bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU536 Pseudoglucagonoma Syndrome: A Rare Complication After Partial Pancreatectomy
Authors: Monsour Elio Paul , Badour Sanna , Tuna Kubra Melek , Leey Julio , Lamas Marcos 
Published: October 2023

Abstract
Disclosure: E.P. Monsour: None. S. Badour: None. K.M. Tuna: None. J. Leey: None. M. Lamas: None.
Introduction/Background: Necrolytic migratory erythema (NME) is a specific cutaneous eruption associated with glucagonoma, an alpha-cell secreting pancreatic neuroendocrine tumor. Glucagonoma syndrome is a paraneoplastic syndrome characterized by NME, diabetes, stomatitis, anemia, weight loss, and gastrointestinal disturbances. Rarely NME can occur in the absence of an alpha-cell tumor of the pancreas, termed pseudoglucagonoma syndrome, seen in other clinical entities such as hepatic disease and intestinal malabsorption. Here, we describe a rare case of pseudoglucagonoma syndrome as a long-term complication following partial pancreatectomy. Clinical Case: A 45-year-old male with a history of benign pancreatic head cyst s/p partial pancreatectomy, pancreatic exocrine insufficiency, and pancreatogenic diabetes reported a 2-week history of a rash on his bilateral upper and lower extremities that was accompanied with blistering and skin peeling. Associated symptoms included tongue pain, diarrhea, and worsening paresthesias. Medications included subcutaneous insulin aspart, pantoprazole, and pancrelipase. Physical examination revealed a patchy rash with hyperpigmented plaques and shellac-like scales, a smooth red tongue, and symmetric hyperreflexia. Preliminary punch biopsy was concerning for NME; thus, the patient was evaluated for possible glucagonoma. Laboratory evaluation revealed normocytic anemia with hemoglobin of 9.8 mg/dL, plasma glucose of 104 mg/dL, and glucagon level of 103 ng/L (RR: &lt;208 ng/L). MRCP was negative for any pancreatic lesions. The patient was further evaluated for nutritional deficiencies and had strinkingly low vitamin A, D, E, K, B6, serum copper, and zinc levels. Plasma amino acids revealed low phenylalanine and tryptophan levels. He was started on a multivitamin (with minerals) and oral nutritional supplements with resolution of rash and subsequent improvement in symptoms. Final pathology of punch biopsy revealed parakeratosis with dermal edema, most compatible with nutritional deficiency. Discussion and conclusion: The pathogenesis and etiology of NME in glucagonoma and pseudoglucagonoma syndromes are not entirely understood. NME is thought to be multifactorial to multiple (essential) nutrient and vitamin deficiencies, as seen in our patient and other nutrient deficiency dermatoses such as zinc deficiency, necrolytic acral erythema, and pellagra. After further investigation, the patient reported poor adherence to pancrelipase supplementation, likely contributing to his clinical presentation and symptoms. Whereas in glucagonoma, excess glucagon levels cause a state of catabolism and exert its effect on the liver to increase gluconeogenesis via amino acid catabolism leading to deficiency. It is essential for clinicians to be aware of this rare and underrecognized phenomenon.
Presentation: Thursday, June 15, 2023
THU557 Effects Of Two Experimental Monocarbonyl Analogs Of Curcumin (MACs) On Breast Cancer Growth, Migration, And Epithelial-To-Mesenchymal Transition (EMT)
Authors: Stojchevski Radoslav , Hadzi-Petrushev Nikola , Mladenov Mitko , Bogdanov Jane , Velichkovikj Sara , Poretsky Leonid , Avtanski Dimiter B 
Published: October 2023

Abstract
Disclosure: R. Stojchevski: None. N. Hadzi-Petrushev: None. M. Mladenov: None. J. Bogdanov: None. S. Velichkovikj: None. L. Poretsky: None. D.B. Avtanski: None.
