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Drug: Velcade

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Total 70 results found since Jan 2013.

Bortezomib induces apoptosis and suppresses cell growth and metastasis by inactivation of Stat3 signaling in chondrosarcoma.
Abstract Bortezomib, formerly known as PS341, is a novel proteasome inhibitor with in vitro and in vivo antineoplastic effects in many malignancies. However, diverse antitumor mechanisms of bortezomib have been identified in many investigations and preclinical studies. Understanding the molecular and cellular mechanisms through which bortezomib acts will improve the therapeutic utility of this drug in different cancer types. In the present study, we investigated the in vitro and in vivo effects of bortezomib on chondrosarcoma. Bortezomib selectively inhibited cell growth in chondrosarcoma cells but not in norma...
Source: International Journal of Oncology - December 13, 2016 Category: Cancer & Oncology Authors: Bao X, Ren T, Huang Y, Ren C, Yang K, Zhang H, Guo W Tags: Int J Oncol Source Type: research

Abstract A164: The small molecule UAE inhibitor TAK-243 (MLN7243) prevents DNA damage repair and reduces cell viability/tumor growth when combined with radiation, carboplatin and docetaxel
Clinical results of VELCADE® (bortezomib) For Injection have prompted evaluation of other enzymes within the ubiquitin proteasome system (UPS) as druggable targets for human cancer. We have identified a first in class investigational drug, TAK-243 (MLN7243), which targets the ubiquitin activating enzyme, UAE (UBA1), an essential cellular enzyme responsible for activating > 99% of all cellular ubiquitin. Ubiquitin is involved in multiple cellular processes including ubiquitin-dependent protein turnover, cell cycle progression, regulation of apoptosis, protein localization and response to DNA damage. Experiments combi...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Milhollen, M. A., Shi, J., Traore, T., Huck, J., Sappal, D., Duffy, J., Lightcap, E., Ishii, Y., Ciavarri, J., Fleming, P., Bence, N., Hyer, M. L. Tags: Therapeutic Agents: Other: Poster Presentations - Proffered Abstracts Source Type: research

Upregulation of CCL2 via ATF3/c-Jun interaction mediated the Bortezomib-induced peripheral neuropathy
Publication date: Available online 10 November 2015 Source:Brain, Behavior, and Immunity Author(s): Cuicui Liu, Shuo Luan, Handong OuYang, Zhenzhen Huang, Shaoling Wu, Chao Ma, Jiayou Wei, Wenjun Xin Bortezomib (BTZ) is a frequently used chemotherapeutic drug for the treatment of refractory multiple myeloma and hematological neoplasms. The mechanism by which the administration of BTZ leads to painful peripheral neuropathy remains unclear. In present study, we found that application of BTZ at 0.4 mg/kg for consecutive 5 days significantly increased the expression of CCL2 in DRG, and intrathecal administration of n...
Source: Brain, Behavior, and Immunity - November 13, 2015 Category: Neurology Source Type: research

Upregulation of CCL2 via ATF3/c-Jun interaction mediated the Bortezomib-induced peripheral neuropathy.
Abstract Bortezomib (BTZ) is a frequently used chemotherapeutic drug for the treatment of refractory multiple myeloma and hematological neoplasms. The mechanism by which the administration of BTZ leads to painful peripheral neuropathy remains unclear. In present study, we found that application of BTZ at 0.4 mg/kg for consecutive 5 days significantly increased the expression of CCL2 in DRG, and intrathecal administration of neutralizing antibody against CCL2 inhibited the mechanical allodynia induced by BTZ. We also found an increased expression of c-Jun in DRG, and that inhibition of c-Jun signaling prevented the...
Source: Brain, Behavior, and Immunity - November 7, 2015 Category: Neurology Authors: Liu C, Luan S, OuYang H, Huang Z, Wu S, Ma C, Wei J, Xin W Tags: Brain Behav Immun Source Type: research

Synergistic anti‐myeloma activity of the proteasome inhibitor marizomib and the IMiD® immunomodulatory drug pomalidomide
Abstract The proteasome inhibitor bortezomib is an effective therapy for the treatment of relapsed and refractory multiple myeloma (RRMM); however, prolonged treatment can be associated with toxicity, peripheral neuropathy and drug resistance. Our earlier studies showed that the novel proteasome inhibitor marizomib is distinct from bortezomib in its chemical structure, mechanisms of action and effects on proteasomal activities, and that it can overcome bortezomib resistance. Pomalidomide, like lenalidomide, has potent immunomodulatory activity and has been approved by the US Food and Drug Administration for the treatment o...
Source: British Journal of Haematology - October 12, 2015 Category: Hematology Authors: Deepika S. Das, Arghya Ray, Yan Song, Paul Richardson, Mohit Trikha, Dharminder Chauhan, Kenneth C. Anderson Tags: Research Paper Source Type: research

