A5065874736- DNA Repair Mechanisms
- Cancer therapeutics and mechanisms
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Plant Genetic and Mutation Studies
- RNA Interference and Gene Delivery
- vaccines and immunoinformatics approaches
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced biosensing and bioanalysis techniques
- Bioactive Compounds and Antitumor Agents
- Immune Cell Function and Interaction
- Synthesis and bioactivity of alkaloids
- HIV/AIDS drug development and treatment
- Advanced Proteomics Techniques and Applications
- Antibiotics Pharmacokinetics and Efficacy
- RNA and protein synthesis mechanisms
- Immunotherapy and Immune Responses
- Signaling Pathways in Disease
- Cell Adhesion Molecules Research
- Polyomavirus and related diseases
- CAR-T cell therapy research
- Telomeres, Telomerase, and Senescence
- Chromosomal and Genetic Variations
Kanagawa Prefectural Hospital Organization
2019-2024
Kanagawa Cancer Center
2019-2024
BrightPath Biotherapeutics (Japan)
2019-2024
Yokohama City University
2003-2012
Kihara Institute for Biological Research
2003-2012
Topoisomerase II (Top2) is a ubiquitous nuclear enzyme that relieves torsional stress in chromosomal DNA during various cellular processes. Agents target Top2, involving etoposide, doxorubicin, and mitoxantrone, are among the most effective anticancer drugs used clinic. Mammalian cells possess two genetically distinct Top2 isoforms, both of which these agents. Top2alpha essential for cell proliferation highly expressed vigorously growing cells, whereas Top2beta nonessential growth has...
Targeted gene disruption is a powerful tool for studying function in cells and animals. In addition, this technology includes potential to correct disease-causing mutations. However, constructing targeting vectors laborious step the gene-targeting strategy, even apart from low efficiency of homologous recombination mammals. Here, we introduce quick simplified method construct vectors. This based on commercially available MultiSite Gateway® technology. The sole critical design primers PCR...
In higher animal cells, the principal limitation of gene-targeting technology is extremely low efficiency targeted integration, which occurs three to four orders magnitude less frequently than random integration. Assuming that integration mechanistically involves non-homologous end-joining (NHEJ), inactivation this pathway should reduce and may enhance gene targeting. To test possibility, we examined frequencies in NHEJ-deficient chicken DT40 human Nalm-6 cell lines. As expected, loss NHEJ...
Gene targeting provides a powerful means for analyzing gene function, as exemplified by knockout mouse studies and recent work with the highly recombinogenic chicken DT40 B-lymphocyte line. In human cultured cells, however, low frequency of is serious barrier to efficiently generate clones. Moreover, commonly used cell lines are karyotypically abnormal or unstable. Here, we show using promoterless constructs that Nalm-6, pre-B ALL line, proficient homologous recombination. Indeed, efficiency...
Neoantigens derived from tumor-specific genetic mutations might be suitable targets for cancer immunotherapy because of their high immunogenicity. In the current study, we evaluated immunogenicity 10 driver that are frequently expressed in various cancers using peripheral blood mononuclear cells healthy donors (n = 25). Of synthetic peptides (27-mer) these mutations, six KRAS-G12D, KRAS-G12R, KRAS-G13D, NRAS-Q61R, PIK3CA-H1047R, and C-Kit-D816V induced T cell responses, suggesting frequent...
Accurately identifying neoantigens is crucial for developing effective cancer vaccines and improving tumor immunotherapy. Mass spectrometry-based immunopeptidomics has emerged as a promising approach to human leukocyte antigen (HLA) peptides presented on the surface of cells, but false-positive identifications remain significant challenge. In this study, liquid chromatography-tandem mass proteomics next-generation sequencing were utilized identify HLA-presenting neoantigenic resulting from...
Artemis is a recently identified factor involved in V(D)J recombination and nonhomologous end joining (NHEJ) of DNA double-strand break (DSB) repair. Here, we performed targeted disruption the gene (ARTEMIS) human pre-B cell line Nalm-6. Unexpectedly, found that cells lacking exhibit increased sensitivity to low doses, but not high ionizing radiation. We also show ARTEMIS-deficient are hypersensitive topoisomerase II inhibitor etoposide, much lesser extent than ligase IV, critical component...
DNA topoisomerase II (Top2) inhibitors are useful as anticancer agents, mostly by virtue of their ability to induce double-strand breaks (DSBs). These DSBs repaired almost exclusively Rad52-dependent homologous recombination (HR) in yeast. However, we have recently shown that vertebrate cells such lesions primarily nonhomologous end-joining, but not HR. This finding, taken together with previous observations disruption RAD52 does severely affect HR cells, makes it highly unlikely Rad52...