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K.-H. William Lau,Nicoleta L. Popa,Charles H. Rundle 대한골대사학회 2014 대한골대사학회지 Vol.21 No.3
Background: Cyclo-oxygenase-2 (Cox-2) is an inflammatory mediator that is necessaryfor the tissue repair, including bone fracture healing. Although the application of Cox-2gene therapy to a murine closed femoral fracture has accelerated bony union, but thebeneficial effect was not observed until the endochondral stage of bone repair that iswell after the inflammatory stage normally subsides. Methods: To identify the molecularpathways through which Cox-2 regulates fracture healing, we examined gene expres-sion profile in fracture tissues in response to Cox-2 gene therapy during the endochon-dral bone repair phase. Cox-2 gene therapy was applied to the closed murine femurfracture model. Microarray analysis was performed at 10 days post-fracture to examineglobal gene expression profile in the fracture tissues during the endochondral bone re-pair phase. The entire repertoire of significantly expressed genes was examined by geneset enrichment analysis, and the most up-regulated individual genes were evaluatedfurther. Results: The genes that normally promote inflammation were under-represent-ed in the microarray analysis, and the expression of several inflammatory chemokineswas significantly down-regulated. There was an up-regulation of two key transcriptionfactor genes that regulate hematopoiesis and erythropoiesis. More surprisingly, therewas no significant up-regulation in the genes that are normally involved in angiogenesisor bone formation. However, the expression of two tissue remodeling genes was up-regulated. Conclusions: The down-regulation of the inflammatory genes in response toCox-2 gene therapy was unexpected, given the pro-inflammatory role of prostaglandins. Cox-2 gene therapy could promote bony union through hematopoietic precursor prolif-eration during endochondral bone repair and thereby enhances subsequently fracturecallus remo deling that leads to bony union of the fracture gap.
The Efficacy of Herbal Supplement Danggui Buxue Tang for Relieving Menopausal Symptoms
( Eliza L. Y. Wong ),( Annie W. L. Cheung ),( C. J. Haines ),( C. C. Wang ),( Chun-kwok Wong ),( Karl W. K. Tsim ),( William K. F. Cheng ),( Ping-chung Leung ) 대한폐경학회 2022 대한폐경학회지 Vol.28 No.1
Objectives: This study aimed to further explore the efficacy and safety of Danggui Buxue Tang (DBT), a simple herbal formula, for improving the quality of life of women suffering from menopausal symptoms. Methods: A third clinical trial to determine the clinical efficacy of high-dose DBT for a period of 12 weeks was carried out. The standard Menopause-Specific Quality of Life (MENQOL) assessment chart was used for the evaluation. Safety was defined as an absence of direct estrogenic effects, serum inflammatory cytokines. Notably, interleukin IL-6, IL-8 and tumor necrosis factor TNF-α, known to be directly related to estrogenic reactions in menopause studies, were monitored. Results: The third clinical trial indicated an overall improvement in the four domains of MENQOL, offering further proof of the efficacy of DBT demonstrated in the two previous trials. The serial checks of the three cytokines related to estrogen activities did not show either upward or downward trends. The haphazard behavior reactions of the three cytokines offered indirect indications that DBT improved the MENQOL independently from estrogen activities. Conclusions: The three clinical trials using DBT to relieve menopausal syndrome have offered solid evidence for its efficacy. The uncertainty regarding whether the “phytoestrogen” contained in DBT had bioactivities similar to estrogen was alleviated through the confirmation that no strict estrogenic bioactivities were observed. The issue of safety was further clarified via laboratory platform studies on DBT, which not only showed the lack of similarity with estrogen actions but also confirmed the value of combining the two herbs in the classic formula.
