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https://www.readbyqxmd.com/read/29622656/a-phase-i-study-of-romidepsin-and-ifosfamide-carboplatin-etoposide-for-the-treatment-of-patients-with-relapsed-or-refractory-peripheral-t-cell-lymphoma
#1
Paolo Strati, Dai Chihara, Yasuhiro Oki, Luis E Fayad, Nathan Fowler, Loretta Nastoupil, Jorge E Romaguera, Felipe Samaniego, Naveen Garg, Lei Feng, Emily T Wesson, Charnelle E Ruben, Mildred D Stafford, Yago Nieto, Issa F Khouri, Chitra Hosing, Sandra B Horowitz, Rammurti T Kamble, Michelle A Fanale
No abstract text is available yet for this article.
April 5, 2018: Haematologica
https://www.readbyqxmd.com/read/29531362/social-deficits-in-shank3-deficient-mouse-models-of-autism-are-rescued-by-histone-deacetylase-hdac-inhibition
#2
Luye Qin, Kaijie Ma, Zi-Jun Wang, Zihua Hu, Emmanuel Matas, Jing Wei, Zhen Yan
Haploinsufficiency of the SHANK3 gene is causally linked to autism spectrum disorder (ASD), and ASD-associated genes are also enriched for chromatin remodelers. Here we found that brief treatment with romidepsin, a highly potent class I histone deacetylase (HDAC) inhibitor, alleviated social deficits in Shank3-deficient mice, which persisted for ~3 weeks. HDAC2 transcription was upregulated in these mice, and knockdown of HDAC2 in prefrontal cortex also rescued their social deficits. Nuclear localization of β-catenin, a Shank3-binding protein that regulates cell adhesion and transcription, was increased in Shank3-deficient mice, which induced HDAC2 upregulation and social deficits...
March 12, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29526921/-romidepsin-istodax-%C3%A2-for-intravenous-injection-10-mg-pharmacokinetics-pharmacodynamics-and-clinical-study-outcome
#3
Tokihiro Ro, Naoki Nakayama, Hiroyuki Achiwa, Tomoko Ohtsu
Romidepsin (Brand name: ISTODAX® for Injection 10 mg) is a novel antitumor drug that inhibits histone deacetylase (HDAC). Romidepsin strongly inhibited class I HDAC activity in vitro and demonstrated a strong antitumor activity against human tumor cell line xenograft in vivo. Based on its demonstrated efficacy against T-cell lymphoma in early clinical studies, multicenter phase II clinical studies in overseas with romidepsin were conducted in patients with cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL), followed by approval for the treatment of CTCL and PTCL in the U...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29515768/cxcr2-is-a-negative-regulator-of-p21-in-p53-dependent-and-independent-manner-via-akt-mediated-mdm2-in-ovarian-cancer
#4
Rosa Mistica C Ignacio, Yuan-Lin Dong, Syeda M Kabir, Hyeongjwa Choi, Eun-Sook Lee, Andrew J Wilson, Alicia Beeghly-Fadiel, Margaret M Whalen, Deok-Soo Son
Ovarian cancer (OC) has the highest rate of mortality among gynecological malignancy. Chemokine receptor CXCR2 in OC is associated with poor outcomes. However, the mechanisms by which CXCR2 regulates OC proliferation remain poorly understood. We generated CXCR2-positive cells from parental p53 wild-type (WT), mutant and null OC cells, and assessed the roles of CXCR2 on proliferation of OC cells in p53-dependent and independent manner. CXCR2 promoted cell growth rate: p53WT > mutant = null cells. Nutlin-3, a p53 stabilizer, inhibited cell proliferation in p53WT cells, but had little effect in p53-mutant or null cells, indicating p53-dependence of CXCR2-mediated proliferation...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29515392/large-cell-transformed-mycosis-fungoides-coexisting-with-mycosis-fungoides-bullosa-a-case-report-and-review-of-the-literature
#5
Saneerat Porntharukcharoen, Suthinee Rutnin, Natta Rajatanavin
Mycosis fungoides is the most common form of cutaneous T-cell lymphoma. Both large-cell transformed mycosis fungoides and mycosis fungoides bullosa are rare presentations and predict unfavorable prognosis. We report the case of a 61-year-old woman who presented with generalized erythematous scaly annular plaques, and histopathology confirmed the diagnosis of mycosis fungoides. She was treated with various conventional therapies but only achieved partial response and always relapsed after discontinuation of treatment...
