Exosomes are discrete populations of small (40-200 nm in diameter) membranous vesicles that are released into the extracellular space by most cell types, eventually accumulating in the circulation. As molecular messengers, exosomes exert a broad array of vital physiologic functions by transporting information between different cell types. Because of these functional properties, they may have potential as biomarker sources for prognostic and diagnostic disease. Recent research has found that exosomes have potential to be utilized as drug delivery agents for therapeutic targets. However, basic researches on exosomes and researches on their therapeutic potential both require the existence of effective and rapid methods for their separation from human samples. In the current absence of a standardized method, there are several methods available for the separation of exosomes, but very few studies have previously compared the efficiency and suitability of these different methods. This review summarized and compared the available traditional and novel methods for the extraction of exosomes from human samples and considered their advantages and disadvantages for use in clinical laboratories and point-of-care settings.

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Abstract. The occurrence and development of pancreatic cancer is a complex process convoluted by multi-pathogenies, multi-stages and multi-factors. S100 proteins are members of the S100 family that regulate multiple cellular pathways related to pancreatic cancer progression and metastasis. S100 proteins have a broad range of intracellular and extracellular functions, including the regulation of protein phosphorylation and enzyme activity, calcium homeostasis and the regulation of cytoskeletal components and transcriptional factors. S100 proteins interact with receptor for advanced glycation end-products (RAGE), p53 and p21, which play a role in the degradation of the extracellular matrix (ECM) and metastasis, and also interact with cytoskeletal proteins and the plasma membrane in pancreatic cancer progression and metastasis. S100A11 and S100P are significant tumor markers for pancreatic cancer and unfavorable predictors for the prognosis of patients who have undergone surgical resection. Recently, S100A2 has been suggested to be a negative prognostic biomarker in pancreatic cancer, and the expression of S100A6 may be an independent prognostic impact factor. The expression of S100A4 and S100P is associated with drug resistance, differentiation, metastasis and clinical outcome. This review summarizes the role and significance of the S100 family signaling network and related proteins in pancreatic cancer.

The tumor microenvironment (TME) is a complex multicellular functional compartment that includes fibroblasts, myofibroblasts, endothelial cells, immune cells, and extracellular matrix (ECM) elements. The microenvironment provides an optimum condition for the initiation, growth, and dissemination of hepatocellular carcinoma (HCC). As one of the critical and abundant components in tumor microenvironment, cancer-associated fibroblasts (CAFs) have been implicated in the progression of HCC. Through secreting various growth factors and cytokines, CAFs contribute to the ECM remodeling, stem features, angiogenesis, immunosuppression, and vasculogenic mimicry (VM), which reinforce the initiation and development of HCC. In order to restrain the CAFs-initiated HCC progression, current strategies include targeting specific markers, engineering CAFs with tumor-suppressive phenotype, depleting CAFs’ precursors, and repressing the secretions or downstream signaling. In this review, we update the emerging understanding of CAFs in HCC, with particular emphasis on cellular origin, phenotypes, biological functions and targeted strategies. It provides insights into the targeting CAFs for HCC treatment.

The presence of IGHG1 in pancreatic cancer cells might constitute an important element responsible for tumor cell proliferation and immune evasion mechanisms.

S100A11 is a member of S100 protein family, and our previous study showed that S100A11 is one of the up-regulated proteins that have not been reported to be associated with pancreatic carcinoma. The purpose of this study was to investigate the relation between S100A11 expression and the clinicopathological variables and clinical outcome in patients with pancreatic adenocarcinoma. Immunohistochemistry analysis was performed for S100A11 in 78 pairs of specimens of human pancreatic adenocarcinoma tissues and adjacent nontumorous tissues. The univariate and multivariate survival analyses were also performed to determine its prognostic significance. S100A11 expression in pancreatic adenocarcinoma (62/78) was significantly higher than that in the adjacent nontumorous tissues (19/78) (P = 0.000). High expression of S100A11 was associated with the lymph node metastasis and histological differentiation (P = 0.003 and 0.004, respectively). Univariate analysis showed that S100A11 expression was associated with poor prognosis (P = 0.0000). Multivariate analysis using the Cox regression model indicated that age ≥ 65 years, CA19-9 ≥ 1,000 U/ml and positive S100A11 were independent prognostic indicators of pancreatic adenocarcinoma (P = 0.002, 0.004 and 0.001, respectively). These results suggested that S100A11 might be a significant tumor marker for pancreatic adenocarcinoma and an unfavorable predictor for prognosis of patients who have undergone surgical resection.

Highlights d Synchronous expression of PD-L1 and PD-L2 is dependent on super-enhancers d The PD-L1L2-SE is a super-enhancer located between the genes encoding PD-L1 and PD-L2 d PD-L1L2-SE mediates immune evasion by driving PD-L1 and PD-L2 expression d The activation of PD-L1L2-SE associates with PD-L1 and PD-L2 in cancer patients