CD206 modulates the role of M2 macrophages in the origin of metastatic tumors.

Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have focused on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we hypothesized a novel mode for cancer metastasis. We show that the phagocytosis of apoptotic tumor cells by macrophages leads to their polarization into the M2 phenotype, and that the expression of stem cell related as well as drug resistance related genes was induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source, at least in part, of the distal tissue tumor metastasis. This assumption is supported by the presence of fused cells with characteristics of both macrophage and tumor cell observed in the peripheral blood and ascites of patients with ovarian cancer. By eliminating the expression of CD206 in M2 macrophages using siRNA, we show that the growth and metastasis of tumors was suppressed using both in vitro cell line and with experimental in vivo mouse models. In summary, we show that M2 macrophages in the blood circulation underwent a "change of loyalty" to become "cancer cells" that transformed into distal tissue metastasis, which could be suppressed by the knockdown of CD206 expression.

Disulfiram reduces the severity of mouse acute pancreatitis by inhibiting RIPK1-dependent acinar cell necrosis.

Acute pancreatitis (AP) is a frequent abdominal inflammatory disease. Despite the high morbidity and mortality, the management of AP remains unsatisfactory. Disulfiram (DSF) is an FDA-proved drug with potential therapeutic effects on inflammatory diseases. In this study, we aim to investigate the effect of DSF on pancreatic acinar cell necrosis, and to explore the underlying mechanisms. Cell necrosis was induced by sodium taurocholate or caerulein, AP mice model was induced by nine hourly injections of caerulein. Network pharmacology, molecular docking, and molecular dynamics simulation were used to explore the potential targets of DSF in protecting against cell necrosis. The results indicated that DSF significantly inhibited acinar cell necrosis as evidenced by a decreased ratio of necrotic cells in the pancreas. Network pharmacology, molecular docking, and molecular dynamics simulation identified RIPK1 as a potent target of DSF in protecting against acinar cell necrosis. qRT-PCR analysis revealed that DSF decreased the mRNA levels of RIPK1 in freshly isolated pancreatic acinar cells and the pancreas of AP mice. Western blot showed that DSF treatment decreased the expressions of RIPK1 and MLKL proteins. Moreover, DSF inhibited NF-κB activation in acini. It also decreased the protein expression of TLR4 and the formation of neutrophils extracellular traps (NETs) induced by damage-associated molecular patterns released by necrotic acinar cells. Collectively, DSF could ameliorate the severity of mouse acute pancreatitis by inhibiting RIPK-dependent acinar cell necrosis and the following formation of NETs.

Endothelial cells in colorectal cancer.

The dependence of tumor growth on neovascularization has become an important aspect of cancer biology. Tumor angiogenesis is one of the key mechanisms of tumorigenesis, growth and metastasis. The key events involved in this process are endothelial cell proliferation, migration, and vascular formation. Recent studies have revealed the importance of tumor-associated endothelial cells (TECs) in the development and progression of colorectal cancer (CRC), including epithelial proliferation, stem cell maintenance, angiogenesis, and immune remodeling. Decades of research have identified that the molecular basis of tumor angiogenesis includes vascular endothelial growth factors (VEGFs) and their receptor family, which are the main targets of antiangiogenesis therapy. VEGFs and their receptors play key roles in the pathology of angiogenesis, and their overexpression indicates poor prognosis in CRC. This article reviews the characteristics of the tumor vasculature and the role of TECs in different stages of CRC and immune remodeling. We also discuss the biological effects of VEGFs and their receptor family as angiogenesis regulators and emphasize the clinical implications of TECs in clinical treatment.

Oxaliplatin-based adjuvant chemotherapy without radiotherapy can improve the survival of locally-advanced rectal cancer.

OBJECTIVE: To assess the impact of oxaliplatin-containing adjuvant chemotherapy on the survival of patients with locally-advanced rectal cancer. METHODS: Data on patients with pathologically-confirmed T3/4 or N1/2 rectal cancer who accepted radical surgery at our center from January 2002 to June 2009 were reviewed retrospectively. The patients' 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were analyzed by comparing those who accepted radical surgery only (Group S) with those who accepted radical surgery and oxaliplatin-containing adjuvant chemotherapy (Group SO). RESULTS: A total of 236 patients were analyzed (Group S 135; Group SO 101). Group S patients were older and had a higher proportion with stage II disease and more perioperative complications than those in Group SO (P<0.05). The OS and DSS of patients with stage III disease under 50 years of age or with mucinous adenocarcinoma were higher in Group SO than Group S (P<0.05). In addition, the OS of patients with stage N2b disease was higher in Group SO than Group S (P = 0.016), and the OS of patients with stage N1a or N2b disease who received more than 8 weeks of oxaliplatin-containing chemotherapy was also higher in Group SO than Group S (P<0.05). Although the OS and DSS of patients with stage II disease in Group SO showed a tendency towards improvement, the differences between the groups were not statistically significant. CONCLUSION: Adjuvant oxaliplatin-containing chemotherapy can improve the survival of patients with locally-advanced low and middle rectal cancers in comparison with observation. Randomized, prospective trials are warranted to confirm this benefit of oxaliplatin for rectal cancer.