Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma.

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we screened 18 artificial diets for anticancer activity in a challenging animal model of renal cell carcinoma. The model was established by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine, and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential and mechanism of action of this simple and inexpensive anticancer strategy.

Systematic review on the use of anticholinergic scales in poly pathological patients.

PURPOSE: Anticholinergic drugs may increase the risk of cognitive and functional disorders in older patients. There are anticholinergic scales on which said risk is estimated. The objectives of this study are: to identify the scales described in literature that are applicable to polypathological patients and analyze their clinical outcomes. MATERIAL AND METHODS: A systematic review was performed. Data sources were MEDLINE, EMBASE and Web of Science which were consulted until August 2014. INCLUSION CRITERIA: (1) studies that specify the list of drugs, describe the methodology for their elaboration and how they calibrate the anticholinergic potential and (2) studies that use the scales identified as a tool to measure exposure to anticholinergic drugs in polypathological patients or those with similar characteristics. The main differences between the scales and main results on cognitive, functional and mortality status were collected. RESULTS: 25 articles were included. 10 scales were identified. For their preparation, 8 were based on literature about drugs with anticholinergic activity and/or previously published scales as well as expert opinions. Exposure to anticholinergic drugs has been linked to cognitive disorders (basically measured with Anticholinergic Risk Scale (ARS), Anticholinergic Cognitive Burden Scale (ACB) and Drug Burden Index (DBI)) and functional scale (with ARS and DBI). However, there is no clear relationship with mortality. The Anticholinergic Drug Scale was the only one that obtained no association with any of the variables studied. CONCLUSIONS: There is a great variety of scales published and applied to older patients. The clinical results are different depending on the scale used which is probably due to the different methodology in their elaboration.