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Cancer: Myeloma

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Total 122 results found since Jan 2013.

TRAF6 is required for BLyS-mediated NF-κB signaling in multiple myeloma cells
Abstract Tumor necrosis factor receptor-associated factor 6 (TRAF6) transduces signals from members of the IL-1R/TLR and TNFR superfamilies to the transcription factors NF-κB and AP1. Elevated expression of the TNF family member B-lymphocyte stimulator (BLyS) in multiple myeloma (MM) has been described recently. However, the precise process by which BLyS signals in myeloma cell remains unknown. Here, we identified increased expression of TRAF6 in MM patient cells and the MM cell lines U266, RPMI8226, and KM3. Furthermore, rhBLyS induced TRAF6 up-regulation in these cells in a dose-dependent manner. Both the clas...
Source: Medical Oncology - September 3, 2015 Category: Cancer & Oncology Source Type: research

Abstract LB-136: The role of ER chaperone GRP94 in endometrial cancer progression
This study expands our understanding of GRP94 function in the progression of solid tumors and provides the first evidence that GRP94 could be a target for combating endometrial cancer.Citation Format: Jieli Shen, Yvonne G. Lin, Louis Dubeau, Amy S. Lee. The role of ER chaperone GRP94 in endometrial cancer progression. [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 LB-136. doi:10.1158/1538-7445.AM2015-LB-136
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Shen, J., Lin, Y. G., Dubeau, L., Lee, A. S. Tags: Tumor Biology 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 325: Multiple myeloma in a physiologically relevant Me-HA -3D Hydrogel: Discovering new phenotypes of drug resistance
In this study we have shown that Hyaluronic acid (HA) based 3D hydrogel support human metastatic MM cancer cells survival and thus reveal new oncogenic mechanisms of drug resistant cancer stem cells.Experimental approaches: Bone marrow derived CD138 positive cells and BMSCs were isolated from MM patient samples (with IRB approval) using magnetically labeled CD138 MicroBeads (autoMACS Pro Starting Kit). Bone marrow stromal cells (BMSCs) were cultured as described by us earlier. Cell viability measurements and quantitative RT-PCR for c-myc and other related gene targets were performed using total RNA. Me-HA-3D hydrogels were...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Narayanan, B. A., Duan, B., Narayanan, N. K., Butcher, J. B., Mazumder, A. Tags: Tumor Biology Source Type: research

Lactate, a putative survival factor for myeloma cells, is incorporated by myeloma cells through monocarboxylate transporters 1
Conclusions The present data suggest that lactate is produced by MM cell lines and stromal cells, and contributes to the survival of such MM cells in autocrine or paracrine manners. Suppression of lactate incorporation by targeting MCT1 may provide a novel therapeutic strategy for MM which may be applicable for other B-cell neoplasms.
Source: Experimental Hematology and Oncology - April 21, 2015 Category: Cancer & Oncology Source Type: research

eIF4E and eIF4GI have distinct and differential imprints on multiple myeloma's proteome and signaling.
This study is the first to directly assess the relative contribution of eIF4F components to the expressed cellular proteome, transcription factors, microRNAs, and phenotype in a malignancy known for extensive protein synthesis-multiple myeloma (MM). Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets. Here, we demonstrated that eIF4E/eIF4GI indeed have individual influences on cell proteome. We used an objective, high throughput assay of mRNA microarrays to examine the significance of eIF4E/eIF4GI silencing to s...
Source: Oncotarget - February 28, 2015 Category: Cancer & Oncology Tags: Oncotarget 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

Two death pathways induced by sorafenib in myeloma cells: Puma-mediated apoptosis and necroptosis
Conclusion Our results demonstrate a key role for Puma in the triggering of sorafenib-induced apoptosis and that this drug can also induce death by necroptosis in multiple myeloma cells.
Source: Clinical and Translational Oncology - February 1, 2015 Category: Cancer & Oncology Source Type: research

Importin β1 mediates nuclear factor-κB signal transduction into the nuclei of myeloma cells and affects their proliferation and apoptosis.
In conclusion, our results clearly show that Importin β1 mediates the translocation of NF-κB into the nuclei of myeloma cells, thereby regulating proliferation and blocking apoptosis, which provides new insights for targeted myeloma therapies. PMID: 25643631 [PubMed - as supplied by publisher]
Source: Cellular Signalling - January 30, 2015 Category: Cytology Authors: Yan W, Li R, He J, Du J, Hou J Tags: Cell Signal Source Type: research

