Jessica A. Martinez
- Assistant Research Professor, Nutritional Sciences
- Ph.D. Nutritional Sciences
- University of Arizona, Tucson, Arizona, United States
- Bioavailability and disposition of the anti-cancer agent, d-limonene, and implications for breast cancer prevention
- University of Arizona, Tucson, Arizona (2013 - Ongoing)
- Top 17 Abstracts for ASPO conference
- American Society for Preventive Oncology (ASPO), Spring 2020
- CALS Research Innovation Challenge
- Fall 2015
Licensure & Certification
- Certificate in College Teaching, University of Arizona (2009)
No activities entered.
Independent StudyNSC 599 (Fall 2019)
Nutrigeno Disease Prv+InNSC 475 (Spring 2018)
Nutrigeno Disease Prv+InNSC 575 (Spring 2018)
Honors ThesisNSC 498H (Spring 2016)
- Martinez, J. A. (2016). Effects of Mediterranean Diet on the Metabolome. In Mediterranean Diet.
- Martinez, J. A. (2020). [ASPO Abstract] Oxylipins Correlate with Quality of Life in Women Taking Aromatase Inhibitors for Breast Cancer. Cancer Epidemiology Biomarkers and Prevention, 3, 691. doi:DOI:10.1158/1055-9965.EPI-20-0054More infoOne of the 17 highest scoring abstracts of those submitted for presentation at the 44th Annual ASPO meeting held March 22–24, 2020, in Tucson, AZ.
- Martinez, J. A., Miller, R. H., & Martinez, R. A. (2020). Patient Questions Surrounding Mask Use for Prevention of COVID-19 and Physician Answers from an Evidence-Based Perspective: a Narrative Review. Journal of general internal medicine.More infoRecent mandates to wear masks in public places across the USA combined with conflicting messaging from the media and government agencies have generated a lot of patient questions surrounding the appropriate use and efficacy of cloth masks. Here, we have organized the evidence in the context of real patient questions and have provided example answers from a physician's perspective. The purpose of this review is to offer healthcare providers with examples of how to respond to patient questions about masks in a way that encourages responsible decision-making. We conclude, based on the evidence showing a benefit for cloth masks and the recent reports supporting a role for aerosols in the transmission of SARS-CoV-2, that cloth masks will be effective when used correctly. We further assert that stronger public messaging surrounding cloth masks in the community setting is needed, and should specify that 2-3 layer, fitted face masks be worn at all times in public as another layer of protection in addition to social distancing, not just when social distancing cannot be maintained.
- Jacobs, E. T., Lance, P., Mandarino, L. J., Ellis, N. A., Chow, H. S., Foote, J., Martinez, J. A., Hsu, C. P., Batai, K., Saboda, K., & Thompson, P. A. (2019). Selenium supplementation and insulin resistance in a randomized, clinical trial. BMJ open diabetes research & care, 7(1), e000613.More infoWhile controversial, observational and randomized clinical trial data implicate the micronutrient selenium (Se) in the development of type 2 diabetes (T2D). The aim of this study was to test the hypothesis that Se supplementation adversely affects pancreatic β-cell function and insulin sensitivity.
