RESUMO
Objective:To explore the expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances.Methods:The clinical data of 57 patients diagnosed as pancreatic ductal carcinoma (PDAC) at the Affiliated Cancer Hospital of Xiangya Medical College of Central South University from January 2014 to December 2018 were retrospectively analyzed. The relative expressions of LINC00673 in pancreatic cancer tissues and paracancerous normal tissues (within 3 cm from the edge of cancer tissues) were examined by using quantificational reverse transcription-polymerase chain reaction (qRT-PCR). The ISG15 protein expressions in pancreatic cancer tissues and paracancerous normal tissues were examined by using immunohistochemistry. The difference in LINC00673 expression between ISG15 protein positive and negative patients was compared. The correlation between LINC00673 and ISG15 protein expressions in pancreatic cancer was analyzed by Spearman rank correlation analysis. Moreover, the correlations of LINC00673 and ISG15 protein expressions with clinical stage and pathological classification of pancreatic cancer patients were analyzed.Results:The positive expression of ISG15 protein in pancreatic cancer tissues was 40.4% (23/57), which was higher than that in paracancerous normal tissues [15.8% (9/57)] ( χ2 = 7.90, P = 0.004), and the relative expression of LINC00673 in pancreatic cancer tissues was 0.99±0.36, which was lower than that in paracancerous normal tissues (1.26±0.41) ( t = 4.80, P < 0.001). For 23 (40.4%) ISG15-positive patients and 34 (59.7%) ISG15-negative patients, the relative expression of LINC00673 was 0.77±0.46 and 0.45±0.27 ( P < 0.001). Spearman analysis showed that there was a correlation between LINC00673 and ISG15 protein expressions ( ρ = -0.429, P = 0.001). The relative expression of LINC00673 decreased in patients with low differentiated or undifferentiated tumor, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between LINC00673 expression and patients' age, tumor site, preoperative CA199 level, and TNM stage (all P > 0.05); ISG15 protein expression increased in patients with low differentiated or undifferentiated tumor, TNM stage Ⅲ-Ⅳ, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between ISG15 protein expression and patients' gender, age, tumor site, and preoperative CA199 level (all P > 0.05). Conclusions:The expression of LINC00673 in pancreatic cancer is related to vascular invasion, tumor differentiation degree and lymph node metastasis, and the expression of ISG15 in pancreatic cancer is related to vascular invasion, tumor differentiation degree, lymph node metastasis and TNM stage. The combined detection of LINC00673 and ISG15 protein could be a valuable prognostic indicator for pancreatic cancer. The therapies targeting LINC00673 and ISG15 protein signaling pathways are expected to be a potential option for immunotherapy of pancreatic cancer.
RESUMO
Chemotherapy is an important adjuvant treatment of glioma, while the efficacy is far from satisfactory, due not only to the biological barriers of blood‒brain barrier (BBB) and blood‒tumor barrier (BTB) but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as up-regulation of P-glycoprotein (P-gp). To address these limitations, we report a bacteria-based drug delivery strategy for BBB/BTB transportation, glioma targeting, and chemo-sensitization. Bacteria selectively colonized into hypoxic tumor region and modulated tumor microenvironment, including macrophages repolarization and neutrophils infiltration. Specifically, tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin (DOX)-loaded bacterial outer membrane vesicles (OMVs/DOX). By virtue of the surface pathogen-associated molecular patterns derived from native bacteria, OMVs/DOX could be selectively recognized by neutrophils, thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting effect. Moreover, the P-gp expression on tumor cells was silenced by bacteria type III secretion effector to sensitize the efficacy of DOX, resulting in complete tumor eradication with 100% survival of all treated mice. In addition, the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk, and cardiotoxicity of DOX was also avoided, achieving excellent compatibility. This work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy.