ObjectiveTo summarize the therapeutic targets of pancreatic cancer (PC). MethodsThe related literatures about the therapeutic targets of PC were reviewed. ResultsPC was one of the most challenging tumor in worldwide, and was characterized as a highly aggressive disease with poor overall prognosis and a high mortality rate. The hallmark of PC was its poor response to radio-and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches which could significantly improve the clinical outcome of PC had been described, involving signal-transduction pathways, immune response, stroma reaction, and epigenetic changes. ConclusionsMany therapeutic targets are involved in the treatment of PC. As current therapies failed to significantly improve the progression and the survival of PC, new therapeutic approaches and clinical studies are strongly required.
ObjectiveTo investigate the effects of overexpression of alpha/beta hydrolase domain-containing protein 5 (ABHD5) on the invasion and migration of human colon cancer cell line HCT116 and the pathway of adenosine monophosphate-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR).MethodsThe expression of ABHD5 in colon cancer tissues and its relationship with clinicopathological features was analyzed by UALCAN database. HCT116 cells were cultured in vitro and transfected with ABHD5 recombinant plasmid, then they were divided into control group, negative transfection group and ABHD5 transfection group. Real time quantitative PCR (qRT-PCR) was used to detect the expression of ABHD5 mRNA in HCT116 cells. The proliferation of HCT116 cells was detected by CCK-8 method. Transwell assay was used to detect the invasion and migration of HCT116 cells. The expression of matrix metalloprotein 9 (MMP-9), E-cadherin, Snail, and AMPK/mTOR pathway proteins p-AMPK, AMPK, p-mTOR and mTOR were detected by Western blot.ResultsThe results of the UALCAN showed that compared with normal colon tissues, the expression of ABHD5 mRNA in colon cancer tissues was decreased (P<0.05), and which in the adenocarcinoma and the N1 stage was lower than that of the mucinous adenocarcinoma (P<0.05) and N0 stage (P<0.05), respectively. Compared with the control group and the negative transfection group, the expression of ABHD5 mRNA in the ABHD5 transfection group was increased (P<0.05), the proliferation inhibition rate of HCT116 cells in the ABHD5 transfection group was increased (P<0.05), the numbers of migration and invasion cells in the ABHD5 transfection group were decreased (P<0.05), the expressions of MMP-9, Snail, p-mTOR and mTOR were reduced, and the expressions of E-cadherin, p-AMPK and AMPK were increased (P<0.05).ConclusionsThe overexpression of ABHD5 can inhibit the invasion and migration of colon cancer HCT116 cells, activate AMPK, and inhibit the expression of mTOR. It suggests that ABHD5 may play a role in inhibiting colon cancer by affecting AMPK/mTOR pathway.
ObjectiveTo understand the molecular mechanisms and targeted therapy research progress of gastric cancer associated with the RTK/RAS signaling pathway, in order to provide reference for treatment of gastric cancer. MethodThe related literatures about the molecular mechanism and targeted therapy of RTK/RAS signaling pathway related gastric cancer at home and abroad in recent years were reviewed. ResultsTargeted therapy had been widely applied in the treatment of gastric cancer associated with the RTK/RAS signaling pathway, showing good efficacy and significantly prolonging patients’ survival time, further deepening the understanding of the molecular mechanisms of gastric cancer. Targeted therapies for gastric cancer associated with the RTK/RAS signaling pathway focused on human epidermal growth factor receptor 2 (HER-2), epidermal growth factor receptor, fibroblast growth factor receptor 2, cellular-mesenchymalepithelial transition factor and Kirsten ratsarcoma viral oncogene homolog associated targets. Currently, there were many drugs targeting HER-2 target, while research on other targets mostly remains in the clinical trial stage, and showing promising prospects. ConclusionTargeted therapy can benefit most patients with gastric cancer, but the drug resistance and multi-drug combination therapy are still difficult problems that we need to overcome in the future.
Liposome is an ideal drug carrier with many advantages such as excellent biocompatibility, non-immunogenicity, and easy functionalization, and has been used for the clinical treatment of many diseases including tumors. For the treatment of tumors, liposome has some passive targeting capability, but the passive targeting effect alone is very limited in improving the drug enrichment in tumor tissues, and active targeting is an effective strategy to improve the drug enrichment. Therefore, active targeting liposome drug-carriers have been extensively studied for decades. In this paper, we review the research progresses on active targeting liposome drug-carriers based on the specific binding of the carriers to the surface of tumor cells, and summarize the opportunities, challenges and future prospects in this field.
