bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-LB93 Mineralocorticoid Receptor Mediates Sex-Dependent Anticontractile Effect of Perivascular Adipose Tissue in Obese Mice
Authors: Victorio Jamaira A , Freitas Israelle Netto , Guizoni Daniele Mendes , Davel Ana Paula 
Published: May 2020

Abstract
Obesity, a condition of excessive fat mass and subclinical inflammation, reached epidemic proportions with higher prevalence in women compared to men worldwide. Expansion of the perivascular adipose tissue (PVAT) is observed in obesity and clinical studies indicate a positive correlation between PVAT amount and body mass index. PVAT, a fat depot surrounding most of the vessels, modulates vascular function by releasing PVAT-derived factors such as adipokines that exert anticontractile effect in health individuals. Despite sexual dimorphism on PVAT morphology, it is still unknown whether or not there is sex differences in the PVAT modulating vascular function in the setting of obesity. Aldosterone-mineralocorticoid receptor (MR) signaling pathway has been demonstrated to be adipogenic and proinflammatory in classical fat depots and treatment with MR antagonists (A) might reverse vascular dysfunction and remodeling in obese models, especially in female sex. Therefore, we aimed to evaluate the anticontractile effect of PVAT in male and female obese mice and hypothesized that MR signaling would be involved in possible sex differences in PVAT dysfunction in obesity. Male and female C57Bl6/J mice were fed a chow or a high-fat diet (HFD, 60% energy from fat) for 20 weeks. At the last 4 weeks of HFD, female and male mice were treated with the MRA spironolactone (Spi, 100 mg/kg/day). HFD feeding significantly increased body weight and visceral adipose tissue, which was not modified by Spi treatment in both sexes. Resistance mesenteric arteries were isolated with or without PVAT and mounted in a wire myograph to evaluate vascular contractile responses. Lean male and female mice PVAT had an anticontractile effect in the response to phenylephrine that was greater in females than males. The anticontractile effect of PVAT was significantly impaired in obese females but not modified in males. HFD-induced dysfunctional PVAT was prevented by Spi treatment in females. Next, we evaluated the protein expression of aldosterone-synthase CYP11B2, serum and glucocorticoid-regulated kinase 1 (SGK1), and epithelial sodium channel subunits (ENaCs) in isolated mesenteric PVAT of lean and obese male and female mice. There was an increased expression of CYP11B2, SGK1 and ENaCs only in obese female PVAT. Protein expression of adiponectin, a major PVAT-released adipokine was also increased in female mesenteric PVAT. In conclusion, the findings suggest sexual dimorphism in PVAT function in health and in obesity. Although anticontractile role of PVAT was exacerbated in lean female mice, female sex was more susceptible to develop PVAT dysfunction in the setting of obesity which was prevented by MR blockade. HFD-induced PVAT dysfunction in females was associated with increased expression of SGK1 and ENaCs. Therefore, data suggest MR activation as a mechanism mediating sex differences in PVAT dysfunction.
FAPESP, CAPES.
MON-LB69 Calcitriol-Mediated Hypercalcemia in a Patient With Metastatic Gastrointestinal Stromal Tumor
Authors: Betlachin Anna , Kim Sarah Sangnim Rhee , Oxman Rachael 
Published: May 2020

