Mechanical Stress as the Common Denominator between Chronic Inflammation, Cancer, and Alzheimer's Disease.

The pathogenesis of common diseases, such as Alzheimer's disease (AD) and cancer, are currently poorly understood. Inflammation is a common risk factor for cancer and AD. Recent data, provided by our group and from others, demonstrate that increased pressure and inflammation are synonymous.

Overview of Methods for Overcoming Hindrance to Drug Delivery to Tumors, with Special Attention to Tumor Interstitial Fluid.

Every drug used to treat cancer (chemotherapeutics, immunological, monoclonal antibodies, nanoparticles, radionuclides) must reach the targeted cells through the tumor environment at adequate concentrations, in order to exert their cell-killing effects. For any of these agents to reach the goal cells, they must overcome a number of impediments created by the tumor microenvironment (TME), beginning with tumor interstitial fluid pressure (TIFP), and a multifactorial increase in composition of the extracellular matrix (ECM). A primary modifier of TME is hypoxia, which increases the production of growth factors, such as vascular endothelial growth factor and platelet-derived growth factor.

Tumor interstitial fluid: proteomic determination as a possible source of biomarkers.

Tumor interstitial fluid (TIF) is formed largely by an imbalance between the forces that govern the filtration of liquid between the luminal and abluminal parts of tumor neo-vessels. TIF is a dynamic solution that varies according to tumor type, and is generally rich in proteins, lipids, and various enzyme-derived substances. These enzyme-derived substances can have important roles as both regulatory and inflammatory factors.

Update on the challenges and recent advances in cancer immunotherapy.

This overview provides an analysis of some of the immunotherapies currently in use and under investigation, with a special focus on the tumor microenvironment, which we believe is a major factor responsible for the general failure of immunotherapy to date. It is our expectation that combining immunotherapy with methods of altering the tumor microenvironment and targeting regulatory T cells and myeloid cells will yield favorable results.

Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin.

Cellular metabolic alterations are now well described as implicated in cancer and some strategies are currently developed to target these different pathways. In previous papers, we demonstrated that a combination of molecules (namely alpha-lipoic acid and hydroxycitrate, i.e.