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https://www.readbyqxmd.com/read/28933264/from-a-better-understanding-of-the-mechanisms-of-action-of-histone-deacetylases-inhibitors-to-the-progress-of-the-treatment-of-malignant-lymphomas-and-plasma-cell-myeloma
#1
Romeo-Gabriel Mihăilă
BACKGROUND: Notable progress has been made in chemo- and immunotherapy of B-cell lymphomas, but less in the treatment of T-cell lymphomas. OBJECTIVE: Histone deacetylases inhibitors are a potentially useful therapeutic mean, as an epigenetic dysregulation is present in lymphomas, and especially in T-cell types. We aimed to study the progress made in this area. METHOD: A minireview was achieved using the articles published in PubMed in the last two years and the new patents made in this field...
September 19, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28932644/romidepsin-alone-or-in-combination-with-anti-cd20-chimeric-antigen-receptor-expanded-natural-killer-cells-targeting-burkitt-lymphoma-in-vitro-and-in-immunodeficient-mice
#2
Yaya Chu, Ashlin Yahr, Brian Huang, Janet Ayello, Matthew Barth, Mitchell S Cairo
Facilitating the development of alternative targeted therapeutic strategies is urgently required to improve outcome or circumvent chemotherapy resistance in children, adolescents, and adults with recurrent/refractory de novo mature B-cell (CD20) non-Hodgkin lymphoma, including Burkitt lymphoma (BL). Romidepsin, a histone deacetylase inhibitor (HDACi), has been used to treat cutaneous T-cell lymphoma. We have demonstrated the significant anti-tumor effect of anti-CD20 chimeric antigen receptor (CAR) modified expanded peripheral blood natural killer (exPBNK) against rituximab-sensitive and -resistant BL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28923081/erratum-to-romidepsin-for-the-treatment-of-relapsed-refractory-peripheral-t-cell-lymphoma-prolonged-stable-disease-provides-clinical-benefits-for-patients-in-the-pivotal-trial
#3
Francine Foss, Steven Horwitz, Barbara Pro, H Miles Prince, Lubomir Sokol, Barbara Balser, Julie Wolfson, Bertrand Coiffier
No abstract text is available yet for this article.
September 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28858522/chemical-editing-of-macrocyclic-natural-products-and-kinetic-profiling-reveal-slow-tight-binding-histone-deacetylase-inhibitors-with-picomolar-affinities
#4
Betül Kitir, Alex R Maolanon, Ragnhild G Ohm, Ana R Colaço, Peter Fristrup, Andreas S Madsen, Christian A Olsen
Histone deacetylases (HDACs) are validated targets for treatment of certain cancer types and play numerous regulatory roles in biology, ranging from epigenetics to metabolism. Small molecules are highly important as tool compounds for probing these mechanisms as well as for the development of new medicines. Therefore, detailed mechanistic information and precise characterization of the chemical probes used to investigate the effects of HDAC enzymes are vital. We interrogated Nature's arsenal of macrocyclic nonribosomal peptide HDAC inhibitors by chemical synthesis and evaluation of more than 30 natural products and analogues...
September 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28853310/responses-to-romidepsin-in-patients-with-cutaneous-t-cell-lymphoma-and-prior-treatment-with-systemic-chemotherapy
#5
Madeleine Duvic, Susan E Bates, Richard Piekarz, Robin Eisch, Youn H Kim, Adam Lerner, Tadeusz Robak, Alexey Samtsov, Jürgen C Becker, William McCulloch, Joel Waksman, Sean Whittaker
Cutaneous T-cell lymphomas (CTCL) are a group of non-Hodgkin lymphomas that typically present in the skin but can progress to systemic involvement. The optimal treatment for patients who relapse from or are refractory to systemic chemotherapy remains unclear. Romidepsin is a potent, class-I selective histone deacetylase inhibitor approved for the treatment of patients with CTCL who have had ≥1 prior systemic therapy. Here, we present a subanalysis of two phase-2 trials (NCT00106431, NCT00007345) of romidepsin in patients with CTCL who had prior treatment with systemic chemotherapy...
