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Cancer: Myeloma

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Total 122 results found since Jan 2013.

Ribonucleotide reductase large subunit (RRM1) as a novel therapeutic target in multiple myeloma.
Conclusions: Our results therefore demonstrate that RRM1 is a novel therapeutic target in MM in preclinical setting, and provide the basis for clinical evaluation of RRM1 inhibitor, alone or in combination with DNA damaging agents, to improve patient outcome in MM. PMID: 28442502 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - April 25, 2017 Category: Cancer & Oncology Authors: Sagawa M, Ohguchi H, Harada T, Samur MK, Tai YT, Munshi NC, Kizaki M, Hideshima T, Anderson KC Tags: Clin Cancer Res Source Type: research

The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma.
Ocio EM Abstract Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor if this proteins, has demonstrated activity in heavily pretreated multiple myeloma patients. The aim of this work was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect.The ability of filanesib to enhance the activity of pomalidomide plus dexamethasone was studied in several in vitro and in vivo models. Mechanisms of this synergistic combinati...
Source: Haematologica - August 31, 2017 Category: Hematology Authors: Hernández-García S, San-Segundo L, González-Méndez L, Corchete LA, Misiewicz-Krzeminska I, Martín-Sánchez M, López-Iglesias AA, Algarín EM, Mogollón P, Díaz-Tejedor A, Paíno T, Tunquist B, Mateos MV, Gutiérrez NC, Díaz-Rodriguez E, Garayoa M, Tags: Haematologica Source Type: research

Preclinical activity of DCZ3301, a novel aryl-guanidino compound in the therapy of multiple myeloma
We synthesized a novel aryl-guanidino compound, DCZ3301, and found that it has potent cytotoxicity against multiple human cancer cell lines. The anticancer activity was most potent against multiple myeloma (MM). DCZ3301 induced cytotoxicity in MM cell lines, as well as patient myeloma cells, in part by decreasing mitochondrial membrane potential to induce apoptosis. In contrast, DCZ3301 had no cytotoxic effect on normal cells. DCZ3301 also inhibited cell cycling and caused a G2/M accumulation that corresponded with downregulation of Cdc25C, CDK1, and Cyclin B1. DCZ3301 retained its activity against MM cells in the presence...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Minjie Gao, Bo Li, Xi Sun, Yunfei Zhou, Yingcong Wang, Van S. Tompkins, Zhijian Xu, Nekitsing Indima, Houcai Wang, Wenqin Xiao, Lu Gao, Gege Chen, Huiqun Wu, Xiaosong Wu, Yuanyuan Kong, Bingqian Xie, Yiwen Zhang, Gaomei Chang, Liangning Hu, Guang Yang, Bo Tags: Research Paper Source Type: research

10 Knockdown of transforming growth factor beta regulator 4 (tbrg4) promotes apoptosis in human lung cancer cell line h1299 via regulating ddit3, cav1 and rrm2
Abstract Transforming growth factor beta regulator 4 (TBRG4) gene is located on 7 p14-p13, a region correlated with many cancer types, such as hematologic malignancies, head and neck squamous cell carcinoma, and multiple myeloma. However, the role of TBRG4 in human lung cancer is largely unknown. Thus, in the present study, the TBRG4 mRNA level was evaluated in the lung cancer cell line H1299 by quantitative PCR (qPCR) after knocking down TBRG4 using lentivirus-mediated small interfering RNA (siRNA). The result showed that TBRG4 was significantly inhibited in H1299 by RNAi. Microarray analysis revealed 586 differentially-e...
Source: Journal of Investigative Medicine - November 24, 2017 Category: Research Authors: Wang, A., Liu, X., Su, W., Duan, G., Xie, Z., Chu, S. Tags: Abstracts Source Type: research

Different Adaptive Responses to Hypoxia in Normal and Multiple Myeloma Endothelial Cells
Conclusion: These findings provide further information on how hypoxia may affect EC survival and could be important for a better understanding of EC physiology under normal and pathological conditions, such as in multiple myeloma.Cell Physiol Biochem 2018;46:203 –212
Source: Cellular Physiology and Biochemistry - March 26, 2018 Category: Cytology Source Type: research

Inhibition of mTOR complex 2 restrains tumor angiogenesis in multiple myeloma.
Authors: Lamanuzzi A, Saltarella I, Desantis V, Frassanito MA, Leone P, Racanelli V, Nico B, Ribatti D, Ditonno P, Prete M, Solimando AG, Dammacco F, Vacca A, Ria R Abstract The mammalian Target of Rapamycin (mTOR) is an intracellular serine/threonine kinase that mediates intracellular metabolism, cell survival and actin rearrangement. mTOR is made of two independent complexes, mTORC1 and mTORC2, activated by the scaffold proteins RAPTOR and RICTOR, respectively. The activation of mTORC1 triggers protein synthesis and autophagy inhibition, while mTORC2 activation promotes progression, survival, actin reorganization...
Source: Oncotarget - May 15, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

ILK promotes angiogenic activity of mesenchymal stem cells in multiple myeloma.
Authors: Zhao W, Zhang X, Zang L, Zhao P, Chen Y, Wang X Abstract Angiogenic activity in solid tumors has been demonstrated to promote metastasis through the activation of certain proteins involved in the epithelial-mesenchymal transition-associated process. The molecular mechanism underlying multiple myeloma-induced angiogenesis involves angiogenic cytokines by plasma cells as well as their induction within the microenvironment. Integrin-linked kinase (ILK) is a highly evolutionarily conserved intracellular protein that was originally identified as an integrin-interacting protein, and extensive genetic and biochem...
Source: Oncology Letters - July 4, 2018 Category: Cancer & Oncology Tags: Oncol Lett Source Type: research

