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Li K.-C.,National Tsing Hua University | Chang Y.-H.,Chang Gung University | Lin C.-Y.,National Tsing Hua University | Hwang S.-M.,Food Industry Research and Development Institute | And 2 more authors.
Tissue Engineering - Part A | Year: 2015

We recently developed hybrid baculovirus (BV) vectors that exploited FLPo/Frt-mediated DNA minicircle formation. Engineering of adipose-derived stem cells (ASCs) with the FLPo/Frt-based BV vectors enabled prolonged transgene expression and, after cell implantation into rabbits, ameliorated cartilage regeneration and bone repair. To translate the hybrid BV one step further toward clinical applications, here we assessed the biosafety profiles of the hybrid BV-engineered human ASCs (hASCs) in vitro and evaluated the immune responses elicited by the engineered porcine ASCs (pASCs) in large animals. We confirmed that the hybrid BV did not compromise the hASCs viability, immunosuppressive capacity, and surface characteristics. Neither did the hybrid BV cause chromosomal abnormality/transgene integration in vitro nor did it induce tumorigenicity in vivo. In the large animal study, pASCs were engineered with the hybrid BV expressing bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) and implanted into femoral bone defects in mini pigs. The hybrid BV-engineered pASCs enabled prolonged BMP2/VEGF expression and triggered the healing of massive segmental bone defects, while only eliciting transient antibody, cytokine, and local cellular immune responses stemming from the implantation procedure itself. These data altogether demonstrated the safety of the hybrid BV vectors for ASCs engineering and bone healing in large animals, hence implicating the potential in clinical applications. © 2015, Mary Ann Liebert, Inc. 2015. Source

Yu M.-C.,Chang Gung Memorial Hospital | Yu M.-C.,Chang Gung University | Chan K.-M.,Chang Gung Memorial Hospital | Lee C.-F.,Chang Gung Memorial Hospital | And 5 more authors.
Journal of Gastrointestinal Surgery | Year: 2011

Backgrounds: Surgical resection remains the first line of treatment for earlier stages of hepatocellular carcinoma (HCC), and it offers the best prognosis for long-term survival. Nevertheless, the recurrence rates after resection are still high in reports. Therefore, it is still essential to explore any potential prognostic factors to attain relatively longer-term survival of HCC patients. Materials and Methods: In the period from 1983 to 2005, 1,685 patients who underwent hepatectomy at Chang Gung Memorial hospital were enrolled in the study, and their clinicopathological data were retrospectively reviewed for survival analysis. Results: The 1-,3-,5-, and 10-year disease-free survival (DFS) rates in this series were 60.3%, 39.7%, 31.3%, and 24.0%, respectively, whereas the 1-,3-,5-, and 10-year overall survival (OS) rates were 80.1%, 59.1%, 46.6%, and 27.7%, respectively. Gross vascular invasion, tumor status, lymph node involvement, satellite lesion, positive surgical margin, alkaline phosphatase (ALP), albumin, presence of cirrhosis, and Child grade B or C were independent prognostic factors for prediction of DFS; while α-fetoprotein, ALP, surgical factors, including complications, blood transfusion, positive resection margin, and tumor characters including tumor status, vascular invasion, and lack of tumor encapsulation were found to be independent predicting factors for OS, as determined by Cox regression analysis. Interestingly, we found that preoperative level of ALP was one of the most important independent predictors of recurrence, even more important that α-fetoprotein (AFP) as we noticed that elevation of ALP above (82 U/L) predicted poor prognosis in patients where AFP levels was less than 66 ng/ml. It is worth to mention that ALP was statistically related to other liver function tests, but not tumor characters by hierarchical clustering; which means that we were able to correlate ALP with prognosis statistically, but not with pathological criteria of the tumor; to elucidate these finding, further basic science research is required. Conclusion: ALP among liver function tests, in addition to other tumor characters were independent factors for DFS and OS; our results suggest that preoperative ALP levels could be utilized to monitor and predict recurrence in high risk HCC patients. © 2011 The Society for Surgery of the Alimentary Tract. Source

Yu M.-C.,Chang Gung Memorial Hospital | Yu M.-C.,Chang Gung University | Lee Y.-S.,Ming Chuan University | Lee Y.-S.,Genomic Medicine Research Core Laboratory | And 6 more authors.
Annals of Surgical Oncology | Year: 2012

