bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU502 CYR61, A Member Of The CCN Protein Family, Regulates IGF1 In Metastatic Prostate Cancer
Authors: Ortiz Hernandez Greisha L , Walker Mya , Woods-Burnham Leanne , Kittles Rick A , Casiano Carlos A , Neuhausen Susan L 
Published: October 2023

Abstract
Disclosure: G.L. Ortiz Hernandez: None. M. Walker: None. L. Woods-Burnham: None. R.A. Kittles: None. C.A. Casiano: None. S.L. Neuhausen: None.
The cysteine-rich angiogenic inducer 61 (CYR61) is a member of the cellular communication network (CCN) protein family that can be induced by growth factors. CYR61-specific functions are dependent on cellular context. In prostate cancer (PCa), CYR61 contributes to cell growth and survival through its interactions with extracellular ligands, such as integrins avb3 and a6b4, in the extracellular matrix space. Interestingly, CYR61 contains an insulin-like growth factor-binding protein domain suggesting that it may interact with insulin-like growth factor-1 (IGF1). High serum levels of IGF1 are directly linked to PCa development and recently have been studied as a predictor of metastatic disease. Given the important roles that IGF1 and CYR61 play in PCa and their potential interaction, it is critical to investigate their molecular interplay. We hypothesize that the interaction of CYR61 and IGF1 contributes to aggressive tumor properties (e.g., proliferation, tumorsphere formation) in PCa. Using immunoblotting, we demonstrated that CYR61 is upregulated in the androgen receptor-negative and glucocorticoid receptor-positive (AR-/GR+) metastatic cell line, PC3, and downregulated in the docetaxel-resistant cell line PC3-DR. Furthermore, optimized knockdown of CYR61 using siRNA significantly reduced PC3 cell proliferation, viability, and prostasphere formation. To examine the underlying mechanisms associated with IGF1 signaling, we assessed the activation of the PI3/Akt and MAPK pathways in PC3 cells with CYR61 silenced. CYR61 siRNA-mediated knockdown decreased activation of the PI3/Akt pathway but did not alter the MAPK pathway. We also initiated studies to determine the co-localization of CYR61 and IGF1 using immunofluorescence microscopy (IF). Based on the initial IF observations, we will proceed to examine if their interaction is primarily intra- or extra-cellular and whether interactions differ based on AR signaling. Using both PC3 and MDA-PCa-2b, which is AR+/GR+, we will co-immunoprecipitate CYR61 with IGF1 to assess intracellular interactions and use the AVidity-based EXtracellular Interaction Screen (AVEXIS) system for extracellular interactions. The correlation between PCa aggressiveness and circulating levels of CYR61 and IGF1 is poorly studied. Therefore, our goal is to establish the contribution of CYR61-IGF1 protein-protein interaction to PCa cell proliferation and tumor aggressiveness.
Presentation: Thursday, June 15, 2023
THU511 Somatostatin Analogs Or Active Surveillance In Sporadic And MEN1 Associated Non-functioning Pancreatic Neuroendocrine Tumors
Authors: Raia Salvatore , Chiloiro Sabrina , Maratta Maria Grazia , Maiorano Brigida , Rossi Ernesto , Brizi Maria Gabriella , Rufini Vittoria , De Marinis Laura , Rindi Guido , Schinzari Giovanni , Pontecorvi Alfredo , Tortora Giampaolo , Bianchi Antonio 
Published: October 2023

Abstract
Disclosure: S. Raia: None. S. Chiloiro: None. M. Maratta: None. B. Maiorano: None. E. Rossi: None. M. Brizi: None. V. Rufini: None. L. De Marinis: None. G. Rindi: None. G. Schinzari: None. A. Pontecorvi: None. G. Tortora: None. A. Bianchi: None.
