A5062505521- Lung Cancer Treatments and Mutations
- Synthetic Organic Chemistry Methods
- Asymmetric Synthesis and Catalysis
- Carbohydrate Chemistry and Synthesis
- Chemical Synthesis and Analysis
- Chemical synthesis and alkaloids
- Lung Cancer Research Studies
- Colorectal Cancer Treatments and Studies
- Cancer therapeutics and mechanisms
- Microbial Natural Products and Biosynthesis
- RNA modifications and cancer
- HER2/EGFR in Cancer Research
- Oxidative Organic Chemistry Reactions
- Chemical Synthesis and Reactions
- Cancer Genomics and Diagnostics
- Marine Sponges and Natural Products
- Cancer-related gene regulation
- Cytokine Signaling Pathways and Interactions
- Heat shock proteins research
- Biochemical and Molecular Research
- Asymmetric Hydrogenation and Catalysis
- Liver Disease Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Traditional and Medicinal Uses of Annonaceae
- Advanced Synthetic Organic Chemistry
Harvard University
2016-2025
Beth Israel Deaconess Medical Center
2016-2025
Chiba Cancer Center
2018-2025
National Cancer Center
2018-2025
The University of Tokyo
1996-2024
Tokyo University of Science
2011-2024
National Cancer Center Hospital East
2019-2024
National Center for Global Health and Medicine
2024
Harvard Stem Cell Institute
2014-2023
Toyokawa City Hospital
2015-2023
Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in specimens from patients with non-small-cell lung cancer who a response to anilinoquinazoline EGFR inhibitors. Despite dramatic responses such inhibitors, most ultimately relapse. The mechanism drug resistance is unknown. Here we report case patient EGFR-mutant, gefitinib-responsive, advanced had relapse after two years complete remission during treatment gefitinib. DNA sequence his tumor biopsy specimen at...
The EML4-ALK fusion oncogene represents a novel molecular target in small subset of non-small-cell lung cancers (NSCLC). To aid identification and treatment these patients, we examined the clinical characteristics outcomes patients who had NSCLC with without EML4-ALK.Patients were selected for genetic screening on basis two or more following characteristics: female sex, Asian ethnicity, never/light smoking history, adenocarcinoma histology. was identified by using fluorescent situ...
CSF Concentration of the Anaplastic Lymphoma Kinase Inhibitor Crizotinib Case ReportWe describe case a 29-year-old white man with neversmoking history and EML4-ALK-E20A20 stage IV non-small-cell lung cancer (NSCLC) whose disease had progressed after first-line cisplatin plus pemetrexed second-line erlotinib.He started crizotinib at 200 mg twice daily attained significant symptomatic improvement minor tumor regression his intrathoracic best classified as stable disease. 1 Before start...
Lysophosphatidic acid (LPA), together with sphingosine 1-phosphate, is a bioactive lipid mediator that acts on G-protein-coupled receptors to evoke multiple cellular responses, including Ca<sup>2+</sup> mobilization, modulation of adenylyl cyclase, and mitogen-activated protein (MAP) kinase activation. In this study, we isolated human cDNA encoding novel receptor, designated EDG7, characterized it as receptor for LPA. The amino sequence the EDG7 53.7 48.8% identical those functional LPA EDG2...
Crystal structure and detailed analysis of different EGFR mutants explain why some mutations in exon 20 make lung cancers resistant to inhibitors others them more sensitive.
Background Epidermal growth factor receptor (EGFR) mutations are present in the majority of patients with non-small cell lung cancer (NSCLC) responsive to EGFR tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib. These EGFR-dependent tumors eventually become TKI resistant, and common secondary T790M mutation accounts for half acquired resistance gefitinib. However, key proapoptotic proteins involved TKI-induced death other remain unclear. The objective this study was identify mechanism...
Interleukin (IL)-18 was identified as a molecule that induces IFN-γ production and enhances NK cell cytotoxicity. In this paper, we report upon the purification characterization of human IL-18 receptor (hIL-18R). We selected Hodgkin's disease line, L428, most strongly hIL-18R-expressing line based on results binding assays. This inhibited by but not IL-1β. The dissociation constant (K d) of125I-IL-18 to L428 cells about 18.5 nm, with 18,000 sites/cell. After immunizing mice cloning, single...