Curcumin, a polyphenol found in turmeric (Curcuma longa), has been reported to have a range of potential therapeutic effects, including anti-inflammatory and antioxidant properties. However, curcumin’s poor bioavailability has limited its use in medicine. Monocarbonyl analogs of curcumin (MACs) have been developed to overcome this challenge and have shown promise in various medical applications, including cancer. Our previous experiments in animals showed that these two analogs possess potent antioxidant properties. The aim of this study was to investigate the in vitro effects of two experimental MACs (C66 (C22H16F6O) and B2BrBC (C20H16Br2O)) on breast cancer cell growth and epithelial-to-mesenchymal transition (EMT). Both C66 and B2BrBC significantly suppressed MCF-7 and BT-474 viability shown by MTT assay. These two analogs also suppressed breast cancer cell migration, demonstrated by scratch migration wound-healing assay using MCF-7 and MDA-MB-231 cells. Further, using qRT-PCR, we investigated the effects of C66 and B2BrBC on the expression of various epithelial (E-cadherin, cytokeratin-18) and mesenchymal (snail, slug, fibronectin, and vimentin) genes in MCF-7 cells subjected to EMT induction (a media supplement containing Wnt-5a, TGFβ1, anti-E-cadherin, anti-sFRP1, and anti-Dkk-1 antibodies). Since the EMT-induction media significantly downregulated the epithelial markers’ and upregulated the mesenchymal markers’ mRNA expression, these effects were significantly abolished when C66 or B2BrBC were introduced. Taken together, these data demonstrate that C66 and B2BrBC are potent agents for suppressing breast cancer cell growth and EMT in vitro. Further investigation is needed to determine the potential clinical use of these compounds in breast cancer treatment.
Presentation: Thursday, June 15, 2023
OR05-05 A Novel Model Of Prostate Cancer Suggests Enzalutamide Functions Through The Immune System To Diminish Castration Resistant And Metastatic Growth
Authors: Kregel Steven 
Published: October 2023

Abstract
Disclosure: S. Kregel: None.
Background: There exists a tremendous need for establishing prostate cancer (PCa) murine models capable of recapitulating the progress of human PCa. By itself, the murine prostate does not form sporadic tumors and is anatomically and developmentally different from the human prostate. Engineered mouse models, however, lack the heterogeneity of human disease, are often driven in a contrived manner, and rarely (if ever) establish metastatic growth. Human xenografts represent an alternative, but they rely on tumor growth in an immunocompromised host, thus preventing the study of tumor-immune interactions and immunotherapies. Accordingly, we generated PCa xenograft models in a murine system with an intact human immune system (huNOG mice) to test the hypothesis that humanizing tumor-immune interactions would improve modeling of metastatic PCa as well as our ability to model the impact of hormonal and immunotherapies. Methods: Male huNOG and huNOG-EXL mice were produced at Taconic Biosciences by engrafting juvenile NOG mice with human CD34+ hematopoietic stem cells. These mice stably maintained multiple human cell lineages, including functional human T-cells. We utilized two human PCa xenograft cell line models transduced with luciferase to assay organ-specific metastatic growth. First, castrated and intact control mice were injected subcutaneously with 22Rv1 cells. When tumors reached &gt;100 mm3, half of the castrated mice were treated with enzalutamide (enza), and tumor growth was then monitored to endpoint. Additionally, VCaP tumor-bearing mice were castrated when the tumors reached ∼200 mm3, and once the tumor grew back, they were randomized and treated with enza and/or the anti-PD-1 antibody, pembrolizumab (pembro) as well as with vehicle controls. At sacrifice, organs were ex vivo analyzed for metastatic growth, tumor infiltrating lymphocytes, and splenic immune reconstitution. Results: In 22Rv1 tumor-bearing mice, subcutaneous tumor size was not significantly altered across conditions. However, the extent and growth at the secondary sites differed markedly in castrate huNOG vs conventional NOG mice treated with enza. VCaP xenograft tumors showed marked decreases in growth with enza and pembro treatments in huNOG mice, while no effect was observed with either of these treatments in NOG mice. Furthermore, immune responses to enza treatment in huNOG and NOG mice were distinct, as enza treatment only increased intra-tumor CD3+ T-cells as well as CD3+ T-cell activation in huNOG mice. Conclusions: These results illustrate, to the best of our knowledge, the first model of human PCa that metastasizes to clinically relevant locations, has an intact human immune system, and responds to standard-of-care hormonal therapies in a manner similar to responses observed under clinical settings.
