157 results on '"Ming-Cheng Chang"'
Search Results
2. Develop companion radiopharmaceutical YKL40 antibodies as potential theranostic agents for epithelial ovarian cancer
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Ming-Cheng Chang, Ping-Fang Chiang, Yu-Jen Kuo, Cheng-Liang Peng, I.-Chun Chen, Chia-Yen Huang, Chi-An Chen, and Ying-Cheng Chiang
- Subjects
Epithelial ovarian cancer ,Radiopharmaceutical agent ,In-111/Lu-177-DTPA-YKL40 neutralizing antibodies ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Epithelial ovarian cancer (EOC) is usually diagnosed at an advanced stage and has poor prognosis. Theranostic agents are the current trend in drug development, but are lacking in EOC. YKL40 is predominantly expressed and involved in tumorigenesis in EOC. In this study, we developed a companion theranostic agent targeting YKL40. We measured YKL40 expression levels in ascites using ELISA and correlated them with the clinical outcomes of patients with EOC. We developed radionuclide labeled In-111/Lu-177-DTPA-YKL40 neutralizing antibodies and investigated their radiochemical purity, SPECT/CT imaging, bio-distribution, and therapeutic responses in ovarian cancer xenograft mice. We demonstrated that YKL40 expression levels in ascites were significantly higher in EOC patients with serous histological type, high tumor grade, advanced stage, tumor recurrence, chemoresistance, and tumor-related death. The radiochemical purity of In-111/Lu-177-DTPA-YKL40 neutralizing antibodies reached more than 90% after 24 h of labeling. SPECT/CT imaging showed significant accumulation of In-111-DTPA-YKL40 and Lu-177-DTPA-YKL40 antibodies at the tumor site of ovarian cancer xenograft mice 24 h after administration. Lu-177-DTPA-YKL40 antibodies significantly inhibited tumor growth in ovarian cancer xenograft mice. Our study indicated that In-111/Lu-177-DTPA-YKL40 neutralizing antibodies could be potential companion theranostic agents for patients with EOC.
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- 2022
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3. Multifunctional Cyanine-Based Theranostic Probe for Cancer Imaging and Therapy
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Cheng-Liang Peng, Ying-Hsia Shih, Ping-Fang Chiang, Chun-Tang Chen, and Ming-Cheng Chang
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multi-modality ,cyanine dye ,near-infrared fluorescence imaging ,nuclear imaging ,photothermal therapy ,targeted radionuclide therapy ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Cancer is one of the leading causes of death in the world. A cancer-targeted multifunctional probe labeled with the radionuclide has been developed to provide multi-modalities for NIR fluorescence and nuclear imaging (PET, SPECT), for photothermal therapy (PTT), and targeted radionuclide therapy of cancer. In this study, synthesis, characterization, in vitro, and in vivo biological evaluation of the cyanine-based probe (DOTA-NIR790) were demonstrated. The use of cyanine dyes for the selective accumulation of cancer cells were used to achieve the characteristics of tumor markers. Therefore, all kinds of organ tumors can be targeted for diagnosis and treatment. The DOTA-NIR790 labeled with lutetium-111 could detect original or metastatic tumors by using SPECT imaging and quantify tumor accumulation. The β-emission of 177Lu-DOTA-NIR790 can be used for targeted radionuclide therapy of tumors. The DOTA-NIR790 enabled imaging by NIR fluorescence and by nuclear imaging (SPECT) to monitor in real-time the tumor accumulation and the situation of cancer therapy, and to guide the surgery or the photothermal therapy of the tumor. The radionuclide-labeled heptamethine cyanine based probe (DOTA-NIR790) offers multifunctional modalities for imaging and therapies of cancer.
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- 2021
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4. Effect of Cerenkov Radiation-Induced Photodynamic Therapy with 18F-FDG in an Intraperitoneal Xenograft Mouse Model of Ovarian Cancer
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Yi-An Chen, Jia-Je Li, Syue-Liang Lin, Cheng-Hsiu Lu, Sain-Jhih Chiu, Fong-Shya Jeng, Chi-Wei Chang, Bang-Hung Yang, Ming-Cheng Chang, Chien-Chih Ke, and Ren-Shyan Liu
- Subjects
ovarian cancer ,photodynamic therapy ,Cerenkov radiation ,18F-FDG ,photosensitizer ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Ovarian cancer (OC) metastases frequently occur through peritoneal dissemination, and they contribute to difficulties in treatment. While photodynamic therapy (PDT) has the potential to treat OC, its use is often limited by tissue penetration depth and tumor selectivity. Herein, we combined Cerenkov radiation (CR) emitted by 18F-FDG accumulated in tumors as an internal light source and several photosensitizer (PS) candidates with matched absorption bands, including Verteporfin (VP), Chlorin e6 (Ce6) and 5′-Aminolevulinic acid (5′-ALA), to evaluate the anti-tumor efficacy. The in vitro effect of CR-induced PDT (CR-PDT) was evaluated using a cell viability assay, and the efficiency of PS was assessed by measuring the singlet oxygen production. An intraperitoneal ES2 OC mouse model was used for in vivo evaluation of CR-PDT. Positron emission tomography (PET) imaging and bioluminescence-based imaging were performed to monitor the biologic uptake of 18F-FDG and the therapeutic effect. The in vitro studies demonstrated Ce6 and VP to be more effective PSs for CR-PDT. Moreover, VP was more efficient in the generation of singlet oxygen and continued for a long time when exposed to fluoro-18 (18F). Combining CR emitted by 18F-FDG and VP treatment not only significantly suppressed tumor growth, but also prolonged median survival times compared to either monotherapy.
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- 2021
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- View/download PDF
5. Apply DEMATEL to Analyzing Key Barriers to Implementing the Circular Economy: An Application for the Textile Sector
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Wen-Kuo Chen, Venkateswarlu Nalluri, Hsing-Chun Hung, Ming-Cheng Chang, and Ching-Torng Lin
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circular economy (CE) ,key barriers ,Fuzzy Delphi Method (FDM) ,decision-making trial and evaluation laboratory (DEMATEL) ,textile sector ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Continuous improvement and innovation are solid foundations for the textile sector to maintain excellent growth and active sustainability. As the limited resources possessed by textile companies generally result in the incapability of implementing circular economy (CE) strategies simultaneously, recently, researchers advocate that organizations should analyze the influential inter-relationship between key barriers to explore the more dominant determinants for designing improved actions for implementing CE in the textile sector. CE implementation in the textile sector appears to be in its infancy. Although much attention has been paid to CE implementation barriers, the present study tries to fill this research gap by analyzing the causal relationships among the CE barriers in the textile sector. Therefore, the twelve barriers are identified by an extensive literature review, and the application of the Fuzzy Delphi Method (FDM) based on the expert options from the textile sector. Subsequently, the causal inter-relationship among the key CE barriers is based on expert opinions using the decision-making trial and evaluation laboratory (DEMATEL). The results of this study indicate that three key barriers require quick action: “consumers lack knowledge and awareness about reused/recycle (B1)”, “lack of successful business models and frameworks to implement CE (B3)”, and “lack of an information exchange system between different stakeholders (B8)”. In addition, the results provide significant managerial implications, including implementations of CE in the textile sector. Not only should the government build regulations and friendly laws and encourage environmentally-friendly materials but the textile companies should also focus or monitor the recycling methods and quality to overcome the CE implementation issues. In addition, this study contributes to the textile sector transition toward CE by using the novel methodology for determining and prioritizing the key barriers. Finally, this work would help top management and the practitioners to better design effective infrastructural strategies for the textile sector transition towards CE.
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- 2021
- Full Text
- View/download PDF
6. Translating Research for the Radiotheranostics of Nanotargeted 188Re-Liposome
- Author
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Chih-Hsien Chang, Ming-Cheng Chang, Ya-Jen Chang, Liang-Cheng Chen, Te-Wei Lee, and Gann Ting
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liposome ,nanoliposome ,nuclear imaging ,radiotheranostics ,rhenium-188 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Nanoliposomes are one of the leading potential nano drug delivery systems capable of targeting chemotherapeutics to tumor sites because of their passive nano-targeting capability through the enhanced permeability and retention (EPR) effect for cancer patients. Recent advances in nano-delivery systems have inspired the development of a wide range of nanotargeted materials and strategies for applications in preclinical and clinical usage in the cancer field. Nanotargeted 188Re-liposome is a unique internal passive radiotheranostic agent for nuclear imaging and radiotherapeutic applications in various types of cancer. This article reviews and summarizes our multi-institute, multidiscipline, and multi-functional studied results and achievements in the research and development of nanotargeted 188Re-liposome from preclinical cells and animal models to translational clinical investigations, including radionuclide nanoliposome formulation, targeted nuclear imaging, biodistribution, pharmacokinetics, radiation dosimetry, radiation tumor killing effects in animal models, nanotargeted radionuclide and radio/chemo-combination therapeutic effects, and acute toxicity in various tumor animal models. The systemic preclinical and clinical studied results suggest 188Re-liposome is feasible and promising for in vivo passive nanotargeted radionuclide theranostics in future cancer care applications.
- Published
- 2021
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7. Hyaluronan-Loaded Liposomal Dexamethasone–Diclofenac Nanoparticles for Local Osteoarthritis Treatment
- Author
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Ming-Cheng Chang, Ping-Fang Chiang, Yu-Jen Kuo, Cheng-Liang Peng, Kuan-Yin Chen, and Ying-Cheng Chiang
- Subjects
liposomal nanoparticle ,dexamethasone ,diclofenac ,osteoarthritis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Osteoarthritis (OA) remains one of the common degenerative joint diseases and a major cause of pain and disability in older adult individuals. Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) (such as diclofenac, DIC) or intra-articular injected gluco-corticosteroids (such as dexamethasone, DEX) were the conventional treatment strategies for OA to reduce joint pain. Current limitations for both drugs including severe adverse effects with risks of toxicity were noted. The aim of the present study was to generate a novel OA treatment formulation hyaluronic acid (HA)-Liposomal (Lipo)-DIC/DEX to combat joint pain. The formulation was prepared by constructing DIC with DEX-loaded nanostructured lipid carriers Lipo-DIC/DEX mixed with hyaluronic acid (HA) for prolonged OA application. The prepared Lipo-DIC/DEX nanoparticles revealed the size as 103.6 ± 0.3 nm on average, zeta potential as −22.3 ± 4.6 mV, the entrapment efficiency of 90.5 ± 5.6%, and the DIC and DEX content was 22.5 ± 4.1 and 2.5 ± 0.6%, respectively. Evidence indicated that HA-Lipo-DIC/DEX could reach the effective working concentration in 4 h and sustained the drug-releasing time for at least 168 h. No significant toxicities but increased cell numbers were observed when HA-Lipo-DIC/DEX co-cultured with articular chondrocytes cells. Using live-animal In vivo imaging system (IVIS), intra-articular injection of each HA-Lipo-DIC/DEX sufficed to reduce knee joint inflammation in OA mice over a time span of four weeks. Single-dose injection could reduce the inflammation volume down to 77.5 ± 5.1% from initial over that time span. Our results provided the novel drug-releasing formulation with safety and efficiency which could be a promising system for osteoarthritis pain control.
