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Panobinostat

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https://www.readbyqxmd.com/read/28710768/panobinostat-sensitizes-kras-mutant-non-small-cell-lung-cancer-to-gefitinib-by-targeting-taz
#1
Wen-Ying Lee, Pin-Cyuan Chen, Wen-Shin Wu, Han-Chung Wu, Chun-Hsin Lan, Yen-Hua Huang, Chia-Hsiung Cheng, Ku-Chung Chen, Cheng-Wei Lin
Mutation of KRAS in non-small cell lung cancer (NSCLC) shows a poor response to epidermal growth factor receptor (EGFR) inhibitors and chemotherapy. Currently, there are no direct anti-KRAS therapies available. Thus, new strategies have emerged for targeting KRAS downstream signaling. Panobinostat is a clinically available histone deacetylase inhibitor for treating myelomas and also shows potentiality in NSCLC. However, the therapeutic efficacy of panobinostat against gefitinib-resistant NSCLC is unclear. In this study, we demonstrated that panobinostat overcame resistance to gefitinib in KRAS-mutant/EGFR-wild type NSCLC...
July 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28690313/the-hdac-inhibitor-panobinostat-lbh589-exerts-in-vivo-anti-leukaemic-activity-against-mll-rearranged-acute-lymphoblastic-leukaemia-and-involves-the-rnf20-rnf40-wac-h2b-ubiquitination-axis
#2
P G Castro, E H J van Roon, S S M Pinhanços, L Trentin, P Schneider, M Kerstjens, G Te Kronnie, O Heidenreich, R Pieters, R W Stam
MLL-rearranged acute lymphoblastic leukaemia (ALL) represents an aggressive malignancy in infants (<1 year of age), associated with poor outcome. Current treatment intensification is not further possible, and novel therapy strategies are needed. Notably, MLL-rearranged ALL is characterised by a strongly deregulated epigenome and shows sensitivity to epigenetic perturbators. Here, we demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) using xenograft mouse models of MLL-rearranged ALL...
July 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28685863/efficacy-and-tolerability-of-the-histone-deacetylase-inhibitor-panobinostat-in-clinical-practice
#3
Marc-Andrea Baertsch, Jens Hillengass, Joanna Blocka, Stefan Schönland, Ute Hegenbart, Hartmut Goldschmidt, Marc S Raab
The histone deacetylase inhibitor panobinostat has shown efficacy in phase-II and phase-III trials for multiple myeloma and has recently received market approval in combination with bortezomib and dexamethasone. Here, we retrospectively report our single center experience with panobinostat/bortezomib/dexamethasone (FVD) in a heavily pretreated patient population (n = 24) with a high degree of refractoriness to proteasome inhibitors (PI) and immunomodulatory drugs (IMiD). Median age was 67 years (range 49-87) and the median number of prior therapies was 5 (range 2-17)...
July 7, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28679737/how-i-treat-first-relapse-of-myeloma
#4
Jean Luc Harousseau, Michel Attal
The standard treatment of relapsed multiple myeloma (MM) was either lenalidomide-dexamethasone (RD) or bortezomib-dexamethasone (VD) but it is changing rapidly for two reasons. Firstly lenalidomide and bortezomib are currently used in frontline treatment and many patients become resistant to these agents early in the course of their disease. Secondly six second-line new agents have been recently developed and offer new possibilities (pomalidomide, carfilzomib and ixazomib, panobinostat, elotuzumab and daratumumab)...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28671573/histone-deacetylase-inhibitors-as-anticancer-drugs
#5
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/28669336/the-safety-efficacy-and-therapeutic-potential-of-histone-deacetylase-inhibitors-with-special-reference-to-panobinostat-in-gastrointestinal-tumors-a-review-of-preclinical-and-clinical-studies
#6
Avineesh Singh, Preeti Patel, Jageshwar, Vijay Kumar Patel, Deepak Kumar Jain, M Kamal, Harish Rajak
Histone deacetylase inhibitors (HDACi) have demonstrated as an emerging class of anticancer drugs involved in regulation of gene expression and chromatin remodeling thus indicating valid targets for different types of cancer therapeutics. The pan-deacetylase inhibitor panobinostat (Farydac®, LBH589) is developed by Novartis Pharmaceuticals and a newly US FDA approved drug for the multiple myeloma. It is under clinical investigation for a range of hematological and solid tumors worldwide in both oral and intravenous formulations...
June 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28667459/clinical-pharmacokinetics-and-pharmacodynamics-of-panobinostat
#7
REVIEW
Mathilde Van Veggel, Elsbeth Westerman, Paul Hamberg
Histone deacetylase (HDAC) inhibitors cause an increase in acetylation that leads to an increase in DNA transcription and accumulation of different proteins, reducing cell proliferation and inducing cell death. Panobinostat is a first-in-line HDAC inhibitor approved for treating multiple myeloma in combination with bortezomib and dexamethasone. It is a pan-deacetylase inhibitor and therefore inhibits not only HDAC but also other deacetylases. The main mechanism of action of panobinostat is to inhibit HDAC, which causes cell cycle arrest and apoptosis, leading to it being an antineoplastic drug...
