Mammalian target of rapamycin inhibition in hepatocellular carcinoma

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 activity in advanced HCC, but dual mTOR (mTORC1 and mTORC2) inhibition has greater therapeutic potential in HCC treatment which warrants further clinical investigation.     

Percutaneous coronary interventions and cardiovascular outcomes for patients with chronic total occlusions

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Level V in therapeutic neck dissections for papillary thyroid carcinoma

Neck dissection for papillary thyroid carcinoma (PTC) is the standard of care for patients with clinical evidence of regional metastases. However, the extent of neck dissection is debatable. The purpose of the current study was to develop evidence‐based recommendations for when to include level V, or 1 of its sublevels, among patients with PTC undergoing neck dissection. A literature review of all studies evaluating the occurrence of metastases in level V in patients with regional metastases from PTC undergoing neck dissection was performed. Occurrence of metastases at level V is low in most series (5% to 10%), although a wide range was noticed. In cases in which metastases were found at level V, they occurred almost exclusively at sublevel VB. Sublevel VA was rarely, if ever, involved with metastatic lymph nodes. However, only recently have investigators begun to specify which sublevels of level V are at risk. Therapeutic dissection of level V is indicated when there is clinical evidence of disease involving this zone. Elective dissection of sublevel VB is indicated when there is involvement of level IV, or possibly multiple nodes at levels II and III. Under these circumstances, dissection of sublevel VB is indicated but sublevel VA may be spared. © 2012 Wiley Periodicals, Inc. Head Neck, 2013     

Intraosseous carcinoma of the jaws—A clinicopathologic review. Part I: Metastatic and salivary‐type carcinomas

This is the first part of a 3‐part comprehensive review of intraosseous carcinoma of the jaws. We have outlined 4 groups of intraosseous carcinoma of the jaws (metastatic, salivary‐type, odontogenic, and primary intraosseous carcinoma), emphasizing the need for accurate diagnosis and the problems associated with changing classification systems, standardization of diagnostic criteria and nomenclature, and the accuracy of existing literature. In this first part, the features of metastatic and the very rare salivary‐type carcinomas of the jaws are examined with particular emphasis on histologic and immunohistochemical characteristics, diagnostic difficulties, and uncertainties. © 2012 Wiley Periodicals, Inc. Head Neck, 2012