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Article ; Online: Efficacy and safety of full-dose dabrafenib and trametinib combination therapy in a patient on hemodialysis with metastatic melanoma.

Hayakawa, Kazuma / Wakimoto, Hiroko / Mae, Kenichihro / Irisawa, Ryokichi / Harada, Kazutoshi

2020 Volume 60, Issue 4, Page(s) 516–517

MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Humans ; Imidazoles ; Melanoma/drug therapy ; Mutation ; Oximes/adverse effects ; Proto-Oncogene Proteins B-raf/genetics ; Pyridones ; Pyrimidinones ; Renal Dialysis ; Skin Neoplasms/drug therapy
Chemical Substances	Imidazoles ; Oximes ; Pyridones ; Pyrimidinones ; trametinib (33E86K87QN) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; dabrafenib (QGP4HA4G1B)
Language	English
Publishing date	2020-11-09
Publishing country	England
Document type	Letter
ZDB-ID	412254-9
ISSN	1365-4632 ; 0011-9059 ; 1461-1244
ISSN (online)	1365-4632
ISSN	0011-9059 ; 1461-1244
DOI	10.1111/ijd.15298
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Article ; Online: Inhibition of miR-199a-3p in a murine hypertrophic cardiomyopathy (HCM) model attenuates fibrotic remodeling.

Zalivina, Irina / Barwari, Temo / Yin, Xiaoke / Langley, Sarah R / Barallobre-Barreiro, Javier / Wakimoto, Hiroko / Zampetaki, Anna / Mayr, Manuel / Avkiran, Metin / Eminaga, Seda

Journal of molecular and cellular cardiology plus

2023 Volume 6, Page(s) 100056

Abstract: Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder, characterized by cardiomyocyte hypertrophy, cardiomyocyte disarray and fibrosis, which has a prevalence of ∼1: 200-500 and predisposes individuals to heart failure ... ...

Abstract	Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder, characterized by cardiomyocyte hypertrophy, cardiomyocyte disarray and fibrosis, which has a prevalence of ∼1: 200-500 and predisposes individuals to heart failure and sudden death. The mechanisms through which diverse HCM-causing mutations cause cardiac dysfunction remain mostly unknown and their identification may reveal new therapeutic avenues. MicroRNAs (miRNAs) have emerged as critical regulators of gene expression and disease phenotype in various pathologies. We explored whether miRNAs could play a role in HCM pathogenesis and offer potential therapeutic targets. Methods and results: Using high-throughput miRNA expression profiling and qPCR analysis in two distinct mouse models of HCM, we found that miR-199a-3p expression levels are upregulated in mutant mice compared to age- and treatment-matched wild-type mice. We also found that miR-199a-3p expression is enriched in cardiac non-myocytes compared to cardiomyocytes. When we expressed miR-199a-3p mimic in cultured murine primary cardiac fibroblasts and analyzed the conditioned media by proteomics, we found that several extracellular matrix (ECM) proteins ( Conclusions: Altogether, our results suggest that miR-199a-3p may contribute to cardiac fibrosis in HCM through its actions in cardiac fibroblasts. Thus, inhibition of miR-199a-3p in mild-to-moderate HCM may offer therapeutic benefit in combination with complementary approaches that target the primary defect in cardiac myocytes.
Language	English
Publishing date	2023-12-22
Publishing country	Netherlands
Document type	Journal Article
ISSN	2772-9761
ISSN (online)	2772-9761
DOI	10.1016/j.jmccpl.2023.100056
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Article ; Online: Photodynamic augmentation of oncolytic virus therapy for central nervous system malignancies.

Shimizu, Kazuhide / Kahramanian, Andranik / Jabbar, Muzammil Arif Din Abdul / Turna Demir, Fatma / Gokyer, Dilan / Uthamacumaran, Abicumaran / Rajan, Anant / Saad, Mohammad Ahsan / Gorham, Joshua / Wakimoto, Hiroko / Martuza, Robert L / Rabkin, Samuel D / Hasan, Tayyaba / Wakimoto, Hiroaki

Cancer letters

2023 Volume 572, Page(s) 216363

Abstract: Oncolytic viruses (OVs) have emerged as a clinical therapeutic modality potentially effective for cancers that evade conventional therapies, including central nervous system malignancies. Rationally designed combinatorial strategies can augment the ... ...

