Meta-analysis of Seven Randomized Control Trials to Assess the Efficacy and Toxicity of Combining EGFR-TKI with Chemotherapy for Patients with Advanced NSCLC who Failed First-Line Treatment

Xiao, Bing-Kun,Yang, Jian-Yun,Dong, Jun-Xing,Ji, Zhao-Shuai,Si, Hai-Yan,Wang, Wei-Lan,Huang, Rong-Qing Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Background: Some recent clinical trials have been conducted to evaluate a combination of EGFR- TKI with chemotherapy for advanced NSCLC patients as second-line therapy, but the results on the efficacy of such trials are inconsistent. The aim of this meta-analysis was to evaluate the efficacy and safety of combination of EGFR-TKI and chemotherapy for patients with advanced NSCLC who failed first-line treatment. Materials and Methods: We searched relative trials from PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Library and Clinical Trials.gov. Outcomes analyzed were overall response rate (ORR), progression- free survival (PFS), overall survival (OS) and major toxicity. Results: Seven trails eventually were included in this meta-analysis, covering 1,168 patients. The results showed that the combined regimen arm had a significant higher ORR (RR 1.76 [1.16, 2.66], p=0.007) and longer PFS (HR 0.75 [0.66-0.85], p<0.00001), but failed to show effects on OS (HR 0.88 [0.68-1.15], p=0.36). In terms of subgroup results, continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance confered no improvement in ORR (RR 0.95 [0.68, 1.33], p=0.75) and PFS (HR 0.89[0.69, 1.15], p=0.38), and OS was even shorter (HR1.52 [1.05-2.21], p=0.03). However, combination therapy with EGFR-TKI and chemotherapy after failure of first-line chemotherapy significantly improved the ORR (RR 2.06 [1.42, 2.99], p=0.0002), PFS (HR 0.71 [0.61, 0.82], p<0.00001) and OS (HR 0.74 [0.62-0.88], p=0.0008), clinical benefit being restricted to combining EGFR-TKI with pemetrexed, but not docetaxel. Grade 3-4 toxicity was found at significantly higher incidence in the combined regimen arm. Conclusions: Continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance should be avoided. Combination therapy of EGFR-TKI and pemetrexed for advanced NSCLC should be further investigated for prognostic and predictive factors to find the group with the highest benefit of the combination strategy.

Retinoic Acid Promotes Interleukin-4 Plasmid-Dimethylsulfoxide Topical Transdermal Delivery for Treatment of Psoriasis

( Zhong Wen Chen ),( Yin Bing Zhang ),( Xaing Jun Chen ),( Xiao Liu ),( Zhen Wang ),( Xi Kun Zhou ),( Ji Qiu ),( Nan Nan Zhang ),( Xiu Teng ),( Yong Qiu Mao ),( Chang Yong Liu ),( Yu Quan Wei ),( Jion 대한피부과학회 2015 Annals of Dermatology Vol.27 No.3

Background: Psoriasis is an autoimmune disease that is caused by a shift in the Th1/Th2 balance toward Th1- dominant immunity. It has been established as an effective treatment to counteract psoriasis by subcutaneous injection of recombinant interleukin (IL)-4, and IL-4 gene therapy by topical transdermal penetration has shown its antipsoriatic effect in mice. Retinoic acid (RA) and dimethylsulfoxide can increase the efficiency of gene transfection in the topical transdermal delivery system. Objective: We investigated whether RA could improve anti-psoriasis efficiency using IL-4 expression plasmid pORF-mIL-4 (pIL-4) via transdermal delivery system in K14-vascular endothelial growth (K14- VEGF) factor transgenic mice. Methods: After pretreatment with RA, plasmid pIL-4 in 10% dimethylsulfoxide was applied to the ear skin by topical transdermal penetration. Hematoxylin- eosin staining and immunohistochemistry were performed with ear samples to evaluate anti-psoriasis efficiency in mice. Results: The psoriasis pathological features were relieved and psoriasis-associated factors were significantly reduced. Conclusion: Our results reveal that topical application of pIL-4 in dimethylsulfoxide by transdermal delivery with RA pretreatment can improve psoriasis significantly. (Ann Dermatol 27(2) 121∼127, 2015)

Retinoic Acid Promotes Interleukin-4 Plasmid-Dimethylsulfoxide Topical Transdermal Delivery for Treatment of Psoriasis

( Zhong Wen Chen ),( Yin Bing Zhang ),( Xaing Jun Chen ),( Xiao Liu ),( Zhen Wang ),( Xi Kun Zhou ),( Ji Qiu ),( Nan Nan Zhang ),( Xiu Teng ),( Yong Qiu Mao ),( Chang Yong Liu ),( Yu Quan Wei ),( Jion 대한피부과학회 2015 Annals of Dermatology Vol.27 No.2

