Abstract:
:Mantle cell lymphoma (MCL) is an aggressive form of Non-Hodgkin-lymphoma (NHL) with an ongoing need for novel treatments. Apart from the translocation t(11:14), which facilitates constitutive transcription of cyclin D1, additional aberrations are frequently observed in MCL, including a recurrent dysregulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. mTOR, a key component of this pathway, is pivotal for the assembly of mTOR complex (mTORC) 1 and 2. Temsirolimus, an analog of the mTOR inhibitor rapamycin, is approved for the treatment of relapsed MCL. Response rates, however, are low and response durations are short. We demonstrate that inhibition of mTORC1 by rapamycin or blocking of mTORC1 and mTORC2 in conjunction with PI3K by NVP-BEZ235 reduces proliferation of MCL cell lines to a similar extent. However, only NVP-BEZ235 is able to sufficiently inhibit the downstream pathway of mTOR and to mediate cell death through activation of the intrinsic apoptosis pathway. Further analysis demonstrated that the anti-apoptotic Bcl-2 family member Mcl-1 plays a central role in regulation of MCL survival. While Mcl-1 protein levels remained unchanged after coculture with rapamycin, they were down-regulated in NVP-BEZ235 treated cells. Furthermore, inhibition of Mcl-1 by the BH3-only mimetic obatoclax or down-regulation of constitutive Mcl-1, but not of Bcl-2 or Bcl-xL, by siRNA facilitated cell death of MCL cells and enhanced NVP-BEZ235's capacity to induce cell death. Our findings may help to lay the foundation for further improvements in the treatment of MCL.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Müller A,Zang C,Chumduri C,Dörken B,Daniel PT,Scholz CWdoi
10.1002/ijc.28206subject
Has Abstractpub_date
2013-10-15 00:00:00pages
1813-24issue
8eissn
0020-7136issn
1097-0215journal_volume
133pub_type
杂志文章abstract::The antigen recognized by the MOv18 MAb (Ca-MOv18) was recently shown to be a glycosylphosphatidylinositol (GPI)-linked protein. In this report we show that GPI-anchorage is not limited to IGROVI cells nor to other ovary carcinoma cell lines, but Ca-MOv18 was also found to be sensitive to phosphatidylinositol-specific...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910510326
更新日期:1992-05-28 00:00:00
abstract::Medullary thyroid carcinoma (MTC) is a rare tumor, partially explained by mutations in the rearranged during transfection (RET) proto-oncogene. The nonsynonymous RET polymorphism G691S has been reported as associated with MTC, but findings are discordant. We sought to clarify the role of G691S in MTCs through in silic...
journal_title:International journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1002/ijc.27967
更新日期:2013-06-15 00:00:00
abstract::The steady-state mRNA level of nucleophosmin/B23 in HeLa cells increased after UV irradiation. Nucleophosmin/B23 antisense transfection potentiated ultraviolet (UV)-induced cell killing. A block in G(2)/M phase, larger peak of apoptotic cells and higher caspase-3 in vitro activity were noted in nucleophosmin/B23 antis...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1606
更新日期:2002-01-20 00:00:00
abstract::We investigated whether variants in sex steroid hormone metabolism genes modify the effect of hormone therapy (HT) on endometrial cancer risk in postmenopausal non-Hispanic white women. A nested case-control study was conducted within the California Teachers Study (CTS). We genotyped htSNPs in six genes involved in th...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.26163
更新日期:2012-04-01 00:00:00
abstract::Evidence indicates that acquired resistance of cancers to chemotherapeutic agents can occur via epigenetic mechanisms. Down-regulation of expression of argininosuccinate synthetase (ASS1), the rate-limiting enzyme in the biosynthesis of arginine, has been associated with the development of platinum resistance in ovari...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24546
更新日期:2009-09-15 00:00:00
abstract::The causes of childhood cancers are largely unknown. Birth order has been used as a proxy for prenatal and postnatal exposures, such as frequency of infections and in utero hormone exposures. We investigated the association between birth order and childhood cancers in a pooled case-control dataset. The subjects were d...
