A 55-year-old male patient with hepatitis B-related liver cirrhosis was found to have advanced hepatocellular carcinoma.His AFP was initially 9828μg/L and rapidly dropped to 5597μg/L in ten days after oral sorafenib...A 55-year-old male patient with hepatitis B-related liver cirrhosis was found to have advanced hepatocellular carcinoma.His AFP was initially 9828μg/L and rapidly dropped to 5597μg/L in ten days after oral sorafenib treatment.However,he developed acute renal failure, hyperkalemia,and hyperuricemia 30 d after receiving the sorafenib treatment.Tumor lysis syndrome was suspected and intensive hemodialysis was performed. Despite intensive hemodialysis and other supportive therapy,he developed multiple organ failure(liver, renal,and respiratory failure)and metabolic acidosis. The patient expired 13 d after admission.展开更多
Hepatocellular carcinoma(HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is ...Hepatocellular carcinoma(HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is the only available systemic agent for treatment of HCC that improves overall survival for patients with advanced stage disease; unfortunately, an effective second-line agent for the treatment of progressive or sorafenib-resistant HCC has yet to be identified. This review focuses on components of the mammalian target of rapamycin(mTOR) pathway, its role in HCC pathogenesis, and dual mTOR inhibition as a therapeutic option with potential efficacy in advanced HCC. There are several important upstream and downstream signals in the mTOR pathway, and alternative tumor-promoting pathways are known to exist beyond mTORC1 inhibition in HCC. This review analyzes the relationships of the upstream and downstream regulators of mTORC1 and mTORC2 signaling; it also provides a comprehensive global picture of the interaction between mTORC1 and mTORC2 which demonstrates the pre-clinical relevance of the mTOR pathway in HCC pathogenesis and progression. Finally, it provides scientific rationale for dual mTORC1 and mTORC2 inhibition in the treatment of HCC. Clinical trials utilizing mTORC1 inhibitors and dual mTOR inhibitors in HCC are discussed as well. The mTOR pathway is comprised of two main components, mTORC1 and mTORC2; each has a unique role in the pathogenesis and progression of HCC. In phase Ⅲ studies, mTORC1 inhibitors demonstrate anti-tumor ac-tivity in advanced HCC, but dual mTOR(mTORC1 and mTORC2) inhibition has greater therapeutic potential in HCC treatment which warrants further clinical investigation.展开更多
Objective: To investigate the feasibility of intra-operative radiation therapy (IORT) in hepato-cellular carcinoma (HCC). Methods: Based on the dosage distribution of tumor and adjacent sensitive organs, and dose-volu...Objective: To investigate the feasibility of intra-operative radiation therapy (IORT) in hepato-cellular carcinoma (HCC). Methods: Based on the dosage distribution of tumor and adjacent sensitive organs, and dose-volume histogram (DVH), Topslane three-dimensional therapy plan was used to compare IORT and three-dimensional conformal radiation therapy (3D-CRT) in 12 cases of HCC. Results: Taking the center of tumors as the isodose center, the V90 (volume of 90% dose distribution) of IORT was significantly better than that of 3D-CRT, and median absorbed doses of normal organs in IORT was significantly lower than that in 3D-CRT. Conclusion: The V90 of IORT is better than that of 3D-CRT in HCC, and neighboring sensitive organs were effectively protected by IORT. The tumors absorbed dose and local control rate are improved in IORT.展开更多
文摘A 55-year-old male patient with hepatitis B-related liver cirrhosis was found to have advanced hepatocellular carcinoma.His AFP was initially 9828μg/L and rapidly dropped to 5597μg/L in ten days after oral sorafenib treatment.However,he developed acute renal failure, hyperkalemia,and hyperuricemia 30 d after receiving the sorafenib treatment.Tumor lysis syndrome was suspected and intensive hemodialysis was performed. Despite intensive hemodialysis and other supportive therapy,he developed multiple organ failure(liver, renal,and respiratory failure)and metabolic acidosis. The patient expired 13 d after admission.
文摘Hepatocellular carcinoma(HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is the only available systemic agent for treatment of HCC that improves overall survival for patients with advanced stage disease; unfortunately, an effective second-line agent for the treatment of progressive or sorafenib-resistant HCC has yet to be identified. This review focuses on components of the mammalian target of rapamycin(mTOR) pathway, its role in HCC pathogenesis, and dual mTOR inhibition as a therapeutic option with potential efficacy in advanced HCC. There are several important upstream and downstream signals in the mTOR pathway, and alternative tumor-promoting pathways are known to exist beyond mTORC1 inhibition in HCC. This review analyzes the relationships of the upstream and downstream regulators of mTORC1 and mTORC2 signaling; it also provides a comprehensive global picture of the interaction between mTORC1 and mTORC2 which demonstrates the pre-clinical relevance of the mTOR pathway in HCC pathogenesis and progression. Finally, it provides scientific rationale for dual mTORC1 and mTORC2 inhibition in the treatment of HCC. Clinical trials utilizing mTORC1 inhibitors and dual mTOR inhibitors in HCC are discussed as well. The mTOR pathway is comprised of two main components, mTORC1 and mTORC2; each has a unique role in the pathogenesis and progression of HCC. In phase Ⅲ studies, mTORC1 inhibitors demonstrate anti-tumor ac-tivity in advanced HCC, but dual mTOR(mTORC1 and mTORC2) inhibition has greater therapeutic potential in HCC treatment which warrants further clinical investigation.
基金Supported by the Science and Technology Research Foundation of Shaanxi Province (2005k09-G5)
文摘Objective: To investigate the feasibility of intra-operative radiation therapy (IORT) in hepato-cellular carcinoma (HCC). Methods: Based on the dosage distribution of tumor and adjacent sensitive organs, and dose-volume histogram (DVH), Topslane three-dimensional therapy plan was used to compare IORT and three-dimensional conformal radiation therapy (3D-CRT) in 12 cases of HCC. Results: Taking the center of tumors as the isodose center, the V90 (volume of 90% dose distribution) of IORT was significantly better than that of 3D-CRT, and median absorbed doses of normal organs in IORT was significantly lower than that in 3D-CRT. Conclusion: The V90 of IORT is better than that of 3D-CRT in HCC, and neighboring sensitive organs were effectively protected by IORT. The tumors absorbed dose and local control rate are improved in IORT.