Presentation: Thursday, June 15, 2023
SAT634 The Androgen Receptor Does Not Directly Regulate The Transcription Of DNA Damage Response Genes
Authors: Hasterok Sylwia , Scott Thomas G , Roller Devin G , Spencer Adam , Dutta Arun B , Sathyan Kizhakke Mattada , Frigo Daniel E , Guertin Michael J , Gioeli Daniel 
Published: October 2023

Abstract
Disclosure: S. Hasterok: None. T.G. Scott: None. D.G. Roller: None. A. Spencer: None. A.B. Dutta: None. K. Sathyan: None. D.E. Frigo: None. M.J. Guertin: None. D. Gioeli: None.
The clinical success of combined androgen deprivation therapy (ADT) and radiation therapy (RT) in prostate cancer (PCa) created interest in understanding the mechanistic links between androgen receptor (AR) signaling and the DNA damage response (DDR). Convergent data have led to a model where AR both regulates, and is regulated by, the DDR. Integral to this model is that the AR regulates the transcription of DDR genes both at steady state and in response to ionizing radiation (IR). In this study, we sought to determine which immediate transcriptional changes are induced by IR in an AR-dependent manner. Using PRO-seq to quantify changes in nascent RNA transcription in response to IR, the AR antagonist enzalutamide, or the combination of the two, we find that enzalutamide treatment significantly decreased expression of canonical AR target genes but had no effect on DDR gene sets in PCa cells. Surprisingly, we also found that the AR is not a primary regulator of DDR genes either in response to IR or at steady state in asynchronously growing PCa cells. Our data indicate that the clinical benefit of ADT and RT is not due to the direct regulation of DDR gene transcription by AR and that the clinical benefit of this therapeutic combination is instead likely due to both treatments independently reducing tumor cell fitness.
Presentation: Saturday, June 17, 2023
SAT636 Obesity And Aging Interactions Modify The Breast Tissue Microbiome Influencing Cancer Risk
Authors: Iyengar Neil M , Chiba Akiko , Howard-McNatt Marissa , Thomas Alexandra , Soto-Pantoja David R , Cook Katherine Loree 
Published: October 2023

Abstract
Disclosure: N.M. Iyengar: None. A. Chiba: None. M. Howard-McNatt: None. A. Thomas: None. D.R. Soto-Pantoja: None. K.L. Cook: None.
