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Your search keyword '"Shih HJ"' showing total 3 results
Start Over Author "Shih HJ" Topic lung neoplasms
3 results on '"Shih HJ"'

1. Response to Brigatinib Targeted Therapy in Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 19 Deletion, T790M, and cis-C797S Triple Mutations: A Case Report.

Author

Chen ZW, Lin G, Shih HJ, and Wu CE

Subjects
Humans, Female, ErbB Receptors metabolism, Mutation, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Drug Resistance, Neoplasm genetics, Aniline Compounds therapeutic use, Aniline Compounds pharmacology, Exons, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology
Abstract

Epidermal growth factor receptor ( EGFR ) triple mutations with exon 19 deletion (del19), T790M, and cis-C797S (del19/T790M/cis-C797S mutations) frequently occur in patients with non-small cell lung cancer (NSCLC), while progression to frontline EGFR -tyrosine kinase inhibitors (TKIs) and osimertinib was resistant to all clinically available EGFR -TKIs. Brigatinib monotherapy may be a potential treatment for NSCLC harboring del19/T790M/cis-C797S mutations based on preclinical studies; however, no clinical report has evaluated its efficacy on EGFR del19/T790M/cis-C797S mutations. Herein, we present a case of a female patient with EGFR del19-mutated NSCLC treated with afatinib followed by osimertinib due to acquired T790M mutation. The EGFR del19/T790M/cis-C797S mutations were detected following osimertinib treatment. Complete response of skull metastasis was confirmed after brigatinib treatment (90 mg daily). Unfortunately, she experienced intolerable adverse events; therefore, brigatinib was discontinued after three-month usage. This report provides the first reported evidence for the use of brigatinib monotherapy in patients with NSCLC harboring EGFR del19/T790M/cis-C797S mutations after progression to previous EGFR -TKIs.

Published
2022
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2. N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity.

Author

Hua KT, Tan CT, Johansson G, Lee JM, Yang PW, Lu HY, Chen CK, Su JL, Chen PB, Wu YL, Chi CC, Kao HJ, Shih HJ, Chen MW, Chien MH, Chen PS, Lee WJ, Cheng TY, Rosenberger G, Chai CY, Yang CJ, Huang MS, Lai TC, Chou TY, Hsiao M, and Kuo ML

Subjects
Acetyltransferases metabolism, Aged, Cell Movement, Female, Humans, Lung Neoplasms enzymology, Lung Neoplasms metabolism, Male, Middle Aged, N-Terminal Acetyltransferase A, N-Terminal Acetyltransferase E, Rho Guanine Nucleotide Exchange Factors, Acetyltransferases physiology, Guanine Nucleotide Exchange Factors metabolism, Lung Neoplasms pathology, Neoplasm Metastasis prevention & control, cdc42 GTP-Binding Protein antagonists & inhibitors, rac1 GTP-Binding Protein antagonists & inhibitors
Abstract

N-α-acetyltransferase 10 protein, Naa10p, is an N-acetyltransferase known to be involved in cell cycle control. We found that Naa10p was expressed lower in varieties of malignancies with lymph node metastasis compared with non-lymph node metastasis. Higher Naa10p expression correlates the survival of lung cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Published
2011
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3. Loss of p53 and MCT-1 overexpression synergistically promote chromosome instability and tumorigenicity.

Author

Kasiappan R, Shih HJ, Chu KL, Chen WT, Liu HP, Huang SF, Choy CO, Shu CL, Din R, Chu JS, and Hsu HL

Subjects
Aneuploidy, Animals, Antineoplastic Agents, Phytogenic pharmacology, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung pathology, Cell Adhesion physiology, Cell Cycle Proteins metabolism, Cell Movement physiology, Cell Proliferation, Cytogenetic Analysis, Drug Synergism, Etoposide pharmacology, Female, Flow Cytometry, Humans, Immunoblotting, Immunoenzyme Techniques, Lung Neoplasms metabolism, Lung Neoplasms pathology, Mice, Mice, Inbred BALB C, Microscopy, Fluorescence, Mutagens pharmacology, Oncogene Proteins metabolism, Proto-Oncogene Proteins c-raf genetics, Proto-Oncogene Proteins c-raf metabolism, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Translocation, Genetic, Tumor Cells, Cultured, Tumor Suppressor Protein p53 metabolism, Carcinoma, Non-Small-Cell Lung genetics, Cell Cycle Proteins genetics, Chromosomal Instability, Lung Neoplasms genetics, Oncogene Proteins genetics, Tumor Suppressor Protein p53 genetics
Abstract

MCT-1 oncoprotein accelerates p53 degradation by means of the ubiquitin-dependent proteolysis. Our present data show that induction of MCT-1 increases chromosomal translocations and deregulated G(2)-M checkpoint in response to chemotherapeutic genotoxin. Remarkably, increases in chromosome copy number, multinucleation, and cytokinesis failure are also promoted while MCT-1 is induced in p53-deficient cells. In such a circumstance, the Ras-mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-mitogen-activated protein kinase signaling activity and the expression of metastatic molecules are amplified. Given a p53-silencing background, MCT-1 malignantly transforms normal breast epithelial cells that are satisfactory for stimulating cell migration/adhesion and tumorigenesis. Detailed analyses of MCT-1 oncogenicity in H1299 p53-null lung cancer cells have shown that ectopically expressed MCT-1 advances xenograft tumorigenicity and angiogenesis, which cannot be completely suppressed by induction of p53. MCT-1 counteracts mutually with p53 at transcriptional levels. Clinical validations confirm that MCT-1 mRNA levels are differentially enriched in comparison between human lung cancer and nontumorigenic tissues. The levels of p53 mRNA are comparatively reduced in a subset of cancer specimens, which highly present MCT-1 mRNA. Our results indicate that synergistic promotions of chromosomal imbalances and oncogenic potency as a result of MCT-1 expression and p53 loss play important roles in tumor development.

Published
2009
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