Abstract：
:DNA repair status is recognized as an important determinant of the clinical efficacy of cancer chemotherapy. To assess the role that a mammalian DNA glycosylase plays in modulating the toxicity and clastogenicity of the chemotherapeutic DNA cross-linking alkylating agents, we compared the sensitivity of wild-type murine cells to that of isogenic cells bearing homozygous null mutations in the 3-methyladenine DNA glycosylase gene (Aag). We show that Aag protects against the toxic and clastogenic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea and mitomycin C (MMC), as measured by cell killing, sister chromatid exchange, and chromosome aberrations. This protection is accompanied by suppression of apoptosis and a slightly reduced p53 response. Our results identify 3-methyladenine DNA glycosylase-initiated base excision repair as a potentially important determinant of the clinical efficacy and, possibly, the carcinogenicity of these widely used chemotherapeutic agents. However, Aag does not contribute significantly to protection against the toxic and clastogenic effects of several chemotherapeutic nitrogen mustards (namely, mechlorethamine, melphalan, and chlorambucil), at least in the mouse embryonic stem cells used here. We also compare the Aag null phenotype with the Fanconi anemia phenotype, a human disorder characterized by cellular hypersensitivity to DNA cross-linking agents, including MMC. Although Aag null cells are sensitive to MMC-induced growth delay and cell cycle arrest, their sensitivity is modest compared to that of Fanconi anemia cells.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Allan JM,Engelward BP,Dreslin AJ,Wyatt MD,Tomasz M,Samson LDsubject
Has Abstractpub_date
1998-09-01 00:00:00pages
3965-73issue
17eissn
0008-5472issn
1538-7445journal_volume
58pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Many malignancies exhibit distinct patterns of metastasis that appear to be mediated by receptor/ligand-like interactions between tumor cells and organ-specific vascular endothelium. In order to study endothelial cell surface molecules involved in the binding of metastatic cells, we developed a perfusion method to iso...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:MCF-7 cells have been shown to contain estrogen receptor in several cell fractions following homogenization: nuclei, microsomes, and cytosol. The amount of 17 beta-estradiol-binding capacity found in each cellular compartment depended on the inclusion of detergent in homogenization buffers and on the use of 0.25 M suc...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-09-01 00:00:00
abstract：:Prostate cancer has become epidemic, and environmental factors such as cadmium may be partly responsible. This study reports malignant transformation of the nontumorigenic human prostatic epithelial cell line RWPE-1 by in vitro cadmium exposure. The cadmium-transformed cells exhibited a loss of contact inhibition in v...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-01-15 00:00:00
abstract：:Hypoxia is a common feature of solid tumors. Prolyl hydroxylase enzymes (PHD1-3) are molecular oxygen sensors that regulate hypoxia-inducible factor activity, but their functions in metastatic disease remain unclear. Here, we assessed the significance of PHD enzymes during the metastatic spread of colorectal cancer. P...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-1474
更新日期：2016-04-15 00:00:00
abstract：:Synovial sarcomas are aggressive spindle cell sarcomas containing in some cases areas of epithelial differentiation. They consistently show a specific t(X;18;p11;q11), which usually represents either of two gene fusions, SYT-SSX1 or SYT-SSX2, encoding putative transcriptional proteins differing at 13 amino acid positi...