August 30, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28845251/a5%C3%A2-peripheral-blood-cells-contribute-to-hiv-1-viremia-induced-by-romidepsin
#6
A Winckelmann, K Barton, B Hiener, W Shao, L Østergaard, T Rasmussen, O Søgaard, M Tolstrup, S Palmer
No abstract text is available yet for this article.
March 2017: Virus Evolution
https://www.readbyqxmd.com/read/28829415/simultaneous-measurement-of-hdac1-and-hdac6-activity-in-hela-cells-using-uhplc-ms
#7
Claudia A Simões-Pires, Vincent Zwick, Sylvian Cretton, Muriel Cuendet
The search for new histone deacetylase (HDAC) inhibitors is of increasing interest in drug discovery. Isoform selectivity has been in the spotlight since the approval of romidepsin, a class I HDAC inhibitor for cancer therapy, and the clinical investigation of HDAC6-specific inhibitors for multiple myeloma. The present method is used to determine the inhibitory activity of test compounds on HDAC1 and HDAC6 in cells. The isoform activity is measured using the ultra-high-performance liquid chromatography - mass spectrometry (UHPLC-MS) analysis of specific substrates incubated with treated and untreated HeLa cells...
August 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28671573/histone-deacetylase-inhibitors-as-anticancer-drugs
#8
REVIEW
Tomas Eckschlager, Johana Plch, Marie Stiborova, Jan Hrabeta
Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc...
July 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28664499/romidepsin-in-japanese-patients-with-relapsed-or-refractory-peripheral-t-cell-lymphoma-a-phase-i-ii-and-pharmacokinetics-study
#9
Dai Maruyama, Kensei Tobinai, Michinori Ogura, Toshiki Uchida, Kiyohiko Hatake, Masafumi Taniwaki, Kiyoshi Ando, Kunihiro Tsukasaki, Takashi Ishida, Naoki Kobayashi, Kenichi Ishizawa, Yoichi Tatsumi, Koji Kato, Toru Kiguchi, Takayuki Ikezoe, Eric Laille, Tokihiro Ro, Hiromi Tamakoshi, Sanae Sakurai, Tomoko Ohtsu
This phase I/II multicenter study evaluated romidepsin treatment in Japanese patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Patients aged ≥20 years received romidepsin via a 4-h intravenous infusion on days 1, 8, and 15 of each 28-day cycle. Phase I used a 3 + 3 design to identify any dose-limiting toxicity (DLT) for regimens of romidepsin 9 and 14 mg/m(2). The primary endpoints for phase I and II were DLT and overall response rate (ORR), respectively...
June 29, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28649848/mogamulizumab-for-the-treatment-of-t-cell-lymphoma
#10
Shinichi Makita, Kensei Tobinai
T-cell lymphoma is a relatively rare hematologic malignancy that accounts for 10-20% of non-Hodgkin lymphomas. Treatment strategies for T-cell lymphomas are different from that for B-cell lymphomas and have poor prognoses. Among various subtypes of T-cell lymphomas, adult T-cell leukemia-lymphoma (ATL) has the worst prognosis. To achieve further improvement in the treatment outcome of T-cell lymphomas, several novel agents such as brentuximab vedotin, lenalidomide, romidepsin, and pralatrexate are actively being studied...
September 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28641053/the-discovery-and-development-of-romidepsin-for-the-treatment-of-t-cell-lymphoma
#11
REVIEW
Piotr Smolewski, Tadeusz Robak
Romidepsin is a potent and selective inhibitor of histone deacetylases (HDCAi). It is also the only bicyclic inhibitor to undergo clinical assessment and is considered a promising drug for the treatment of T-cell lymphomas. The cellular action of romidepsin results in enhanced histone acetylation, as well as the acetylation of other nuclear or cytoplasmic proteins, influencing cell cycle, apoptosis, and angiogenesis. In phase II studies involving patients with relapsed or refractory of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL), romidepsin produced overall response rates (ORR) of 34-35% and 25-38%, with complete response (CR) rates of 6% and 15-18%, respectively...
