Protein kinase C inhibitor sotrastaurin selectively inhibits the growth of CD79 mutant diffuse large B-cell lymphomas.

Abstract:

:The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) correlates with poor prognosis. The ABC subtype of DLBCL is associated with constitutive activation of the NF-κB pathway, and oncogenic lesions have been identified in its regulators, including CARD11/CARMA1 (caspase recruitment domain-containing protein 11), A20/TNFAIP3, and CD79A/B. In this study, we offer evidence of therapeutic potential for the selective PKC (protein kinase C) inhibitor sotrastaurin (STN) in preclinical models of DLBCL. A significant fraction of ABC DLBCL cell lines exhibited strong sensitivity to STN, and we found that the molecular nature of NF-κB pathway lesions predicted responsiveness. CD79A/B mutations correlated with STN sensitivity, whereas CARD11 mutations rendered ABC DLBCL cell lines insensitive. Growth inhibitory effects of PKC inhibition correlated with NF-κB pathway inhibition and were mediated by induction of G₁-phase cell-cycle arrest and/or cell death. We found that STN produced significant antitumor effects in a mouse xenograft model of CD79A/B-mutated DLBCL. Collectively, our findings offer a strong rationale for the clinical evaluation of STN in ABC DLBCL patients who harbor CD79 mutations also illustrating the necessity to stratify DLBCL patients according to their genetic abnormalities.

journal_name

Cancer Res

journal_title

Cancer research

authors

Naylor TL,Tang H,Ratsch BA,Enns A,Loo A,Chen L,Lenz P,Waters NJ,Schuler W,Dörken B,Yao YM,Warmuth M,Lenz G,Stegmeier F

doi

10.1158/0008-5472.CAN-10-2525

subject

Has Abstract

pub_date

2011-04-01 00:00:00

pages

2643-53

issue

7

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-10-2525

journal_volume

71

pub_type

杂志文章
  • Combination therapies against chronic myeloid leukemia: short-term versus long-term strategies.

    abstract::During therapy for chronic myeloid leukemia (CML), decline of the number of BCR-ABL transcripts has been shown to follow a biphasic pattern, with a fast phase followed by a slower phase. Hence, sustained remission requires a long phase of therapy. Data indicate that a combination of different available targeted drugs ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-1959

    authors: Komarova NL,Wodarz D

    更新日期:2009-06-01 00:00:00

  • A comparison of the effects of daunomycin and adriamycin on various DNA polymerases.

    abstract::The effects of the anthracycline antiboties, daunomycin and adriamycin, on the DNA-directed activities of DNA polymerases from murine sarcoma virus, rat liver (high-molecular-weight species), Escherichia coli, and Micrococcus luteus were determined. Under all conditions tested, these compounds had greater inhibitory e...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Zunino F,Gambetta R,Di Marco A,Zaccara A,Luoni G

    更新日期:1975-03-01 00:00:00

  • Prolonged ornithine decarboxylase induction in regenerating carcinogen-treated liver.

    abstract::A cascade of events leading to hypertrophy has been proposed and implicated in growth regulation in a variety of normal and neoplastic cells and tissues. There is a tightly coupled temporal sequence: (a) cyclic adenosine 3':5'-monophosphate-dependent protein kinase (cAPK) activation; (b) ornithine decarboxylase (ODC) ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Olson JW,Russell DH

    更新日期:1980-12-01 00:00:00

  • Bcl-2/adenovirus E1B 19 kDa interacting protein-3 knockdown enables growth of breast cancer metastases in the lung, liver, and bone.

    abstract::The mouse breast cancer cell lines 4T1, 4T07, and 67NR are highly tumorigenic but vary in metastatic potential: 4T1 widely disseminates, resulting in secondary tumors in the lung, liver, bone, and brain; 4T07 spreads to the lung and liver but is unable to establish metastatic nodules; 67NR is unable to metastasize. Th...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-3091

    authors: Manka D,Spicer Z,Millhorn DE

    更新日期:2005-12-15 00:00:00

  • An osteoprotegerin-like peptidomimetic inhibits osteoclastic bone resorption and osteolytic bone disease in myeloma.

    abstract::Multiple myeloma is a B-cell malignancy characterized by the uncontrolled growth of plasma cells in the bone marrow and the development of osteolytic bone disease. Myeloma cells express the receptor activator of nuclear factor kappaB ligand (RANKL), induce RANKL expression in the bone marrow, and down-regulate express...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-1287

    authors: Heath DJ,Vanderkerken K,Cheng X,Gallagher O,Prideaux M,Murali R,Croucher PI

    更新日期:2007-01-01 00:00:00

  • Behavior of transaldolase (EC 2.2.1.2) and transketolase (EC 2.2.1.1) Activities in normal, neoplastic, differentiating, and regenerating liver.