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- 2021
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8. Developing a Prognostic Gene Panel of Epithelial Ovarian Cancer Patients by a Machine Learning Model
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Tzu-Pin Lu, Kuan-Ting Kuo, Ching-Hsuan Chen, Ming-Cheng Chang, Hsiu-Ping Lin, Yu-Hao Hu, Ying-Cheng Chiang, Wen-Fang Cheng, and Chi-An Chen
- Subjects
chemotherapy ,microarray ,ovarian cancer ,predictive model ,machine learning ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Epithelial ovarian cancer patients usually relapse after primary management. We utilized the support vector machine algorithm to develop a model for the chemo-response using the Cancer Cell Line Encyclopedia (CCLE) and validated the model in The Cancer Genome Atlas (TCGA) and the GSE9891 dataset. Finally, we evaluated the feasibility of the model using ovarian cancer patients from our institute. The 10-gene predictive model demonstrated that the high response group had a longer recurrence-free survival (RFS) (log-rank test, p = 0.015 for TCGA, p = 0.013 for GSE9891 and p = 0.039 for NTUH) and overall survival (OS) (log-rank test, p = 0.002 for TCGA and p = 0.016 for NTUH). In a multivariate Cox hazard regression model, the predictive model (HR: 0.644, 95% CI: 0.436⁻0.952, p = 0.027) and residual tumor size < 1 cm (HR: 0.312, 95% CI: 0.170⁻0.573, p < 0.001) were significant factors for recurrence. The predictive model (HR: 0.511, 95% CI: 0.334⁻0.783, p = 0.002) and residual tumor size < 1 cm (HR: 0.252, 95% CI: 0.128⁻0.496, p < 0.001) were still significant factors for death. In conclusion, the patients of high response group stratified by the model had good response and favourable prognosis, whereas for the patients of medium to low response groups, introduction of other drugs or clinical trials might be beneficial.
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- 2019
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9. High-risk human papillomavirus, other than type 16/18, in predominantly older Taiwanese women with high-grade cervical preinvasive lesions
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Ying-Cheng Chiang, Wen-Fang Cheng, Yu-Li Chen, Ming-Cheng Chang, Chang-Yao Hsieh, Ming-Chieh Lin, and Chi-An Chen
- Subjects
high-grade squamous intraepithelial lesion ,human papillomavirus ,Taiwanese women ,Gynecology and obstetrics ,RG1-991 - Abstract
Objective: To investigate the various genotypes of human papillomavirus (HPV) in Taiwanese women patients with abnormal cervical cytology and analyze the associations between HPV types, cervical preinvasive lesions, and the medical characteristics of these patients. Materials and Methods: We performed HPV genotyping GeneChip procedures and colposcopies for 784 women with abnormal Papanicolaou smears. The characteristics of the patients and the status of the HPV infection were correlated. Results: A total of 706 (90.1%) of the 784 women were positive for HPV infection, including 641 patients with high-risk HPV (HR-HPV). Among the patients with high-grade squamous intraepithelial lesions (HSILs), the average age of the 273 patients with other HR-HPV types (48.6 ± 13.8 years) was significantly older than the 222 patients infected with HPV 16/18 (39.8 ± 11.8 years) (p
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- 2013
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10. New primers for methylation-specific polymerase chain reaction enhance specificity of detecting STAT1 methylation
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Ming-Cheng Chang, Ying-Cheng Chiang, Chih-Ming Ho, Yu-Li Chen, Chi-An Chen, Wen-Fang Cheng, and Cheng-Yang Chou
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methylation ,polymerase chain reaction ,signal transducer and activator of transcription 1 ,Gynecology and obstetrics ,RG1-991 - Abstract
Objective: Signal transducer and activator of transcription (STAT)1 is a key tumor suppressor, which is always methylated in a variety of human cancers. However, nonspecific primers for the detection of specific promoter hypermethylation of STAT1 gene can lead to false-positive or false-negative results for gene methylation. Materials and Methods: We designed new primers for the detection of STAT1 methylation and compared the sensitivities and specificities of these new primers with prior published primers by methylation-specific polymerase chain reaction (PCR) from ovarian clear cell carcinomas. The mRNA expression levels of STAT1 in these cancerous tissues were also evaluated by reverse-transcriptase PCR and correlated with the results of promoter methylation of STAT1 gene. Results: Nine (39%) of the 23 samples detected by the new primers and 13 samples (56%) detected by prior published primers showed STAT1 methylation. A direct DNA sequencing test revealed that four of the 13 samples (30.8%) showed false positivity for STAT1 methylation using the prior published primers. In contrast, none of the nine samples was false-positive for the detection of STAT1 methylation using the new primers. The new primers for the detection of STAT1 methylation showed 100% specificity and 100% sensitivity without false positivity. Conclusion: Specific primers for methylation-specific PCR are mandatory for the accurate detection of STAT1 gene methylation. Besides, specific primers can generate correct interpretation of STAT1 gene methylation, and its correlation with the clinicopathological characteristics and outcome of cancer patients.
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- 2012
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11. Fusion protein vaccines targeting two tumor antigens generate synergistic anti-tumor effects.
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Wen-Fang Cheng, Ming-Cheng Chang, Wei-Zen Sun, Yu-Wei Jen, Chao-Wei Liao, Yun-Yuan Chen, and Chi-An Chen
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Medicine ,Science - Abstract
INTRODUCTION: Human papillomavirus (HPV) has been consistently implicated in causing several kinds of malignancies, and two HPV oncogenes, E6 and E7, represent two potential target antigens for cancer vaccines. We developed two fusion protein vaccines, PE(ΔIII)/E6 and PE(ΔIII)/E7 by targeting these two tumor antigens to test whether a combination of two fusion proteins can generate more potent anti-tumor effects than a single fusion protein. MATERIALS AND METHODS: In vivo antitumor effects including preventive, therapeutic, and antibody depletion experiments were performed. In vitro assays including intracellular cytokine staining and ELISA for Ab responses were also performed. RESULTS: PE(ΔIII)/E6+PE(ΔIII)/E7 generated both stronger E6 and E7-specific immunity. Only 60% of the tumor protective effect was observed in the PE(ΔIII)/E6 group compared to 100% in the PE(ΔIII)/E7 and PE(ΔIII)/E6+PE(ΔIII)/E7 groups. Mice vaccinated with the PE(ΔIII)/E6+PE(ΔIII)/E7 fusion proteins had a smaller subcutaneous tumor size than those vaccinated with PE(ΔIII)/E6 or PE(ΔIII)/E7 fusion proteins alone. CONCLUSION: Fusion protein vaccines targeting both E6 and E7 tumor antigens generated more potent immunotherapeutic effects than E6 or E7 tumor antigens alone. This novel strategy of targeting two tumor antigens together can promote the development of cancer vaccines and immunotherapy in HPV-related malignancies.
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- 2013
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12. Depletion of regulatory T lymphocytes reverses the imbalance between pro- and anti-tumor immunities via enhancing antigen-specific T cell immune responses.
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Yu-Li Chen, Ming-Cheng Chang, Chi-An Chen, Han-Wei Lin, Wen-Fang Cheng, and Chung-Liang Chien
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Medicine ,Science - Abstract
BACKGROUND: The regulatory T cells (Tregs) can actively suppress the immune responses. However, literature about detailed changes of host effective and suppressive immunities before and after depletion of Tregs in ovarian carcinomas, is rare. MATERIALS AND METHODS: Ovarian cancer patients and the ascitogenic animal model were employed. Immunologic profiles with flow cytometric analyses, immunohistochemistric staining, RT-PCR, ELISA, and ELISPOT assays were performed. In vivo depletion of Treg cells with the mAb PC61was also performed in the animal model. RESULTS: The cytokines, including IL-4 (p=0.017) and TNF-α (p=0.046), significantly decreased while others such as TGF-β (p=0.013), IL-6 (p=0.016), and IL-10 (p=0.018) were elevated in ascites of ovarian cancer patients, when the disease progressed to advanced stages. The ratio of CD8(+) T cell/Treg cell in ascites was also lower in advanced diseases than in early diseases (advanced 7.37 ± 0.64 vs. early 14.25 ± 3.11, p=0.037). The kinetic low-dose CD25 Ab depletion group had significantly lower intra-peritoneal tumor weight (0.20 ± 0.03 g) than the sequential high-dose (0.69 ± 0.06 g) and sequential low-dose (0.67 ± 0.07 g) CD25 Ab deletion groups (p=0.001) after 49 days of tumor challenge in the animal. The kinetic low-dose CD25 Ab depletion group generated the highest number of IFN-γ-secreting, mesothelin-specific T lymphocytes compared to the other groups (p
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- 2012
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13. Living Arrangements and Social Interaction of the Elderly in Taiwan
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Te-hsiung, Sun, primary and Ming-cheng, Chang, additional
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- 2018
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14. Enabling medium thick gate oxide devices in 22FDX® technology for switch and high-performance amplifier application
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Tom Herrmann, Alban Zaka, Zhixing Zhao, Binit Syamal, Wafa Arfaoui, Ruchil Jain, Ming-Cheng Chang, Sameer Jain, and Shih Ni Ong
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Materials Chemistry ,Electrical and Electronic Engineering ,Condensed Matter Physics ,Electronic, Optical and Magnetic Materials - Published
- 2023
15. Multifunctional Cyanine-Based Theranostic Probe for Cancer Imaging and Therapy
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Ying-Hsia Shih, Ming-Cheng Chang, Cheng-Liang Peng, Chun-Tang Chen, and Ping-Fang Chiang
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Near-Infrared Fluorescence Imaging ,Nuclear imaging ,Lutetium ,Theranostic Nanomedicine ,Mice ,chemistry.chemical_compound ,Medicine ,Cyanine ,Biology (General) ,Spectroscopy ,nuclear imaging ,Quinolinium Compounds ,Optical Imaging ,General Medicine ,Computer Science Applications ,Chemistry ,Female ,multi-modality ,Single Photon Emission Computed Tomography Computed Tomography ,photothermal therapy ,QH301-705.5 ,Mice, Nude ,cyanine dye ,Article ,Catalysis ,Inorganic Chemistry ,near-infrared fluorescence imaging ,In vivo ,Spect imaging ,Animals ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,QD1-999 ,neoplasms ,Fluorescent Dyes ,Radioisotopes ,business.industry ,Organic Chemistry ,Cancer ,Neoplasms, Experimental ,Photothermal therapy ,HCT116 Cells ,medicine.disease ,targeted radionuclide therapy ,chemistry ,A549 Cells ,Cancer cell ,Cancer research ,business - Abstract
Cancer is one of the leading causes of death in the world. A cancer-targeted multifunctional probe labeled with the radionuclide has been developed to provide multi-modalities for NIR fluorescence and nuclear imaging (PET, SPECT), for photothermal therapy (PTT), and targeted radionuclide therapy of cancer. In this study, synthesis, characterization, in vitro, and in vivo biological evaluation of the cyanine-based probe (DOTA-NIR790) were demonstrated. The use of cyanine dyes for the selective accumulation of cancer cells were used to achieve the characteristics of tumor markers. Therefore, all kinds of organ tumors can be targeted for diagnosis and treatment. The DOTA-NIR790 labeled with lutetium-111 could detect original or metastatic tumors by using SPECT imaging and quantify tumor accumulation. The β-emission of 177Lu-DOTA-NIR790 can be used for targeted radionuclide therapy of tumors. The DOTA-NIR790 enabled imaging by NIR fluorescence and by nuclear imaging (SPECT) to monitor in real-time the tumor accumulation and the situation of cancer therapy, and to guide the surgery or the photothermal therapy of the tumor. The radionuclide-labeled heptamethine cyanine based probe (DOTA-NIR790) offers multifunctional modalities for imaging and therapies of cancer.