Introduction: Non-functioning (NF), sporadic and MEN1 associated, G1-G2 pancreatic neuroendocrine tumors (PanNETs) usually display an indolent course. Surgery is the first-choice treatment for localized tumors &gt;2 cm. Unresectable or metastatic PanNETs expressing somatostatin receptors (SSTRs) are treated with somatostatin analogs (SSAs). The standard treatment for patients with PanNETs ≤2cm is active surveillance (AS). Yet no evidence of the value of SSA treatment exist in such patient population. Aim(s): To assess the clinical value of SSAs in patients with PanNETs ≤2cm. Material and methods: Data from patients (pts) NF, G1-G2 PanNETs≤2cm were retrospectively collected. Median progression-free survival (mPFS) and response rate (RR) were analyzed in SSA group and AS group. Results: From June 2007 to June 2022, data from 46 pts were considered: 29 pts, who declined an AS program but had not indication for surgery, entered in the SSA group (21 sporadic and 8 MEN1 associatd PanNET) and 17 in the AS group. At a median follow-up of 64.8 months for sporadic and of 63.9 for MEN1 associated PanNET, no disease progression (PD) was reported in the SSA group, without differences between sporadic and MEN1 associated PanNET. While the PD rate was 23.5 % in the AS group, with a mPFS of 36.2 months. Conclusion: SSAs therapy showed significant antiproliferative activity in patients with both sporadic and MEN1 associated NF, G1-G2 PanNETs ≤2cm. SSAs treatment delay tumor progression and distant spread in small lesions that sometimes may reveal an unpredictable aggressiveness.
Presentation: Thursday, June 15, 2023
FRI219 Pheochromocytoma Presenting As A Case Of Worsening Diabetes Mellitus
Authors: Eapen Jane , Singer Elizabeth Sedlis , Lu Tiffany Xin , Shapiro Joshua Nathan 
Published: October 2023

Abstract
Disclosure: J. Eapen: None. E. Sedlis Singer: None. T.X. Lu: None. J.N. Shapiro: None.
Introduction: Pheochromocytoma is often diagnosed incidentally during unrelated abdominal imaging, in patients with a family history of known disease, or in patients presenting with the classic triad of symptoms: episodic headache, sweating, and tachycardia. We describe an atypical case of pheochromocytoma presenting as acute decompensation of DM. Case presentation: A 79 year old female with DM previously well-controlled on glimepiride for 4 years presented with an acute worsening of symptoms notable for abdominal fullness, weakness and weight loss. Laboratory results revealed an increase in HbA1c from 6% to 14% (nl &lt;5.7%) since 3 months prior. Metformin and basal insulin were added to her regimen with a subsequent improvement in HbA1c. An abdominal CT scan was done given the acuity of progression in her DM, which revealed a 5.8cm adrenal mass. The patient denied easy bruising, striae, mood changes, dizziness, or hypertension. Biochemical evaluation demonstrated normal potassium level 3.7 (3.5-5.3 mmol/dL) and aldosterone 8ng/mL (&lt;28), non-suppressed cortisol 7.8mcg/dL after dexamethasone 1mg given the night prior, but Cushing’s Disease was ruled out by normal salivary cortisol 0.08 mcg/dL (nl 0.04-0.56 mcg/dL) and urine free cortisol 22.8 mcg/ 24h (nl 4-50 mcg/24h), and further testing revealed elevated metanephrines and catecholamines during 24 hour urine collection, Epinephrine 129 mcg/24h (nl 2-24 mcg/24h), Metanephrine 7121 mcg/24h (nl 90-315 mcg/24h) and Normetanephrine 2078 mcg/ 24h (nl 122-676 mcg/24h).Repeat CT scan again showed an indeterminate 5.4 x 3.8 x 5.5 cm right adrenal mass, a 6.9mm lipid-rich left adrenal adenoma, and left adrenal gland hyperplasia. Consequently, the patient underwent laparoscopic right adrenalectomy with pathology revealing a diagnosis of pheochromocytoma. Post-op plasma fractionated metanephrines normalized and have remained normal. Immediately post-op, all diabetes medications (including insulin, glimepiride, and metformin) were stopped and she has had resolution of diabetes with HbA1c 6 on no medications when 1-year post-op. Discussion: Excess catecholamines are known to cause disruption of glucose and insulin homeostasis from desensitization of the beta-adrenergic receptor and increased insulin resistance1. Despite this, less than a handful of pheochromocytoma cases have been reported to be presenting as an acute glycemic derangement as in our patient. References: 1. Ronen JA, Gavin M, Ruppert MD, Peiris AN. Glycemic Disturbances in Pheochromocytoma and Paraganglioma. Cureus. 2019 Apr 27;11(4):e4551.doi: 10.7759/cureus.4551. PMID: 31275775; PMCID: PMC6592834.
Presentation: Friday, June 16, 2023
THU516 An Unusual Neck Mass
Authors: Rios Paola , Kalara Niketa , Shyam Tharun , Velez Jaylou , Gomez Carmen , Menendez Silvia Gra 
Published: October 2023

Abstract
Disclosure: P. Rios: None. N. Kalara: None. T. Shyam: None. J. Velez: None. C. Gomez: None. S. Gra Menendez: None.
Background: Parathyroid carcinoma is a rare tumor which presents with a neck mass and hypercalcemia. Non-functional parathyroid tumors account for 10% of all parathyroid carcinomas and are associated with decrease or impaired secretion of PTH, having normal calcium, being difficult to diagnose. We present a case of a patient who presented with a neck mass and normocalcemia, who was diagnosed of non-functional parathyroid tumor, were immunohistochemistry played a useful role in differentiating an unsuspected parathyroid lesion from a thyroid neoplasm. Clinical Case: 49-year-old woman presented with a 6-month history of a firm mass on the left side of her neck that was initially stable but then started to grow and was painful. On examination, she was noted to have a 5 cm firm thyroid mass with bilateral level 2 lymphadenopathy. Patient had a calcium of 9.9 mg/dL (8.6-10.3 mg/dL), normal kidney function and was euthyroid. An ultrasound of the thyroid revealed a left mass near the thyroid lobe, measuring 3.1 x 4 x 2.5 cm. Fine-needle aspiration of the mass revealed a poorly differentiated carcinoma possible originating from the thyroid. The patient underwent total thyroidectomy with central compartment dissection, bilateral neck dissection and radical resection of the tumor. Frozen section revealed malignancy highly concerning for anaplastic thyroid. Immunohistochemistry (IHC) showed that the differentiated component was positive for PTH, chromogranin, PAX8 and GATA-3, while negative for TTF-1, thyroglobulin, BRAF and p53. The higher-grade component was positive for GATA-3, p53, TTF1 (weak focal), PAX-8 (weak focal) and negative for thyroglobulin, chromogranin, PTH and BRAF which was suggestive of parathyroid tissue. The final pathology report was a differentiated parathyroid carcinoma transitioning to a high-grade carcinoma with anaplastic features, 5.6 cm in the largest dimension with invasion to thyroid tissue, skeletal muscle and angiolymphatic invasion. The tumor was a pT3N0Mn/a. Next-Generation Sequencing (NGS) of the tumor showed a high tumor mutational burden as well as high microsatellite instability being beneficial Pembrolizumab for treatment if required. IHC showed PD-L1, were Nivolumab and Pembrolizumab could work in the future if needed. Also, TP53 was detected on the NGS. She completed 32 Gy/16 fractions of adjuvant radiotherapy and continues to be on active surveillance 8 months after diagnosis without evidence of recurrence of the cancer. Conclusion: Non-functional parathyroid carcinoma is a very rare tumor that should be on the differential diagnosis in a patient with normocalcemia and neck mass. Immunohistochemistry would help in the diagnosis between thyroid or parathyroid lesion as described in this case.