journal_title：Cancer research
pub_type： 杂志文章,多中心研究
doi：
更新日期：2002-01-01 00:00:00
abstract：:The conditions for growing preneoplastic mammary epithelial cells in primary cell cultures with serum-free factor-defined medium were established in a series of experiments. The cells, grown in Dulbecco's modified Eagle's medium with 0.6 mM Ca2+, epidermal growth factor, transferrin, insulin, and Na2SeO3, were fibrobl...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-11-01 00:00:00
abstract：:TNF-α, produced by most malignant cells, orchestrates the interplay between malignant cells and myeloid cells, which have been linked to tumor growth and metastasis. Although TNF-α can exist as one of two isoforms, a 26-kDa membrane tethered form (mTNF-α) or a soluble 17-kDa cytokine (sTNF-α), the vast majority of pub...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-0002
更新日期：2013-07-01 00:00:00
abstract：:Cell cycle arrest in G2 phase is a common response to a variety of DNA-damaging agents. The coupling between DNA damage and G2 arrest was studied in synchronized HeLa cells using camptothecin, a highly specific inhibitor of topoisomerase I that damages DNA through the formation of reversible topoisomerase I-DNA cleava...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-04-01 00:00:00
abstract：:Cervical cancer develops from precancerous high-grade cervical intraepithelial neoplasia (CIN) harboring a transforming infection with high-risk human papillomavirus, which is characterized by p16(INK4a) overexpression. Once such a lesion has developed, progression toward an invasive squamous cell carcinoma (SCC) may ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-2478
更新日期：2009-01-15 00:00:00
abstract：:It is estimated that familial aggregation and genetic susceptibility play a role in as many as 10% of pancreatic ductal adenocarcinomas. To investigate the role of germ-line mutations in the etiology of pancreatic cancer, we have analyzed samples from patients with pancreatic cancer enrolled in the NFPTR for mutations...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-07-01 00:00:00
abstract：:Some, but not all, epidemiological studies have suggested that dichlorodiphenyltrichloroethane (DDT) may play a role in the development of breast cancer. These investigations have been conducted in countries where this substance has been banned for at least 20 years. We conducted a study in Mexico, a country in which ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：:The objective of this study is to elucidate the association between high-arsenic artesian well water and cancers in endemic area of blackfoot disease, a unique peripheral vascular disease related to continuous arsenic exposure. As compared with the general population in Taiwan, both the standardized mortality ratio (S...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:Using Mth1 and Ogg1 knockout mice, we evaluated the roles of these enzymes to prevent tumorigenesis and the accumulation of 8-oxoguanine (8-oxoG) in DNA. We found that lung adenoma/carcinoma spontaneously developed in Ogg1 knockout mice approximately 1.5 years after birth in which 8-oxoG was found to accumulate in the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-03-01 00:00:00
abstract：:Splenocytes from mice bearing a cachexia-inducing tumor (MAC16) have been fused with mouse myeloma cells to produce hybridomas, which have been cloned to produce antibody reactive to a material which copurified with a lipid-mobilizing factor isolated from the same tumor. The monoclonal antibody has been used to invest...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-03-15 00:00:00
abstract：:The correlation between the clinical outcome in patients with esophageal squamous cell carcinoma and coamplification of the proto-oncogenes int-2 and hst-1, which are partially homologous to angiogenesis-inducing fibroblast growth factor, was analyzed retrospectively. Coamplification of these genes was examined by slo...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:The glutathione transferase P (GST-P) gene is known for its specific expression during chemical hepatocarcinogenesis of the rat and is used as a tumor marker for hepatocellular carcinoma. We have shown recently that the upstream 2.9-kb region of the GST-P gene is sufficient for conferring tumor-specific expression of ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-06-15 00:00:00
abstract：:Tumor-initiating properties of complete carcinogens such as 7,12-dimethylbenz(a)anthracene (DMBA) are well known but not the mechanism of DMBA-mediated tumor promotion. Our hypothesis is that interleukin (IL)-1alpha, an early proinflammatory cytokine that initiates a cascade of other cytokines and growth factors, is u...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-01-15 00:00:00
