ABSTRACT
Primary pulmonary carcinoid tumors are a group of relatively rare lung neoplasms.In the 2015 World Health Organization classification of lung tumors,lung carcinoid tumors(including both the classical and atypical types)were included in the category of pulmonary neuroendocrine tumors along with large cell neuroendocrine carcinomas and small cell lung carcinomas.Due to the low in-cidence and lack of specific clinical manifestations,the diagnosis and management of pulmonary carcinoid tumors remain relatively challenging.Current consensus supports surgery as the only curative option for localized,resectable pulmonary carcinoid tumors.How-ever,some inconsistencies exist between the guideline recommendations for systemic therapies that have resulted in a lack of consen-sus in regard to the standardized treatment for the metastatic or unresectable disease.This review intends to summarize the latest rec-ommendations for the diagnosis and multidisciplinary treatment of pulmonary carcinoid tumors.
ABSTRACT
Objective To investigate the effects of CD24 on CCl4-induced murine liver fibrosis and to analyze the possible molecular mechanism.Methods Wild type (WT) and CD24 knockout (CD24-/-) C57BL/6 mice were treated with CCl4 through intraperitoneal injection.Levels of ALT in serum samples were detected and liver tissues were stained with hematoxylin and eosin (HE) to assess liver tissue injury.Sirius Red staining was used to observe liver fibrosis.Real-time PCR was performed to detect the expression of α-SMA (α-smooth muscle actin), Col1a1 (Collagen, typeⅠ, alpha 1), TGF-β1 (transforming growth factor-β1) and CD24 at mRNA level in liver tissues.Western blot was performed to analyze the expression of α-SMA and Col1a1 at protein level.Flow cytometry analysis was used to detect the macrophages in liver tissues.ELISA was used to detect the expression of TGF-β1 in the culture supernatants of M1 and M2 macrophages.Results The expression of CD24 at both mRNA and protein levels were up-regulated in mice with CCl4-induced liver fibrosis.HE staining showed that liver inflammation in CD24-/-mice was more severe than that in WT mice after treated with CCl4.Sirius Red staining of paraffin-embadded liver sections revealed that compared with WT mice, CD24-/-mice presented with more severe liver fibrosis.Moreover, α-SMA and Col1a1, indicators of liver fibrosis, in CD24-/-mice were significantly higher than those in WT mice.Flow cytometry analysis showed that murine hepatic macrophages significantly increased in CD24-/-mice than in WT mice following CCl4 treatment.Real-time PCR analysis also confirmed that significantly enhanced expression of TGF-β1 at mRNA level in liver tissues was observed in CD24-/-mice than in WT mice.TGF-β1 secreted in the culture supernatant of M2 macrophages derived from CD24-/-mice group was more than that of the WT mice group.No significant difference in TGF-β1 secretion in culture supernatant of M1 macrophages was observed between the two groups.Conclusion Taken together, these data suggest that CD24 plays an important role in attenuating CCl4-induced chronic inflammation and hepatic fibrosis in mice.The mechanism of CD24 in alleviating liver fibrosis might be through regulating intrahepatic macrophages, inhibiting the secretion of TGF-β1 by M2 macrophages and suppressing the activation of hepatic stellate cells.