Abstract:
:The thymidylate synthase inhibitor 5-fluorouracil (5-FU) continues to play a pivotal role in the treatment of cancer. A downstream event of thymidylate synthase inhibition involves the induction of a self-defeating base excision repair process. With the depletion of TTP pools, there is also an increase in dUMP. Metabolism of dUMP to the triphosphate dUTP results in elevated pools of this atypical precursor for DNA synthesis. Under these conditions, there is a destructive cycle of dUMP incorporation into DNA, removal of uracil by the base excision repair enzyme uracil-DNA glycosylase (UDG), and reincorporation of dUMP during the synthesis phase of DNA repair. The end point is DNA strand breaks and loss of DNA integrity, which contributes to cell death. Evidence presented here indicates that both the nuclear and the mitochondrial isoforms of UDG are modulated by FdUrd (and 5-FU) treatment in certain cell lines but not in others. Modulation occurs at the transcriptional and post-translational levels. Under normal conditions, nUDG protein appears in G(1) and is degraded during the S to G(2) phase transition. The present study provides evidence that, in certain cell lines, FdUrd mediates an atypical turnover of nUDG. Additional data indicate that, for cell lines that do not down-regulate nUDG, small interfering RNA-mediated knockdown of nUDG significantly increases resistance to the cytotoxic effects of FdUrd. Results from these studies show that nUDG is an additional determinant in FdUrd-mediated cytotoxicity and bolster the notion that the self-defeating base excision repair pathway, instigated by elevated dUTP (FdUTP) pools, contributes to the cytotoxic consequences of 5-FU chemotherapy.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Fischer JA,Muller-Weeks S,Caradonna SJdoi
10.1158/0008-5472.CAN-06-0540subject
Has Abstractpub_date
2006-09-01 00:00:00pages
8829-37issue
17eissn
0008-5472issn
1538-7445pii
66/17/8829journal_volume
66pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Increased activity, membrane association, and secretion of cathepsin B have been shown to correlate positively with invasiveness and the metastatic properties of many tumor entities. Cathepsin B is able to directly facilitate invasion by degrading extracellular matrix components or to indirectly facilitate invasion by...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract::Donor lymphocyte infusions (DLI) provide effective therapy for patients with multiple myeloma who have relapsed after allogeneic bone marrow transplantation. However, the immunological mechanisms of the graft-versus-myeloma (GVM) effect have not been defined, and the target antigens of this response have not been iden...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-05-15 00:00:00
abstract::In this study of the role of microfloral beta-glucuronidase in colonic carcinogenesis, the effect of beta-glucuronidase inhibitor was evaluated. Starting at 5 weeks of age, male Donryu rats were fed either a semisynthetic diet or the same diet containing 0.1% beta-glucuronidase inhibitor as N-cyclohexyl-5-O-acetyl-2,4...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::4-Hydroxyandrostenedione (CGP32349; 4-OHA) is a clinically effective treatment for advanced postmenopausal breast cancer by both the parenteral and p.o. routes, as a result of its inhibition of aromatase and consequent suppression of plasma estrogen levels. Thirty patients were randomized to treatment with 250 mg 4-OH...
