Searchable abstracts of presentations at key conferences in endocrinology

ea0089b4 | Basic Science | NANETS2022

Simultaneous Inhibition of DNA Methylation and Histone De-acetylation for Enhanced SSTR2 Expression In Vitro

Whitt Jason , Houson Hailey , Guenter Rachael , Murphy Madisen , Lapi Suzanne , Jaskula-Sztul Renata

Background: Neuroendocrine tumor (NET) patients with diminished SSTR2 expre-ssion are not eligible for any type of SSTR2-specific imaging or treatment. Herein, we propose to epigenetically enhance and enable somatostatin receptor type 2 (SSTR2)-targeted theranostics for patients with NETs. Specifically, we have found that simultaneous inhibition of DNA methylation and his-tone de-ace-tylation enhanced SSTR2 expression and in vitro binding of [68Ga]DOTATATE....

ea0089b9 | Basic Science | NANETS2022

Deletion of Notch1 Signaling in Pancreatic Neuroendocrine Tumors Reduces Metastatic Properties

Chen Weisheng , Guenter Rachael , Herring Brendon , Jaskula-Sztul Renata , Bart Rose J. , Chen Herbert

Background: The 5-year survival rate for patients with unresectable, metastatic pancreatic neuroendocrine tumors (pNETs) remains less than 30%, emphasizing the need for new and effective treatment options for patients with advanced pNETs. Notch1 signaling is a critical cell-cell communication pathway responsible for regulating differentiation, cell fate determination, and epithelial-mesenchymal transition (EMT). Notch1 plays a critical role in the differentiation state of NE c...

ea0089b12 | Basic Science | NANETS2022

Transcriptomic Influences of Racial Disparities in Black Patients with Pancreatic Neuroendocrine Tumors

Herring Brendon , Guenter Rachael , Dhall Deepti , Chen Herbert , Yates Clayton , Bart Rose J.

Background: There are known outcome disparities between Black and White patients with pancreatic neuroendocrine tumors (pNETs). Recently, Black patients were shown to have higher rates of lymph node metastasis in smaller tumors than White patients, indicating possible differences in tumor biology. Numerous prognostic gene expression differences between racial groups have been reported in other cancers, but no such analysis has been conducted in pNETs. This study evaluated pNET...

ea0098b10 | Basic Science | NANETS2023

Notch1 and Notch3 signaling interplay regulates pancreatic neuroendocrine cell proliferation

Guenter Rachael , Chen Weisheng , Golivi Yuvasri , Robledo Mario , Jaskula-Sztul Renata , Chen Herbert , Rose Bart

Background: The 5-year survival rate for patients with advanced pancreatic neuroendocrine tumors (pNETs) is less than 30%. Notch signaling is a transmembrane receptor pathway with four distinct isoforms, activation of which is linked to cellular differentiation, cell fate, and viability. Both Notch1 and Notch3 signaling have been shown to be dysregulated in pNETs. Notch3 activation has been shown to repress Notch1 activity in other cancers. We hypothesize that activation of No...

ea0098b11 | Basic Science | NANETS2023

The Notch1 pathway is a critical regulator of SSTR2 expression in neuroendocrine tumors

Guenter Rachael , Whitt Jason , Chen Weisheng , Houson Hailey , Bart Rose J. , Chen Herbert , Lapi Suzanne , Jaskula-Sztul Renata

Background: Patients with neuroendocrine tumors (NETs) have a 5-year survival rate of 30-60%. Surgery, and newly approved ‘tar-geted radionuclide therapy (TRT)’ with [177Lu]DOTATATE, are the only curative options for patients with NETs. TRT is limited to pa--tients that have high levels of somatostatin receptor subtype 2 (SSTR2) and can im-prove the survival of patients with low-grade tumors, but has little effect on high-grade NETs that express low SSTR2 ...

ea0098p7 | Population Science | NANETS2023

Validity of geographic-level social determinant of health metrics in pancreatic neuroendocrine tumors

