Review
Oncology
Darren Pan, Tarek H. Mouhieddine, Ranjan Upadhyay, Nicole Casasanta, Angela Lee, Nicole Zubizarreta, Erin Moshier, Joshua Richter
Summary: This study retrospectively analyzed the efficacy and safety of Panobinostat-based combinations in heavily pretreated multiple myeloma patients. The results showed that Panobinostat, when combined with other drugs, achieved modest response rates but had significant toxicities in this patient population.
SEMINARS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shunda Li, Chunlong Zhao, Guozhen Zhang, Qifu Xu, Qian Liu, Wei Zhao, C. James Chou, Yingjie Zhang
Summary: The novel pyrrolo[2,3-d]pyrimidine-based HDAC inhibitors demonstrated potent inhibitory activities and selectivities against HDAC6, showing superior antiproliferative activity against human multiple myeloma cell lines while maintaining low cytotoxicity. In addition, one representative compound showed good metabolic stability and in vivo anti-multiple myeloma potency in a xenograft model.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sang Wu Lee, Soo-Keun Yeon, Go Woon Kim, Dong Hoon Lee, Yu Hyun Jeon, Jung Yoo, So Yeon Kim, So Hee Kwon
Summary: The HDAC6-selective inhibitor A452 has been shown to overcome bortezomib resistance in multiple myeloma by decreasing the activation of resistant markers and synergistically inhibiting cancer cell growth when used in combination with other drugs. This discovery highlights the potential of A452 as a promising therapy for bortezomib-chemoresistant multiple myeloma patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Man-Si Wu, Xiao-Juan Li, Chen-Yue Liu, Qiuyue Xu, Jun-Qing Huang, Simeng Gu, Jia-Xu Chen
Summary: Major depressive disorder (MDD) is a complex disease influenced by environmental, genetic, psychological, and biological factors. This review explores the role of histone modifications in MDD and discusses the potential use of histone deacetylase inhibitors (HDACis) as a treatment. It also discusses the impact of traditional Chinese medicine (TCM) therapies, such as Xiaoyaosan (XYS), on histone modification in MDD.
CURRENT NEUROPHARMACOLOGY
(2022)
Review
Cell Biology
Bingyi Zhou, Deliang Liu, Yuyong Tan
Summary: Cancer is the second leading cause of death worldwide, with digestive system cancers being a primary contributor. Acetylation and deacetylation play crucial roles in cancer development, with HDAC6 being a widely studied enzyme that is upregulated in various tumors and associated with clinicopathological characteristics. There is ongoing research on HDAC6 inhibitors and their potential in inhibiting tumor growth.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
M. Naveen Sadhu, Dhanalakshmi Sivanandhan, Chandru Gajendran, Subramanyam Tantry, Purushottam Dewang, Kannan Murugan, Srinatha Chickamunivenkatappa, Mohd Zainuddin, Sreekala Nair, Krishnakumar Vaithilingam, Sridharan Rajagopal
Summary: The article introduces a novel LSD1 and HDAC6 dual inhibitor, which has shown good efficacy in multiple myeloma in experiments, providing a new treatment strategy for various cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Oncology
Bryan J. Neth, Samantha N. Balakrishnan, Ivan D. Carabenciov, Joon H. Uhm, David J. Daniels, Sani H. Kizilbash, Michael W. Ruff
Summary: This article reports the clinical outcomes of panobinostat in adults with H3 K27M-mutant DMG. The study found that panobinostat was well-tolerated at the dosage schedule described, with no serious adverse effects observed throughout the study period. The median overall survival was 42 months, and the median progression-free survival was 19 months.
JOURNAL OF NEURO-ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yunpeng Zhao, Tao Liang, Xuben Hou, Hao Fang
Summary: Histone deacetylation plays crucial roles in chromatin remodeling and gene expression, and aberrant modification can lead to various diseases. HDAC6, a critical member of the HDAC family, serves as a key modulator in many physiological processes, and abnormal expression is linked to cancer, neurodegeneration, and other diseases. Recent advances have been made in the physiological functions, protein structure, and development of HDAC6 selective inhibitors.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Kavinda E. Herath, Ishadi K. M. Kodikara, Mary Kay H. Pflum
Summary: HDAC1 plays a key role in diverse cellular processes and its aberrant expression is linked to many diseases. Nonhistone substrates of HDAC1 have been discovered, revealing its diverse roles beyond epigenetics. We tested the robustness of HDAC1 substrate trapping with multiple mutants and found that using a single mutant yielded more biologically interesting hits. Carnosine N-methyltransferase 1 (CARNMT1) was validated as an HDAC1 substrate. Mutant trapping is an effective method for discovering unanticipated HDAC substrates and linking HDAC activity to unexpected biological functions.
