Selective Inhibitors of Nuclear Export in the Treatment of Hematologic Malignancies

We report results of preclinical studies and clinical trials, and discuss the mechanism of action of SINEs and their effects in multiple myeloma, non-Hodgkin lymphomas, lymphoblastic leukemia, and acute and chronic myeloid leukemia. In the future, the numerous experimental studies currently underway will allow us to define the role of SINEs and will possibly permit these substances to be introduced into daily clinical practice.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research

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We reported results of preclinical studies and clinical trials and discussed the mechanism of action of SINEs and their effects in multiple myeloma, non-Hodgkin lymphomas, lymphoblastic leukaemia, acute and chronic myeloid leukaemia.In the next future the numerous experimental studies currently underway will allow us to define the role of the SINEs and the possibility of introducing these substances into daily clinical practice.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
We report results of preclinical studies and clinical trials, and discuss the mechanism of action of SINEs and their effects in multiple myeloma, non-Hodgkin lymphomas, lymphoblastic leukemia, and acute and chronic myeloid leukemia.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Review Source Type: research
We reported results of preclinical studies and clinical trials and discussed the mechanism of action of SINEs and their effects in multiple myeloma, non-Hodgkin lymphomas, lymphoblastic leukaemia, acute and chronic myeloid leukaemia.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Review Article Source Type: research
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
This study proposed a pilot study of a new tool for a reliable and accurate stratification of patients with acute leukemia based on an integrative model of leukemia behavior, cell characterization, and clinical features, in addition, to an evaluation of intra-tumor and inter-tumor heterogeneity. Together our approach allows us to introduce an integrative quantitative approach to use zebrafish and tumor characterization as a prediction tool for the behavior of acute leukemia in young adults. Materials and Methods Animal Care and Handling Zebrafish wild-type (A/B and TAB5) adults were raised and maintained according to st...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, the high structural diversity of these compounds pinpoints the significant range of inhibition strategies that can be conceived to target the class I methyltransferases. Although the structural details of the various members of this family are unique, the success stories of drug design for several enzymes belonging to this family portends the likely achievement of discovering potent and selective inhibitors of METTL3/METTL14. Author Contributions AF and AP wrote the manuscript. ZI revised and edited manuscript and prepared figures. Funding This work was supported by Associazione Italiana Ricerca sul Canc...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study analyzes patient and hospital characteristics of patients undergoing BMT, in addition the study describes resource utilization and outcomes of BMT among various hematological cancers.Methods: We performed a retrospective cohort analysis of the National Inpatient Sample 2014 Database (HCUP-NIS). Patients were included in the study if they had a procedure diagnosis of BMT and a medical diagnosis of acute or chronic leukemia (ALL, AML, CLL, CML), lymphoma (HL and NHL), MM, MDS or HLH. HSCT or BMT includes both Allogeneic and Autologous Stem Cell Transplant however we did not differentiate one from the other since B...
Source: Blood - Category: Hematology Authors: Tags: 902. Health Services Research-Malignant Diseases: Poster III Source Type: research
Immunotherapy is a promising approach to improve treatment responses in hematological malignancies. Accumulating evidence suggests a role for natural killer (NK) cells in controlling hematological malignancies. However, mechanisms regulating sensitivity or resistance of hematologic cancer cells to the effector function of NK cells are incompletely understood. Here, we performed genome-scale CRISPR-Cas9 loss-of-function screens to systematically map genes that regulate sensitivity of hematologic malignancies to NK cells.To screen for genes involved in the interaction between NK and cancer cells, we infected human cancer cel...
Source: Blood - Category: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Pre-clinical T and NK Cell Immunotherapies Source Type: research
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