journal_title:International journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1002/ijc.25593
更新日期:2011-06-01 00:00:00
abstract::Human T-lymphotropic virus type I (HTLV-I) carriers often have abnormal lymphocytes (Ably) that resemble malignant cells of adult T-cell leukemia (ATL). To identify predictors of the level of Ably in a longitudinal study of asymptomatic HTLV-I carriers, we analyzed data from 215 subjects (67 men and 148 women) with mu...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19980717)77:2<188::aid-ijc
更新日期:1998-07-17 00:00:00
abstract::Treatment of mouse Lewis lung carcinoma with razoxane or dacarbazine was protracted for 10 transplant generations. While the capacity of the treated tumors to grow locally in immuno-competent or in immuno-depressed hosts was retained and not significantly modified, the metastatic phenotype was eliminated when the trea...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970917)72:6<1056::aid-ij
更新日期:1997-09-17 00:00:00
abstract::Some studies suggest a favorable role of antioxidants on breast cancer risk but this is still inconclusive. The aim of this study was to assess whether overall dietary antioxidant capacity, as assessed by dietary ferric reducing antioxidant potential (FRAP), and individual dietary antioxidant intake were associated wi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29249
更新日期:2015-05-01 00:00:00
abstract::We have analysed expression of the first 7 members of the family of heparin-binding fibroblast growth factor (FGFs) and their 4 high-affinity receptors (FGFRs) in human pancreatic carcinoma cell lines, both at the mRNA and protein levels. In cell lines expressing FGFRs, 2 typical patterns were observed: (i) expression...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910590515
更新日期:1994-12-01 00:00:00
abstract::The cytogenetic response to G2-phase X-irradiation was examined in phytohemagglutinin-stimulated peripheral-blood lymphocytes from 69 individuals, a few of whom were cancer patients. The cancer patients had not received radiation or chemotherapy. The responses of cells arrested by Colcemid 30 to 90 min after X-irradia...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910540412
更新日期:1993-06-19 00:00:00
abstract::We have previously shown that AEV infection of leukosis-free chickens provokes an erythroleukemia in the infected birds, and that the target cell for virus transformation is most likely an early pro-erythroblast comparable to the BFU-E. The virus infection correlates with a block in differentiation which was studied a...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910290511
更新日期:1982-05-15 00:00:00
abstract::Sera samples from 111 women, including 73 breast cancer patients and 38 patients with benign diseases of the breast, were examined. These were compared with samples from healthy women or from patients carrying tumors of origin other than breast as controls. This was done to determine whether antibodies against GCDFP-1...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19991222)84:6<568::aid-ijc
更新日期:1999-12-22 00:00:00
abstract::Studies have shown an increased risk of malignancies in women with endometriosis. Little is known about the impact of endometriosis on cancer survival. We investigated whether the survival after a diagnosis of a malignancy differs in women with a previously diagnosed endometriosis compared to other women. Women with a...
journal_title:International journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1002/ijc.25718
更新日期:2011-08-15 00:00:00
abstract::Although the existence of a humoral response against tumor-associated antigens is well appreciated, a systematic analysis of its possible induction by the tumor remains missing. We compared the specific IgG response of Stage IV melanoma patients during vaccination. Patients had been treated within 2 clinical trials wi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.11537
更新日期:2004-01-10 00:00:00
abstract::Acquired chemoresistance is a critical issue for advanced bladder cancer patients during long-term treatment. Recent studies reveal that a fraction of tumor cells with enhanced tumor-initiating potential, or cancer stem-like cells (CSCs), may particularly contribute to acquired chemoresistance and recurrence. Thus, CS...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32505
更新日期:2020-02-15 00:00:00
abstract::Epigenetic silencing of MLH1 is the most common cause of defective DNA mismatch repair in endometrial and colorectal cancers. We hypothesized that variation in the MLH1 gene might contribute to the risk for MLH1 methylation and epigenetic silencing. We undertook a case-control study to test for the association between...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22406
更新日期:2007-04-15 00:00:00
abstract::Two factors potentially determining the consistent overexpression of sialyl-Le(x) antigen in colon carcinoma and metastases were investigated: (i) the expression of the mucins MUC1 and MUC2, known to carry sialyl-Le(x), by Northern blotting; (ii) the extent of sialic acid O-acetylation, by Western blotting and HPLC. R...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970717)72:2<258::aid-ijc
