6 results on '"Gatt, Moshe E."'
Search Results
2. Efficacy and safety of salvage therapy using Carfilzomib for relapsed or refractory multiple myeloma patients: a multicentre retrospective observational study.
- Author
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Muchtar E, Gatt ME, Rouvio O, Ganzel C, Chubar E, Suriu C, Tadmor T, Shevetz O, Lavi N, Shochat T, Cohen YC, Avivi I, Raanani P, and Magen H
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Drug Resistance, Neoplasm, Female, Humans, Male, Middle Aged, Multiple Myeloma pathology, Neoplasm Staging, Oligopeptides administration & dosage, Oligopeptides adverse effects, Proteasome Inhibitors administration & dosage, Proteasome Inhibitors adverse effects, Proteasome Inhibitors therapeutic use, Recurrence, Retrospective Studies, Salvage Therapy adverse effects, Salvage Therapy methods, Survival Analysis, Time Factors, Treatment Outcome, Antineoplastic Agents therapeutic use, Multiple Myeloma drug therapy, Oligopeptides therapeutic use
- Abstract
Carfilzomib has been established in previous years as a treatment for patients with relapsed and/or refractory multiple myeloma (RR-MM). A retrospective multicentre study to evaluate the clinical use of carfilzomib for RR-MM outside of a clinical trial setting was conducted by our group. One hundred and thirty-five patients were included. All patients had been previously exposed to bortezomib and 93% had also been treated with lenalidomide. The vast majority of patients received carfilzomib as part of a two- or three-drug combination. The overall response rate was 47·2%. Multivariate analysis revealed bortezomib resistance, lenalidomide resistance and albumin <35 g/l to negatively impact the likelihood of achieving response. The median duration of response was 8·4 months, and was significantly higher in patients receiving three-drug combination and patients presenting without extramedullary disease. The median progression-free survival and overall survival for the entire cohort was 4·9 months (95% confidence interval [CI] 3·8-6·4) and 12·2 months (95% CI 9-not reached), respectively. Toxicity was manageable, although treatment-related death was seen in 5% of patients. In the setting of progressive multiple myeloma, carfilzomib in a combination regimens yields effective results with a manageable toxicity., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
3. Phase I/II study exploring ImMucin, a pan-major histocompatibility complex, anti-MUC1 signal peptide vaccine, in multiple myeloma patients.
- Author
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Carmon L, Avivi I, Kovjazin R, Zuckerman T, Dray L, Gatt ME, Or R, and Shapira MY
- Subjects
- Aged, B7-H1 Antigen blood, B7-H1 Antigen immunology, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes pathology, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes pathology, Cancer Vaccines immunology, Cancer Vaccines pharmacology, Cell Proliferation drug effects, Epitopes, B-Lymphocyte immunology, Epitopes, T-Lymphocyte immunology, Female, Humans, Interferon-gamma blood, Interferon-gamma immunology, Male, Middle Aged, Mucin-1 immunology, Multiple Myeloma blood, Multiple Myeloma immunology, Cancer Vaccines administration & dosage, Epitopes, B-Lymphocyte administration & dosage, Epitopes, T-Lymphocyte administration & dosage, Mucin-1 administration & dosage, Multiple Myeloma drug therapy, Protein Sorting Signals, Vaccination
- Abstract
ImMucin, a 21-mer cancer vaccine encoding the signal peptide domain of the MUC1 tumour-associated antigen, possesses a high density of T- and B-cell epitopes but preserves MUC1 specificity. This phase I/II study assessed the safety, immunity and clinical response to 6 or 12 bi-weekly intradermal ImMucin vaccines, co-administered with human granulocyte-macrophage colony-stimulating factor to 15 MUC1-positive multiple myeloma (MM) patients, with residual or biochemically progressive disease following autologous stem cell transplantation. Vaccination was well tolerated; all adverse events were temporal grade 1 2 and spontaneously resolved. ImMucin vaccination induced a robust increase in γ-interferon (IFN-γ-producing CD4+ and CD8+ T-cells (≤80-fold), a pronounced population of ImMucin multimer CD8+ T-cells (>2%), a 9·4-fold increase in peripheral blood mononuclear cells proliferation and 6·8-fold increase in anti-ImMucin antibodies, accompanied with T-cell and antibody-dependent cell-mediated cytotoxicity. A significant decrease in soluble MUC1 levels was observed in 9/10 patients. Stable disease or improvement, persisting for 17·5-41·3 months (ongoing) was achieved in 11/15 patients and appeared to be associated with low-intermediate PDL1 (CD274) bone marrow levels pre- and post-vaccination. In summary, ImMucin, a highly tolerable cancerous vaccine, induces robust, diversified T- and B-cell ImMucin-specific immunity in MM patients, across major histocompatibility complex-barrier, resulting in at least disease stabilization in most patients., (© 2014 John Wiley & Sons Ltd.)
- Published
- 2015
- Full Text
- View/download PDF
4. Bortezomib-induced peripheral neuropathy is related to altered levels of brain-derived neurotrophic factor in the peripheral blood of patients with multiple myeloma.