- Pearson, T., Caporaso, J. G., Yellowhair, M., Bokulich, N. A., Padi, M., Roe, D. J., Wertheim, B. C., Linhart, M., Martinez, J. A., Bilagody, C., Hornstra, H., Alberts, D. S., Lance, P., & Thompson, P. A. (2019). Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development. Cancer medicine, 8(2), 617-628.More infoIt has been previously reported that ursodeoxycholic acid (UDCA), a therapeutic bile acid, reduced risk for advanced colorectal adenoma in men but not women. Interactions between the gut microbiome and fecal bile acid composition as a factor in colorectal cancer neoplasia have been postulated but evidence is limited to small cohorts and animal studies. Using banked stool samples collected as part of a phase III randomized clinical trial of UDCA for the prevention of colorectal adenomatous polyps, we compared change in the microbiome composition after a 3-year intervention in a subset of participants randomized to oral UDCA at 8-10 mg/kg of body weight per day (n = 198) or placebo (n = 203). Study participants randomized to UDCA experienced compositional changes in their microbiome that were statistically more similar to other individuals in the UDCA arm than to those in the placebo arm. This reflected a UDCA-associated shift in microbial community composition (P 0.05). These UDCA-associated shifts in microbial community distance metrics from baseline to end-of-study were not associated with risk of any or advanced adenoma (all P > 0.05) in men or women. Separate analyses of microbial networks revealed an overrepresentation of Faecalibacterium prausnitzii in the post-UDCA arm and an inverse relationship between F prausnitzii and Ruminococcus gnavus. In men who received UDCA, the overrepresentation of F prausnitzii and underrepresentation of R gnavus were more prominent in those with no adenoma recurrence at follow-up compared to men with recurrence. This relationship was not observed in women. Daily UDCA use modestly influences the relative abundance of microbial species in stool and affects the microbial network composition with suggestive evidence for sex-specific effects of UDCA on stool microbial community composition as a modifier of colorectal adenoma risk.
- Garcia, D. O., Morrill, K. E., Aceves, B., Valdez, L. A., Rabe, B. A., Bell, M. L., Hakim, I. A., Martinez, J. A., & Thomson, C. A. (2018). Feasibility and acceptability of a beverage intervention for Hispanic adults: results from a pilot randomized controlled trial. Public health nutrition, 1-11.More infoTo assess the feasibility and acceptability of a beverage intervention in Hispanic adults.
- Karl, S., Fallon, M., Palitsky, R., Martinez, J. A., Gündel, H., & O'Connor, M. F. (2018). Low-Dose Aspirin for Prevention of Cardiovascular Risk in Bereavement: Results from a Feasibility Study. Psychotherapy and psychosomatics, 87(2), 112-113.
- Martinez, J. A. (2018). Celecoxib use and circulating oxylipins in a colon polyp prevention trial. PLOS ONE.
- Martinez, J. A., Yang, J., Wertheim, B. C., Roe, D. J., Schriewer, A., Lance, P., Alberts, D. S., Hammock, B. D., & Thompson, P. A. (2018). Celecoxib use and circulating oxylipins in a colon polyp prevention trial. PloS one, 13(4), e0196398.More infoDrugs that inhibit cyclooxygenase (COX)-2 and the metabolism of arachidonic acid (ARA) to prostaglandin E2 are potent anti-inflammatory agents used widely in the treatment of joint and muscle pain. Despite their benefits, daily use of these drugs has been associated with hypertension, cardiovascular and gastrointestinal toxicities. It is now recognized that ARA is metabolized to a number of bioactive oxygenated lipids (oxylipins) by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Currently, the contribution of individual variability in ARA metabolism in response to the COX-2 inhibitors and potential adverse effects remains poorly understood. Using patient samples from the randomized, placebo-controlled phase III selenium/celecoxib (Sel/Cel) trial for the prevention of colorectal adenomatous polyps, we analyzed plasma concentrations of 74 oxylipins in a subset of participants who received celecoxib (n = 90) or placebo (n = 95). We assessed the effect of celecoxib (with and without low dose aspirin) on circulating oxylipins and systolic blood pressure (SBP). Individual CYP450- and LOX- but not COX-derived metabolites were higher with celecoxib than placebo (P
- Morrill, K. E., Aceves, B., Valdez, L. A., Thomson, C. A., Hakim, I. A., Bell, M. L., Martinez, J. A., & Garcia, D. O. (2018). Feasibility and Acceptability of a Beverage Intervention for Hispanic Adults: A Protocol for a Pilot Randomized Controlled Trial. Nutrition Journal.
