A5037490457- Chromatin Remodeling and Cancer
- DNA Repair Mechanisms
- Induction Heating and Inverter Technology
- Advanced DC-DC Converters
- Multilevel Inverters and Converters
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Genomics and Chromatin Dynamics
- Lung Cancer Treatments and Mutations
- Mechanisms of cancer metastasis
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- Fusion materials and technologies
- Genetics and Neurodevelopmental Disorders
- Cancer-related Molecular Pathways
- Lung Cancer Diagnosis and Treatment
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- Medical Imaging and Pathology Studies
- Retinoids in leukemia and cellular processes
- Ubiquitin and proteasome pathways
- Fungal and yeast genetics research
- Nuclear Materials and Properties
- Silicon Carbide Semiconductor Technologies
National Cancer Centre Japan
2011-2025
Japan Research Institute
2015
National Cancer Center
2013-2014
Tohoku University
2004-2014
Kyoto University
1994-2014
National Cancer Research Institute
2010-2014
National Center for Global Health and Medicine
2014
National Cancer Institute
2014
Center for Cancer Research
2014
Institute of Predictive and Personalized Medicine of Cancer
2014
The occurrence of inactivating mutations in SWI/SNF chromatin-remodeling genes common cancers has attracted a great deal interest. However, mechanistic strategies to target tumor cells carrying such are yet be developed. This study proposes synthetic-lethality therapy for treating deficient the catalytic (ATPase) subunit, BRG1/SMARCA4. strategy relies upon inhibition BRM/SMARCA2, another subunit with BRG1-related activity. Immunohistochemical analysis cohort non-small-cell lung carcinomas...
Abstract Purpose: To identify druggable oncogenic fusions in invasive mucinous adenocarcinoma (IMA) of the lung, a malignant type lung which KRAS mutations frequently occur. Experimental Design: From an IMA cohort 90 cases, consisting 56 cases (62%) with and 34 without (38%), we conducted whole-transcriptome sequencing 32 IMAs, including 27 mutations. We used data to gene fusions, then performed functional analyses fusion products. Results: identified that occurred mutually exclusively...
Abstract The SWI/SNF chromatin-remodeling family contains various protein complexes, which regulate gene expression during cellular development and influence DNA damage response in an ATP- complex-dependent manner, of details remain elusive. Recent human genome sequencing cancer cells revealed frequent mutations factors, especially ARID1A, a variant subunit the BRG1-associated factor (BAF) complex family. We combined live-cell analysis gene-suppression experiments to show that suppression...
Loss-of-function mutations in the CBP/CREBBP gene, which encodes a histone acetyltransferase (HAT), are present variety of human tumors, including lung, bladder, gastric, and hematopoietic cancers. Consequently, development molecular targeting method capable specifically killing CBP-deficient cancer cells would greatly improve therapy. Functional screening synthetic-lethal genes cancers identified CBP paralog p300/EP300 Ablation p300 CBP-knockout induced G1-S cell-cycle arrest, followed by...
The design progress in a compact low aspect ratio (low A ) DEMO reactor, ‘SlimCS’, and its issues are reported. study focused mainly on the torus configuration including blanket, divertor, materials maintenance scheme. For continuity with Japanese ITER-TBM, blanket is based water-cooled solid breeder blanket. vertical stability of elongated plasma high beta access, segmented into replaceable permanent blankets sector-wide conducting shell arranged inbetween these blankets. numerical...
Recent studies have shown that homologous recombination (HR) requires chromatin repression as well relaxation at DNA double strand breaks (DSBs). HP1 and SUV39H1/2 are repressive factors essential for HR. Here, we identify SETDB1 an additional compacting factor promoting Depletion of HP1, SUV39, or BRCA1 confer identical phenotypes. The factors, like BRCA1, dispensable the initiation resection but promote extension step causing diminished RPA RAD51 foci HR in irradiated G2 cells. does not...
Abstract SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex, is causative gene rhabdoid tumors and epithelioid sarcomas. Here, we identify paralog pair CBP p300 as synthetic lethal target in SMARCB1-deficient cancers by using dual siRNA screening method based on “simultaneous inhibition pair” concept. Treatment with CBP/p300 inhibitors suppresses growth cell lines tumor xenografts derived from cells but not SMARCB1-proficient cells. SMARCB1-containing complexes localize H3K27me3...