August 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28615266/antitumor-effects-of-epidrug-ifn%C3%AE-combination-driven-by-modulated-gene-signatures-in-both-colorectal-cancer-and-dendritic-cells
#12
Alessandra Fragale, Giulia Romagnoli, Valerio Licursi, Maria Buoncervello, Giorgia Del Vecchio, Caterina Giuliani, Stefania Parlato, Celeste Leone, Marta De Angelis, Irene Canini, Elena Toschi, Filippo Belardelli, Rodolfo Negri, Imerio Capone, Carlo Presutti, Lucia Gabriele
Colorectal cancer results from the progressive accumulation of genetic and epigenetic alterations. IFN signaling defects play an important role in the carcinogenesis process, in which the inability of IFN transcription regulatory factors (IRF) to access regulatory sequences in IFN-stimulated genes (ISG) in tumors and in immune cells may be pivotal. We reported that low-dose combination of two FDA-approved epidrugs, azacytidine (A) and romidepsin (R), with IFNα2 (ARI) hampers the aggressiveness of both colorectal cancer metastatic and stem cells in vivo and triggers immunogenic cell death signals that stimulate dendritic cell (DC) function...
July 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28601492/new-agents-in-multiple-myeloma-an%C3%A2-examination-of-safety-profiles
#13
REVIEW
Sara Bringhen, Edwin De Wit, Meletios-Athanassios Dimopoulos
Numerous treatments are available for relapsed and/or refractory multiple myeloma (MM), with safety profiles varying across drug classes and across agents within the same class. Thus, it is important to understand the toxicities of each antimyeloma agent when making treatment decisions. Neutropenia is commonly associated with lenalidomide and pomalidomide, and may be common with histone deacetylase (HDAC) inhibitors, but is relatively unusual with thalidomide, bortezomib, and carfilzomib. Infection was common in trials of lenalidomide and pomalidomide, and upper respiratory tract infection and pneumonia have been seen with carfilzomib...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28566628/histone-deacetylase-inhibitors-sensitize-murine-b16f10-melanoma-cells-to-carbon-ion-irradiation-by-inducing-g1-phase-arrest
#14
Katsuyo Saito, Tomoo Funayama, Yuichiro Yokota, Takashi Murakami, Yasuhiko Kobayashi
Epigenetic processes, in addition to genetic abnormalities, play a critical role in refractory malignant diseases and cause the unresponsiveness to various chemotherapeutic regimens and radiotherapy. Herein we demonstrate that histone deacetylase inhibitors (HDACis) can be used to sensitize malignant melanoma B16F10 cells to carbon ion irradiation. The cells were first treated with HDACis (romidepsin [FK228, depsipeptide], trichostatin A [TSA], valproic acid [VPA], and suberanilohydroxamic acid [SAHA, vorinostat]) and were then exposed to two types of radiation (carbon ions and gamma-rays)...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28560733/complete-remission-with-romidepsin-in-a-patient-with-t-cell-acute-lymphoblastic-leukemia-refractory-to-induction-hyper-cvad
#15
Mark W Brunvand, John Carson
T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) are neoplasms that originate from T-cell precursors. Outcomes in adult patients with T-ALL/LBL remain unsatisfactory; early relapse following intensive induction chemotherapy is a concern, and patients with relapsed or refractory disease have a poor prognosis. Romidepsin is a potent, class 1 selective histone deacetylase inhibitor approved for the treatment of patients with peripheral T-cell lymphoma who have had ≥1 prior therapy and patients with cutaneous T-cell lymphoma who have had ≥1 prior systemic therapy...
May 30, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28551413/applying-the-chicken-embryo-chorioallantoic-membrane-assay-to-study-treatment-approaches-in-urothelial-carcinoma
#16
Margaretha A Skowron, Anuja Sathe, Andrea Romano, Michèle J Hoffmann, Wolfgang A Schulz, Gommert A van Koeveringe, Peter Albers, Roman Nawroth, Günter Niegisch
BACKGROUND: Rapid development of novel treatment options demands valid preclinical screening models for urothelial carcinoma (UC). The translational value of high-throughput drug testing using 2-dimensional (2D) cultures is limited while for xenograft models handling efforts and costs often become prohibitive for larger-scale drug testing. Therefore, we investigated to which extent the chicken chorioallantoic membrane (CAM) assay might provide an alternative model to study antineoplastic treatment approaches for UC...