Background: Early detection and following appropriate treatments of hepatocellular carcinoma (HCC) is still the gold standard for favored outcome of HCC patients; nevertheless, a small portion of hepatitis B virus (HBV)-related small HCC (<5 cm) patients got poor prognosis. Furthermore, the study for small HBV-HCC was limited. Therefore, the aim of this study was to explore the potential genetic signature for HBV-related small HCC as novel prognostic factors. Methods: We examined expression profiles of HBV-related small HCC using an Affymetrix U133A GeneChip, evaluated differential gene expression by quantitative real-time polymerase chain reaction (qRT-PCR), and finally validated these expression patterns by immunohistochemistry (IHC). Results:: A total of 57 genes were differentially expressed between tumor and normal parts (n = 20 pairs) using Affymetrix U133A chip, and 16 genes were further evaluated by qRT-PCR. The result was compatible with the finding of oligonucleotide microarray (Pearson's correlation, r = 0.87). Furthermore, the expression pattern in HCC tissue by IHC in another group of small HBV-HCC (n = 100) showed overexpression of either osteopontin (OPN) or glypican 3 (GPC3) is an independent prognostic factor for disease-free survival (DFS) in HBV-positive small HCC (P < 0.01 and 0.03, respectively). Long-term DFS and overall survival (OS) for small HBV-HCC patients with high risk (both elevated GPC3 +/OPN+) were DFS 0%, OS 0%, respectively; on the other hand, DFS and OS in patients with moderate (only 1 gene elevated) or low (OPN-/GPC3-) risk were 35.0 and 46.5%, respectively. Conclusions: Elevation of both OPN and GPC3 may act as an adverse indicator for HBV-related small HCC patients after curative resection. © 2011 Society of Surgical Oncology. Source

Tran N.T.T.,National Taiwan University of Science and Technology | Wang T.-H.,Chang Gung University | Wang T.-H.,Genomic Medicine Research Core Laboratory | Lin C.-Y.,Chang Gung University | Tai Y.,National Taiwan University of Science and Technology
Biochemical Engineering Journal | Year: 2013

We have developed a simple approach to synthesize gold nanoparticle (AuNP) by utilizing the anti-cancer drug, methotrexate (MTX), as both the reducing agent and the capping molecule. MTX-conjugated AuNPs (MTX-AuNPs) of various sizes (~3 and ~20. nm) can be obtained in a one-pot synthesis. We utilized transmission electron microscopy, X-ray diffraction, and UV-vis spectroscopy to characterize these nanoparticles, and Fourier-transform infrared (FTIR) spectroscopy and Raman spectroscopy to investigate the chemical interactions between the MTX and AuNPs. To examine the cancer therapeutic effect of these nanoparticles, we applied the lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay tests. The results demonstrated that the MTX-AuNPs of small size (~3. nm) exhibited considerably high cytotoxic effects in human choriocarcinoma cell lines compared to the effects of equal doses of free MTX; these results suggest that anti-cancer drug-conjugated AuNPs have an enhanced therapeutic effect. © 2013 Elsevier B.V. Source

Yang S.-W.,Chang Gung University | Tsai C.-N.,Chang Gung University | Lee Y.-S.,Ming Chuan University | Lee Y.-S.,Genomic Medicine Research Core Laboratory | Chen T.-A.,Chang Gung University
Journal of Oral and Maxillofacial Surgery | Year: 2011

Purpose: To evaluate the associated factors of recurrence in patients who received laser surgery for dysplastic oral leukoplakia. Materials and Methods: Clinicopathologic data of patients and their human papillomavirus genome status were used to analyze their association with recurrence after surgery. Results: Of 114 enrolled patients, 90 were men and 24 were women with an average age of 49.7 ± 12.2 years, and follow-up was 1.75 to 9.1 years (mean, 3.4 ± 1.3 years). Recurrence after surgery occurred in 20 patients (17.5%). Thirteen patients had malignant transformation (11.4%). Twenty patients showed positivity for human papillomavirus (21.7%). Univariate analysis showed that patients who did not quit smoking or chewing betel quid after surgical treatment or whose oral leukoplakia took the form of widespread multiple-focus lesions, nonhomogeneous leukoplakia, and higher-grade dysplasia tended to have recurrence. Among these significant risk factors, continuous smoking after surgical treatment (odds ratio, 3.82) and widespread multiple-focus lesions (odds ratio, 4.54) were the independent prognostic factors for recurrence using multivariate logistic regression analysis. Those who did not quit chewing betel quid or smoking cigarettes were 19.8 or 9.7 times, respectively, more likely to develop recurrence than those who did quit. Conclusions: This study suggests that continuous smoking after surgical treatment and widespread multiple-focus lesions are the prognostic indicators for recurrence after laser surgery. Changes in oral habits can be of great importance to the outcome of laser surgery of dysplastic oral leukoplakia. © 2011 American Association of Oral and Maxillofacial Surgeons. Source

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