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Total 71 results found since Jan 2013.
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
The Role of Thrombin Deficiency on Skeletal Health
ConclusionThis study seeks to understand the underlying mechanism for bone disease in hemophilia. The results indicate that >85% prothrombin knockdown in wild-type mice starting at 3 weeks of age does not significantly alter skeletal health. This suggests that either 1) thrombin deficiency is not involved in the mechanism of decreased skeletal health in hemophilia or; 2) the role of thrombin deficiency occurs early in bone development (prior to 3 weeks of age). To evaluate these two potential explanations, thrombin deficiency needs to be evaluated earlier in development. Thrombin deficient mice are embryonically lethal....
Source: Blood - November 21, 2018 Category: Hematology Authors: Taylor, H. J., Goldscheitter, G., Taylor, J. A. Tags: 321. Blood Coagulation and Fibrinolytic Factors Source Type: research
A Critical Role of Growth Arrest-Specific Gene 6-Mer Axis in the Pathogenesis of Endothelial Damage Contributing to Thrombotic Microangiopathy Associated with Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation
Graft-versus-host disease (GVHD) and thrombotic microangiopathy (TMA) are severe complications of allogeneic hematopoietic stem cell transplantation (allo-SCT). Host endothelial cells are targets of alloreactive donor cytotoxic T lymphocytes or various proinflammatory cytokines following allo-SCT, and endothelial damage plays an important role in the pathogenic mechanism(s) of TMA associated with GVHD. However, the detailed mechanism(s) of TMA as well as GVHD have not yet been fully elucidated. Growth arrest-specific (Gas) 6 structurally belongs to the family of plasma vitamin K-dependent proteins working as a cofactor for...
Source: Blood - November 21, 2018 Category: Hematology Authors: Furukawa, M., Xintao, W., Ohkawara, H., Fukatsu, M., Alkebsi, L., Noji, H., Ogawa, K., Ikezoe, T. Tags: 701. Experimental Transplantation: Basic Biology, Pre-Clinical Models: Poster III 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 XIAP Via Degradation of MDM-2 By MX69 in Aggressive Lymphomas
Conclusion: Our data suggests that in vitro exposure of a wide variety of B-cell lymphoma cell lines (including BL, DLBCL, MCL or RRCL) to MX69 resulted in anti-tumor activity. Perhaps related to its anti-tumor effects, MX69 inhibited XIAP levels. These findings are similar to prior SiRNA XIAP knockdown experiments. Strong synergistic activity was observed when XIAP was combined with various chemotherapy agents and small molecules inhibitors (such as Venetoclax, ixazomib or ibrutinib). Ex vivo experiments using primary tumor cells isolated from lymphoma patients and lymphoma mouse models are been planned. Targeting Mdm2 an...
Source: Blood - November 21, 2018 Category: Hematology Authors: Khan, S., Runckel, K., Mavis, C., Barth, M. J., Hernandez-Ilizaliturri, F. J. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents Source Type: research
Functional Analysis of CD99 Upregulation in Acute Myeloid Leukemia
Conclusion: In summary, our results suggests that even though CD99 enhances AML cell proliferation, it also enhances homotypic cell interaction and cell aggregation, which results in increased cell apoptosis as well as a decrease in cell migration and possibly responsible for the decrease leukemia engraftment. Further investigations are ongoing to determine the effect of homotypic interaction of CD99 in AML.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Vaikari, V. P., Yang, J., Akhtari, M., Alachkar, H. Tags: 603. Oncogenes and Tumor Suppressors Source Type: research
Topoisomerase I-DNA Covalent Complexes in Myeloid Malignancies: A Potential Biomarker for Topoisomerase I Inhibitor Sensitivity
Conclusions: Based on recent clinical results, there has been renewed interested in topoisomerase I inhibitors, especially for aggressive and transformed MPNs. Topoisomerase I-DNA complex repair/downregulation has been a hallmark of drug resistance to topoisomerase I inhibitors. Therefore, detecting and quantifying these complexes in treated samples has been hypothesized to provide insight into the drug sensitivity, which is particularly important in camptothecins and platinating agents given their narrow therapeutic windows. Immunodetection techniques using an anti-TopIcc antibody may help predict sensitivity of AML to to...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kohorst, M. A., Flatten, K. S., Peterson, K. L., Schneider, P. A., Correia, C., Pratz, K. W., Smith, B. D., Kaufmann, S. H. Tags: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases 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
Vitamin A-coupled liposomes containing siRNA against HSP47 ameliorate skin fibrosis in chronic graft-versus-host disease
Chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (SCT) is characterized by multiorgan fibrosis and profoundly affects the quality of life of transplant survivors. Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, plays a critical role in collagen synthesis in myofibroblasts. We explored the role of HSP47 in the fibrotic process of cutaneous chronic GVHD in mice. Immunohistochemical analysis showed massive fibrosis with elevated amounts of collagen deposits and accumulation of F4/80+ macrophages, as well as myofibroblasts expressing HSP47 and retinol-bin...
Source: Blood - March 29, 2018 Category: Hematology Authors: Yamakawa, T., Ohigashi, H., Hashimoto, D., Hayase, E., Takahashi, S., Miyazaki, M., Minomi, K., Onozawa, M., Niitsu, Y., Teshima, T. Tags: Transplantation Source Type: research
Role of platelets, neutrophils, and factor XII in spontaneous venous thrombosis in mice
This study challenges the proposed roles of neutrophils and FXII in venous thrombosis pathophysiology.
Source: Blood - May 25, 2016 Category: Hematology Authors: Heestermans, M., Salloum-Asfar, S., Salvatori, D., Laghmani, E. H., Luken, B. M., Zeerleder, S. S., Spronk, H. M. H., Korporaal, S. J., Wagenaar, G. T. M., Reitsma, P. H., van Vlijmen, B. J. M. Tags: Phagocytes, Granulocytes, and Myelopoiesis, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
DUSP4-mediated accelerated T-cell senescence in idiopathic CD4 lymphopenia
Idiopathic CD4 lymphopenia (ICL) is a rare heterogeneous immunological syndrome of unclear etiology. ICL predisposes patients to severe opportunistic infections and frequently leads to poor vaccination effectiveness. Chronic immune activation, expansion of memory T cells, and impaired T-cell receptor (TCR) signaling have been reported in ICL, but the mechanistic and causative links remain unclear. We show that late-differentiated T cells in 20 patients with ICL displayed defective TCR responses and aging markers similar to those found in T cells from elderly subjects. Intrinsic T-cell defects were caused by increased expre...
Source: Blood - April 16, 2015 Category: Hematology Authors: Bignon, A., Regent, A., Klipfel, L., Desnoyer, A., de la Grange, P., Martinez, V., Lortholary, O., Dalloul, A., Mouthon, L., Balabanian, K. Tags: Immunobiology 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