Abstract 5472: Selinexor, a selective inhibitor of nuclear export (SINE), acts through NF-{kappa}B deactivation and combines with proteasome inhibitors to synergistically induce tumor cell death
Conclusion: Inhibition of NF-κB transcriptional activity through forced nuclear retention of IκB appears to be an important mechanism in the selective tumor cell cytotoxicity of selinexor and related SINE compounds. Furthermore, the combination of selinexor and proteasome inhibitors, which are also known to act at least in part through inhibition of NF-κB, leads to synergistic activity in vitro and in vivo, suggesting that such combinations may provide clinically more effective than the single agents. A Phase 1 trial to study the safety and efficacy of selinexor in combination with carfilzomib in multiple myeloma is ong...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Landesman, Y., Kashyap, T., Crochiere, M., Klebanov, B., Friedlander, S., Senapedis, W., Carlson, R., Kauffman, M., Shacham, S. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 4969: Metformin causes AR degradation via Skp2-mediated ubiquitination
This study supports that use of metformin in combination with Enza or other ARSI drugs may not only block autophagy survival but also cause AR degradation that leads to PC cell death.Citation Format: Joy C. Yang, Allen C. Gao, Christopher P. Evans. Metformin causes AR degradation via Skp2-mediated ubiquitination. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4969. doi:10.1158/1538-7445.AM2015-4969
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Yang, J. C., Gao, A. C., Evans, C. P. Tags: Molecular and Cellular Biology Source Type: research

Abstract P2-06-04: Proteosome inhibitor bortezomib inhibits NF{kappa}B and effectively overcomes cancer stem cell escape triggered by Wnt inhibitor therapy in FOXC1+ basal-Like/claudin-low breast cancer
In this study, we sought to investigate the link between Wnt signaling and FOXC1 and its potential in regulating CSC biology in basal-Like/claudin-low breast cancer. We observed that exposure of the MDA-MB-231 basal-like/claudin-low cell line (low constitutive FOXC1 expressor) to Wnt3a (a canonical Wnt signaling ligand), resulted in increased expression of FOXC1. Reciprocally, overexpression of FOXC1 in MCF10A human mammary epithelial cells led to a pronounced increase in Wnt signaling activity, strongly suggestive of a direct or indirect positive feedback loop between Wnt signaling and FOXC1. More importantly, BT549 and H...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: Ray, P. S., Tsai, C. Y., Ray, T., Kim, B., Jensen, T. W. Tags: Poster Session Abstracts Source Type: research

PRIMA-1Met induces apoptosis in Waldenström's Macroglobulinemia cells independent of p53.
In this study, we evaluated the anti- tumor activity of PRIMA-1Met alone and in combination with dexamethasone or bortezomib in WM cell lines and primary samples. Treatment of WM cells with PRIMA-1Met resulted in induction of apoptosis, inhibition of migration and suppression of colony formation. Upon PRIMA-1Met treatment, p73 was upregulated and Bcl-xL was down-regulated while no significant change in expression of p53 was observed. Furthermore, siRNA knockdown of p53 in WM cell line did not influence the PRIMA-1Met-induced apoptotic response whereas silencing of p73 inhibited latter response in WM cells. Importantly, com...
Source: Cancer Biology and Therapy - March 24, 2015 Category: Cancer & Oncology Authors: Sobhani M, Abdi J, Chen C, Chang H Tags: Cancer Biol Ther Source Type: research

Repression of breast cancer cell growth by proteasome inhibitors in vitro: impact of mitogen-activated protein kinase phosphatase 1.
Abstract Mitogen activated protein kinase phosphatase-1 (MKP-1) has emerged as an important protein mediating breast cancer oncogenesis and chemoresistance to cancer chemotherapies, especially proteasome inhibitors. In this in vitro study, we utilized the breast cancer epithelial cell lines MCF-7 and MDA-MB-231, in comparison to MCF-10A control cells, to examine the impact of MKP-1 on breast cancer cell growth and repression by proteasome inhibitors. We confirm that proteasome inhibitors MG-132 and bortezomib induce MKP-1 protein upregulation and we show that one of the ways in which bortezomib increases MKP-1 in ...
Source: Cancer Biology and Therapy - March 16, 2015 Category: Cancer & Oncology Authors: Patel BS, Co WS, Donat C, Wang M, Che W, Prabhala P, Schuster F, Schulz V, Martin JL, Ammit AJ Tags: Cancer Biol Ther Source Type: research

