bluuebunny/crossref_metadata_2025_split huggingface dataset:
6425 Impact Of Adrenalectomy On Mood, Sleep, And Quality Of Life In Patients With Mild Autonomous Cortisol Secretion: A Prospective Longitudinal Study
Authors: Saini Jasmine , Fell Vanessa , Atkinson Beth , Achenbach Sara , Bancos Irina 
Published: October 2024

Abstract
Disclosure: J. Saini: None. V. Fell: None. B. Atkinson: None. S. Achenbach: None. I. Bancos: None.
Background: Patients with mild autonomous cortisol secretion (MACS) have an impaired quality of life and a higher prevalence of sleep and mood disturbances as compared to patients with nonfunctioning adrenal adenomas. The impact of adrenalectomy on quality of life, mood, and sleep is unclear. Objective: To determine the impact of adrenalectomy on quality of life, sleep, and mood in patients with MACS Methods: We conducted a single-center prospective longitudinal study of adults with MACS scheduled for adrenalectomy and referent subjects evaluated between 2018 and 2023. MACS was defined as serum cortisol&gt;1.8 mcg/dL after 1 mg dexamethasone suppression test in patients with adrenal adenomas and no features of overt hypercortisolism. Referent subjects were included if they had abdominal imaging and had no adrenal disorders. Patients and referent subjects had a baseline and a follow-up evaluation at least 10 months later. Differences were assessed using paired t-tests for (1) Quality of life using Short Form-36 (SF 36) survey (Physical and Mental component summary score), sex and age-adjusted (2) Mood using Beck’s Depression Inventory (BDI) (3) Sleep using Pittsburgh Sleep Quality Index (PSQI). Results: We evaluated 41 patients before and after adrenalectomy, and 31 referent subjects at baseline and follow-up visit, at a similar interval (median 1.6, IQR 1.2-2.0 vs 1.5 years, IQR 1.0-2.2, P=0.759). While sex distribution was similar between the groups (66% vs 84% women, P=0.086), patients with MACS were older than the referent group (median age 57.3, IQR 48.8-66.9 vs 49.0, IQR 41.7-57.9 years, P=0.005). After adrenalectomy, patients improved their mood with a mean decrease of -4.71 (SD: 9.11), P=0.002 on the BDI questionnaire. Patients also demonstrated improvement in the SF-36 mental component score by a mean of 6.48 (SD: 10.97), P&lt;0.001. While the overall SF36 physical component score did not improve after adrenalectomy (1.953 (SD: 11.02), P=0.269), one of the PCS components, role-physical limitation, increased by a mean of 6.25 (SD: 13.03). Patients reported better sleep with PSQI score decreasing by a mean of -2.59 (SD: 3.64), P&lt;0.001. No differences in BDI, SF36, and PSQI were observed between baseline and follow-up in referent subjects. Conclusions: After adrenalectomy, patients with MACS showed an improvement in sleep, mood, and mental component of quality of life.
Presentation: 6/3/2024
8523 An Unconventional Estrogen Receptor Conformation Induces SUMO Expression In Breast Cancer Cells
Authors: Hancock Govinda R , Young Kristen , Greene Geoffrey L , William Fanning Sean 
Published: October 2024

Abstract
Disclosure: G.R. Hancock: None. K. Young: None. G.L. Greene: None. S.W. Fanning: None.
An Unconventional Estrogen Receptor Conformation Induces SUMO Expression in Breast Cancer Cells Govinda Hancock, Kristen Young, Geoffrey L. Greene, Sean W. Fanning Competitive allosteric regulators, selective estrogen receptor modulators (SERMs)/degraders (SERDs) differentially manipulate receptor structure to treat and prevent metastatic breast cancers. However, their utility is limited by the ∼40% rate of disease progression due to acquired therapy resistance. In this study, a new SERM based on a tetrahydro-6-isoquinoline (T6I) scaffold reveals the relationship between ERα conformation and therapeutic transcriptional pathways in drug-resistant breast cancers. Optimization of structure-activity relationships produced unique lead compound that engages transcriptional programs similar to the clinically approved SERD fulvestrant. Notably, both drugs induce the expression of small ubiquitin-like modifier-1 (SUMO1), in opposition to the pathogenic hormone 17β-estradiol. SUMOylation is a post-translational modification affecting protein-protein interactions, localization, stability and functional properties. High expression of SUMO1 is associated with better patient prognosis in ERα+ disease. SUMOylation in breast cancer will be elucidated through understanding how it’s induced, its structural basis, and its role in therapeutic response of antiestrogen treatments.
Presentation: 6/3/2024
12407 Assessing Human Monocyte Migration And Co-culture With Adrenocortical Cancer Cells
Authors: Hong C , Feely S , Challapalli R , Mullen N , Sorushanova A , Hantel C , Griffin M D , Dennedy M C 
Published: October 2024

Abstract
Disclosure: C. Hong: None. S. Feely: None. R. Challapalli: None. N. Mullen: None. A. Sorushanova: None. C. Hantel: None. M.D. Griffin: None. M.C. Dennedy: None.
Adrenocortical carcinoma (ACC) is a lipid, typically steroidogenic cancer which carries a 5-year prognosis of &lt;10%. Therapeutic options are limited including surgery and mitotane – a poorly tolerated and efficacious insecticide. Recent data have demonstrated that the immune environment of adrenocortical carcinoma is deficient in lymphocytes while demonstrating a relative rich monocyte/macrophage population in the tumour microenvironment. We have investigated the gradient for migration of circulating peripheral monocytes to ACC. ACC cells were seeded in the bottom chamber of the transwell system. Monocytes were isolated from human peripheral blood, by negative selection using magnetic beads with high purity (&gt;95%) and quality. Migration of monocytes at 24/48h was evaluated by identifying those remaining in the top chamber, the floating fraction in the bottom chamber and those adherent to ACC cells in the bottom chamber. Analysis of monocyte/macrophages was undertaken by flow cytometry using the following markers: Sytox Blue, CD45, CD14, CD16 and HLA-DR. At 24h, when compared to control conditions, more monocytes had migrated to the ACC cells seeded lower chamber and attached to the bottom. Similar results were observed in migration at 48h. Predominantly Classical monocytes (CD14++CD16-HLA-DR+) migrated to metastatic cancer cells (MUC1), and Non-Classical monocytes (CD14+CD16+HLA-DR+) migrated to primary cancer cells (H295R/ HAC15) at 48h. We then investigated the polarization cytokine profile of migrated monocytes with or without ACC cells at 72 h by multiplex bead-based assay. Migrated monocytes indicated a significant shift toward the M2 phenotype in the presence of H295R or HAC15. The production of the pro-inflammatory factors of IL-6, TNF-alpha, etc. decreased and immunosuppressive factors of IL-10, TARC, etc. increased. MUC1 didn’t increase M2 or M1 cytokine secretion. Moreover, surface markers of migrated monocytes were evaluated at 72h by flow cytometry. When compared to the control group, all 3 ACC cell lines switched monocytes/ macrophages into M2 phenotype, as evidenced by the decrease in the expression of the M1 marker CD86 and the increase in the expression of the M2 markers CD163 and CD206. We demonstrate monocytes migrate and associate with ACC cells: (i) subpopulations differ in transmigration properties in response to ACC cells (ii) monocytes/macrophages exhibit M2 polarization phenotype.
Presentation: 6/2/2024
7274 Assessing The Interactome Of Hexose-6-Phosphate Dehydrogenase In Breast Cancer Cells And Identifying Anterior Gradient Protein 2 As Interacting Partner By Using A BioID Method
Authors: Sakalauskaite Gabriele , Weingartner Michael , Bock Thomas , Birk Julia , Tsachaki Maria , Odermatt Alex 
Published: October 2024