Presentation: Thursday, June 15, 2023
THU519 Large Congenital Facial Teratoma: A Case Report
Authors: Solis Pazmiño Andrea Paola , Pazmino-Chavez Camila , Solano Vanessa , Garcia Cristhian 
Published: October 2023

Abstract
Disclosure: A.P. Solis Pazmiño: None. C. Pazmino-Chavez: None. V. Solano: None. C. Garcia: None.
Background: Craniocervical teratomas are congenital tumors that arise from the endoderm, mesoderm, and ectoderm germ cell layers. In order to have adequate and prompt management for better outcomes, information about its clinical manifestations and prenatal assessment must be widely disseminated because it can cause death in neonatal patients. The purpose of this case report is to deepen understanding of craniocervical teratoma because there is a dearth of information on the subject. Clinical case: A boy infant was brought in with a significant right mass that had existed from birth. He was delivered by cesarean section at the 38th week of gestation by a 26-year-old primiparous female with one living and healthy child. An extended facial appendage measuring 54 x 23 x 49 mm (L x B x W), with a capacity of 32 mL, was seen during prenatal ultrasonography (Figure 1a). On color Doppler imaging, the appendage was shown as a smoothing, hypodense cystic lesion without any vascularity to be concerned about (Figure 1b). The patient underwent an elective cesarean section at term, the pregnancy developed normally overall, and the newborn was delivered in generally healthy condition. The youngster does not experience pain, have trouble opening his lips, have trouble hearing, or have any other neurological deficits, according to the child’s parents. At the time of examination, the mass measured approximately 6.5 cm by 5 cm by 4 cm in the lateral half of the face (Figure 2) and extended superiorly to the right pterygoid region to the sub-maxillary ipsilateral side. Clinical lessons: Although craniocervical teratoma incidence is low, it is important to identify the appendage on neonatal ultrasound to plan correct management ahead of the baby’s delivery. Additionally, using the 3D-printed model makes it easier to organize the surgery and reduces blood loss while debulking.
Presentation: Thursday, June 15, 2023
THU545 Growth Hormone Receptor Antagonist As A Novel Combination Therapy Against Triple Negative Breast Cancer
Authors: Mora-Criollo Patricia , Basu Reetobrata , Kopchick John Joseph 
Published: October 2023

Abstract
Disclosure: P. Mora-Criollo: None. R. Basu: None. J.J. Kopchick: None.
Triple Negative breast (TNBC) cancer is classified based on the absence of ER-, PR-, and HER2- receptors and is associated with high metastatic potential. TNBC accounts for approximately 15-20% of new breast cancer diagnoses and is responsible for most breast cancer-related deaths. First-line treatment of anticancer drugs can be effective in 30-70% of patients with TNBC, but during treatment, more than half of the patients develop resistance and progress into metastatic disease. Previous studies have demonstrated the link between growth hormone receptor (GHR) expression and mammary carcinogenesis and established that GHR signaling promotes breast cancer development and progression. Conversely, inhibition of GHR expression has been shown to arrest tumor initiation and reduce metastasis of mammary carcinoma cells. Here we present the feasibility studies for employing GHR as a target for novel combination therapeutic approaches in TNBC. We performed retrospective analysis of GHR transcript expression and survival in TNBC patients, followed by experimental data in cellular models using combinations of Pegvisomant (an FDA-approved GHR antagonist) with chemotherapeutic agents, as a potential therapeutic option in TNBC. Survival probability plots from the TCGA dataset of 405 TNBC samples showed that patients expressing high levels of the GHR showed a significantly poor survival (27 months, p=0.038) compared to patients expressing low GHRs (40.37 months). Additionally, human breast cancer MDA-MB-453 cells, when treated with human (hGH)(2.5 nM) increased activation of JAK2, STAT5, SRC, ERK1/2, and AKT, associated with cancer progression. Importantly, treatment of the cells with Paclitaxel (1 nM) + (hGH)(2.5 nM) increased ABCG2 expression and the epithelial-to-mesenchymal transition (EMT) makers (SLUG, SNAIL, N-cad) associated with drug resistance and tumor progression. On the contrary, when cells were treated with Pegvisomant (500 nM) in combination with Paclitaxel + GH, a significant decrease in protein and RNA expression of ABCG2 as well as EMT markers was observed. Next, serum collected from GH antagonist (GHA) mice and WT as control, were used to treat PY8119 mouse cells in combination with Paclitaxel (1 nM) + bovine (bGH)(2.5 nM). Downregulation of protein and RNA expression levels of ABCG2 as well EMT makers in GHA serum treatment compared to WT was also found. This preliminary data shows that the GHR antagonist, Pegvisomant, in combination with anticancer drugs, can be effective in attacking drug resistance in TNBC. Key words: Pegvisomant, growth hormone receptor
Presentation: Thursday, June 15, 2023
THU547 Role Of NAD+ Synthesis Pathway In PARP Inhibitor Resistance
Authors: Myong Subin , Challa Sridevi 
Published: October 2023

Abstract
Disclosure: S. Challa: None.