September 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/29484736/pharmacological-or-transcriptional-inhibition-of-both-hdac1-and-2-leads-to-cell-cycle-blockage-and-apoptosis-via-p21-waf1-cip1-and-p19-ink4d-upregulation-in-hepatocellular-carcinoma
#6
Hengyu Zhou, Ying Cai, Dina Liu, Menghui Li, Yu Sha, Wenlu Zhang, Kai Wang, Jianping Gong, Ni Tang, Ailong Huang, Jie Xia
OBJECTIVES: Histone deacetylases (HDACs) are commonly dysregulated in cancer and represent promising therapeutic targets. However, global HDAC inhibitors have shown limited efficacy in the treatment of solid tumours, including hepatocellular carcinoma (HCC). In this study, we investigated the therapeutic effect of selectively inhibiting HDAC1 and 2 in HCC. METHODS: HDAC1 inhibitor Tacedinaline (CI994), HDAC2 inhibitor Santacruzamate A (CAY10683), HDAC1/2 common inhibitor Romidepsin (FK228) and global HDAC inhibitor Vorinostat (SAHA) were used to treat HCC cells...
February 27, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29423093/combination-of-a-hypomethylating-agent-and-inhibitors-of-parp-and-hdac-traps-parp1-and-dnmt1-to-chromatin-acetylates-dna-repair-proteins-down-regulates-nurd-and-induces-apoptosis-in-human-leukemia-and-lymphoma-cells
#7
Benigno C Valdez, Yang Li, David Murray, Yan Liu, Yago Nieto, Richard E Champlin, Borje S Andersson
Combination of drugs that target different aspects of aberrant cellular processes is an efficacious treatment for hematological malignancies. Hypomethylating agents (HMAs) and inhibitors of poly(ADP-ribose) polymerases (PARPis) and histone deacetylases (HDACis) are clinically active anti-tumor drugs. We hypothesized that their combination would be synergistically cytotoxic to leukemia and lymphoma cells. Exposure of AML and lymphoma cell lines to the combination of the PARPi niraparib (Npb), the HMA decitabine (DAC) and the HDACi romidepsin (Rom) or panobinostat (Pano) synergistically inhibited cell proliferation by up to 70% via activation of the ATM pathway, increased production of reactive oxygen species, decreased mitochondrial membrane potential, and activated apoptosis...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29397528/the-future-of-combination-therapies-for-peripheral-t-cell-lymphoma-ptcl
#8
REVIEW
Helen Ma, Ardy Davarifar, Jennifer E Amengual
PURPOSE OF REVIEW: Peripheral T cell lymphoma is a rare heterogeneous group of diseases which are characterized by poor outcomes to treatment and short overall survival. In the past decade, several new therapies targeting T cell biology have been approved in the relapsed setting. These new therapies, such as pralatrexate, romidepsin, belinostat, and brentuximab vedotin, have begun to make their way into practice. Despite these advances, outcomes have not changed dramatically. In recent years, efforts have been made to incorporate these new therapies into combination strategies to treat this challenging disease entity...
February 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29391350/overcoming-resistance-to-dna-targeted-agents-by-epigenetic-activation-of-schlafen-11-slfn11-expression-with-class-i-histone-deacetylase-inhibitors
#9
Sai Wen Tang, Anish Thomas, Junko Murai, Jane Trepel, Susan E Bates, Vinodh N Rajapakse, Yves Pommier
PURPOSE: Schlafen 11 (SLFN11), a putative DNA/RNA helicase is a dominant genomic determinant of response to DNA damaging agents and is frequently not expressed in cancer cells. Whether histone deacetylase (HDAC) inhibitors can be used to release SLFN11 and sensitize SLFN11-inactivated cancers to DNA-targeted agents is tested here. EXPERIMENTAL DESIGN: SLFN11 expression was examined in The Cancer Genome Atlas (TCGA), in cancer cell line databases and in patients treated with romidepsin...