Abstract	Oncolytic viruses (OVs) have emerged as a clinical therapeutic modality potentially effective for cancers that evade conventional therapies, including central nervous system malignancies. Rationally designed combinatorial strategies can augment the efficacy of OVs by boosting tumor-selective cytotoxicity and modulating the tumor microenvironment (TME). Photodynamic therapy (PDT) of cancer not only mediates direct neoplastic cell death but also primes the TME to sensitize the tumor to secondary therapies, allowing for the combination of two potentially synergistic therapies with broader targets. Here, we created G47Δ-KR, clinical oncolytic herpes simplex virus G47Δ that expresses photosensitizer protein KillerRed (KR). Optical properties and cytotoxic effects of G47Δ-KR infection followed by amber LED illumination (peak wavelength: 585-595 nm) were examined in human glioblastoma (GBM) and malignant meningioma (MM) models in vitro. G47Δ-KR infection of tumor cells mediated KR expression that was activated by LED and produced reactive oxygen species, leading to cell death that was more robust than G47Δ-KR without light. In vivo, we tested photodynamic-oncolytic virus (PD-OV) therapy employing intratumoral injection of G47Δ-KR followed by laser light tumor irradiation (wavelength: 585 nm) in GBM and MM xenografts. PD-OV therapy was feasible in these models and resulted in potent anti-tumor effects that were superior to G47Δ-KR alone (without laser light) or laser light alone. RNA sequencing analysis of post-treatment tumor samples revealed PD-OV therapy-induced increases in TME infiltration of variable immune cell types. This study thus demonstrated the proof-of-concept that G47Δ-KR enables PD-OV therapy for neuro-oncological malignancies and warrants further research to advance potential clinical translation.
MeSH term(s)	Humans ; Oncolytic Virotherapy ; Central Nervous System Neoplasms ; Meningioma ; Oncolytic Viruses/genetics ; Glioblastoma ; Meningeal Neoplasms ; Tumor Microenvironment
Language	English
Publishing date	2023-08-22
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2023.216363
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Article ; Online: Paradoxical adverse events in the oral cavity caused by anti-tumor necrosis factor-α therapy for pustulotic arthro-osteitis.

Ito, Sonoko / Kato, Yukihiko / Wakimoto, Hiroko / Nishiwaki, Kaoru / Onishi, Kae / Mori, Tasuo / Yokogawa, Naoto

The Journal of dermatology

2020 Volume 47, Issue 9, Page(s) e317–e319

MeSH term(s)	Humans ; Mouth ; Osteitis ; Psoriasis
Language	English
Publishing date	2020-06-25
Publishing country	England
Document type	Letter
ZDB-ID	800103-0
ISSN	1346-8138 ; 0385-2407
ISSN (online)	1346-8138
ISSN	0385-2407
DOI	10.1111/1346-8138.15469
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Article ; Online: Efficacy of autologous dermal sheath cup cell transplantation in male and female pattern hair loss: A Single-Arm, Multi-Center, phase III equivalent clinical study.

Harada, Kazutoshi / Ohyama, Manabu / Niiyama, Shiro / Irisawa, Ryokichi / Mae, Kenichiro / Mori, Miho / Wakimoto, Hiroko / Kinoshita-Ise, Misaki / Fukuyama, Masahiro / Hayakawa, Reina / Takagi, Masaya / Yamazaki, Masako / Miyoshi, Mami / Nishikawa, Saori / Sato, Seiji / Nakazawa, Yosuke / Sugimoto, Takaki / Ogo, Masashi / Tsuboi, Ryoji

The Journal of dermatology

2023 Volume 50, Issue 12, Page(s) 1539–1549

Abstract: A previous, proof-of-concept clinical study suggested that dermal sheath cup cell injections into the affected areas of male/female pattern hair loss (PHL) may have some amelioratory effects, the clinical efficacy of which needs further examination. A ... ...

Abstract	A previous, proof-of-concept clinical study suggested that dermal sheath cup cell injections into the affected areas of male/female pattern hair loss (PHL) may have some amelioratory effects, the clinical efficacy of which needs further examination. A phase III equivalent clinical study was conducted to further probe the therapeutic potential of this novel approach and verify its safety and efficacy in improving the appearance of PHL. Thirty-six participants with PHL were injected with dermal sheath cup cell harvested from non-affected occipital hair follicles twice in quarterly intervals. Global photographic assessment and phototrichogram were performed in a blinded manner. Patient-reported outcomes were assessed for 12 months. On global photographic assessment, 30% of the participants showed improvement. The analysis of phototricogram data detected the increases in the cumulative hair diameter, hair cross-sectional area, and mean hair diameter of 107.6 ± 152.6 μm/cm
MeSH term(s)	Female ; Humans ; Male ; Alopecia/surgery ; Cell Transplantation ; Hair ; Hair Follicle ; Treatment Outcome
Language	English
Publishing date	2023-09-26
Publishing country	England
Document type	Clinical Trial, Phase III ; Journal Article ; Multicenter Study
ZDB-ID	800103-0
ISSN	1346-8138 ; 0385-2407
ISSN (online)	1346-8138
ISSN	0385-2407
DOI	10.1111/1346-8138.16957
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Article ; Online: Pathogenesis of Cardiomyopathy Caused by Variants in

