Abstract：
:Four poly(ADP-ribose) polymerase (PADPRP) inhibitors [3-aminobenzamide, benzamide, 3,4-dihydro-5-methoxyisoquinolin-1(2H)-one (PD 128763) and 8-hydroxy-2-methylquinazolin-4(3H)-one (NU1025)] were compared with respect to their effects on a number of biological end points. The following parameters were assessed: their ability to inhibit the enzyme in permeabilised L1210 cells; their ability to potentiate the cytotoxicity of temozolomide (including the cytotoxicity of the compounds per se); their ability to increase net levels of temozolomide-induced DNA strand breaks and inhibit temozolomide-induced NAD depletion. PD 128763 and NU1025 were equipotent as PADPRP inhibitors, and 40- and 50-fold more potent than benzamide and 3-aminobenzamide respectively. All the compounds acted in a concentration-dependent manner to potentiate the cytotoxicity and increase DNA strand break levels in cells treated with temozolomide. There was an excellent correlation between the potency of the compounds as PADPRP inhibitors and their effects on cell survival and DNA repair. Temozolomide treatment caused a decrease in cellular NAD levels, and this was abolished by the PADPRP inhibitors. In conclusion, the new generation of PADPRP inhibitors are at least 50-fold more effective than 3-aminobenzamide as chemopotentiators, and can be used at micromolar rather than millimolar concentrations in intact cells.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Boulton S,Pemberton LC,Porteous JK,Curtin NJ,Griffin RJ,Golding BT,Durkacz BWdoi
10.1038/bjc.1995.423subject
Has Abstractpub_date
1995-10-01 00:00:00pages
849-56issue
4eissn
0007-0920issn
1532-1827journal_volume
72pub_type
杂志文章abstract：BACKGROUND:Malignancy alters cellular complex lipid metabolism and membrane lipid composition and turnover. Here, we investigated whether tumorigenesis in cancer-derived prostate epithelial cell lines influences protein kinase C-linked turnover of ethanolamine phosphoglycerides (EtnPGs) and alters the pattern of ethano...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.457
更新日期：2014-10-14 00:00:00
abstract：:Cancer survival rates decrease in the presence of disseminated disease. However, there are few therapies that are effective at eliminating the primary tumour while providing control of distant stage disease. Photodynamic therapy (PDT) is an FDA-approved modality that rapidly eliminates local tumours, resulting in cure...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603792
更新日期：2007-06-18 00:00:00
abstract：:Heterogeneity of DNA content in multiple hepatocellular carcinomas (HCCs) was investigated by flow cytometry in 62 tumours from 26 patients who had undergone surgical treatment for multiple synchronous HCCs. Heterogeneity of DNA content was defined (a) when tumours had a different DNA ploidy pattern or (b) when the di...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.387
更新日期：1997-01-01 00:00:00
abstract：:Cells of a patient with Turcot's syndrome and of her parents were evaluated for the presence of molecular alterations in the p53 and the Ki-ras gene. Deletions on chromosome 17p, overexpression and point mutations of the p53 gene as well as mutations of the Ki-ras gene were detected in primary and metastatic tumour bu...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.379
更新日期：1993-09-01 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：:An apparently unique circulating common oncofoetal protein has been identified in rat small-bowel, colonic and pancreatic adenocarcinomas. The tumours were induced by ionizing radiation (small bowel), an alkyl hydrocarbon, 1,2-dimethylhydrazine (colon) and a polyaromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (pa...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.120
更新日期：1981-06-01 00:00:00
abstract：:The formation of cyclic AMP was studied in normal liver, subcutaneous hepatomas derived from MH1C1 cells, and premalignant liver and primary hepatomas induced by the carcinogens 2-acetylaminofluorene (AAF) and 4-dimethylamino-azobenzene (DAB). While only very slight effects of prostaglandins (PG) were seen in slices o...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1978.281
更新日期：1978-12-01 00:00:00
abstract：BACKGROUND:Colorectal cancer (CRC) diagnoses and disease-specific survival (DSS) vary between ethnic groups in the United States. However, few studies have assessed differences among Asian subgroups. METHODS:The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with invasive CRC...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.97
更新日期：2013-04-16 00:00:00
abstract：:We investigated the effects of individual fatty acids on breast cancer in a prospective study of 35,298 Singapore Chinese women aged 45-74 years, who were enrolled during April 1993 to December 1998 (The Singapore Chinese Health Study). At recruitment, each study subject was administered, in-person, a validated, semiq...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601340
更新日期：2003-11-03 00:00:00