JOURNAL OF PROTEOMICS
(2023)
Article
Chemistry, Medicinal
Negar Omidkhah, Razieh Ghodsi
Summary: NO-HDAC dual inhibitors have demonstrated satisfactory therapeutic effects in various diseases and possess high therapeutic potential.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Mitsuhito Hirano, Yoichi Imai, Yuta Kaito, Takahiko Murayama, Kota Sato, Tadao Ishida, Junichi Yamamoto, Takumi Ito, Muneyoshi Futami, Masaki Ri, Hiroshi Yasui, Tamami Denda, Yukihisa Tanaka, Yasunori Ota, Masanori Nojima, Yasuhiko Kamikubo, Noriko Gotoh, Shinsuke Iida, Hiroshi Handa, Arinobu Tojo
Summary: The study found that the combination of HDAC inhibitor and Akt inhibitor holds promise for the treatment of relapsed/refractory MM, as HDAC inhibitors suppressed drug-resistant MM cell growth and enhanced antibody-dependent cellular cytotoxicity, while also downregulating c-Myc through GSK-3 phosphorylation blockage.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Tiewei Cheng, Kendall Kiser, Leslie Grasse, Lakesla Iles, Geoffrey Bartholomeusz, Felipe Samaniego, Robert Z. Orlowski, Joya Chandra
Summary: This study investigated the expression of HDAC family members in bortezomib sensitive vs. resistant myeloma cell lines, with findings showing differential expression of HDAC6 and HDAC7 in these cells. Panobinostat was effective in inducing cell death and modulating HDAC expression in resistant cells. Inhibition of HDAC7 suppressed cell growth, while pharmacological inhibition of HDAC6 enhanced cell death induced by panobinostat, indicating distinct roles for these enzymes in bortezomib resistance.
CANCER DRUG RESISTANCE
(2021)
Article
Chemistry, Medicinal
Mariana Brutt Pacheco, Vania Camilo, Nair Lopes, Filipa Moreira-Silva, Margareta P. Correia, Rui Henrique, Carmen Jeronimo
Summary: The combined treatment of DNA methylation inhibitor hydralazine and histone deacetylase inhibitors panobinostat and valproic acid showed synergistic growth inhibitory effects on prostate cancer cells, particularly in DU145 cells. This suggests that these drugs may be potential therapeutic tools to counteract the progression of prostate cancer.
Article
Oncology
Reeder M. Robinson, Ashton P. Basar, Leticia Reyes, Ravyn M. Duncan, Hong Li, Nathan G. Dolloff
Summary: The histone deacetylase inhibitor panobinostat is approved for the treatment of relapsed/refractory multiple myeloma but is rarely used due to its toxicity profile. In this study, we propose a treatment regimen combining panobinostat with LTI6426, a protein disulfide isomerase inhibitor, that effectively enhances anti-MM activity and reduces toxicity. We also identify potential biomarkers for response to this novel treatment approach.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Geer Chen, Xiaoyu Zhu, Jiaqi Li, Yao Zhang, Xiaoxuan Wang, Ren Zhang, Xinchen Qin, Xi Chen, Junyi Wang, Weilin Liao, Zongjin Wu, Lu Lu, Weiyu Wu, Haijie Yu, Lijuan Ma
Summary: Alterations in histone modification have been shown to be related to cancer development and progression. Celastrol, a Chinese herbal compound, exhibits potent anti-tumor effects through multiple signaling pathways. This study demonstrates that histone modifications, especially histone acetylation associated with the NuA4 histone acetyltransferase complex, are involved in the anti-proliferation actions of celastrol. Combination therapy with celastrol and histone deacetylase inhibitors (HDACi) synergistically suppresses cancer cell proliferation. The results suggest that the combination of celastrol and HDACi could be a potential novel therapeutic approach for lung cancer patients.