Agarwal, Radhika / Wakimoto, Hiroko / Paulo, Joao A / Zhang, Qi / Reichart, Daniel / Toepfer, Christopher / Sharma, Arun / Tai, Angela C / Lun, Mingyue / Gorham, Joshua / DePalma, Steven R / Gygi, Steven P / Seidman, J G / Seidman, Christine E

Circulation

2022 Volume 146, Issue 22, Page(s) 1674–1693

Abstract: Background: ALPK3: Methods: We explored the putative kinase activity of ALPK3 and the consequences of damaging variants using isogenic human induced pluripotent stem cell-derived cardiomyocytes, mice, and human patient tissues.: Results: Multiple ... ...

Abstract	Background: ALPK3 Methods: We explored the putative kinase activity of ALPK3 and the consequences of damaging variants using isogenic human induced pluripotent stem cell-derived cardiomyocytes, mice, and human patient tissues. Results: Multiple sequence alignment of all human α-kinase domains and their orthologs revealed 4 conserved residues that were variant only in ALPK3, demonstrating evolutionary divergence of the ALPK3 α-kinase domain sequence. Phosphoproteomic evaluation of both ALPK3 kinase domain inhibition and overexpression failed to detect significant changes in catalytic activity, establishing ALPK3 as a pseudokinase. Investigations into alternative functions revealed that ALPK3 colocalized with myomesin proteins (MYOM1, MYOM2) at both the nuclear envelope and the sarcomere M-band. Conclusions: ALPK3 is an essential cardiac pseudokinase that inserts in the nuclear envelope and the sarcomere M-band. Loss of ALPK3 causes mislocalization of myomesins, critical force-buffering proteins in cardiomyocytes, and also dysregulates M-band proteins necessary for sarcomere protein turnover. We conclude that
MeSH term(s)	Adult ; Animals ; Child ; Humans ; Mice ; Cardiomyopathies/genetics ; Cardiomyopathies/metabolism ; Connectin/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Muscle Proteins/genetics ; Myocytes, Cardiac/metabolism ; Sarcomeres/metabolism ; Protein Kinases/genetics
Chemical Substances	Connectin ; Muscle Proteins ; Alpk3 protein human ; Protein Kinases (EC 2.7.-)
Language	English
Publishing date	2022-11-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.122.059688
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Article ; Online: Histone deacetylase inhibitors enhance oncolytic herpes simplex virus therapy for malignant meningioma.

Kawamura, Yoichiro / Hua, Lingyang / Gurtner, Alessandra / Wong, Ego / Kiyokawa, Juri / Shah, Nadia / Gorham, Joshua / Wakimoto, Hiroko / Rabkin, Samuel D / Martuza, Robert L / Wakimoto, Hiroaki

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2022 Volume 155, Page(s) 113843

Abstract: Approximately 20% of meningiomas are not benign (higher grade) and tend to relapse after surgery and radiation therapy. Malignant (anaplastic) meningioma (MM) is a minor subset of high-grade meningioma that is lethal with no effective treatment options ... ...

Abstract	Approximately 20% of meningiomas are not benign (higher grade) and tend to relapse after surgery and radiation therapy. Malignant (anaplastic) meningioma (MM) is a minor subset of high-grade meningioma that is lethal with no effective treatment options currently. Oncolytic herpes simplex virus (oHSV) is a powerful anti-cancer modality that induces both direct cell death and anti-tumor immunity, and has shown activity in preclinical models of MM. However, clinically meaningful efficacy will likely entail rational mechanistic combination approaches. We here show that epigenome modulator histone deacetylase inhibitors (HDACi) increase anti-cancer effects of oHSV in human MM models, IOMM-Lee (NF2 wild-type) and CH157 (NF2 mutant). Minimally toxic, sub-micromolar concentrations of pan-HDACi, Trichostatin A and Panobinostat, substantively increased the infectability and spread of oHSV G47Δ within MM cells in vitro, resulting in enhanced oHSV-mediated killing of target cells when infected at low multiplicity of infection (MOI). Transcriptomics analysis identified selective alteration of mRNA processing and splicing modules that might underlie the potent anti-MM effects of combining HDACi and oHSV. In vivo, HDACi treatment increased intratumoral oHSV replication and boosted the capacity of oHSV to control the growth of human MM xenografts. Thus, our work supports further translational development of the combination approach employing HDACi and oHSV for the treatment of MM.
MeSH term(s)	Humans ; Meningioma/drug therapy ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/therapeutic use ; Panobinostat ; Neoplasm Recurrence, Local ; Simplexvirus/genetics ; Herpes Simplex ; Meningeal Neoplasms ; RNA, Messenger
Chemical Substances	Histone Deacetylase Inhibitors ; Panobinostat (9647FM7Y3Z) ; RNA, Messenger
Language	English
Publishing date	2022-10-08
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2022.113843
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Article ; Online: AAV9 Delivery of shRNA to the Mouse Heart.

