Objective To investigate the effects of Mus81 gene silencing on the chemosensitivity of human colon cancer HCT116 cells to oxaliplatin and explore the underlying mechanisms. Methods lentiviral-mediated RNAi was employed to inhibit Mus81 gene in human colon cancer HCT116 cells. MTT assay was employed to evaluate oxaliplatin chemosensitivity of HCT116. Cell apoptosis rate was detected by Annexin V-APC staining and the expression levels of p53, while Bax and Bcl-2 in HCT116 cells were detected by Real-time PCR and Western blot. Results Oxaliplatin IC50 of Mus81 depleted HCT116 cells was significantly decreased. After oxaliplatin treatment, the cell apoptosis rate of Mus81 silenced HCT116 cells was increased by 77.6% (P < 0.05), and the expression of p53 and Bax in these cells was obviously increased but the expression of Bcl-2 was significantly decreased (P < 0.01). Introducing Mus81 gene in Mus81 depleted HCT116 cells could reduce apoptosis rate. Conclusion Mus81 gene silencing can significantly improve oxliplatin chemosensitivity of HCT116 cells possibly by promoting cell apoptosis through regulating the expression of p53, Bax and Bcl-2.

Objective To observe the levels of serum VEGF in different molecular subtypes of breast cancer and explore its relationship with response to neoadjuvant chemotherapy. Methods Levels of serum VEGF in 110 cases with breast cancer underwent neoadjuvant chemotherapy were detected by ELISA prior to and after 3 cycles of neoadjuvant chemotherapy. Clinical response to neoadjuvant chemotherapy was evaluated by physical examination and ultrasonography. Results Levels of serum VEGF were significantly increased in breast cancer patients with≥4 lymph node metastasis than those with < 4 lymph node[(307.31 ± 101.42) pg/mL vs. (170.16 ± 73.07) pg/mL,P = 0.017]. Patients with positive HER-2 status had significantly higher levels of serum VEGF than those with HER-2 negative status [(235.15 ± 88.42 ) pg/mL vs. (179.82 ± 69.90) pg/mL, P = 0.024]. No significant difference was observed among age , menopausal status and hormone status. In patients with neoadjuvant chemotherapy of cCR and Cpr,the mean levels of serum VEGF were (205.75 ± 78.12) pg/mL and (226.04 ± 89.04) pg/mL, respectively. After 3 cycles of chemotherapy, levels of serum VEGF decreased to (145.15 ± 67.08) pg/mL and (161.27 ± 93.57) pg/mL. There was significant difference between two groups (P=0.009,0.014). In patients with SD or PD response, no significant difference was observed between levels of serum VEGF before and after chemotherapy (P = 0.577). Conclusions Levels of serum VEGF in breast cancer correlate with lymph nodes metastasis and HER-2 status and may decrease after neoadjuvant chemotherapy. However,whether or not the levels of serum VEGF can be used as a biomarker for response to neoadjuvant chemotherapy needs more further studies.

Objective:To compare the baseline difference in the quantitative hepatitis B core antibody levels (qAnti-HBc) between non-response and response group in children with HBeAg-positive chronic hepatitis B (CHB) who received antiviral therapy, and further explore the proportion and functional activity of CD8 + memory T lymphocyte subsets with different qAnti-HBC levels in peripheral blood of children.Methods:The baseline anti-HBc quantification (qAnti-HBc) levels of 85 children with HBeAg-positive CHB who visited the Department of Infectious Diseases, Children's Hospital of Chongqing Medical University from June 2018 to December 2020 were detected retrospectively. The relationship between the baseline qAnti-HBc level and HBeAg serological response in 37 children who received antiviral therapy was analyzed. The proportion of CD8 + memory T lymphocyte subsets and the secretion levels of interferon (IFN) γ, and tumor necrosis factor (TNF) α in peripheral blood of 59 children at baseline were detected by flow cytometry. The relationship between qAnti-HBc level and the proportion and functional activity of CD8 + memory T lymphocyte subsets was analyzed. Pearson’s Chi-square test was used to compare the count data. Mann-Whitney U test or Kruskal-Wallis test was used to compare measurement data between two or more groups, and Spearman’s rank correlation analysis was used for the correlation between continuous variables. Results:Among 37 children who received entecavir (ETV, 21/37 cases) or pegylated interferon (Peg-IFN, 16/37 cases), 18 cases had developed HBeAg seroconversion (10/ 21 cases in the ETV group, 8/16 cases in the Peg-IFN group). The baseline qAnti-HBc level was significantly higher in the response group [4.71 (4.64~4.81) log 10IU/ml] than the non-response group children [4.54 (4.45~4.64) log 10IU/ml, Z = -3.316, P = 0.001]. The proportion of CD8 + Tem, CD38 +CD8 + Tem, CD38 +CD8 + Temra cells and the levels of IFNγ and TNFα secreted by CD8 + T lymphocytes were significantly higher in the high-qAnti-HBc group than the low-qAnti-HBc group ( P < 0.05). The proportion of CD8 + Tem, CD38 +CD8 + Tem and CD38 +CD8 + Temra cells was significantly higher in ALT > 1× upper limit of normal value (ULN) group than ALT≤1×ULN group ( P < 0.05). However, there were no significant differences in the levels of IFNγ and TNFα secreted by CD8 + T lymphocytes between the two groups ( P > 0.05). Spearman’s correlation analysis showed that qAnti-HBc was positively correlated with the proportion of CD8 + Tem, CD38 +CD8 + Tem, CD38 +CD8 + Temra cells and the level of IFNγ secreted by CD8 +T lymphocytes ( P < 0.05). Additionally, ALT was only positively correlated with the proportion of CD38 +CD8 + TEM and CD38 + CD8 + Temra cells ( P < 0.05). Conclusion:Raised baseline qAnti-HBc level is related to the HBeAg serological response to antiviral therapy in children with CHB. Peripheral blood effector CD8+ T lymphocytes of CHB children with higher qAnti-HBc show stronger phenotype and functional activation characteristics, which may shed some light on the underlying immune mechanism related to antiviral therapy efficacy in children with CHB.