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- 2021
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16. Effect of Cerenkov Radiation-Induced Photodynamic Therapy with 18F-FDG in an Intraperitoneal Xenograft Mouse Model of Ovarian Cancer
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Jia Je Li, Ren Shyan Liu, Chien Chih Ke, Yi An Chen, Syue Liang Lin, Sain Jhih Chiu, Chi Wei Chang, Bang Hung Yang, Ming Cheng Chang, Fong Shya Jeng, and Cheng Hsiu Lu
- Subjects
0301 basic medicine ,photosensitizer ,medicine.medical_treatment ,Photodynamic therapy ,chemistry.chemical_compound ,0302 clinical medicine ,Photosensitizer ,Biology (General) ,Spectroscopy ,Ovarian Neoplasms ,Mice, Inbred BALB C ,Radiation ,medicine.diagnostic_test ,Singlet oxygen ,General Medicine ,Verteporfin ,Computer Science Applications ,Chemistry ,ovarian cancer ,photodynamic therapy ,Positron emission tomography ,030220 oncology & carcinogenesis ,Female ,Injections, Intraperitoneal ,medicine.drug ,QH301-705.5 ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,In vivo ,Fluorodeoxyglucose F18 ,Cerenkov radiation ,Cell Line, Tumor ,medicine ,Animals ,Viability assay ,Physical and Theoretical Chemistry ,Molecular Biology ,QD1-999 ,Organic Chemistry ,18F-FDG ,medicine.disease ,Xenograft Model Antitumor Assays ,030104 developmental biology ,chemistry ,Photochemotherapy ,Cancer research ,Ovarian cancer - Abstract
Ovarian cancer (OC) metastases frequently occur through peritoneal dissemination, and they contribute to difficulties in treatment. While photodynamic therapy (PDT) has the potential to treat OC, its use is often limited by tissue penetration depth and tumor selectivity. Herein, we combined Cerenkov radiation (CR) emitted by 18F-FDG accumulated in tumors as an internal light source and several photosensitizer (PS) candidates with matched absorption bands, including Verteporfin (VP), Chlorin e6 (Ce6) and 5′-Aminolevulinic acid (5′-ALA), to evaluate the anti-tumor efficacy. The in vitro effect of CR-induced PDT (CR-PDT) was evaluated using a cell viability assay, and the efficiency of PS was assessed by measuring the singlet oxygen production. An intraperitoneal ES2 OC mouse model was used for in vivo evaluation of CR-PDT. Positron emission tomography (PET) imaging and bioluminescence-based imaging were performed to monitor the biologic uptake of 18F-FDG and the therapeutic effect. The in vitro studies demonstrated Ce6 and VP to be more effective PSs for CR-PDT. Moreover, VP was more efficient in the generation of singlet oxygen and continued for a long time when exposed to fluoro-18 (18F). Combining CR emitted by 18F-FDG and VP treatment not only significantly suppressed tumor growth, but also prolonged median survival times compared to either monotherapy.
- Published
- 2021
- Full Text
- View/download PDF
17. Apply DEMATEL to Analyzing Key Barriers to Implementing the Circular Economy: An Application for the Textile Sector
- Author
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Ching-Torng Lin, Wen-Kuo Chen, Venkateswarlu Nalluri, Hsing-Chun Hung, and Ming-Cheng Chang
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Process management ,media_common.quotation_subject ,key barriers ,Fuzzy Delphi Method (FDM) ,010501 environmental sciences ,Business model ,lcsh:Technology ,01 natural sciences ,lcsh:Chemistry ,circular economy (CE) ,0502 economics and business ,General Materials Science ,Quality (business) ,textile sector ,lcsh:QH301-705.5 ,Instrumentation ,Implementation ,Information exchange ,0105 earth and related environmental sciences ,media_common ,Fluid Flow and Transfer Processes ,Government ,lcsh:T ,Process Chemistry and Technology ,Circular economy ,05 social sciences ,General Engineering ,lcsh:QC1-999 ,Computer Science Applications ,lcsh:Biology (General) ,lcsh:QD1-999 ,lcsh:TA1-2040 ,Sustainability ,decision-making trial and evaluation laboratory (DEMATEL) ,Business ,lcsh:Engineering (General). Civil engineering (General) ,Textile (markup language) ,lcsh:Physics ,050203 business & management - Abstract
Continuous improvement and innovation are solid foundations for the textile sector to maintain excellent growth and active sustainability. As the limited resources possessed by textile companies generally result in the incapability of implementing circular economy (CE) strategies simultaneously, recently, researchers advocate that organizations should analyze the influential inter-relationship between key barriers to explore the more dominant determinants for designing improved actions for implementing CE in the textile sector. CE implementation in the textile sector appears to be in its infancy. Although much attention has been paid to CE implementation barriers, the present study tries to fill this research gap by analyzing the causal relationships among the CE barriers in the textile sector. Therefore, the twelve barriers are identified by an extensive literature review, and the application of the Fuzzy Delphi Method (FDM) based on the expert options from the textile sector. Subsequently, the causal inter-relationship among the key CE barriers is based on expert opinions using the decision-making trial and evaluation laboratory (DEMATEL). The results of this study indicate that three key barriers require quick action: “consumers lack knowledge and awareness about reused/recycle (B1)”, “lack of successful business models and frameworks to implement CE (B3)”, and “lack of an information exchange system between different stakeholders (B8)”. In addition, the results provide significant managerial implications, including implementations of CE in the textile sector. Not only should the government build regulations and friendly laws and encourage environmentally-friendly materials but the textile companies should also focus or monitor the recycling methods and quality to overcome the CE implementation issues. In addition, this study contributes to the textile sector transition toward CE by using the novel methodology for determining and prioritizing the key barriers. Finally, this work would help top management and the practitioners to better design effective infrastructural strategies for the textile sector transition towards CE.
- Published
- 2021
- Full Text
- View/download PDF
18. The new ophthalmic formulation for infection control by combining collagen/gelatin/alginate biomaterial with liposomal chloramphenicol
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Luo Tsai-Yueh, Cheng-Yu Huang, Lung-Kun Yeh, Kuan-Yin Chen, Cheng-Liang Peng, and Ming-Cheng Chang
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Drug ,endocrine system ,food.ingredient ,Alginates ,Polymers ,media_common.quotation_subject ,medicine.medical_treatment ,Administration, Ophthalmic ,Bacillus ,Biocompatible Materials ,Microbial Sensitivity Tests ,Pharmacology ,Eye ,Gelatin ,Cornea ,food ,Drug Delivery Systems ,Microscopy, Electron, Transmission ,medicine ,Escherichia coli ,Humans ,General Nursing ,media_common ,Liposome ,Chemistry ,Chloramphenicol ,Biomaterial ,Reproducibility of Results ,Eye drop ,Epithelial Cells ,Biodegradable polymer ,Anti-Bacterial Agents ,Culture Media ,Drug delivery ,Calibration ,Liposomes ,Collagen ,Ophthalmic Solutions ,medicine.drug - Abstract
Eye drops are a conventional method of drug delivery to the eye, accounting for 90% of currently accessible ophthalmic formulations. The major problem with eye drop treatments is rapid pre-corneal drug loss. Furthermore, the need for frequent administration of eye drops can profoundly affect the quality of life of ophthalmological patients. In the current study, we developed a liposomal nanoparticle encapsulated with chloramphenicol mixed with biodegradable materials against ophthalmological disease. We first established a protocol for chloramphenicol (CAP) loaded into liposomal nanoparticle (LipoCAP). We also established the collagen/gelatin/sodium alginate (CGA) as the component of biodegradable polymers and calibrated the novel drug-releasing formulation. Finally, we combined LipoCAP with CGA to generate an 8-hour degradable ophthalmic chloramphenicol gel, CGA-LipoCAP-8. CGA-LipoCAP-8 reached the effective working concentration in 75 minutes and prolonged the drug-releasing time for at least 12 hours. In addition, CGA-LipoCAP-8 could stably and continuously inhibit E. coli proliferation. The inhibiting phenomenon was more pronounced over time. Furthermore, there were no significant toxicities observed when CGA-LipoCAP-8 co-cultured with ocular epithelial cells. In conclusion, CGA-LipoCAP-8 achieved effective CAP dose concentrations in a short time and sustained CAP release for a prolonged period. Our results provide an innovative concept in relation to novel drug-release formulations, with safety and efficiency supporting use in future treatments for ophthalmological diseases.
- Published
- 2021
19. Hyaluronan-Loaded Liposomal Dexamethasone–Diclofenac Nanoparticles for Local Osteoarthritis Treatment
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Yu-Jen Kuo, Ying-Cheng Chiang, Ming-Cheng Chang, Kuan-Yin Chen, Ping-Fang Chiang, and Cheng-Liang Peng
- Subjects
0301 basic medicine ,Neutrophils ,Osteoarthritis ,Pharmacology ,lcsh:Chemistry ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Oral administration ,hemic and lymphatic diseases ,Hyaluronic acid ,polycyclic compounds ,Hyaluronic Acid ,lcsh:QH301-705.5 ,Spectroscopy ,Drug Carriers ,Molecular Structure ,General Medicine ,Computer Science Applications ,Joint pain ,Toxicity ,medicine.symptom ,liposomal nanoparticle ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,circulatory and respiratory physiology ,Diclofenac ,dexamethasone ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Adverse effect ,Molecular Biology ,Dexamethasone ,business.industry ,Organic Chemistry ,medicine.disease ,osteoarthritis ,Drug Liberation ,Kinetics ,030104 developmental biology ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,Liposomes ,Nanoparticles ,business ,Leukocyte Elastase ,030217 neurology & neurosurgery - Abstract
Osteoarthritis (OA) remains one of the common degenerative joint diseases and a major cause of pain and disability in older adult individuals. Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) (such as diclofenac, DIC) or intra-articular injected gluco-corticosteroids (such as dexamethasone, DEX) were the conventional treatment strategies for OA to reduce joint pain. Current limitations for both drugs including severe adverse effects with risks of toxicity were noted. The aim of the present study was to generate a novel OA treatment formulation hyaluronic acid (HA)-Liposomal (Lipo)-DIC/DEX to combat joint pain. The formulation was prepared by constructing DIC with DEX-loaded nanostructured lipid carriers Lipo-DIC/DEX mixed with hyaluronic acid (HA) for prolonged OA application. The prepared Lipo-DIC/DEX nanoparticles revealed the size as 103.6 ±, 0.3 nm on average, zeta potential as &minus, 22.3 ±, 4.6 mV, the entrapment efficiency of 90.5 ±, 5.6%, and the DIC and DEX content was 22.5 ±, 4.1 and 2.5 ±, 0.6%, respectively. Evidence indicated that HA-Lipo-DIC/DEX could reach the effective working concentration in 4 h and sustained the drug-releasing time for at least 168 h. No significant toxicities but increased cell numbers were observed when HA-Lipo-DIC/DEX co-cultured with articular chondrocytes cells. Using live-animal In vivo imaging system (IVIS), intra-articular injection of each HA-Lipo-DIC/DEX sufficed to reduce knee joint inflammation in OA mice over a time span of four weeks. Single-dose injection could reduce the inflammation volume down to 77.5 ±, 5.1% from initial over that time span. Our results provided the novel drug-releasing formulation with safety and efficiency which could be a promising system for osteoarthritis pain control.
- Published
- 2021
20. Liposomal dexamethasone-moxifloxacin nanoparticle combinations with collagen/gelatin/alginate hydrogel for corneal infection treatment and wound healing
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Lung-Kun Yeh, Ming-Cheng Chang, Yu-Jen Kuo, Kuo-Hsuan Hung, Kuan-Yin Chen, and Cheng-Liang Peng
- Subjects
Corneal Infection ,Time Factors ,Moxifloxacin ,Anti-Inflammatory Agents ,Bacillus ,Biocompatible Materials ,02 engineering and technology ,Pharmacology ,Gelatin ,Dexamethasone ,Corneal Diseases ,Cornea ,Mice ,Drug Delivery Systems ,Edema ,media_common ,Hydrogels ,021001 nanoscience & nanotechnology ,Lipids ,Drug delivery ,Collagen ,0210 nano-technology ,medicine.drug ,Drug ,endocrine system ,food.ingredient ,Alginates ,media_common.quotation_subject ,0206 medical engineering ,Biomedical Engineering ,Bioengineering ,Infectious Keratitis ,Biomaterials ,food ,medicine ,Escherichia coli ,Animals ,Humans ,Particle Size ,Inflammation ,Wound Healing ,business.industry ,Epithelial Cells ,020601 biomedical engineering ,Mice, Inbred C57BL ,Liposomes ,Wound healing ,business - Abstract
Infectious keratitis is still one of the major causes of visual impairment and blindness, often affecting developing countries. Eye-drop therapy to reduce disease progression is the first line of treatment for infectious keratitis. The current limitations in controlling ophthalmic infections include rapid precorneal drug loss and the inability to provide long-term extraocular drug delivery. The aim of the present study was to develop a novel ophthalmic formulation to treat corneal infection. The formulation was prepared by constructing moxifloxacin (MFX) and dexamethasone (DEX)-loaded nanostructured lipid carriers (Lipo-MFX/DEX) mixed with a collagen/gelatin/alginate (CGA) biodegradable material (CGA-Lipo-MFX/DEX) for prolonged ocular application. The characteristics of the prepared Lipo-MFX/DEX nanoparticles were as follows: average size, 132.1 ± 73.58 nm; zeta potential, −6.27 ± 4.95 mV; entrapment efficiency, 91.5 ± 3.5%; drug content, 18.1 ± 1.7%. Our results indicated that CGA-Lipo-MFX/DEX could release an effective working concentration in 60 min and sustain the drug release for at least 12 h. CGA-Lipo-MFX/DEX did not produce significant toxicities, but it increased cell numbers when co-cultured with ocular epithelial cells. An animal study also confirmed that CGA-Lipo-MFX/DEX could inhibit pathogen microorganism growth and improve corneal wound healing. Our results suggest that CGA-Lipo-MFX/DEX could be a useful anti-inflammatory formulation for ophthalmological disease treatment.
