keyword
https://read.qxmd.com/read/38529413/synergistic-integration-of-histone-deacetylase-inhibitors-apparently-enhances-the-cytokine-induced-killer-cell-efficiency-in-multiple-myeloma-via-the-nkg2d-pathway
#1
JOURNAL ARTICLE
Jingjing Pu, Amit Sharma, Ting Liu, Jian Hou, Ingo Gh Schmidt-Wolf
OBJECTIVES: The rapid recognition of epigenetic manipulation's potential in restricting cancer cell capabilities spurred translational initiatives, including histone deacetylase inhibitors (HDACis). Clinical trials on multiple myeloma (MM) demonstrated substantial benefits of HDACis, coupled with promising outcomes from cytokine-induced killer cell (CIK) immunotherapy. Intriguingly, the unexplored synergy of HDACis and CIK cell immunotherapy in MM prompted our study. METHODS: We examined clinically relevant HDACis (panobinostat/LBH589 and romidepsin) alongside CIK cells derived from peripheral blood mononuclear cells across diverse MM cell lines (U266, RPMI8226, OPM-2 and NCI-H929)...
2024: Clinical & Translational Immunology
https://read.qxmd.com/read/38523117/attenuation-of-neuronal-ferroptosis-in-intracerebral-hemorrhage-by-inhibiting-hdac1-2-microglial-heterogenization-via-the-nrf2-ho1-pathway
#2
JOURNAL ARTICLE
Zhiwen Jiang, Heng Yang, Wei Ni, Xinjie Gao, Xu Pei, Hanqiang Jiang, Jiabin Su, Ruiyuan Weng, Yuchao Fei, Yanqin Gao, Yuxiang Gu
AIM: The class I histone deacetylases (HDACs) implicate in microglial heterogenization and neuroinflammation following Intracerebral hemorrhage (ICH). Ferroptosis has also been reported in the ICH model. However, the relationship between HDAC1/2's role in microglial heterogenization and neuronal ferroptosis remains unclear. METHODS: In both in vivo and in vitro models of ICH, we used Romidepsin (FK228), a selective HDAC1/2 inhibitor, to investigate its effects on microglial heterogenization and neuronal ferroptosis...
March 2024: CNS Neuroscience & Therapeutics
https://read.qxmd.com/read/38517235/phase-ii-study-of-the-novel-antifolate-agent-pralatrexate-in-combination-with-the-histone-deacetylase-inhibitor-romidepsin-for-the-treatment-of-patients-with-mature-t-cell-lymphoma
#3
JOURNAL ARTICLE
Yun Kyoung Ryu Tiger, Salvia Jain, Stefan K Barta, Seda Tolu, Brian Estrella, Ahmed Sawas, Jennifer K Lue, Mark M Francescone, Barbara Pro, Jennifer E Amengual
Previously, we conducted a Phase I study of the combination of pralatrexate and romidepsin in patients with relapsed/refractory (R/R) lymphomas and subsequently conducted a multicenter Phase II study in patients with untreated or R/R mature T cell lymphomas (MTCL). Patients received pralatrexate 25 mg/m2 and romidepsin 12 mg/m2 every 2 weeks. Fourteen patients were evaluable for efficacy. Overall response rate was 35.7% with CR in 14.3% and disease control in 50%. The mDOR was 8.2 months, mPFS was 3...
March 22, 2024: Leukemia & Lymphoma
https://read.qxmd.com/read/38500302/systemic-histone-deacetylase-inhibition-ameliorates-the-aberrant-responses-to-acute-stress-in-socially-isolated-male-mice
#4
JOURNAL ARTICLE
Luis Gustavo Hernandez Carballo, Pei Li, Rachel Senek, Zhen Yan
Adverse experiences in early life can induce maladaptive responses to acute stress in later life. Chronic social isolation during adolescence is an early life adversity that can precipitate stress-related psychiatric disorders. We found that male mice after 8 weeks of adolescent social isolation (SI) have markedly increased aggression after being exposed to 2 h of restraint stress (RS), which was accompanied by a significant increase of AMPA receptor- and NMDA receptor-mediated synaptic transmission in prefrontal cortex (PFC) pyramidal neurons of SIRS males...
