The purpose of this study is to create a prospective investigation to examine the effects of montelukast, almonds/almond oil, and specialized pro-resolving mediators (SPMs) on lipid profiles and tumor-associated macrophages (TAMs) in cancer patients (colorectal cancer, sarcoma, brain tumors, endometrial cancer, and ovarian cancer). The focus will be on assessing changes in lipid mediator concentrations, TAM reprogramming, and immune cell function in treated versus untreated patients. It is hypothesized that montelukast will reduce the pro-inflammatory effects of leukotriene B4 (LTB4), while SPMs and almonds/almond oil will shift the balance toward pro-resolving mediators, enhancing anti-inflammatory and immune-stimulatory responses and reprogramming TAMs.
This prospective study investigates the effects of montelukast, almonds/almond oil, and specialized pro-resolving mediators (SPMs) on lipid profiles and tumor-associated macrophages (TAMs) in patients with colorectal cancer (CRC), sarcoma, brain tumors (BT), endometrial cancer (EC), and ovarian cancer (OvCa). Patients receiving these treatments will be compared to untreated controls, with tissue samples collected post-surgery for analysis. A cohort of patients who have undergone tumor resection will be included for the assessment of lipid mediator concentrations (approximately 65 arachidonic acid pathway lipids) and TAM reprogramming, with an emphasis on comparing treated and untreated groups. The study will also examine peripheral blood mononuclear cells (PBMCs) and plasma concentrations of lipid mediators before and after treatment, focusing on changes in PBMC function and phenotype. It is hypothesized that montelukast, an LTB4/ cysteinyl leukotriene receptor 1 (CYSLTR1) inhibitor, will reduce the pro-inflammatory effects of LTB4 in cancer tissues. Furthermore, it is anticipated that SPMs and almonds/almond oil will shift the lipid mediator balance toward pro-resolving mediators, enhancing anti-inflammatory responses, stimulating immune function, and reprogramming TAMs.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
56
No study treatment other than the standard of care management.
Sports Pro Resolve 4 tabs (2 g) twice daily
Double Wood SPM 4 tabs (2 g) twice daily
10 California Sweet Almonds twice daily
Montelukast 10 Mg Oral Tablet daily
Montelukast 10 Mg Oral Tablet and SPM 4 g
Cold- Pressed Almond Oil 30 mL every morning
Tampa General Hospital
Tampa, Florida, United States
University of South Florida
Tampa, Florida, United States
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).
Time frame: Day 14 of treatment
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).
Time frame: Day 14 of treatment
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.
Time frame: Day 14 of treatment
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.
Time frame: Day 14 of treatment
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.
Time frame: Day 14 of treatment
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.
Time frame: Day 0 and Day 14
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