Marcia R. Cruz-Correa, Ph.D. - US grants

DESCRIPTION (provided by applicant): Dr. Cruz-Correa is currently an Associate Professor of Medicine at the University of Puerto Rico Comprehensive Cancer Center (UPRCCC) and visiting Assistant Professor of Medicine at Johns Hopkins University (JHU). She completed a gastroenterology fellowship at JHU and finished a doctorate degree in Clinical Investigation at the Johns Hopkins Bloomberg School of Public Health, while completing her current K07 NCI Mentored Award. Her immediate career goals are to transition into an independent investigator having the financial and time resources to complete her current hypothesis in a timely fashion. Her long-term objectives are to become a leader in the field of gastrointestinal oncology with emphasis in epigenetics, clinical outcomes and prevention. Specifically, Dr. Cruz-Correa envisions a translational gastrointestinal research institute integrated by: (1) a basic laboratory unit, and (2) a clinical research unit, working together evaluating multiple hypotheses to sequentially elucidate mechanisms of gastrointestinal carcinogenesis. The UPRCCC is fully committed to the development of Dr. Cruz-Correa's career, and will provide all the needed personnel, laboratory, clinical resources as well as the protected time required for successful completion of this investigation. This award will enable her to continue to develop the necessary skills for a successful independent career in clinical research with the support of her current mentors and co-investigators, Dr. Francis Giardiello, Dr. Andrew Feinberg (Johns Hopkins University), Dr. Steven Wexner (Cleveland Clinic Florida), and Dr. Reynold Lopez (UPRCCC). This project will test the hypothesis that abnormal imprinting of the IGF2 gene is a biomarker for colorectal cancer (CRC) predisposition, with a diffuse tissue distribution, which exerts its increased risk via the IGF axis, resulting in specific pathological and molecular characteristics and a unique CRC phenotype. Loss of imprinting (LOI) of IGF2 is an independent risk factor for CRC, but the underlying carcinogenic mechanisms remain unclear. LOI of IGF2 is present in the peripheral blood lymphocytes (PBL) of patients with CRC and is not associated with common environmental exposures. This investigation will determine the clinicopathological impact of LOI of IGF2 and delineate the underlying molecular mechanisms of the IGF2 system in CRC patients using a feasible cross-sectional and matched case-control design. Specifically, it will evaluate the association of LOI of IGF2 with the IGF2 peptide, proliferation index, apoptosis index and micro-vascular density in CRC patients. It will also examine the association between LOI and rectal cancer recurrence. LOI of IGF2 has potential as a new biomarker for colorectal cancer predisposition, and may change our current risk-stratification, screening, and surveillance colorectal cancer paradigms.

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is the second leading cause of cancer in Puerto Rico (PR) accounting for approximately 1,500 individuals annually, which represent 12% of all cancer cases in the island. The genetic epidemiology of CRC among Hispanic populations is not well studied, hence studies focused on large, well defined ethnic groups such as Puerto Ricans, are clearly warranted. The first step towards evaluating the molecular, environmental, and genetic epidemiology of CRC in PR is to establish a population-based familial CRC registry. The following specific aims have been proposed: Specific Aim 1: To prospectively identify and recruit approximately 300 CRC probands from two distinct geographical areas in PR (Metropolitan and Southern Region). From each proband we will obtain a pedigree extended to second-degree relatives and cousins. Assuming 10% will be positive for a family history of CRC, we will then recruit all 30 probands with a family history of CRC and a sample of 15 family-history negative probands and obtain: paraffin-embedded tumors blocks, blood samples, risk factor and food frequency questionnaires. Specific Aim 2: To prospectively identify and recruit selected relatives (parents, grandparents, and same generation relatives - cousins and siblings) from the 45 probands identified in Specific Aim 1. In addition, for siblings and cousins of probands (i.e. relatives in the same generation as the proband), we will obtain risk factor and food frequency questionnaires, and for colorectal cancer cases, tumor blocks and pathology reports of their cancers. Specific Aim 3: To estimate from this pilot study the following parameters: (a) response rate of probands and their selected relatives;(b) response rate of participants for each data item;(c) family history of CRC and other cancers;(d) number of living first- and second-degree relatives and cousins of probands;(e) number of these relatives who live in the same household and region/municipality;(f) prevalence/distribution of selected risk factors from the administered questionnaires. During this two-year pilot study we propose to determine the feasibility for implementation of a population- based familial CRC registry in PR. Our long-term objective is to conduct a large, island-wide, population- based, genetic-epidemiologic study of familial CRC in PR. Data obtained from this two-year pilot study will serve as the foundation for our large, island-wide, population-based, genetic-epidemiologic study of familial CRC in Puerto Rico.

There is an urgent need for reducing or eliminating many health disparities that affect underserved minority populations. Despite important advances in knowledge about the basic mechanisms of disease, translation of this knowledge to treatment and prevention of disease has been limited and slow, in particular for these underserved ethnic and racial minorities. The Puerto Rico Clinical and Translational Research Consortium (PRCTRC) will be established as the concept that will advance this translation of knowledge and have an impact on these disparities. It will be a centralized clinical and translational research program focused on health problems prevalent in an underserved minority population and establishing a multidisciplinary and collaborative effort between three major academic health care institutions in Puerto Rico. The major programmatic goals are to: 1) To enhance and integrate existing infrastructure for clinical and translational research to support and expand Clinical and Translational Research in the Health Disparities; 2) To enhance and support existing training and mentoring programs to increase the number of new minority investigators in Clinical and Translational Research; 3)To facilitate the translation of knowledge from the bench into the community. To accomplish these goals we will integrate, expand and enhance: 1) Participant and Clinical Interaction Resources 2) Clinical and Translational Research core resources in Biostatistics and Data Management 3) Core laboratories and technologies 4) Training and developmental programs 5) Support for regulatory compliance resources 6)informatic resources 7) Community interactions and participation programs. The proposed program will be integrative, incorporating resources and leadership from all three institutions, many of these under the RCMI-Clinical Research Center (RCMI-CRC) and the Comprehensive Center for Health Disparities (CCHD) but fusing under a single administrative structure. The proposed program will be inclusive, incorporating leadership from all the participating institutions at several levels of administrative responsibility. It will be novel, because it will provide a unique opportunity to incorporate resources and have an impact across a state-size territory composed primarily of a minority population.