- Morrill, K. E., Aceves, B., Valdez, L. A., Thomson, C. A., Hakim, I. A., Bell, M. L., Martinez, J. A., & Garcia, D. O. (2018). Feasibility and acceptability of a beverage intervention for Hispanic adults: a protocol for a pilot randomized controlled trial. Nutrition journal, 17(1), 16.More infoIn the U.S., Hispanics have among the highest rates of overweight and obesity when compared to other racial/ethnic groups placing them at a greater risk for obesity-related disease. Identifying intervention strategies to reduce caloric intake and/or improve cardiometabolic health in Hispanics is critical to reducing morbidity and mortality among this large and growing population. Evidence exists to support diet-specific behavioral interventions, including beverage modifications, in reducing obesity-related health risks. However, the acceptability and feasibility of a beverage intervention in obese Hispanic adults has not been robustly evaluated.
- Nguyen, M. M., Martinez, J. A., Hsu, C. H., Sokoloff, M., Krouse, R. S., Gibson, B. A., Nagle, R. B., Parnes, H. L., Cordova, C., & Chow, H. S. (2018). Bioactivity and prostate tissue distribution of metformin in a preprostatectomy prostate cancer cohort. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP), 27(6), 557-562.More infoMetformin has recently been shown to have potential to reduce prostate cancer risk. We conducted a randomized, double-blind, placebo-controlled trial to determine the modulating effects of metformin on tissue and systemic biomarkers of drug activity and its distribution into the prostate tissue. Twenty patients with prostate cancer scheduled to undergo prostatectomy were randomly assigned to receive either extended-release metformin or placebo for a median of 34 days before surgery. Prostatectomy and serum samples were analyzed for metformin concentrations, serum biomarkers of drug activity (prostate-specific antigen, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein 3, sex hormone-binding globulin, and testosterone) and tissue biomarkers of proliferation, apoptosis, cell cycle regulation, and mTOR inhibition. For participants in the metformin arm, the prostate tissue and serum metformin concentrations ranged from 0.88 to 51.2 μg/g tissue and from not detectable to 3.6 μg/ml, respectively. There were no differences between the two groups in either the postintervention tissue biomarker expression in the prostatectomy tissue or pre to postintervention changes in serum biomarkers. We conclude that metformin distributes to human prostate tissue, suggesting that metformin could exert its effects directly on tissue targets. However, there was no difference in tissue and systemic drug effect biomarkers between the two treatment arms. Future studies with longer intervention duration and larger sample size should be considered in order to evaluate the potential of metformin for prostate cancer prevention.
- Guthrie, A. R., Chow, H. S., & Martinez, J. A. (2017). Effects of resveratrol on drug- and carcinogen-metabolizing enzymes, implications for cancer prevention. Pharmacology research & perspectives, 5(1), e00294.More infoResveratrol is a polyphenol found in grape skins and peanuts that has demonstrated many health benefits including protection against aging, cardiovascular and metabolic disease, neurological decline, and cancer. The anticancer properties of resveratrol have been attributed to a variety of mechanisms, including its general inhibition of phase I metabolism and induction of phase II metabolism. The effects of resveratrol on these enzymes, however, are still unclear, as in vitro evidence often contrasts with animal studies and clinical trials. Reasons for these variances could include the low bioavailability of resveratrol and the effects of resveratrol metabolites. Due to resveratrol's interactions with drug-metabolizing enzymes and drug transporters, individuals concurrently taking pharmacological doses of resveratrol with other supplements or medications could potentially experience nutrient-drug interactions. This review summarizes the known effects of resveratrol and its main metabolites on drug metabolism in order to help characterize which populations might benefit from resveratrol for the prevention of cancer, as well as those that may need to avoid supplementation due to potential drug interactions.
- Karl, S., Fallon, M., Palitsky, R., Martinez, J. A., Gundel, H., & O'Connor, M. O. (2017). Low-dose aspirin for prevention of cardiovascular risk in bereavement: results from a feasibility study. Psychotherapy and Psychosomatics.
- Martinez, J. A. (2017). Prostate Tissue Disposition and Bioactivity of Metformin in a Pre-prostatectomy Prostate Cancer Cohort. Cancer Prevention Research.