March 18, 2024: Journal of Physiology
https://read.qxmd.com/read/38497997/pyroptosis-tuning-in-intestinal-cryptosporidiosis-via-the-natural-histone-deacetylase-inhibitor-romidepsin
#5
JOURNAL ARTICLE
Noha E Shalaby, Zeinab S Shoheib, Nabila A Yassin, Heba H El-Kaliny, Marwa A Hasby Saad
Cryptosporidium is an opportunistic protozoan, with many species of cross-human infectivity. It causes life-threatening diarrhoea in children and CD4-defective patients. Despite its limited efficacy, nitazoxanide remains the primary anti-cryptosporidial drug. Cryptosporidium infects the intestinal brush border (intracellular-extracytoplasmic) and down-regulates pyroptosis to prevent expulsion. Romidepsin is a natural histone deacetylase inhibitor that triggers pyroptosis. Romidepsin's effect on cryptosporidiosis was assessed in immunocompromised mice via gasdermin-D (GSDM-D) immunohistochemical expression, IFN-γ, IL-1β and IL-18 blood levels by ELISA, and via parasite scanning by modified Ziehl-Neelsen staining and scanning electron microscopy (SEM)...
March 2024: Parasite Immunology
https://read.qxmd.com/read/38480975/romidepsin-exhibits-anti-esophageal-squamous-cell-carcinoma-activity-through-the-ddit4-mtorc1-pathway
#6
JOURNAL ARTICLE
Wei-Feng Xia, Xiao-Li Zheng, Wen-Yi Liu, Yu-Tang Huang, Chun-Jie Wen, Hong-Hao Zhou, Qing-Chen Wu, Lan-Xiang Wu
Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent...
March 13, 2024: Cancer Gene Therapy
https://read.qxmd.com/read/38466561/establishment-and-characterization-of-two-novel-patient-derived-cell-lines-from-giant-cell-tumor-of-bone-ncc-gctb8-c1-and-ncc-gctb9-c1
#7
JOURNAL ARTICLE
Yuki Adachi, Rei Noguchi, Yuki Yoshimatsu, Yooksil Sin, Julia Osaki, Takuya Ono, Shuhei Iwata, Taro Akiyama, Ryuto Tsuchiya, Yu Toda, Shin Ishihara, Koichi Ogura, Eisuke Kobayashi, Naoki Kojima, Akihiko Yoshida, Hideki Yokoo, Akira Kawai, Tadashi Kondo
Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor consisting of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. Although GCTB predominantly exhibits benign behavior, the tumor carries a significant risk of high local recurrence. Furthermore, GCTB can occasionally undergo malignant transformation and distal metastasis, making it potentially fatal. The standard treatment is complete surgical resection; nonetheless, an optimal treatment strategy for advanced GCTB remains unestablished, necessitating expanded preclinical research to identify appropriate therapeutic options...
March 11, 2024: Human Cell
https://read.qxmd.com/read/38453702/a-real-world-pharmacovigilance-study-investigating-the-toxicities-of-histone-deacetylase-inhibitors
#8
JOURNAL ARTICLE
Wenjie Li, Yiming Fu, Wei Wang
Histone deacetylase (HDAC) inhibitors are emerging as promising treatments for hematological malignancies, with potential applications extending to solid tumors in the future. Given their wide-ranging biological effects, there is a pressing need for a thorough understanding of the toxicities linked to HDAC inhibition. In this study, a pharmacovigilance analysis was conducted using the FDA Adverse Event Reporting System database. Suspected adverse events linked to HDAC inhibitors were detected through various statistical methodologies, including reporting odds ratio, proportional reporting ratio, information component, and Empirical Bayes Geometric Mean...