Gillis Andrea , Herring Brendon , Guenter Rachael , Chen Weisheng , Chen Dai , Chen Herbert , Bart Rose J. , Manne Upender , Bhatia Smita

Background: Various social determinant of health (SDOH) metrics and indices are utilized to evaluate access to cancer care and to explain disparities in outcome in pancreatic neuroendocrine tumors (PNETs). Little prior work has compared the validity of various geographic metrics. Therefore we aimed to examine different geographic metrics validity (from smallest to largest: census block group< census tract< zip code< county) utilizing single institutional data in a ...

ea0098p8 | Population Science | NANETS2023

Influence of social determinants of health on pancreatic neuroendocrine tumor stage at presentation

Gillis Andrea , Herring Brendon , Guenter Rachael , Chen Weisheng , Chen Dai , Chen Herbert , Bart Rose J. , Manne Upender , Bhatia Smita

Background: Tumor size and lymph node involvement (stage) have been utilized to prognosticate pancreatic neuroendocrine tumors (PNETs) but the influence of race and social vulnerability on these factors remains unexplored. Therefore we sought to explore this in a racially and socioeconomically diverse cohort.Methods: We reviewed records of all patients who underwent surgical resection for PNETs from 2006-2022 at a single NCI-designated cancer center in t...

ea0089b6 | Basic Science | NANETS2022

Detecting Cell Surface Expression of Calreticulin in Pancreatic Neuroendocrine Tumors Using a Novel [68Ga]-Radiolabeled Peptide

Guenter Rachael , Ducharme Maxwell , Herring Brendon , Montes Odalyz , McCaw Tyler , Lee Goo , Dhall Deepti , MacVicar Caroline , Chen Herbert , Lapi Suzanne E. , Larimer Benjamin , Bart Rose J.

Background: Current theragnostic techniques for pancreatic neuroendocrine tumors (pNETs) exploit the overexpression of somatostatin receptors (SSTRs) on the cell surface. However, approximately 25% of low-grade and most high-grade pNETs do not express SSTRs, requiring alternative theranostics. Calreticulin (CALR) is a protein linked to reticular calcium homeostasis and immunogenic cell death. Upon sufficient cellular insult, CALR translocates from the endoplasmic reticulum (ER...

ea0098b12 | Basic Science | NANETS2023

Notch1 receptor-mediated metabolic flexibility promotes a survival advantage in pancreatic neuroendocrine neoplasms

Chen Weisheng , Guenter Rachael , Herring Brendon , Golivi Yuvasri , Whitt Jason , Sammy Melissa , Adams Cole , Jaskula-Sztul Renata , Chen Herbert , Rose Bart

Background: Cancer cells utilize both oxidative phosphorylation (OXPHOS) and glycolysis to generate energy. Switching between OXPHOS and glycolysis can promote tumor progression. The mechanisms governing oncogenic metabolic flexibility are largely unknown, but recent data has suggested that Notch1 dysregulation in cancer cells can contribute to altered metabolic phenotypes. We hypothesized that Notch1 signaling supports metabolic flexibility in pancreatic neuroendocrine tumor ...

ea0098b23 | Basic Science | NANETS2023

Calreticulin is associated with clinical characteristics in pancreatic neuroendocrine tumors

Herring Brendon , Macvicar Caroline , Guenter Rachael , Chen Weisheng , Elhussin Isra , Yates Clayton , Dhall Deepti , Chen Herbert , Lee Goo , Bart Rose J.

Background: Following IHC of CALR, H-scoring was performed by a pathologist. H-scoring was validated by MIF of the same tissue, wherein random-forest machine learning (ML) classifiers were employed to classify cells. ML classifiers were trained to distinguish between pNET cells and tumor stroma using approximately 30% of cells for the respective cell population of interest in each TMA core. Pearson’s correlations were used to evaluate the relationship between H-scoring an...