abstract：:High response rates have been reported in the treatment of advanced gastric cancer with epirubicin, cisplatin and continuous infusion 5-fluorouracil (ECF), including instances of unresectable disease being rendered operable by chemotherapy. We report our experience with ECF as neoadjuvant treatment in gastric and lowe...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1996.604
更新日期：1996-11-01 00:00:00
abstract：:In resection tissue samples of colorectal carcinomas, the concentration of urokinase-type plasminogen activator (u-Pa) was found to be significantly higher than in the normal parent mucosal tissue, while there was less tissue-type plasminogen activator (t-PA). u-PA and t-PA were also determined in endoscopic biopsies ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.293
更新日期：1989-09-01 00:00:00
abstract：:The efficacy of radioimmunotherapy of tumours with radiolabelled monoclonal antibodies (MAbs) depends on the amount of antibody taken up by the tumour and on its intratumoral distribution. In the case of MAbs directed against intracellular antigens, increasing the permeability of the cytoplasmic membrane may augment t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.468
更新日期：1995-11-01 00:00:00
abstract：:The topical carcinogenicity to mouse skin of smoke condensates obtained from a tobacco substitute (NSM), alone or in combination with tobacco, has been compared with condensate from tobacco and with acetone, the solvent used. Sixteen different types of cigarette were used to make the condensates, and the age-standardi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1977.47
更新日期：1977-03-01 00:00:00
abstract：:Although cancer of the cervix is traditionally considered not to be responsive to steroid hormones, an in vitro study has reported that the addition of oestrogen increased cellular proliferation in a cervix cancer cell line that was inhibited by progesterone. We investigated whether the reported in vitro effects of oe...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.97
更新日期：1997-01-01 00:00:00
abstract：:Effects of c-Myc overexpression on the DNA damage-induced G2/M checkpoint were studied in finite lifespan, normal human mammary epithelial cells (HMECs). Previously, we showed that c-Myc attenuates G1/S arrest and leads to an inappropriate entry of cells with damaged DNA into the S phase, following treatment with ioni...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601307
更新日期：2003-10-20 00:00:00
abstract：:The lability of cell surface histocompatibility antigens of 2 murine lymphomata was examined. These 2 tumours differ greatly in their capacity to metastasize in syngeneic hosts. Cells of the metastatic lymphoma released histocompatibility antigens in vivo and in vitro at a greater rate than cells of the non-metastasiz...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1976.2
更新日期：1976-01-01 00:00:00
abstract：METHODS:Maternally reported congenital abnormalities (CAs) were examined in a case-control study of 278 cases of paediatric germ cell tumours (GCTs) and 423 controls. RESULTS AND CONCLUSIONS:Germ cell tumours were significantly associated with cryptorchidism in males (OR=10.8, 95% CI: 2.1-55.1), but not with any other...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605169
更新日期：2009-08-04 00:00:00
abstract：BACKGROUND:Cancer survival statistics are typically reported by using measures discounting the impact of other-cause mortality, such as net survival. This is a hypothetical measure and is interpreted as excluding the possibility of cancer patients dying from other causes. Crude probability of death partitions the all-c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0597-0
更新日期：2019-11-01 00:00:00
abstract：BACKGROUND:Cabazitaxel is approved for treatment of castration-resistant metastatic prostate cancer. The current dosing strategy of cabazitaxel is based on body surface area (BSA). Body surface area is known as a poor predictor for total systemic exposure to drugs, since it does not take into account variability in act...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2017.91
更新日期：2017-05-09 00:00:00
abstract：:A retrospective seroepidemiologic study was performed to examine the association between human papillomaviruses (HPV) 16 infection and carcinomas of the oropharynx, the oesophagus, penis and vagina. Sera were selected from the serum bank from the Antoni van Leeuwenhoek Hospital (Netherlands Cancer Institute) and the S...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600870
更新日期：2003-04-07 00:00:00
abstract：BACKGROUND:To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). METHODS:Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 ...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究
doi：10.1038/bjc.2017.92
更新日期：2017-06-06 00:00:00
abstract：BACKGROUND:Cervical cancer screening coverage remains insufficient in most countries. Our objective was to assess whether in-home vaginal self-sampling with a dry swab for high-risk human papillomavirus (HR-HPV) testing is effective and cost-effective in increasing participation in cervical cancer screening. METHODS:I...
