Targeting cluster of differentiation 47 improves the efficacy of anti-cytotoxic T-lymphocyte associated protein 4 treatment via antigen presentation enhancement in pancreatic ductal adenocarcinoma.

Treatment with cluster of differentiation 47 (CD47) monoclonal antibody has exhibited promising antitumor effects in various preclinical cancer models. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In the present study, the CD47 expression level was measured in PDAC patient samples. The effects of CD47 on antigen presentation and anti-tumor immunity were evaluated using phagocytotic assays and animal models. The results indicated that CD47 was overexpressed in the tumor tissue of PDAC patients compared with that in normal adjacent tissues. In the human samples, antigen-presenting cells (macrophages and dendritic cells) in tumors with high CD47 expression demonstrated low CD80 and CD86 expression levels. In an in vitro co-culture tumor cell system, CD47 overexpression was observed to inhibit the function of phagocytic cells. Furthermore, in a PDAC mouse model, CD47 overexpression was indicated to reduce antigen-presenting cell tumor infiltration and T-cell priming in tumor-draining lymph nodes. Anti-CD47 treatment appeared to enhance the efficacy of the approved immune checkpoint blockade agent anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA4) in suppressing PDAC development in a mouse model. Therefore, it was concluded that CD47 overexpression suppressed antigen presentation and T-cell priming in PDAC. Anti-CD47 treatment may enhance the efficacy of anti-CTLA4 therapy and may therefore be a potential strategy for the treatment of PDAC patients in the future.

A study on the mechanism of rapamycin mediating the sensitivity of pancreatic cancer cells to cisplatin through PI3K/AKT/mTOR signaling pathway.

PURPOSE: To study the mechanism of rapamycin mediating the sensitivity of pancreatic cancer cells to cisplatin through phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in vitro. METHODS: SW1990 cells were cultured in vitro and treated with rapamycin, cisplatin, and rapamycin combined with cisplatin, respectively, with dimethyl sulphoxide (DMSO) as the control. Cell Counting Kit-8 (CCK-8) and flow cytometry were adopted for determination of cell proliferation and apoptosis levels, respectively. The changes in PI3K/AKT/mTOR signal transmission were detected via Western blotting and reverse transcription polymerase chain reaction (RT-PCR), respectively. RESULTS: 1: Compared with those in DMSO blank control group, the proliferation level of pancreatic cancer cells was markedly decreased and the cell apoptosis rate was remarkably increased in simple drug group (p<0.05). 2: The combined administration group had markedly decreased proliferation level and remarkably increased cell apoptosis rate of human pancreatic cancer cells, compared with those in the rapamycin alone group or cisplatin alone group (p<0.05). 3: Rapamycin combined with cisplatin could inhibit the expressions of PI3K, AKT and phosphorylated mTOR (p-mTOR) in pancreatic cancer cells (p<0.05). CONCLUSION: Rapamycin combined with cisplatin can alter the PI3K/AKT/mTOR signal transduction pathway which leads to markedly increased cell apoptosis rate, indicating that rapamycin can mediate the sensitivity of pancreatic cancer cells to cisplatin.

MiR-17-5p promotes cancer cell proliferation and tumorigenesis in nasopharyngeal carcinoma by targeting p21.

MicroRNAs (miRNAs) may act as either tumor suppressors or oncogenes in various types of cancers. Previous studies have indicated that miR-17-5p is involved in the initiation and development of human tumors. However, its mechanism and function in nasopharyngeal carcinoma (NPC) remain largely unclear. In this study, we evaluated the expression profiles of miR-17-5p and p21 in NPC cell lines and tissues by quantitative real-time PCR (qRT-PCR). For the analysis, we have established a stable overexpression or depletion of miR-17-5p NPC cell lines for analyzing the effects of cell proliferation by MTT, colony formation, and cell cycle assay. A nude mice xenograft model was used to verify the tumor growth in vivo. MiR-17-5p was overexpressed, whereas the expression of p21 was downregulated in NPC cell lines and tissues. The miR-17-5p expression level was inversely correlated with the p21 mRNA level in NPC samples. Furthermore, analysis of 2-ΔΔCt value in 81 NPC patients suggested that the elevated expression level of miR-17-5p or the downregulated expression level of p21 was significantly correlated with tumor size (T classification) and tumor stage, and Kaplan-Meier survival analysis revealed a correlation between miR-17-5p or p21 expression level and overall survival times in 81 NPC patients. MiR-17-5p promoted cell growth in vivo and in vitro by directly targeting p21. Our results indicate that miR-17-5p can promote the occurrence of NPC and it may serve as a potential novel diagnostic maker or therapeutic target for NPC in the future.

[Prognostic analysis of 116 patients with mucoepidermoid carcinoma of the parotid gland].

BACKGROUND & OBJECTIVE: Mucoepidermoid carcinoma is the most common malignant tumor of the salivary, but mucoepidermoid carcinoma of the parotid gland has seldom been reported. This study was to summarize the clinicopathologic prognostic factors of mucoepidermoid carcinoma of the parotid gland. METHODS: Clinical data of 116 patients with mucoepidermoid carcinoma of the parotid gland, treated in Cancer Center of Sun Yat-sen University from May 1980 to Dec. 2000, were analyzed with Cox univariate and multivariate models. RESULTS: The overall 5-, 10-, and 15-year survival rates of the 116 patients were 75.64%, 64.55%, and 60.39%, respectively. Univariate survival analysis showed that 12 factors were prognostic factors of mucoepidermoid carcinoma of the parotid gland, such as age, alcohol drinking, T stage, and so on. Multivariate analysis showed that T stage (P = 0.006, OR > 1), pathologic grade (P < 0.001, OR > 1), and distant metastasis (P < 0.001, OR > 1) were independent prognostic factors of mucoepidermoid carcinoma of the parotid gland. CONCLUSION: T stage, pathologic grade and distant metastasis are independent prognostic factors of mucoepidermoid carcinoma of the parotid gland.