Sun Yat Sen Cancer Center

Taipei, Taiwan

Sun Yat Sen Cancer Center

Taipei, Taiwan

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Yang P.S.,Sun Yat Sen Cancer Center | Yang P.S.,National Yang Ming University | Chen C.M.,Sun Yat Sen Cancer Center | Liu M.C.,Sun Yat Sen Cancer Center | And 7 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: To define a subgroup of patients at high risk of locoregional recurrence (LRR) who might be benefit from postmastectomy radiotherapy in invasive breast cancer and tumor size <5 cm with one to three involved axillary lymph nodes (T1-2 N1). Methods and Materials: Between April 1991 and December 2005, 544 patients with T1-2 N1 invasive breast cancer were treated with modified radical mastectomy. Of the 544 patients, 383 patients (70.4%) had no radiotherapy, and 161 patients (29.6%) received radiotherapy. We retrospectively compared these two patient groups. Results: With a median follow-up of 40.3 months, LRR occurred in 40 (7.4%) of 544 patients. On univariate analysis, high nuclear grade (p = 0.04), negative estrogen receptor (ER) status (p = 0.001), presence of lymphovascular invasion (LVI) (p = 0.003), and no radiotherapy (p = 0.0015) were associated with a significantly higher rate of LRR. Negative ER status (hazard ratio = 5.1) and presence of LVI (hazard ratio = 2.5) were the risk factors for LRR with statistical significance in the multivariate analysis. Radiotherapy reduced the LRR in patients with the following characteristics: age <40 years, T2 stage, high nuclear grade, negative ER status, and presence of LVI. For 41 patients with negative ER and positive LVI status, radiotherapy can reduce LRR from 10 of 25 (40%) to 2 of 16 (12.5%) and increase the 5-year overall survival from 43.7% to 87.1%. Conclusion: Radiotherapy can reduce LRR and increase survival in T1-2 N1 breast cancer patients with negative ER status and presence of LVI. © 2010 Elsevier Inc. All rights reserved.


Wang B.-Y.,Sun Yat Sen Cancer Center | Wang B.-Y.,Chung Shan Medical University | Wang B.-Y.,Taipei Veterans General Hospital | Tu C.-C.,Taipei Veterans General Hospital | And 3 more authors.
Annals of Thoracic Surgery | Year: 2013

Background: Reports of single-incision thoracoscopic lobectomy and segmentectomy are rare. In this article, we present our experience with single-incision thoracoscopic lobectomy and segmentectomy and radical mediastinal lymph node dissection. Methods: Nineteen patients with early-stage malignancy or benign lung disease were treated with single-incision thoracoscopic lobectomy and segmentectomy at our institution between November 2010 and May 2012. The surgical approach began with a single incision at the fifth or sixth intercostal space at the anterior axillary line. A 10-mm video camera and working instruments were used at the same time in this incision site throughout the surgery. The perioperative variables and outcomes were collected and analyzed retrospectively. Results: For the 19 patients included in the final analysis, 14 lobectomies and 5 segmentectomies were performed successfully without need for conversion. Among the 19 patients who underwent single-port video-assisted thoracoscopic surgery (VATS), 15 cases of cancer and 4 cases of benign pulmonary disease were noted. The mean operative time was 156 ± 46 minutes, and the median number of lymph nodes retrieved was 22.9 ± 9.8. Average blood loss was 38.4 ± 25.9 mL. There were no deaths 30 days after surgery, and 2 cases of atelectasis were observed. Conclusions: Single-port VATS lobectomy and segmentectomy is safe and feasible for selected patients. © 2013 by The Society of Thoracic Surgeons.