Abstract
Background: Hypercalcemia is a common complication of advanced malignancy, affecting up to 30% of cancer patients through various mechanisms (1). Hypercalcemia has rarely been described in gastrointestinal stromal tumors (GIST), with fewer than ten case reports as of 2018 (1,2). We describe a case of calcitriol-mediated hypercalcemia in a patient with GIST. Clinical Case: An 80-year-old woman with a history of metastatic GIST and nivolumab-induced type 1 diabetes and thyroiditis presented with dramatic progression of metastatic peritoneal disease and new severe hypercalcemia with acute kidney injury. On hospital admission, calcium (Ca) was 15.1 mg/dL (8.6-10.3 mg/dL), ionized Ca was 1.98 mmol/L (1.09-1.29 mmol/L), and creatinine was 2.56 mg/dL (0.6-1.3 mg/dL, baseline 1.8 mg/dL). She was treated with IV fluids and 45 mg of IV pamidronate with initial Ca improvement to 10.7 mg/dL over the next 48 hours. Additional workup showed that 25-hydroxyvitamin D was 18 ng/dL (20-50 ng/dL), PTH was 9 pg/mL (11-51 pg/mL), PTHrP was 3.1 pmol/L (0.0-3.4 pmol/L), and calcitriol was elevated to 172 pg/mL (19.9-79.3 pg/mL). Prior chest/abdomen/pelvis CT scans had not shown bony metastases or granulomas. After stopping IV fluids, Ca rose to 12.2 mg/dL the next day. Prednisone 20 mg daily was started which stabilized Ca levels and lowered calcitriol to 17.4 pg/mL after two weeks. She also began a new regimen of cabozantinib. Prednisone was tapered to 10 mg daily and she continues to maintain normal Ca levels with the addition of home health IV fluids three times a week. Conclusion: GIST tumors are a rare cause of hypercalcemia of malignancy. Although hypercalcemia of malignancy is most often due to tumor-secreted PTHrP or bony metastases, a small percentage of cases are mediated by excess calcitriol production. There is a growing number of case reports, including this case, to suggest that calcitriol-mediated hypercalcemia is the most common cause of hypercalcemia in GIST tumors (2-4). Glucocorticoids may be used to decrease calcitriol production and help maintain eucalcemia. Definitive therapy for hypercalcemia in these patients involves decreasing tumor burden by treatment of the underlying malignancy (3). References: (1) Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005;352(4):373-9. (2) Hart T, Sinitsky D, Shamsiddinova A, Rohatgi A. Refractory hypercalcaemia secondary to localised gastrointestinal stromal tumour. Ann R Coll Surg Engl. 2018;100(6):e136-e138. (3) Hygum K, Wulff CN, Harsløf T, et al. Hypercalcemia in metastatic GIST caused by systemic elevated calcitriol: a case report and review of the literature. BMC Cancer. 2015;15:788. (4) Barbaryan A, Bailuc S, Poddutoori P, et al. Gastrointestinal Stromal Tumor Induced Hypercalcemia. Case Rep Oncol Med.2017;4972017.
SAT-LB308 Primary Hyperparathyroidism and Meningioma as a Part of Multiple Endocrine Neoplasm Type 1 (MEN Type 1)
Authors: ElEbrashy Shady Ibrahim , Ehab ElRefaay 
Published: May 2020

Abstract
Background: Meningioma is a rare association of Multiple endocrine neoplasia type 1 (MEN 1) and very few cases has been reported in literature. Clinical Case: a 75-year-old woman showed severe headache, disturbed consciousness and convulsions. A diagnosis of cerebral meningioma was made and surgical excision was done, histopathological examination confirmed meningioma; patient was transferred to the ICU postoperatively for monitoring. Patient’s consciousness was not regained in full and remained in delirium, follow up investigations revealed: serum calcium of 13.2 mg/dl (8.5 to 10.5 mg/dl), serum sodium 141 mmol/L (135-145 mmol/L) and potassium 4.9 mmol/L (3.5-5 mmol/L), serum parathormone of 850 pg/mL (10-65 pg/mL), primary hyperparathyroidism was suspected; further investigations revealed inferior parathyroid adenoma on ultrasound which elicited focal tracer uptake on sesta-mibi parathyroid scintigraphy. Patient did excision of the lesion and was confirmed by histopathological examination to be parathyroid adenoma. Patient recovered well postoperatively, consciousness was regained and no neurological defects ware present. Genetic studies where performed and was found positive for MEN type 1 gene. Whole body Ga-DOTATATE PET/CT was then done to exclude any associated tumors and no tracer uptake was found. Patient was discharged, family members were offered genetic analysis and were counselled on the importance of screening. Conclusion: MEN type 1 can rarely present with meningiomas with symptoms very similar and easily confused with hypercalcemia and the diagnosis can be missed.
MON-LB75 Stratifying the Risk of Malignancy in Indeterminate Thyroid Nodules
Authors: Imam Shahnawaz , Paparodis Rodis , Jaume Juan Carlos 
Published: May 2020

