Dietary Bioactives and Human Prostate Carcinogenesis DISSERTATION Presented in Partial ...

189 Pages·2015·2.93 MB·English

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Dietary Bioactives and Human Prostate Carcinogenesis

DISSERTATION

Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy
in the Graduate School of The Ohio State University

By
Kristen Michelle Roberts, MS
The Ohio State University Nutrition Program
The Ohio State University
2015

Dissertation Committee:
Steven Clinton “Advisor”
Colleen Spees
Steven Schwartz
Martha Belury
Copyright by
Kristen Michelle Roberts
2015
Abstract

It is estimated that dietary risk factors contribute to one in three cancers in
Western nation. Prostate cancer (PCa) is associated with an affluent dietary pattern and
lifestyle typical of North America and Northern Europe. Diets limited in fruits and
vegetables are one characteristic of these high risk nations. Although difficult to study
epidemiologically, a number of phytochemicals found in various fruits and vegetables,
including berries, have been shown in laboratory studies (in vitro and with rodent
models) to have anti-cancer activity. At OSU, the last decade has seen a focus upon
black raspberries (BRB), a rich source of bioactive phytochemicals, and a crop of
substantial importance to the state. BRB contain high concentrations of various
polyphenols, of which ellagitannins and anthocyanins are best known. We propose to
examine the potential of BRB to impact human PCa by fully characterizing a consistent
BRB food product that is rich in phytochemicals, safe, and provides excellent
compliance. We tested two novel food products (nectar and a confection) in two doses
(low and high) in men with localized PCa, who have selected surgical prostatectomy as
curative therapy. Various ellagitannin metabolites were measured by HPLC/MS/MS in
the blood, urine, and prostate tissue. Most critically, we had three control groups (typical
American diet, low polyphenol diet, and low ellagitannin diet) as no studies have thus far
carefully defined by HPLC/MS/MS the background pattern/quantity of “berry derived”
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phytochemicals in blood, urine, and tissue. Lastly, the exploration of the vascular
architecture (VA) in these men and two additional cohorts was investigated to determine
the potential for VA being a biomarker for nutrition intervention studies. We have
concluded from this data that our BRB food products deliver a consistent bioactive
profile, are safe and have excellent compliance in a 4-week intervention trial. Quantified
urolithins in the urine of the men was consistent with baseline diet ellagitannin intake and
the dose of the BRB food product. Lastly, utilizing the vascular architecture as a
biomarker for nutrition intervention studies is still in its infancy. Measurement of the
vascular architecture is dependent upon the aggressiveness of the PCa, the endothelial
cell marker used to identify the blood vessels and the technology used to analyze the
architecture.

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Dedication

This dissertation work is dedicated to my loving and supportive husband who
encouraged me to pursue my academic dreams and to my family for providing me with
the foundation to be independent and driven allowing me to achieve my goals. I love you
all.

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Acknowledgments

First and foremost I want to thank my advisor Steven Clinton. It has been an
honor and privilege to work under the mentorship of such an accomplished leader who is
dedicated to elucidating the link between diet and cancer for cancer prevention. I would
also like to thank Drs. Elizabeth Grainger and Jennifer Thomas-Ahner. Thank you Beth
for exemplifying professionalism in every aspect of your career and the invaluable
guidance you offered throughout my doctoral degree and to Jen for the countless hours of
education you provided which allowed me to transition from a clinical dietitian to a
translational scientist. I can’t thank you both enough for your dedication and guidance
throughout this process. I would also like to thank Dr. Nancy Moran for pushing me to
be a better scientist and asking the tough questions! Last, but not least I want to thank
my fellow students and colleagues, Dr. Lei Wan, Ashley Schmitz, Christi Simpson and
Junnan Gu for their unconditional support over the years.

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Vita

June 1999…………………………………...Crestwood High School

2003................................................................B.S. Dietetics, Bowling Green State
University
2005................................................................M.S. Human Nutrition, Arizona State
University
2011 to present ..............................................Fellow, Department of Human Nutrition,
The Ohio State University

Publications

Winham D, Johnston C, Rhoda K. Maternal Weight Gain is Associated with Infant
Insulin Concentrations During the 1st Year of Life. Diabetes Care. 2006. 29:949.

Rhoda KM, Chhatriwalla EG, Parekh NR. Transitional Feeding: Challenges and
Approaches. Support Line. 2008. 30:21-28.

Rhoda K, Parekh N, Lennon E, Kirby D, Quintini C, Steiger E, Shay-Downer C. The
Multidisciplinary Approach to the Care of Intestinal Failure at a Tertiary Care Facility.
Nutr Clin Prac. 2009. 25(2):183-204.

Shatnawei A, Parekh N, Rhoda K, et al. Intestinal Failure Management at the Cleveland
Clinic. Arch Surg. 2010. 145(6):521-527.

Rhoda KM, Suryadevara S, Steiger E. “Home Parenteral Nutrition.” In: Dudrick S,
Sanchez J. (Eds.) Surgical Clinics of North America. 2011. 91:913-932.
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Rhoda K, Porter M. Developing a Plan of Care for Fluid and Electrolyte Management.
Support Line. 2011. 33(3):7-12.

Rhoda K, Porter MJ. Fluid and Electrolyte Management: Putting a Plan in Motion. J
Parenter Enteral Nutr. 2011. 35(6): 675-685.

John BK, Khan MA, Speerhas R, Rhoda K, et al. Ethanol lock therapy in reducing
catheter-related blood stream infections in adult home parenteral nutrition patients:
results of a retrospective study. J Parenter Enteral Nutr. 2012. 36:603-610.

Barco KT, Alberino MJ, Roberts KM, Wolff J, et al. “Common Gastrointestinal
Symptoms.” In: Matarese LE, Mullin GE, Raymond JL. (Eds.) The Health Professional’s
Guide to Gastrointestinal Nutrition. 2014. 63-78.

Fields of Study

Major Field: The Ohio State University Nutrition Program
Specialization: Biomedical Clinical and Translational Science

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Table of Contents

Abstract……………………………………………………………………………………ii
Dedication………………………………………………………………………………...iv
Acknowledgments…………………………………………………………………………v
Vita………………………………………………………………………………………..vi
List of Tables…...................................................................................................................x
List of Figures………………………………………………………………………...…xiii
Chapter 1: Introduction to Dietary Bioactives and Prostate Cancer……….…...................1
Chapter 2: Introduction to Berry Polyphenols and Prostate Cancer……………………..12
Chapter 3: Urinary polyphenol metabolites in men on usual diet, a low polyphenol diet,
or low ellagitannin diet..…………………………………………………………………20
Chapter 4: Functional Food Intervention and Prostate Carcinogenesis……………….....51
Chapter 5: Introduction: Angiogenesis in Epidemiology and Intervention
Studies……………………………………………………………………………………76
Chapter 6: Health Professionals Follow-up Study and Angiogenesis………………...…86
Chapter 7: Tomato-Soy Juice and Angiogenesis……………………...………………..119
Chapter 8: Integration of Angiogenesis Cohorts: lessons learned……………...……....145
Chapter 9: Final Summary on Dietary Bioactives and Prostate Carcinogenesis……….160
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References………………………………………………………………………………162
Appendix A: Usual Diet……………………………………………………………...…170
Appendix B: Low Polyphenol Diet……………………...……………………………...172
Appendix C: Low Ellagitannin Diet…………………………………………................174

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