Abstract A total of 176 genes homozygously deleted in human lung cancer were identified by DNA array‐based whole genome scanning 52 cell lines and subsequent genomic PCR 74 lines, including the scanned. One or more exons these one (1%) to 20 (27%) lines. These included known tumor suppressor genes, e.g., CDKN2A/p16, RB1, SMAD4, candidate whose hemizygous homozygous deletions reported several types cancers, such as FHIT, KEAP1, LRP1B/LRP‐DIP . CDKN2A/p16 p14ARF located 9p21 most frequently...
Chromosomal deoxyribonucleic acid and histone proteins form a highly condensed structure known as chromatin. Chromatin remodeling regulate transcription, synthesis repair by changing nucleosomal composition in an adenosine triphosphate-dependent manner mediate access of acid-binding to double strands. Recently, large-scale genome sequencing studies identified somatic mutations genes encoding chromatin variety human solid cancers. Notably, inactivating the catalytic regulatory subunits...
Inhibitors of poly(ADP-ribose) polymerase (PARP) are promising anticancer drugs, particularly for the treatment tumors deficient in DNA damage response (DDR). However, it is challenging to design effective therapeutic strategies use these compounds against cancers without DDR deficiencies. In this context, combination therapies which PARP inhibitors used alongside have elicited a great deal interest. Curcumin, component turmeric ( Curcuma longa ), has been tested clinical studies its...
Oncogenic RET fusion, caused by an inversion in chromosome 10, was recently identified as a driver mutation for the development of lung adenocarcinoma (LADC). Nevertheless, molecular mechanism(s) underlying rearrangement locus during carcinogenesis are unknown.Genomic segments containing breakpoint junctions fusions were cloned and analyzed genomic polymerase chain reaction genome capture sequencing using next-generation sequencer to identify mechanisms involved DNA strand breaks...
Histone acetylation at DNA double-strand break (DSB) sites by CBP and p300 histone acetyltransferases (HATs) is critical for the recruitment of DSB repair proteins to chromatin. Here, we show that HATs also function in transcriptionally activating BRCA1 RAD51 genes, which are involved homologous recombination (HR), a major system. siRNA-mediated depletion impaired HR activity downregulated protein mRNA levels. Chromatin immunoprecipitation assays showed bind promoter regions and/or reduces...
Background and Purpose To understand the mechanisms involved in strong killing effect of carbon-ion beam irradiation on cancer cells with TP53 tumor suppressor gene deficiencies. Materials Methods DNA damage responses after or X-ray isogenic HCT116 colorectal cell lines without (p53+/+ p53-/-, respectively) were analyzed as follows: survival by clonogenic assay, death modes morphologic observation DAPI-stained nuclei, double-strand breaks (DSBs) immunostaining phosphorylated H2AX (γH2AX),...
Polynucleotide kinase and aprataxin-like forkhead-associated protein (PALF, also called aprataxin- PNK-like factor (APLF)) has been shown to have nuclease activity use its domain bind x-ray repair complementing defective in Chinese hamster cells 4 (XRCC4). Because XRCC4 is a key component of the ligase IV complex that central nonhomologous DNA end joining (NHEJ) pathway, this raises possibility PALF might play role NHEJ. For reason, we further studied nucleolytic properties PALF, searched...
Histone acetylation is a post-translational modification of histones that catalyzed by histone acetyltransferases (HATs) and plays an essential role in cellular processes. The HAT domain EP300/CBP has recently emerged as potential drug target for cancer therapy. Here, we describe the identification novel, highly potent, selective inhibitor DS-9300. Our optimization efforts using structure-based design approach based on cocrystal structures EP300 complex with compounds 2 3 led to possessing...
<p>Downregulation of <i>KREMEN2</i> through CBP/p300 inhibition in SMARCA4/SMARCA2-deficient and SS18–SSX fusion cancer cells induces apoptosis via KREMEN1. <b>A</b> <b>B,</b> Viability DMS114 (<b>A</b>) Fuji (<b>B</b>) cell lines transfected with the indicated siRNAs. Cells were siRNAs for 48 hours, reseeded, an additional hours. The then reseeded again incubated 7 days. Data are presented as mean ± SEM; <i>n</i>...