Yang P.-S.,National Yang Ming University | Yang P.-S.,Mackay Memorial Hospital | Yin P.-H.,Taipei Veterans General Hospital | Tseng L.-M.,National Yang Ming University | And 7 more authors.
Cancer Science | Year: 2011

The expression of Rab proteins has been associated with cancer. However, few data are available on Rab5A expression in human breast cancer or its impact on disease progression. First, we examined the functional role of Rab5A in breast cancer cells. The expression of Rab5A in MDA-MB-231 cells can be stimulated by epidermal growth factor in a dose-dependent manner. The epidermal growth factor-induced increase of Rab5A expression correlated well with enhanced migration in wound healing migration assays in these cells. Furthermore, we evaluated the expression of Rab5A in breast cancer specimens using immunohistochemical staining, then analyzed the relationship between the expression of Rab5A and clinicopathological parameters. The increased expression of Rab5A protein in 123 breast cancer samples was associated with higher histological grade (P=0.004), more lymphovascular invasion (P=0.027), more axillary lymph node (LN) metastasis (P=0.008), and a higher number of axillary LN metastases (P=0.043). Among 218 axillary LNs of more than 10 breast cancer patients with node metastases, 167 metastatic LNs were found to have increased Rab5A expression. Rab5A is associated with axillary LN metastasis in breast cancer patients. © 2011 Japanese Cancer Association.


Chen Y.J.,National Taiwan University | Tsai K.S.,National Taiwan University Hospital | Chiu C.Y.,National Taiwan University | Yang T.H.,National Taiwan University Hospital | And 5 more authors.
Journal of Orthopaedic Research | Year: 2013

Osteoarthritis (OA) is a degenerative joint disease involving a combination of cartilage degradation and inflammation. EGb761, a standardized extract of Ginkgo biloba leaves, holds an anti-inflammatory potency. Here, we determined whether EGb761 could inhibit lipopolysaccharide (LPS)- and IL-1β-induced inflammatory responses in human articular chondrocytes and apply the chondroprotection in OA rats. We found that LPS markedly induced the productions of PGE2 and NO and the protein expressions of COX-2 and iNOS in human chondrocytes. LPS was also seen to up-regulate the expressions of toll-like receptor-4 (TLR4), its downstream signal TNF receptor-associated factor 6 (TRAF6), and nuclear factor (NF)-κB signaling. These LPS-induced inflammatory responses were efficaciously reversed by EGb761 and its active components quercetin and kampferol. The similar results could be observed by using IL-1β as an in vitro model to mimic an inflammatory response. In an OA rat model, PGE2 and NO levels in blood, the histological alterations, and COX-2 and nitrotyrosine expressions in cartilages were markedly increased, which were effectively reversed by EGb761. Our results suggested that EGb761 exerts the anti-inflammatory effects on human articular chondrocytes and OA rats. © 2013 Orthopaedic Research Society.


Chen Y.J.,National Taiwan University | Tsai K.S.,National Taiwan University Hospital | Chan D.C.,National Taiwan University Hospital | Lan K.C.,Tri Service General Hospital | And 4 more authors.
Journal of Orthopaedic Research | Year: 2014

Proinflammatory cytokine interleukin-1β (IL-1β) stimulates several mediators of cartilage degradation and plays an important role in the pathogenesis of osteoarthritis (OA). Honokiol, a low molecular weight natural product isolated from the Magnolia officinalis, has been shown to possess anti-inflammatory effect. Here, we used an in vitro model of cartilage inflammation to investigate the therapeutic potential of honokiol in OA. Human OA chondrocytes were cultured and pretreated with honokiol (2.5-10 μM) with or without IL-1β (10 ng/ml). Nitric oxide (NO) production was quantified by Griess reagent. Prostaglandin (PG)E2, metalloproteinase-13 (MMP-13), and interleukin-6 (IL-6) productions were quantified by enzyme-linked immunosorbent assay. The expressions of collagen II, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor κB (NF-κB)-related signaling molecules were determined by Western blotting. Our data showed that IL-1β markedly stimulated the expressions of iNOS and COX-2 and the productions of NO, PGE2, and IL-6, which could be significantly reversed by honokiol. Honokiol could also suppress the IL-1β-triggered activation of IKK/IκBα/NF-κB signaling pathway. Moreover, honokiol significantly inhibited the IL-1β-induced MMP-13 production and collagen II reduction. Taken together, the present study suggests that honokiol may have a chondroprotective effect and may be a potential therapeutic choice in the treatment of OA patients. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:573-580, 2014. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.


