Fatty Acid Mediators in the Tumor Microenvironment.

Patients with cancer frequently overexpress inflammatory cytokines with an associated neutrophilia both of which may be downregulated by diets with high omega-3 polyunsaturated fatty acids (ω-3 PUFA). The anti-inflammatory activity of dietary ω-3 PUFA has been suggested to have anticancer properties and to improve survival of cancer patients. Currently, the majority of dietary research efforts do not differentiate between obesity and dietary fatty acid consumption as mediators of inflammatory cell expansion and tumor microenvironmental infiltration, initiation, and progression.

Immune regulation and anti-cancer activity by lipid inflammatory mediators.

Rodent and clinical studies have documented that myeloid cell infiltration of tumors is associated with poor outcomes, neutrophilia and lymphocytopenia. This contrasts with increased lymphocyte infiltration of tumors, which is correlated with improved outcomes. Lifestyle parameters, such as obesity and diets with high levels of saturated fat and/or omega (ω)-6 polyunsaturated fatty acids (PUFAs), can influence these inflammatory parameters, including an increase in extramedullary myelopoiesis (EMM).

Long-Chain Omega-3 Polyunsaturated Fatty Acids Modulate Mammary Gland Composition and Inflammation.

Studies in rodents have shown that dietary modifications as mammary glands (MG) develop, regulates susceptibility to mammary tumor initiation. However, the effects of dietary PUFA composition on MGs in adult life, remains poorly understood. This study investigated morphological alterations and inflammatory microenvironments in the MGs of adult mice fed isocaloric and isolipidic liquid diets with varying compositions of omega (ω)-6 and long-chain (Lc)-ω3FA that were pair-fed.

Lipid Inflammatory Mediators in Cancer Progression and Therapy.

Rodent and clinical studies have documented that myeloid cell infiltration of tumors is associated with neutrophilia, lymphocytopenia and poor patient outcomes. This contrasts with lymphocyte infiltration of tumors, which is associated with improved outcomes. Lifestyle parameters such as high fat diet s and omega (ω)-6 polyunsaturated fatty acids (PUFA) intake may influence these inflammatory parameters including extramedullary myelopoiesis that can contribute to a metastatic "niche".

Dietary omega-3 and omega-6 polyunsaturated fatty acids modulate hepatic pathology.

Recent evidence has suggested that dietary polyunsaturated fatty acids (PUFAs) modulate inflammation; however, few studies have focused on the pathobiology of PUFA using isocaloric and isolipidic diets and it is unclear if the associated pathologies are due to dietary PUFA composition, lipid metabolism or obesity, as most studies compare diets fed ad libitum. Our studies used isocaloric and isolipidic liquid diets (35% of calories from fat), with differing compositions of omega (ω)-6 or long chain (Lc) ω-3 PUFA that were pair-fed and assessed hepatic pathology, inflammation and lipid metabolism. Consistent with an isocaloric, pair-fed model we observed no significant difference in diet consumption between the groups.

Improved therapy for neuroblastoma using a combination approach: superior efficacy with vismodegib and topotecan.

Aberrant activation/expression of pathways/molecules including NF-kB, mTOR, hedgehog and polo-like-kinase-1 (PLK1) are correlated with poor-prognosis neuroblastoma. Therefore, to identify a most efficacious treatment for neuroblastoma, we investigated the efficacy of NF-kB/mTOR dual-inhibitor 13-197, hedgehog inhibitor vismodegib and PLK1 inhibitor BI2536 alone or combined with topotecan against high-risk neuroblastoma. The in vitro efficacy of the inhibitors alone or combined with topotecan on cell growth/apoptosis and molecular mechanism(s) were investigated.

Changes in the frequencies of human hematopoietic stem and progenitor cells with age and site.

This study enumerated CD45(hi)/CD34(+) and CD45(hi)/CD133(+) human hematopoietic stem cells (HSCs) and progenitor granulocyte-macrophage colony forming cells (GM-CFCs) in blood and trochanteric and femoral bone marrow in 233 individuals. Stem cell frequencies were determined with multiparameter flow cytometry and using an internal control to determine the intrinsic variance of the assays. Progenitor cell frequency was determined using a standard colony assay technique.