March 8, 2024: Annals of Hematology
https://read.qxmd.com/read/38364196/romidepsin-plus-cyclophosphamide-doxorubicin-vincristine-and-prednisone-versus-cyclophosphamide-doxorubicin-vincristine-and-prednisone-in-patients-with-previously-untreated-peripheral-t-cell-lymphoma-final-analysis-of-the-ro-chop-trial
#9
JOURNAL ARTICLE
Vincent Camus, Catherine Thieblemont, Philippe Gaulard, Morgane Cheminant, Rene-Olivier Casasnovas, Loïc Ysebaert, Gandhi Laurent Damaj, Stéphanie Guidez, Gian Matteo Pica, Won Seog Kim, Soon Thye Lim, Marc Andre, Norma Gutiérrez, Maria Jesus Penarrubia, Philipp B Staber, Judith Trotman, Andreas Hüttmann, Vittorio Stefoni, Alessandra Tucci, Patrick Fogarty, Hassan Farhat, Julie Abraham, Wajed Abarah, Fatiha Belmecheri, Vincent Ribrag, Marie-Helene Delfau-Larue, Anne-Ségolène Cottereau, Emmanuel Itti, Ju Li, Richard Delarue, Laurence de Leval, Franck Morschhauser, Emmanuel Bachy
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The primary analysis of the Ro-CHOP phase III randomized controlled trial (ClinicalTrials...
February 16, 2024: Journal of Clinical Oncology
https://read.qxmd.com/read/38261805/a-multidimensional-platform-of-patient-derived-tumors-identifies-drug-susceptibilities-for-clinical-lenvatinib-resistance
#10
JOURNAL ARTICLE
Lei Sun, Arabella H Wan, Shijia Yan, Ruonian Liu, Jiarui Li, Zhuolong Zhou, Ruirui Wu, Dongshi Chen, Xianzhang Bu, Jingxing Ou, Kai Li, Xiongbin Lu, Guohui Wan, Zunfu Ke
Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens...
January 2024: Acta Pharmaceutica Sinica. B
https://read.qxmd.com/read/38219917/romidepsin-and-afatinib-abrogate-jak-stat-signaling-and-elicit-synergistic-antitumor-effects-in-cutaneous-t-cell-lymphoma
#11
JOURNAL ARTICLE
Bobby B Shih, Cindy Ma, Jose R Cortes, Clara Reglero, Hannah Miller, S Aidan Quinn, Robert Albero, Anouchka P Laurent, Adam Mackey, Adolfo A Ferrando, Larisa Geskin, Teresa Palomero
Cutaneous T-cell lymphomas (CTCL) are mature lymphoid neoplasias resulting from the malignant transformation of skin-resident T cells. A distinctive clinical feature of CTCL is their sensitivity to treatment with histone deacetylase (HDAC) inhibitors. However, responses to HDAC inhibitor therapy are universally transient and non-curative, highlighting the need for effective and durable drug combinations. Here we demonstrate that the combination of romidepsin, a selective class I HDAC inhibitor, with afatinib, an epidermal growth factor receptor (EGFR) family inhibitor, induces strongly synergistic antitumor effects in CTCL models in vitro and in vivo via abrogation of JAK-STAT signalling...
January 12, 2024: Journal of Investigative Dermatology
https://read.qxmd.com/read/38199657/improving-gastrointestinal-quality-of-life-romidepsin-to-tucidinostat-in-a-case-of-angioimmunoblastic-t-cell-lymphoma
#12
JOURNAL ARTICLE
Atsushi Isoda, Yukie Terasaki, Shuhei Kanaya, Akio Saito
Relapsed/refractory (R/R) peripheral T cell lymphoma (PTCL) has a poor prognosis, with limited treatment options and generally no durable response. However, long-term remission with the histone deacetylase (HDAC) inhibitor romidepsin has been reported, especially in angioimmunoblastic T cell lymphoma (AITL). Recently, tucidinostat, a novel oral HDAC inhibitor that selectively inhibits class I and class IIb HDACs, was approved for R/R PTCL in China and Japan. We present the case of a patient with AITL whose gastrointestinal symptoms and health-related quality of life improved after switching from romidepsin to tucidinostat as maintenance therapy...
