A5063835750- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Acute Lymphoblastic Leukemia research
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Virus-based gene therapy research
- PI3K/AKT/mTOR signaling in cancer
- Microtubule and mitosis dynamics
- Cancer Research and Treatments
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Occupational and environmental lung diseases
- Gastrointestinal disorders and treatments
- Gastrointestinal Tumor Research and Treatment
- Radioactive contamination and transfer
- Genetic factors in colorectal cancer
- Signaling Pathways in Disease
- Advanced Breast Cancer Therapies
- Chemical Synthesis and Reactions
- Gastric Cancer Management and Outcomes
Aichi Medical University
2015-2024
Sidney Kimmel Comprehensive Cancer Center
2005-2023
Johns Hopkins University
2004-2023
Tokyo Medical University
2023
National Institutes for Quantum Science and Technology
2023
University of Chittagong
2022
Kansai University
2022
Tokyo Medical University Hachioji Medical Center
2017
Kyoto Prefectural University of Medicine
2017
Tokyo Women's Medical University
2000-2015
Abstract In this study, we report for the first time reduced expression of let-7 microRNA in human lung cancers. Interestingly, 143 cancer cases that had undergone potentially curative resection could be classified into two major groups according to unsupervised hierarchical analysis, showing significantly shorter survival after with (P = 0.0003). Multivariate COX regression analysis showed prognostic impact independent disease stage (hazard ratio 2.17; P 0.009). addition, overexpression...
The phosphatidylinositol 3-kinases (PI3Ks) are known regulators of cellular growth and proliferation. It has recently been reported that somatic mutations within the PI3K subunit p110? (PIK3CA) present in human colorectal other cancers. Here we show thirteen fifty-three breast cancers (25%) contain PIK3CA, with majority located kinase domain. These results demonstrate PIK3CA is most mutated oncogene cancer support a role for epithelial carcinogenesis.
The phosphatidylinositol 3-kinase subunit PIK3CA is frequently mutated in human cancers. Here we used gene targeting to "knock in" mutations into breast epithelial cells identify new therapeutic targets associated with oncogenic PIK3CA. Mutant knockin were capable of epidermal growth factor and mTOR-independent cell proliferation that was AKT, ERK, GSK3beta phosphorylation. Paradoxically, the inhibitors lithium chloride SB216763 selectively decreased colorectal cancer lines led a decrease...
Biallelic inactivation of cancer susceptibility gene BRCA1 leads to breast and ovarian carcinogenesis. Paradoxically, deficiency in mice results early embryonic lethality, similarly, lack human cells is thought result cellular lethality view 's essential function. To survive homozygous during tumorigenesis, precancerous must accumulate additional genetic alterations, such as p53 mutations, but this requirement for an extra “hit” contradicts the two-hit theory accelerated carcinogenesis...
Recently, several expression-profiling experiments have shown that adenocarcinoma can be classified into subgroups also reflect patient survival. In this study, we examined the expression patterns of 44 genes selected by these studies to test whether their were relevant prognosis in our cohort as well, and create a prognostic model applicable clinical practice.Expression levels determined 85 patients quantitative reverse transcriptase polymerase chain reaction. Cluster analysis was...
Tamoxifen is widely used for the treatment of hormonally responsive breast cancers. However, some resistant cancers develop a growth proliferative response to this drug, as evidenced by tumor regression upon its withdrawal. To elucidate molecular mediators paradox, tissue samples from patient with tamoxifen-stimulated cancer were analyzed. These studies revealed that loss cyclin-dependent kinase inhibitor p21 was associated tamoxifen growth-inducing phenotype. Immortalized human epithelial...
Abstract The oncogenic function of mutant ras in mammalian cells has been extensively investigated using multiple human and animal models. These systems include overexpression exogenous transgenes, conditionally expressed knock-in mouse models, somatic cell knockout wild-type genes cancer lines. However, phenotypic discrepancies between mice transgenic prompted us to evaluate the consequences targeted an K-ras mutation nontumorigenic breast epithelial line MCF-10A hTERT-immortalized mammary...
Although a high frequency of androgen receptor (AR) expression in human breast cancers has been described, exploiting this knowledge for therapy challenging. This is part because androgens can either inhibit or stimulate cell proliferation pre-clinical models cancer. In addition, many co-express other steroid hormone receptors that affect AR signaling, further obfuscating the effects on cancer cells. To create better-defined signaling epithelial cells, we took estrogen (ER)-α-negative and...
Abstract Malignant pleural mesothelioma ( MPM ), an asbestos‐related occupational disease, is aggressive and incurable tumor of the thoracic cavity. Despite recent advances in treatment, overall survival patients with very low. Recent studies have implicated that PI 3K/Akt signaling involved cell development. To investigate effects Akt inhibitors on survival, we examined nine selective inhibitors, namely, afuresertib, Akti‐1/2, AZD 5363, GSK 690693, ipatasertib, MK ‐2206, perifosine, PHT...
Abstract 5′ adenosine monophosphate–activated protein kinase–related kinase 5 (ARK5) is involved in mitochondrial ATP production and associated with poor prognosis of multiple myeloma (MM). However, the molecular mechanisms ARK5 MM remain largely unknown. This study examined pathogenic role mitochondria by using genetically modified isogenic cell clones or without human lines, KMS-11 Sachi, which overexpress . The biallelic knockout (ARK5-KO) inhibited proliferation, colony formation,...
Highlights•Tandem paired nicking promotes targeted knockin with substantial efficiency•Tandem scarcely creates indels at the edited genomic loci•DNA recombination elicited by tandem is analogous to Holliday's model•Targeted shows no reciprocal interference p53SummaryTargeted mediated double-stranded DNA cleavage accompanied unwanted insertions and deletions (indels) on-target off-target sites. A nick-mediated approach generates but exhibits reduced efficiency of knockin. Here, we demonstrate...
The properties of constitutive promoters within adeno-associated viral (AAV) vectors have not yet been fully characterized. In this study, AAV vectors, in which enhanced GFP expression was directed by one the six (human β-actin, human elongation factor-1α, chicken β-actin combined with cytomegalovirus early enhancer, (CMV), simian virus 40, and herpes simplex thymidine kinase), were constructed introduced into HCT116, DLD-1, HT-1080, MCF-10A cell lines. Quantification signals infected cells...
ABSTRACT Splice variants of certain genes impact on genetic biodiversity in mammals. The tumor suppressor TP53 gene (encoding p53) plays an important role the regulation tumorigenesis hepatocellular carcinoma (HCC). Δ40p53α is a naturally occurring p53 isoform that lacks N-terminal transactivation domain, yet little known about development HCC. Here, we first report HCC cell lines. In TP53+/Δ40 clones, clonogenic activity and survival dramatically decreased, whereas percentage...
Abstract Ameloblastoma is a rare odontogenic benign tumor accounting for less than 1% of head and neck tumors. Advanced next generation sequencing (NGS) analyses identified high frequency BRAF V600E SMO L412F mutations in ameloblastoma. Despite the existence whole genomic sequence information from patients with ameloblastoma, entire molecular signature characteristics ameloblastoma cells are still obscure. In this study, we sought to uncover basis determine cellular phenotype mutations. Our...
Abstract The selective pressures leading to cancers with mutations in both KRAS and PIK3CA are unclear. Here, we show that somatic cell knockin of G12V oncogenic human breast epithelial cells results cooperative activation the phosphoinositide 3-kinase (PI3K) mitogen-activated protein kinase (MAPK) pathways vitro, leads tumor formation immunocompromised mice. Xenografts from double-knockin retain single copies mutant PIK3CA, suggesting does not require increased copy number either oncogene,...