Objective To explore the application value of time of flight magnetic resonance angiography (TOF-MRA) in target bypass surgery for moyamoya disease. Methods The data of patients with moyamoya disease in Affiliated Drum Tower Hospital, Medical College, Nanjing University between May 1 and August 30, 2020 were retrospectively analyzed. Patients were divided into navigation group and control group according to whether navigation technology was used during operation. All patients completed TOF-MRA evaluation before operation, and all patients completed surgical treatment. One week after operation, TOF-MRA was reviewed to evaluate the patency of anastomotic stoma. The intraoperative and postoperative conditions of the two groups were compared. Results Finally, 48 patients with moyamoya disease were included. 22 patients who used intraoperative navigation were included in the navigation group, and 26 patients with moyamoya disease who did not use intraoperative navigation in the same period were included in the control group. There was no significant difference between the two groups in gender, age, Suzuki stage before operation, proportion of posterior circulation involvement, proportion of bleeding type, proportion of hypertension and proportion of diabetes (P>0.05). The operation duration [(3.3±0.4) vs. (3.6±0.6) h] and postoperative hospital stay [(7.3±1.9) vs. (8.8±2.7) d] in the navigation group were shorter than those in the control group (P<0.05). There was no significant difference between the two groups in the proportion of patients who completed bypass surgery, the proportion of middle meningeal artery retained, the postoperative patency rate, the proportion of temporary dysfunction, and the proportion of serious complications (P>0.05). Conclusion TOF-MRA sequence combined with navigation technology can effectively guide the surgical scheme design and postoperative evaluation of moyamoya disease.
The drug-target protein interaction prediction can be used for the discovery of new drug effects. Recent studies often focus on the prediction of an independent matrix filling algorithm, which apply a single algorithm to predict the drug-target protein interaction. The single-model matrix-filling algorithms have low accuracy, so it is difficult to obtain satisfactory results in the prediction of drug-target protein interaction. AdaBoost algorithm is a strong multiple classifier combination framework, which is proved by the past researches in classification applications. The drug-target interaction prediction is a matrix filling problem. Therefore, we need to adjust the matrix filling problem to a classification problem before predicting the interaction among drug-target protein. We make full use of the AdaBoost algorithm framework to integrate several weak classifiers to improve performance and make accurate prediction of drug-target protein interaction. Experimental results based on the metric datasets show that our algorithm outperforms the other state-of-the-art approaches and classical methods in accuracy. Our algorithm can overcome the limitations of the single algorithm based on machine learning method, exploit the hidden factors better and improve the accuracy of prediction effectively.
This study reports a case of a 56-year-old female patient with BRAF-mutated non-small cell lung cancer (NSCLC) who successfully underwent curative surgery after neoadjuvant targeted therapy with the BRAF inhibitor dabrafenib combined with the MEK inhibitor trametinib. The chest drainage tube was removed 2 days postoperatively, and the patient was discharged smoothly. Postoperative pathology indicated invasive adenocarcinoma, moderately to highly differentiated, with 80% being lepidic type, and the maximum tumor diameter was 4 cm. No vascular invasion, nerve invasion, air cavity dissemination, pleural invasion, or lymph node metastasis were observed. The postoperative staging was ypT2aN0M0. The patient continued with adjuvant treatment with dabrafenib combined with trametinib postoperatively, and no signs of recurrence were found in the follow-up examination six months after surgery.
Objective To explore the role of cyclin B1 (CCNB1), cyclin B2 (CCNB2) and cyclin dependent kinase 1 (CDK1) in lung adenocarcinoma (LUAD) using bioinformatic data. Methods First, RNA expression data were downloaded from two datasets in Gene Expression Omnibus (GEO), and DESeq2 software was used to identify deferentially expressed genes (DEGs). Subsequent analyses were conducted based on the results of these DEGs: protein-protein interaction (PPI) network was constructed with STRING database; the modules in PPI network were analyzed by Molecular Complex Detection software, and the most significant modules were selected, the genes included in these modules were the hub genes; high-throughput RNA sequencing data from other databases were used to verify the expression of these hub genes to confirm whether they were DEGs; survival curve analyses of the confirmed DEGs were conducted to select genes that had significant influence on the survival of LUAD; the expression of these hub genes in different stages of LUAD were also analyzed. Then, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for these selected hub genes using KOBAS database. MuTarget tool was used to analyze the correlations between the expression of these selected hub genes and gene mutation status in LUAD. The potential value of these hub genes in the treatment of LUAD was explored based on the drug information in GDSC database. Finally, immunohistochemical data from Human Protein Atlas (HPA) database were used to verify the expression of these hub genes in LUAD again. Results According to the expression data in GEO, 594 up-regulated genes and 651 down-regulated genes were identified (P<0.05), among which 30 hub genes were selected for subsequent analyses. The RNA high-throughput sequencing data of other databases verified that 18 genes were DEGs, among which 8 hub genes had significant impact on disease-free survival in LUAD (P<0.05). Moreover, the 8 genes were differentially expressed in different stages of LUAD, which were higher in the middle and late stage of LUAD. Among the 8 genes. CCNB1, CCNB2 and CDK1 were significantly enriched in the cell cycle pathway. The expression of CCNB1, CCNB2 and CDK1 in LUAD was closely related to the TP53 mutation status. In addition, CDK1 was associated with four drugs, revealing the potential value of CDK1 in the treatment of LUAD. Finally, immunohistochemical data from HPA database verified that CCNB1, CCNB2 and CDK1 were highly expressed in LUAD in the protein level. Conclusion Overexpression of CCNB1, CCNB2 and CDK1 are associated with poor prognosis of LUAD, indicating that the three genes may be prognostic biomarkers of LUAD and CDK1 is a potential therapeutic target for LUAD.