Wakimoto, Hiroko / Seidman, J G / Foo, Roger S Y / Jiang, Jianming

Current protocols in molecular biology

2016 Volume 115, Page(s) 23.16.1–23.16.9

Abstract: RNA interference (RNAi) is a rapid approach to dissect loss-of-function phenotype for a gene of interest. However, it is challenging to perform RNAi in specific organs and tissues in vivo. Engineered viruses can provide a useful tool for delivery of ... ...

Abstract	RNA interference (RNAi) is a rapid approach to dissect loss-of-function phenotype for a gene of interest. However, it is challenging to perform RNAi in specific organs and tissues in vivo. Engineered viruses can provide a useful tool for delivery of small RNAs in vivo. Recombinant adeno-associated viruses (rAAVs) are the preferred method for delivering genes or gene modulators to target cells due to their high titer, low immune response, ability to transduce many types of cell, and overall safety. In this unit, we describe protocols for use of rAAVs as a cargo to deliver miRNA backbone-based shRNA controlled by a cardiac-specific promoter into the mouse heart. © 2016 by John Wiley & Sons, Inc.
MeSH term(s)	Animals ; Dependovirus/genetics ; Gene Transfer Techniques ; Genetic Engineering ; HEK293 Cells ; Humans ; Mice ; Myocardium/metabolism ; RNA Interference ; RNA, Small Interfering/administration & dosage ; RNA, Small Interfering/genetics ; Transduction, Genetic
Chemical Substances	RNA, Small Interfering
Language	English
Publishing date	2016-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1934-3647
ISSN (online)	1934-3647
DOI	10.1002/cpmb.9
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Article ; Online: Isolation of single-stranded DNA.

Wakimoto, Yuji / Jiang, Jianming / Wakimoto, Hiroko

Current protocols in molecular biology

2014 Volume 107, Page(s) 2.15.1–9

Abstract: Single-stranded DNA (ssDNA) is often used for DNA sequencing as well as microarray and hybridization technologies. Asymmetric PCR or exonuclease digestion followed by urea gel separation and isolation on streptavidin-coated magnetic beads are commonly ... ...

Abstract	Single-stranded DNA (ssDNA) is often used for DNA sequencing as well as microarray and hybridization technologies. Asymmetric PCR or exonuclease digestion followed by urea gel separation and isolation on streptavidin-coated magnetic beads are commonly used for this purpose. These two methods may not yield large amounts of highly purified ssDNA. This protocol for ssDNA isolation from PCR-amplified DNA involves biotin labeling of one strand and subsequent strand separation utilizing streptavidin-coated magnetic beads.
MeSH term(s)	DNA, Single-Stranded/chemistry ; DNA, Single-Stranded/isolation & purification ; Magnetic Fields ; Polymerase Chain Reaction/methods ; Streptavidin/chemistry
Chemical Substances	DNA, Single-Stranded ; Streptavidin (9013-20-1)
Language	English
Publishing date	2014-07-01
Publishing country	United States
Document type	Journal Article
ISSN	1934-3647
ISSN (online)	1934-3647
DOI	10.1002/0471142727.mb0215s107
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Article: Cardiomyocyte Proliferative Capacity Is Restricted in Mice With

Onoue, Kenji / Wakimoto, Hiroko / Jiang, Jiangming / Parfenov, Michael / DePalma, Steven / Conner, David / Gorham, Joshua / McKean, David / Seidman, Jonathan G / Seidman, Christine E / Saito, Yoshihiko

Frontiers in cardiovascular medicine

2021 Volume 8, Page(s) 639148

Abstract: ... ...

Abstract	LMNA
Language	English
Publishing date	2021-06-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2021.639148
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