RESUMO
The prevalence of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) has emerged as a major public health concern in China. When patients with HIV infection undergo surgical treatment, there are two main challenges. Firstly, medical staff face a high risk of HIV infection due to occupational exposure. Secondly, the patient's immune function is impaired, increasing the risk of opportunistic infections and postoperative complications. The surgical treatment of such patients is unique, and the risk of occupational exposure during the operation primarily depends upon the viral load of HIV/AIDS patients. Therefore, perioperative antiretroviral therapy is of paramount importance in order to standardize the perioperative antiretroviral therapy (ART) for HIV/AIDS patients. The Surgery Group of the Chinese Association of STD and AIDS Prevention and Control, in collaboration with the Treatment Association, and Surgery Group of the Chinese Medical Association of Tropical Diseases and Parasitology, has developed an expert consensus on perioperative antiretroviral therapy for HIV/AIDS patients. This consensus encompasses various aspects, including surgical risk assessment, selection of perioperative antiretroviral therapy regimens, prevention of opportunistic infections, and the crucial focus on rapid preoperative viral load reduction and immune function reconstruction for HIV/AIDS patients.
RESUMO
Tumor self-seeding occurs when circulating malignant cells reinfiltrate the original tumor. The process may breed more aggressive tumor cells, which may contribute to cancer progression. In this study, we observed tumor self-seeding in mouse xenograft models of hepatocellular carcinoma (HCC) for the first time. We confirmed that circulating tumor cell uptake of tumor-derived exosomes, which are increasingly recognized as key instigators of cancer progression by facilitating cell-cell communication, promoted tumor self-seeding by enhancing the invasive and migration capability of recipient HCC cells. Horizontal transfer of exosomal microRNA-25-5p to anoikis-resistant HCC cells significantly enhanced their migratory and invasive abilities, whereas inhibiting microRNA-25-5p alleviated these effects. Our experiments delineate an exosome-based novel pathway employed by functional microRNA from the original tumor cells that can influence the biological fate of circulating tumor cells.
Assuntos
Carcinoma Hepatocelular/genética , Movimento Celular/genética , Exossomos/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Animais , Carcinoma Hepatocelular/patologia , Comunicação Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/genéticaRESUMO
Hook1 is a member of the hook family of coiled-coil proteins, which is recently found to be associated with malignant tumors. However, its biological function in hepatocellular carcinoma is yet unknown. Here, we evaluated the Hook1 levels in human hepatocellular carcinoma samples and matched peritumoral tissues by real-time polymerase chain reaction. Small interfering RNA knockdown and a transforming growth factor-ß-induced epithelial-mesenchymal transition model were employed to investigate the biological effects of Hook1 in hepatocellular carcinoma. Our results indicated that Hook1 levels were significantly lower in hepatocellular carcinoma tissues than in the peritumoral tissues. In addition, Hook1 expression was significantly associated with hepatocellular carcinoma malignancy. Hook1 was downregulated after transforming growth factor-ß-induced epithelial-mesenchymal transition. Moreover, Hook1 knockdown promoted epithelial-mesenchymal transition and attenuated the sensitivity of hepatocellular carcinoma cells to doxorubicin. In summary, our results indicate that downregulation of Hook1 plays a pivotal role in hepatocellular carcinoma progression via epithelial-mesenchymal transition. Hook1 may be used as a novel marker and therapeutic molecular target in hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Hepáticas/genética , Proteínas Associadas aos Microtúbulos/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Doxorrubicina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/patologia , Proteínas Associadas aos Microtúbulos/biossíntese , RNA Interferente Pequeno , Fator de Crescimento Transformador beta/genéticaRESUMO
Based on characteristic UV spectrum of the ene-diyne chromophore, one new polyacetylene glucoside and three known polyacetylene glucosides have been isolated from the EtOH extract of Coreopsis tinctoria. Their chemical structures were determined by detailed spectroscopic analysis and by comparison with literature data. Compounds 1-2 were tested for their antiadipogenic effects on 3T3-L1 adipocytes, and both of them reduced lipid accumulation dose-dependently in 3T3-L1 adipocytes.
Assuntos
Adipócitos/efeitos dos fármacos , Coreopsis/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Poli-Inos/isolamento & purificação , Poli-Inos/farmacologia , Células 3T3-L1/efeitos dos fármacos , Animais , Medicamentos de Ervas Chinesas/química , Flavonoides/farmacologia , Glucosídeos/química , Camundongos , Estrutura Molecular , Poli-Inos/químicaRESUMO
mTOR is aberrantly activated in hepatocellular carcinoma (HCC) and plays pivotal roles in tumorigenesis and chemoresistance. Rapamycin has been reported to exert antitumor activity in HCC and sensitizes HCC cells to cytotoxic agents. However, due to feedback activation of AKT after mTOR complex 1 (mTORC1) inhibition, simultaneous targeting of mTORC1/2 may be more effective. In this study, we examined the interaction between the dual mTORC1/2 inhibitor OSI-027 and doxorubicin in vitro and in vivo. OSI-027 was found to reduce phosphorylation of both mTORC1 and mTORC2 substrates, including 4E-BP1, p70S6K, and AKT (Ser473), and inhibit HCC cell proliferation. Similar to OSI-027 treatment, knockdown of mTORC2 induced G0-G1 phase cell-cycle arrest. In contrast, rapamycin or knockdown of mTORC1 increased phosphorylation of AKT (Ser473), yet had little antiproliferative effect. Notably, OSI-027 synergized with doxorubicin for the antiproliferative efficacy in a manner dependent of MDR1 expression in HCC cells. The synergistic antitumor effect of OSI-027 and doxorubicin was also observed in a HCC xenograft mouse model. Moreover, AKT was required for OSI-027-induced cell-cycle arrest and downregulation of MDR1. Our findings provide a rationale for dual mTORC1/mTORC2 inhibitors, such as OSI-027, as monotherapy or in combination with cytotoxic agents to treat HCC. Mol Cancer Ther; 14(8); 1805-15. ©2015 AACR.