Sun J.-H.,Chang Gung University | Tsai J.-S.,Sun Yat Sen Cancer Center | Huang C.-H.,Chang Gung University | Lin C.-H.,Chang Gung University | And 5 more authors.
Diabetes Research and Clinical Practice | Year: 2012

Aims: To elucidate the risk factors for lower extremity amputation (LEA) in patients of diabetic foot disease with different Wagner gradings. Methods: This study was conducted in a multidisciplinary diabetic foot care center. Demographic characteristics, laboratory data, disease history, ankle brachial pressure index (ABI) and Wagner classification were considered as independent variables to predict the therapeutic outcome (major LEA, minor LEA, and non-amputation). Risk factors for LEA in different Wagner grades were further analyzed. Multivariate stepwise ordinal logistic regression was performed. Results: Of 789 study subjects, 19.9% received major LEA and 22.9% received minor LEA. Higher Wagner grade, lower ABI, serum albumin and hemoglobin, and elevated white blood cell (WBC) count were significantly associated with an increased risk of LEA. When stratified by Wagner classification, most of the above predictors and estimated glomerular filtration (eGFR) were detected only in grade 3. While in grades 2 and 4, WBC count was identified as primary predictor positively associated with an increased risk of LEA. Conclusions: Wagner classification remarkably influenced the potential risk factors for LEA, showing different predictors in different grades. The traditionally recognized predictors for diabetic foot amputation such as lower ABI, albumin or eGFR were almost exclusively found in patients with Wagner grade 3. © 2011 Elsevier Ireland Ltd.


Peng H.-C.,Tamkang University | Wang Y.-H.,Sun Yat Sen Cancer Center | Wen C.-C.,Tamkang University | Wang W.-H.,Tamkang University | And 2 more authors.
Comparative Biochemistry and Physiology - C Toxicology and Pharmacology | Year: 2010

We used a green fluorescent kidney line, Tg(wt1b:GFP), as a model to access the acetaminophen (AAP)-induced nephrotoxicity dynamically. Zebrafish (Danio rerio) embryos at different developmental stages (12-60 hpf) were treated with different dosages of AAP (0-45 mM) for different time courses (12-60 h). Results showed that zebrafish embryos exhibited no evident differences in survival rates and morphological changes between the mock-treated control (0 mM) and 2.25 mM AAP-exposure (12-72 hpf) groups. In contrast, after higher doses (22.5 and 45 mM) of exposure, embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tube, pronephric duct, and a cystic and atrophic glomerulus. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AAP increased. Interestingly, under the same exposure time course (12 h) and dose (22.5 mM), embryos displayed higher percentages of severe defects at earlier developmental stage of exposure (12-24 hpf), whereas embryos displayed higher percentages of mild defects at later exposure (60-72 hpf). With an exposure time course less than 24 h of 45 mM AAP, no embryo survived by the developmental stage of 72 hpf. These results indicated that AAP-induced nephrotoxicity depended on the exposure dose, time course and developmental stages. Immunohistochemical experiments showed that the cells' morphologies of the pronephric tube, pronephric duct and glomerulus were disrupted by AAP, and consequently caused cell death. Real-time RT-PCR revealed embryos after AAP treatment decreased the expression of cox2 and bcl2, but increased p53 expression. In conclusion, AAP-induced defects on glomerulus, pronephric tube and pronephric duct could be easily and dynamically observed in vivo during kidney development in this present model. © 2010 Elsevier Inc. All rights reserved.


Huang W.-T.,Yuanpei University | Shih K.-N.,Yuanpei University | Lin Y.-Z.,Yuanpei University | Lin Y.-Z.,Sun Yat Sen Cancer Center
Journal of Bionanoscience | Year: 2013

This study evaluated the synergistic effects of the hot water extract of Radix Dipsaci, a type of Chinese herbal medicine, with low-intensity pulsed ultrasound stimulation on the survival rate, alkaline phosphatase (ALP) activity, and mineralization of osteoblast-like cells (MG-63) to provide a basic reference of adjuvant therapy for bone fractures. We examined the synergistic effect of 50 μg/ml Radix Dipsaci solution combined with low-intensity pulsed ultrasound (LIPUS) at the intensity of 0.05, 0.15, and 0.3 W/cm2 in pulsed mode at 20% (2:8 duty cycle). The study results indicate that: (1) the survival rate of MG-63 cells at the three stimulation levels was 115%, 114%, and 104%. Under 0.3 W/cm2 intensity, the addition of the Radix Dipsaci water extract significantly increased the cell proliferation rate (24.5±4.3%; p <.05); (2) compared to LIPUS stimulation, additional use of Radix Dipsaci significantly improved the ALP activity in MG-63 cells (p < .05), where the ALP activity observed at the first day was 106%, and the figure at the second day was 105%; (3) the combination of Radix Dipsaci and LIPUS increased the mineralization level by approximately 2.3%, which was similar to the effect of using LIPUS alone. The combination of Radix Dipsaci and LIPUS slightly improved the ALP activity and mineralization level of MG-63 cells. Copyright © 2013 American Scientific Publishers. All rights reserved.