- Published
- 2020
21. Immuno-modulators enhance antigen-specific immunity and anti-tumor effects of mesothelin-specific chimeric DNA vaccine through promoting DC maturation
- Author
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Chi-An Chen, Wei-Zen Sun, Wen-Fang Cheng, Nai-Yun Sun, Ying-Cheng Chiang, Ming-Cheng Chang, Yu-Li Chen, and Han-Wei Lin
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Mesothelioma ,0301 basic medicine ,Cancer Research ,Lung Neoplasms ,medicine.medical_treatment ,Cell ,GPI-Linked Proteins ,Cancer Vaccines ,Catechin ,DNA vaccination ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immunity ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,Vaccines, DNA ,medicine ,Animals ,Mesothelin ,integumentary system ,biology ,Mesothelioma, Malignant ,Connective Tissue Growth Factor ,Antibodies, Monoclonal ,Drug Synergism ,Dendritic Cells ,Immunotherapy ,Xenograft Model Antitumor Assays ,Tumor antigen ,CTGF ,Poly I-C ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Female ,CD8 - Abstract
As a tumor antigen, mesothelin (MSLN) can be identified in various malignancies. MSLN is potential for antigen-specific cancer vaccines. We generated a novel chimeric DNA vaccine using antigen-specific connective tissue growth factor lined with MSLN (CTGF/MSLN). The anti-tumor effects of the CTGF/MSLN DNA vaccine combined with anti-CD40 Ab and toll-like receptor 3 ligand-poly(I:C) were validated in an MSLN-expressing model. CTGF/MSLN DNA with anti-CD40Ab and poly(I:C) vaccinated mice demonstrated potent anti-tumor effects with longer survival and less tumor volumes. An increase in MSLN-specific CD8+ T cells and anti-MSLN Ab titers was also noted in CTGF/MSLN DNA with anti-CD40Ab and poly(I:C) vaccinated mice. The CTGF/MSLN DNA vaccine combined with immuno-modulator EGCG also generated potent anti-tumor effects. Immuno-modulators could enhance the antigen-specific anti-tumor effects of CTGF/MSLN DNA vaccine through promoting the DC maturation. In addition, MSLN-specific cell-based vaccine with AAV-IL-12 and the CTGF/MSLN DNA vaccine with anti-CD40Ab/polyp(I:C) generated more potent anti-tumor effects than the other combinational regimens. The results indicate that an MSLN-specific DNA vaccine combined with immuno-modulators may be an effective immunotherapeutic strategy to control MSLN-expressing tumors including ovarian and pancreastic cancers, and malignant mesothelioma.
- Published
- 2018
22. The role of intergenerational relations in the association between life stressors and depressive symptoms
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Weinstein, Maxine, Glei, Dana A., Ming-Cheng, Chang, and Yamazaki, Ai
- Subjects
Aged -- Physiological aspects ,Depression, Mental -- Research ,Psychology and mental health ,Seniors - Abstract
This study investigates the association between intergenerational relations and depressive symptoms of older adults in Taiwan. Using data from two waves of the Surveys of Health and Living Status of the Elderly in Taiwan, a population-based sample of adults aged 60 and older, the links between intergenerational relations between parents and their adult children, life stressors (major life events and daily hassles), and depressive symptoms are examined. The authors find that higher reports of exposure to stressors--both daily hassles and major life events--are associated with higher levels of psychological distress. Intergenerational ties with children appear to have only a modest effect on levels of depressive symptoms that depends on both the kind of stressor and the aspect of the parent-child relationship. Keywords: intergenerational relations; stress; depression
- Published
- 2004
23. Developing a Prognostic Gene Panel of Epithelial Ovarian Cancer Patients by a Machine Learning Model
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Kuan-Ting Kuo, Chen Cy, Ming-Cheng Chang, Chi-An Chen, Wen-Fang Cheng, Yu Hao Hu, Hsiu-Ping Lin, Ying-Cheng Chiang, and Tzu-Pin Lu
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Microarray ,medicine.medical_treatment ,chemotherapy ,lcsh:RC254-282 ,Article ,predictive model ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cancer genome ,Gene panel ,medicine ,Epithelial ovarian cancer ,Chemotherapy ,Tumor size ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Clinical trial ,030104 developmental biology ,ovarian cancer ,machine learning ,030220 oncology & carcinogenesis ,business ,Ovarian cancer ,microarray - Abstract
Epithelial ovarian cancer patients usually relapse after primary management. We utilized the support vector machine algorithm to develop a model for the chemo-response using the Cancer Cell Line Encyclopedia (CCLE) and validated the model in The Cancer Genome Atlas (TCGA) and the GSE9891 dataset. Finally, we evaluated the feasibility of the model using ovarian cancer patients from our institute. The 10-gene predictive model demonstrated that the high response group had a longer recurrence-free survival (RFS) (log-rank test, p = 0.015 for TCGA, p = 0.013 for GSE9891 and p = 0.039 for NTUH) and overall survival (OS) (log-rank test, p = 0.002 for TCGA and p = 0.016 for NTUH). In a multivariate Cox hazard regression model, the predictive model (HR: 0.644, 95% CI: 0.436&ndash, 0.952, p = 0.027) and residual tumor size <, 1 cm (HR: 0.312, 95% CI: 0.170&ndash, 0.573, p <, 0.001) were significant factors for recurrence. The predictive model (HR: 0.511, 95% CI: 0.334&ndash, 0.783, p = 0.002) and residual tumor size <, 1 cm (HR: 0.252, 95% CI: 0.128&ndash, 0.496, p <, 0.001) were still significant factors for death. In conclusion, the patients of high response group stratified by the model had good response and favourable prognosis, whereas for the patients of medium to low response groups, introduction of other drugs or clinical trials might be beneficial.
- Published
- 2019
- Full Text
- View/download PDF
24. CDH1, DLEC1 and SFRP5 methylation panel as a prognostic marker for advanced epithelial ovarian cancer
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Chi-An Chen, Ying-Cheng Chiang, Tzu-Pin Lu, Wen-Fang Cheng, Ming-Cheng Chang, Chi-Feng Fu, Han-Wei Lin, and Hsiu-Ping Lin
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0301 basic medicine ,Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Bisulfite sequencing ,Carcinoma, Ovarian Epithelial ,CDH1 ,03 medical and health sciences ,0302 clinical medicine ,Antigens, CD ,Internal medicine ,Genetics ,medicine ,Biomarkers, Tumor ,Humans ,Epithelial ovarian cancer ,Eye Proteins ,Gene ,Adaptor Proteins, Signal Transducing ,Aged ,Ovarian Neoplasms ,biology ,Tumor Suppressor Proteins ,Hazard ratio ,Membrane Proteins ,Methylation ,DNA Methylation ,Middle Aged ,Cadherins ,Survival Analysis ,030104 developmental biology ,030220 oncology & carcinogenesis ,DNA methylation ,Cohort ,biology.protein ,Female - Abstract
Aim: To investigate the CDH1, DLEC1 and SFRP5 gene methylation panel for advanced epithelial ovarian carcinoma (EOC). Materials & methods: One hundred and seventy-seven advanced EOC specimens were evaluated by methylation-specific PCR. We also used The Cancer Genome Atlas dataset to evaluate the panel. Results: The presence of two or more methylated genes was significant in recurrence (hazard ratio [HR]: 1.91 [1.33–2.76]; p = 0.002) and death (HR: 1.96 [1.26–3.06]; p = 0.006) in our cohort. In The Cancer Genome Atlas dataset, the presence of two or three methylated genes was significant in death (HR: 1.59 [1.15–2.18]; p = 0.0047) and close to the significance level in recurrence (HR: 1.37 [0.99–1.88]; p = 0.058). Conclusion: The CDH1, DLEC1 and SFRP5 methylation panel is a potential prognostic biomarker for advanced EOC.
- Published
- 2018
25. A multistate model of fecundability and sterility
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Wood, James W., Holman, Darryl J., Yashin, Anatoli I., Peterson, Raymond J., Weintein, Maxine, and Ming-Cheng Chang
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Infertility -- Analysis ,Fertility -- Analysis ,Conception -- Analysis ,Family and marriage ,Sociology and social work - Abstract
Use of a multistate hazards model to analyze data on time between marriage and first conception helps simultaneously predict sterility and fecundability. The model accounts for separate nonsterile and sterile conditions, distinguishes between already present sterility and sterility that commences after the beginning of follow-up and has a log-normal distribution of the chance of conception in fertile couples. Analysis of data from the differing populations of Sri Lanka, Taiwan and an Old Order Amish community in Pennsylvania reveals that sterility might be a significant determinant of natural fertility only after the age of 40.
- Published
- 1994
26. Overexpression of CHI3L1 is associated with chemoresistance and poor outcome of epithelial ovarian carcinoma
- Author
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Wen-Fang Cheng, Ying-Cheng Chiang, Han-Wei Lin, Shu-Feng Hsieh, Tsung-Ching Chen, Ming-Cheng Chang, Chi-An Chen, Chi-Feng Fu, and Chi-Fang Chang
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Paclitaxel ,Blotting, Western ,Adipokine ,Apoptosis ,Carcinoma, Ovarian Epithelial ,Disease-Free Survival ,CHI3L1 ,chemistry.chemical_compound ,Adipokines ,RNA interference ,Cell Line, Tumor ,Lectins ,Outcome Assessment, Health Care ,Biomarkers, Tumor ,Humans ,Medicine ,Chitinase-3-Like Protein 1 ,Neoplasms, Glandular and Epithelial ,Aged ,Proportional Hazards Models ,Ovarian Neoplasms ,Analysis of Variance ,epithelial ovarian carcinoma ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Proportional hazards model ,chemoresistance ,Middle Aged ,Prognosis ,In vitro ,Gene Expression Regulation, Neoplastic ,Serous fluid ,Oncology ,chemistry ,Drug Resistance, Neoplasm ,Cancer research ,Myeloid Cell Leukemia Sequence 1 Protein ,Female ,RNA Interference ,business ,Research Paper - Abstract
We propose CHI3L1 as a prognostic biomarker for patients with epithelial ovarian carcinoma (EOC) and also suggest possible biological functions of CHI3L1. We measured CHI3L1 expression with quantitative real time-polymerase chain reaction (qRT-PCR) in 180 women with EOC and evaluated correlations between CHI3L1 expression, clinicopathological characteristics, and the outcomes of the patients. The expression of CHI3L1 was higher in cancerous tissues than in normal tissues. The expression of CHI3L1 was also higher in patients with a serous histological type, advanced stage, and chemoresistance. Patients with high CHI3L1 expression had a shorter progression-free survival (p < 0.001) and overall survival (p < 0.001). Patients with high CHI3L1 expression also had a high risk of recurrence (p < 0.001) and death (p < 0.001). In vitro studies showed that CHI3L1 up-regulated the expression of anti-apoptotic Mcl-1 protein and hampered paclitaxel-induced apoptosis of ovarian cancer cells. These results suggest that CHI3L1 shows potential as a prognostic biomarker for EOC. CHI3L1 may promote chemoresistance via inhibition of drug-induced apoptosis by up-regulating Mcl-1.