journal_title:Cancer research
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1989-03-01 00:00:00
abstract::The lymphatic absorption and tissue distribution of free [14C]Adriamycin, "empty" [3H]liposomes, free [14C]Adriamycin plus empty [3H]liposomes, and [14C]Adriamycin entrapped into [3H]liposomes have been examined at intervals after i.p. injection into rats. Following treatment with empty [3H]liposomes, almost 30% of th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-04-01 00:00:00
abstract::Prior investigations on the beneficial effect of dietary processed tomato products and lycopene on prostate cancer risk suggested that lycopene may require the presence of other constituents to exert its chemopreventive potential. We investigated whether ketosamines, a group of carbohydrate derivatives present in dehy...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0108
更新日期:2008-06-01 00:00:00
abstract::Twenty-eight cervicovaginal tracts from approximately 2-year-old female BALB/cCrgl mice neonatally exposed to ovarian steroids were cut into small segments and transplanted into syngeneic hosts. Within six months, six of 28 host animals developed tumors. Three tumors were from progesterone-exposed mice, two were from ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-07-01 00:00:00
abstract::We have screened 57 cases of primary, nonfunctional, pituitary adenomas for loss of heterozygosity of markers on chromosome 9p. Using a panel of 11 microsatellite markers, we found hemizygous deletion with at least one of the markers in 18 tumors (31.5%). The frequency of loss was similar in both noninvasive (8 of 26;...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-07-01 00:00:00
abstract::Multiple copies of N-myc proto-oncogene are only rarely detected in localized neuroblastomas (NBs), and the prognostic relevance of amplification in this subset of patients is not clear. We analyzed a series of 850 children with NB admitted to a Pediatric Oncology Group NB Biology Study and identified six patients wit...
journal_title:Cancer research
pub_type: 杂志文章,多中心研究
doi:
更新日期:1995-02-15 00:00:00
abstract::Mouse bladder tumor (MBT-2), derived from a carcinogen-induced transitional cell carcinoma of the bladder, has proven a useful model for study of pathogenesis and prediction of cytotoxic drug sensitivity of human bladder carcinoma. To define optimal conditions for activity of the potent interferon inducer polyriboinos...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::Local chemotherapy with biodegradable polymers prolongs survival with minimal morbidity in patients with intracranial high-grade gliomas. However, use of local chemotherapy for metastatic brain tumors has not been defined. We studied the safety and the efficacy of locally delivered chemotherapy with and without concur...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-11-15 00:00:00
abstract::Whole-slide histology images contain information that is valuable for clinical and basic science investigations of cancer, but extracting quantitative measurements from these images is challenging for researchers who are not image analysis specialists. In this paper, we describe HistomicsML2, a software tool for learn...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-0668
更新日期:2020-12-21 00:00:00
abstract::Brain invasion by glioblastoma determines prognosis, recurrence, and lethality in patients, but no master factor coordinating the invasive properties of glioblastoma has been identified. Here we report evidence favoring such a role for the noncanonical WNT family member Wnt5a. We found the most invasive gliomas to be ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1693
更新日期:2017-02-15 00:00:00
abstract::This study identifies ataxia-telangiectasia mutated (ATM) as a further component of the complex signaling network of radiation-induced DNA damage in nontargeted bystander cells downstream of ataxia-telangiectasia and Rad3-related (ATR) and provides a rationale for molecular targeted modulation of these effects. In dir...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0545
更新日期:2008-09-01 00:00:00
abstract::Curcumin, a plant polyphenol, is a widely studied chemopreventive agent with demonstrated antitumor activities in preclinical studies and low toxicity profiles in multiple clinical trials against human malignancies. We previously showed that curcumin radiosensitizes cervical tumor cells without increasing the cytotoxi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-3025
更新日期:2010-03-01 00:00:00
abstract::We have recently identified a new gene, interleukin-17 receptor-like (IL-17RL), which is expressed in normal prostate and prostate cancer. This investigation is focused on the role of IL-17RL in prostate cancer. We found that IL-17RL was expressed at significantly higher levels in several androgen-independent prostate...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1130
更新日期:2006-01-01 00:00:00
abstract::Glioblastoma multiforme (GBM) is the most frequent and incurable type of brain tumor of adults. Hypoxia has been shown to direct GBM toward a more aggressive and malignant state. Here we show that hypoxia increases Notch1 activation, which in turn induces the expression of transient receptor potential 6 (TRPC6) in pri...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-2654