DESCRIPTION (provided by applicant): The current model of colorectal carcinogenesis is characterized by a gradual accumulation of genetic alterations leading to the development of polyps, which subsequently become primary carcinomas. Recent studies have suggested that Human Papillomavirus (HPV) infections may also play a role in the development of colorectal cancer (CRC). HPV infections are the most frequently sexually transmitted diseases in the world and some evidence supports that hematogenous spread of this virus may also be possible. The association between HPV infections and the development of cervical and anogenital cancer has been clearly established. Several studies have identified the presence of HPV in colorectal tissues suggesting that infection may be associated with the development and progression of CRC. However, the possible role of HPV and the mechanistic pathways leading to colorectal carcinogenesis remain to be defined. The overall objective of this application is to detect the presence, integration status and viral load of HPV, and to determine the expression level of key HPV oncogenes (E6 and E7) to elucidate if HPV is a risk factor for CRC. Our central hypothesis is that integration of the HPV oncogenes (E6 and E7) into the human genome cause cell cycle dysregulation, leading to the development of neoplasia in colorectal tissues. The following aims have been proposed: (1) Aim 1. To assess the prevalence of HPV DNA in malignant (cases) and non- malignant (controls) colorectal tissues in order to determine if there is an association between HPV infection and CRC (using nested PCR to detect HPV-16 and HPV-18 DNA; sequencing of PCR products for HPV genotyping). (2) Aim 2. To examine the genotype distribution of HPV in colorectal tissues HPV L1 positive cases, and determine integration of HPV genes into tumor genome (using nested PCR with primers specific for HPV-16 E6/E7, and HPV-18 E6/E7 viral oncogenes; integration status assessed with quantitative Real- Time PCR). (3) Aim 3. To quantify the mRNA expression levels of the HPV-16 and HPV-18 viral oncogenes E6 and E7 in HPV-positive cases (using QRT-PCR Taqman reaction strategy). We propose to describe the relationship of HPV infection and CRC, using a sound study design and validated laboratory methods, in a well-characterized population of Hispanic patients. We anticipate that our proposal will fill an existing gap regarding the role of HPV-infection in CRC and will examine the biological mechanisms responsible for colon carcinogenesis. Identification of HPV as an etiologic factor in CRC carcinogenesis may impact current molecular models, prevention strategies and treatment algorithms.

ABSTRACT Hyperthermia induced by magnetic nanoparticles in high frequency alternating magnetic fields (AMF), or Magnetic Fluid Hyperthermia (MFH), is based on the delivery of thermal energy at the nano-scale to tumors using iron oxide based magnetic nanoparticles (MNP) and an externally applied AMF. This phenomenon is the result of particle rotation or movement of the magnetic dipole. The fact that energy is only dissipated under high-frequency and moderate amplitude fields that can be constrained to the tumor region make MFH a highly promising form of non-invasive, externally activated cancer treatment To this date, the prevailing paradigm in the field is that delivery of nanoscale particles to tumors can be achieved by passive targeting due to the enhanced permeation and retention (EPR) effect. However, in vivo experiments tumors suggest otherwise, thus, posing potential limitations on the successful translation of such systems to the clinic. The aforementioned discrepancy reveals a need to understand the in vivo spatial and temporal behavior of nanoparticles as a result of their surface physicochemical properties. To our knowledge, the relationship between surface properties and the resulting temporal and spatial behavior has not been investigated in orthotopic mouse models of cancer. T The long-term goal of this project is to develop MNPs as a clinically feasible tool by providing a comprehensive understanding from fundamental particle design to clinical application. The main objective of this proposal is to pursue the optimization ofthe spatial and temporal behavior of Magnetic Nanoparticle Heaters (MNH) and perform an in vivo efficacy assessment of targeted or

DESCRIPTION (provided by applicant): This is a renewal application for the Partnership for Excellence in Cancer Research between The University of Puerto Rico (UPR) and The University of Texas MD Anderson Cancer Center (MDACC). The Partnership proposes structured initiatives to further enhance the research infrastructure within these two institutions to reduce the burden of cancer health disparities. Funds granted in this award will be used to support two full and one pilot research projects. The first full project examines the role of West African ancestry in prostate cancer risk and aggressiveness. Pilot data show an association of several ancestral genetic markers, body mass index, and socioeconomic status with higher-grade prostate cancer. The second full project focuses on magnetic nanoparticle based hyperthermia for ovarian cancer. Pilot project data show a marked decrease in the associated tumor size when treated with nanoparticles. The pilot study is a smoking cessation intervention in oncology clinics. Together, these projects comprise a multidisciplinary research portfolio representing the T l to T3 stages of the translational research continuum. Partnership funds will also be used to: 1) enhance existing collaborations and establish new collaborations; 2) restructure the training pipeline to include customized career development tracks for physicians, scientists and physician scientists interested in cancer medicine to accelerate the development of a critical mass of faculty for the UPR Comprehensive Cancer Center (UPRCCC); 3) implement a cancer education curriculum; and 4) maintain and expand the Outreach Program, including core services and an outreach research project designed to reduce the burden of colorectal cancer among Puerto Ricans. Thus far, the Partnership has established a dynamic collaborative team that is working towards fortifying and stabilizing the developing infrastructure at the UPRCCC as evidenced by a newly constructed UPRCCC Research Center (opened 6/2009); the UPRCCC hospital will be completed in 2016. Funding for a second renewal is critical to cement and build on the substantial momentum and success achieved by the Partnership over the last ten years. The Partnership is poised to fulfill its long-term goal of positioning the UPRCCC to become a frontrunner in addressing health disparities that affect Hispanic populations across the cancer continuum (prevention, early detection, diagnosis, treatment and survivorship). RELEVANCE: This renewal seeks to foster and support an existing collaboration between the UPR and MDACC. By addressing differences in incidence, prevalence, mortality, and burden of cancer that exist among Hispanic populations in the US, the Partnership strives to reduce these disparities through efforts in Cancer Research, Training, Education and Outreach. Partnership contributions will also aid in building a stronger national cancer program through the development of a pipeline of well-trained, Hispanic cancer researchers.

