Discovery of DNA repair inhibitors by combinatorial library profiling.

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 Res

journal_title

Cancer research

authors

Moeller BJ,Sidman RL,Pasqualini R,Arap W

doi

10.1158/0008-5472.CAN-10-2361

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

1816-24

issue

5

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-10-2361

journal_volume

71

pub_type

杂志文章
  • Expression of the O6-methylguanine-DNA methyltransferase gene MGMT in MER+ and MER- human tumor cells.

    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:

    authors: Fornace AJ Jr,Papathanasiou MA,Hollander MC,Yarosh DB

    更新日期:1990-12-15 00:00:00

  • The effect of exposure to dibutyryl cyclic adenylic acid on the membrane antigenicity of SV40 tumor cells.

    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:

    authors: Hannon WH,Anderson NG,Coggin JH Jr

    更新日期:1976-09-01 00:00:00

  • Recognition and killing of brain tumor stem-like initiating cells by CD8+ cytolytic T cells.

    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

    authors: Brown CE,Starr R,Martinez C,Aguilar B,D'Apuzzo M,Todorov I,Shih CC,Badie B,Hudecek M,Riddell SR,Jensen MC

    更新日期:2009-12-01 00:00:00

  • Differentiation of lobular versus ductal breast carcinomas by expression microarray analysis.

    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:

    authors: Korkola JE,DeVries S,Fridlyand J,Hwang ES,Estep AL,Chen YY,Chew KL,Dairkee SH,Jensen RM,Waldman FM

    更新日期:2003-11-01 00:00:00

  • Human Pluripotent Stem Cell-Derived TSC2-Haploinsufficient Smooth Muscle Cells Recapitulate Features of Lymphangioleiomyomatosis.

    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

    authors: Julian LM,Delaney SP,Wang Y,Goldberg AA,Doré C,Yockell-Lelièvre J,Tam RY,Giannikou K,McMurray F,Shoichet MS,Harper ME,Henske EP,Kwiatkowski DJ,Darling TN,Moss J,Kristof AS,Stanford WL

    更新日期:2017-10-15 00:00:00

  • Purification of an anemia-inducing factor from human placenta and its application to diagnosis of malignant neoplasms.

    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:

    authors: Oh-Uti K,Inoue S,Minato S

    更新日期:1980-05-01 00:00:00

  • Formation of glutathione conjugates by reactive metabolites of vinylidene chloride in microsomes and isolated hepatocytes.

    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:

    authors: Liebler DC,Meredith MJ,Guengerich FP

    更新日期:1985-01-01 00:00:00

  • Effects of Anticancer Drugs on Chromosome Instability and New Clinical Implications for Tumor-Suppressing Therapies.

    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

    authors: Lee HS,Lee NC,Kouprina N,Kim JH,Kagansky A,Bates S,Trepel JB,Pommier Y,Sackett D,Larionov V

    更新日期:2016-02-15 00:00:00

  • Adsorption of messenger RNA of Novikoff hepatoma, normal liver, and regenerating liver on complementary DNA-cellulose affinity matrices.

    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:

    authors: Hirsch FW,Nall KN,Hayes LC,Raju KS,Spohn WH,Busch H

    更新日期:1977-10-01 00:00:00

  • Reductive activation of mitomycin C by NADH:cytochrome b5 reductase.

    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:

    authors: Hodnick WF,Sartorelli AC

    更新日期:1993-10-15 00:00:00

  • Inhibition by the dopamine antagonist haloperidol of experimental carcinogenesis induced by azoxymethane in rat colon.

    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:

    authors: Iishi H,Baba M,Tatsuta M,Okuda S,Taniguchi H

    更新日期:1991-11-15 00:00:00

  • Chemical characterization of the degradation products of vinblastine dihydrogen sulfate.

    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:

    authors: Thimmaiah KN,Sethi VS

    更新日期:1985-11-01 00:00:00

  • Serum acute-phase proteins and immunoglobulins in patients with gliomas.

    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:

    authors: Weiss JF,Morantz RA,Bradley WP,Chretien PB

    更新日期:1979-02-01 00:00:00

  • Centrosome amplification and overexpression of aurora A are early events in rat mammary carcinogenesis.

    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:

    authors: Goepfert TM,Adigun YE,Zhong L,Gay J,Medina D,Brinkley WR

    更新日期:2002-07-15 00:00:00

  • Genomic aberrations occurring in subsets of serrated colorectal lesions but not conventional adenomas.