更新日期:2010-01-01 00:00:00
abstract::Elevated expression of Bmi-1 is associated with many cancers, including breast cancer. Here, we examined the oncogenic potential of Bmi-1 in MCF10A cells, a spontaneously immortalized, nontransformed strain of human mammary epithelial cells (HMEC). Bmi-1 overexpression alone in MCF10A cells did not result in oncogenic...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1636
更新日期:2007-11-01 00:00:00
abstract::Up-regulation of vascular endothelial growth factor (VEGF) expression is a major event leading to neovascularization in malignant gliomas. Hypoxia is believed to be the crucial environmental stimulus for this up-regulation. To critically assess this hypothesis, we asked whether the mechanisms defined previously for hy...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract::The expression of epidermal growth factor (EGF) receptor was examined immunohistochemically in a total of 122 gastric and 61 colonic carcinomas, out of which 16 gastric and 8 colonic carcinomas were also examined by 125I-labeled EGF binding analysis and Western blotting. The values of EGF binding were 12.68 +/- 1.98 (...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::The mechanism of action of the clinically used iron(III) chelator, desferrioxamine (DFO), on preventing iron (Fe) uptake from transferrin (Tf) has been investigated using the human melanoma cell line SK-MEL-28. This investigation was initiated due to the paucity of information on the mechanisms of action of DFO in neo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
abstract::N-Hydroxyarylamides are metabolically activated to nucleic acid-binding species by the action of N,O-acyltransferase (AT). The substrate specificity of these enzymes in rat, guinea pig, monkey, baboon, pig, and human liver has been examined by measuring the AT-mediated nucleic acid binding of the N-formyl, N-acetyl, a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-03-01 00:00:00
abstract::Monoclonal antibodies (mAb) are widely used in the treatment of non-Hodgkin's lymphoma and autoimmune diseases. Although the mechanism of action in vivo is not always known, the therapeutic activity of several approved mAbs depends on the binding of the Fcgamma regions to low-affinity Fcgamma receptors (FcgammaR) expr...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-0696
更新日期:2007-09-15 00:00:00
abstract::Age-adjusted mortality rates for non-Hodgkin's lymphoma in counties of the contiguous United States were examined by sex and race during 1950 to 1975 and were correlated through 1969 with demographic and industrial data. Mortality was consistently elevated in counties with large populations, especially in those with h...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-08-01 00:00:00
abstract::Antitumor effects of a soluble form dominant negative of the type I insulin-like growth factor receptor (IGF-IR) designated as 486/STOP were evaluated in CaOV-3 human ovarian cancer cells by establishing stable transformants overexpressing 486/STOP and by administration of 486/STOP recombinant protein. Expression of 4...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-11-15 00:00:00
abstract::7-Hydroxystaurosporine (UCN-01) is a protein kinase inhibitor that is under development as an anticancer agent in the United States and Japan. Long-term exposure of human A549 non-small cell lung cancer cells to UCN-01 furnished cells (A549/UCN) with acquired resistance against UCN-01. In this study, the sensitivity o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::Deoxycytidine kinase (DCK) is a key enzyme for the activation of a broad spectrum of nucleoside-based chemotherapy drugs (e.g., gemcitabine); low DCK activity is one of the most important causes of cancer drug-resistance. Noninvasive imaging methods that can quantify DCK activity are invaluable for assessing tumor res...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-3565
更新日期:2019-05-15 00:00:00
abstract::Synovial sarcoma is a soft tissue malignancy characterized by the fusion of SS18 to either SSX1, SSX2, or SSX4 genes. SS18 and SSX are transcriptional cofactors involved in activation and repression of gene transcription, respectively. SS18 interacts with SWI/SNF, whereas SSX associates with the polycomb chromatin rem...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0092
更新日期:2008-06-01 00:00:00
abstract::Despite the apparent similarity of the dexamethasone-receptor concentration in the rat liver and Novikoff hepatoma cytoplasms, the in vitro translocation of the dexamethasone-receptor complex into liver or hepatoma nuclei was three times greater from liver as compared to hepatoma cytosol; both cytosols showed an appar...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-06-01 00:00:00
abstract::8-Carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H) -one (mitozolomide) demonstrates curative action against a range of murine tumor model systems. At single doses of between 20 and 40 mg/kg, the latter of which approximates the 10% lethal dose value in mice, the compound elicited cures against the L121...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-07-01 00:00:00