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 Resjournal_title
Cancer researchauthors
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 Fdoi
10.1158/0008-5472.CAN-10-2525subject
Has Abstractpub_date
2011-04-01 00:00:00pages
2643-53issue
7eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-10-2525journal_volume
71pub_type
杂志文章相关文献
CANCER RESEARCH文献大全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
更新日期：2009-06-01 00:00:00
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：
更新日期：1975-03-01 00:00:00
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：
更新日期：1980-12-01 00:00:00
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
更新日期：2005-12-15 00:00:00
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
更新日期：2007-01-01 00:00:00
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：
更新日期：1976-09-01 00:00:00
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：
更新日期：2000-10-01 00:00:00
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：
更新日期：1994-05-01 00:00:00
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：
更新日期：1995-03-01 00:00:00
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：
更新日期：1975-05-01 00:00:00
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：
更新日期：2001-12-01 00:00:00
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：
更新日期：1995-10-01 00:00:00
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：
更新日期：1988-07-15 00:00:00
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
更新日期：2004-02-01 00:00:00
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
更新日期：2012-08-01 00:00:00
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
更新日期：2020-11-10 00:00:00
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
更新日期：2010-10-15 00:00:00
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
更新日期：2006-03-01 00:00:00
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
更新日期：2009-10-01 00:00:00
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：
更新日期：1985-09-01 00:00:00
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
更新日期：2015-08-15 00:00:00
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：
更新日期：1996-07-15 00:00:00
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：
更新日期：2003-09-15 00:00:00
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：
更新日期：2002-03-01 00:00:00
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：
更新日期：1992-11-01 00:00:00
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：
更新日期：1991-10-01 00:00:00
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：
更新日期：2001-10-01 00:00:00
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：
更新日期：1977-09-01 00:00:00
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
更新日期：2016-12-01 00:00:00
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
更新日期：2006-04-01 00:00:00