- Banerjee, B., Shaheen, N. J., Martinez, J. A., Hsu, C. H., Trowers, E., Gibson, B. A., Della'Zanna, G., Richmond, E., & Chow, H. H. (2016). Clinical Study of Ursodeoxycholic Acid in Barrett's Esophagus Patients. Cancer prevention research (Philadelphia, Pa.), 9(7), 528-33.More infoPrior research strongly implicates gastric acid and bile acids, two major components of the gastroesophageal refluxate, in the development of Barrett's esophagus and its pathogenesis. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to protect esophageal cells against oxidative stress induced by cytotoxic bile acids. We conducted a pilot clinical study to evaluate the clinical activity of UDCA in patients with Barrett's esophagus. Twenty-nine patients with Barrett's esophagus received UDCA treatment at a daily dose of 13 to 15 mg/kg/day for 6 months. The clinical activity of UDCA was assessed by evaluating changes in gastric bile acid composition and markers of oxidative DNA damage (8-hydroxydeoxyguanosine), cell proliferation (Ki67), and apoptosis (cleaved caspase-3) in Barrett's esophagus epithelium. The bile acid concentrations in gastric fluid were measured by liquid chromatography/mass spectrometry. At baseline, UDCA (sum of unchanged and glycine/taurine conjugates) accounted for 18.2% of total gastric bile acids. After UDCA intervention, UDCA increased significantly to account for 93.4% of total gastric bile acids (P < 0.0001). The expression of markers of oxidative DNA damage, cell proliferation, and apoptosis was assessed in the Barrett's esophagus biopsies by IHC. The selected tissue biomarkers were unchanged after 6 months of UDCA intervention. We conclude that high-dose UDCA supplementation for 6 months resulted in favorable changes in gastric bile acid composition but did not modulate selected markers of oxidative DNA damage, cell proliferation, and apoptosis in the Barrett's esophagus epithelium. Cancer Prev Res; 9(7); 528-33. ©2016 AACRSee related article by Brian J. Reid, p. 512.
- Martinez, J. A. (2016). Clinical Study of Ursodeoxycholinc Acid in Barrett’s Patients. Cancer Prevention Research.
- Martinez, J. A. (2016). Phase II Study of Metformin for Reduction of Obesity-Associated Breast Cancer Risk: A Randomized Controlled Trial Protocol. BMC Cancer.
- Martinez, J. A. (2017). Effect of resveratrol on phase I and II metabolism, implications for cancer prevention. Pharmacology, Research & Perspectives.
- Martinez, J. A. (2017). Physical activity modifies the effect of dietary protein on the lean mass of postmenopausal women. Journal of the Academy of Nutrition and Dietetics.
- Martinez, J. A., Chalasani, P., Thomson, C. A., Roe, D., Altbach, M., Galons, J., Stopeck, A., Thompson, P. A., Villa-Guillen, D. E., & Chow, H. S. (2016). Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol. BMC cancer, 16, 500.More infoTwo-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk.
- Martinez, J. A., Wertheim, B. C., Thomson, C. A., Bea, J. W., Wallace, R., Allison, M., Snetselaar, L., Chen, Z., Nassir, R., & Thompson, P. A. (2016). Physical Activity Modifies the Association between Dietary Protein and Lean Mass of Postmenopausal Women. Journal of the Academy of Nutrition and Dietetics.More infoMaintenance of lean muscle mass and related strength is associated with lower risk for numerous chronic diseases of aging in women.