- Author
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Azoulay D, Lavie D, Horowitz N, Suriu C, Gatt ME, Akria L, Perlman R, Braester A, and Ben-Yehuda D
- Subjects
- Aged, Boronic Acids administration & dosage, Bortezomib, Female, Humans, Male, Middle Aged, Multiple Myeloma drug therapy, Multiple Myeloma genetics, Multiple Myeloma metabolism, Pyrazines administration & dosage, Boronic Acids adverse effects, Brain-Derived Neurotrophic Factor blood, Multiple Myeloma blood, Peripheral Nervous System Diseases blood, Peripheral Nervous System Diseases chemically induced, Pyrazines adverse effects
- Published
- 2014
- Full Text
- View/download PDF
5. TRIM13 (RFP2) downregulation decreases tumour cell growth in multiple myeloma through inhibition of NF Kappa B pathway and proteasome activity.
- Author
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Gatt ME, Takada K, Mani M, Lerner M, Pick M, Hideshima T, Carrasco DE, Protopopov A, Ivanova E, Sangfelt O, Grandér D, Barlogie B, Shaughnessy JD Jr, Anderson KC, and Carrasco DR
- Subjects
- Apoptosis genetics, Cell Cycle genetics, Cell Division genetics, Cell Line, Tumor, Cell Survival genetics, Chromosome Deletion, Chromosomes, Human, Pair 13, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Down-Regulation, Gene Expression Profiling, Gene Knockdown Techniques, Humans, Multiple Myeloma metabolism, NF-kappa B genetics, NF-kappa B metabolism, Proteasome Endopeptidase Complex genetics, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, DNA-Binding Proteins biosynthesis, Multiple Myeloma genetics, Multiple Myeloma pathology, NF-kappa B antagonists & inhibitors, Proteasome Endopeptidase Complex metabolism, Tumor Suppressor Proteins biosynthesis
- Abstract
Multiple myeloma (MM) is an incurable neoplasm caused by proliferation of malignant plasma cells in the bone marrow (BM). MM is characterized frequently by a complete or partial deletion of chromosome 13q14, seen in more than 50% of patients at diagnosis. Within this deleted region the tripartite motif containing 13 (TRIM13, also termed RFP2) gene product has been proposed to be a tumour suppressor gene (TSG). Here, we show that low expression levels of TRIM13 in MM are associated with chromosome 13q deletion and poor clinical outcome. We present a functional analysis of TRIM13 using a loss-of-function approach, and demonstrate that TRIM13 downregulation decreases tumour cell survival as well as cell cycle progression and proliferation of MM cells. In addition, we provide evidence for the involvement of TRIM13 downregulation in inhibiting the NF kappa B pathway and the activity of the 20S proteasome. Although this data does not support a role of TRIM13 as a TSG, it substantiates important roles of TRIM13 in MM tumour survival and proliferation, underscoring its potential role as a novel target for therapeutic intervention., (© 2013 John Wiley & Sons Ltd.)
- Published
- 2013
- Full Text
- View/download PDF
6. Phase I/ II study exploring ImMucin, a pan-major histocompatibility complex, anti- MUC1 signal peptide vaccine, in multiple myeloma patients.
- Author
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Carmon, Lior, Avivi, Irit, Kovjazin, Riva, Zuckerman, Tsila, Dray, Lillian, Gatt, Moshe E., Or, Reuven, and Shapira, Michael Y.
- Subjects
MULTIPLE myeloma treatment ,CANCER vaccines ,PEPTIDE drugs ,MAJOR histocompatibility complex ,CELLULAR signal transduction ,CELLULAR immunity - Abstract
ImMucin, a 21-mer cancer vaccine encoding the signal peptide domain of the MUC1 tumour-associated antigen, possesses a high density of T- and B-cell epitopes but preserves MUC1 specificity. This phase I/ II study assessed the safety, immunity and clinical response to 6 or 12 bi-weekly intradermal ImMucin vaccines, co-administered with human granulocyte-macrophage colony-stimulating factor to 15 MUC1-positive multiple myeloma ( MM) patients, with residual or biochemically progressive disease following autologous stem cell transplantation. Vaccination was well tolerated; all adverse events were temporal grade 1 2 and spontaneously resolved. ImMucin vaccination induced a robust increase in γ-interferon ( IFN-γ-producing CD4+ and CD8+ T-cells (≤80-fold), a pronounced population of ImMucin multimer CD8+ T-cells (>2%), a 9·4-fold increase in peripheral blood mononuclear cells proliferation and 6·8-fold increase in anti-ImMucin antibodies, accompanied with T-cell and antibody-dependent cell-mediated cytotoxicity. A significant decrease in soluble MUC1 levels was observed in 9/10 patients. Stable disease or improvement, persisting for 17·5-41·3 months (ongoing) was achieved in 11/15 patients and appeared to be associated with low-intermediate PDL1 ( CD274) bone marrow levels pre- and post-vaccination. In summary, ImMucin, a highly tolerable cancerous vaccine, induces robust, diversified T- and B-cell ImMucin-specific immunity in MM patients, across major histocompatibility complex-barrier, resulting in at least disease stabilization in most patients. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
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