June 30, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28653400/panobinostat-plus-bortezomib-and-dexamethasone-impact-of-dose-intensity-and-administration-frequency-on-safety-in-the-panorama-1-trial
#8
Jesús F San-Miguel, Vania T M Hungria, Sung-Soo Yoon, Meral Beksac, Meletios A Dimopoulos, Ashraf Elghandour, Wieslaw W Jedrzejczak, Andreas Guenther, Thanyaphong Na Nakorn, Noppadol Siritanaratkul, Robert L Schlossman, Jian Hou, Philippe Moreau, Sagar Lonial, Jae-Hoon Lee, Hermann Einsele, Hans Salwender, Monika Sopala, Suman Redhu, Sofia Paul, Claudia Corrado, Paul G Richardson
Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (Panobinostat Oral in Multiple Myeloma 1) trial. Despite this benefit, patients in the panobinostat arm experienced higher rates of adverse events (AEs) and higher rates of discontinuation due to AEs. This PANORAMA 1 subanalysis examined AEs between 2 treatment phases of the study (TP1 and TP2), in which administration frequency of bortezomib and dexamethasone differed per protocol...
June 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28622959/a-phase-i-ii-trial-of-panobinostat-in-combination-with-lenalidomide-in-patients-with-relapsed-or-refractory-hodgkin-lymphoma
#9
Joseph J Maly, Beth A Christian, Xiaohua Zhu, Lai Wei, Jennifer L Sexton, Samantha M Jaglowski, Steven M Devine, Todd A Fehniger, Nina D Wagner-Johnston, Mitch A Phelps, Nancy L Bartlett, Kristie A Blum
BACKGROUND: Lenalidomide and panobinostat have shown single-agent efficacy of 14% to 50% and 27% to 58%, respectively, in Hodgkin lymphoma (HL). This phase I/II study was conducted to determine the maximum tolerated dose (MTD), safety, and efficacy of lenalidomide combined with panobinostat in relapsed/refractory HL. PATIENTS AND METHODS: In the phase I trial, previously treated patients with classical or lymphocyte-predominant HL received escalating doses of lenalidomide on days 1 to 21 and panobinostat 3 times a week (TIW) every 28 days...
June 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28601492/new-agents-in-multiple-myeloma-an%C3%A2-examination-of-safety-profiles
#10
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...
May 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28599306/panobinostat-a-histone-deacetylase-inhibitor-suppresses-leptomeningeal-seeding-in-a-medulloblastoma-animal-model
#11
Ji Hoon Phi, Seung Ah Choi, Pil Ae Kwak, Ji Yeoun Lee, Kyu-Chang Wang, Do Won Hwang, Seung-Ki Kim
Leptomeningeal seeding is a strong negative prognostic factor for medulloblastoma (MB). The mechanism of leptomeningeal seeding is unclear but may involve epigenetic regulation. In this study, we evaluated the feasibility of a histone deacetylase (HDAC) inhibitor, panobinostat, in the suppression of MB leptomeningeal seeding.Panobinostat decreased the cell viability and proliferation, inducing cell cycle arrest and apoptosis in MB cell lines. The migration and adhesion capabilities were significantly decreased...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28560392/the-blueberry-component-pterostilbene-has-potent-anti-myeloma-activity-in-bortezomib-resistant-cells
#12
Gege Chen, Zhijian Xu, Gaomei Chang, Jun Hou, Liangning Hu, Yiwen Zhang, Dandan Yu, Bo Li, Shuaikang Chang, Yongsheng Xie, Yong Zhang, Rong Wei, Huiqun Wu, Wenqin Xiao, Xi Sun, Yi Tao, Lu Gao, Bojie Dai, Jumei Shi, Weiliang Zhu
Multiple myeloma (MM) is an incurable hematologic malignancy because of its drug resistance. Pterostilbene (Pter) is found mainly in blueberries and grapes. The effects of Pter and its exact pharmacologic mechanisms on chemoresistant myeloma are not known. Herein, we investigated the anti-myeloma activity of Pter in bortezomib-resistant cell line H929R and explored the related mechanism of action for the first time. We found that Pter inhibited proliferation of H929R cells and promoted apoptosis of the cells through a caspase-dependent pathway, loss of mitochondrial membrane potential, and activation of Akt and p38 mitogen-activated protein kinase (MAPK) signaling pathways...
May 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28556890/recent-progress-in-relapsed-multiple-myeloma-therapy-implications-for-treatment-decisions
#13
REVIEW
Philippe Moreau, Edwin de Wit
The availability of novel therapies for the treatment of multiple myeloma has had a dramatic impact on the depth of response that can be expected on initial treatment. Despite these advances, disease relapse remains inevitable in most patients and brings with it a different set of priorities for therapy. The most recent wave of novel agents may have a particular impact in the relapsed setting. In this review, we examine the evidence currently available from clinical trials for the use of novel agents, particularly in the formation of triplet therapy...