DESCRIPTION (provided by applicant): This is a renewal application for the Partnership for Excellence in Cancer Research between The University of Puerto Rico (UPR) and The University of Texas MD Anderson Cancer Center (MDACC). The Partnership proposes structured initiatives to further enhance the research infrastructure within these two institutions to reduce the burden of cancer health disparities. Funds granted in this award will be used to support two full and one pilot research projects. The first full project examines the role of West African ancestry in prostate cancer risk and aggressiveness. Pilot data show an association of several ancestral genetic markers, body mass index, and socioeconomic status with higher-grade prostate cancer. The second full project focuses on magnetic nanoparticle based hyperthermia for ovarian cancer. Pilot project data show a marked decrease in the associated tumor size when treated with nanoparticles. The pilot study is a smoking cessation intervention in oncology clinics. Together, these projects comprise a multidisciplinary research portfolio representing the T l to T3 stages of the translational research continuum. Partnership funds will also be used to: 1) enhance existing collaborations and establish new collaborations; 2) restructure the training pipeline to include customized career development tracks for physicians, scientists and physician scientists interested in cancer medicine to accelerate the development of a critical mass of faculty for the UPR Comprehensive Cancer Center (UPRCCC); 3) implement a cancer education curriculum; and 4) maintain and expand the Outreach Program, including core services and an outreach research project designed to reduce the burden of colorectal cancer among Puerto Ricans. Thus far, the Partnership has established a dynamic collaborative team that is working towards fortifying and stabilizing the developing infrastructure at the UPRCCC as evidenced by a newly constructed UPRCCC Research Center (opened 6/2009); the UPRCCC hospital will be completed in 2016. Funding for a second renewal is critical to cement and build on the substantial momentum and success achieved by the Partnership over the last ten years. The Partnership is poised to fulfill its long-term goal of positioning the UPRCCC to become a frontrunner in addressing health disparities that affect Hispanic populations across the cancer continuum (prevention, early detection, diagnosis, treatment and survivorship). RELEVANCE: This renewal seeks to foster and support an existing collaboration between the UPR and MDACC. By addressing differences in incidence, prevalence, mortality, and burden of cancer that exist among Hispanic populations in the US, the Partnership strives to reduce these disparities through efforts in Cancer Research, Training, Education and Outreach. Partnership contributions will also aid in building a stronger national cancer program through the development of a pipeline of well-trained, Hispanic cancer researchers.

ABSTRACT Early recruitment of underrepresented minorities from underserved communities into biomedical and health research training and education is essential to ensure that society's diversity is reflected in those professions. Given the critical cancer health disparities faced in Hispanic populations,in this 2 competitive renewal of the Training Program between UPR and MDACC we will continue to develop a comprehensive pipeline of trainees from undergraduates to postgraduates to increase the number of Hispanic clinicians, scientists, physicianscientists and health professionals knowledgeable and committed to careers in cancer research and medicine, as well as foster a faculty career development and mentoring program for junior faculty and for senior faculty transitioning to careers in cancer research. The UPR and MDACC Co-leaders have designed the training program to focus on several key areas including biomedical, clinical and translational research. Training methodology will include didactics, research experiences, enrichment opportunities, an MD/PhD program, postgraduate biomedical and clinical training, and training in cancer prevention and health disparities. The training program will be supplemented and enhanced by a new Cancer Education Core which offers a core curriculum in cancer and didactics in cancer health disparifies. This separate core will develop a curriculum in cancer that will be integrated into the training program. Career development will enhance existing programs to build both academic skills such as grant wrifing, publishing in high impact peer-reviewed journals, and giving effecfive presentations, as well as professional skills in negotiating and effective communication. Senior faculty transifioning to a career in cancer research and medicine will participate in the career development program. The Training and Career Development Core (TCDC) will collaborate with the planning evaluafion core to use outcomes-based logic modeling to evaluate qualitative and quantitative data so as to measure impact ofthe programs. Qualitative surveys will be ufilized to obtain feedback from trainees and junior faculty on their immediate and long-term needs and interests, as well as to rate their experiences participating in various programs. A clear plan will be developed and implemented to enable the UPRCCC to independently sustain outstanding training and career development programs in cancer medicine and research. The TCDC, along with the new Education Core (Section E.2), functions as an integrated training, career development, and education program to fill a knowledge gap and foster a bridge to success for the next generation of Hispanic cancer researchers and physicians.