    abstract::The objective of this investigation was to throw light on the biological behavior and metabolic regulation of hepatic enzymes of the nonoxidative branch of the pentose phosphate pathway. The activities of transaldolase (EC 2.2.1.2) and trasketolase (EC 2.2.1.1) Were compared in biological conditions that involve modu...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Heinrich PC,Morris HP,Weber G

    更新日期:1976-09-01 00:00:00

  • Comparison of different busulfan analogues for depletion of hematopoietic stem cells and promotion of donor-type chimerism in murine bone marrow transplant recipients.

    abstract::Busulfan (1,4-butanediol dimethanesulfonate, BU) is relatively unique among other standard chemotherapy compounds in its ability to deplete noncycling primitive stem cells in the host and consequently to allow for high levels of long-term, donor-type engraftment after bone marrow transplantation (BMT). Such a property...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Westerhof GR,Ploemacher RE,Boudewijn A,Blokland I,Dillingh JH,McGown AT,Hadfield JA,Dawson MJ,Down JD

    更新日期:2000-10-01 00:00:00

  • Increased methotrexate resistance and dhfr gene amplification as a consequence of induced Ha-ras expression in NIH 3T3 cells.

    abstract::Oncogene activation and loss of tumor suppressor genes are known to play a role in tumor initiation as well as its progression. The potential roles of these genes in perturbation of genome stability has become a major interest. To better understand the relationship between expression of an oncogene and genetic instabi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Wani MA,Xu X,Stambrook PJ

    更新日期:1994-05-01 00:00:00

  • Suppression of Bcl-2 messenger RNA production may mediate apoptosis after ionizing radiation, tumor necrosis factor alpha, and ceramide.

    abstract::Recent studies have proposed that tumor necrosis factor alpha (TNF-alpha) and ionizing radiation induce apoptosis by activating hydrolysis of sphingomyelin to ceramide. Bcl-2 and a related gene, Bcl-X, inhibit several forms of apoptosis. Herein, we report that internucleosomal DNA fragmentation, characteristic of apop...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Chen M,Quintans J,Fuks Z,Thompson C,Kufe DW,Weichselbaum RR

    更新日期:1995-03-01 00:00:00

  • Early and late changes in nonhistone chromatin proteins accompanying rat liver regeneration.

    abstract::Chromatin was isolated from 0.025 M citric acid nuclei of regenerating rat liver at 1,5,18,24, and 48 hr posthepatectomy. The total protein to DNA ratios did not change significantly during this time period. However, 2-dimensional polyacrylamide gel electrophoresis of nonhistone proteins of "Chromatin Fraction II" rev...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yeoman LC,Taylor CW,Jordan JJ,Busch H

    更新日期:1975-05-01 00:00:00

  • Fusion of ETV6 to fibroblast growth factor receptor 3 in peripheral T-cell lymphoma with a t(4;12)(p16;p13) chromosomal translocation.

    abstract::Fusions of the ETV6/TEL gene to receptor or protein tyrosine kinases (TKs), such as PDGFRbeta, JAK2, ABL, ABL2, TRKC, and Syk, have been reported in various hematological malignancies. Expression of the resultant chimeric proteins is believed to lead to constitutive TK activity through activation by the helix-loop-hel...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yagasaki F,Wakao D,Yokoyama Y,Uchida Y,Murohashi I,Kayano H,Taniwaki M,Matsuda A,Bessho M

    更新日期:2001-12-01 00:00:00

  • Transformation of astrocytes in transgenic mice expressing SV40 T antigen under the transcriptional control of the glial fibrillary acidic protein promoter.

    abstract::There are many animal models of glioma, but few that represent the biology of low-grade tumors and allow the study of the genetic mechanisms of glial oncogenesis. We report the in vivo transformation of astrocytic cells in transgenic mice by the SV40 T antigen under the control of the 5'-flanking sequence of the murin...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Danks RA,Orian JM,Gonzales MF,Tan SS,Alexander B,Mikoshiba K,Kaye AH

    更新日期:1995-10-01 00:00:00

  • Effects of tumor cell viability and inoculum density on growth parameters in the human tumor, soft-agar clonogenic assay.

    abstract::Four hundred and forty-seven human tumor specimens were accessioned and processed for clonogenic assay, yielding 374 specimens, representing 23 different histiotypes, adequate for culture. Different levels of viable cell inoculum density produced contrasting effects between 255 solid tumors as compared to 72 malignant...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Page RH,Tilchen EJ,Davis HL

    更新日期:1988-07-15 00:00:00

  • Simultaneous suppression of epidermal growth factor receptor and c-erbB-2 reverses aneuploidy and malignant phenotype of a human ovarian carcinoma cell line.

