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Cancer: Myeloma
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Total 13 results found since Jan 2013.
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
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
Silencing Long Non-Coding RNA ST3GAL6-AS1 Inhibits Adhesion and Migration of Myeloma Cells in Vitro
Conclusions: Knockdown of ST3GAL6-AS1 in MM cells significantly inhibits adhesion, migration and invasion in vitro, indicating that ST3GAL6-AS1 may play an important role in the malignant behavior of MM cells. The co-expression between ST3GAL6-AS1 and gene ST3GAL6 has been demonstrated in our previous study, which was further confirmed in present study. Researches are ongoing to address the potential mechanism among them in MM.Figure 1.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Shen, Y., Feng, Y., Chen, H., Jia, Y., Peng, Y., Zhang, R., Yang, Y., Wang, J.-L., Bai, J., Wang, F.-X., Xu, Y., Hu, J., He, A. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research
PDZ Binding Kinase (PBK) - a Novel Gene Driving Genomic Evolution in Multiple Myeloma
As in all cancers, genomic instability leads to ongoing acquisition of new genetic changes in multiple myeloma (MM). This adaptability underlies the development of drug resistance and progression in MM. This genomic instability is driven by cellular processes, mainly related with DNA repair and perturbed by functional changes in limited number of genes. Since kinases play a critical role in the regulation of biological processes, including DNA damage/repair signaling and are relatively easy to screen for inhibitors, we investigated for novel genes involved in the acquisition of new genomic changes in MM. Using a large geno...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kumar, S., Buon, L., Talluri, S., Shi, J., Avet-Loiseau, H., Samur, M. K., Shammas, M. A., Munshi, N. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research
Effective Lipidoid Nanoparticle Delivery In Vivo of siRNA Targeting Kappa Light Chain Production in a Murine Xenograft Model
CONCLUSIONS: We have previously shown that siIGKC, a pool of siRNA directed at consensus sequences in the LC constant region gene, can significantly reduce LC production in clonal plasma cells from patients, in human myeloma cell lines, and in vivo in a flank plasmacytoma xenograft model. In this work, we show that 8B-3 is a promising LPN for delivery of siRNA to human plasma cells and, when loaded with siIGKC, can with relative safety significantly reduce circulating LC in the NSG JJN3 IP model after 3 daily IP injections despite rapid tumor growth. We also show the utility of the NSG JJN3 IP model for the study of LC dir...
Source: Blood - November 21, 2018 Category: Hematology Authors: Ma, X., Zhou, P., Kugelmass, A., Toskic, D., Warner, M., Lee, L. X., Fogaren, T., Wang, M., Li, Y., Yang, L., Xu, Q., Comenzo, R. Tags: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster II Source Type: research
Blockade of Ubiquitin Receptor PSMD4/Rpn10 Triggers Cytotoxicity and Overcomes Bortezomib-Resistance in Multiple Myeloma
ConclusionOur preclinical data validates targeting 19S proteasome ubiquitin receptor Rpn10 upstream of the proteasome in the ubiquitin proteasomal cascade, and provides the framework for clinical evaluation of Rpn10 inhibitors to overcome PI resistance and improve patient outcome in MM.DisclosuresAnderson: C4 Therapeutics: Equity Ownership, Other: Scientific founder; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; Millennium Takeda: Consultancy; OncoPep: Equity Ownership, Other: Scientific founder.
Source: Blood - November 21, 2018 Category: Hematology Authors: Song, Y., Ray, A., Chauhan, D., Anderson, K. Tags: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster II Source Type: research
Chidamide, a Novel Histone Deacetylase Inhibitor, Inhibits Multiple Myeloma Cells Proliferation through Succinate Dehydrogenase Subunit a
Most patients with multiple myeloma (MM) would finally relapse. Current chemotherapy regimens have limited effect on relapse MM patients. As a new histone deacetylase inhibitor, chidamide has been used in malignancy treatment such as peripheral T-cell lymphoma. However, it is still unknown if chidamide can be used in MM.To determine the target gene of chidamide in MM patients, we performed RNA-Seq analysis using 3 MM patients' bone marrow mononuclear cells. Their BMMCs were cultured with 6μM chidamide or not, and six of the most significantly changed coding genes were selected. Realtime RT-PCR showed that compared with ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Sun, Y., Liu, P., Li, J. Tags: 653. Myeloma: Therapy, excluding Transplantation: Poster I Source Type: research
Identifying a Murine Xenograft Model Relevant to Light-Chain Specific Approaches to Human Ig Light-Chain Diseases
CONCLUSIONS: The ALMC-1, RPMI 8226 and H929 IP models did not meet the criteria we required in order to effectively test specific interventions on circulating LC (Table 1). The NSG JJN3 IP model had a short latency period for LC, β2M and FLUX measurements, and had significant correlations among these measurements. The NSG JJN3 model met our criteria. We are currently evaluating soluble BCMA levels in this model also, These measurements will allow investigators to distinguish the impact of interventions on LC specifically, independent of tumor cells. We have used this model successfully to test an RNAi approach to redu...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kugelmass, A., Zhou, P., Ma, X., Toskic, D., Godara, A., Warner, M., Lee, L. X., Fogaren, T., Varga, C., Comenzo, R. L. Tags: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy Source Type: research
Targeting Insulin-like Growth Factor in Multiple Myeloma: Novel Strategies in the Treatment of Proteasome Inhibitor Resistant Cells
Conclusion: The IGF1 signaling pathway is involved in proteasome inhibitor sensitivity and plays a key role in chemokine production of the HUVEC. Our data also suggested that administration of IGF1R inhibitor, linsitinib, might be a powerful strategy against myeloma cells and enhance cytotoxic effects of proteasome inhibitors in those residual MM cells.DisclosuresOhyashiki: MSD,: Honoraria, Research Funding; Bristol Meyer Squibb KK,: Honoraria, Research Funding; Kyowakko Kirin KK,: Research Funding; Celegene KK,: Honoraria, Research Funding; Pfizer KK,: Honoraria, Research Funding; Novartis KK,: Honoraria, Research Funding...
Source: Blood - November 21, 2018 Category: Hematology Authors: Tanaka, Y., Okabe, S., Tauchi, T., Ito, Y., Ohyashiki, K. Tags: 605. Molecular Pharmacology, Drug Resistance-Lymphoid and Other Diseases 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
One siRNA pool targeting the {lambda} constant region stops {lambda} light-chain production and causes terminal endoplasmic reticulum stress
In systemic light-chain amyloidosis, light chains produced by clonal plasma cells cause organ damage and early death. In pursuit of novel therapy, we developed 1 pool of short interfering RNA (siRNA) targeting the constant region of light chains that substantially and promptly reduces -light-chain production and secretion by human plasma cells regardless of sequence diversity. In clones producing intact immunoglobulin G (IgG) antibodies (containing paired heavy and light chains), the secretion of intact antibodies is reduced, and all 3 branches of the unfolded protein response are activated by accumulation of unpaired IgG ...
Source: Blood - May 29, 2014 Category: Hematology Authors: Zhou, P., Ma, X., Iyer, L., Chaulagain, C., Comenzo, R. L. Tags: Multiple Myeloma, Lymphoid Neoplasia Source Type: research