Outcomes-oriented Evaluation Methodology To strengthen the current evaluation process of the Planning and Evaluation Core (PEC), the Pis have recruited an experienced evaluator from the UPR School of Public Health's Center for Evaluation and Sociomedical Research (CESR), which is a centralized UPR resource, to serve as one ofthe co-leaders. CESR staff members are trained on the latest techniques and approaches to evaluation as well as guidelines to tailor evaluations to fit specific research projects and programs across the cancer continuum (prevention, early detection, diagnosis, treatment and survivorship). CESR is a recognized leader in the science and practice of evaluation of training programs and basic, translational and population-based research, as well as the development of novel innovative approaches to measure success and identify areas that require immediate attention from the Partnership's Pis. CESR currently leads the evaluation processes of the Puerto Rico Clinical and Translational Research Consortium Grant and the CDC's Comprehensive Control Plan. Strategically, this approach leverages the integration of UPR-centralized resources for sustainability and it creates an evaluative culture within the Partnership for effective monitoring, evaluation and analysis of outcomes.

Cl. Outcomes-oriented Evaluation Methodology To strengthen the current evaluation process ofthe Planning and Evaluation Core (PEC), the Pis have recruited an experienced evaluator from the UPR School of Public Health's Center for Evaluation and Sociomedical Research (CESR), which is a centralized UPR resource, to serve as one ofthe co-leaders. CESR staff members are trained on the latest techniques and approaches to evaluation as well as guidelines to tailor evaluations to fit specific research projects and programs across the cancer continuum (prevention, early detection, diagnosis, treatment and survivorship). CESR is a recognized leader in the science and practice of evaluation of training programs and basic, translational and population-based research, as well as the development of novel innovative approaches to measure success and identify areas that require immediate attention from the Partnership's Pis. CESR currently leads the evaluation processes of the Puerto Rico Clinical and Translational Research Consortium Grant and the CDC's Comprehensive Control Plan, Strategically, this approach leverages the integration of UPR-centralized resources for sustainability and it creates an evaluative culture within the Partnership for effective monitoring, evaluation and analysis of outcomes.

anticancer research; University of Texas M D Anderson Cancer Center;

This is an application for the 2nd competitive renewal ofthe Partnership for Excellence in Cancer Research (Partnership) between the University of Puerto Rico (UPR) and the University of Texas MD Anderson Cancer Center (MDACC), two institutions which share a singular vision to eradicate cancer health disparities in underserved communities and socio-economically disadvantaged populations in Puerto Rico, Houston, and Latin America in general. This application represents a true partnership in which both institutions profit from distinct expertise and mutual benefits in the creation and implementation of fully integrated team science, outreach, training, career development, and education initiatives. As a continuation of the National Cancer Institute's (NCI) noteworthy commitment and investment to elevate the University of Puerto Rico Comprehensive Cancer Center (UPRCCC)* to a competitive level on par with other national cancer programs, this application outlines steps to: 1) solidify, strengthen and expand the relationship between UPR and MDACC and 2) transition the UPRCCC into an independently-functioning and self-sustaining institution. Without this long-standing, synergistic partnership as a catalyst for change, some of the objectives met thus far would have taken years to accomplish: other objectives would not have even been possible. Key elements of this application to advance the Partnership include: ¿ An evidence-based logic model approach (Section C) for tracking and evaluating Partnership outcomes; ¿ Multidisciplinary collaborative research projects (Section D) that represent stages of the translational research continuum (Tl to T3) according to NCI's Translational Research Working Group; ¿ A comprehensive cancer-focused training and career development core (Section E) to attract, engage and retain trainees and junior faculty as part of a training pipeline for future faculty positions with the UPRCCC; ¿ The development of a new educational curriculum, Core Curriculum in Cancer Medicine, Science, and Health Disparities, (Section E.2) to enhance the knowledge, skills and cultural competencies of current and future clinicians, scientists and physician-scientists; ¿ Outreach efforts (Section F) to build community capacity for the implementation and sustainability of cancer control programs; and ¿ A Biostatistics, Epidemiology and Bioinformatics Core (Section G), which augments and improves upon existing infrastructure developed during the last renewal. To facilitate the UPRCCC's transition towards independence, UPR and UPRCCC Pis took on a leadership role in developing the specific aims with the full support of the MDACC Pis. Over the next five years, both institutions recognize that while the Partnership will remain a joint effort, it will become imperative for the UPR and UPRCCC Pis to give impetus to developing, advancing, and advocating the UPRCCC's cancer-focused missions in research, training, education, and outreach. Therefore, with the goals ofthe U54 PAR in mind, a critical outcome to measure the success of this Partnership at the end of this renewal is whether or not the UPRCCC is sufficiently prepared and positioned to become a frontrunner in addressing the unequal burden of cancer that effects Hispanic populations across the cancer continuum (prevention, early detection, diagnosis, treatment and survivorship).