Abstract
Disclosure: G. Sakalauskaite: None. M. Weingartner: None. T. Bock: None. J. Birk: None. M. Tsachaki: None. A. Odermatt: None.
Hexose-6-phosphate dehydrogenase (H6PD) catalyzes the first two steps of the pentose-phosphate pathway in the endoplasmic reticulum (ER). It is so far the only enzyme shown to generate NADPH in the ER. H6PD is involved in physiological processes such as glucose and steroid metabolism, redox regulation, and response to ER-stress. So far, only one H6PD interacting partner, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), has been reported. This enzyme uses NADPH for its well-reported role in glucocorticoid activation. However, H6PD has 11β-HSD1-independent functions, such as the recently described modulation of breast cancer cell properties. Here, we adapted the BioID approach to identify novel H6PD interacting partners in the ER. First, we generated a triple negative breast cancer cell line MDA-MB 231 stably expressing a H6PD-biotin ligase fusion protein. Then, we validated the method to confirm the known interaction between H6PD and 11β-HSD1. Next, we analyzed enriched biotinylated proteins by mass spectrometry and further assessed potential candidates by co-immunoprecipitation and functional assays. The resulting interactome revealed a potential hit cluster of protein disulfide isomerase (PDI) family members, different ER-resident chaperones and luminal calcium binding proteins. Due to its association with breast cancer, we further examined the PDI Anterior gradient protein 2 (AGR2) as H6PD interacting partner. Physical interaction between AGR2 and H6PD was confirmed by co-immunoprecipitation assay in MCF7 cells. Downregulation of AGR2 by siRNA resulted in elevated H6PD protein levels but decreased activity. Furthermore, increased H6PD activity was observed when this protein was co-expressed with AGR2 in HEK-293 cells. In conclusion, the results validated the use of the BioID approach to identify protein interactions within the ER and they revealed that AGR2 physically interacts with H6PD, thereby controlling its expression and enzyme activity.
Presentation: 6/3/2024
7401 Development And Evaluation Of Ruthenium-Based Photoactivated Chemotherapeutic Agents
Authors: Wilson Auden , Cejudo Briseily , Enkhbold Khuslen , Chung Yuna , Chiaino Samantha , Norris Michael R , Pollock Julie 
Published: October 2024

Abstract
Disclosure: A. Wilson: None. B. Cejudo: None. K. Enkhbold: None. Y. Chung: None. S. Chiaino: None. M.R. Norris: None. J. Pollock: None.
Photoactivated Chemotherapy (PACT) represents an opportunity to limit the off-target toxicity inherent to traditional chemotherapies. Selective activation of toxic effects would allow effective chemical treatment of solid tumors without the normally associated side effects. Expanding on previous work in our lab (1), we have evaluated the potential of ruthenium-based compounds as PACT agents by testing light activation, cell viability in breast cancer and lung cancer cells, biocompatibility, and DNA interactions. We have observed that active ruthenium-complexes with increased lipophilicity tend to be more toxic to the cancer cells. In addition, we have ligated known anticancer compounds (2) to our ruthenium cages, evaluated the capacity to mask the general cytotoxic effects, and examined the release of a fully active drug after light exposure. We can successfully release the active drugs with light, but when using light at 450 nm it takes about six hours of direct exposure in a cuvette to see successful conversion. We are currently systematically exploring different wavelengths of light to reduce activation time and increase potential clinical utility (3). Once optimal wavelengths are determined, cancer cell viability experiments will be performed in the absence and presence of light in order to evaluate the therapeutic window for these ruthenium-complexes. References: (1) Paul, L. et. al. J. Inorg. Biochem.2022, 235: 111930. (2) Peerzada, M. N. et. al. Eur. J. Med. Chem.2018, 155: 13-23. (3) Dunkel, P. & Ilaš, J. T. Cancers2021, 13: 40-42.
Presentation: 6/2/2024
12514 Elucidating The Interactions Between IQGAP1-YAP-ECM Stiffness In Liver Cancer
Authors: Hobbs S E , Kimmel H , Underhill G , Anakk S 
Published: October 2024

Abstract
Disclosure: S.E. Hobbs: None. H. Kimmel: None. G. Underhill: None. S. Anakk: None.
Hepatocellular Carcinoma (HCC) is the second leading cause of cancer associated-deaths worldwide. Complex signaling mechanisms and several cellular processes in cancer are coordinated using scaffolding proteins. One such scaffold, IQ motif-containing GTPase Activating Protein 1 (IQGAP1) is associated with metastasis, inflammation and tumor growth. Previous work has shown that overexpression of IQGAP1 activates Yes-associated Protein (YAP) in mice and both proteins are induced in clinical HCC samples. Conversely, we found YAP inhibition, also reduces IQGAP1 levels. Extracellular matrix (ECM) stiffness, due to liver fibrosis in HCC, can activate YAP to promote tumor progression. Our preliminary data show that IQGAP1 protein stains in a punctate manner. The characteristics of this puncta are being investigated currently. Remarkably, we find IQGAP1 protein induction and predominant localization at the plasma membrane when HepG2 cells (an HCC cell line) are grown onto a stiff ECM (25 kPa). But the stiffness did not change the IQGAP1 transcript levels. ECM stiffness led to IQGAP1 induction, and high YAP staining in the nucleus. Intriguingly, we find that IQGAP1 colocalizes with actin, a mediator of biomechanical signals in HepG2 cells. This colocalization with actin is maintained irrespective of the stiffness. When we inhibit the actin polymerization with LatA, we noted increased IQGAP1 protein expression. Based on this data, we speculate that IQGAP1 levels may be regulated by actin dynamics and that IQGAP1-Actin-YAP-Stiffness impact hepatic carcinogenesis.
Presentation: 6/2/2024
8127 HOMA-IR Predicts Muscle Wasting During Androgen Deprivation Therapy
Authors: Caeiro Lucas , Jayne Anderson Lindsey , Liu Haiming , Manuel Garcia Jose 
Published: October 2024