- Navarro, S. L., Neuhouser, M. L., Cheng, T. D., Tinker, L. F., Shikany, J. M., Snetselaar, L., Martinez, J. A., Kato, I., Beresford, S. A., Chapkin, R. S., & Lampe, J. W. (2016). The Interaction between Dietary Fiber and Fat and Risk of Colorectal Cancer in the Women's Health Initiative. Nutrients, 8(12).More infoCombined intakes of specific dietary fiber and fat subtypes protect against colon cancer in animal models. We evaluated associations between self-reported individual and combinations of fiber (insoluble, soluble, and pectins, specifically) and fat (omega-6, omega-3, and docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), specifically) and colorectal cancer (CRC) risk in the Women's Health Initiative prospective cohort (n = 134,017). During a mean 11.7 years (1993-2010), 1952 incident CRC cases were identified. Cox regression models computed multivariate adjusted hazard ratios to estimate the association between dietary factors and CRC risk. Assessing fiber and fat individually, there was a modest trend for lower CRC risk with increasing intakes of total and insoluble fiber (p-trend 0.09 and 0.08). An interaction (p = 0.01) was observed between soluble fiber and DHA + EPA, with protective effects of DHA + EPA with lower intakes of soluble fiber and an attenuation at higher intakes, however this association was no longer significant after correction for multiple testing. These results suggest a modest protective effect of higher fiber intake on CRC risk, but not in combination with dietary fat subtypes. Given the robust results in preclinical models and mixed results in observational studies, controlled dietary interventions with standardized intakes are needed to better understand the interaction of specific fat and fiber subtypes on colon biology and ultimately CRC susceptibility in humans.
- Miller, J. A., Pappan, K., Thompson, P. A., Want, E. J., Siskos, A. P., Keun, H. C., Wulff, J., Hu, C., Lang, J. E., & Chow, H. S. (2015). Plasma Metabolomic Profiles of Breast Cancer Patients after Short-term Limonene Intervention. Cancer prevention research (Philadelphia, Pa.), 8(1), 86-93.More infoLimonene is a lipophilic monoterpene found in high levels in citrus peel. Limonene demonstrates anticancer properties in preclinical models with effects on multiple cellular targets at varying potency. While of interest as a cancer chemopreventive, the biologic activity of limonene in humans is poorly understood. We conducted metabolite profiling in 39 paired (pre/postintervention) plasma samples from early-stage breast cancer patients receiving limonene treatment (2 g QD) before surgical resection of their tumor. Metabolite profiling was conducted using ultra-performance liquid chromatography coupled to a linear trap quadrupole system and gas chromatography-mass spectrometry. Metabolites were identified by comparison of ion features in samples to a standard reference library. Pathway-based interpretation was conducted using the human metabolome database and the MetaCyc database. Of the 397 named metabolites identified, 72 changed significantly with limonene intervention. Class-based changes included significant decreases in adrenal steroids (P < 0.01), and significant increases in bile acids (P ≤ 0.05) and multiple collagen breakdown products (P < 0.001). The pattern of changes also suggested alterations in glucose metabolism. There were 47 metabolites whose change with intervention was significantly correlated to a decrease in cyclin D1, a cell-cycle regulatory protein, in patient tumor tissues (P ≤ 0.05). Here, oral administration of limonene resulted in significant changes in several metabolic pathways. Furthermore, pathway-based changes were related to the change in tissue level cyclin D1 expression. Future controlled clinical trials with limonene are necessary to determine the potential role and mechanisms of limonene in the breast cancer prevention setting. Cancer Prev Res; 8(1); 86-93. ©2014 AACR.
- Tredwell, G. D., Miller, J. A., Chow, H. S., Thompson, P. A., & Keun, H. C. (2014). Metabolomic characterization of nipple aspirate fluid by (1)H NMR spectroscopy and GC-MS. Journal of proteome research, 13(2), 883-9.More infoNipple aspirate fluid (NAF) is a noninvasively obtained biofluid from the duct openings of the breast. NAF components are constantly secreted, metabolized, and reabsorbed by the epithelial lining of the lactiferous ducts of the breast. NAF has been studied as a potential breast tissue surrogate for the discovery of novel breast cancer risk, early detection, and treatment response biomarkers. We report the first unsupervised metabolite characterization of nipple aspirate fluid using NMR and GC-MS using convenience samples previously collected from four premenopausal and four postmenopausal women. A total of 38 metabolites were identified using the two analytical techniques, including amino acids, organic acids, fatty acids, and carbohydrates. Analytical reproducibility of metabolites in NAF by GC-MS was high across different extraction and analysis days. Overall, 31 metabolites had a coefficient of variation below 20%. By GC-MS, there were eight metabolites unique to NAF, 19 unique to plasma, and 24 shared metabolites. Correlative analysis of shared metabolites between matched NAF and plasma samples from pre- and postmenopausal women shows almost no correlations, with the exception being lactic acid, which was significantly negatively correlated (R(2) = 0.57; P = 0.03). These results suggest that NAF is metabolically distinct from plasma and that the application of metabolomic strategies may be useful for future studies investigating breast cancer risk and intervention response biomarkers.