Abstract: The overarching goals of the Outreach Program are twofold: 1) to provide core support to the U54 for training on community-based participatory research (CBPR), direct community outreach and education, and capacity building for implementation and sustainment of evidence-based cancer control programs, and; 2) to conduct an outreach research project to reduce the burden of colorectal cancer among Puerto Ricans. This proposal describes both outreach core activities (under Aim 1) and the required outreach research project (Aim 2) as follows: AIM 1: Expand the existing CCCOP to provide core support to the U54 infrastructure, clinical research projects, and trainees with respect to direct community outreach, researcher and community capacity building, CBPR training, and participant recruitment and retention. AIM 2: Develop and evaluate the effectiveness, cost effectiveness, and budget impact of a tailored intervention to increase CRCS in PR among patients of FQHCs. Reducing morbidity and mortality associated with cancer in PR requires continuous efforts to address cancer-related behaviors and environmental conditions such as health care access. For example, although colorectal cancer (CRC) is the second leading cause of cancer-related mortality in women and the third in men, and is largely preventable through screening and treatment of precancerous polyps, colorectal cancer screening (CRCS) is significantly underutilized in PR among age-eligible patients compared to their U.S. counterparts. The proposed Outreach Program represents a continuation and extension of the Puerto Rico Cancer Control Community Outreach Program (CCCOP) which began as a pilot project in 2006 and expanded to a full U54 Outreach Core in the current funding cycle. The CCCOP will use existing community partnerships, infrastructure, data, and programs to 1) provide training on community-based participatory research (CBPR) to researcher, trainees and community partners, 2) conduct direct community outreach and education, 3) build capacity for implementation and sustainment of evidence-based cancer control programs in communities and primary care settings, 4) leverage existing data, partnerships and progress to expand research and intervention activities in the identified priority areas, and; 5) conduct an outreach research project to reduce the burden of colorectal cancer among Puerto Ricans. Through collaboration with community partners, the U54 Outreach Core will continue to identify innovative outreach strategies to reach the most vulnerable and underserved populations. These strategies include the use of community health educators, interactive and mobile technologies, and collaboration with Federally Qualified Health Centers (FQHCs). We will provide training and technical assistance to community partners, trainees and researchers on issues such as identifying cancer control needs, developing or adapting evidence based interventions, implementation, and evaluation. We will also focus on increasing community participation in clinical trials and biobanking in PR in order to promote effective prevention, diagnostic, and treatment methods for cancer. The cancer burden in PR is well documented by the CCCOP, and there is a significant need for continued community outreach efforts and research to reduce it. The CCCOP is committed to continue work in multiple cancer control topics as part of its Outreach Core, and to strengthen these outreach activities by prioritizing research. As a result, interventions developed through outreach efforts and community-based participatory research (CBPR) approaches can be rigorously evaluated, adopted, implemented and maintained to have the greatest possible impact on the health of Puerto Ricans.

ABSTRACT Continued tobacco smoking following a diagnosis of cancer is associated with decreased survival time, increased risk of recurrence, second primary malignancies, increased treatment complications and treatment failure. Despite the adverse health effects of continued smoking, 50% of patients with cancer who smoked prior to diagnosis continue to do so after diagnosis. Unfortunately, tobacco use treatment is not considered a core service at most ofthe National Cancer Institute (NCI) cancer centers, leaving the majority of cancer patients who want to quit with no formal assistance. In addition, there have been few smoking cessation trials for cancer patients and many ofthe trials that have been conducted have lacked biochemical verification of abstinence. There are very few smoking cessation clinical trials that have targeted Hispanic smokers, and we are unaware of any that have targeted Hispanic smokers currently undergoing cancer treatment. A recent NCI Conference on Treating Tobacco Dependence at Cancer Centers (NCl-CTTDCC) highlighted the need for improvement in these treatments, and has called for studies that evaluate methods for integrating cessation treatment into care delivery and sustaining cessation. There is evidence that cancer patients are more nicotine dependent and have more comorbid emotional and mood symptoms than the general population of smokers, suggesting that they may need more intensive forms of treatment than what is available through standard of care approaches. Quitlines have been found to significantly increase abstinence rates compared to brief interventions. While the effectiveness of quitiines in providing cessation support to smokers in the general population is well established, the willingness of cancer patients who are currently undergoing cancer treatment to use quitlines is unknown. In line with the recommendations of the NCl-CTTDCC to evaluate strategies for integrating cessation treatment into cancer care, the current pilot study will assess the feasibility of adding a quitline counseling component to clinical practice guideline-based brief counseling provided by medical staff; and estimate the effect size of the combined brief intervention counseling and quitline (BC+) compared to the brief counseling alone (BC) on abstinence at 3 and 6 month follow-ups. To accomplish these aims, cancer patients undergoing cancer treatment who are current smokers will be randomly assigned to receive brief counseling plus smoking cessation pharmacotherapy delivered in the oncology clinic setting (BC) or the BC intervention plus 7 counseling sessions delivered by the Puerto Rico Quitline (BC+). Smoking outcomes will be assessed at 3 and 6 months post-cessation. Data from this trial will be used to support larger scale clinical trials evaluating quitline delivered smoking cessation treatments for Hispanic cancer patients.

ABSTRACT Important ethnic and racial differences exist in Prostate Cancer (PCA) epidemiology. PCA mortality is higher among both African American (AA) and Puerto Rican (PR) Hispanic men when compared with other Hispanic and Caucasian men in the United States. Among AA PCA patients molecular differences in the disease characteristics at the DNA, mRNA, and protein levels have been discovered and may play a role in disease aggressiveness. Both AA and PR populations are heterogeneous with respect to West African Ancestry , (WAA), which is a risk factor for PCA incidence and (potentially) mortality. In fact, recent data from the Puerto Rican Cancer Registry show that many of the municipalities with the highest PCA mortality also have the greatest concentration of inhabitants of WAA. Therefore, one could postulate that increased mortality among PR men could be related to genetic admixture and specifically WAA. PCA is a complex disease; there is a need to study these two populations at increased risk for mortality in a comprehensive manner, integrating genetic markers of disease aggressiveness, WAA, environment interactions, influence of behaviors (exercise, smoking); socioeconomic status (SES), and comorbidities to determine if such variables enhance the prediction of PCA and its aggressiveness over standard clinical variables (i.e., serum prostate specific antigen [PSA] and digital rectal examination [DRE]). In our current project (Pilot Project E), we have accrued a cohort of both PR and AA prostate cancer cases and controls to begin to characterize the variables that contribute to both disease presence and the aggressive phenotype. The long-term goal of our research, which is carried forward in the renewal is to characterize features of PCA and its aggressive phenotype among at risk PR and AA men as a step toward decreasing PCA mortality among the two populations. The objective of our newly proposed study (Full Project A) is to design multivariable models to define key factors associated with the detection of PCA and its aggressive features in both high risk populations. Our hypotheses, derived in part from our preliminary data (see Preliminary Studies) is that: 1) specific genetic (i.e., WAA, and /or other PCA genetic polymorphisms) environmental, and lifestyle factors contribute to PCA incidence Or virulence, and 2) an assessment of these variables could enhance the prediction of PCA or its behavior among our two high risk populations.