Abstract
Disclosure: L. Caeiro: None. L.J. Anderson: None. H. Liu: None. J.M. Garcia: None.
Androgen deprivation therapy (ADT) is the primary treatment for advanced and metastatic prostate cancer. However, it induces adverse effects like reduced muscle mass and function, increased adiposity, and insulin resistance (IR). While muscle wasting is a known complication of ADT-induced hypogonadism, the extent to which other factors determine the variability in muscle loss remains unknown. In other diseases, IR is associated with muscle wasting, but its role in this setting of ADT has yet to be addressed. We hypothesized that patients with greater IR pre-ADT would display larger decreases of muscle mass and function after six months of ADT. Insulin and glucose (to calculate HOMA-IR), body composition, and physical function were assessed in patients with prostate cancer prior to and after three and six months of ADT. Body composition was assessed by dual x-ray absorptiometry and physical function by VO2 peak and 6-minute walk test (6MWT). Fasting blood samples were obtained to measure insulin and glucose in plasma. Pre-ADT, HOMA-IR was directly correlated with body mass index (BMI) (r=0.65, p&lt;0.001, n=49), fat mass (r=0.55, p&lt;0.001, n=49), and appendicular skeletal muscle index (ASMI) (r=0.33, p=0.021, n=49) and was inversely correlated with VO2 peak (r= -0.39, p=0.007, n=46). After three months, fat mass (p=0.015) and IR (p=0.0014) increased and VO2 peak decreased (p=0.0007), which persisted at the six-month visit. Appendicular lean mass and ASMI decreased after six months (p&lt;0.0001). Pre HOMA-IR was negatively associated with delta BMI (r=-0.49, p&lt;0.001, n=46), delta lean mass (r=-0.58, p&lt;0.001, n=46), delta ASMI (r=-0.52, p&lt;0.001, n=46), and delta 6MWT (r=-0.37, p=0.011, n=45) and positively correlated with delta VO2 peak (r=0.44, p=0.007, n=36). No associations were found with Pre-ADT HOMA-IR and changes in fat mass. In conclusion, those with greater Pre-ADT HOMA-IR lost more muscle mass, body weight, and 6MWT while unexpectedly showing less decrease in VO2 peak. This data suggests that HOMA-IR could potentially serve as a predictor of muscle mass loss in patients undergoing ADT. We propose that the significant decrease in muscle mass seen with ADT can be exacerbated by pre-existing IR.
Presentation: 6/3/2024
6667 IGF1 Induces The Expression of CYR61 In Metastatic Prostate Cancer
Authors: Ortiz Hernández Greisha Lee , Walker Mya , Woods-Burnham Leanne , Kittles Rick A , Casiano Carlos A , Neuhausen Susan L 
Published: October 2024

Abstract
Disclosure: G.L. Ortiz Hernández: 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. CYR61 contains an insulin-like growth factor-binding protein domain suggesting that it may interact with insulin-like growth factor-I (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. The correlation between PCa aggressiveness and circulating levels of CYR61 and IGF1 is poorly studied. Our goal was to assess the contribution of the interaction of CYR61-IGF1 to PCa cell proliferation. Their combined role may explain a proportion of aggressive PCa. This study was designed to characterize the role of IGF1-induced expression of CYR61 in metastatic PCa cellular models and to determine if this interaction contributes to aggressive tumor properties (e.g., proliferation, migration, tumorsphere formation). Using immunoblotting, we demonstrated that CYR61 is upregulated in the metastatic cell line PC3. 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 either the PI3/Akt and MAPK pathways in PC3 cells with CYR61 silencing. CYR61 siRNA-mediated knockdown decreased activation of the PI3/Akt pathway but did not affect the MAPK pathway. In addition, we found that IGF1 induces protein expression of CYR61 in a time-dependent manner, validated by both immunoblotting and confocal microscopy. PC3 cell lines are androgen receptor negative (AR-) and glucocorticoid receptor positive (GR+), which is characteristic of aggressive, advanced metastatic castration-resistant prostate cancer (mCRPC). Currently, we are conducting the same experiments in LNCaP cells, which are AR+/GR-, to determine if the CYR61-IGF1 interplay also occurs in PCa cells capable of AR signaling. In conclusion, we found that CYR61 expression is induced by IGF1 and its inhibition decreased the capacity of metastatic PCa cells to proliferate. Our results suggest that CYR61 inhibition may have the potential for treating metastatic PCa.
Presentation: 6/1/2024
5149 In-Vitro Combo Treatment of Human Liver Cancer Cell (Hep-G2) Line With Vitamin-A And RU-486
Authors: Ramaraj Pandurangan 
Published: October 2024

