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Pancreatic Neoplasms: HELP
Articles by Jih-Hsiang Lee
Based on 2 articles published since 2010
(Why 2 articles?)
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Between 2010 and 2020, Jih-Hsiang Lee wrote the following 2 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Role of CYB5A in pancreatic cancer prognosis and autophagy modulation. 2014

Giovannetti, Elisa / Wang, Qiuyan / Avan, Amir / Funel, Niccola / Lagerweij, Tonny / Lee, Jih-Hsiang / Caretti, Viola / van der Velde, Arjan / Boggi, Ugo / Wang, Yisong / Vasile, Enrico / Peters, Godefridus J / Wurdinger, Thomas / Giaccone, Giuseppe. ·Affiliations of authors: Department of Medical Oncology (EG, AA, GJP) and Department of Neurosurgery (TL, VC, TW), VU University Medical Center, and Centre for Integrative Bioinformatics (AvdV), VU University, Amsterdam, the Netherlands · Department of Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, University of Pisa, Pisa, Italy (NF, UB, EV) · Department of Neurology, Stanford University, Stanford, CA (VC) · Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA (TW) · Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (QW, J-HL, YW, GG). ·J Natl Cancer Inst · Pubmed #24301457.

ABSTRACT: BACKGROUND: Loss of 18q22.3 is a prognostic marker in pancreatic ductal adenocarcinoma (PDAC). This study investigated genes encoded by this cytoband. METHODS: We studied mRNA/protein expression in radically resected (n = 130) and metastatic patients (n = 50). The role of CYB5A was tested in 11 PDAC cell lines and five primary cultures through retrovirus-mediated upregulation and small interfering RNA using wound-healing, invasion, annexin-V, electron microscopy, and autophagic assays, as well as autophagy genes and kinases arrays. CYB5A+ orthotopic models (n = 6 mice/group) were monitored by Firefly and Gaussia-luciferase bioluminescence, magnetic resonance imaging, and high-frequency ultrasound. Data were analyzed by t test, Fisher exact-test, log-rank test and Cox proportional hazards models. All statistical tests were two-sided. RESULTS: Both resected and metastatic patients with low mRNA or protein expression of CYB5A had statistically significantly shorter survival (eg, median = 16.7 months, 95% confidence interval [CI] = 13.5 to 19.9; vs median = 24.8 months, 95% CI = 12.8 to 36.9; P = .02, two-sided log-rank test; n = 82 radically resected PDACs), and multivariable analyses confirmed prognostic relevance. Moreover, we characterized a novel function to CYB5A, autophagy induction, concomitant with reduced proliferation and migration/invasion of PDAC cells. Network analysis of proautophagic pathways suggested CYB5A interaction with TRAF6, which was confirmed by TRAF6 downregulation after CYB5A reconstitution (-69% in SU.86.86-CYB5A+; P = .005, two-sided t test). CYB5A silencing had opposite effects, restoring TRAF6 expression and wound healing. In vivo studies showed that CYB5A induced autophagy while inhibiting tumor growth/metastasis and increasing survival (median = 57 days, 95% CI = 52 to 61; vs median = 44 days, 95% CI = 21 to 57; P = .03, two-sided log-rank test). CONCLUSIONS: These results define CYB5A as a novel prognostic factor for PDAC that exerts its tumor-suppressor function through autophagy induction and TRAF6 modulation.

2 Article Loss of 18q22.3 involving the carboxypeptidase of glutamate-like gene is associated with poor prognosis in resected pancreatic cancer. 2012

Lee, Jih-Hsiang / Giovannetti, Elisa / Hwang, Jin-Hyeok / Petrini, Iacopo / Wang, Qiuyan / Voortman, Johannes / Wang, Yonghong / Steinberg, Seth M / Funel, Niccola / Meltzer, Paul S / Wang, Yisong / Giaccone, Giuseppe. ·Medical Oncology Branch, Genetic Branch, and Biostatistics and Data Management Section, National Cancer Institute, NIH, Bethesda, MD 20892, USA. ·Clin Cancer Res · Pubmed #22128300.

ABSTRACT: PURPOSES: Pancreatic cancer is the fourth leading cause of cancer-related death, and studies on the clinical relevance of its genomic imbalances are warranted. EXPERIMENTAL DESIGN: Recurrent copy number alterations of cytobands and genes were analyzed by array comparative genomic hybridization (aCGH) in 44 resected pancreatic cancer specimens. Prognostic markers identified by aCGH were validated by PCR gene copy number assay in an independent validation cohort of 61 resected pancreatic cancers. The functions of gene identified were evaluated by proliferation, cell cycle, and migration assays in pancreatic cancer cells. RESULTS: We showed recurrent copy number gains and losses in the first cohort. Loss of 18q22.3 was significantly associated with short-term overall survival in the first cohort (P = 0.019). This cytoband includes the carboxypeptidase of glutamate-like (CPGL) gene. CPGL gene deletion was associated with shorter overall survival in the validation cohort (P = 0.003). CPGL deletion and mutations of TP53 or Kras seem to be independent events. A Cox model analysis of the two cohorts combined showed that loss of 18q22.3/deletion of the CPGL gene was an independent poor prognostic factor for overall survival (HR = 2.72, P = 0.0007). Reconstitution of CPGL or its splicing variant CPGL-B into CPGL-negative pancreatic cancer cells attenuated cell growth, migration, and induced G(1) accumulation. CONCLUSION: Loss of 18q22.3/deletion of the CPGL gene is a poor prognostic marker in resected pancreatic cancer, and functional studies suggest the CPGL gene as growth suppressor gene in pancreatic cancer.