Establishing a living biobank of patient-derived organoids of intraductal papillary mucinous neoplasms of the pancreas.

Pancreatic cancer (PaCa) is the third leading cause of cancer-related deaths in the United States. There is an unmet need to develop strategies to detect PaCa at an early, operable stage and prevent its progression. Intraductal papillary mucinous neoplasms (IPMNs) are cystic PaCa precursors that comprise nearly 50% of pancreatic cysts detected incidentally via cross-sectional imaging. Since IPMNs can progress from low- and moderate-grade dysplasia to high-grade dysplasia and invasion, the study of these lesions offers a prime opportunity to develop early detection and prevention strategies. Organoids are an ideal preclinical platform to study IPMNs, and the objective of the current investigation was to establish a living biobank of patient-derived organoids (PDO) from IPMNs. IPMN tumors and adjacent normal pancreatic tissues were successfully harvested from 15 patients with IPMNs undergoing pancreatic surgical resection at Moffitt Cancer Center & Research Institute (Tampa, FL) between May of 2017 and March of 2019. Organoid cultures were also generated from cryopreserved tissues. Organoid count and size were determined over time by both Image-Pro Premier 3D Version 9.1 digital platform and Matlab application of a Circular Hough Transform algorithm, and histologic and genomic characterization of a subset of the organoids was performed using immunohistochemistry and targeted sequencing, respectively. The success rates for organoid generation from IPMN tumor and adjacent normal pancreatic tissues were 81% and 87%, respectively. IPMN organoids derived from different epithelial subtypes showed different morphologies in vitro, and organoids recapitulated histologic and genomic characteristics of the parental IPMN tumor. In summary, this preclinical model has the potential to provide new opportunities to unveil mechanisms of IPMN progression to invasion and to shed insight into novel biomarkers for early detection and targets for chemoprevention.

The Florida Pancreas Collaborative Next-Generation Biobank: Infrastructure to Reduce Disparities and Improve Survival for a Diverse Cohort of Patients with Pancreatic Cancer.

Background: Well-annotated, high-quality biorepositories provide a valuable platform to support translational research. However, most biorepositories have poor representation of minority groups, limiting the ability to address health disparities. Methods: We describe the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective cohort study and biorepository designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L). We provide an overview of stakeholders; study eligibility and design; recruitment strategies; standard operating procedures to collect, process, store, and transfer biospecimens, medical images, and data; our cloud-based data management platform; and progress regarding recruitment and biobanking. Results: The FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and questionnaires (62%). Conclusions: This biorepository addresses a critical gap in PaCa research and has potential to advance translational studies intended to minimize disparities and reduce PaCa-related morbidity and mortality.

Circulating Cathelicidin Concentrations in a Cohort of Healthy Children: Influence of Age, Body Composition, Gender and Vitamin D Status.

Cathelicidin is an antimicrobial peptide whose circulating levels are related to vitamin D status in adults. This study sought to determine if circulating cathelicidin concentrations in healthy children are related to the age of the child, body composition and vitamin D status at birth and at the time of the study visit. Blood samples were obtained during yearly visits from 133 children, ages 2-7, whose mothers had participated in a pregnancy vitamin D supplementation RCT. Radioimmunoassay and ELISA were performed to analyze 25(OH)D and cathelicidin, respectively. Statistical analyses compared cathelicidin concentrations with concentrations of 25(OH)D at various time points (maternal levels throughout pregnancy, at birth, and child's current level); and with race/ethnicity, age, gender, BMI, percent fat, and frequency of infections using Student's t-test, χ2, Wilcoxon ranked-sum analysis, and multivariate regression. The cohort's median cathelicidin concentration was 28.1 ng/mL (range: 5.6-3368.6) and did not correlate with 25(OH)D, but was positively correlated with advancing age (ρ = 0.236 & p = 0.005, respectively). Forty patients evaluated at two visits showed an increase of 24.0 ng/mL in cathelicidin from the first visit to the next (p<0.0001). Increased age and male gender were correlated with increased cathelicidin when controlling for race/ethnicity, percent fat, and child's current 25(OH)D concentration (p = 0.028 & p = 0.047, respectively). This study demonstrated that as children age, the concentration of cathelicidin increases. Furthermore, male gender was significantly associated with increased cathelicidin concentrations. The lack of association between vitamin D status and cathelicidin in this study may be due to the narrow range in observed 25(OH)D values and warrants additional studies for further observation.