Proteasome inhibitor-resistant cells cause EMT-induction via suppression of E-cadherin by miR-200 and ZEB1.
Abstract Downregulation of E-cadherin (gene: CDH1) plays an important role in epithelial-mesenchymal transition (EMT), which is critical for normal development and disease states. As a result of long-term treatment of endometrial carcinoma Ishikawa cells with epoxomicin (EXM), the cells exhibited the phenotype for EXM-resistance (Ish/EXM cells). Moreover, CDH1 mRNA and its protein were suppressed and EMT was induced in Ish/EXM cells. Ish/EXM cells exhibited drug-resistance to other proteasome inhibitors, MG-132, PSI and PS-341 (Bortezomib). The proteasome inhibitor-resistant cells acquired invasiveness as a result...
Source: International Journal of Oncology - March 4, 2015 Category: Cancer & Oncology Authors: Asakura T, Yamaguchi N, Ohkawa K, Yoshida K Tags: Int J Oncol Source Type: research

PGC-1α is responsible for survival of multiple myeloma cells under hyperglycemia and chemotherapy.
Authors: Yu W, Cao D, Zhou H, Hu Y, Guo T Abstract The association between hyperglycemia and outcomes during chemotherapy has been reported in several tumors, including multiple myeloma (MM). However, the underlying mechanism of how hyperglycemia affects the survival of MM cells during chemotherapy remain to be elucidated. MM cells were cultured in 10 mM glucose with or without chemotherapeutic agents. Following treatment of MM cells with dexamethasone or bortezomib, an MTT assay was used to evaluate the toxicity of dexamethasone or bortezomib on cell proliferation, and changes of reactive oxygen species (ROS) lev...
Source: Oncology Reports - February 21, 2015 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

Inhibition of PGC-1α after chemotherapy-mediated insult confines multiple myeloma cell survival by affecting ROS accumulation.
Authors: Cao D, Jin L, Zhou H, Yu W, Hu Y, Guo T Abstract Peroxisome proliferator‑activated receptor-γ coactivator-1α (PGC-1α) is a key regulator of reactive oxygen species (ROS). However, whether it has the same role in multiple myeloma (MM), especially after treatement with chemotherapy, remains unclear. After treating cells with bortezomib or dexamethasone, the expression of PGC-1α, superoxide dismutase 2 (SOD-2) and catalase (CAT) was examined by RT-PCR. PGC-1α expression was also analyzed by western blotting. Small‑interference RNA (siRNA) was applied to inhibit the expression of PGC-1α after c...
Source: Oncology Reports - December 6, 2014 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

Bortezomib Sensitizes Primary Meningioma Cells to TRAIL-Induced Apoptosis by Enhancing Formation of the Death-Inducing Signaling Complex
AbstractA meningioma is the most common primary intracranial tumor in adults. Here, we investigated the therapeutic potential of the tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in 37 meningiomas. Freshly isolated primary meningioma cells were treated with TRAIL with or without different sensitizing protocols, and apoptotic cell death was then quantified. Mechanisms of TRAIL sensitization were determined by a combination of Western blotting, flow cytometry, receptor complex immunoprecipitation, and siRNA-mediated knockdown experiments. Tumor necrosis factor–related apoptosis-inducing ligand receptor ...
Source: Journal of Neuropathology and Experimental Neurology - October 24, 2014 Category: Neurology Tags: Original Articles Source Type: research

Abstract 2254: Pro-angiogenic CXCL8 signalling underpins microenvironment-induced relapse to anti-androgen therapy of prostate cancer
Conclusion: Our data suggests that targeting CXCL8 signalling may therefore be a relevant strategy to enhance tumor response to anti-androgen therapies. Inhibiting signalling of this chemokine attenuates key transcriptional approaches induced in the hypoxic microenvironment of bicalutamide-treated tumors. Moreover, inhibition of CXCL8 signalling may prevent the re-vascularization previously observed in hypoxic LNCaP tumors. Citation Format: Melanie McKechnie, Pamela J. Maxwell, David J. J. Waugh. Pro-angiogenic CXCL8 signalling underpins microenvironment-induced relapse to anti-androgen therapy of prostate cancer. [abstrac...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: McKechnie, M., Maxwell, P. J., Waugh, D. J. J. Tags: Molecular and Cellular Biology Source Type: research