- Published
- 2015
27. Age Patterns of Fecundability*
- Author
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Weinstein, Maxine, primary, Wood, James, additional, and Ming-Cheng, Chang, additional
- Published
- 1993
- Full Text
- View/download PDF
28. IL17a and IL21 combined with surgical status predict the outcome of ovarian cancer patients
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Ching Ting Huang, Wen-Fang Cheng, Han Wei Lin, Cheng Yang Chou, Chi-An Chen, Ming Cheng Chang, Yu Li Chen, and Shu Feng Hsieh
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Enzyme-Linked Immunosorbent Assay ,Endocrinology ,Internal medicine ,Ovarian carcinoma ,Ascites ,Biomarkers, Tumor ,medicine ,Humans ,Prospective Studies ,Derivation ,Neoplasm Staging ,Ovarian Neoplasms ,Framingham Risk Score ,Receiver operating characteristic ,business.industry ,Interleukins ,Medical record ,Interleukin-17 ,Middle Aged ,Prognosis ,medicine.disease ,Adenocarcinoma, Mucinous ,Cystadenocarcinoma, Serous ,Endometrial Neoplasms ,Survival Rate ,ROC Curve ,Female ,IL17A ,Neoplasm Grading ,Neoplasm Recurrence, Local ,medicine.symptom ,Ovarian cancer ,business ,Adenocarcinoma, Clear Cell ,Follow-Up Studies - Abstract
Aside from tumor cells, ovarian cancer-related ascites contains the immune components. The aim of this study was to evaluate whether a combination of clinical and immunological parameters can predict survival in patients with ovarian cancer. Ascites specimens and medical records from 144 ovarian cancer patients at our hospital were used as the derivation group to select target clinical and immunological factors to generate a risk-scoring system to predict patient survival. Eighty-two cases from another hospital were used as the validation group to evaluate this system. The surgical status and expression levels of interleukin 17a (IL17a) and IL21 in ascites were selected for the risk-scoring system in the derivation group. The areas under the receiver operating characteristic (AUROC) curves of the overall score for disease-free survival (DFS) of the ovarian cancer patients were 0.84 in the derivation group, 0.85 in the validation group, and 0.84 for all the patients. The AUROC curves of the overall score for overall survival (OS) of cases were 0.78 in the derivation group, 0.76 in the validation group, and 0.76 for all the studied patients. Good correlations between overall risk score and survival of the ovarian cancer patients were demonstrated by sub-grouping all participants into four groups (P for trend
- Published
- 2015
29. Cohort Profile: The Social Environment and Biomarkers of Aging Study (SEBAS) in Taiwan
- Author
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Hsia-Yuan Liu, Jennifer C. Cornman, Dana A. Glei, Maxine Weinstein, Hui-Sheng Lin, Yu-Hsuan Lin, Baai-Shyun Hurng, I-Wen Liu, Yi-Li Chuang, Noreen Goldman, Shu-Hui Lin, and Ming-Cheng Chang
- Subjects
Male ,Gerontology ,Aging ,Longitudinal study ,Waist ,Epidemiology ,Health Status ,Population ,Taiwan ,Social Environment ,Social class ,03 medical and health sciences ,0302 clinical medicine ,Biomarkers of aging ,Humans ,Medicine ,Longitudinal Studies ,030212 general & internal medicine ,education ,Cohort Profiles ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Stressor ,Social environment ,General Medicine ,Middle Aged ,Social Class ,Cohort ,Female ,business ,Biomarkers ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
The Social Environment and Biomarkers of Aging Study (SEBAS) is a nationally representative longitudinal survey of Taiwanese middle-aged and older adults. It adds the collection of biomarkers and performance assessments to the Taiwan Longitudinal Study of Aging (TLSA), a nationally representative study of adults aged 60 and over, including the institutionalized population. The TLSA began in 1989, with follow-ups approximately every 3 years; younger refresher cohorts were added in 1996 and 2003. The first wave of SEBAS, based on a sub-sample of respondents from the 1999 TLSA, was conducted in 2000. A total of 1023 respondents completed both a face-to-face home interview and, several weeks later, a hospital-based physical examination. In addition to a 12-h (7 pm–7 am) urine specimen collected the night before and a fasting blood specimen collected during the examination, trained staff measured blood pressure, height, weight and waist and hip circumferences. A second wave of SEBAS was conducted in 2006 using a similar protocol to SEBAS 2000, but with the addition of performance assessments conducted by the interviewers at the end of the home interview. Both waves of SEBAS also included measures of health status (physical, emotional, cognitive), health behaviours, social relationships and exposure to stressors. The SEBAS data, which are publicly available at [http://www.icpsr.umich.edu/icpsrweb/NACDA/studies/3792/version/5], allow researchers to explore the relationships among life challenges, the social environment and health and to examine the antecedents, correlates and consequences of change in biological measures and health.
- Published
- 2014
30. Metronomic chemotherapy and immunotherapy in cancer treatment
- Author
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Wen-Fang Cheng, Yu-Li Chen, and Ming-Cheng Chang
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Angiogenesis Inhibitors ,Antineoplastic Agents ,Disease ,Drug resistance ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Maintenance therapy ,Internal medicine ,Neoplasms ,medicine ,Animals ,Humans ,Immunologic Factors ,Chemotherapy ,Dose-Response Relationship, Drug ,Neovascularization, Pathologic ,business.industry ,Immunotherapy ,medicine.disease ,Metronomic Chemotherapy ,030104 developmental biology ,Treatment Outcome ,030220 oncology & carcinogenesis ,Immunology ,Administration, Metronomic ,Tumor Escape ,business - Abstract
Systemic chemotherapy given at maximum tolerated doses (MTD) has been the mainstay of cancer treatment for more than half a century. In some chemosensitive diseases such as hematologic malignancies and solid tumors, MTD has led to complete remission and even cure. The combination of maintenance therapy and standard MTD also can generate good disease control; however, resistance to chemotherapy and disease metastasis still remain major obstacles to successful cancer treatment in the majority of advanced tumors. Metronomic chemotherapy, defined as frequent administration of chemotherapeutic agents at a non-toxic dose without extended rest periods, was originally designed to overcome drug resistance by shifting the therapeutic target from tumor cells to tumor endothelial cells. Metronomic chemotherapy also exerts anti-tumor effects on the immune system (immunomodulation) and tumor cells. The goal of immunotherapy is to enhance host anti-tumor immunities. Adding immunomodulators such as metronomic chemotherapy to immunotherapy can improve the clinical outcomes in a synergistic manner. Here, we review the anti-tumor mechanisms of metronomic chemotherapy and the preliminary research addressing the combination of immunotherapy and metronomic chemotherapy for cancer treatment in animal models and in clinical setting.
- Published
- 2016
31. Interferon-gamma in ascites could be a predictive biomarker of outcome in ovarian carcinoma
- Author
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Chi-An Chen, Yu-Li Chen, Chung-Liang Chien, Han-Wei Lin, Ching-Ting Huang, Ming-Cheng Chang, and Wen-Fang Cheng
- Subjects
Adult ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Disease-Free Survival ,Interferon-gamma ,Immune system ,Ovarian carcinoma ,Internal medicine ,Ascites ,Biomarkers, Tumor ,medicine ,Humans ,Interferon gamma ,Aged ,Proportional Hazards Models ,Ovarian Neoplasms ,business.industry ,Carcinoma ,Hazard ratio ,Obstetrics and Gynecology ,Immunotherapy ,Middle Aged ,medicine.disease ,Cytokine ,Immunology ,Female ,Neoplasm Grading ,medicine.symptom ,Ovarian cancer ,business ,medicine.drug - Abstract
The ovarian cancer-associated ascites is an ideal material for evaluating the interaction between the host immune system and cancer cells in the tumor micro-environment. The aim of this study was to investigate whether the selected target cytokine expression levels in ascites could serve as an immune biomarker for predicting outcomes in ovarian cancer.Eighty-eight specimens of ovarian cancer-associated ascites were evaluated to select the target cytokine by a cytokine profiling kit. The 144 total samples were subsequently analyzed for this target cytokine. The correlation between the target cytokine and clinical characteristics was analyzed.Interferon-gamma (IFN-γ) was identified as the target cytokine. Higher levels of IFN-γ in the ascites of the tumor micro-environment were associated with advanced disease (p=0.012), higher tumor histological grading (p=0.004), and sub-optimal surgical status (p=0.040). By multivariate analysis, the adjusted hazard ratios (HRs) were 2.74 (95% confidence interval (CI) 1.85-4.05, p0.001) for disease-free survival (DFS) and 1.72 (95% CI 1.01-2.93, p=0.048) for overall survival (OS) for a 10-fold increase in IFN-γ concentration in the ascites. An inverse dose-response relationship between IFN-γ level and survival was also noted (Ptrend0.001 for DFS and Ptrend0.042 for OS).Patients with ovarian cancer and higher IFN-γ expression levels in cancer-associated ascites will have shorter DFS and OS. IFN-γ levels in the ascites may be a prognostic marker and a potential reference for immunotherapy targeting IFN-γ.
- Published
- 2013
32. Epigenetic silencing of BLU through interfering apoptosis results in chemoresistance and poor prognosis of ovarian serous carcinoma patients
- Author
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Chi-An Chen, Ming Cheng Chang, Pao Jen Chen, Wen-Fang Cheng, Ying-Cheng Chiang, Meei Maan Wu, and Chang-Yao Hsieh
- Subjects
Epigenomics ,Oncology ,Cancer Research ,medicine.medical_specialty ,Paclitaxel ,Endocrinology, Diabetes and Metabolism ,Antineoplastic Agents ,Apoptosis ,Carcinoma, Ovarian Epithelial ,Biology ,Methylation ,CDH1 ,Endocrinology ,Cell Line, Tumor ,Internal medicine ,Ovarian carcinoma ,Biomarkers, Tumor ,medicine ,Carcinoma ,Humans ,Neoplasm ,Gene Silencing ,Neoplasms, Glandular and Epithelial ,RNA, Small Interfering ,Ovarian Neoplasms ,Tumor Suppressor Proteins ,Prognosis ,medicine.disease ,Cytoskeletal Proteins ,Drug Resistance, Neoplasm ,DNA methylation ,biology.protein ,Female ,Cisplatin ,Ovarian cancer - Abstract
Epithelial ovarian carcinoma is usually present at the advanced stage, during which the patients generally have poor prognosis. Our study aimed to evaluate the correlation of gene methylation and the clinical outcome of patients with advanced-stage, high-grade ovarian serous carcinoma. The methylation status of eight candidate genes was first evaluated by methylation-specific PCR and capillary electrophoresis to select three potential genes including DAPK, CDH1, and BLU (ZMYND10) from the exercise group of 40 patients. The methylation status of these three genes was further investigated in the validation group consisting of 136 patients. Patients with methylated BLU had significantly shorter progression-free survival (PFS; hazard ratio (HR) 1.48, 95% CI 1.01–2.56, P=0.013) and overall survival (OS; HR 1.83, 95% CI 1.07–3.11, P=0.027) in the multivariate analysis. Methylation of BLU was also an independent risk factor for 58 patients undergoing optimal debulking surgery for PFS (HR 2.37, 95% CI 1.03–5.42, P=0.043) and OS (HR 3.96, 95% CI 1.45–10.81, P=0.007) in the multivariate analysis. A possible mechanism of BLU in chemoresistance was investigated in ovarian cancer cell lines by in vitro apoptotic assays. In vitro studies have shown that BLU could upregulate the expression of BAX and enhance the effect of paclitaxel-induced apoptosis in ovarian cancer cells. Our study suggested that methylation of BLU could be a potential prognostic biomarker for advanced ovarian serous carcinoma.