February 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29312470/combined-inhibition-of-bet-proteins-and-class-i-hdacs-synergistically-induces-apoptosis-in-urothelial-carcinoma-cell-lines
#10
Alexander S Hölscher, Wolfgang A Schulz, Maria Pinkerneil, Günter Niegisch, Michèle J Hoffmann
Background: New efficient therapies for urothelial carcinoma (UC) are urgently required. Small-molecule drugs targeting chromatin regulators are reasonable candidates because these regulators are frequently mutated or deregulated in UC. Indeed, in previous work, Romidepsin, which targets class I histone deacetylases (HDAC), efficiently killed UC cells, but did not elicit canonical apoptosis and affected benign urothelial cells indiscriminately. Combinations of HDAC inhibitors with JQ1, an inhibitor of bromodomain-containing acetylation reader proteins like BRD4, which promote especially the transcription of pro-tumorigenic genes, have shown efficacy in several tumor types...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29209628/inhibitors-of-histone-deacetylases-are-weak-activators-of-the-fmr1-gene-in-fragile-x-syndrome-cell-lines
#11
Alexander A Dolskiy, Vladimir O Pustylnyak, Andrey A Yarushkin, Natalya A Lemskaya, Dmitry V Yudkin
Fragile X syndrome is the most common cause of inherited intellectual disability in humans. It is a result of CGG repeat expansion in the 5' untranslated region (5' UTR) of the FMR1 gene. This gene encodes the FMRP protein that is involved in neuronal development. Repeat expansion leads to heterochromatinization of the promoter, gene silencing, and the subsequent absence of FMRP. To date, there is no specific therapy for the syndrome. All treatments in clinic practice provide symptomatic therapy. The development of drug therapy for Fragile X syndrome treatment is connected with the search for inhibitors of enzymes that are responsible for heterochromatinization...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29191068/an-exploratory-cost-effectiveness-analysis-of-systemic-treatments-for-cutaneous-t-cell-lymphoma
#12
Larisa Geskin, Daniel C Malone
PURPOSE: To conduct an exploratory cost-effectiveness analysis of systemic treatment options for more advanced cutaneous T-cell lymphoma (CTCL). METHODS: A cost-effectiveness model compared systemic bexarotene, denileukin diftitox, interferon-α, methotrexate, pralatrexate, romidepsin, vorinostat, and extracorporeal photopheresis (ECP) treatment of CTCL. Treatment effectiveness data were extracted from published studies and/or US product labeling. Overall response, the primary effectiveness measure, was defined as the proportion of patients achieving complete or partial response...
December 18, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29141948/a-phase-1-study-of-romidepsin-and-pralatrexate-reveals-marked-activity-in-relapsed-and-refractory-t-cell-lymphoma
#13
Jennifer E Amengual, Renee Lichtenstein, Jennifer Lue, Ahmed Sawas, Changchun Deng, Emily Lichtenstein, Karen Khan, Laine Atkins, Aishling Rada, Hye A Kim, Codruta Chiuzan, Matko Kalac, Enrica Marchi, Lorenzo Falchi, Mark A Francescone, Lawrence Schwartz, Serge Cremers, Owen A O'Connor
Peripheral T-cell lymphomas (PTCL) are a group of rare malignancies characterized by chemotherapy resistance and poor prognosis. Romidepsin and pralatrexate were approved by the US Food and Drug Administration for patients with relapsed/refractory PTCL, exhibiting response rates of 25% and 29% respectively. Based on synergy in preclinical models of PTCL, we initiated a phase 1 study of pralatrexate plus romidepsin in patients with relapsed/refractory lymphoma. This was a single institution dose-escalation study of pralatrexate plus romidepsin designed to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetic profile, and response rates...
January 25, 2018: Blood
https://www.readbyqxmd.com/read/29135083/comparison-of-the-anticancer-properties-of-a-novel-valproic-acid-prodrug-to-leading-histone-deacetylase-inhibitors
#14
Nataly Tarasenko, Hanna Chekroun-Setti, Abraham Nudelman, Ada Rephaeli
The HDAC inhibitory activity of valproic acid (VPA) has led to on-going evaluation of it as an anticancer agent. The histone deacetylase (HDAC) inhibitor AN446, a prodrug of VPA, releases the acid upon metabolic degradation. AN446 is >60-fold more potent than VPA in killing cancer cells in vitro. Herein, we compare the activities of AN446, as an anticancer agent, to those of representative types from each of the four major classes of HDAC inhibitors (HDACIs): vorinostat, romidepsin, entinostat, and VPA. AN446 exhibited the greatest selectivity and HDAC inhibitory activity against cancer cells...