PHARMACOLOGICAL RESEARCH
(2022)
Letter
Biophysics
Mitsuhito Hirano, Koji Jimbo, Miho Ogawa, Kiyosumi Ochi, Junya Makiyama, Toyotaka Kawamata, Kazuaki Yokoyama, Takashi Tanaka, Yoshihiro Inamoto, Yoshihisa Yamano, Takahiro Fukuda, Kaoru Uchimaru, Yoichi Imai, Arinobu Tojo
BONE MARROW TRANSPLANTATION
(2018)
Review
Oncology
Masayuki Kobayashi, Arinobu Tojo
Article
Oncology
Mariko Ishibashi, Risa Takahashi, Asako Tsubota, Makoto Sasaki, Hiroshi Handa, Yoichi Imai, Norina Tanaka, Yutaka Tsukune, Sakae Tanosaki, Shigeki Ito, Toshio Asayama, Mika Sunakawa, Yuta Kaito, Yasuko Kuribayashi-Hamada, Asaka Onodera, Keiichi Moriya, Norio Komatsu, Junji Tanaka, Takeshi Odajima, Hiroki Sugimori, Koiti Inokuchi, Hideto Tamura
MOLECULAR CANCER RESEARCH
(2020)
Article
Multidisciplinary Sciences
Muneyoshi Futami, Keisuke Suzuki, Satomi Kato, Saori Ohmae, Yoshio Tahara, Masanori Nojima, Yoichi Imai, Takayuki Mimura, Yoshihiro Watanabe, Arinobu Tojo
Article
Hematology
Masayuki Kobayashi, Shohei Ando, Toyotaka Kawamata, Junya Makiyama, Kazuaki Yokoyama, Yoichi Imai, Arinobu Tojo
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2020)
Article
Oncology
Yasuo Matsubara, Masayuki Kobayashi, Yasuki Hijikata, Yasunori Ota, Yoshihiro Hirata, Lay Ahyoung Lim, Hiroshi Yotsuyanagi, Arinobu Tojo
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
(2020)
Editorial Material
Oncology
Yoichi Imai
Article
Oncology
Hiroshi Yasui, Masayuki Kobayashi, Kota Sato, Kanya Kondoh, Tadao Ishida, Yuta Kaito, Hideto Tamura, Hiroshi Handa, Yutaka Tsukune, Makoto Sasaki, Norio Komatsu, Norina Tanaka, Junji Tanaka, Masahiro Kizaki, Toyotaka Kawamata, Junya Makiyama, Kazuaki Yokoyama, Seiya Imoto, Arinobu Tojo, Yoichi Imai
Summary: The study showed that circulating cell-free DNA (cfDNA) in the peripheral blood can serve as a biomarker for multiple myeloma (MM) relapse, detecting relapse more sensitively than conventional serum examination and potentially guiding early intervention.
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
(2021)
Review
Hematology
Shingo Sato, Masayuki Kobayashi, Ken Suzaki, Ittoku Nanke, Nobuharu Kosugi
Summary: PEL is an extremely rare type of AML, with cell features similar to solid tumor metastasis, requiring integration of multiple methods for assessment.
HEMATOLOGY REPORTS
(2022)
Article
Infectious Diseases
Mitsuhito Hirano, Yasunori Ota, Tomohiko Koibuchi, Tomomi Takei, Reina Takeda, Toyotaka Kawamata, Kazuaki Yokoyama, Kaoru Uchimaru, Hiroshi Yotsuyanagi, Yoichi Imai, Arinobu Tojo
JAPANESE JOURNAL OF INFECTIOUS DISEASES
(2019)
Article
Medicine, General & Internal
Yukiko Komeno, Yasunori Ota, Tomohiko Koibuchi, Yoichi Imai, Kuniko Iihara, Tomiko Ryu
AMERICAN JOURNAL OF CASE REPORTS
(2018)
Letter
Hematology
Masayuki Kobayashi, Kazuaki Yokoyama, Eigo Shimizu, Nozomi Yusa, Mika Ito, Rui Yamaguchi, Seiya Imoto, Satoru Miyano, Arinobu Tojo
ANNALS OF HEMATOLOGY
(2018)
Letter
Hematology
Miho Ogawa, Kazuaki Yokoyama, Mitsuhito Hirano, Koji Jimbo, Kiyosumi Ochi, Toyotaka Kawamata, Nobuhiro Ohno, Eigo Shimizu, Nozomi Yokoyama, Rui Yamaguchi, Seiya Imoto, Kaoru Uchimaru, Naoto Takahashi, Satoru Miyano, Yoichi Imai, Arinobu Tojo
BRITISH JOURNAL OF HAEMATOLOGY
(2018)