- Published
- 2013
33. Culture of Chicken Gonadal Primordial Germ Cells (gPGCs) in Chicken Embryonic Fibroblast (CEF) Cells Conditioned Medium and in vivo Migration
- Author
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Lih-Ren Chen, Chein Tai, Jen-Wen Shiau, Ming-Cheng Chang, Jui-Jane Tailiu, and Jenn-Fa Liou
- Subjects
medicine.medical_specialty ,General Veterinary ,Biology ,Embryonic stem cell ,Cell biology ,Endocrinology ,medicine.anatomical_structure ,In vivo ,Internal medicine ,medicine ,Conditioned medium ,Germ ,Fibroblast ,Agronomy and Crop Science - Published
- 2012
34. Cloning and Characterization of Oviduct Tubular Gland Cell Tissue-Specific Promoters of White Leghorn Chicken
- Author
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Jen-Wen Shiau, Ming-Cheng Chang, Chein Tai, Chan Chang-Hsin, Jui-Jane Tailiu, Lih-Ren Chen, and Jenn-Fa Liou
- Subjects
Cloning ,medicine.anatomical_structure ,General Veterinary ,White Leghorn Chicken ,Cell ,medicine ,Oviduct ,Tissue specific ,Biology ,Tubular gland ,Agronomy and Crop Science ,Molecular biology - Published
- 2012
35. Cord blood stem-cell-derived dendritic cells generate potent antigen-specific immune responses and anti-tumour effects
- Author
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Yu Hao Hu, Yu-Li Chen, Chi-An Chen, Chien-Nan Lee, Wei-Zen Sun, Ying-Cheng Chiang, Ming-Cheng Chang, and Wen-Fang Cheng
- Subjects
medicine.medical_treatment ,Antigen presentation ,chemical and pharmacologic phenomena ,Biology ,p38 Mitogen-Activated Protein Kinases ,Peripheral blood mononuclear cell ,Immune system ,Cell Line, Tumor ,Neoplasms ,medicine ,Humans ,Cytotoxic T cell ,Phosphorylation ,Extracellular Signal-Regulated MAP Kinases ,Antigen Presentation ,Immunity, Cellular ,Stem Cells ,ELISPOT ,Cell Differentiation ,hemic and immune systems ,Dendritic Cells ,General Medicine ,Immunotherapy ,Fetal Blood ,Culture Media ,Cord blood ,Immunology ,Cytokines ,Stem cell ,K562 Cells ,Proto-Oncogene Proteins c-akt ,HeLa Cells ,Signal Transduction - Abstract
The aim of the present study was to investigate whether CBSCs [(umbilical) cord blood stem cells] can be a new source of DCs (dendritic cells), which can generate more potent antigen-specific immune responses and anti-tumour effects. CBSCs and PBMCs (peripheral blood mononuclear cells) were collected, cultured and differentiated into DCs. Surface markers, secreting cytokines, antigen-presentation activity, antigen-specific cell-mediated immunity and cytotoxic killing effects induced by these two DC origins were evaluated and compared. CBSCs were expanded ~17-fold by ex vivo culture. The expression of surface markers in CBSC-derived DCs were higher than those in PBMC-derived DCs treated with LPS (lipopolysaccharide). The CBSC-derived DCs mainly secreted IL (interleukin)-6, IL-10 and TNF (tumour necrosis factor)-α, whereas PBMC-derived DCs mainly secreted IL-5 and IFN (interferon)-γ. The CBSC-derived DCs had better antigen-presentation abilities when stimulated with LPS or TNF-α, induced higher numbers of IFN-γ-secreting antigen-specific CD8+ T-cells, as assessed using an ELISpot (enzyme-linked immunosorbent spot) assay, and stimulated more potent antigen-specific CTL (cytotoxic T-cell) activities (P
- Published
- 2012
36. Anti-CD40 antibody and toll-like receptor 3 ligand restore dendritic cell-mediated anti-tumor immunity suppressed by morphine
- Author
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Ming-Cheng, Chang, Yu-Li, Chen, Ying-Cheng, Chiang, Ya-Jung, Cheng, Yu-Wei, Jen, Chi-An, Chen, Wen-Fang, Cheng, and Wei-Zen, Sun
- Subjects
Original Article - Abstract
The influence of morphine on host immunity and the underlying mechanism are still unclear. In the current study, we investigated the influence of morphine on dendritic cells (DCs), its possible mechanism of action, and the molecules that could reverse these effects. Morphine suppressed DC maturation, antigen presenting abilities, and the ability to activate antigen-specific CD8(+) T cells. Morphine-treated DCs also secreted higher concentrations of IL-10, but lower IL-6 and TNF-α. Morphine-treated DCs showed decreased ERK1/2 phosphorylation and reduced p38 dephosphorylation. The in vivo administration of immuno-modulators, anti-CD40 Ab and TLR3 ligand-poly(I:C), enhanced antigen-specific immunity, promoted the anti-tumor effects, and prolonged the survival of morphine-treated, tumor-bearing mice by promoting the maturation and function of BMM-derived DCs by enhancing ERK1/2 phosphorylation and p38 dephosphorylation. We concluded that morphine can inhibit DC-mediated anti-tumor immunity by suppressing DC maturation and function. Immuno-modulators, such as anti-CD40 Abs and TLR agonists, can restore the DC-mediated anti-tumor immunity. Use of immuno-modulators could serve as a useful approach to overcome the immunocompromised state generated by morphine.
- Published
- 2015
37. Serous ovarian carcinoma patients with high alpha-folate receptor had reducing survival and cytotoxic chemo-response
- Author
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Yu-Li Chen, Ying-Cheng Chiang, Han-Wei Lin, Chang-Yao Hsieh, Chi-An Chen, Ming-Cheng Chang, Chia-Yen Huang, and Wen-Fang Cheng
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Cell Survival ,medicine.medical_treatment ,Immunoblotting ,Antineoplastic Agents ,In Vitro Techniques ,Biology ,chemistry.chemical_compound ,Cell Line, Tumor ,Internal medicine ,Ovarian carcinoma ,Genetics ,medicine ,Humans ,Immunoprecipitation ,Folate Receptor 1 ,Cystadenocarcinoma ,Ovarian Neoplasms ,Vintafolide ,Chemotherapy ,Hazard ratio ,Farletuzumab ,General Medicine ,Flow Cytometry ,medicine.disease ,Cystadenocarcinoma, Serous ,Serous fluid ,chemistry ,Papers ,Molecular Medicine ,Female ,Ovarian cancer - Abstract
The alpha‐folate receptor (α‐FR) is highly‐expressed in various non‐mucinous tumors of epithelial origin, including ovarian carcinoma. The aim of this study was to investigate the relationship between alpha‐folate receptor (α‐FR) and the clinico‐pathologic features and outcomes of serous ovarian carcinoma patients and the possible mechanism of α‐FR to chemo‐resistance. Therefore, semi‐quantitative reverse‐transcription polymerase chain reactions for α‐FR expression were performed in the 91 specimens of serous ovarian carcinomas. The expression of α‐FR in each ovarian cancer tissue specimen was defined as the ratio of density of α‐FR to density of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH). In vitro apoptotic experiments were tested in the original OVCAR‐3 tumor cells and various OVCAR‐3 α‐FR‐transfectants. Patients with an increased α‐FR expression level had poorer responses to chemotherapy (per α‐FR expression level increase: odds ratio (OR): 8.97 (95% confidence interval (CI): 1.40–57.36), p = 0.021). An increased α‐FR expression level was an independently poor prognostic factor for disease free interval (DFI) (per α‐FR expression level increase: hazard ratio (HR): 2.45 (95% CI: 1.16–5.18), p = 0.02) and had a negative impact on overall survival (OS) of these serous ovarian cancer patients (per α‐FR expression level increase: HR: 3.6 (95% CI: 0.93–13.29), p = 0.03) by multivariate analyses. α‐FR inhibited cytotoxic drug‐induced apoptosis in our in vitro apoptotic assays. α‐FR could induce chemo‐resistance via regulating the expression of apoptosis‐related molecules, Bcl‐2 and Bax. Therefore, α‐FR can be a potential biomarker for the prediction of chemotherapeutic responses and clinical prognosis. It also could be the target of ovarian cancer treatment.
- Published
- 2011
38. Influence of morphine on host immunity
- Author
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Shou-Zen Fan, Wei-Zen Sun, Ming-Cheng Chang, Po-Ni Hsiao, and Wen-Fang Cheng
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Drug ,media_common.quotation_subject ,T-Lymphocytes ,Analgesic ,Immune system ,Phagocytosis ,Cell Movement ,medicine ,Animals ,Humans ,media_common ,Innate immune system ,Morphine ,Mechanism (biology) ,business.industry ,Immunity ,General Medicine ,medicine.disease ,Acquired immune system ,Substance abuse ,Killer Cells, Natural ,Anesthesiology and Pain Medicine ,Immune System ,Immunology ,business ,medicine.drug - Abstract
Morphine is a widely used drug for analgesia and substance abuse. It has been accepted as a safe medication with great analgesic efficacy. Previous studies have reported that morphine is highly associated with the risk of immunosuppressive effects. Although the observed clinical effects suggest that morphine has the immunomodulatory capabilities, the mechanism of its action is still unclear. Here we review morphine on the bench to improve our understanding of the drug on the host immunity at the bedside. Studies of the effects of morphine on the innate and adaptive immune systems as well as immune responses are also discussed.
- Published
- 2011
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39. Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects
- Author
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Po-Ni Hsiao, Yun-Yuan Chen, Ying-Cheng Chiang, Chi-An Chen, Stella Chen, Ming Cheng Chang, Wen-Fang Cheng, Wei-Zen Sun, and Chun-Yu Hsieh
- Subjects
Injections, Intradermal ,Papillomavirus E7 Proteins ,Recombinant Fusion Proteins ,Genetic enhancement ,Dose-Response Relationship, Immunologic ,Epitopes, T-Lymphocyte ,Enzyme-Linked Immunosorbent Assay ,Buffers ,CD8-Positive T-Lymphocytes ,Biology ,Cancer Vaccines ,Epitope ,DNA vaccination ,Gene gun ,Mice ,chemistry.chemical_compound ,Antigen ,Cell Line, Tumor ,Neoplasms ,Burns, Chemical ,Pressure ,Vaccines, DNA ,Genetics ,Animals ,Luciferases ,Molecular Biology ,Gene ,Cells, Cultured ,Drug Carriers ,Dendritic Cells ,Dermis ,Neoplasms, Experimental ,Biolistics ,Flow Cytometry ,Virology ,CD11c Antigen ,Mice, Inbred C57BL ,Microscopy, Fluorescence ,chemistry ,Naked DNA ,Molecular Medicine ,Female ,Gold ,Immunotherapy ,DNA - Abstract
Genetic immunization strategies have largely focused on the use of plasmid DNA with a gene gun. However, there remains a clear need to further improve the efficiency, safety, and cost of potential DNA vaccines. The gold particle-coated DNA format delivered through a gene gun is expensive, time and process consuming, and raises aseptic safety concerns. This study aims to determine whether a low-pressured gene gun can deliver noncarrier naked DNA vaccine without any particle coating, and generate similarly strong antigen-specific immunologic responses and potent antitumor effects compared with gold particle-coated DNA vaccine. Our results show that mice vaccinated with noncarrier naked chimeric CRT/E7 DNA lead to dramatic increases in the numbers of E7-specific CD8+ T-cell precursors and markedly raised titers of E7-specific antibodies. Furthermore, noncarrier naked CRT/E7 DNA vaccine generated potent antitumor effects against subcutaneous E7-expressing tumors and pre-established E7-expressing metastatic pulmonary tumors. In addition, mice immunized with noncarrier naked CRT/E7 DNA vaccine had significantly less burning effects on the skin compared with those vaccinated with gold particle-coated CRT/E7 DNA vaccine. We conclude that noncarrier naked CRT/E7 DNA vaccine delivered with a low-pressured gene gun can generate similarly potent immunologic responses and effective antitumor effects has fewer side effects, and is more convenient than conventional gold particle-coated DNA vaccine.
