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)
- 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.
- 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.
- Martinez, J. A. (2018). Celecoxib use and circulating oxylipins in a colon polyp prevention trial. PLOS ONE.
- Martinez, J. A. (2018). Effect of Ursodeoxycholic Acid on the Gut Microbiome and Colorectal Adenoma Development. Cancer Medicine.
- 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.
- 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.
- 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. (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.
- 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.
- 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.