May 30, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28546581/a-phase-1b-2b-multicenter-study-of-oral-panobinostat-plus-azacitidine-in-adults-with-mds-cmml-or-aml-with-%C3%A2-30-blasts
#14
G Garcia-Manero, M A Sekeres, M Egyed, M Breccia, C Graux, J D Cavenagh, H Salman, A Illes, P Fenaux, D J DeAngelo, R Stauder, K Yee, N Zhu, J-H Lee, D Valcarcel, A MacWhannell, Z Borbenyi, L Gazi, S Acharyya, S Ide, M Marker, O G Ottmann
Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts...
May 26, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28539449/anti-hiv-1-adcc-antibodies-following-latency-reversal-and-treatment-interruption
#15
Wen Shi Lee, Anne B Kristensen, Thomas A Rasmussen, Martin Tolstrup, Lars Østergaard, Ole S Søgaard, Bruce D Wines, P Mark Hogarth, Arnold Reynaldi, Miles P Davenport, Sean Emery, Janaki Amin, David A Cooper, Virginia L Kan, Julie Fox, Henning Gruell, Matthew S Parsons, Stephen J Kent
There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRAs) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC...
August 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28516379/panobinostat-enhances-growth-suppressive-effects-of-progestin-on-endometrial-carcinoma-by-increasing-progesterone-receptor-and-mitogen-inducible-gene-6
#16
Hirofumi Ando, Tsutomu Miyamoto, Hiroyasu Kashima, Shotaro Higuchi, Koichi Ida, David Hamisi Mvunta, Tanri Shiozawa
Although progestin has been used to treat endometrial hyperplasia and endometrial carcinoma (EC), its therapeutic efficacy is limited. In order to improve this, the underlining mechanisms of the effects of progestin need to be elucidated in more detail. In the present study, we examined the involvement of mitogen-inducible gene-6 (MIG6), a negative regulator of the EGF receptor, in the progestin-mediated growth suppression of endometrial epithelia. The immunohistochemical expression of MIG6 was elevated in the early to mid-secretory phases of normal endometrium and also with endometrial hyperplasia after medroxyprogesterone acetate (MPA) therapy...
August 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28507307/a-novel-indication-for-panobinostat-as-a-senolytic-drug-in-nsclc-and-hnscc
#17
Leleesha Samaraweera, Alfred Adomako, Alicia Rodriguez-Gabin, Hayley M McDaid
Panobinostat (pano) is an FDA-approved histone deacetylase inhibitor. There is interest in evaluating alternate dosing schedules and novel combinations of pano for the treatment of upper aerodigestive and lung malignancies; thus we evaluated it in combination with Taxol, a chemotherapeutic with activity in both diseases. Dose-dependent synergy was observed in Non-Small Cell Lung Cancer (NSCLC) and Head and Neck Squamous Cell Carcinoma (HNSCC) cell lines and was due to senescence rather than potentiation of cell death...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28505595/epigenetic-drug-combination-induces-remission-in-mouse-xenograft-models-of-pediatric-acute-myeloid-leukemia
#18
Anilkumar Gopalakrishnapillai, E Anders Kolb, Suzanne M McCahan, Sonali P Barwe
Aberrations in epigenetic modifications contribute to leukemogenesis in childhood acute myeloid leukemia (AML). We combined DNA hypomethylating agent azacitidine with histone deacetylase inhibitor panobinostat in preclinical models of childhood AML. Synergistic cytotoxic effect upon treatment with azacitidine and panobinostat with combination indices <1.0 was observed. Azacitidine and panobinostat increased median survival by 26 and 6days respectively in MV4;11 xenografted mice. Mice treated with both drugs showed a drastic reduction in leukemic burden leading to complete remission sustained for the duration of the experimental period lasting more than 519days...
July 2017: Leukemia Research
https://www.readbyqxmd.com/read/28482026/pre-clinical-drug-screen-reveals-topotecan-actinomycin-d-and-volasertib-as-potential-new-therapeutic-candidates-for-etmr-brain-tumor-patients
#19
Christin Schmidt, Nil A Schubert, Sebastian Brabetz, Norman Mack, Benjamin Schwalm, Jennifer A Chan, Florian Selt, Christel Herold-Mende, Olaf Witt, Till Milde, Stefan M Pfister, Andrey Korshunov, Marcel Kool
Background: Embryonal tumor with multilayered rosettes (ETMR) is a rare and aggressive embryonal brain tumor that solely occurs in infants and young children and has only recently been recognized as a separate brain tumor entity in the WHO classification for CNS tumors. Patients have a very dismal prognosis with a median survival of 12 months upon diagnosis despite aggressive treatment. The aim of this study was to develop novel treatment regimens in a pre-clinical drug screen in order to inform potentially more active clinical trial protocols...
May 8, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28476749/panobinostat-induces-cd38-upregulation-and-augments-the-anti-myeloma-efficacy-of-daratumumab
#20
Estefanía García-Guerrero, Tea Gogishvili, Sophia Danhof, Martin Schreder, Celine Pallaud, Jose Antonio Pérez-Simón, Hermann Einsele, Michael Hudecek
No abstract text is available yet for this article.
May 5, 2017: Blood
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