Abstract
Background Thyroid cancer is the most common endocrine cancer globally, and accounts for 3.4% of all new cancer cases in the US. Although several clinical guidelines to detect/manage thyroid nodules are available, a great deal of controversy still exists around the optimal approach for diagnosis. Approximately 20-30% of cytology results from thyroid fine-needle aspiration (FNA) fall into one of three indeterminate diagnostic categories. In recent years, a number of molecular and gene mutation diagnostic tests have been developed to diagnose the indeterminate thyroid nodules in FNA specimens. However, nearly half of patients recommended for surgery based on these tests were found to have a benign nodule. Therefore, there is a need for a more accurate predictive and prognostic test for thyroid cancer. In case of Euthyroid Hashimoto Thyroiditis condition (EHT), where patient required a partial thyroxin replacement dose, having about 48% risk of thyroid cancer. However, there is still not a very accurate predictive marker for early detection of thyroid cancer in EHT. Invention DescriptionResearchers at the University of Toledo have found that thyroid nodule microenvironment cell profiling can be used as a predictive and prognostic marker for thyroid cancer. This approach uniquely focuses on the phenotype, rather than the genotype, of the microenvironment. Recently described Double Negative (DN) T-cells were significantly more abundant in lymphocytic infiltrates of thyroid cancer. They were shown to downregulate proliferation and cytokine production of activated effector T cells present in the tumor microenvironment and contribute to tumor tolerance and active avoidance of tumor immunity. If the quantify of DN T cells exceeds the defined threshold, it indicates a likelihood of cancer presence. Aside from immune cell profiling, our approach further establishes an integration of the information derived from transcriptome/meta-analysis of the genome and cytokine/chemokine signal analysis all from thyroid FNA. Applications[[Unsupported Character - Symbol Font •]] Diagnosis of thyroid cancer from FNA samples[[Unsupported Character - Symbol Font •]] Predictive tool of severity of disease Advantages[[Unsupported Character - Symbol Font •]] Microenvironment profiling can provide a unique way to diagnose and assess disease progression[[Unsupported Character - Symbol Font •]] Sheds light on cellular cross-talk; more accurate diagnose; can prevent unnecessary surgery IP Status:​Patent Pending
SUN-LB98 RAAS Triple-A Analysis for the Screening of Primary Aldosteronism
Authors: Burrello Jacopo , Buffolo Fabrizio , Domenig Oliver , Tetti Martina , Pecori Alessio , Monticone Silvia , Poglitsch Marko , Mulatero Paolo 
Published: May 2020

Abstract
Primary aldosteronism (PA) is recognized as the most frequent cause of secondary hypertension, and its screening is expected to become a routine evaluation in most patients with hypertension. The interference of antihypertensive therapies with the aldosterone-to-renin ratio (ARR) during screening process is a major confounder. Renin-Angiotensin-Aldosterone System Triple-A (RAAS Triple-A) testing is a novel mass-spectrometry based assay for quantification of Angiotensin I (Ang I), Angiotenisn II (Ang II) and Aldosterone in a single sample of serum by RAAS equilibrium analysis. Obtained hormone levels are used to calculate markers for plasma-renin-activity (PRA-S, Ang I + Ang II), plasma angiotensin-converting-enzyme activity (ACE-S, Ang II-to-Ang I ratio) and adrenal function (AA2-Ratio, Aldosterone-to-Ang II ratio), with the latter being useful to screen for PA in hypertension. We performed a comparative evaluation of the diagnostic performance of the AA2-Ratio and 5 renin-based diagnostic ratios, differing in methods to determine aldosterone levels and renin activity in a cohort of 110 patients with hypertension (33 patients with confirmed primary aldosteronism and 77 with essential hypertension). All ratios showed comparable areas under the curves ranging between 0.924 and 0.970 without significant differences between each other. The evaluation of the ACE-S revealed persistent drug intake in some patients as cause for suppressed renin-based diagnostic ratios, while the AA2-Ratio remained unaffected. The Youden index optimal cutoff value for the AA2-Ratio was 6.6 ([pmol/L]/[pmol/L]) with a sensitivity of 90% and a specificity of 93%, proving non-inferiority compared with the ARR while pointing to the potential for an interference-free application in patients under ACE inhibitor therapy. This study shows for the first time the accuracy and reliability of RAAS Triple-A analysis for the screening of primary aldosteronism that can be applied in clinical routine.
SUN-LB132 Frequency and Impact of Mutations in Tumor Suppressor Gene CDC73 in General Population and Malignant Tumors
Authors: Li Yulong , Chen Haobin 
Published: May 2020