April 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29102679/cutaneous-t-cell-lymphomas-focusing-on-novel-agents-in-relapsed-and-refractory-disease
#15
REVIEW
Lisa Argnani, Alessandro Broccoli, Pier Luigi Zinzani
Patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) display a dismal prognosis and their therapy represents an unmet medical need, as the best treatment strategy is yet to be determined. Exciting data on novel targeted agents are now emerging from recently concluded and ongoing clinical trials in patients with relapsed and refractory CTCL. Three FDA approved compounds are used as single agents including the oral retinoid bexarotene and histone deacetylase inhibitors romidepsin and vorinostat...
December 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29025909/histone-deacetylase-inhibitors-downregulate-ccr4-expression-and-decrease-mogamulizumab-efficacy-in-ccr4-positive-mature-t-cell-lymphomas
#16
Akihiro Kitadate, Sho Ikeda, Fumito Abe, Naoto Takahashi, Norio Shimizu, Kosei Matsue, Hiroyuki Tagawa
Histone deacetylase inhibitors are promising agents for various T-cell lymphomas, including cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and adult T-cell lymphoma/leukemia. CCR4 is an important therapeutic target molecule because mogamulizumab, an anti-CCR4 antibody, has shown promising efficacy against various T-cell lymphomas. In this study, we examined the in vitro synergistic effects of mogamulizumab and histone deacetylase inhibitors against various T-cell lymphomas. First, we examined the expression of CCR4 mRNA and surface CCR4 in various T-cell lymphoma cell lines and found that it was downregulated upon treatment with vorinostat, a pan-histone deacetylase inhibitor...
January 2018: Haematologica
https://www.readbyqxmd.com/read/29018892/novel-treatment-opportunities-for-sulfur-mustard-related-cancers-genetic-and-epigenetic-perspectives
#17
REVIEW
Soheila Rahmani, Mohammad Abdollahi
Sulfur mustard (SM), also known as mustard gas, is a chemical weapon which by now has been used in many wars. The most concerning SM toxic effect is probable carcinogenicity. In this study, the genetic and epigenetic mechanisms of SM carcinogenicity, by focusing on treatment of SM-associated malignancies, particularly gene therapeutics, cancer vaccines, and epigenetic medications, have been criticized. The required data were collected through an organized search on valid scientific databases. For SM carcinogenicity due to acute or chronic exposure, the entire original and review articles were evaluated...
December 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28972015/synergy-of-bcl2-and-histone-deacetylase-inhibition-against-leukemic-cells-from-cutaneous-t-cell-lymphoma-patients
#18
Benoit M Cyrenne, Julia M Lewis, Jason G Weed, Kacie R Carlson, Fatima N Mirza, Francine M Foss, Michael Girardi
The presence and degree of peripheral blood involvement in patients with cutaneous T-cell lymphoma (CTCL) portend a worse clinical outcome. Available systemic therapies for CTCL may variably decrease tumor burden and improve quality of life, but offer limited effects on survival; thus, novel approaches to the treatment of advanced stages of this non-Hodgkin lymphoma are clearly warranted. Mutational analyses of CTCL patient peripheral blood malignant cell samples suggested the antiapoptotic mediator B-cell lymphoma 2 (BCL2) as a potential therapeutic target...
November 9, 2017: Blood
https://www.readbyqxmd.com/read/28946015/peripheral-t-cell-lymphomas-focusing-on-novel-agents-in-relapsed-and-refractory-disease
#19
REVIEW
Alessandro Broccoli, Lisa Argnani, Pier Luigi Zinzani
Patients with relapsed or refractory peripheral T-cell lymphoma display a dismal prognosis and their therapy represents an unmet medical need, as the best treatment strategy is yet to be determined. Exciting data on novel targeted agents are now emerging from recently concluded and ongoing clinical trials in patients with relapsed and refractory PTCL. Four recently approved compounds are used as single agents: pralatrexate, a novel antifolate agent; romidepsin and belinostat, both histone deacetylase (HDAC) inhibitors; brentuximab vedotin, an anti-CD30 drug-conjugated monoclonal antibody...
November 2017: Cancer Treatment Reviews
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
#20
Romeo G Mihaila
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 mini-review was achieved using the articles published in PubMed in the last two years and the new patents made in this field...
November 20, 2017: Recent Patents on Anti-cancer Drug Discovery
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