    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

    authors: Burnett-Hartman AN,Newcomb PA,Potter JD,Passarelli MN,Phipps AI,Wurscher MA,Grady WM,Zhu LC,Upton MP,Makar KW

    更新日期:2013-05-01 00:00:00

  • Effect of progressive neoplastic growth on the decarboxylation of DL-[1-14C]ornithine by lymphocytes from C3H/He tumor hosts.

    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:

    authors: Vaage J,Agarwal S,Reinertsen JL

    更新日期:1978-08-01 00:00:00

  • Induction of lymphomas in mice by busulfan and chloramphenicol.

    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:

    authors: Robin E,Berman M,Bhoopalam N,Cohen H,Fried W

    更新日期:1981-09-01 00:00:00

  • Intact nitric oxide synthase II gene is required for interferon-beta-mediated suppression of growth and metastasis of pancreatic adenocarcinoma.

    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:

    authors: Wang B,Xiong Q,Shi Q,Le X,Abbruzzese JL,Xie K

    更新日期:2001-01-01 00:00:00

  • Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesis.

    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:

    authors: Pan Q,Kleer CG,van Golen KL,Irani J,Bottema KM,Bias C,De Carvalho M,Mesri EA,Robins DM,Dick RD,Brewer GJ,Merajver SD

    更新日期:2002-09-01 00:00:00

  • Acid pH in tumors and its potential for therapeutic exploitation.

    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:

    authors: Tannock IF,Rotin D

    更新日期:1989-08-15 00:00:00

  • Therapeutic antibody targeting of CD47 eliminates human acute lymphoblastic leukemia.

    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

    authors: Chao MP,Alizadeh AA,Tang C,Jan M,Weissman-Tsukamoto R,Zhao F,Park CY,Weissman IL,Majeti R

    更新日期:2011-02-15 00:00:00

  • Heme-oxygenase-1 Production by Intestinal CX3CR1+ Macrophages Helps to Resolve Inflammation and Prevents Carcinogenesis.

    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

    authors: Marelli G,Erreni M,Anselmo A,Taverniti V,Guglielmetti S,Mantovani A,Allavena P

    更新日期:2017-08-15 00:00:00

  • Preclinical antilymphoma activity of a humanized anti-CD40 monoclonal antibody, SGN-40.

    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

    authors: Law CL,Gordon KA,Collier J,Klussman K,McEarchern JA,Cerveny CG,Mixan BJ,Lee WP,Lin Z,Valdez P,Wahl AF,Grewal IS

    更新日期:2005-09-15 00:00:00

  • Effect of liposome composition and other factors on the targeting of liposomes to experimental tumors: biodistribution and imaging studies.

    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:

    authors: Gabizon A,Price DC,Huberty J,Bresalier RS,Papahadjopoulos D

    更新日期:1990-10-01 00:00:00

  • Minimal determinant expressed by a recombinant vaccinia virus elicits therapeutic antitumor cytolytic T lymphocyte responses.

    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:

    authors: McCabe BJ,Irvine KR,Nishimura MI,Yang JC,Spiess PJ,Shulman EP,Rosenberg SA,Restifo NP

    更新日期:1995-04-15 00:00:00

  • miR-483-5p promotes invasion and metastasis of lung adenocarcinoma by targeting RhoGDI1 and ALCAM.

    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

    authors: Song Q,Xu Y,Yang C,Chen Z,Jia C,Chen J,Zhang Y,Lai P,Fan X,Zhou X,Lin J,Li M,Ma W,Luo S,Bai X

    更新日期:2014-06-01 00:00:00

  • Dose-dependent reduction of N-2-fluorenylacetamide-induced liver cancer and enhancement of bladder cancer in rats by butylated hydroxytoluene.

    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:

    authors: Maeura Y,Weisburger JH,Williams GM

    更新日期:1984-04-01 00:00:00

  • DNA double-strand break repair pathways and cellular tolerance to inhibitors of topoisomerase II.

    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:

    authors: Caldecott K,Banks G,Jeggo P

    更新日期:1990-09-15 00:00:00

  • Functional hyaluronan receptors are expressed on a squamous cell lung carcinoma cell line but not on other lung carcinoma cell lines.

    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:

    authors: Teder P,Bergh J,Heldin P

    更新日期:1995-09-01 00:00:00

  • The reduction of N-hydroxy-4-acetylaminobiphenyl by the intestinal microflora of the rat.

    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:

    authors: Wheeler LA,Soderberg FB,Goldman P

    更新日期:1975-11-01 00:00:00