journal_title：British journal of cancer
pub_type： 杂志文章,随机对照试验
doi：10.1038/bjc.2014.510
更新日期：2014-11-25 00:00:00
abstract：:We analysed 26 metastases from 25 patients with sporadic cutaneous malignant melanoma for alterations in the CDKN2 gene by a combined polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP)/nucleotide sequencing approach. Eleven alterations (one in exon 1, five in exon 2 and five in the 3' non-cod...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.59
更新日期：1996-02-01 00:00:00
abstract：BACKGROUND:Chronic antigenic stimulation may initiate non-Hodgkin (NHL) and Hodgkin lymphoma (HL) development. Antecedent, infection-related conditions have been associated, but evidence by lymphoproliferative subtype is limited. METHODS:From the US SEER-Medicare database, 44,191 NHL, 1832 HL and 200,000 population-ba...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.173
更新日期：2014-05-27 00:00:00
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 ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.116
更新日期：1991-04-01 00:00:00
abstract：:This study has been designed to verify the specific toxicity of saporin, a type 1 ribosome-inactivating protein (RIP), with the same activity as ricin A chain, targeted by a bispecific monoclonal antibody (bimAb) recognising both the CD25 antigen and the RIP. The CD25 antigen is expressed by lymphoid populations upon ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.233
更新日期：1993-06-01 00:00:00
abstract：:The met proto-oncogene is the tyrosine kinase growth factor receptor for hepatocyte growth factor. In the present study, we investigated the role of met expression on the modulation of apoptosis in colorectal tumours. The gene expressions of c-met and the anti-apoptotic bcl-2 family, including bcl-2, bcl-x(L)and bcl-w...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1301
更新日期：2000-09-01 00:00:00
abstract：:The well-known peak of bone cancer during the second decade was found to be closely associated with changes in growth velocity at the adolescent growth spurt, for males and females in England and Wales. Distinct accumulations in the second and third decades could be recognized for cancers of ovary, testis, prostate an...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1970.24
更新日期：1970-06-01 00:00:00
abstract：BACKGROUND:Neutropenia is a common adverse reaction of chemotherapy. We assessed whether chemotherapy-induced neutropenia could be a predictor of survival for patients with non-small-cell lung cancer (NSCLC). METHODS:A total of 387 chemotherapy-naïve patients who received chemotherapy (vinorelbine and gemcitabine foll...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605348
更新日期：2009-11-03 00:00:00
abstract：:To design hybrid tumour necrosis factor-alpha (TNF-alpha) applicable to systemic anti-tumour therapeutic use, we assessed the relationships among the molecular size of hybrid TNF-alpha, in vitro bioactivity and in vivo anti-tumour potency. Natural human TNF-alpha was covalently modified with polyethylene glycol (PEG) ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.495
更新日期：1996-10-01 00:00:00