January 10, 2024: BMJ Case Reports
https://read.qxmd.com/read/38170178/staphylococcus-aureus-induce-drug-resistance-in-cancer-t-cells-in-s%C3%A3-zary-syndrome
#13
JOURNAL ARTICLE
Chella Krishna Vadivel, Andreas Willerslev-Olsen, Martin Rich Javadi Namini, Ziao Zeng, Lang Yan, Maria Danielsen, Maria Gluud, Emil Marek Heymans Pallesen, Karolina Wojewoda, Amra Osmancevic, Signe Hedebo, Yun-Tsan Chang, Lise M Lindahl, Sergei B Koralov, Larisa J Geskin, Susan E Bates, Lars Iversen, Thomas Litman, Rikke Bech, Marion Wobser, Emmanuella Guenova, Maria R Kamstrup, Niels Odum, Terkild B Buus
Patients with Sézary syndrome (SS), a leukemic variant of cutaneous T cell lymphoma (CTCL), are prone to Staphylococcus aureus (S. aureus) infections and have a poor prognosis due to treatment-resistance. Here, we report that S. aureus and staphylococcal enterotoxins (SE) induce drug resistance in malignant T-cells against therapeutics commonly used in CTCL. Supernatant from patient-derived, SE-producing S. aureus and recombinant SE significantly inhibit cell death induced by HDAC inhibitor romidepsin in primary malignant T-cells from SS patients...
January 3, 2024: Blood
https://read.qxmd.com/read/38151817/the-methyltransferases-mettl7a-and-mettl7b-confer-resistance-to-thiol-based-histone-deacetylase-inhibitors
#14
JOURNAL ARTICLE
Robert W Robey, Christina M Fitzsimmons, Wilfried M Guiblet, William J E Frye, José M González Dalmasy, Li Wang, Drake A Russell, Lyn M Huff, Andrew J Perciaccante, Fatima Ali-Rahmani, Crystal C Lipsey, Heidi M Wade, Allison V Mitchell, Siddhardha S Maligireddy, David Terrero, Donna Butcher, Elijah F Edmondson, Lisa M Jenkins, Tatiana Nikitina, Victor B Zhurkin, Amit K Tiwari, Anthony D Piscopio, Rheem A Totah, Susan E Bates, H Efsun Arda, Michael M Gottesman, Pedro J Batista
Histone deacetylase inhibitors (HDACis) are part of a growing class of epigenetic therapies used for the treatment of cancer. Although HDACis are effective in the treatment of T-cell lymphomas, treatment of solid tumors with this class of drugs has not been successful. Overexpression of the multidrug resistance protein P-glycoprotein (P-gp), encoded by ABCB1, is known to confer resistance to the HDACi romidepsin in vitro, yet increased ABCB1 expression has not been associated with resistance in patients, suggesting that other mechanisms of resistance arise in the clinic...
December 28, 2023: Molecular Cancer Therapeutics
https://read.qxmd.com/read/38143259/establishment-and-characterization-of-ncc-pmp2-c1-a-novel-patient-derived-cell-line-of-pseudomyxoma-peritonei-with-signet-ring-cells
#15
JOURNAL ARTICLE
Rei Noguchi, Yuki Yoshimatsu, Yooksil Sin, Takuya Ono, Ryuto Tsuchiya, Hiroshi Yoshida, Tohru Kiyono, Yutaka Yonemura, Tadashi Kondo
Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP...
December 25, 2023: Human Cell
https://read.qxmd.com/read/38124624/histone-deacetylase-inhibition-sensitizes-p53-deficient-b-cell-precursor-acute-lymphoblastic-leukemia-to-chemotherapy
#16
JOURNAL ARTICLE
Willem P J Cox, Nils Evander, Dorette S Van Ingen Schenau, Gawin R Stoll, Nadia Anderson, Lieke De Groot, Kari J T Grünewald, Rico Hagelaar, Miriam Butler, Roland P Kuiper, Laurens T Van der Meer, Frank N Van Leeuwen
In pediatric Acute Lymphoblastic Leukemia (ALL), mutations/deletions affecting the TP53 gene are rare at diagnosis. However, at relapse about 12% of the patients show TP53 aberrations, predicting a very poor outcome. Since p53-mediated apoptosis is an endpoint for many cytotoxic drugs, loss of p53 function frequently leads to therapy failure. In this study, we show that CRISPR/Cas9-induced loss of TP53 drives resistance to a large majority of drugs used to treat relapsed ALL, including novel agents such as inotuzumab ozogamicin...