abstract：:Breast cancer-initiating cells have been recently identified in breast carcinoma as CD44+/CD24(-/low) cells, which exclusively retain tumorigenic activity and display stem cell-like properties. However, at present, direct evidence that breast cancer-initiating cells can be propagated in vitro is still lacking. We repo...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-0626
更新日期：2005-07-01 00:00:00
abstract：:Cytogenetic analysis has indicated that deletion of chromosome 9p occurs in a significant number of non-small cell lung and mesothelioma tumors. Using paired oligonucleotide primers, we have undertaken an extensive analysis of 9p markers to determine homozygous and heterozygous loss of marker sequences. Homozygous los...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:The potential of transforming growth factor-alpha (TGF-alpha) to function as an autocrine growth factor was evaluated in numerous ovarian carcinoma cell lines. All 17 lines which were examined expressed the epidermal growth factor receptor and 16 cell lines, in addition, concomitantly secreted TGF-alpha. Radioimmunoas...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-01-15 00:00:00
abstract：:We have developed a defined serum-free medium for the in vitro growth of normal and neoplastic urothelium. Growth of epithelial cells in this medium was stimulated while proliferation of fibroblasts was inhibited. The medium allowed for the isolation of a new line from a high grade human bladder carcinoma. Several str...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-04-15 00:00:00
abstract：:We and others have reported previously that adults with glioma are 1.5- to 4-fold less likely than controls to report a variety of allergic conditions. The consistent nature of this relationship calls for a biological explanation so that preventative or therapeutic modalities can be explored. We enrolled 403 newly dia...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-1706
更新日期：2004-11-15 00:00:00
abstract：:To study antitumor functions of T-lymphocyte subpopulations in the blood [peripheral blood lymphocytes (PBLs)] and tumor-draining lymph nodes (LNs) of patients (n = 26) with squamous cell carcinoma of the head and neck (SCCHN), antibody-coated devices were used to positively select CD8+ or CD4+ cells. The mean percent...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Recently, we have reported that the toxicity of the membrane-active agent valinomycin (VM) can be reduced with maintenance and/or enhancement of its antitumor activity by incorporation in liposomes (S. S. Daoud and Juliano, Cancer Res., 46:5518-5525, 1986). Since the underlying defect(s) in multidrug resistance reside...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-05-15 00:00:00
abstract：:Monoclonal antibodies (MoAbs) against human osteosarcoma cells were obtained by the fusion of NS/1 mouse myeloma cells with spleen cells from the human osteosarcoma cell line-immunized BALB/c mice. Two hybrid clones were established and designated as 2H10 and 2D3. Both MoAbs reacted strongly with all osteosarcoma tiss...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-04-15 00:00:00
abstract：:The capacity for tumor cells to metastasize efficiently is directly linked to their ability to colonize secondary sites. Here we identify Six2, a developmental transcription factor, as a critical regulator of a breast cancer stem cell program that enables metastatic colonization. In several triple-negative breast canc...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-18-1791
更新日期：2019-02-15 00:00:00
abstract：:Although chrysotile asbestos is a proven human carcinogen, several studies have concluded that these fibers are not mutagenic to cultured mammalian cells. We show here, on the other hand, that when tested using the AL cell system that detects both intragenic and multilocus mutations, chrysotile is indeed mutagenic and...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-11-15 00:00:00
abstract：:Interleukin 4, a T cell-derived 20-kDa glycoprotein, plays an important role in regulating the immune response of B cells, T cells, and macrophages against infections and malignant cells. For this reason recombinant human interleukin 4 (rhIL-4) has entered early clinical trials in cancer patients. In the present study...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-05-15 00:00:00
abstract：:It has been hypothesized that complement inhibitors expressed on the surface of tumor cells prevent effective immune-mediated clearance. Whereas there are in vitro data to support this hypothesis, the species-selective activity of complement inhibitors has been a hindrance to investigating the role of membrane-bound c...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
abstract：:Although ethanol has generally not been found to induce cancer in experimental animals, the consumption of alcoholic beverages has been linked to increased risks of several cancers in humans. Risks of oral, pharyngeal, laryngeal, esophageal, and liver cancer are elevated among drinkers, typically in proportion to the ...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：
更新日期：1992-04-01 00:00:00
