Refractoriness of acute myeloid leukemia (AML) cells to chemotherapeutics represents a major clinical barrier. Suicide gene therapy for cancer has been attractive but with limited clinical efficacy. In this study, we investigated the potential application of herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) based system to inhibit chemoresistant AML cells. We first generated Ara-C resistant K562 cells and doxorubicin-resistant THP-1 cells. We found that the HSV-TK/GCV anticancer system suppressed drug resistant leukemic cells in culture. Chemoresistant AML cell lines displayed similar sensitivity to HSV-TK/GCV. Moreover, HSV-TK/GCV killing of leukemic cells was augmented to a mild but significant extent by all-trans retinoic acid (ATRA) with concomitant upregulation of Connexin 43, a major component of gap junctions. Interestingly, HSV-TK/GCV killing was enhanced by expression of vesicular stomatitis virus G glycoprotein (VSV-G), a fusogenic membrane protein, which also increased leukemic cell fusion. Co-culture resistant cells expressing HSV-TK and cells stably transduced with VSV-G showed that expression of VSV-G could promote the bystander killing effect of HSV-TK/GCV. Furthermore, combination of HSV-TK/GCV with VSV-G plus ATRA produced more pronounced antileukemia effect. These results suggest that the HSV-TK/GCV system in combination with fusogenic membrane proteins and/or ATRA could provide a strategy to mitigate the chemoresistance of AML.
Cell Fusion ; Cell Line ; Coculture Techniques ; Connexin 43 ; Cytarabine ; Gap Junctions ; Genetic Therapy ; Glycoproteins* ; Homicide* ; K562 Cells ; Leukemia, Myeloid, Acute ; Membrane Proteins ; Simplexvirus* ; Suicide ; Thymidine* ; Tretinoin ; Up-Regulation ; Vesicular Stomatitis*

OBJECTIVE To study the effects and m echanism of eriocalyxin B （EriB）on epithelial -mesenchymal transition （EMT）of colon cancer cells . METHODS The colon cancer cells HT 29 and HCT 116 as research objects . Scratch-healing assay and Transwell assay were used to detect the effects of EriB on migration and invasion of two kinds of cells . Western blot method was used to detect the effects of EriB （1.0 μmol/L），EriB+Wnt/β-catenin signaling pathway agonist Licl （1.0 μmol/L EriB+ 10 mmol/L Licl）or EriB+Wnt/ β-catenin signaling pathway inhibitor XAV 939（1.0 μmol/L EriB+ 10 μmol/L XAV 939）on the expressions of EMT related proteins [E-cadherin，N-cadherin，Snail] and Wnt/ β-catenin signaling pathway related proteins [β-catenin，c-myc， cyclin D 1，TCF4]. RESULTS EriB can significantly inhibit the invasion and migration of two kinds of cells （P＜0.01）. EriB significantly reduced the protein expressions of N -cadherin，Snail，β-catenin，c-myc，cyclin D 1 and TCF 4 while increases the protein expression of E -cadherin（P＜0.05 or P＜0.01）. After EriB combined with Licl ，the protein expressions of β-catenin，c- myc，cyclin D 1 and TCF 4 in the two kinds of cells were reverse d（P＜0.05 or P＜0.01）. After combined with XAV 939，the protein expressions of β-catenin and N -cadherin were further down -regulated（P＜0.05 or P＜0.01）；the protein expression of E -cadherin was further up -regulated（P＜0.01），while migration rate was decreased significantly （P＜0.01）. CONCLUSIONS EriB can inhibit the epithelial -mesenchymal transition of colon 19SXHZ0351） cancer cells by inhibiting the activation of Wnt/ β -catenin

Objective    To evaluate the survival results of surgical resection (SR) and CT-guided percutaneous ablation (PA) for stageⅠnon-small cell lung cancer (NSCLC). Methods    The PubMed, Web of Science, EMbase, The Cochrane Library, CNKI, VIP, Wanfang databases from inception to June 2021 were searched to collect comparative studies on the survival results between SR and CT-guided PA treatment for stageⅠNSCLC. RevMan 5.3 software was used for statistical analysis of data. Results    A total of 3 114 patients were included in 11 studies. The results of meta-analysis showed that compared with the PA group, the SR group had a higher 2-year postoperative overall survival (OS) rate (OR=1.44, 95%CI 1.00-2.06, P=0.05), 3-year postoperative OS rate (OR=2.37, 95%CI 1.47-3.81, P<0.001), 5-year OS rate (OR=1.64, 95%CI 1.19-2.28, P<0.01), 5-year progression-free survival rate after operation (OR=2.43, 95%CI 1.54-3.82, P<0.001) and lower local recurrence rate (OR=0.26, 95%CI 0.13-0.54, P<0.001). There were no statistical differences between the two groups in terms of 1-year postoperative OS rate, 1-year, 2-year, and 3-year tumor-related survival rates, 1-year, 2-year tumor-free survival rates, or distant postoperative recurrence rate (P>0.05). Conclusion    For patients with stageⅠNSCLC with optimal basic conditions, surgery is a more appropriate treatment. For patients who cannot withstand surgical injuries or refuse surgery, CT-guided PA is also a potential alternative treatment. However, this conclusion needs  to be verified by prospective controlled trials with larger sample sizes and a more rigorous design.