A solid tumor consists of cancer and stromal cells, which comprise the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are usually abundant in the TME, contributing to tumor progression. In cases of peritoneal dissemination of gastric cancer (GC), the contribution of intraperitoneal TAMs remains unclear. Macrophages from peritoneal washings of GC patients were analyzed, and the link between intraperitoneal TAMs and GC cells was investigated to clarify the interaction between them in peritoneal dissemination. Macrophages were predominant among leukocytes constituting the microenvironment of the peritoneal cavity. The proportion of CD163-positive TAMs was significantly higher in stage IV than in stage I GC. Co-culture with TAMs potentiated migration and invasion of GC. IL-6 was the most increased in the medium of in vitro co-culture of macrophages and GC, and IL-6 elevation was also observed in the peritoneal washes with peritoneal dissemination. An elevated concentration of intraperitoneal IL-6 was correlated with a poor prognosis in clinical cases. In conclusion, intraperitoneal TAMs are involved in promoting peritoneal dissemination of GC via secreted IL-6. TAM-derived IL-6 could be a potential therapeutic target for peritoneal dissemination of GC.
Background
Peritoneal dissemination often develops in gastric cancer. Tumor-associated macrophages (TAMs) are present in the peritoneal cavity of gastric cancer patients with peritoneal dissemination, facilitating tumor progression. However, the mechanism by which macrophages differentiate into tumor-associated macrophages in the peritoneal cavity is not well understood. In this study, the interplay between gastric cancer-derived extracellular vesicles (EVs) and macrophages was investigated.
Methods
The association between macrophages and EVs in peritoneal ascitic fluid of gastric cancer patients, or from gastric cancer cell lines was examined, and their roles in differentiation of macrophages and potentiation of the malignancy of gastric cancer were further explored.
Results
Immunofluorescent assays of the ascitic fluid showed that M2 macrophages were predominant along with the cancer cells in the peritoneal cavity. EVs purified from gastric cancer cells, as well as malignant ascitic fluid, differentiated peripheral blood mononuclear cell-derived macrophages into the M2-like phenotype, which was demonstrated by their morphology and expression of CD163/206. The macrophages differentiated by gastric cancer-derived EVs promoted the migration ability of gastric cancer cells, and the EVs carried STAT3 protein.
Conclusion
EVs derived from gastric cancer play a role by affecting macrophage phenotypes, suggesting that this may be a part of the underlying mechanism that forms the intraperitoneal cancer microenvironment.
Highlights
A chronic expanding hematoma of the adrenal gland is extremely rare.
Chronic expanding hematomas mimic sarcomatous lesions.
Gallium scintigraphy may help the differential diagnosis between chronic expanding hematomas and sarcomatous lesions.
Complete resection of chronic expanding hematomas is the gold standard.
Preoperative arterial embolization may reduce intraoperative bleeding on complete tumor removal.
We herein report the case of an 85-year-old woman presenting with right internal jugular vein candidal thrombophlebitis associated with central venous catheters (CTCVC). The infecting agent was Candida albicans, which caused recurrent candidemia five times in total. Micafungin (MCFG) alone was ineffective; however, the combination of MCFG with fosfluconazole (F-FLCZ) successfully treated the patient without a need for any anticoagulant or surgical therapies. To the extent of our knowledge, this is the first report of CTCVC being successfully treated with a combination of F-FLCZ and MCFG. These new antifungal agents have better efficacy, tolerability and bioavailability; therefore, they can be useful alternatives to classical combination therapies such as amphotericin-B and 5-fluorocytosine.
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