May 25, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28529033/high-throughput-characterization-of-hiv-1-reservoir-reactivation-using-a-single-cell-in-droplet-pcr-assay
#17
Robert W Yucha, Kristen S Hobbs, Emily Hanhauser, Louise E Hogan, Wildaliz Nieves, Mehmet O Ozen, Fatih Inci, Vanessa York, Erica A Gibson, Cassandra Thanh, Hadi Shafiee, Rami El Assal, Maja Kiselinova, Yvonne P Robles, Helen Bae, Kaitlyn S Leadabrand, ShuQi Wang, Steven G Deeks, Daniel R Kuritzkes, Utkan Demirci, Timothy J Henrich
Reactivation of latent viral reservoirs is on the forefront of HIV-1 eradication research. However, it is unknown if latency reversing agents (LRAs) increase the level of viral transcription from cells producing HIV RNA or harboring transcriptionally-inactive (latent) infection. We therefore developed a microfluidic single-cell-in-droplet (scd)PCR assay to directly measure the number of CD4(+) T cells that produce unspliced (us)RNA and multiply spliced (ms)RNA following ex vivo latency reversal with either an histone deacetylase inhibitor (romidepsin) or T cell receptor (TCR) stimulation...
June 2017: EBioMedicine
https://www.readbyqxmd.com/read/28506690/romidepsin-induces-caspase-dependent-cell-death-in-human-neuroblastoma-cells
#18
Shane V Hegarty, Katie L Togher, Eimear O'Leary, Franziska Solger, Aideen M Sullivan, Gerard W O'Keeffe
Neuroblastoma is the most common extracranial pediatric solid tumor, arising from the embryonic sympathoadrenal lineage of the neural crest, and is responsible for 15% of childhood cancer deaths. Although survival rates are good for some patients, those children diagnosed with high-risk neuroblastoma have survival rates as low as 35%. Thus, neuroblastoma remains a significant clinical challenge and the development of novel therapeutic strategies is essential. Given that there is widespread epigenetic dysregulation in neuroblastoma, epigenetic pharmacotherapy holds promise as a therapeutic approach...
July 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28467787/the-histone-deacetylase-inhibitor-romidepsin-as-a-potential-treatment-for-pulmonary-fibrosis
#19
Franco Conforti, Elizabeth R Davies, Claire J Calderwood, Thomas H Thatcher, Mark G Jones, David E Smart, Sumeet Mahajan, Aiman Alzetani, Tom Havelock, Toby M Maher, Philip L Molyneaux, Andrew J Thorley, Teresa D Tetley, Jane A Warner, Graham Packham, A Ganesan, Paul J Skipp, Benjamin J Marshall, Luca Richeldi, Patricia J Sime, Katherine M A O'Reilly, Donna E Davies
Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406576/antitumor-activity-and-pharmacologic-characterization-of-the-depsipeptide-analog-as-a-novel-histone-deacetylase-phosphatidylinositol-3-kinase-dual-inhibitor
#20
Ken Saijo, Hiroo Imai, Sonoko Chikamatsu, Koichi Narita, Tadashi Katoh, Chikashi Ishioka
Histone deacetylase (HDAC)/phosphatidylinositol 3-kinase (PI3K) dual inhibition is a promising strategy for the treatment of intractable cancers because of the advantages of overcoming potential resistance and showing synergistic effects. Therefore, development of an HDAC/PI3K dual inhibitor is reasonably attractive. Romidepsin (FK228, depsipeptide) is a potent HDAC inhibitor. We previously reported that depsipeptide and its analogs have an additional activity as PI3K inhibitors and are defined as HDAC/PI3K dual inhibitors...
July 2017: Cancer Science
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