Objective:To compare the efficacy, safety, and influencing factors among children with hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B (CHB) who received short-term therapy with pegylated interferon alfa-2a (Peg-IFNα-2a) or continuous therapy with entecavir (ETV).Methods:Quantitative data were compared using analysis of variance to compare the differences between groups. Enumeration data were compared by χ2 test (or Fisher's exact test). Univariate and multivariate logistic regressions were used to analyze the influencing factors. Results:Peg-IFNα-2a, ETV, and untreated group had HBsAg clearance rates of 46.2%, 5.3%, and 0 after 52 weeks of therapy, respectively. HBsAg clearance in the patients' group with Peg-IFNα-2a and ETV was all accompanied by anti-HBS positive conversion, and the difference was statistically significant ( χ2=13.616, P=0.001). Peg-IFNα-2a group was followed-up for 104 weeks. Peg-IFNα-2a, ETV, and the untreated group had HBsAg clearance rates of 46.2%, 10.5%, and 0%, respectively, and the differences were statistically significant ( χ2=11.056, P=0.004). Only one of the two children with HBsAg clearance in the ETV group had achieved anti-HBs antibodies, and the difference was statistically significant ( χ2=13.616, P=0.001). Univariate and multivariate logistic regression analysis showed that HBsAg clearance was associated with age and antiviral therapy. During treatment, adverse events such as fever ( n=4, 30.8%), rash ( n=4, 30.8%), fatigue ( n=1, 7.7%), leukopenia ( n=7, 53.8%), arthritis ( n=1, 7.7%), and alopecia ( n=3, 23.1%) were observed in the Peg-IFNα-2a group, while none were observed in the ETV group. Conclusion:Peg-IFNα-2a antiviral therapy produced higher HBsAg clearance than ETV in five-year-old and younger children with HBeAg-positive CHB, while ETV had fewer adverse events and was safer than Peg-IFNα-2a.

Nanotechnology-based photothermal therapy has attracted great attention in the past decade. Nevertheless, photothermal therapy has some inherent drawbacks, such as the uneven heat production and limited laser penetration, often leading to insufficient treatment outcomes. Here, we developed a combination strategy to improve cancer therapy. The biomimetic albumin-modified gold nanorods (AuNRs) were prepared with incorporation of paclitaxel (PTX). This therapeutic system was characterized by several features. First, the albumin modification enhanced the biocompatibility and colloidal stability. Second, the surface-coated albumin promoted cellular uptake the albumin-binding protein pathway. Third, PTX was incorporated hydrophobic interaction between PTX and the albumin lipophilic domain. Fourth, the system can be used for combined photothermo-chemotherapy for yielding synergistic effects. The antitumor activity of the system was evaluated both and using the HCT116 colon cancer cell and tumor model. The combination therapy was found with an enhanced treatment efficiency and no obvious side effect. Most importantly, the thermal effect was also discovered with the ability to modulate the tumor microenvironments and suppress the macrophages polarization towards the M2 pro-tumor phenotype. It could be a mechanism for photothermal immunotherapy. The combination strategy and the system provide a potential method for cancer therapy.

An essential step for cancer vaccination is to break the immunosuppression and elicit a tumor-specific immunity. A major hurdle against cancer therapeutic vaccination is the insufficient immune stimulation of the cancer vaccines and lack of a safe and efficient adjuvant for human use. We discovered a novel cancer immunostimulant, trichosanthin (TCS), that is a clinically used protein drug in China, and developed a well-adaptable protein-engineering method for making recombinant protein vaccines by fusion of an antigenic peptide, TCS, and a cell-penetrating peptide (CPP), termed an "all-in-one" vaccine, for transcutaneous cancer immunization. The TCS adjuvant effect on antigen presentation was investigated and the antitumor immunity of the vaccines was investigated using the different tumor models. The vaccines were prepared

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.