Background: Psoriasis is an autoimmune disease that is caused by a shift in the Th1/Th2 balance toward Th1- dominant immunity. It has been established as an effective treatment to counteract psoriasis by subcutaneous injection of recombinant interleukin (IL)-4, and IL-4 gene therapy by topical transdermal penetration has shown its antipsoriatic effect in mice. Retinoic acid (RA) and dimethylsulfoxide can increase the efficiency of gene transfection in the topical transdermal delivery system. Objective: We investigated whether RA could improve anti-psoriasis efficiency using IL-4 expression plasmid pORF-mIL-4 (pIL-4) via transdermal delivery system in K14-vascular endothelial growth (K14- VEGF) factor transgenic mice. Methods: After pretreatment with RA, plasmid pIL-4 in 10% dimethylsulfoxide was applied to the ear skin by topical transdermal penetration. Hematoxylin- eosin staining and immunohistochemistry were performed with ear samples to evaluate anti-psoriasis efficiency in mice. Results: The psoriasis pathological features were relieved and psoriasis-associated factors were significantly reduced. Conclusion: Our results reveal that topical application of pIL-4 in dimethylsulfoxide by transdermal delivery with RA pretreatment can improve psoriasis significantly.(Ann Dermatol 27(2) 121∼127, 2015)

Resveratrol enhances the functionality and improves the regeneration of mesenchymal stem cell aggregates

Yi-Jing Wang,Pan Zhao,Bing-Dong Sui,Nu Liu,Cheng-Hu Hu,Ji Chen,Chen-Xi Zheng,An-Qi Liu,Kun Xuan,Ya-Ping Pan,Yan Jin 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Mesenchymal stem cell (MSC)-based regeneration, specifically cell aggregate or cell sheet engineering, is a promising approach for tissue reconstruction. Considering the advantages of ease of harvest and lack of immune rejection, the application of autologous MSCs (i.e., patients’ own MSCs) in regenerative medicine has developed considerable interest. However, the impaired cell viability and regenerative potential following MSCs impacted by disease remain a major challenge. Resveratrol (RSV) exhibits reliable and extensive rejuvenative activities that have received increasing clinical attention. Here, we uncovered that resveratrol enhances the functionality and improves the regeneration of mesenchymal stem cell aggregates. Periodontal ligament MSCs (PDLSCs) from normal control subjects (N-PDLSCs) and periodontitis patients (P-PDLSCs) were investigated. Compared to N-PDLSCs, P-PDLSCs were less capable of forming cell aggregates, and P-PDLSC aggregates showed impaired osteogenesis and regeneration. These functional declines could be mimicked in N-PDLSCs by tumor necrosis factor alpha (TNF-α) treatment. Notably, a TNF-α-induced functional decline in N-PDLSC aggregates was rescued by RSV application. More importantly, in both N-PDLSCs and P-PDLSCs, RSV promoted cell aggregate formation and improved their osteogenic potential. Furthermore, as proven ectopically in vivo, the tissue regenerative capability of P-PDLSC aggregates was also enhanced after RSV treatment during aggregate formation in vitro. Finally, in a rat in situ regeneration model, we successfully applied both N-PDLSC aggregates and P-PDLSC aggregates to repair periodontal defects upon long-term functional improvements by RSV preconditioning. Together, our data unravel a novel methodology for using pharmacology (i.e., RSV)-based cell aggregate engineering to improve the functionality and facilitate the regeneration of MSCs from both healthy and inflammatory microenvironments, shedding light on improving the application of autologous MSC-mediated regenerative medicine.

Versicolols A and B, two new prenylated isocoumarins from endophytic fungus Aspergillus versicolor and their cytotoxic activity

Min Zhou,Jie Lou,Yin-Ke Li,Yue-De Wang,Kun Zhou,Bing-Kun Ji,Wei Dong,Xue-Mei Gao,Gang Du,Qiu-Fen Hu 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.1

Versicolols A and B (1 and 2), two rareprenylated isocoumarin derivatives, along with five knownisocoumarins (3–7) were isolated from the fermentationproducts of an endophytic fungus Aspergillus versicolor. Their structures were elucidated on the basis of extensivespectroscopic analysis, including 1D- and 2D-NMR techniques. Compounds 1 and 2 were evaluated for their cytotoxicityagainst five human tumor cell lines. The resultsshowed that compounds 1 exhibited weak cytotoxicityagainst A549 and MCF7 cells with IC50 values of 9.4 and8.8 lm, and compound 2 exhibited weak cytotoxicityagainst SHSY5Y and MCF7 cells with IC50 values of 8.2and 6.8 lm, respectively.