- Published
- 2009
40. Morphine induces apoptosis of human endothelial cells through nitric oxide and reactive oxygen species pathways
- Author
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Po-Ni Hsiao, Wen-Fang Cheng, Chang-Yao Hsieh, Chi-An Chen, Wei-Zen Sun, Ming-Cheng Chang, and Han-Wei Lin
- Subjects
Programmed cell death ,Cell Survival ,Angiogenesis ,Blotting, Western ,Apoptosis ,(+)-Naloxone ,Biology ,Nitric Oxide ,Toxicology ,medicine.disease_cause ,Cell Line ,Membrane Potentials ,Nitric oxide ,chemistry.chemical_compound ,medicine ,Humans ,Immunoprecipitation ,Caspase 7 ,chemistry.chemical_classification ,Reactive oxygen species ,Dose-Response Relationship, Drug ,Morphine ,Caspase 3 ,NF-kappa B ,Endothelial Cells ,Hydrogen Peroxide ,Flow Cytometry ,Cell biology ,Analgesics, Opioid ,Endothelial stem cell ,chemistry ,Mitochondrial Membranes ,Immunology ,Reactive Oxygen Species ,Oxidative stress - Abstract
Morphine has been widely used for pain management. Other than analgesia, it has effects on vascular endothelial cells, including angiogenesis and apoptosis. An in vitro model of human umbilical vein endothelial cells (HUVECs) was made to investigate the effects and comprehensive mechanisms of morphine on vascular endothelial cells. Morphine enhanced apoptosis of HUVECs, increased intracellular reactive oxygen species (ROS), and reduced mitochondrial membrane potentials (MMPs). It also induced the release of NO and activated NF-κB in HUVECs. Naloxone, the opioid receptor antagonist, could reverse cell apoptosis and ROS generation, NO production, and MMP loss. Expression levels of Bak and Bax, and the activation of caspases 3 and 7 in HUVECs significantly increased when treated with morphine. Inhibition of NO production by NO synthase inhibitor reduced morphine-induced apoptosis. Morphine could induce apoptosis of HUVECs through both the NO and ROS pathways. Thus, inhibiting NO or ROS may be a potential target in blocking morphine-induced apoptosis of endothelial cells.
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- 2009
41. Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism
- Author
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Ming Cheng Chang, Yi Ning Su, Chien-Nan Lee, Wei-Zen Sun, Chi-An Chen, Chang-Yao Hsieh, Wen-Fang Cheng, and Hsiu-Ping Lin
- Subjects
CD4-Positive T-Lymphocytes ,Cell Survival ,Papillomavirus E7 Proteins ,Genetic enhancement ,medicine.medical_treatment ,CD8-Positive T-Lymphocytes ,Biology ,Cancer Vaccines ,Immediate-Early Proteins ,DNA vaccination ,Mice ,Immune system ,Antigen ,Cell Line, Tumor ,Neoplasms ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Antigen Presentation ,integumentary system ,Connective Tissue Growth Factor ,Immunotherapy, Active ,Dendritic Cells ,Genetic Therapy ,Oncogene Proteins, Viral ,Immunotherapy ,Xenograft Model Antitumor Assays ,Tumor antigen ,CTGF ,Immunology ,Intercellular Signaling Peptides and Proteins ,Molecular Medicine ,Cancer vaccine ,Genetic Engineering - Abstract
A novel method for generating an antigen-specific cancer vaccine and immunotherapy has emerged using a DNA vaccine. However, antigen-presenting cells (APCs) have a limited life span, which hinders their long-term ability to prime antigen-specific T cells. Connective tissue growth factor (CTGF) has a role in cell survival. This study explored the intradermal administration of DNA encoding CTGF with a model tumor antigen, human papilloma virus type 16 E7. Mice vaccinated with CTGF/E7 DNA exhibited a dramatic increase in E7-specific CD4(+) and CD8(+) T-cell precursors. They also showed an impressive antitumor effect against E7-expressing tumors compared with mice vaccinated with the wild-type E7 DNA. The delivery of DNA encoding CTGF and E7 or CTGF alone could prolong the survival of transduced dendritic cells (DCs) in vivo. In addition, CTGF/E7-transduced DCs could enhance a higher number of E7-specific CD8(+) T cells than E7-transduced DCs. By prolonging the survival of APCs, DNA vaccine encoding CTGF linked to a tumor antigen represents an innovative approach to enhance DNA vaccine potency and holds promise for cancer prophylaxis and immunotherapy.
- Published
- 2008
42. DNA vaccine encoding heat shock protein 60 co-linked to HPV16 E6 and E7 tumor antigens generates more potent immunotherapeutic effects than respective E6 or E7 tumor antigens
- Author
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Ming-Cheng Chang, Chi-An Chen, Chien-Nan Lee, Yi-Ning Su, Wen-Fang Cheng, Chang-Yao Hsieh, Yi-Chun Lin, and Chia-Yen Huang
- Subjects
CD4-Positive T-Lymphocytes ,Papillomavirus E7 Proteins ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,Transfection ,DNA vaccination ,Mice ,Immune system ,Antigen ,Heat shock protein ,Vaccines, DNA ,Animals ,Humans ,biology ,Papillomavirus Infections ,fungi ,Obstetrics and Gynecology ,Chaperonin 60 ,DNA ,Dendritic Cells ,Neoplasms, Experimental ,Oncogene Proteins, Viral ,Tumor antigen ,Killer Cells, Natural ,Mice, Inbred C57BL ,Repressor Proteins ,Vaccination ,Oncology ,Immunology ,biology.protein ,Female ,HSP60 ,Antibody ,T-Lymphocytes, Cytotoxic - Abstract
Objective. Vaccination based on tumor antigen is an attractive strategy for cancer prevention and therapy. Cervical cancer is highly associated with human papillomavirus, especially type 16. We developed DNA vaccines encoding heat shock protein 60 (HSP60) linked to HPV16 E6 or E7 to test if HSP60 chimeric DNA vaccines may generate strong E6 and/or E7-specific immune response and anti-tumor effects in vaccinated mice. Methods. In vivo antitumor effects such as preventive, therapeutic, and antibody depletion experiments were performed. In vitro assays such as intracellular cytokine stainings, ELISA for Ab responses, and direct and cross-priming effects, were also performed. Results. HSP60 chimeric DNA vaccines generated strong E6- or E7-specific immune responses and anti-tumor effects in vaccinated mice via direct and cross-priming effects. HSP60 was also linked with both E6 and E7 antigens and the HSP60/E6/E7 chimeric DNA vaccine generated more potent immunotherapeutic effects on E6- and E7-expressing tumors than HSP60/E6 or HSP60/E7 chimeric DNA vaccine alone. Conclusion. Utilization of both E6 and E7 tumor antigens can advance the therapy of tumors associated with HPV-infections. The DNA vaccine encoding heat shock protein 60 co-linked to HPV16 E6 and E7 tumor antigens can generate more potent immunotherapeutic effects than E6 or E7 tumor antigens alone.
- Published
- 2007
43. IL-6-Encoding Tumor Antigen Generates Potent Cancer Immunotherapy Through Antigen Processing and Anti-apoptotic Pathways
- Author
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Chi-An Chen, Yi-Ning Su, Wen-Fang Cheng, Ming-Cheng Chang, Chia-Yen Huang, Chang-Yao Hsieh, and Chien-Nan Lee
- Subjects
medicine.medical_treatment ,Apoptosis ,Major histocompatibility complex ,DNA vaccination ,Mice ,Antigen ,Cancer immunotherapy ,Antigens, Neoplasm ,Neoplasms ,Drug Discovery ,Vaccines, DNA ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,DNA Primers ,Pharmacology ,Immunity, Cellular ,Base Sequence ,biology ,Interleukin-6 ,Antigen processing ,Immunotherapy ,Tumor antigen ,Mice, Inbred C57BL ,Naked DNA ,Immunology ,biology.protein ,Molecular Medicine ,Female ,T-Lymphocytes, Cytotoxic - Abstract
A naked DNA vaccine delivered by gene gun into antigen-presenting cells (APCs) has emerged as an attractive strategy for antigen-specific cancer immunotherapy. However, APCs have a limited lifespan, hindering their long-term ability to prime antigen-specific T cells. Furthermore, the potency of DNA vaccines is limited by their inability to process and present antigens. Interleukin-6 (IL-6) could play a role in immunity and cell apoptosis. We explored how the DNA vaccine encodes IL-6 to a model tumor antigen, human papilloma virus type-16 (HPV-16) E7. Mice vaccinated with IL-6/E7 DNA exhibited dramatic increases in E7-specific T-cell immunities, anti-E7 antibody responses, and impressive anti-tumor effects against E7-expressing tumors. The in vitro results revealed that IL-6 enhances DNA vaccine potency through the major histocompatibility complex class I pathway via direct and cross-priming effects. In addition, the delivery of IL-6/E7 DNA prolonged the survival of transduced dendritic cells (DCs) in vivo. Our results indicated that the IL-6/E7 DNA vaccine combined the mechanisms of enhancing antigen processing and presentation with prolonging the survival of DCs. Using IL-6 represents an innovative approach to enhancing DNA vaccine potency and holds promise for cancer prevention and immunotherapy.
- Published
- 2007
44. Influence of diet and physical activity on aging-associated body fatness and anthropometric changes in older Taiwanese
- Author
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Alan C. Tsai, Ming-Cheng Chang, Jenn-Chang Liou, and Yi-Li Chuang
- Subjects
Gerontology ,education.field_of_study ,Nutrition and Dietetics ,business.industry ,Endocrinology, Diabetes and Metabolism ,Population ,Physical activity ,Physical exercise ,Anthropometry ,Circumference ,medicine.disease ,Obesity ,Endocrinology ,Ageing ,Medicine ,business ,education ,Body mass index ,Demography - Abstract
The aims of this study were to evaluate the impact of aging on body fatness and body muscle status and to assess the association of diet and physical activity with aging-associated anthropometric changes. The study analyzed the data of a 1999 population-based cross-sectional survey in men and women, aged 53 years or older, in Taiwan. In-home, in-person interviews elicited the participants’ sociodemographic status, weight and height, physical activity, and intake frequency of food items and measured their midarm circumference (MAC) and calf circumference (CC). Linear regression analyzed the correlates of these anthropometric parameters. Results based on body mass index (BMI, kg/m 2 ) indicate that the prevalence of overweight-obesity was 31.1% for men and 33.7% for women by the World Health Organization definition (BMI, N25) or 43.1% for men and 45.4% for women by the Taiwanese definition (BMI, N24). Average height losses were 1.0 cm for men and 1.3 cm for women, and weight losses were 2.9 and 3.2 kg per decade for men and women, respectively. Aging was associated with decreasing BMI, MAC, and CC. The female sex was associated with higher BMI but smaller MAC and CC. Physical activity was positively associated with BMI, MAC, and CC. Body mass index was positively associated with fruit consumption but negatively with milk consumption. Midarm circumference was positively associated with fish and fruit but negatively with egg and legume consumptions. Calf circumference was positively associated with vegetable consumption. In conclusion, aging-associated anthropometric changes in older Taiwanese are comparable with those observed in Western populations. Both diet and physical activity can modulate aging-associated anthropometric changes in older individuals.
- Published
- 2007
45. The effects of Taiwan's National Health Insurance on access and health status of the elderly
- Author
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Shyh-Dye Lee, Hui-Sheng Lin, Yu-Hsuan Lin, Ya-Ling Chiu, Ming-Cheng Chang, Likwang Chen, and Winnie Yip
- Subjects
Male ,National Health Programs ,Health Services for the Aged ,Health Status ,Taiwan ,MEDLINE ,Health Services Accessibility ,Health services ,Residence Characteristics ,Environmental health ,Humans ,Medicine ,Longitudinal Studies ,Mortality ,Aged ,Aged, 80 and over ,Inpatient care ,business.industry ,Health Policy ,Causal effect ,Equity (finance) ,Chronic disease ,Socioeconomic Factors ,National health insurance ,Chronic Disease ,Female ,General health ,business - Abstract
The primary objective of this paper is to evaluate the impact of Taiwan's National Health Insurance program (NHI), established in 1995, on improving elderly access to care and health status. Further, we estimate the extent to which NHI reduces gaps in access and health across income groups. Using data from a longitudinal survey, we adopt a difference-in-difference methodology to estimate the causal effect of Taiwan's NHI. Our results show that Taiwan's NHI has significantly increased utilization of both outpatient and inpatient care among the elderly, and such effects were more salient for people in the low- or middle-income groups. Our findings also reveal that although Taiwan's NHI greatly increased the utilization of both outpatient and inpatient services, this increased utilization of health services did not reduce mortality or lead to better self-perceived general health status for Taiwanese elderly. Measures more sensitive than mortality and self-perceived general health may be necessary for discerning the health effects of NHI. Alternatively, the lack of NHI effects on health may reflect other quality and efficiency problems inherent in the system not yet addressed by NHI.