ABSTRACT The Biostatistics, Epidemiology and Bioinformatics Core (BEBiC) will provide professional expertise in biostatistics, epidemiology and bioinformatics for all research studies within the Partnership. The Core will be a comprehensive, multilateral resource for data acquisition and management, design of laboratory experiments, epidemiological studies and clinical trials, statistical analysis, and publishing translational research generated by the Partnership. The BEBiC will incorporate sound experimental design principles within all projects and programs; carry out data analyses using appropriate statistical methodology; and contribute to interpretation of results through written reports and frequent interaction with project and program co-leaders. The Core will provide an integrated data management system to facilitate communication among all projects and cores, which will be customized to meet the needs ofthe Partnership. This process includes prospective data collection, data quality control, data security, and patient confidentiality. Thus, from inception to reporting, projects and programs will benefit from collaboration with the BEBiC. In addition, the BEBiC will organize different workshops related with the statistical and bioinformatics needs for every research study, particularly with all types of regression modeling and variable selection, survival analysis and optimization of dynamic treatment regimes, clinical trials, sample size, power calculations and statistics and algorithms for bioinformatics. Also, the BEBiC's personnel will develop new statistical methodologies in cancer research according to the projects needs.

The long term goal of this project is to formalize a graduate degree curriculum based on cancer medicine, cancer science and cancer health disparities. The main goal is to enhance research capacity at UPRCCC by development of an Education Core that complements and is integral to the Training and Career Development Core. Although UPR offers a wide variety of basic science courses, no specific courses or customized curricula are offered that address topics in cancer medicine, science, and health disparities. The proposed educational curriculum will provide a foundation in these topics that initially will complement education received by the students pursuing careers in science, biomedical sciences, medicine and other health sciences careers who are enrolled in UPR and the collaborating institutions. The Education Core will provide this academic offer by different strategies; short intensive courses, core curricular sequences composed of modules (one module by semester), seminar series and scientific meetings, among others. All of the educational activities offered and coordinated by the Education Core will account to registered, credit granting courses, at UPR. Two short courses have already been developed, originally as part of the Training Program, one on Cancer Biology and one in Cancer Genetics. These take advantage of the availability of expert faculty from the partnering institution, MDACC, along with the expertise and experience of the UPRCCC on the particularities of the Hispanic populations. Based on the successful experience with these intensive short courses, plans are directed towards the creation of additional courses in topics such as. Emerging Technologies in Cancer Medicine, Cancer Prevention and Cancer Health Disparities. Another innovation proposed is a modular curricular core on skills necessary to be successful in research, aimed to offer fundamental knowledge to undergraduate students interested in pursuing careers related to cancer and health disparities. One module will be offered each semester; Responsible Conduct of Research, Enhancing verbal, analytical reading and writing skills. Fundamental Skills for Research & Introduction to Biostatics and Bioinformatics. The intent is that the trainees complete the sequence of modules in two (2) years. Although the Education Core is based on the University of Puerto Rico System, the idea is to develop collaboration with other accredited academic institutions in Puerto Rico, starting with the Ponce School of Medicine. One of the objectives of the Educational Core is to lay the foundation for the development of a formal graduate program at UPR with a curriculum based on cancer medicine, cancer science and cancer health disparities.

DESCRIPTION (provided by applicant): The Puerto Rico Clinical and Translational Research Consortium (PRCTRC) is an innovative model of collaboration, bringing together and leveraging the intellectual and physical resources of three major medical and health science centers in Puerto Rico: The University of Puerto Rico Medical Sciences Campus (UPRMSC), the Universidad del Caribe Central (UCC), and the Ponce School of Medicine & Health Sciences (PSM&HS) to address and reduce health disparities that most impact Hispanic populations. The mission is to serve as a vital and catalytic element in the efforts to understand, define, and address health disparities in Hispanic populations. Our efforts are guided by four strategic goals: 1) Facilitate the generation and translation of knowledge from the bench into the community by establishing a centralized program focused on reducing health disparities among Hispanic populations; 2) Enhance and support existing training and mentoring programs to increase the number of new minority investigators in Clinical and Translational Research; 3) Encourage collaborations among basic, clinical, and social scientists and community networks and health programs; and 4) Enhance and integrate existing infrastructure for clinical and translational research across Puerto Rico to support and expand Clinical and Translational Research in health disparities The PRCTRC has fostered a synergistic environment that supports research across the clinical and translational research continuum, with an emphasis on four disease states that post the greatest threats to Hispanic health: HIV/AIDS, neurological diseases, cardiovascular and metabolic diseases, and cancer. The PRCTRC provides this integrated infrastructure to investigators through nine Cores: Regulatory Knowledge and Support, Research Design and Biostatistics, clinical Research Resources and Facilities, Technology Resources for Core Laboratories, Biomedical Informatics, Collaborations and Partnerships, Professional Development, Clinical and Translational Pilot Project Program, and Community-based Research. Oversight is provided by an Administrative Core and formative and summative evaluation is provided by an Evaluation Core.

