Abstract：
:Small molecule inhibitors of DNA repair are emerging as potent and selective anticancer therapies, but the sheer magnitude of the protein networks involved in DNA repair processes poses obstacles to discovery of effective candidate drugs. To address this challenge, we used a subtractive combinatorial selection approach to identify a panel of peptide ligands that bind DNA repair complexes. Supporting the concept that these ligands have therapeutic potential, we show that one selected peptide specifically binds and noncompetitively inactivates DNA-PKcs, a protein kinase critical in double-strand DNA break repair. In doing so, this ligand sensitizes BRCA-deficient tumor cells to genotoxic therapy. Our findings establish a platform for large-scale parallel screening for ligand-directed DNA repair inhibitors, with immediate applicability to cancer therapy.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Moeller BJ,Sidman RL,Pasqualini R,Arap Wdoi
10.1158/0008-5472.CAN-10-2361subject
Has Abstractpub_date
2011-03-01 00:00:00pages
1816-24issue
5eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-10-2361journal_volume
71pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:DNA probes prepared from human O6-methylguanine-DNA methyltransferase complementary DNA were hybridized to mRNA isolated from human liver and fifteen human tumor cell lines proficient (Mer+) or deficient (Mer-) in transferase activity. Liver and Mer+ cells contained levels of transferase-specific mRNA that correlated ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-12-15 00:00:00
abstract：:When SV40 tumor cells (F5-1) in culture were treated with dibutyryl cyclic adenylic acid (DbcAMP),marked alterations occurred in their growth and morphology. Additionally, the incorporation or uptake of labeled thymidine, uridine, phenylalanine, and choline were reduced by this treatment. These modifications with DbcA...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-09-01 00:00:00
abstract：:Solid tumors contain a subset of stem-like cells that are resistant to the cytotoxic effects of chemotherapy/radiotherapy, but their susceptibility to cytolytic T lymphocyte (CTL) effector mechanisms has not been well characterized. Using a panel of early-passage human brain tumor stem/initiating cell (BTSC) lines der...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-2687
更新日期：2009-12-01 00:00:00
abstract：:Invasive lobular and ductal breast tumors have distinct histologies and clinical presentation. Other than altered expression of E-cadherin, little is known about the underlying biology that distinguishes the tumor subtypes. We used cDNA microarrays to identify genes differentially expressed between lobular and ductal ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-11-01 00:00:00
abstract：:Lymphangioleiomyomatosis (LAM) is a progressive destructive neoplasm of the lung associated with inactivating mutations in the TSC1 or TSC2 tumor suppressor genes. Cell or animal models that accurately reflect the pathology of LAM have been challenging to develop. Here, we generated a robust human cell model of LAM by...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-0925
更新日期：2017-10-15 00:00:00
abstract：:An anemia-inducing substance was isolated from the human placenta and designated placental anemia-inducing factor (PAIF). An amount of 2.8 mg was purified from about 70 total placentas (total wet weight, 42 kg). PAIF caused hemolysis of human erythrocytes in vitro and reduced the number of erythrocytes in rabbits to 8...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-05-01 00:00:00
abstract：:Oxidation of the vinyl halide carcinogen and hepatotoxin vinylidene chloride (VDC) by microsomal cytochrome P-450 yields 2,2-dichloroacetaldehyde, 2-chloroacetyl chloride, 2-chloroacetic acid, and 1,1-dichloroethylene oxide. The roles of these metabolites in covalent modification of proteins and reduced glutathione (G...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：:Whole chromosomal instability (CIN), manifested as unequal chromosome distribution during cell division, is a distinguishing feature of most cancer types. CIN is generally considered to drive tumorigenesis, but a threshold level exists whereby further increases in CIN frequency in fact hinder tumor growth. While this ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-1617
更新日期：2016-02-15 00:00:00
abstract：:Complementary DNA (cDNA)-oligodeoxythmidylate-celluloses were prepared from cDNA copies of polysomal messenger RNA (mRNA) of Novikoff hepatoma, normal rat liver, and regenerating rat liver. cDNA synthesis with reverse transcriptase was approximately 46% with respect to input mRNA with oligodeoxythymidylate-cellulose p...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-10-01 00:00:00
abstract：:Mitomycin C requires bioreduction in order to exert its cytotoxic action. Activation of mitomycin C to an electrophile was equally supported by NADPH and NADH in EMT6 tumor cell sonicates under hypoxia. No alkylation was observed under aerobic conditions. Purified NADH:cytochrome b5 reductase catalyzed the reduction o...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-10-15 00:00:00
abstract：:The effects of the dopamine agonist bromocriptine and antagonist haloperidol on the incidence and histology of colon tumors induced by azoxymethane and on the labeling index of colon mucosa were investigated in Wistar rats. Rats received weekly s.c. injections of 7.4 mg/kg of body weight azoxymethane for 10 weeks and ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-11-15 00:00:00
abstract：:Vinblastine was incubated in 0.2 M glycine buffer (pH 7.4 or 8.8) containing bovine serum albumin (1%) at 37 degrees C for 72 h. The reaction mixture was extracted with CH2Cl2, and the extract gave 6 major peaks (A, B, C, D, E, and F) with retention times of 5.0, 7.5, 11.0, 13.0, 23.0, and 30.0 min, respectively, in a...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:Cellular immune competence was found to be impaired in previous studies of patients with malignant brain tumors. In patients with nonneural tumors, we recently found that serum levels of acute-phase proteins were related to immune status as well as to tumor extent. To determine whether the serum proteins in patients w...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-02-01 00:00:00
abstract：:The cells of many solid tumors have been found to contain supernumerary centrosomes, a condition known as centrosome amplification. Centrosome amplification, accompanied by the overexpression of an associated kinase, Aurora A (AurA), has been implicated in mechanisms leading to mitotic spindle aberrations, aneuploidy,...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-07-15 00:00:00