- Published
- 2007
46. Urokinase-type Plasminogen Activator Resulting from Endometrial Carcinogenesis Enhances Tumor Invasion and Correlates with Poor Outcome of Endometrial Carcinoma Patients
- Author
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Wen-Fang Cheng, Kuan-Ting Kuo, Yu-Chien Tang, Chi-An Chen, Chia-Yen Huang, Ming-Cheng Chang, Wei Yun Huang, Hsien Da Huang, and Ching-Ting Huang
- Subjects
Adult ,MAP Kinase Signaling System ,Biology ,p38 Mitogen-Activated Protein Kinases ,Article ,Prostate cancer ,Breast cancer ,Cell Movement ,In vivo ,Cell Line, Tumor ,medicine ,Carcinoma ,Cluster Analysis ,Humans ,Neoplasm Invasiveness ,RNA, Messenger ,Neoplasm Metastasis ,Aged ,Neoplasm Staging ,Urokinase ,Neoplasm Grading ,Multidisciplinary ,Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase ,Molecular pathology ,Gene Expression Profiling ,Reproducibility of Results ,Middle Aged ,Prognosis ,medicine.disease ,Urokinase-Type Plasminogen Activator ,Endometrial Neoplasms ,stomatognathic diseases ,Cell Transformation, Neoplastic ,Cancer research ,Female ,Proto-Oncogene Proteins c-akt ,Plasminogen activator ,Signal Transduction ,medicine.drug - Abstract
The purpose of this study was to identify the dysregulated genes involved in the tumorigenesis and progression of endometrial endometrioid adenocarcinoma (EEC) and their possible mechanisms. Endometrial specimens including normal endometrial tissues, atypical endometrial hyperplasia and EEC were analyzed. The expression profiles were compared using GeneChip Array. The gene expression levels were determined by real-time RT-PCR in the training and testing sets to correlate the clinico-pathological parameters of EEC. Immunoblotting, in vitro cell migration and invasion assays were performed in human endometrial cancer cell lines and their transfectants. In microarray analysis, seven dysregulated genes were identified. Only the levels of urokinase-type plasminogen activator (uPA) were higher in EEC with deep myometrial invasion, positive lympho-vascular space invasion, lymph node metastasis and advanced stages. After multivariate analysis, uPA was the only independent poor prognostic factor for disease-free survival in the EEC patients (hazard ratio: 4.65, p = 0.03). uPA may enhance the migratory and invasive capabilities of endometrial tumor cells by the phosphorylation of ERK1/2, Akt and p38 molecules. uPA is a dysregulated gene involved in the tumorigenesis, bio-pathological features and outcomes of EEC. uPA may be a potential molecule and target for the detection and treatment of EEC.
- Published
- 2015
47. Food patterns that correlate to health and nutrition status in elderly Taiwanese
- Author
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Jenn-Chang Liou, Ming-Cheng Chang, and Alan C. Tsai
- Subjects
Consumption (economics) ,Gerontology ,Food intake ,education.field_of_study ,Nutrition and Dietetics ,business.industry ,Endocrinology, Diabetes and Metabolism ,Population ,Physical exercise ,Food Patterns ,medicine.disease ,Malnutrition ,Digestive problems ,Endocrinology ,Environmental health ,medicine ,Soy food ,business ,education - Abstract
The objective of this study was to assess food intake patterns and their correlates in men and women in Taiwan 53 years of age or older. The study analyzed data generated in a cross-sectional population-based survey conducted in 1999. An in-home questionnaire interview elicited respondents' sociodemographic status, physical activity, and the consumption frequency of major food categories. Results showed that fish was the most frequently consumed protein-rich food, followed by meat and poultry. More than 50% of older adults consumed milk less than twice per week, whereas more than 40% consumed soy food more than 3 times per week. More than 90% of elderly Taiwanese consumed vegetables everyday or almost everyday, but only 60% consumed fruits everyday or almost everyday. Elderly Taiwanese men consumed meat, fish, seafood, eggs, and tea more often than did elderly women, whereas the opposite was true for dairy, fruits, and vegetables. Advanced aging was associated with a decline in the consumption frequency of most major food categories, a decrease in appetite status and an increase in digestive problems. Higher education and frequent daily physical exercise were associated with an increase in the consumption frequency of most food categories. Results suggest that age, sex, education, and physical activity impact food intake patterns and that risk of malnutrition does exist in some elderly in Taiwan.
- Published
- 2006
48. Chimeric DNA Vaccine Reverses Morphine-Induced Immunosuppression and Tumorigenesis
- Author
-
Chien-Nan Lee, Wen-Fang Cheng, Po-Ni Hsiao, Ming-Cheng Chang, Yi-Ning Su, Huei-Jiuan Jeng, Chang-Yao Hsieh, Li-Kuei Chen, Wei-Zen Sun, and Chi-An Chen
- Subjects
CD4-Positive T-Lymphocytes ,Narcotic Antagonists ,Papillomavirus E7 Proteins ,medicine.medical_treatment ,Transplantation, Heterologous ,Apoptosis ,(+)-Naloxone ,CD8-Positive T-Lymphocytes ,Pharmacology ,Biology ,medicine.disease_cause ,Cancer Vaccines ,DNA vaccination ,Mice ,Immunity ,Cell Line, Tumor ,Drug Discovery ,Vaccines, DNA ,Genetics ,medicine ,Animals ,Molecular Biology ,bcl-2-Associated X Protein ,Immunosuppression Therapy ,Morphine ,Vaccination ,Immunosuppression ,Neoplasms, Experimental ,Analgesics, Opioid ,Mice, Inbred C57BL ,Transplantation ,Proto-Oncogene Proteins c-bcl-2 ,Molecular Medicine ,Female ,Carcinogenesis ,Neoplasm Transplantation ,CD8 - Abstract
Although long-term use of morphine has been shown to promote tumor growth, the question whether tumorigenesis occurs as a result of an immunosuppressive effect remains to be investigated. In mice rendered tolerant to morphine, the efficacy and mechanism of a vaccination to rescue morphine-induced immunosuppression and prevent tumor growth was assessed both in vitro and in vivo. Herein, we found that morphine-injected mice exhibited higher tumor growth rates and lower percentages of CD8+ T lymphocytes. The mechanism of morphine suppression of immunity might be through the suppression of E7-specific CD8+ T lymphocyte proliferation and the promotion of apoptosis of these cells by the Bcl-2 and Bax pathways. The suppressive effect of E7-specific CD8+ T lymphocytes by morphine could be reversed by naloxone. We have previously shown that calreticulin linked with E7 (CRT/E7) could enhance the CD8+ T cell response and the anti-tumor effects (W. F. Cheng et al. (2001) J. Clin. Invest. 108, 669-678). CRT/E7 DNA vaccine could overcome the immunosuppressive effect of morphine and suppress tumor growth. Our findings reveal that long-term morphine treatment dose-dependently promotes tumor growth and a DNA vaccine may serve as a useful approach to treat the profound immunosuppressive function and prevent tumorigenesis after long-term morphine treatment.
- Published
- 2006
49. Establishment of a New Ovarian Cancer Cell Line CA5171
- Author
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Wen-Fang Cheng, Ming-Cheng Chang, Chi-An Chen, Chang-Yao Hsieh, Tzu-Pin Lu, Ying-Cheng Chiang, Kuan-Ting Kuo, and Hsiu-Ping Lin
- Subjects
Oncology ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,DNA Copy Number Variations ,Paclitaxel ,Class I Phosphatidylinositol 3-Kinases ,Antineoplastic Agents ,Biology ,Carcinoma, Ovarian Epithelial ,Polymorphism, Single Nucleotide ,Phosphatidylinositol 3-Kinases ,Undifferentiated Ovarian Carcinoma ,Cell Movement ,Internal medicine ,Cell Line, Tumor ,medicine ,Biomarkers, Tumor ,Doubling time ,PTEN ,Humans ,Genetic Predisposition to Disease ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Neoplasms, Glandular and Epithelial ,Cell Shape ,Cell Proliferation ,Cisplatin ,Ovarian Neoplasms ,Cell growth ,PTEN Phosphohydrolase ,Obstetrics and Gynecology ,Original Articles ,Middle Aged ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Phenotype ,Cell culture ,Doxorubicin ,Drug Resistance, Neoplasm ,Mutation ,Cancer research ,biology.protein ,Female ,Tumor Suppressor Protein p53 ,Ovarian cancer ,medicine.drug - Abstract
A new cell line, CA5171, derived from a chemotherapy-naive, high-grade undifferentiated ovarian carcinoma was established and characterized. The CA5171 cells presented with cobblestone morphology and a doubling time of 24 hours. Gene mutation analysis showed that the cells belonged to the type II ovarian cancer pathway with mutations of PIK3CA, PTEN, and TP53. Single-nucleotide polymorphism array analysis showed no homozygous gene deletion; however, several loci of gene copy number gains were noted in chromosome 1, 2, 5, 9, 10, 12, 15, 16, 20, and X. The in vitro and in vivo experiments showed that the cells were sensitive to paclitaxel and doxorubicin, but resistant to cisplatin. The cells also presented epithelial-mesenchymal transition properties that may have been related to their invasion and migration potential. The CA5171 cells show the potential as a new cell line for studies on epithelial ovarian carcinoma.
- Published
- 2014
50. Mesothelin-specific cell-based vaccine generates antigen-specific immunity and potent antitumor effects by combining with IL-12 immunomodulator
- Author
-
Chi-An Chen, Ying-Cheng Chiang, Ming Cheng Chang, Yu-Li Chen, Tang Yc, Wen-Fang Cheng, Wei-Zen Sun, and Tzer-Ming Chen
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,Cytotoxicity, Immunologic ,endocrine system diseases ,Antibodies, Neoplasm ,medicine.medical_treatment ,CD8-Positive T-Lymphocytes ,GPI-Linked Proteins ,Cancer Vaccines ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Antigen ,Antigens, Neoplasm ,Cell Line, Tumor ,Genetics ,medicine ,Cytotoxic T cell ,Animals ,Humans ,Mesothelin ,Molecular Biology ,Ovarian Neoplasms ,biology ,fungi ,Vaccination ,Immunotherapy ,Dependovirus ,medicine.disease ,Interleukin-12 ,Tumor antigen ,Mice, Inbred C57BL ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Molecular Medicine ,Interleukin-2 ,Female ,Antibody ,Ovarian cancer ,T-Lymphocytes, Cytotoxic - Abstract
Ovarian cancer is a gynecologic malignancy with a high mortality rate. In the present study, we developed a novel cell-based vaccine, Meso-VAX, to generate mesothelin antigen-specific immune responses and immunotherapy against ovarian cancer. Mesothelin, a secreted protein anchored at the cell membrane, has recently been identified as a potential new tumor antigen for ovarian cancer. In this study, mice vaccinated with Meso-VAX and adeno-associated virus (AAV)-IL-12 exhibited dramatic increases in the number of mesothelin-specific CD4(+) helper and CD8(+) cytotoxic T-cell precursors, higher titers of anti-mesothelin Abs and in vitro tumor killing activity, and all of these mice were tumor-free after 60 days of tumor challenge. In addition, a significant reduction in peritoneal tumors and longer survival were noted in the mice vaccinated with Meso-VAX combined with AAV-IL-12. CD4(+) helper and CD8(+) cytotoxic T lymphocytes were essential for the antitumor effect generated by Meso-VAX combined with AAV-IL-12. The post-vaccination sera of the mice vaccinated with Meso-VAX and AAV-IL-12 also showed mesothelin-specific complement-dependent cell-mediated cytotoxicity. Our results suggest that a Meso-VAX cell-based vaccine combined with AAV-IL-12 can generate antigen-specific immunological responses and antitumor effects on ovarian cancer.
- Published
- 2014
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