Abstract
Background: CDC73 gene is a putative tumor suppressor gene, and somatic and germline mutations of this gene have been linked with parathyroid tumors. There are also some reports suggesting that germline CDC73 mutations may increase risk of jaw, kidney and uterine tumors. However, the incidence and significance of CDC73 somatic mutations is largely unknown in tumors other than parathyroid tumors.
Methods/Design: 1) Assess CDC73 germline mutation frequency and genotypes in general population using ExAC (Exome Aggregation Consortium) and gnomAD (Genome Aggregation Database); 2) Assess CDC73 somatic mutation frequency in various type of tumors using the Cancer Genome Atlas (TCGA) and non-TCGA datasets; 3) Examine significance of CDC73 mutation in uterine endometrial carcinoma (UCEC). Overall survival, CDC73 mutation signature, gene expression profile (GEP) and tumor immune microenvironment were compared between the UCEC samples with and without CDC73 mutations.
Results: In ExAC and gnomAD databases, most of CDC73 germline mutations were mapped to the intron regions of the CDC73 gene and nonsynonymous CDC73 mutations are very rare, with allele frequency ranging from 8.24e-06 to 9.92e-05 and 3.97e-06 to 7.43e-05, respectively. Missense mutations accounted for more than 95% of the nonsynonymous mutations in the CDC73 gene in both databases. 2) In 155 cancer genomics studies including both TCGA and non-TCGA datasets with no overlapping samples, CDC73 was mutated in 0.7% cases and missense mutations comprised 78% of the CDC73 mutations. CDC73 somatic mutations were undetected or rarely detected in endocrine tumors except for parathyroid tumors. 3) UCEC is the tumor type that has the second highest CDC73 somatic mutation rate (8%) after parathyroid tumors. The UCEC with CDC73 mutations had a significantly better overall survival with a logrank p-value of 0.033 compared to the tumors with CDC73 WT. GEP analysis revealed that the CDC73-mutated UCEC tumors had significant upregulation of immunological markers and enriched immunologic signature compared to the CDC73-WT tumors. In silico analysis of tumor immune microenvironment showed higher fractions of cytotoxic CD8 cells, T follicular helper cells and M1 macrophage in the CDC73-mutated UCEC tumors. The majority of the CDC73-mutated tumors were POLE ultra-mutated and microsatellite instability (MSI) subtypes, which likely account for a better survival and an increased immune-cell infiltrate of these tumors. Conclusion: CDC73 mutations is rare in general population and tumors except for parathyroid carcinoma and UCEC. CDC73 mutation is a marker for better prognosis in UCEC and is associated with increased immune cell infiltrate in tumor microenvironment, likely due to majority of the CDC73-mutated tumors were POLE ultra-mutated and microsatellite instability (MSI) subtypes.
SUN-490 Mass Cord Compression: Metastasis of Insular Thyroid Cancer
Authors: Jaber Dina , Vazques Bianca , Nagamoto Gary , Horani Mohamad Hosam 
Published: May 2020

Abstract
Intro: Insular thyroid cancer is a rare and complex form of thyroid cancer, often referred to as poorly differentiated carcinoma. The exact incidence of insular thyroid cancers is difficult to assess due to controversial classification of this thyroid cancer over the years. It is termed poorly differentiated as it falls between the well-differentiated and undifferentiated carcinomas both morphologically and biologically[1].
Case: A 41 year old Hispanic female, with a history of prolactinoma and hyperparathyroidism, presented to the hospital with 10 days of progressive lower extremity weakness and paresthesias from T4 downwards, inability to bear weight, and no bowel movement for 12 days. MRI revealed a large thoracic soft tissue mass (7x4x4cm) centered in the posterior and medial aspect of the chest wall at T4-T5 with involvement of the spinal cord and vertebral bodies. She was also found to have a right sided thyroid mass (4.5x5x4 cm) with tracheal deviation-
HerThyoid function test, were normal Intact PTH was 261, Thyroglobulin over 300, and Thyroid Antibodies were negative. Patient underwent T3-T6 laminectomy, T2-T7 fusion, and T4-T5 tumor resection, which was subtotal due to vascularity. Second procedure included a right thoracotomy, chest wall resection of ribs 4 and 5 with full resection of paraspinal mass, total thyroidectomy, parathyroidectomy with central cervical lymphadenectomy. Pathology results of paraspinal mass showed insular thyroid carcinoma.
Post operatively, the patient reported improvement of sensation and strength in lower extremities. Genetic testing for MEN syndrome was negative.
Discussion: Insular thyroid carcinoma, also referred to as poorly differentiated carcinoma is a rare form of thyroid cancer. Insular carcinoma was characterized by to include the following complex histologic features, “formation of solid clusters (insulae) of tumor cells containing a variable number of small follicles; variable but consistently present mitotic activity, capsular and blood vessel invasion; and frequent necrotic foci, sometimes leading to formation of peritheliomatous patterns”[1]. The cells originate from follicular epithelium and possess the potential to concentrate radioiodine[2]. Unlike anaplastic carcinoma of the thyroid, p53 and p21 staining was negative in insular carcinomas[3]. Thyroglobulin staining is generally positive[4]. Distant metastasis occurs in about 31% of patients with insular thyroid carcinoma[5]. In cases of distant metastasis, treatment with thyroidectomy and radioiodine therapy were shown to independently improve survival[5].
The Constellation of Insular thyroid cancer, hyperparathyroidism and Prolactinoma, has not been reported before.
References:
[1]. Am J Surg Pathol. 1984;8:655-
[2] J of Nuc Med 32(7), 1358
[3] Ann of Surg vol. 231,3 (2000): 329
[4] JCEM 99. 1167–9. 10.1210/jc.2014
[5] Cancer. 2012 Jul;118(13) 3260
SUN-LB118 Mice With Skeletal Muscle-Specific DRP1 Deficiency Are Resistant to Obesity and Diabetes Induced by a High Fat Diet
Authors: Jensen Renato Daniel , Peterson Joshua , Allington Benjamin , Dieter Alayna , Cheng Linhai , Soto Jamie , Alambert Renata Pereira , Correia Marcelo , Abel Evan Dale 
Published: May 2020