Blockade of deubiquitinase USP7 overcomes bortezomib resistance by suppressing NF- κB signaling pathway in multiple myeloma.
Blockade of deubiquitinase USP7 overcomes bortezomib resistance by suppressing NF-κB signaling pathway in multiple myeloma. J Leukoc Biol. 2018 Jul 19;: Authors: Yao Y, Zhang Y, Shi M, Sun Y, Chen C, Niu M, Zhang Q, Zeng L, Yao R, Li H, Yang J, Li Z, Xu K Abstract The treatment of multiple myeloma (MM) with bortezomib (BTZ) is promising; however, the emergence of resistance is challenging in the clinical treatment. Thus, a novel targeted treatment or exploring the mechanism underlying BTZ resistance is an urgent requisite. The current data showed that high expression of USP7 in myeloma was a predicto...
Source: Journal of Leukocyte Biology - July 19, 2018 Category: Hematology Authors: Yao Y, Zhang Y, Shi M, Sun Y, Chen C, Niu M, Zhang Q, Zeng L, Yao R, Li H, Yang J, Li Z, Xu K Tags: J Leukoc Biol Source Type: research

Sirtuin 6 promotes cell aging of myeloma cell line KM-HM_(31) by via Hippo signal pathway.
CONCLUSIONS: We showed that sirtuin 6 facilitates CP-induced myeloma cell KM-HM_(31) aging via suppressing Hippo. PMID: 30402853 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - November 9, 2018 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Matrix Metalloproteinase and Tissue Inhibitor of Metalloproteinases Is Associated with Multiple Myeloma Progression, Prognosis and Extramedullary Plasmacytoma
Conclusions: Our results suggest that TIMP1, 2 and MMP14, 24 were associated with EMP formation. Among those factors, TIMP1 is the one which may play a key role for MM progression and chemo-resistance based on the results revealing its upregulation by antineoplastic agents and association with poor prognosis of MM patients. Our results is consistent with a previous report describing that high serum TIMP1 concentration was associated with poor prognosis of MM. TIMP is recently shown to play another role besides negative regulator for MMP, so further study to elucidate its specific role for chemo-resistance contributes to de...
Source: Blood - November 21, 2018 Category: Hematology Authors: Ishihara, R., Murakami, Y., Homma, K., Watanabe, S., Oda, T., Sunaga, M., Yamane, E., Kobayashi, N., Osaki, Y., Ishizaki, T., Shimizu, H., Iriuchishima, H., Koiso, H., Tsukamoto, N., Yokohama, A., Nanami, G., Ino, R., Saitoh, T., Murakami, H., Handa, H. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II Source Type: research

Multiple Myeloma Cell-Derived Interleukin-32gamma Increases the Immunosuppressive Function of Macrophages By Promoting Indoleamine 2,3-Dioxygenase (IDO) Expression
Conclusion: Our study showed that MM cell-derived IL-32 induced IDO production in Ms through PR3 and the downstream STAT3 and NF-B pathways, resulting in the suppression of the proliferation and effector function of CD4+ T cells. High IL-32 expression in MM may contribute to an immunosuppressive microenvironment by upregulating IDO production in Ms and promote MM progression.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Yan, H., He, D., Huang, X., Fan, Z. E., Huang, H., Cai, Z. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II Source Type: research

CIC-Mutation As a Potential Molecular Mechanism of Acquired Resistance to Combined BRAF/MEK Inhibition in CNS Multiple Myeloma
Central nervous system (CNS) involvement is an extremely rare extramedullary multiple myeloma (MM) manifestation, diagnosed in less than 1% of patients. It is considered an ultimate high-risk feature, associated with unfavorable cytogenetics, and, even with intense treatment applied, survival is short, reaching less than 12 months in most cases.In June 2017 an 81 years old male with a light chain MM was referred to our institution for an isolated CNS MM relapse. His cerebrospinal fluid (CSF) demonstrated a high load of clonal plasma cells, however, the patient's bone marrow infiltration was very little with a percentage of...
Source: Blood - November 21, 2018 Category: Hematology Authors: Da Via', M. C., Solimando, A. G., Garitano-Trojaola, A., Barrio, S., Rodhes, N., Strifler, S., Teufel, E., Lapa, C., Einsele, H., Beilhack, A., Kortum, K. M. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II Source Type: research

JAK-STAT3 Pathway Regulates CD38 Expression on Multiple Myeloma Cells
In this study, we evaluated the impact of bone marrow stromal cells (BMSCs) from MM patients on CD38 expression and anti-CD38 Antibody-induced ADCC.We first cultured MM cells (RPMI8226, MM.1S, MOLP8) with culture supernatant from BMSCs and measured CD38 expression by flow cytometry. A significant reduction of CD38 expression on all MM cell lines was noted in a time-dependent fashion. For example, CD38 expression (mean fluorescence intensity) was reduced 44%, 32%, and 42% on RPMI8226, MM.1S and MOLP8 cells, respectively, after 48 h culture with BMSC supernatants. To identify mediators of this effect, we next examined the ef...
Source: Blood - November 21, 2018 Category: Hematology Authors: Ogiya, D., Liu, J., Ohguchi, H., Tai, Y.-T., Hideshima, T., Anderson, K. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

MiR-221/222 Promote Dexamethasone Resistance of Multiple Myeloma through Inhibition of Autophagy By Targeting ATG12
In conclusion, our data reveal that upregulation of miR-221/222 promotes Dex resistance of MM cells through inhibition of autophagy by targeting ATG12. Therefore, miR-221/222-ATG12 autophagy-regulatory axis may potentially be applied in glucocorticoid resistance prediction and treatment.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Xu, J., Su, Y., Xu, A., Fan, F., Huang, H., Hu, Y., Sun, C. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research