    abstract::Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47-68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of c...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.can-03-1982

    authors: Pack SD,Alper OM,Stromberg K,Augustus M,Ozdemirli M,Miermont AM,Klus G,Rusin M,Slack R,Hacker NF,Ried T,Szallasi Z,Alper O

    更新日期:2004-02-01 00:00:00

  • NF-κB hyperactivation in tumor tissues allows tumor-selective reprogramming of the chemokine microenvironment to enhance the recruitment of cytolytic T effector cells.

    abstract::Tumor infiltration with effector CD8(+) T cells (T(eff)) predicts longer recurrence-free survival in many types of human cancer, illustrating the broad significance of T(eff) for effective immunosurveillance. Colorectal tumors with reduced accumulation of T(eff) express low levels of T(eff)-attracting chemokines such ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-11-4136

    authors: Muthuswamy R,Berk E,Junecko BF,Zeh HJ,Zureikat AH,Normolle D,Luong TM,Reinhart TA,Bartlett DL,Kalinski P

    更新日期:2012-08-01 00:00:00

  • Turnover modulates the need for a cost of resistance in adaptive therapy.

    abstract::Adaptive therapy seeks to exploit intra-tumoral competition to avoid, or at least delay, the emergence of therapy resistance in cancer. Motivated by promising results in prostate cancer, there is growing interest in extending this approach to other neoplasms. As such, it is urgent to understand the characteristics of ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-20-0806

    authors: Strobl MAR,West J,Viossat Y,Damaghi M,Robertson-Tessi M,Brown JS,Gatenby RA,Maini PK,Anderson ARA

    更新日期:2020-11-10 00:00:00

  • Aerobic glycolysis suppresses p53 activity to provide selective protection from apoptosis upon loss of growth signals or inhibition of BCR-Abl.

    abstract::Unlike the growth factor dependence of normal cells, cancer cells can maintain growth factor-independent glycolysis and survival through expression of oncogenic kinases, such as BCR-Abl. Although targeted kinase inhibition can promote cancer cell death, therapeutic resistance develops frequently, and further mechanist...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-10-0608

    authors: Mason EF,Zhao Y,Goraksha-Hicks P,Coloff JL,Gannon H,Jones SN,Rathmell JC

    更新日期:2010-10-15 00:00:00

  • p44 mitogen-activated protein kinase (extracellular signal-regulated kinase 1)-dependent signaling contributes to epithelial skin carcinogenesis.

    abstract::Extracellular signal-regulated kinases (ERK) regulate cellular functions in response to a variety of external signals. However, the specific functions of individual ERK isoforms are largely unknown. Hence, we have investigated the specific function of ERK1 in skin homeostasis and tumorigenesis in ERK1 knockout mice. T...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-3129

    authors: Bourcier C,Jacquel A,Hess J,Peyrottes I,Angel P,Hofman P,Auberger P,Pouysségur J,Pagès G

    更新日期:2006-03-01 00:00:00

  • Adipocytes impair leukemia treatment in mice.

    abstract::Obesity is associated with increased cancer incidence and mortality. We have previously found that obesity in children is associated with a 50% increased recurrence of acute lymphoblastic leukemia (ALL) in high-risk patients. We have therefore developed novel in vivo and in vitro preclinical models to study the mechan...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-0800

    authors: Behan JW,Yun JP,Proektor MP,Ehsanipour EA,Arutyunyan A,Moses AS,Avramis VI,Louie SG,Butturini A,Heisterkamp N,Mittelman SD

    更新日期:2009-10-01 00:00:00

  • Plasma therapy of primary rat mammary carcinoma: dependence of consumption of C3 during absorption of plasma with sepharose derivatives on the anticoagulant.

    abstract::A previous study demonstrated inhibition of growth of primary rat mammary carcinomas after infusion of tumor-bearer plasma absorbed against Sepharose derivatives. In this report we have quantitated changes in individual complement components that occur during absorption of rat plasma with Sepharose derivatives and def...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Nakanishi K,Zbar B,Borsos T

    更新日期:1985-09-01 00:00:00

  • Galectin-Binding O-Glycosylations as Regulators of Malignancy.

    abstract::Cancer cells commonly display aberrant surface glycans and related glycoconjugate scaffolds. Compared with their normal counterparts, cancer cell glycans are variably produced and often structurally distinct, serving as biomarkers of cancer progression or as functional entities to malignancy. The glycan signature of a...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:10.1158/0008-5472.CAN-15-0834

    authors: Dimitroff CJ

    更新日期:2015-08-15 00:00:00

  • Truncation at conserved terminal regions of BRCA1 protein is associated with highly proliferating hereditary breast cancers.