Obesity is one of the few modifiable risk factors for postmenopausal breast cancer. While obesity influences on the gut microbiome are established, the effect of diet and adiposity on tissue resident microbiome populations are underexplored. Studies have shown that breast tissue has a distinct microbiome, which is shifted in the presence of tumors or diet. However, whether obesity and menopause modify the breast microbiome is unknown. Using a cohort of non-cancerous breast tissue samples (n=80) taken at surgery from women that underwent mastectomy for breast cancer, we now demonstrate that obesity and aging interact to shift the breast microbiome. DNA isolated from breast tissue collected at surgery was used to perform V3-V4 amplicon 16S bacterial sequencing. Breast tissue from postmenopausal women with obesity (mean BMI 34.7 ±3.7) displayed a significantly higher α-diversity than breast tissue from postmenopausal lean women (mean BMI 21.9 ±1.7). Postmenopausal women with obesity also displayed a significantly different β-diversity than all other groups (Bray-Curtis; PERMANOVA p&lt;0.02). At the species level, breast tissue from postmenopausal women with obesity had a significantly elevated Akkermansia mucinphila proportional abundance (5.6%) when compared with all other groups (0.05-0.3% proportional abundance), demonstrating obesity and menopause interact to modify the breast tissue microbiome. Akkermansia muciniphila is a mucin-degrading bacteria. Breast tumors display aberrant mucin glycosylation and abundance, which previously were shown to promote carcinogenesis. Staining ER+ breast tumors for mucin-1 from patients with or without obesity indicates patient BMI positively correlates with tumor mucin-1 abundance, suggesting obesity regulation of mucin and/or mucin-degrading bacteria may promote breast tumorigenesis. To determine physiological relevance of breast Akkermansia muciniphila abundance, Western diet-fed MMTV-PyMT mice were intra-nipple injected with saline or Akkermanisa muciniphila bacteria into the mammary gland (MG) at 5, 7, and 9 weeks of age and palpated weekly for tumor formation. Elevated MG Akkermansia presence was associated with increased mammary tumorigenesis and multiplicity. Tumor mucin-1 was decreased with A. muciniphila administration. Flow cytometry analysis of single cell suspensions of breast tumors indicate A. muciniphila modified infiltrating immune populations. Overall, these results suggest obesity and aging may interact to enrich breast mucin-degrading bacteria abundance as a risk factor for postmenopausal breast cancer.
Presentation: Saturday, June 17, 2023
FRI241 Late Diagnosis Of Non-classical CAH In An Elderly Male Previously Diagnosed With Estrogen Producing Adrenal Tumor
Authors: Kaval Roopitha , Subauste Jose 
Published: October 2023

Abstract
Disclosure: R. Kaval: None. J. Subauste: None.
In 2013 a 66-year-old Caucasian male presented to the VA outpatient endocrinology clinic to establish care; the patient carried a diagnosis of estrogen producing left adrenal tumor in 1989 at the age of 42 at an outside facility. On review of records the patient was initially worked up for hypogonadism and was noted to have an elevated estrogen level and a “left adrenal tumor”. He subsequently underwent an unilateral left adrenalectomy for treatment and pathology reported with benign tumor findings. Following surgery, the patient was started on steroid and mineralocorticoid replacement for primary adrenal insufficiency (PAI) and topical testosterone gel for hypogonadism. The question was raised as to why this patient had PAI as he had an intact right adrenal gland on CT scan. On laboratory work-up in 2006 the patient had baseline cortisol of 3.4 ug/dl, ACTH was elevated at 99 pg/ml [7.2- 63.3], and adrenal antibodies (21-OH antibody] were negative. Renin was 2.35 ng/ml/hr [0.167-5.380], Estradiol was 41.8 pg/ml [7.6 - 42.6], LH was low at 0.20 mIU/ml [1.2-8.6] and total testosterone was low at 2.2 ng/ml [1.8-7.8]. Repeat testing yielded ACTH that was elevated at 686.7 pg/ml [7.2- 63.3], electrolytes including sodium and potassium were normal. On physical examination the patient had hyperpigmented skin, normal height, weight and otherwise unremarkable. On CT scan of the abdomen the right adrenal gland was mildly diffusely enlarged. In 2019, 30 years after his initial diagnosis the team questioned whether the adrenal tumor was truly an estrogen producing tumor. As a result, 17-OH progesterone was obtained, and the unstimulated value resulted as 3522 ng/dl [27-199]. With the elevated 17 OH &gt;1000 ng/dL this was diagnostic for Non-classical CAH. The unilateral adrenalectomy likely unmasked the underlying impairment of cortisol production leading to primary AI that is seen with Non-classical CAH patients. The patient was lost to follow up during the pandemic, hence we were not able to perform and further testing.
Presentation: Friday, June 16, 2023
FRI246 A Rare Case Of An Adrenal Gland Hemangioma In A 68-year-old Female
Authors: Daas Rana , Logan Sarah , Voss Rachel , Tarasova Valentina , Glushko Tetiana , Prera Juan Hernandez , Salgado Sarimar Agosto , Hallanger-Johnson Julie , Veloski Colleen 
Published: October 2023

Abstract
Disclosure: R. Daas: None. S. Logan: None. R. Voss: None. V. Tarasova: None. T. Glushko: None. J. Hernandez Prera: None. S. Agosto Salgado: None. J. Hallanger-Johnson: None. C. Veloski: None.