December 21, 2023: Haematologica
https://read.qxmd.com/read/38076968/the-thiol-methyltransferase-activity-of-tmt1a-mettl7a-is-conserved-across-species
#17
José M González Dalmasy, Christina M Fitzsimmons, William J E Frye, Andrew J Perciaccante, Connor P Jewell, Lisa M Jenkins, Pedro J Batista, Robert W Robey, Michael M Gottesman
Although few resistance mechanisms for histone deacetylase inhibitors (HDACis) have been described, we recently demonstrated that TMT1A (formerly METTL7A) and TMT1B (formerly METTL7B) can mediate resistance to HDACis with a thiol as the zinc-binding group by methylating and inactivating the drug. TMT1A and TMT1B are poorly characterized, and their normal physiological role has yet to be determined. As animal model systems are often used to determine the physiological function of proteins, we investigated whether the ability of these methyltransferases to methylate thiol-based HDACis is conserved across different species...
November 17, 2023: bioRxiv
https://read.qxmd.com/read/38073114/histone-deacetylase-mediated-silencing-of-pstpip2-expression-contributes-to-aai-induced-panoptosis
#18
JOURNAL ARTICLE
Chuanting Xu, Qi Wang, Changlin Du, Jiahui Dong, Zhenming Zhang, Na Cai, Jun Li, Cheng Huang, Taotao Ma
BACKGROUND AND PURPOSE: Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by using herbal medicines. Currently, no therapies are available to treat or prevent AAN. Histone deacetylase (HDAC) plays a crucial role in the development and progression of renal disease. We tested whether HDAC inhibitors could prevent AAN and determined the underlying mechanism. EXPERIMENTAL APPROACH: HDACs expression in the aristolochic acid nephropathy model was examined...
December 10, 2023: British Journal of Pharmacology
https://read.qxmd.com/read/38044107/-modulation-of-expression-of-drug-metabolizing-enzymes-and-augmentation-of-anti-cancer-drug-effects-through-epigenetics-and-three-dimensional-cancer-cell-culture-systems
#19
JOURNAL ARTICLE
Shogo Ozawa
Since commencing my role as a professor in a newly established Department of Pharmacodynamics and Molecular Genetics at the School of Pharmacy, Iwate Medical University, on April 1, 2007, my research has focused on modifying gene expression of cytochrome P-450 (CYP) in established human colon cancer cells. Additionally, I have been investigating methods to enhance the anti-tumor effects of irinotecan (CPT-11) and 5-fluorouracil (5-FU) using epigenetic modifying inhibitors of DNA methyltransferase and histone deacetylase...
2023: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://read.qxmd.com/read/37951844/establishment-and-functional-testing-of-a-novel-ex-vivo-extraskeletal-osteosarcoma-cell-model-usz20-esos1
#20
JOURNAL ARTICLE
Kim Harnisch, Sabrina Steiner, Alicia Pliego-Mendieta, Yanjiang Chen, Lara Planas-Paz, Chantal Pauli
Extraskeletal osteosarcoma (ESOS) is a rare malignant mesenchymal tumor that originates in the soft tissue. ESOS accounts for less than 1% of all soft tissue sarcomas and exhibits an aggressive behavior with a high propensity for local recurrence and distant metastasis. Despite advances in treatment, the prognosis for ESOS remains poor, with a five-year survival rate of less than 50% and 27% for metastatic patients. Ex vivo models derived from patient samples are critical tools for studying rare diseases with poor prognoses, such as ESOS, and identifying potential new treatment strategies...
November 11, 2023: Human Cell
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