Abstract
The skeletal muscle of type 2 diabetics exhibits mitochondrial dysfunction associated with increased mitochondrial fission. Dynamin-related protein 1 (DRP1) is responsible for mitochondrial division, whereas mitochondrial-endoplasmic reticulum contacts (MERCs) mark mitochondrial sites where fission occurs. Here, we have shown that skeletal muscle-specific DRP1 knock out (KO) mice are partly protected from high fat diet-induced obesity and diabetes, and exhibit increased insulin and glucose tolerance along with lower insulinemia. We also found that KO mice exhibit increased energy expenditure per unit of lean mass. Isolated DRP1-deficient skeletal muscle fibers from KO mice fed high fat diet have reduced respiratory capacity when exposed to ADP and palmitoyl-carnitine, but not when exposed to ADP, pyruvate, and malate. Additionally, the skeletal muscle of KO mice fed normal chow exhibited altered expression of genes associated with MERCs and increased expression of genes linked to ER stress. We observed substantial increases in gene expression of FGF21, a downstream signal of the ER stress response, in KO mice. However, FGF21 plasma concentration in KO mice was not elevated. Additionally, changes in MERC gene expression could potentially alter calcium signaling between the mitochondria and endoplasmic reticulum, changing insulin sensitivity in KO mice. In conclusion, we have shown that skeletal muscle-specific DRP1 KO mice are resistant to high fat diet-induced obesity and diabetes, perhaps due to elevated energy expenditure and differential mitochondrial respiratory adaptations to different substrates. Although FGF21 does not appear to contribute to this effect, it is possible that other ER-stress signals might help explain the observed phenotype in KO mice.
SUN-LB27 Interleukin-8 - a Possible Target for Melanoma Treatment? In-Vitro Studies Based on Human Melanoma Cell Models
Authors: Ramaraj Pandurangan 
Published: May 2020

Abstract
Previous clinical studies showed that menstruating females were better protected in melanoma than post-menopausal women and men of any age. In addition, epidemiological studies showed an increased male mortality in melanoma. But these studies did not correlate with steroid status in females. Our in-vitro study showed female sex hormone progesterone significantly inhibited human melanoma cell growth. Further in-vitro study showed that progesterone action was mediated by a specific suppression of pro-inflammatory cytokine IL-8. Our research also showed that addition of IL-8 (1 ng/ml) to melanoma cells stimulated cell growth (117%) and suppression of IL-8 by curcumin (100 μM) pre-treatment suppressed human melanoma cell growth (26%) in-vitro. This observation prompted us to check the effect of male sex hormones androstenedione (AD) and testosterone (T) on melanoma cell growth. AD and T also suppressed cell growth and IL-8 secretion, but not as significantly as that of progesterone. However, addition of progesterone (10 μM) along with androgens showed an additive effect on the inhibition of melanoma cell growth and suppression of IL-8 secretion. As steroids (P, AD, T) targeted IL-8 for their action, it was decided to check whether vitamin-D3 also targeted IL-8 secretion and cell growth. Active form of vit-D3 (25 μM) also suppressed IL-8 secretion and cell growth. But, addition of progesterone (50 μM) along with D3 significantly suppressed cell growth and IL-8 secretion. This brought IL-8 into focus as a key molecule regulating melanoma cell growth. In order to check whether IL-8 was the molecule involved in regulating melanoma cell growth, IL-8 rescue experiment after curcumin (25 μM) pre-treatment was carried out. IL-8 (100 ng/ml) was able to rescue cell growth completely after pre-treatment with curcumin, suggesting IL-8 was the molecule involved in regulating melanoma cell growth. Literature also suggested important role for IL-8 in regulating melanoma cell growth. Conditional expression of IL-8 in nude mouse by Dr. Singh et al., indicated in-vivo role of IL-8 in melanoma growth and metastasis. Conclusion: Both, in-vitro and in-vivo studies suggested an important role for IL-8 in regulating melanoma growth and metastasis. So, IL-8 could be targeted to arrest melanoma growth and metastasis in-vivo. Hence, IL-8 could be a potential target for melanoma treatment.