DESCRIPTION (provided by applicant): This is a renewal application for the Partnership for Excellence in Cancer Research between The University of Puerto Rico (UPR) and The University of Texas MD Anderson Cancer Center (MDACC). The Partnership proposes structured initiatives to further enhance the research infrastructure within these two institutions to reduce the burden of cancer health disparities. Funds granted in this award will be used to support two full and one pilot research projects. The first full project examines the role of West African ancestry in prostate cancer risk and aggressiveness. Pilot data show an association of several ancestral genetic markers, body mass index, and socioeconomic status with higher-grade prostate cancer. The second full project focuses on magnetic nanoparticle based hyperthermia for ovarian cancer. Pilot project data show a marked decrease in the associated tumor size when treated with nanoparticles. The pilot study is a smoking cessation intervention in oncology clinics. Together, these projects comprise a multidisciplinary research portfolio representing the T l to T3 stages of the translational research continuum. Partnership funds will also be used to: 1) enhance existing collaborations and establish new collaborations; 2) restructure the training pipeline to include customized career development tracks for physicians, scientists and physician scientists interested in cancer medicine to accelerate the development of a critical mass of faculty for the UPR Comprehensive Cancer Center (UPRCCC); 3) implement a cancer education curriculum; and 4) maintain and expand the Outreach Program, including core services and an outreach research project designed to reduce the burden of colorectal cancer among Puerto Ricans. Thus far, the Partnership has established a dynamic collaborative team that is working towards fortifying and stabilizing the developing infrastructure at the UPRCCC as evidenced by a newly constructed UPRCCC Research Center (opened 6/2009); the UPRCCC hospital will be completed in 2016. Funding for a second renewal is critical to cement and build on the substantial momentum and success achieved by the Partnership over the last ten years. The Partnership is poised to fulfill its long-term goal of positioning the UPRCCC to become a frontrunner in addressing health disparities that affect Hispanic populations across the cancer continuum (prevention, early detection, diagnosis, treatment and survivorship). RELEVANCE: This renewal seeks to foster and support an existing collaboration between the UPR and MDACC. By addressing differences in incidence, prevalence, mortality, and burden of cancer that exist among Hispanic populations in the US, the Partnership strives to reduce these disparities through efforts in Cancer Research, Training, Education and Outreach. Partnership contributions will also aid in building a stronger national cancer program through the development of a pipeline of well-trained, Hispanic cancer researchers.

PROJECT SUMMARY/ABSTRACT Despite increasing adherence to routine screening and advances in therapeutic strategies, colorectal cancer is still a major health problem. Colorectal cancer is the 3rd leading cause of cancer death in the US1. Moreover, the incidence of this disease is projected to increase by 52% by 2030 due to the expansion of the aging population2. Yet, very few colorectal neoplasia (pre-cancerous and cancerous lesion) prevention strategies are available other than routine screening. The etiology of colorectal neoplasia (CRN) is complex; however, modifiable environmental factors including diet, the gut microbiota, and inflammation, are accepted as major contributors to colorectal carcinogenesis. Accumulating evidence supports that diet is one of the most important environmental factors that modulate gut microbiota composition11-13 and the gut microbiota has been implicated in CRN development18, 56, 61, 88. However, the dietary patterns that promote unhealthy changes in the gut microbiota (dysbiosis) and the enrichment of CRN-promoting bacteria are still incompletely understood. A better understanding of the CRN-promoting mechanisms, including the interplay between diet and the gut microbiota, would greatly advance current knowledge and serve as a platform for future studies evaluating diet- based CRN prevention strategies via the modulation of the cancer-promoting gut bacterial populations. Most studies have concentrated on specific bacteria 21, 23, 61, 62 or on profiling gut bacterial species22, 45, 46 associated with CRN. However, the mechanisms by which gut bacteria exert their CRN-promoting effects are not fully elucidated. The main goal of the current proposal is to examine a panel of bacterial genes encoding pro- inflammatory and DNA damaging toxins that may contribute to colorectal carcinogenesis and to evaluate if these genes are associated with pre-cancerous lesions (high-risk adenomas) and specific dietary patterns. The innovative aspect of this study is that it focuses on the evaluation of specific toxin-encoding bacterial genes rather than profiling gut bacterial species. Our central hypothesis is that individuals with high-risk adenomas will have a higher prevalence of these toxic genes and that these toxins contribute to carcinogenesis by causing DNA damage and the perpetuation of inflammation. Our study aims to characterize the toxic bacterial gene profile in stool and colonic tissue and to determine if they are associated with high-risk adenomas. We will also assess if presence of the toxic bacterial genes is associated with inflammation (Aim 1). Furthermore, we will examine dietary patterns and the prevalence of these toxic genes during a 1-year period (Aim 2). The significance of this study is that it addresses a gap in scientific knowledge regarding the CRN-promoting toxic bacterial by-products produced by the gut microbiota and their association with specific dietary patterns. The data generated by this study may shed light on the gut microbiota-driven carcinogenic mechanisms and on future dietary interventions for CRN prevention aiming at reducing exposure to injurious bacterial by-products.