ADP-ribosylation is catalyzed by the poly(ADP-ribose) polymerase (PARP) family of enzymes consisting of 17 members that have distinct structural domains, activities, subcellular localizations, and functions. The catalytic activities of PARP enzymes are intimately tied to the synthesis of NAD+, which is consumed during ADPRylation reactions and, thus, must be regenerated. The intracellular salvage pathway utilizing nicotinamide (NAM) is the primary source of NAD+ in the cell. NAM is converted to nicotinamide mononucleotide (NMN) by NAMPT. Nicotinamide mononucleotide adenylyl transferases (NMNATs) catalyze the final step in the NAD+ salvage pathway, combining NMN and ATP to make NAD+. Three different NMNATs, each with a distinct subcellular localization, control the subcellular levels of NAD+ in each compartment: NMNAT-1 in the nucleus, NMNAT-2 is in the outer membrane of golgi, and NMNAT-3 in the mitochondria. We recently demonstrated that such compartment-specific NAD+ synthesis regulates the levels of ADP-ribosylation. Elevated levels of NMNAT-2, the cytosolic NAD+ synthase, reduces nuclear NAD+ levels and PARP1 activity in adipocytes and ovarian cancer cells.
In the current study, we aim to delineate the role of compartmentalized synthesis of NAD+ in PARP inhibitor resistance in ovarian cancers. To identify these mechanisms, we generated ovarian cancer cells with acquired resistance to Niraparib, an FDA approved PARP inhibitor (NirR). We found that NirR cells have elevated levels of NAD+ biosynthesis. Moreover, treatment of parental cells with NAD+ precursors reduced the sensitivity to Niraparib while inhibition of NAD+ metabolism in NirR cells increased the sensitivity to Niraparib. Interestingly, the resistant cells have comparable levels of PARP1 activation to the parental cells. These data collectively suggests that NAD+ metabolism confers resistance to Niraparib without altering PARP1 activity. In line with this, NirR cells are sensitive to the effects of depletion of the cytosolic NAD+ biosynthesis, suggesting high NAD+ biosynthesis in NirR cells supports processes regulated by the cytosolic NAD+ which may drive the resistance phenotype. There is an urgent need to identify the mechanisms of resistance to PARP inhibitors to increase their clinical efficacy. This study identifies the NAD+ biosynthesis pathway as a key mechanism of PARP inhibitor resistance.
Presentation: Thursday, June 15, 2023
THU549 Targeting The Growth Hormone Receptor Attenuates Tumor Exosome Mediated Propagation Of Chemoresistance In Melanoma
Authors: Kulkarni Prateek , Basu Reetobrata , Bonn Taylor , Kopchick John Joseph 
Published: October 2023

Abstract
Disclosure: P. Kulkarni: None. R. Basu: None. T. Bonn: None. J.J. Kopchick: None.