Kang, Y.-K.,Yau, T.,Park, J.-W.,Lim, H. Y.,Lee, T.-Y.,Obi, S.,Chan, S. L.,Qin, SK.,Kim, R. D.,Casey, M.,Chen, C.,Bhattacharyya, H.,Williams, J. A.,Valota, O.,Chakrabarti, D.,Kudo, M. Oxford University Press 2015 Annals of oncology Vol.26 No.12
<P>Axitinib plus best supportive care failed to meet the primary end point of overall survival in second-line treatment of advanced hepatocellular carcinoma in a randomized phase II study. However, the axitinib arm showed substantially improved progression-free survival, time to tumour progression, and clinical benefit rate compared with the placebo arm, with acceptable safety profile. Background: The efficacy and safety of axitinib, a potent and selective vascular endothelial growth factor receptors 1-3 inhibitor, combined with best supportive care (BSC) was evaluated in a global, randomized, placebo-controlled phase II trial in patients with locally advanced or metastatic hepatocellular carcinoma (HCC). Patients and methods: Patients with HCC and Child-Pugh Class A who progressed on or were intolerant to one prior antiangiogenic therapy were stratified by tumour invasion (presence/absence of extrahepatic spread and/or vascular invasion) and region (Asian/non-Asian) and randomized (2:1) to axitinib/BSC (starting dose 5 mg twice-daily) or placebo/BSC. The primary end point was overall survival (OS). Results: The estimated hazard ratio for OS was 0.907 [95% confidence interval (CI) 0.646-1.274; one-sided stratified P = 0.287] for axitinib/BSC (n = 134) versus placebo/BSC (n = 68), with the median (95% CI) of 12.7 (10.2-14.9) versus 9.7 (5.9-11.8) months, respectively. Results of prespecified subgroup analyses in Asian versus non-Asian patients or presence versus absence of tumour invasion were consistent with the overall population. Improvements favouring axitinib/BSC (P < 0.01) were observed in secondary efficacy end point analyses [progression-free survival (PFS), time to tumour progression (TTP), and clinical benefit rate (CBR)], and were retained among Asian patients in the prespecified subgroup analyses. Overall response rate did not differ significantly between treatments and patient-reported outcomes favoured placebo/BSC. Most common all-causality adverse events with axitinib/BSC were diarrhoea (54%), hypertension (54%), and decreased appetite (47%). Baseline serum analyses identified potential new prognostic (interleukin-6, E-selectin, interleukin-8, angiopoietin-2, migration inhibitory factor, and c-MET) or predictive (E-selectin and stromal-derived factor-1) factors for survival. Conclusions: Axitinib/BSC did not improve OS over placebo/BSC in the overall population or in stratification subgroups. However, axitinib/BSC resulted in significantly longer PFS and TTP and higher CBR, with acceptable toxicity in patients with advanced HCC. Trial Registration: ClinicalTrials.gov, NCT01210495.</P>
Silva, M.,Daheron, L.,Hurley, H.,Bure, K.,Barker, R.,Carr, Andrew J.,Williams, D.,Kim, H.W.,French, A.,Coffey, Pete J.,Cooper-White, Justin J.,Reeve, B.,Rao, M.,Snyder, Evan Y.,Ng, Kelvin S.,Mead, Ben Cell Press 2015 Cell stem cell Vol.16 No.1
Induced pluripotent stem cells (iPSCs) have the potential to transform drug discovery and healthcare in the 21<SUP>st</SUP> century. However, successful commercialization will require standardized manufacturing platforms. Here we highlight the need to define standardized practices for iPSC generation and processing and discuss current challenges to the robust manufacture of iPSC products.
BAIK, MYUNGGI,HARROLD, ROBERT L.,CHOI, CHANG B.,SLANGER, WILLIAM D.,SUNG, CHANG K.,PARK, CHUNG S. 충남대학교 생물공학연구소 1993 생물공학연구지 Vol.3 No.-
Effects of testosterone and energy restriction (30%) on enzyme activity and mRNA level of ornithine decarboxylase (ODC) were studied in 19-wkold female Sprague-Dawley rats. Testosterone implantation for 1 wk elicited a sixfold increase in ODC activity and a fourfold increase in ODC mRNA transcripts in the kidney. Energy restriction also increased renal ODC activity. Further, the 56% increase in ODC enzyme activity observed in the testosterone-implanted, energy-restricted group was greater than the 24% increase in the placebo-implanted, energy-restricted group. No changes in renal ODC mRNA levels were observed in the energyrestricted groups. These observations suggest that translational or post-translational mechanism(s) are in-volved in the greater renal OCD activity in energy-restricted rats. J. Nutr. 122: 1056-1061, 1992.