Improving health care for the medically underserved, including our Hispanic population, afflicted by prevalent diseases, such as cancer, cardio-metabolic and infectious diseases, remains a major challenge. The current application is to support the development of Hispanic Alliance for Clinical & Translational Research in Puerto Rico (Alliance), which aims to build on the existing infrastructure of the Puerto Rico Clinical and Translational Research Consortia (PR-CTRC an RCMI-CTR) and the unique expertise on emerging infectious diseases and the study of disaster-related conditions and their impact on Health. The objective of the Alliance is to serve as the catalytic center to enhance the competitiveness of investigators to conduct research and obtain additional funding for clinical and translational research addressing highly prevalent diseases and those that affect the medically underserved in Puerto Rico. The long-term goal of the Alliance is to transform clinical and translational research in Hispanic populations in the Mainland and in Puerto Rico by promoting inter-disciplinary collaboration and leverage of resources to address diseases affecting Hispanic communities. Successful implementation of the Alliance will advance our fundamental knowledge of Hispanic health in this ethnic subgroup, which is increasingly represented in the U.S. mainland population. The Alliance is innovative because it will: (1) create a Hispanic-centered research hub integrating resources to support researchers in PR and national partners; (2) implement the Hispanic Real World clinical research data warehouse; and (3) establish a Community Health & Research Council comprised of diverse community partners emphasizing a community-centered, bi-directional research focus to impact health policy and ultimately improving health outcomes in our Hispanic community. The Alliance overall aims are specified below. Specific Aim 1: Enhance an island-wide infrastructure and human resource network and synergize with local and national partners to conduct clinical and translational research in Puerto Rico. Specific Aim 2: Provide professional development activities to enhance the ability of investigators to develop competitive clinical and translational research programs with emphasis on Hispanic health needs. Specific Aim 3: Facilitate the generation and dissemination of knowledge to and from the bench and the community to improve health outcomes that affect Hispanic communities in Puerto Rico and across United States. Specific Aim 4: Catalyze and sustain the integration of trans/multi/inter disciplinary collaborations to conduct clinical and translational research within and across institutions, organizations, community networks and health programs in Puerto Rico and other IDeA states.

Addressing the obesity pandemic has been a looming challenge before COVID 19 changed our daily lives. Evidence to date suggest that to achieve full prevention, we should intervene during the first 1000 days of life. This goal requires optimal health and access to essential services as early in pregnancy as possible. Alternatives to mitigate the sequelae of intrauterine exposures are critical as most pregnancies are unplanned. The baby act trial was designed to evaluate the effects of a community based multimodal lifestyle intervention to improve early growth outcomes among participants of the Puerto Rico Women, Infant and Children Special Nutrition Program (PRWIC). Reports on the rate of overweight/obesity in early childhood and women post-partum during 2017-18 fiscal year showed a significant increase with an extremely low percent of women reporting fruit and vegetable consumption. Poor health habits following the first of a series of catastrophic events to take place in our study location remain a major concern. Preliminary data from BAT showed a rate of overweight/obesity prior to pregnancy of 63.7% and reported levels of fruit and vegetable consumption during pregnancy that do not reach the minimal amount needed to achieve health benefits. As subsequent events ensued, the PRWIC standard of care (control condition), was adapted. BAT participants continued to receive the intervention as designed, but our assessment team provided additional support as needed to achieve access to essential services. Navigation for PRWIC registration and information on health and government services was made available. As study implementation have remained responsive to our partner's real-life conditions, it is the goal of this study to assess the impact of the living conditions during the COVID 19 pandemic on women who participated in the PRWIC program and delivered during this global emergency. We will implement intervention mapping strategies to explore differences in the lived experience of transition from pregnancy to motherhood as reported by women who participated in BAT in both conditions, and PRWIC participants who delivered at the San Juan City Hospital that where not enrolled in BAT. Data collected via surveys on healthcare, nutrition, social determinants of health, and clinical measures, will be integrated with qualitative analysis achieved through in-depth interviews with a random group of participants from each group. Our overarching goal is to explore the root cause for minimal compliance with healthy eating behaviors during pregnancy and beyond, the effects of BAT participation on the rate of at-risk weight in both mother and infant. Acceptability of strategies to address women's health screening and coordination of care will be explored. We will address the following aims: 1) Compare the effects of BAT participation on maternal/infant weight and nutritional status, 2) Define the influence of baseline and lockdown living conditions on pregnancy and postpartum/early care outcomes among PRWIC participants, 3) Explore the acceptability of implementing the Implicit Interception Care model to address the needs of women who participated in the PRWIC program.

Improving health care for the medically underserved, including our Hispanic population, afflicted by prevalent diseases, such as cancer, cardio-metabolic and infectious diseases, remains a major challenge. The current application is to support the development of Hispanic Alliance for Clinical & Translational Research in Puerto Rico (Alliance), which aims to build on the existing infrastructure of the Puerto Rico Clinical and Translational Research Consortia (PR-CTRC an RCMI-CTR) and the unique expertise on emerging infectious diseases and the study of disaster-related conditions and their impact on Health. The objective of the Alliance is to serve as the catalytic center to enhance the competitiveness of investigators to conduct research and obtain additional funding for clinical and translational research addressing highly prevalent diseases and those that affect the medically underserved in Puerto Rico. The long-term goal of the Alliance is to transform clinical and translational research in Hispanic populations in the Mainland and in Puerto Rico by promoting inter-disciplinary collaboration and leverage of resources to address diseases affecting Hispanic communities. Successful implementation of the Alliance will advance our fundamental knowledge of Hispanic health in this ethnic subgroup, which is increasingly represented in the U.S. mainland population. The Alliance is innovative because it will: (1) create a Hispanic-centered research hub integrating resources to support researchers in PR and national partners; (2) implement the Hispanic Real World clinical research data warehouse; and (3) establish a Community Health & Research Council comprised of diverse community partners emphasizing a community-centered, bi-directional research focus to impact health policy and ultimately improving health outcomes in our Hispanic community. The Alliance overall aims are specified below. Specific Aim 1: Enhance an island-wide infrastructure and human resource network and synergize with local and national partners to conduct clinical and translational research in Puerto Rico. Specific Aim 2: Provide professional development activities to enhance the ability of investigators to develop competitive clinical and translational research programs with emphasis on Hispanic health needs. Specific Aim 3: Facilitate the generation and dissemination of knowledge to and from the bench and the community to improve health outcomes that affect Hispanic communities in Puerto Rico and across United States. Specific Aim 4: Catalyze and sustain the integration of trans/multi/inter disciplinary collaborations to conduct clinical and translational research within and across institutions, organizations, community networks and health programs in Puerto Rico and other IDeA states.