Chern M.-C.,Sun Yat Sen Cancer Center | Chuang V.P.,Sun Yat Sen Cancer Center | Liang C.-T.,Sun Yat Sen Cancer Center | Lin Z.H.,Sun Yat Sen Cancer Center | Kuo T.-M.,Sun Yat Sen Cancer Center
Journal of Vascular and Interventional Radiology | Year: 2014

Purpose To evaluate the safety and efficacy of transarterial chemoembolization and to identify the prognostic factors associated with survival in patients with hepatocellular carcinoma (HCC) and portal vein (PV) invasion. Materials and Methods From January 2006 to March 2012, 50 patients with HCC invading into the PV (Barcelona Clinic Liver Cancer stage C) were treated with transarterial chemoembolization. The parenchymal tumor and PV tumor were confirmed by multidetector computed tomography (CT) and angiography. There were 14 patients with right PV tumor, 12 patients with left PV tumor, and 24 patients with main PV tumor. The response was evaluated by multidetector CT using Response Evaluation Criteria in Solid Tumors. Patients with residual tumors received repeated transarterial chemoembolization every 6-8 weeks unless the patients achieved complete remission or developed contraindications. Results The median survival period of the entire group was 6.2 months (range, 1.7-50.9 mo), and the overall response rate was 42% (21 of 50 patients). The 6-month, 12-month, 24-month, and 36-month survival rates were 54%, 22%, 10%, and 8%. There were no instances of 30-day mortality or acute liver failure related to transarterial chemoembolization. The median survival of the 21 responders was 10.5 months, and the median survival of the 29 nonresponders was 5.5 months (P <.001). In both univariate and multivariate analyses, only the response to transarterial chemoembolization (hazard ratio = 0.25, P <.001) and the absence of ascites (hazard ratio = 0.24, P =.01) were significant prognostic factors. Conclusions Transarterial chemoembolization is a safe and effective treatment for HCC with major PV invasion. The response to transarterial chemoembolization and the ascites status were the most significant predictive factors for prolonged survival. © 2014 SIR.


Rapidly growing cancer cells secrete growth-promoting polypeptides and have increased proteolytic activity, contributing to tumor progression and metastasis. Their presentation in malignant pleural effusion (MPE) and their predictive value for the outcome of pleurodesis and survival were studied.Between February 2011 and March 2012, MPE samples were prospectively collected from 61 patients. Twenty-five patients with non-malignant pleural effusion in the same period were included as controls. Pleural fluid osteopontin (OPN), vascular endothelial growth factor (VEGF), and urokinase-type plasminogen activator (uPA) concentrations were measured.Patients with MPE had higher pleural fluid OPN, VEGF, and uPA concentrations than those with non-malignant pleural effusion, but only differences in VEGF were statistically significant (p=0.045). Patients with distant metastases had significantly elevated pleural fluid VEGF concentrations than those without (p=0.004). Pleural fluid OPN, VEGF, and uPA concentrations were positively correlated in most patients. However, there was no significant difference in pleural fluid OPN, VEGF, and uPA concentrations between patients with successful pleurodesis and those without. There was also no significant difference in cancer-specific survival between sub-groups with higher and lower pleural fluid OPN, VEGF, or uPA concentrations. Patients with successful pleurodesis had significantly longer cancer-specific survival than those without (p=0.015).Pleural fluid OPN, VEGF, and uPA concentrations are elevated in MPE but are not satisfactory predictors of pleurodesis outcome or survival. Patients with higher pleural fluid VEGF concentration have higher risk of distant metastasis. Evaluating the benefits of therapy targeting the VEGF pathway in these patients warrants further studies.

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