Unfolded protein response inducers tunicamycin and dithiothreitol promote myeloma cell differentiation mediated by XBP-1
Abstract The unfolded protein response (UPR) is an essential pathway for both normal and malignant plasma cells to maintain endoplasmic reticulum (ER) homeostasis in response to the large amount of immunoglobulin (Ig) output. The inositol-requiring enzyme 1-X-box binding protein-1 (IRE1-XBP-1) arm of the UPR pathway has been shown to play crucial roles not only in relieving the ER stress by up-regulating a series of genes favoring ER-associated protein degradation and protein folding, but in mediating terminal plasmacytic differentiation and maturation. Myeloma cells comprise various subsets arrested in diverse d...
Source: Clinical and Experimental Medicine - January 29, 2015 Category: Research 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

Abstract 5112: Histone deacetylase and proteasome inhibitors synergistically induce apoptosis in colon cancer, multiple myeloma and CTCL cells through induction of the immediate early genes ATF3 and JUN
Conclusions: This study provides insight into the mechanistic basis by which combination treatment with HDAC and proteasome inhibitors synergistically induces apoptosis in tumour cells. Citation Format: Janson WT Tse, Anderly C. Chueh, Ian Y. Luk, Fiona Chionh, Yvonne Yeung, Georgia A. Corner, Dominic CH Ng, Hoanh Tran, Amardeep S. Dhillon, John M. Mariadason. Histone deacetylase and proteasome inhibitors synergistically induce apoptosis in colon cancer, multiple myeloma and CTCL cells through induction of the immediate early genes ATF3 and JUN. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Associ...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Tse, J. W., Chueh, A. C., Luk, I. Y., Chionh, F., Yeung, Y., Corner, G. A., Ng, D. C., Tran, H., Dhillon, A. S., Mariadason, J. M. Tags: Molecular and Cellular Biology Source Type: research

Targeting survival and cell trafficking in multiple myeloma and Waldenstrom Macroglobulinemia using pan‐class I PI3K inhibitor, buparlisib
In this study, we characterized the role of pan‐class I PI3K inhibition on cell trafficking and survival of MM and WM cells. We tested the effect of pan‐class I PI3K inhibition by siRNA silencing or pharmacologic inhibition with buparlisib on MM cell survival, apoptosis and cell cycle in vitro and tumor growth and mobilization of MM cells in vivo. We then evaluated buparlisib‐dependent mechanisms of induced MM cell mobilization. Moreover, the effect of buparlisib on cell survival, apoptosis and adhesion of WM cells to bone marrow stromal cells (BMSCs) has been evaluated. We showed that buparlisib induced toxicity in ...
Source: American Journal of Hematology - July 24, 2014 Category: Hematology Authors: Ilyas Sahin, Feda Azab, Yuji Mishima, Michele Moschetta, Brian Tsang, Siobhan V. Glavey, Salomon Manier, Yu Zhang, Antonio Sacco, Aldo M. Roccaro, Abdel Kareem Azab, Irene M. Ghobrial Tags: Research Article Source Type: research

Inhibition of mTOR with everolimus and silencing by vascular endothelial cell growth factor-specific siRNA induces synergistic antitumor activity in multiple myeloma cells
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Source: Cancer Gene Therapy - June 6, 2014 Category: Cancer & Oncology Authors: M KoldehoffD W BeelenA H Elmaagacli Source Type: research

High throughput quantitative reverse transcription PCR assays revealing over‐expression of cancer testis antigen genes in multiple myeloma stem cell‐like side population cells
Summary Multiple myeloma (MM) stem cells, proposed to be responsible for the tumourigenesis, drug resistance and recurrence of this disease, are enriched in the cancer stem cell‐like side population (SP). Cancer testis antigens (CTA) are attractive targets for immunotherapy because they are widely expressed in cancers but only in limited types of normal tissues. We designed a high throughput assay, which allowed simultaneous relative quantifying expression of 90 CTA genes associated with MM. In the three MM cell lines tested, six CTA genes were over‐expressed in two and LUZP4 and ODF1 were universally up‐regulated in...
Source: British Journal of Haematology - May 29, 2014 Category: Hematology Authors: Jianguo Wen, Hangwen Li, Wenjing Tao, Barbara Savoldo, Jessica A. Foglesong, Lauren C. King, Youli Zu, Chung‐Che Chang Tags: Research Paper Source Type: research