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Gluconeogenesis is a fundamental feature of hepatocytes. Whether this gluconeogenic activity is also present in malignant hepatocytes remains unexplored. A better understanding of this biological process may lead to novel therapeutic strategies. Here we show that gluconeogenesis is not present in mouse or human malignant hepatocytes. We find that two critical enzymes 11β-HSD1 and 11β-HSD2 that regulate glucocorticoid activities are expressed inversely in malignant hepatocytes, resulting in the inactivation of endogenous glucocorticoids and the loss of gluconeogenesis. In patients’ hepatocarcinoma, the expression of 11β-HSD1 and 11β-HSD2 is closely linked to prognosis and survival. Dexamethasone, an active form of synthesized glucocorticoids, is capable of restoring gluconeogenesis in malignant cells by bypassing the abnormal regulation of 11β-HSD enzymes, leading to therapeutic efficacy against hepatocarcinoma. These findings clarify the molecular basis of malignant hepatocyte loss of gluconeogenesis and suggest new therapeutic strategies. Hepatocytes use gluconeogenesis to produce glucose, but whether this process is altered in hepatocellular carcinoma (HCC) is unclear. Here, the loss of gluconeogenesis in HCC and altered glucocorticoid regulation is demonstrated and glucocorticoid treatment is shown to reduce tumour burden.

Cellular microparticles are vesicular plasma membrane fragments with a diameter of 100–1,000 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that tumour cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application. Microparticles are small vesicular structures that are shed from cellular plasma membranes. Tang and colleagues show that cells treated with chemotherapeutic drugs produce drug-containing microparticles, which can be used as anticancer agents in mice.

Mast cells are of paramount importance to allergies, pathogen immune responses during infections, and angiogenesis, as well as innate and adaptive immune regulations. Beyond all these roles, mast cells are now more and more being recognized as modulators of tumor microenvironment. Notwithstanding mounting evidences of mast cell accumulation in tumors, their exact role in tumor microenvironment is still incompletely understood. In this review, we discuss the significant role of mast cells in the remodeling of tumor microenvironment by either releasing various factors after activation or interacting with other cells within tumor and, as a result, the possible role of mast cell in cancer invasion and metastasis. We also discuss recent findings that mast cells actively release microparticles, which account for the transfer of membrane-type receptor signal and regulatory molecules such as microRNAs to tumor cells and immune cells. These findings on mast cells provide further insights into the complexity of tumor microenvironment remodeling.

Purpose This study is to develop a new suturing technique for flexor tendon repair by modifying the extant Tsuge repair techniques and to use biomechanical analysis to compare the new method with four established repair techniques and evaluate its clinical efficacy in the repair of 47 flexor tendons in 22 patients. Methods The biomechanical analysis relied on 50 flexor digitorum profundus tendons harvested from fresh cadavers. The tendons were randomly divided into five groups, transected, and repaired by use of a 1. double-loop suture, 2. double modified locking Kessler, 3. four-strand Savage, 4. modified six-strand Savage, and 5. the new technique. The tensile force and breaking force of all repaired tendons were measured by static loading trials. For clinical application, 22 patients with acute flexor tendon injuries were treated with the new modified Tsuge suture and follow-up for more than 12 months. Results While differences in the tensile force and breaking force in the modified Tsuge sutures and modified six-strand Savage sutures were not statistically significant, static loading trials showed the tensile force, in the form of a 2-mm gap formation, and the breaking force of the new modified Tsuge sutures were, statistically, both higher than the ones characteristic of double-loop sutures, double modified locking Kessler, and four-strand Savage sutures. After 12 months, restored functions were observed in all the patients during the postoperative 12 months. Total active motion (TAM) score demonstrated that more than 90% fingers were estimated as excellent or good. Conclusion The new modified Tsuge sutures described here have evident higher tensile and breaking forces compared to other four-strand core suture techniques, suggesting, in turn, that this new technique is a good alternative for flexor tendon repairs in clinical applications.