Abstract
Disclosure: P. Ramaraj: None.
Our previous in-vitro studies involving vitamins (vitamin-A and vitamin-D3) and steroids (progesterone and RU-486) pointed to a combination of vitamin-A and RU-486 as an efficient combo to decrease human melanoma cell growth. We extended this combo treatment to human liver cancer cell (Hep-G2) line. The aim was to check whether vit-A and RU-486 combo would also decrease human liver cancer cell line growth. Liver cancer (Hep-G2) cells were plated in a 96 well plate overnight. Following day, vit-A and RU-486 were added either alone or in different combinations for 48 hrs. After 48 hrs, cell viability and percentage of cell growth were monitored by the MTT assay. Supernatants were collected for Elisarray and quantitation of cytokine(s) by Elisa. Individual vit-A and RU-486 treatments showed a dose-dependent decrease in cell growth. Though various combinations of vit-A (50, 75, 100 μM) and RU-486 (10, 50 100 μM) also showed a decrease in cell growth, an experimentally significant decrease in cell growth was observed at vit-A 75 μM and RU-486 50 μM combination. This combo resulted in 24% cell growth compared to straight vit-A (75 μM) at 44% cell growth and RU-486 (50 μM) at 35% cell growth. Thus, this combo inhibited liver cancer cell growth also. In the future effect of this combo on normal liver cell line and the cytokine(s) if any, playing a central role in cell growth would be identified by Elisarray and quantitated by Elisa.
Presentation: 6/3/2024
8213 A Splicing Modulator Inhibits Proliferation and Steroid Production of H295R Adrenocortical Cancer Cells
Authors: Tanaka T , Ohe K , Yanase T , Kodama S 
Published: October 2024

Abstract
Disclosure: T. Tanaka: None. K. Ohe: None. T. Yanase: None. S. Kodama: None.
Adrenocortical carcinoma (ACC) is a rare cancer, and treatment options are limited. The anti-tumor drug CX-4945 (Silmitasertib) is an inhibitor of Casein kinase 2 (CK2). It also inhibits cdc2-like kinase 2 (CLK2). CLK2 phosphorylates Serine/arginine rich splicing factors (SRSFs)/SR proteins and enhances exonic splicing enhancer (ESE) recognition during the pre-RNA splicing process. Anti-tumor agents targeting RNA splicing have been developed recently, and CLK inhibitors have shown anti-tumor effects against blood cancers. In this study, we analyzed the impact of CX-4945 on NCI-H295R cells. CX-4945 inhibited cell proliferation of H295R (IC50 = 6.4 µM, 72hr), and cortisol and aldosterone secretion in vitro. siRNA-induced CK2 inhibition did not alter H295R proliferation and steroid secretion. CX-4945 (150 mg/kg/day oral, 28 days) significantly reduced tumor weight in mice inoculated with H295R subcutaneously on the back. High-density microarray analysis showed reduced Nuclear receptor 5A1 (NR5A1) expression levels, indicating a possible splicing variant. RT-PCR, using a primer set that amplified the coding region, detected short variants of NR5A that were multiple exon-skipped and were not induced by suppression of CK2. The results of western blotting using an antibody that recognizes phospho-epitope of SRSFs/SR proteins showed that the phosphorylation of SRSF4 was reduced in H295R treated with CX-4945. These results suggest that CX-4945 inhibits CLK2 and decreases phosphorylated SRSF4 and ESE recognition, resulting in NR5A1 multiple exon-skipping. The prognosis of ACC patients with high NR5A1 expression levels is poor, independent of stage. CX-4945 may induce NR5A1 multiple exon-skipping, reduce full-length functional NR5A1, and suppress ACC growth and steroidogenesis, as a possible adjuvant in tackling this devastating cancer.
Presentation: 6/1/2024