    abstract::The existence of two subgroups of BRCA1-associated breast cancer (BC) families has been recently posited: the first with highly proliferating tumors, and the second composed of cases with a low proliferation rate. Our aim was to test whether the proliferation rate of BRCA1-associated breast cancers was affected by the...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Sobol H,Stoppa-Lyonnet D,Bressac-de-Paillerets B,Peyrat JP,Kerangueven F,Janin N,Noguchi T,Eisinger F,Guinebretiere JM,Jacquemier J,Birnbaum D

    更新日期:1996-07-15 00:00:00

  • Role of GRP58 in mitomycin C-induced DNA cross-linking.

    abstract::Mitomycin C (MMC) is an anticancer drug that requires reductive activation to exert its toxicity. MMC is known to cross-link DNA that contributes significantly to the cytotoxicity and consequent cell death. Cytosolic NADPH:quinone oxidoreductase 1 (NQO1) and microsomal enzymes have been shown to mediate MMC-induced DN...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Celli CM,Jaiswal AK

    更新日期:2003-09-15 00:00:00

  • Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in Human breast cancer.

    abstract::Tumor-associated macrophages (TAMs) produce angiogenic factors and in breast cancer are associated with high vascular grade and poor survival. TAMs preferentially migrate to hypoxic areas within tumors and strongly express hypoxia-inducible factor (HIF)-2 alpha. This study examined whether HIF-2 alpha was involved in ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Leek RD,Talks KL,Pezzella F,Turley H,Campo L,Brown NS,Bicknell R,Taylor M,Gatter KC,Harris AL

    更新日期:2002-03-01 00:00:00

  • Identification of the cross-link between human O6-methylguanine-DNA methyltransferase and chloroethylnitrosourea-treated DNA.

    abstract::Chloroethylnitrosoureas induce reactive O6-guanine adducts in DNA that can form either interstrand cross-links or a covalent complex with the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). To test our hypothesis that these end-products are formed from the common precursor, 1-O6-ethanoguanine, we com...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gonzaga PE,Potter PM,Niu TQ,Yu D,Ludlum DB,Rafferty JA,Margison GP,Brent TP

    更新日期:1992-11-01 00:00:00

  • Genetic alterations of the p53 gene are a feature of malignant mesotheliomas.

    abstract::A putative tumor suppressor gene, p53, has been shown to be altered in a variety of human tumor types. The primary mechanism of p53 inactivation is believed to be mutation of one allele followed by loss of the second allele. Malignant mesothelioma is a tumor that has been highly associated with exposure to asbestos fi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Cote RJ,Jhanwar SC,Novick S,Pellicer A

    更新日期:1991-10-01 00:00:00

  • Enhanced uptake of a thermally responsive polypeptide by tumor cells in response to its hyperthermia-mediated phase transition.

    abstract::Elastin-like polypeptides (ELPs) composed of a VPGXG repeat undergo a reversible phase transition in aqueous solution. They are hydrophilic and soluble in aqueous solution below their transition temperature (T(t)), but they become hydrophobic and aggregate when the temperature is raised above their T(t). In this study...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Raucher D,Chilkoti A

    更新日期:2001-10-01 00:00:00

  • High turnover rate of transfer RNA in tumor tissue.

    abstract::Cancer patients and tumor-bearing animals excrete high levels of modified purines and pyrimidines some of which, e.g., N2,N2-dimethylguanosine, can originate only from transfer RNA (tRNA). Until recently, it could not be ascertained whether the high level of excretion of such compounds is due to cell death or specific...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Borek E,Baliga BS,Gehrke CW,Kuo CW,Belman S,Troll W,Waalkes TP

    更新日期:1977-09-01 00:00:00

  • Epigenetic Switch between SOX2 and SOX9 Regulates Cancer Cell Plasticity.

    abstract::Cell differentiation within stem cell lineages can check proliferative potential, but nodal pathways that can limit tumor growth are obscure. Here, we report that lung cancer cell populations generate phenotypic and oncogenic plasticity via a switch between differentiation programs controlled by SOX2 and SOX9, thus al...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-15-3178

    authors: Lin SC,Chou YT,Jiang SS,Chang JL,Chung CH,Kao YR,Chang IS,Wu CW

    更新日期:2016-12-01 00:00:00

  • Using chemopreventive agents to enhance the efficacy of cancer therapy.

    abstract::Emerging evidence suggests that cancer preventative agents might be combined with chemotherapy or radiotherapy for the more effective treatment of cancer. Recent studies suggest that genistein and other dietary compounds that prevent cancer may enhance the efficacy of cancer therapeutics by modifying the activity of k...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:10.1158/0008-5472.CAN-05-4526

    authors: Sarkar FH,Li Y

    更新日期:2006-04-01 00:00:00