Research progress on tumor microenvironment and immune combination therapy of MSS colorectal cancer / 国际肿瘤学杂志

In recent years, immunotherapy, especially immune checkpoint inhibitors, has shown obvious advantages in prolonging the survival of patients with advanced tumors, and the tumor microenvironment is one of the important factors affecting the efficacy of immunity. Patients with microsatellite-stable colorectal cancer exhibit immune responses in combination with immune checkpoint inhibitor therapy. In-depth exploration of the tumor microenvironment characteristics of microsatellite-stable colorectal cancer and the application of combined immune checkpoint inhibitor therapy can provide new ideas and directions for colorectal cancer immunotherapy.

CCR6 promotes liver metastasis of colorectal cancer through epithelial-mesenchymal transition / 国际肿瘤学杂志

Objective:To detect the expressions of chemokine receptor 6 (CCR6), CC chemokine ligand 20 (CCL20) E-cadherin and vimentin in tissues of colorectal cancer and their paired liver metastases, and to investigate the possible mechanism of CCR6 in liver metastasis of colorectal cancer.Methods:A total of 62 cases (54 cases of colon cancer and 8 cases of rectal cancer) of primary colorectal adenocarcinoma resection with wax lumps were selected from the First Hospital of Shanxi Medical University and Shanxi Oncology Hospital from 2009 to 2017 with complete data, including 20 samples of colorectal cancer resection with liver metastasis during the same period. The expressions of CCR6, CCL20, E-cadherin and vimentin in colorectal cancer and liver metastases tissues were detected by immunohistochemistry, and the relationships between the expressions of CCR6, E-cadherin and vimentin and the clinicopathological features of patients were analyzed. Logistic multivariate regression was used to analyze the relationship between liver metastasis and clinicopathological features, CCR6, E-cadherin and vimentin. Spearman correlation was used to analyze the correlations between CCR6 and E-cadherin and vimentin.Results:The positive expression rate of CCR6 in colorectal cancer tissues was 66.1% (41/62), 85.0% (17/20) in colorectal cancer with liver metastasis and 70.0% (14/20) in liver metastasis tissues. The positive expression rate of CCL20 in colorectal cancer tissues was 83.9% (52/62), 90.0% (18/20) in colorectal cancer with liver metastasis and 90.0% (18/20) in liver metastasis tissues. The positive expression rate of E-cadherin in colorectal cancer tissues was 67.7% (42/62), 50.0% (10/20) in colorectal cancer with liver metastasis and 65.0% (13/20) in liver metastasis tissues. The positive expression rate of vimentin in colorectal cancer tissues was 79.0% (49/62), 85.0% (17/20) in colorectal cancer with liver metastasis and 90.0% (18/20) in liver metastasis tissues. The expression of CCR6 was closely related to lymph node metastasis ( χ2=11.142, P=0.001), liver metastasis ( χ2=4.694, P=0.030) and TNM stage ( χ2=21.785, P<0.001). E-cadherin was closely related to lymph node metastasis ( χ2=4.694, P=0.030), liver metastasis ( χ2=4.253, P=0.039) and TNM stage ( χ2=7.867, P=0.005). Vimentin was closely related to lymph node metastasis ( χ2=7.293, P=0.007) and TNM stage ( χ2=5.712, P=0.017). CCR6, E-cadherin and vimentin were independent of gender, age, tumor site, tumor size and differentiation degree of colorectal cancer patients (all P>0.05). Logistic regression analysis showed that the expressions of CCR6 ( OR=6.812, 95% CI: 1.206-38.474, P=0.030) and E-cadherin ( OR=0.256, 95% CI: 0.069-0.945, P=0.041) were independent factors affecting the liver metastasis of colorectal cancer. Spearman correlation analysis showed that CCR6 was associated with E-cadherin expression ( r=0.454, P=0.044) and vimentin expression ( r=0.509, P=0.022) in 20 iver metastasis tissues of colorectal cancer. Conclusion:CCR6 may promote colorectal cancer progress and liver metastasis by part of epithelial-mesenchymal transition.

