Lipid Mediators & Cancer: Montelukast, SPM, and Almonds

Quantity of lipid mediators in a tumor specimen after 2 weeks of study treatment.

Quantitation will be assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS). The absolute quantity of these lipid mediators will be compared to the absolute quantity in the corresponding normal tissue. In preliminary studies, the investigators have used LC-MS/MS to measure \~65 different lipid mediators of the arachidonic acid pathway in colorectal cancer. Interestingly, the investigators found high proportions of pro-inflammation mediators and depressed levels of pro-resolution-of-inflammation mediators in cancer tissue compared with the non-affected tissue of the same patients. Possible study treatments include: specialized pro-resolving mediators vs Montelukast vs almonds/almond oil vs combination).

Quantity of lipid mediators in a non-cancerous (i.e. normal) tissue from the resected surgical specimen after 2 weeks of study treatment.

Quantitation will be assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS). The absolute quantity of these lipid mediators will be compared to the absolute quantity in the corresponding cancer tissue. This change in quantity will enable us to make deductions about the influence of the corresponding study treatment on the tumor and its environment. For example, does the treatment in question make the tumor environment less inflamed/promote healing and therefore make the cancer more susceptible to treatment? Possible study treatments include: specialized pro-resolving mediators vs Montelukast vs almonds/almond oil vs combination).

Quantity of tumor microenvironment subpopulations in a tumor specimen versus corresponding normal tissue after 2 weeks of study treatment.

Tumor microenvironment subpopulations are defined as the various components of the immune system in the tissue surrounding a cancer, i.e.: cluster of differentiation 4 (CD4) T cells, cluster of differentiation 8 (CD8) T cells, B cells, natural killer (NK) cells, macrophages, etc. Quantitation will be assessed using n-counter analysis.

Distribution of tumor-associated macrophage (TAM) phenotype in tumor specimens versus corresponding normal tissue after 2 weeks of study treatment.

There are two main TAM phenotypes: M1 and M2. M1 are the classically activated, anti-tumor macrophages, and M2 are the "bad", pro-inflammation/neoplastic macrophages. Change in distribution will be assessed using multiparameter flow cytometry. M1 versus M2 phenotypes will be identified by utilizing macrophage-specific biomarkers.

Functionality of tumor-associated macrophages in tumor specimens versus corresponding normal tissue after 2 weeks of study treatment.

Change in functionality will be determined using efferocytosis assays.

Change in quantity of lipids in peripheral blood from day 0 to day 14 of study treatment.

Quantitation will be assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS). This assessment will enable us to correlate peripheral blood levels of lipid mediators with tissue penetrance. For example, the investigators may find that a study treatment has a significant impact on the lipid mediator profile of the blood but that same impact is not seen in the corresponding tissue of that patient; therefore, there deductions can be made about tissue penetrance capability.