Background: Adrenal gland hemangiomas are extremely rare, with less than one hundred cases reported in the literature. Although benign and usually asymptomatic, they can be confused with adenomas, pheochromocytomas, or malignant adrenal tumors and preoperative diagnosis is challenging. Clinical Case: A 68-year-old female with a history of breast cancer completes an abdominal/ pelvic MRI due to abdominal and back pain that reveals a 1.4 cm right adrenal mass with T2 bright enhancement prompting concern for pheochromocytoma, lipid poor adenoma, or metastasis. An adrenal protocol contrast CT abdomen redemonstrated a 1.3 cm brightly enhancing right adrenal nodule with precontrast Hounsfield units (HU) of 35, postcontrast HU of 236, and delayed HU of 81. Absolute washout was 77.1%, consistent with an adenoma, however, the enhancement profile was also concerning for pheochromocytoma. Labs showed ACTH 15.2 pg/mL (7.2 - 63.3 pg/mL), cortisol 14.7 ug/dL (3.7 - 19.4 ug/dL), dexamethasone suppression test with cortisol 1.3 ug/dL (3 – 41 ug/dL), aldosterone 12 ng/dL (4.0 - 31.0 ng/dL), renin 0.1 ng/mL/hr (0.5 - 4.0 ng/mL/hr), potassium 4.0 mmol/L (3.4 - 4.5 mmol/L), DHEA-S 122 ug/dL (9 - 246 ud/dL), total testosterone 41.38 ng/dL (3.00 – 41.00 ng/dL), free testosterone 3.7 pg/mL (0.6 - 3.8 pg/mL), plasma normetanephrines 0.82 nmol/L (0 - 0.89 nmol/L), and plasma metanephrines 0.14 nmol/L (0 - 0.49 nmol/L), 24-hour urine: norepinephrine 47 ug/d (14 – 120 ug/d), epinephrine &lt;4 ug/d (1 – 14 ug/d), dopamine 236 ug/d (71 – 485 ug/d), metanephrines 86 ug/d (36 – 229 ug/d), and normetanephrines 258 ug/d (95 – 650 ug/d). The patient was asymptomatic, without high blood pressure, tachycardia, or hypokalemia. Despite the unremarkable lab workup, surgical excision of the nodule was recommended due to concern for silent pheochromocytoma or metastasis given the imaging findings and history of breast cancer. She was pretreated with doxazosin and had a right adrenalectomy. Pathology revealed a 1 cm hemangioma involving the periadrenal adipose tissue with ERG positive, CD31 positive, and D2-40 negative immunohistochemical staining. She was monitored post-operatively for transient hypotension and tachycardia and was discharged in stable condition. Conclusion: The differential diagnosis for adrenal gland incidentalomas is quite broad, however, patient history, along with laboratory and imaging studies, can help guide management. Adrenal gland hemangiomas are rare, non-functional, and have a propensity to bleed, but are benign and have a good prognosis.
Presentation: Friday, June 16, 2023
SAT024 Contribution of 11-Ketotestosterone and 11-Ketodihydrotestosterone to Castration-Resistant Prostate Cancer
Authors: Abu-Lebdeh Haitham S , Heshmati Hassan M 
Published: October 2023

Abstract
Disclosure: H.S. Abu-Lebdeh: None. H.M. Heshmati: None.