Two novel synthetic tetrapeptides, VEID-CHO and DMQD-CHO, could selectively inhibit caspase-6 caspase-3, respectively. We used these inhibitors to dissect the pathway of caspase activation in Fas-stimulated Jurkat cells identify roles each active apoptotic processes. Affinity labeling techniques revealed a branched protease cascade which caspase-8 activates caspase-3 -7, turn, caspase-6. Both -3 have major nuclear apoptosis. Caspase-6 cleaves mitotic apparatus protein (NuMA) mediates...
Abstract Purpose: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) gefitinib and erlotinib benefit some non–small cell lung cancer (NSCLC) patients, but most do not respond (primary resistance) those who initially eventually progress (acquired resistance). EGFR TKI resistance is completely understood has been associated with certain K-RAS mutations MET amplification. Experimental Design: We hypothesized that dual inhibition of the vascular endothelial (VEGF)...
Many patients with non-small-cell lung cancer (NSCLC) who achieve radiographic responses to treatment the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib have somatic mutations in EGFR domain. However, little is known about efficacy of cetuximab, an antibody against extracellular domain, mutant NSCLC.NSCLC cell lines carrying wild-type (A549, H441, H1666) or (H3255, DFCILU-011, PC-9, HCC827) were treated various dilutions cetuximab relative maximal...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereocontrolled synthesis of (+)-negamycin from an acyclic homoallylamine by 1,3-asymmetric inductionYi Fong Wang, Toshio Izawa, Susumu Kobayashi, and Masaji OhnoCite this: J. Am. Chem. Soc. 1982, 104, 23, 6465–6466Publication Date (Print):November 1, 1982Publication History Published online1 May 2002Published inissue 1 November 1982https://pubs.acs.org/doi/10.1021/ja00387a060https://doi.org/10.1021/ja00387a060research-articleACS...
Abstract Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in non–small cell lung cancer specimens from patients responding to anilinoquinazoline EGFR inhibitors. However, clinical resistance inhibitor therapy is commonly observed. Previously, we showed that such can be caused by a second mutation gene, leading T790M amino acid change tyrosine kinase domain and also found CL-387,785, specific irreversible inhibitor, was able overcome this on biochemical...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLewis acid catalyzed cyclocondensations of functionalized dienes with aldehydesSamuel Danishefsky, James F. Kerwin Jr., and Susumu KobayashiCite this: J. Am. Chem. Soc. 1982, 104, 1, 358–360Publication Date (Print):January 1982Publication History Published online1 May 2002Published inissue 1 January 1982https://pubs.acs.org/doi/10.1021/ja00365a095https://doi.org/10.1021/ja00365a095research-articleACS PublicationsRequest reuse permissionsArticle...
A highly regio- and diastereoselective TiCl4-mediated vinylogous Mukaiyama aldol reaction using the chiral vinylketene silyl N,O-acetal has been developed. The present provides a unique effective means of controlling remote asymmetric induction. methyl group at alpha-position is important in achieving high level stereoselectivity. From synthetic point view, this methodology can provide one-step construction delta-hydroxy-alpha,gamma-dimethyl-alpha,beta-unsaturated carbonyl unit that seen...
Sclerosing cholangitis (SC) with autoimmune pancreatitis (AIP) is similar to primary sclerosing (PSC) regard cholangiographic findings, but only the former responds well steroid therapy. This report concentrates on clinical differences between these diseases.The presenting complaint or abnormality, associated disease, pancreatic changes, treatment, and course were studied for several cases of PSC (n = 27) SC AIP 20).SC as a diagnosis occurs abruptly obstructive jaundice compared where often...
Mitogen-activated protein kinase (MAPK) pathway signaling plays an important role in the majority of non-small-cell lung cancers (NSCLCs). In a prior microarray analysis epidermal growth factor receptor (EGFR) inhibition NSCLC cell lines, we noted that several dual specificity phosphatases (DUSPs) were among most highly and immediately regulated genes. DUSPs act as natural terminators MAPK signal transduction therefore, hypothesized tumor suppressive via feedback mechanisms. current study,...
Abstract Purpose: Most lung cancers with activating epidermal growth factor receptor (EGFR) mutations respond to gefitinib; however, resistance this tyrosine kinase inhibitor (TKI) invariably ensues. The T790M mutation occurs in 50% and MET amplification 20% of TKI-resistant tumors. Other secondary (D761Y L747S) are rare. Our goal was determine the effects erlotinib 150 mg/d EGFR mutated patients resistant gefitinib 250 mg/d, because TKI is given at a higher biologically active dose than...