- Miller, J. A., Lang, J. E., Ley, M., Nagle, R., Hsu, C., Thompson, P. A., Cordova, C., Waer, A., & Chow, H. S. (2013). Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer. Cancer prevention research (Philadelphia, Pa.), 6(6), 577-84.More infoLimonene is a bioactive food component found in citrus peel oil that has shown chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open-label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited 43 women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for two to six weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean = 41.3 μg/g tissue), whereas the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P = 0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase-3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, insulin-like growth factor binding protein-3 (IGFBP-3), and interleukin-6 (IL-6) levels were observed following limonene intervention. There was a small but statistically significant postintervention increase in insulin-like growth factor I (IGF-I) levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell-cycle arrest and reduced cell proliferation. Furthermore, placebo-controlled clinical trials and translational research are warranted to establish limonene's role for breast cancer prevention or treatment.
- Miller, J. A., Thompson, P. A., Hakim, I. A., Lopez, A. M., Thomson, C. A., Hsu, C., & Chow, H. S. (2013). Expression of epidermal growth factor, transforming growth factor-β1 and adiponectin in nipple aspirate fluid and plasma of pre and post-menopausal women. Biomarker research, 1(1), 18.More infoNipple aspirate fluid (NAF) contains large amounts of protein thought to reflect the microenvironment of the breast, and is of interest in breast cancer prevention research. The correlation between specific NAF proteins to plasma concentrations have not been well studied in healthy women. We collected matched NAF and plasma from 43 healthy pre and postmenopausal women participating in an early phase clinical study to compare the levels of putative cancer protein biomarkers. We compared baseline NAF and plasma levels of epidermal growth factor (EGF), transforming growth factor-beta 1 (TGF-β1), and adiponectin and evaluated menopausal status and body mass index (BMI) as potential modifying factors.
- Miller, J. A., Thompson, P. A., Hakim, I. A., Lopez, A. M., Thomson, C. A., Chew, W., Hsu, C., & Chow, H. S. (2012). Safety and Feasibility of Topical Application of Limonene as a Massage Oil to the Breast. Journal of cancer therapy, 3(5A).More infoLimonene, a major component in citrus oil, has demonstrated anti-cancer effects in preclinical mammary cancer models. However, the effective oral dose translates to a human dose that may not be feasible for chronic dosing. We proposed to evaluate topical application of limonene to the breast as an alternative dosing strategy.
- Miller, J. A., Thompson, P. A., Hakim, I. A., Chow, H. S., & Thomson, C. A. (2011). d-Limonene: a bioactive food component from citrus and evidence for a potential role in breast cancer prevention and treatment. Oncology Reviews, 5(1), 31--42.
- Chow, H. S., Garland, L. L., Hsu, C., Vining, D. R., Chew, W. M., Miller, J. A., Perloff, M., Crowell, J. A., & Alberts, D. S. (2010). Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer prevention research (Philadelphia, Pa.).More infoResveratrol has been shown to exhibit cancer-preventive activities in preclinical studies. We conducted a clinical study to determine the effect of pharmacologic doses of resveratrol on drug- and carcinogen-metabolizing enzymes. Forty-two healthy volunteers underwent baseline assessment of cytochrome P450 (CYP) and phase II detoxification enzymes. CYP1A2, CYP2D6, CYP2C9, and CYP3A4 enzyme activities were measured by the metabolism of caffeine, dextromethorphan, losartan, and buspirone, respectively. Blood lymphocyte glutathione S-transferase (GST) activity and GST-pi level and serum total and direct bilirubin, a surrogate for UDP-glucuronosyl transferase (UGT) 1A1 activity, were measured to assess phase II enzymes. After the baseline evaluation, study participants took 1 g of resveratrol once daily for 4 weeks. Enzyme assessment was repeated upon intervention completion. Resveratrol intervention was found to inhibit the phenotypic indices of CYP3A4, CYP2D6, and CYP2C9 and to induce the phenotypic index of 1A2. Overall, GST and UGT1A1 activities were minimally affected by the intervention, although an induction of GST-pi level and UGT1A1 activity was observed in individuals with low baseline enzyme level/activity. We conclude that resveratrol can modulate enzyme systems involved in carcinogen activation and detoxification, which may be one mechanism by which resveratrol inhibits carcinogenesis. However, pharmacologic doses of resveratrol could potentially lead to increased adverse drug reactions or altered drug efficacy due to inhibition or induction of certain CYPs. Further clinical development of resveratrol for cancer prevention should consider evaluation of lower doses of resveratrol to minimize adverse metabolic drug interactions.