Background: Prostate cancer is among the most common malignancy in men and represents the second most common cause of cancer-related mortality among men in the US. Androgen-deprivation therapy with surgical or medical castration is widely used to treat hormone-sensitive prostate cancer. Disease progression despite androgen-deprivation therapy is a state defined as castration-resistant prostate cancer that is associated with poor survival rate. This review presents an update on the contribution of two adrenal androgens, 11-ketotestosterone and 11-ketodihydrotestosterone, to the castration-resistant prostate cancer. Methods: A systematic search of literature was conducted using the search terms prostate cancer, testosterone, dihydrotestosterone, adrenal androgens, 11-ketotestosterone, 11-ketodihydrotestosterone, androgen-deprivation therapy, castration, and castration-resistant prostate cancer. Results: In 2022, around 268,490 new cases of prostate cancer were diagnosed in the US with a mortality of 34,500 cases. Although androgen-deprivation therapy with castration is efficient at the beginning, most patients develop a state of castration resistance usually after 2-3 years as a result of the reactivation of androgen-receptor signaling despite low testosterone levels. The adrenal glands produce significant amounts of steroid hormones and metabolites. Among them, 11-ketotestosterone and 11-ketodihydrotestosterone are potent and efficacious androgens with potentially longer activity compared to testosterone and dihydrotestosterone because they are metabolized at a lower rate. Dihydrotestosterone derived from the metabolism of adrenal androgens (e.g., androstenedione and dehydroepiandrosterone) and especially 11-ketotestosterone and 11-ketodihydrotestosterone are important contributors to castration-resistant prostate cancer. In these cases, adrenal suppression with drugs causing a decrease in adrenal androgen production may improve the effectiveness of the androgen-deprivation therapy. Conclusion: In most patients with prostate cancer, androgen-deprivation therapy loses its effectiveness after 2-3 years leading to a state of castration-resistant prostate cancer. Two potent and highly efficacious androgen-receptor agonists of adrenal origin, 11-ketotestosterone and 11-ketodihydrotestosterone, are predominant androgens after castration and play an important role in the development and progression of castration-resistant prostate cancer. Their measurement in blood can be of clinical value during androgen-deprivation therapy. Concomitant treatment aimed to block the production of adrenal androgens is of potential interest in the management of these patients, but more studies are necessary to further investigate the benefits and adverse effects of this approach.
Presentation: Saturday, June 17, 2023
SAT271 Ligand Induced GR Heterodimerization With MR In Living Cells
Authors: Sueyoshi Tatsuya , Perera Lalith , Cidlowski John A 
Published: October 2023

Abstract
Disclosure: T. Sueyoshi: None. L. Perera: None. J.A. Cidlowski: None.
We have established methods for monitoring heterodimer formation between GR and MR in living cells upon the addition of ligands. Two protein fragments derived from NanoBit luciferase (Small Bit peptide composed of 11 amino acids and Large Bit peptide sized 17.6 kDa) can form functional enzyme when protein-protein interaction brings these fragments close proximity. Utilizing the enzyme fragments for fusion protein partners for the hormone receptors, we have constructed expression plasmids for every combination of receptor and enzyme fragments comprising N-terminal or C-terminal fusion proteins. GR and MR fusion proteins with the luciferase fragments were expressed in HEK293 cells and the enzyme activities were determined in time course before and after the addition of ligands (dexamethasone and aldosterone). We observed robust increases of NanoBit luciferase activity in GR and MR transfected cells less than 20 min after the addition of ligands suggesting the heterodimer was formed in the time period. Similar assays detected these receptors formed homodimer after the addition of ligand for each receptor suggesting homodimer and heterodimer co-exists when appropriate ligands are in this assay system. DNA binding null mutations of GR DNA binding domain effectively abolished GR homodimers but not GR - MR heterodimers suggesting mechanistical differences between the homodimer and heterodimer formation. Based on the results only C-terminal NanoBit fusion receptors showed positive heterodimerization-induced enzyme activity, we proposed ligand binding domain 3D structure heterodimer models and found amino acid residues in helix 9, helix 10, and near C-terminus are involved in the heterodimer interaction interface. Thus, this method will be a powerful tool for analyzing molecular mechanisms of GR - MR heterodimer formation in living cells.
Presentation: Saturday, June 17, 2023