent literature suggests that these splice variants have unique functions and subcellular localisatio...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602317
更新日期:2005-01-31 00:00:00
abstract::As part of an NHS Executive Trent regional initiative we considered the role and cost-effectiveness of high dose chemotherapy in the treatment of relapsed Hodgkin's disease and non-Hodgkin's lymphoma. The key trials and case series show an additional patient benefit of 0.8-1.1 life years over standard chemotherapy. We...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1054/bjoc.1999.0880
更新日期:2000-01-01 00:00:00
abstract::Although the presence of axillary node metastases in breast cancer is a key prognostic indicator and may influence treatment decisions, a significant proportion of patients diagnosed as axillary node negative (ANN) using standard histopathological techniques may have occult nodal metastases (OMs). A combination of lim...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.16
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND:Treatment options for patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs) are still limited. We investigated the antitumour activity and safety profile of pazopanib--a multitarget drug with anti-angiogenic activity in patients with metastatic GEP NETs. METHODS:This was a nonran...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.470
更新日期:2013-09-17 00:00:00
abstract::Epithelial cadherin (E-CD) is a member of the cadherin family of cell adhesion molecules and has been implicated as an invasion suppressor molecule in vitro and in vivo. We analysed 174 breast tumours from the Nottingham/Tenovus Breast Cancer Series immunohistochemically for E-CD expression using the mouse monoclonal ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.2178
更新日期:2001-12-14 00:00:00
abstract:BACKGROUND:While lung adenocarcinoma patients can somewhat benefit from anti-angiogenic therapies, patients with squamous cell lung carcinoma (SQLC) cannot. The reasons for this discrepancy remain largely unknown. Soluble VEGF receptor-1, namely sVEGFR1-i13, is a truncated splice variant of the cell membrane-spanning V...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0128-4
更新日期:2018-06-01 00:00:00
abstract::The records of 194 patients with thyroid carcinoma treated with (131)I, representing all cases thus treated in Denmark from 1948 to 1972, were reviewed. Two cases of myeloid leukaemia were found compared with 0·097 expected cases of non-lymphocytic leukaemia (0·05 > P > 0·01). In 5 series of (131)I treated thyroid car...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1973.142
更新日期:1973-09-01 00:00:00
abstract::In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53-associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.207
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND:Anti-EGFR antibody, cetuximab, improves overall survival (OS) in K-ras wild-type chemotherapy-refractory colorectal cancer. Epidermal growth factor receptor ligand epiregulin (EREG) gene expression may further predict cetuximab benefit. METHODS:Tumour samples from a phase III clinical trial of cetuximab plu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.753
更新日期:2014-02-04 00:00:00
abstract::Several radiotherapeutic schedules compatible with continued structural-functional integrity of the gastrointestinal (GI) mucosa were compared utilizing the P815X2 murine mastocytoma grown as a solid subcutaneous tumour. Both the tumour and underlying normal tissues were irradiated during the treatments. The tumour ex...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.29
更新日期:1975-02-01 00:00:00
abstract::The aim of this study was to investigate the expression of the protein tyrosine phosphatases (PTP) PRL-1, PRL-2, and PRL-3 in human breast cancer and to evaluate its clinical and prognostic significance. PRL-PTP mRNA expression was examined in malignant (n = 7) and nonmalignant (n = 7) cryoconserved breast tissue samp...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603261
更新日期:2006-08-07 00:00:00
abstract:BACKGROUND:Childhood cancer survival estimates from developing nations are rare. METHODS:Using the US SEER and the Manila and Rizal Cancer Registry databases in the Philippines, 5-year survival for childhood leukaemia and lymphoma in 2001-2005 among Asian Americans were compared with both Filipinos and Caucasians in t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605703
更新日期:2010-06-29 00:00:00
abstract:BACKGROUND:The Dutch guidelines advise to start radiation therapy (RT) within 5 weeks following breast-conserving surgery (BCS). However, much controversy exists regarding timing of RT. This study investigated its effect on 10-year disease-free survival (DFS) in a Dutch population-based cohort. METHODS:All women diagn...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.159
更新日期:2017-07-11 00:00:00
abstract::Telomerase is a specialized ribonucleoprotein polymerase that directs the synthesis of telomerase repeats at chromosome ends. Accumulating evidence has indicated that telomerase is stringently repressed in normal human somatic tissues but reactivated in cancers and immortal cells, suggesting that activation of telomer...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.363
更新日期:1998-06-01 00:00:00
abstract::Several uncertainties surround optimal management of colorectal cancer. We investigated treatment patterns and factors influencing treatment receipt and mortality in routine clinical practice. We included 15 249 individuals, recorded by the National Cancer Registry (Ireland), with primary invasive colon or rectal tumo...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604467
更新日期:2008-07-22 00:00:00
abstract:BACKGROUND:The aim of this work was to improve the knowledge of the role of histamine in breast cancer by assessing the therapeutic efficacy of histamine and histamine H4 receptor (H4R) ligands in a triple-negative breast cancer (TNBC) model developed in immunocompetent hosts. By using publicly available genomic data, ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0636-x
更新日期:2020-02-01 00:00:00
abstract::In an Italian case-control study of oral cancer, number of missing teeth and other aspects of dental care were similar, but the general condition of the mouth, as indicated by gum bleeding, tartar deposits and mucosal irritation, was worse among oral cancer cases than controls. No differences were detected in sexual p...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1398
更新日期:2000-11-01 00:00:00
abstract::The effect of LiCl on melanoma cell growth and differentiation was studied in mouse and human melanoma cell lines. LiCl markedly inhibited B16 and HT-144 melanoma cell growth in vitro. Clonogenicity in soft agar of the melanoma cells was also markedly inhibited by LiCl. Pretreatment of B16 mouse melanoma cells with Li...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.9
更新日期:1987-01-01 00:00:00
abstract::The p16 protein plays an important role in the transition of cells into the G1 phase of the cell cycle. We have studied the prevalence of p16 protein expression in breast carcinomas in a prospective series of 368 invasive and 52 non-invasive malignancies, as well as in 88 locally recurring tumours and three tumour cel...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.739
更新日期:1998-12-01 00:00:00
abstract::Data obtained from multiple sources indicate that no single mechanism can explain the resistance to chemotherapy exhibited by non-small cell lung carcinomas. The multi-factorial nature of drug resistance implies that the analysis of comprising expression profiles may predict drug resistance with higher accuracy than s...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600463
更新日期:2002-07-29 00:00:00
abstract::Response to endocrine therapy in 51 patients with advanced breast cancer was compared with the amount of elastosis in histological sections from their primary tumours. There appeared to be an association between elastosis and response: tumours with no elastosis showed a lower rate of response than those with gross ela...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1979.98
更新日期:1979-05-01 00:00:00
abstract::Oesophageal adenocarcinoma is believed to arise from metaplastic mucosa in the distal oesophagus, a condition also known as Barrett's oesophagus (BE). BE develops as a result of injury caused by refluxing gastric and duodenal contents and is associated with increased risk of malignant transformation. Matrix metallopro...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.1929
更新日期:2001-08-03 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