Publications by authors named "Hiroshi Ikeuchi"
Identifying the mechanisms of action of anticancer drugs is an important step in the development of new drugs. In this study, we established a comprehensive screening platform consisting of 68 oncogenes (MANO panel), encompassing 243 genetic variants, to identify predictive markers for drug efficacy. Validation was performed using drugs that targeted EGFR, BRAF, and MAP2K1, which confirmed the utility of this functional screening panel.
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- The case study details a 41-year-old African woman who first experienced acute alcoholic pancreatitis and then developed severe alcoholic hepatitis (SAH) weeks later.
- After initially responding well to treatment and stopping alcohol, her condition worsened with significant increases in white blood cell count and bilirubin levels, along with rapid hepatosplenomegaly.
- A liver biopsy confirmed SAH, characterized by ballooned liver cells and inflammation, but her condition improved with supportive care despite the unexpected progression from pancreatitis to hepatitis.
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- E7820 and Indisulam are drugs that work as molecular glues, influencing RNA splicing to target and degrade the splicing factor RBM39, potentially aiding in cancer treatment.
- In studies using patient-derived xenograft mouse models, E7820 showed a 38.1% overall response rate, particularly effective in tumors with loss-of-function mutations in homologous recombination repair (HRR) genes like ATM.
- The drug causes DNA damage, leading to synthetic lethality in HRR-deficient cancer cells, and demonstrates synergistic effects when combined with olaparib, suggesting HRR dysfunction as a key predictive biomarker for treatment efficacy.
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- Scientists are studying brain tumors called gliomas to find better ways to treat them using a special test called TOP2-RNA that looks at genes and their fusions.
- In a study with 124 samples, they found some interesting things, like specific gene fusions in glioblastoma cases, and some genes being overly active in certain tumors.
- The TOP2-RNA test is super good at finding gene problems that might help doctors predict and treat gliomas better than regular tests do.
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- A small percentage (1%) of certain tyrosine kinase fusions have been identified in soft tissue sarcomas through DNA sequencing, but these fusions are not common among the 80% of fusion-negative sarcomas, which remain genetically unexplored.
- The study aims to investigate whether DNA/RNA analysis can reveal genetic changes and identify potential tyrosine kinase fusions in tumor-specific, fusion-negative sarcomas, particularly focusing on their response to drug treatment in vitro.
- Research was conducted on 100 patients with bone and soft tissue sarcomas between 2017 and 2020, with 90 patients being found eligible for the study despite some exclusions due to follow-up
Activating mutations in mitogen-activated protein kinase kinase 1 (MAP2K1) are involved in a variety of cancers and may be classified according to their RAF dependence. Sensitivity to combined BRAF and MEK treatments is associated with co-mutations of MAP2K1 and BRAF; however, the significance of less frequent MAP2K1 mutations is largely unknown. The transforming potential and drug sensitivity of 100 MAP2K1 variants were evaluated using individual assays and the mixed-all-nominated-in-one method.
View Article and Find Full Text PDFThe development of tyrosine kinase inhibitors (TKIs) has improved the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The current research priority is to provide viable treatments for patients who have drug-resistant EGFR mutations. We evaluated the drug sensitivity of various EGFR mutants to monotherapies and combination therapies of EGFR-TKIs.
View Article and Find Full Text PDFVarious genetic alterations of the fibroblast growth factor receptor (FGFR) family have been detected across a wide range of cancers. However, inhibition of FGFR signaling by kinase inhibitors demonstrated limited clinical effectiveness. Herein, we evaluated the transforming activity and sensitivity of 160 nonsynonymous FGFR mutations and ten fusion genes to seven FGFR tyrosine kinase inhibitors (TKI) using the mixed-all-nominated-in-one (MANO) method, a high-throughput functional assay.
View Article and Find Full Text PDFA 30-year-old man presented with constipation and abdominal pain. He was suspected of having ulcerative colitis, and administration of 2400mg/day of oral mesalazine was initiated. After 10 days of treatment, he experienced fever and chest pain.
View Article and Find Full Text PDFC7α-substituted estradiols bind to estrogen receptors in cell nuclei, yet these derivatives remain little used in bioimaging. Here, we describe a fluorescent derivative of estradiol (E2) with a boron-dipyrromethene (BODIPY) moiety attached to C7α, synthesized by olefin metathesis reaction of 7α-allylestradiol and 9-decenyl-BODIPY. In ovariectomized rats and non-ovariectomized mice, E2-BODIPY promoted the growth of uterine tissue similar to the effect of estradiol.
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