- Miller, J. A., Hakim, I. A., Chew, W., Thompson, P., Thomson, C. A., & Chow, H. S. (2010). Adipose tissue accumulation of d-limonene with the consumption of a lemonade preparation rich in d-limonene content. Nutrition and cancer, 62(6), 783-8.More infod-limonene is a bioactive food component found in high concentration in citrus peel oil with anticancer effects in preclinical studies of mammary carcinogenesis. Extrapolation of preclinical data to human cancer is limited, in part, by inadequate information on the oral bioavailability and tissue disposition of d-limonene in humans. As a fat-soluble compound, d-limonene is more likely to deposit in fatty tissues such as the breast. To assess disposition of d-limonene in humans, we conducted a pilot study of oral d-limonene-rich lemonade. Following a 1-wk washout period devoid of citrus, healthy adults consumed 40 oz. of freshly prepared lemonade containing 500 to 600 mg d-limonene daily for 4 wk. On the first and last consumption days, blood and buttock fat biopsy were collected. Matched preintervention and postintervention fat biopsies (n = 7), and matched preintervention and postintervention plasma samples (n = 6), were analyzed for d-limonene levels using gas chromatography and mass spectrometry. There was a significant increase in d-limonene levels in the fat biopsies after 4 wk (P = 0.009); initial levels ranged from nondetectable to 7.79 micromol/kg tissue, and postintervention levels ranged from 53.6 to 294 micromol/kg tissue. Plasma d-limonene levels increased from 0.35 to 0.72 micromol/l initially to postintervention levels of 0.54 to 1.65 micromol/l (P = 0.016). Postintervention adipose d-limonene levels were 51.0 to 195 times higher than plasma levels (P = 0.009). Our results demonstrate accumulation of d-limonene in adipose tissue after oral dosing and support additional studies of d-limonene for chemoprevention in tissues such as the breast that are comprised of a significant fat fraction.
- Miller, J. A., Hakim, I. A., Thomson, C., Thompson, P., & Chow, H. S. (2008). Determination of d-limonene in adipose tissue by gas chromatography--mass spectrometry. Journal of Chromatography B, 870(1), 68--73.
- Martinez, J. A. (2020, March). Oxylipins Correlate with Quality of Life in Women Taking Aromatase Inhibitors for Breast Cancer. American Society of Preventive Oncology Annual Conference. Tucson, Arizona: American Society of Preventive Oncology.More infoPodium Presentation
- Martinez, J. A. (2016, Fall). Imaging and blood-based Biomarkers of aromatase inhibitor musculoskeletal syndrome (AIMSS). Cancer Prevention and Control Seminar. University of Arizona Cancer Center.
- Martinez, J. A. (2015, April). Application of Oxylipin Profiling to a Sulindac Intervention of Aromatase Inhibitor-Induced Pain. University of Arizona Cancer Center Annual Retreat.
- Martinez, J. A. (2015, Aug). Targeting the Hallmarks of Cancer in Prevention Clinical Trials. Waters Corporation Omics Day Conference.