Elevated ATP-binding cassette (ABC) transporters in tumor cells resulting in decreased intracellular drug accumulation is a major reason for chemotherapy resistance in cancer. Mounting evidence indicates that extracellular vesicles (EVs), particularly exosomes, the smallest subset of EVs, play a crucial role in the spread of drug resistance. We have previously shown that growth hormone (GH) decreases therapeutic efficacy in melanoma via upregulating the levels of ABC transporters, whereas when GHR is knocked down or GH/GHR interaction is inhibited by GHR antagonist, Pegvisomant, these ABC transporters are significantly downregulated. No study has yet directly assessed the effect of GH or GHR antagonism on exosomal cargoes in terms of promoting drug resistance. We observe that human melanoma cells (Malme3M, SK-Mel28, and MDA-MB-435) when treated with GH or doxorubicin alone or in combination increase the exosomal protein levels of multiple multi-drug efflux pumps, namely ABCC1, ABCC2, ABCB1, and ABCG2. On adding Pegvisomant to these treatments, we found a significant decrease in the levels of these exosomal drug efflux pumps induced by both autocrine and endogenously added GH. Furthermore, we assessed the role of GH in exosome-mediated dissemination of chemoresistance from drug-resistant to drug-sensitive cells. When GH and doxorubicin-treated melanoma-derived exosomes were administered to treatment-naïve melanoma cells, a significant increase in drug efflux was observed in the latter, compared to the control. On the other hand, when Pegvisomant co-treated melanoma-derived exosomes were administered to treatment-naïve melanoma cells, the drug efflux was attenuated, indicating chemo-sensitization. Collectively, these observations indicate that Pegvisomant suppresses various exosomal cargoes modulating drug resistance in melanoma.
Acknowledgment: This work was supported in part by the State of Ohio’s Eminent Scholar Program includes a gift from Milton and Lawrence Goll, by the AMVETS, Ohio University’s Student Enhancement Award, and Edison Biotechnology Institute.
Presentation: Thursday, June 15, 2023
THU552 Understanding Radiation Therapy Sensitivity In Invasive Lobular Carcinoma Of The Breast
Authors: Boysen Michael Rhinehart , Sikora Matthew Joseph , Shackleford Madeleine , Sottnik Joseph 
Published: October 2023

Abstract
Disclosure: M.R. Boysen: None. M.J. Sikora: None. M. Shackleford: None. J. Sottnik: None.
Invasive lobular carcinoma of the breast (ILC) affects ∼40,000 US women annually and is a top-ten most common cancer affecting women. Despite most ILC having biomarkers of “low risk” disease (e.g. ∼95% are estrogen receptor α /ER-positive), ILC is associated with poorer long-term outcomes and anti estrogen resistance. ILC are also notoriously non-responsive to chemotherapy, critically limiting treatment options for advanced or metastatic ILC. However, ILC are highly responsive to radiation therapy (XRT), which suppresses ILC recurrence and improves survival. We hypothesize that this sensitivity may be due to a dysfunction in DNA damage repair unique to ILC cells. We examined formation and resolution of DNA damage repair foci (namely RAD51, γH2AX and 53BP1 foci) by immunofluorescence with ILC and IDC cell lines treated with ionizing radiation +/- anti-estrogen therapy as surrogates for the initiation and resolution of DNA repair. We also assessed cell growth via 7-day growth assays with ILC and IDC cell lines treated with ionizing radiation. Imaging with immunofluorescence suggested a deficiency in γH2AX foci formation in ILC cells compared to IDC cells following treatment with XRT, despite robust formation of 53BP1 foci. This suggests that a deficiency in performing DNA damage repair in response to XRT is likely present in ILC cells. Additionally, our growth assays demonstrated an inability in ILC cells to recover from ionizing radiation compared to IDC cells. Taken together, the potential dysfunction in γH2AX foci formation in ILC cells suggests that ILC cells may not form the appropriate DNA repair structures to initiate the DNA damage response, suggesting that a form of DNA repair deficiency underlies radiation sensitivity in ILC cells.
Presentation: Thursday, June 15, 2023