Exosomal CircPRRX1 Enhances Doxorubicin Resistance in Gastric Cancer by Regulating MiR-3064-5p/PTPN14 Signaling

Purpose@#Gastric cancer (GC) is a malignant tumor with a high mortality rate. Drug resistance is a major obstacle to GC therapy. This study aimed to investigate the role and mechanism of exosomal circPRRX1 in doxorubicin resistance in GC. @*Materials and Methods@#HGC-27 and AGS cells were exposed to different doses of doxorubicin to construct doxorubicin-resistant cell lines. Levels of circPRRX1, miR-3064-5p, and nonreceptor tyrosine phosphatase 14 (PTPN14) were detected by quantitative real-time PCR or Western blot assay. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, transwell,and Western blot assays were used to explore the function of circPRRX1 in GC cells. Interactions among circPRRX1, miR-3064-5p,and PTPN14 were confirmed by dual-luciferase reporter assay. The in vivo function of circPRRX1 was analyzed in a xenograft tumor model. @*Results@#CircPRRX1 was highly expressed in doxorubicin-resistant GC cell lines. Knockdown of circPRRX1 reversed doxorubicin resistance in doxorubicin-resistant GC cells. Additionally, extracellular circPRRX1 was carried by exosomes to spread doxorubicin resistance. CircPRRX1 silencing reduced doxorubicin resistance by targeting miR-3064-5p or regulating PTPN14. In GC patients,high levels of circPRRX1 in serum exosomes were associated with poor responses to doxorubicin treatment. Moreover, depletion of circPRRX1 reduced doxorubicin resistance in vivo. @*Conclusion@#CircPRRX1 strengthened doxorubicin resistance by modulating miR-3064-5p/PTPN14 signaling and might be a therapeutic target for GC patients.

Application of early goal-directed sedation with bispectral index in sedation management of severe patients in ICU / 中国医师杂志

Objective The bispectral index (BIS) was introduced into the sedation strategy of critical patients in intensive care unit (ICU) and replaced the Richmond agitation sedation scale (RASS).The ventilation time,ICU length of stay,and 90-day mortality were compared between the two groups of patients who performed early goal-directed sedation (EGDS) or standard traditional directed sedation (STDS) strategies.Methods A prospective controlled study of severe patients with mechanical ventilation ≥48 h in ICU (20 cases from April 2016 to May 2017,46 cases from June 2017 to April 2018) were randomly divided into EGDS or STDS group.There were no significant differences in age,gender,and acute physiology and chronic health evaluation score Ⅱ (APACHE Ⅱ) score between the two groups in the two periods.The correlation between RASS and BIS was analyzed in the first period.The BIS of the patients in a RASS range of (-2-1) was 73.65 ± 7.87 in the EGDS group,and that of RASS range of (-3--1) was 64.14 ± 7.25 in the STDS group.The above BIS was applied to the two sedation strategies in the second period respectively.The ventilation time,ICU length of stay,and 90-day mortality were recorded.Results There was no significant difference in the ventilation time between the two groups [(164.12 ± 137.96) h and (155.33 ±64.86)h,P =0.08].ICU length of stay of the EGDS group was longer than that of the STDS group.The 90-day mortality of the EGDS group was higher than that of the STDS group.Conclusions Correlations between RASS and BIS were found in this study,and BIS can be used for sedation assessment in ICU patients.Large sample study is still needed to compare EGDS and STDS with BIS.

Signaling pathways of epithelial-mesenchymal transition in colon cancer / 国际肿瘤学杂志

Epithelial-mesenchymal transition (EMT) plays a critical role in the carcinogenesis of colon cancer,and promotes the tumor invasion and metastasis.Studies have shown several signals are involved including transforming growth factor-β (TGF-β),Wnt/β-catein,Notch,nuclear factor-κB (NF-κB) and PI3K/Akt signal pathway.It is important to elucidate EMT-related signal pathway thereby providing new insights into possible therapeutic interventions of colon cancer.

Scanning electronic microscope observation of bone marrow stem cells transfected by IGF-1 gene and cultured onto ostrich true bone ceramic / 实用口腔医学杂志

Objective:To evaluate the biocompatibility of insulin-like growth factor I (IGF-1) gene transfected bone marrow stem cells (MSCs) with ostrich true bone ceramic (OTBC). Methods:Rat MSCs were transfected with IGF-1 gene, and positive clones were selected by G418. The expression of IGF-1 protein in the MSCs was detected by immunocytochemical technique. The IGF-1 transfected MSCs were cultured with OTBC and the morphology of the cells was observed by scanning electronic microscope(SEM) at different time point. Results:Immunohistochemical staining suggested that the IGF-1 protein was expressed in the IGF-1 transfected MSCs. The cells adhered to OTBC and stretched well after 24 h of culture. The IGF-1 transfected MSCs proliferated on the surface of OTBC with culture time.Conclusion:The OTBC has a good biocompatibility with IGF-1 transfected MSCs.