- Chow, H., Algotar, A., Martinez, J. A., Pinto, L., Trujillo, J., Altbach, M. I., Thomson, C. A., Galons, J., Huang, C., Guillen-Rodriguez, J., Roe, D., Centuori, S., Chalasani, P., Villa Guillen, D., & Tapia, E. (2020, Fall). Effects of metformin on breast density and anthropometric measurements in premenopausal women with components of metabolic syndrome: Findings from a Phase II randomized, double-blind, placebo-controlled trial.. University of Arizona Cancer Center Fall Retreat.More infoTapia E, Villa Guillen D, Chalasani P, Centuori S, Roe D, Guillen-Rodriguez J, Huang C, Galons JP, Thomson CA, Altbach M, Trujillo J1, Pinto L, Martinez JA, Algotar AM,, Chow S. Effects of metformin on breast density and anthropometric measurements in premenopausal women with components of metabolic syndrome: Findings from a Phase II randomized, double-blind, placebo-controlled trial. UACC Fall Retreat. (November 2020).
- Martinez, J. A. (2020, March). Sulindac Improves Stiffness and Quality of Life in Women Taking Aromatase Inhibitors for Breast Cancer. American Society of Preventive Oncology Annual Conference. Tucson, Arizona: American Society of Preventive Oncology.More infoPoster Presentation
- Chow, H., Chow, H., Algotar, A., Algotar, A., Altbach, M. I., Altbach, M. I., Galons, J., Galons, J., Roe, D., Roe, D., Thomson, C. A., Thomson, C. A., Guillen-Rodriguez, J. M., Guillen-Rodriguez, J. M., Martinez, J. A., Martinez, J. A., Chalasani, P., Chalasani, P., Villa Guillen, D. E., , Villa Guillen, D. E., et al. (2018, Fall). Abstract: Phase II clinical study of metformin for breast cancer prevention. UACC Scientific Retreat. UACC Scientific Retreat. Tucson, AZ.
- Martinez, J. A. (2016, April). Clinical Study of Ursodeoxycholic Acid in Barrett’s Esophagus Patients. University of Arizona Cancer Center Annual Retreat.
- Martinez, J. A. (2016, April). Imaging biomarkers of aromatase-inhibitor induced joint pain. University of Arizona Cancer Center Annual Retreat.
- Martinez, J. A. (2016, April). Metabolomic profiling of plasma and fecal water reveal biomarkers of risk for colorectal adenoma recurrence. University of Arizona Cancer Center Annual Retreat.
- Martinez, J. A. (2016, April). Prostate Tissue Distribution and Bioactivity of Metformin in a Pre-prostatectomy Prostate Cancer Cohort.. University of Arizona Cancer Center Annual Retreat.
- Martinez, J. A., Chalasani, P., Witte, R. S., Kwoh, C. K., Hadden, A., Taljanovic, M., Martinez, J. A., Chalasani, P., Witte, R. S., Kwoh, C. K., Hadden, A., & Taljanovic, M. (2016, April). Imaging Biomarkers of Aromatase-Inhibitor Induced Joint Pain. University of Arizona, Cancer Center Retreat. Banner University Medical Center, Tucson, AZ.
- Chow, H., Algotar, A., Altbach, M. I., Galons, J., Roe, D., Thomson, C. A., Guillen-Rodriguez, J. M., Martinez, J. A., Chalasani, P., Villa Guillen, D. E., Tapia, E. O., & Trujillo, J. (2018, Fall). Abstract: Phase II clinical study of metformin for breast cancer prevention. UACC Scientific Retreat. UACC Scientific Retreat. Tucson, AZ.
- Martinez, J. A. (2015, April). Application of lipidomics to a sulindac intervention of aromatase inhibitor-induced pain. American Association for Cancer Research annual conference.
- Martinez, J. A. (2016, Dec). Low dose aspirin reduces baseline cardiovascular risk, cardiovascular reactivity and depressed mood in acutely bereaved.
- Martinez, J. A., Chalasani, P., Witte, R. S., Kwoh, C. K., Hadden, A., & Taljanovic, M. (2016, April). Imaging Biomarkers of Aromatase-Inhibitor Induced Joint Pain. University of Arizona, Cancer Center Retreat.