更新日期:1997-07-17 00:00:00
abstract::Artemisia asiatica Nakai has been used in traditional Asian medicine for the treatment of inflammatory and other disorders. Previous studies have revealed that the formulated ethanol extract (DA-9601) of A. asiatica has pronounced antioxidative and antiinflammatory activities and exhibits cytoprotective effects agains...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10489
更新日期:2002-08-01 00:00:00
abstract::Our aim was to identify plasma microRNA (miRNA)-based signatures to predict 3-year postoperative recurrence risk for patients with stage II and III gastric cancer (GC), so as to provide insights for individualized adjuvant therapy. Plasma miRNA expression was investigated in three phases, involving 407 patients recrui...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30895
更新日期:2017-11-15 00:00:00
abstract::It is well known that the functions of reproductive organs are regulated by sex steroids and their receptors and it is hypothesized that the progression of neoplasms that originate from the reproductive organs is influenced by them. However, the correlation between sex steroids and tumor progression, especially tumor ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10504
更新日期:2002-08-01 00:00:00
abstract::Although viral sequences closely related to feline leukaemia virus are represented in multiple copies in cellular DNA of all domestic cats, a specific fraction was present only in the virus-infected cells. This fraction was detected by viral cDNA enriched by a prior absorption of a total complementary DNA (cDNA) trans...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910220114
更新日期:1978-07-15 00:00:00
abstract::The autophagy lysosome pathway is essential to maintain cell viability and homeostasis in response to many stressful environments, which is reported to play a vital role in cancer development and therapy. However, the association of genetic alterations of this pathway with risk of cancer remains unclear. Based on geno...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31288
更新日期:2018-07-01 00:00:00
abstract::A herpesvirus (RhEBV) was isolated from a lymphoblastoid cell line (LCL) that became established from a malignant lymphoma in a rhesus monkey. The predominant cell marker in the LCL was that of B lymphocytes. RhEBV-induced viral capsid (VCA) and nuclear antigens (NA) in the LCL were serologically related to similar an...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910380319
更新日期:1986-09-15 00:00:00
abstract::A previously published case-control study of agricultural risk factors involved male cases of non-Hodgkin's lymphoma registered under code 202 of the International Classification of Diseases (ICD). This study has been expanded with the inclusion of cases registered under ICD code 200, and additional controls. The expa...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910390206
更新日期:1987-02-15 00:00:00
abstract::Using nationwide Danish registries we examined the long-term risk of cervical cancer in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (including adenocarcinoma in situ (AIS)) on the cone compared to women with a normal cytology test. Initially, we identified women born 1918-1990, who were reco...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31202
更新日期:2018-05-01 00:00:00
abstract::In the perspective of in vivo therapeutic applications, the monoclonal antibody (MAb) MOv18 was selected for its restricted reactivity with human ovarian carcinoma. Using the pH 2.8 desorption assay, we found that the antigen recognized by MOv18 had a high stability on the cell membrane and poor internalization. There...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910410422
更新日期:1988-04-15 00:00:00
abstract::Allogeneic mixed leukocytes reaction has been reported to activate vast numbers of T lymphocytes and produce large amounts of type 1 cytokines that are linked to an initiation of antitumor immunity. Using poor immunogeneic B16-F10 and Lewis lung carcinoma (LLC) tumor model, we evaluated the effects of inactivated allo...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24045
更新日期:2009-03-01 00:00:00
abstract::A new non peptidic farnesyltransferase inhibitor, RPR-115135, in combination with 5-FU was studied in 10 human colon cancer cell lines (HCT-116, RKO, DLD-1, Colo-320, LoVo, SW-620, HT-29, HCT-15, Colo-205 and KM-12) carrying several mutations but well characterized for p53 and Ras status. We found that there was a sli...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10461
更新日期:2002-07-20 00:00:00
abstract::Beta-lapachone and camptothecin are structurally unrelated agents thought to inhibit topoisomerase-I activity through distinct mechanisms. We find that beta-lapachone is much more potent than camptothecin in inducing acute cytotoxic effects on human malignant glioma cells. Acute cytotoxicity induced by both drugs is a...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19971127)73:5<707::aid-ijc
更新日期:1997-11-27 00:00:00