abstract：:A subset of aggressive colorectal cancers exhibit BRAF mutation, MLH1 methylation, and a CpG island methylator phenotype (CIMP), but precursors are poorly established. In this study, we determined the status of these markers in colorectal polyps and evaluated associated risk factors. The study included 771 polyp cases...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-12-3462
更新日期：2013-05-01 00:00:00
abstract：:The reactivity of normal and tumor host lymphocytes incubated with normal serum or with serum or malignant ascites fluid from tumor hosts was measured by the ability of the lymphocytes to synthesize ornithine decarboxylase after phytohemagglutinin stimulation. Each of three tumors tested (a solid fibrosarcoma, an asci...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1978-08-01 00:00:00
abstract：:Busulfan causes long-lasting defects in the hematopoietic stem cells and in the immune system of mice. We designed studies to determine whether chloramphenicol further damaged the already defective hematopoietic stem cells of mice that were pretreated with busulfan, and we unexpectedly observed that mice given injecti...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-09-01 00:00:00
abstract：:Previous studies have shown that enforced expression of IFN-beta suppressed tumor growth and metastasis. In this report, we determined whether the induction of nitric oxide synthase II (NOS II) gene is required for IFN-beta-mediated antitumor activity using syngeneic mice with intact (NOS II+/+) or genetically disrupt...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:Copper plays an essential role in promoting angiogenesis. Tumors that become angiogenic acquire the ability to enter a phase of rapid growth and exhibit increased metastatic potential, the major cause of morbidity in cancer patients. We report that copper deficiency induced by tetrathiomolybdate (TM) significantly imp...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-09-01 00:00:00
abstract：:Measurement of pH in tissue has shown that the microenvironment in tumors is generally more acidic than in normal tissues. Major mechanisms which lead to tumor acidity probably include the production of lactic acid and hydrolysis of ATP in hypoxic regions of tumors. Further reduction in pH may be achieved in some tumo...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-08-15 00:00:00
abstract：:Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and constitutes 15% of adult leukemias. Although overall prognosis for pediatric ALL is favorable, high-risk pediatric patients and most adult patients have significantly worse outcomes. Multiagent chemotherapy is standard of care for both pedi...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-2238
更新日期：2011-02-15 00:00:00
abstract：:CX3CR1+ macrophages in the intestinal lamina propria contribute to gut homeostasis through the immunomodulatory interleukin IL10, but there is little knowledge on how these cells or the CX3CR1 receptor may affect colorectal carcinogenesis. In this study, we show that CX3CR1-deficient mice fail to resolve gut inflammat...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-2501
更新日期：2017-08-15 00:00:00
abstract：:SGN-40 is a humanized IgG1 antihuman CD40 that is currently in a phase I clinical trial for the treatment of multiple myeloma. As surface CD40 expression on B-lineage cells is maintained from pro-B cells to plasma cells, SGN-40 may be applicable to treatment of other B-cell neoplasias, including non-Hodgkin's lymphoma...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-0095
更新日期：2005-09-15 00:00:00
abstract：:We have examined the distribution of radiolabeled liposomes in tumor-bearing mice after i.v. injection. Two mouse tumors (B16 melanoma, J6456 lymphoma) and a human tumor (LS174T colon carcinoma) inoculated i.m., s.c., or in the hind footpad were used in these studies. When various liposome compositions with a mean ves...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
abstract：:Anticancer vaccine strategies can now target intracellular antigens that are involved in the process of malignant transformation, such as oncogene products or mutated tumor suppressor genes. Fragments of these antigens, generally 8-10 amino acids in length and complexed with MHC class I molecules, can be recognized by...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-04-15 00:00:00
abstract：:The nodal regulatory properties of microRNAs (miRNA) in metastatic cancer may offer new targets for therapeutic control. Here, we report that upregulation of miR-483-5p is correlated with the progression of human lung adenocarcinoma. miR-483-5p promotes the epithelial-mesenchymal transition (EMT) accompanied by invasi...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-2193
更新日期：2014-06-01 00:00:00
abstract：:The modifying effect of four dose levels of butylated hydroxytoluene (BHT) on liver and bladder carcinogenesis by N-2-fluorenylacetamide (FAA) was studied in rats. FAA (200 ppm) was fed simultaneously with four levels of BHT (300, 1000, 3000, and 6000 ppm) to male F344 Fischer strain rats. Groups of animals were kille...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-04-01 00:00:00
abstract：:The Chinese hamster ovary cell line xrs-1 is hypersensitive to gamma-radiation. This sensitivity has been attributed to an inability of this cell line to efficiently repair gamma-ray induced double-strand breaks (DSBs). We have recently reported that xrs-1 is also sensitive to topoisomerase II inhibitors that stabiliz...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-09-15 00:00:00
abstract：:We investigated the production of hyaluronan and the presence of hyaluronan receptors in a panel of human lung carcinoma cell lines, consisting of small cell carcinomas (SCLC) and non-small cell carcinomas (non-SCLC). These transformed cell lines produced only minute amounts of hyaluronan, whereas normal lung fibrobla...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:The role of the intestinal flora in the conversion of N-hydroxy-4-acetyl-aminobiphenyl (N-OH-AABP) to 4-acetylaminobiphenyl has been examined. This reaction, which reverses the metabolic activation of the parent carcinogen, can be demonstrated in cultures of some bacteria indigenous to the intestinal microflora. These...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-11-01 00:00:00