Objective To survey the relations between the rural residents’ occupational satisfaction, the health policies and demographic factors in Henan province and then to confirm the health policy order and its key target populations. Methods The questionnaires were distributed to 1 117 rural residents in 156 villages among 44 townships in 19 counties (cities, districts). The frequency analysis, multivariate linear regression analysis and multiple comparisons were conducted. Results The average value of rural residents’ occupational satisfaction scored 68.23, among which the complete dissatisfaction scored 0 accounting for 1.9%, the complete satisfaction scored 100 accounting for 9.0%, the one scoring no more than 50 accounted for 20.9%, and the one scoreing equal 80 or more than 80 accounted for 37.5%. By regarding the occupational satisfaction as the dependent variable, the independent variables stayed in the model were as follows in order according to their influence from heavy to little on the dependent variable: new rural cooperative medical system (NRCMS), occupation, village general practitioner’s work, family formation, age, disease prevention and control efforts. The occupational satisfaction was much higher when there were the following conditions: the higher satisfaction with the NRCMS, the more financial burden relieved by the NRCMS, and the higher satisfaction with village general practitioners’ work. The occupational satisfaction was the highest when villagers lived with their spouses, while it was the lowest when villagers lived with their spouses and children, as well as they lived with their parents, spouses and children. The peasants’ occupational satisfaction was the lowest. The occupational satisfaction had significantly negative correlation with cultural level, and had positive correlation with age. Conclusion The occupational satisfaction is an important indicator for assessing the level of social harmony, and is the basis for policy decision-making, implementation, and evaluation. The overall occupational satisfaction of the rural residents in Henan is lower, so the social harmoniy and stability should be alerted. The priority order of the existing rural health policy should be the NRCMS policy, village general practitioner work policy, and village disease prevention and control policy. When we are formulating and implementing the rural health policy, the key target populations should be considered among the people whose families comprise two or three generations, whose occupations are farmers, whose cultural level is lower, and whose ages are younger.
ObjectiveThis study is aimed to determine the expression of ubiquitin-specific peptidase 39 (USP39) protein in the colorectal cancer (CRC) tissues, and the effect of silencing USP39 gene on the cell growth and cell cycle distribution of CRC cells.Methods① The expressions of USP39 protein in CRC tissues and its paracancerous tissues were determined by immunohistochemical staining method. ② By lentiviral infection, Lv-shUSP39 (KD-1 and KD-2 group) and Lv-shCon (shCon group) were transferred into SW1116 and HCT116 cells, and cells of blank control group did not received any treatment (Con group). To determine the role of USP39 gene in cell growth, MTT assay was performed to draw growth curve, and cell cycle distribution of CRC cells in the 4 groups were determined by flow cytometer.Results① The expression of USP39 protein was higher in CRC tissues compared to adjacent tissues (P=0.007). ② For SW1116 and HCT116 cells, the cell proliferation ability of KD-1 and KD-2 groups were remarkably decreased than those in corresponding shCon and Con groups on 3, 4, and 5-day (P<0.05). ③ Flow cytometry assay showed that, the percentage of G0/G1 phase cells were decreased obviously (P<0.05), while increased significantly in percentage of G2/M phase and number of sub-G1 phase cells in KD-1 group compared with that in the Con group and shCon group of SW1116 and HCT116 cells (P<0.05).ConclusionsThe expression of USP39 protein is highly expressed in CRC tissues. Knockdowning of USP39 gene can inhibit cell proliferation and promote cell apoptosis.