Tolcapone derivative PCDNA inhibits Aβ42 fibrillogenesis and reduces its cytotoxicity / 药学学报

Abnormal aggregation of amyloid-β protein (Aβ) in brain plays a vital role in the occurrence of Alzheimer's disease (AD). Hence, inhibiting Aβ aggregation is one major tactic for therapy of AD. Previous studies have found that tolcapone can inhibit Aβ42 aggregation and reduce the cytotoxicity induced by Aβ42 aggregates, but clinical studies have found that tolcapone has strong liver toxicity. To reduce the liver toxicity of tolcapone, its side chain structure was modified to obtain its derivative phenethyl (E)-2-cyano-3-(3,4 dihydroxy-5-nitrobenzene)-acrylate (PCDNA). Thioflavin T (ThT) and atomic force microscopy (AFM) assays were used to explore the inhibitory effect of PCDNA on Aβ42 fibrillogenesis. The cytotoxicity assays were used to explore the inhibitory effect of PCDNA against the cytotoxicity induced by Aβ42 aggregates. In addition, the depolymerization effect of PCDNA on mature Aβ42 fibrils was also explored. Finally, molecular docking was used to explore the interaction between PCDNA and Aβ42 pentamer. These results lay the foundation for the study of the structural analogues of tolcapone as Aβ inhibitors.

Targeted therapy for lung cancer in the era of precision medicine / 医学研究生学报

With the rapid development of targeted therapy for lung cancer , dramatic changes are under way in the therapeutic means , drugs as well as the treatment concept .This article gives representation of the precision targeted therapy from the following 3 aspects:basic requirements for detection before treatment , higher requirements for selecting targeted drugs according to the subtypes of driver genes , and perfect requirements for dynamic adjustment with molecular changes for drug resistance .Through this review , the essence of precision medicine and whole process management for lung cancer might be better understood .

Design, synthesis, and PPARgamma agonistic activity of novel indenone derivatives / 药学学报

Agonists of peroxisome proliferator-activated receptor gamma (PPARgamma) are of interest as a treatment of type II diabetes, and indenone derivatives are a new class of non-TZD PPARgamma agonists. Based on existing indenone derivatives, a series of novel ones have been designed and synthesized. Meanwhile the structures have been comfirmed with 1H NMR and MS. Among them, 17b and 19 showed higher agonistic activities than rosiglitazone.

Effect of recombinant adenovirus Ad-DT-A in targeted therapy for malignant cancer cell lines with loss of IGF2 imprinting / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the feasibility of IGF2 imprinting system in target gene therapy for tumors.</p><p><b>METHODS</b>The mouse H19 enhancer, DMD and promoter H19 were amplified by PCR from mouse genomic DNA and then cloned into the plasmid pDC312. The EGFP and DT-A fragments were amplified by PCR and cloned into the recombinant plasmid, and then the shuttle plasmid were transfected into HEK293 cells together with the adenoviral vector Ad5, namely, Ad-EGFP and Ad-DT-A. Adenovirus hexon gene expression was applied to confirm the presence of adenovirus infections. The effect of the IGF2 imprinting system was tested by fluorescence microscopy. RT-PCR and Western blotting after transfection of the recombinant adenoviral vectors into cancer cells were used to show loss of IGF2 imprinting (LOI) and maintenance of IGF2 imprinting (MOI), respectively. The anti-tumor effect was assessed by MTT and flow cytometry after the HCT-8 (LOI). Human breast cancer cell line MCF-7 (MOI) and human normal gastric epithelial GES-1 (MOI) cell line were transfected with Ad-DT-A in vitro. The anti-tumor effect was detected by injecting the Ad-DT-A in nude mice carrying HCT-8 tumors.</p><p><b>RESULTS</b>The expression of EGFP protein, DT-A mRNA and DT-A protein were seen to be positive only in the HCT-8 tumor cell line. Infection with Ad-DT-A resulted in obviously growth inhibition in HCT-8 cells (75.4 ± 6.4)% compared with that in the control group, and increased the percentage of apoptosis in the HCT-8 cells (20.8 ± 5.9)%. The anti-tumor effect was further confirmed by injecting the recombinant adenoviruses in HCT-8 tumor-bearing nude mice, and the results showed that the Ad-DT-A inhibited the tumor growth, with on inhibition rate of 36.4%.</p><p><b>CONCLUSIONS</b>The recombinant adenoviruses carrying IGF2 imprinting system and DT-A gene have been successfully constructed, while Ad-DT-A can effectively kill the tumor cells showing loss of IGF2 imprinting. It might play an important role in future target gene therapy against malignant tumors based on loss of IGF2 imprinting.</p>

Erlotinib in the treatment of advanced non-small-cell lung cancer (NSCLC) / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement of survival in non-small-cell lung cancer (NSCLC) after the failure of front-line chemotherapy. The aim of this study was to evaluate the antitumor efficacy and toxicity of Erlotinib in the treatment of advanced NSCLC patients.</p><p><b>METHODS</b>A total of 104 patients with advanced NSCLC admitted in our department during December 2006 to November 2008 were enrolled in this study. Eligible patients received oral Erlotinib 150 mg/d until disease progression or intolerable toxicity. Best clinical response was determined using RECIST criteria, the adverse events were evaluated according to the NCI criteria.</p><p><b>RESULTS</b>The total effective rate was 27.9% (29/104) and the clinical benefit was 76.0% (79/104). The median progression-free survival was 5.1 months (95%CI 4.0 - 8.0). The median survival time was 13.1 months (95%CI 10.0 - 15.7). The 1-year survival rate was 61.5%. Significant survival benefit from erlobinib therapy was observed for patients with good personal status (HR 0.56, P = 0.006), adenocarcinoma (HR 0.43, P = 0.004) and skin rash (HR 0.46, P = 0.005). But patients with smoking (HR 2.75, P < 0.001) and liver metastasis (HR 2.91, P = 0.002) add the risk of death. The adverse events were mild (grade < or = 2), most common toxicities were skin rash in 73.1% (76/104) and diarrhea in 41.3% (43/104). Only 6.7% (7/104) patients got adverse events of grade > or = 3.</p><p><b>CONCLUSION</b>Erlotinib is an effective and well-tolerated treatment option for advanced NSCLC and could offer an alternative for patients after the failure of first-line chemotherapy, unsuitable for or not wishing to receive chemotherapy.</p>

Study on extraction of coumarins in Cnidium monieri by supercritical CO2 and separation of compositions analysis / 中国中药杂志

<p><b>OBJECTIVE</b>To analyze the chemical constituents of supercritical carbon dioxide extraction products from Cnidium monieri.</p><p><b>METHOD</b>Four-factor and three-level orthogonal experimental design was used to optimize the SFE conditions as guided by the content of total coumarins in the extract. The chemical constituents were separated and identified by recrystalization.</p><p><b>RESULT</b>Optimum extraction process was established: 25 MPa as extraction pressure, 50 degrees C as extraction temperature, 6.5 MPa as separation pressure and 60 degrees C as separation temperature.</p><p><b>CONCLUSION</b>Changes in extraction pressure, temperature, time, pulverized degree and separation pressure affect the extracting results remarkably. The two kinds of chemical constituents were separated by recrystallization from C. monieri and identified by the methods of UV, IR, MS, NMR.</p>