bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A093: Investigating alterations in metabolic profile of ovarian carcinoma associated mesenchymal stem cells
Authors: Baruwal Roja , Frisbie Leonard G. , Coffman Lan 
Published: March 2024

Abstract
Ovarian cancer causes more deaths than any other gynecologic cancer. Although aerobic glycolysis has been a hallmark of cancer metabolism, it has been found that ovarian cancer (OvCa) cells are metabolically plastic, also utilizing oxidative phosphorylation (OXPHOS) as an active metabolic pathway for their rapid proliferation and metastasis. A growing body of evidence also shows that cancer cells not only reprogram their own metabolism but also metabolically remodel the tumor microenvironment to meet their ever-increasing energy demand. Our lab has previously demonstrated that OvCa cells epigenetically reprogram their resident tissue mesenchymal stromal/stem cells (MSCs) to develop a cancer-supportive phenotype. These cancer-associated mesenchymal stem cells (CA-MSCs) support OvCa progression through several mechanisms, including enhanced metastasis. Recent work by our lab showed these CA-MSCs enhance metastasis by donating their mitochondria to metabolically vulnerable OvCa cells and increasing OvCa cell OXPHOS. While we have demonstrated the impact of CA-MSC mitochondrial transfer to OvCa cells, what changes are happening in the CA-MSC that allow them to transfer mitochondria to OvCa cells is still unknown. Gene set enrichment analysis performed on RNA sequencing data comparing patient derived CA-MSCs to normal MSCs revealed that OXPHOS is one of the top enriched pathways in CA-MSCs. Furthermore, the cell mito stress test comparing mitochondrial respiratory profile of patient derived normal MSCs and CA-MSCs demonstrated that CA-MSCs have significantly increased mitochondrial respiratory capacity compared to normal MSCs. Uncovering the metabolic profile of ovarian CA-MSCs for the first time, our data demonstrates that ovarian cancer alter the metabolism of the CA-MSC towards OXPHOS. Our current studies are focused on understanding the role of enhanced CA-MSC OXPHOS in mitochondrial transfer to OvCa cells and OvCa metastasis.
Citation Format: Roja Baruwal, Leonard G. Frisbie, Lan Coffman. Investigating alterations in metabolic profile of ovarian carcinoma associated mesenchymal stem cells [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A093.
Abstract A102: ROR2/Wnt5a signaling regulates directional cell migration and early tumor cell invasion in ovarian cancer
Authors: Grither Whitney R. , Baker Breanna , Morikis Vasilios A. , Fuh Katherine C. , Longmore Gregoery D 
Published: March 2024

Abstract
Adhesion to and clearance of the mesothelial monolayer are key events in the early metastatic seeding of ovarian cancer. To identify mediators of ovarian cancer cell adhesion and invasion, we developed and conducted a cellular, high-throughput genetic screen using a human kinome siRNA library. Through this screen, we identified ROR2 as a driver of ovarian cancer adhesion and invasion. ROR2 is a receptor tyrosine kinase that interacts with Wnt5a ligand to activate non-canonical Wnt signaling and has been previously shown to be upregulated in ovarian cancer tissue. However, no prior study has evaluated the mechanistic role of ROR2 in ovarian cancer. Using in vitro adhesion and mesothelial clearance assays, we show that ROR2 promotes ovarian cancer cell adhesion and clearance of the mesothelial monolayer, key early steps in ovarian cancer metastasis. Further, we show that depletion of ROR2 reduces metastatic tumor burden in a syngeneic mouse model of ovarian cancer. Additionally, using a microfluidic device capable of producing stable fluid gradients, we demonstrate that ROR2 expression in ovarian cancer cells serves to drive directed cell migration of tumor cells, preferentially to areas of high Wnt5a ligand. As Wnt5a has been previously shown to be produced and upregulated in the mesothelial cells of the ovarian cancer microenvironment, these findings represent a novel role for ROR2 to promote the homing of ovarian tumor cells to the mesothelial lined metastatic niche by using Wnt5a as a chemotactic cue. These findings support the role of ROR2 as a critical factor contributing to the steps of ovarian cancer metastasis. Therapeutic targeting of the ROR2/Wnt5a signaling axis could provide a means of improving treatment for patients with advanced ovarian cancer.
Citation Format: Whitney R. Grither, Breanna Baker, Vasilios A. Morikis, Katherine C. Fuh, Gregoery D Longmore. ROR2/Wnt5a signaling regulates directional cell migration and early tumor cell invasion in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A102.
Abstract B028: Unraveling the role of matrix metalloproteinase 3 (mmp3) in cisplatin resistance of ovarian cancer
Authors: Rivera-Serrano Mariela , Vivas-Mejía Pablo E. 
Published: March 2024

Abstract
Seventy percent of women with ovarian cancer will develop chemotherapy-resistance to cisplatin. Regardless of the advancements in technology, mortality rates for ovarian cancer have declined only slightly in the last forty years. Therefore, novel and effective second-line therapies for women with ovarian cancer are urgently needed. Previously we showed that Matrix Metalloproteinase 3 (MMP3) expression is upregulated in cisplatin resistant when compared with cisplatin sensitive cells. However, the contribution of MMP3 to cisplatin resistance have not been studied previously. Western blots, ELISAs, and real-time RT-PCR confirmed that the protein and mRNA levels are higher in cisplatin resistant as compared with cisplatin sensitive cells. MMP3 expression levels were also increased by cisplatin treatment of cisplatin resistant cells. Additionally, interrogation of the Kaplan-Meier plotter database showed that ovarian cancer patients with low MMP3 levels live longer than patients with higher MMP3 levels. To understand the impact of targeting MMP3, we employed commercially available chemical inhibitors and small-interference RNA (siRNA) in cell viability, colony formation, invasion, and RNAseq experiments. Notably, MMP3-targeted siRNA significantly reduced cell viability, proliferation, and invasion, particularly when combined with cisplatin treatment. However, the MMP3 chemical inhibitor did not exhibit significant biological effects. RNAseq analysis revealed 415 differentially expressed genes (DEGs) between MMP3-siRNA and negative control (NC)-siRNA groups, as well as 440 DEGs between MMP3-siRNA + cisplatin and NC-siRNA + cisplatin groups. Functional enrichment analysis using Metascape via Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) identified genes associated with potassium and aquaporin mediated transport, clathryn-mediated endocytosis, cell cycle, metabolic processes, cellular response to stress, and extracellular matrix organization. These findings highlight the role of MMP3 upregulation in promoting cisplatin resistance.
Citation Format: Mariela Rivera-Serrano, Pablo E. Vivas-Mejía. Unraveling the role of matrix metalloproteinase 3 (mmp3) in cisplatin resistance of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B028.
Abstract B031: The PLK1 inhibitor Volasertib as a treatment for HSF1 and MYC coamplified ovarian cancer
Authors: O'Malley Matthew , Williams Imade W. , Walker Bobby , Ray Haimanti , Nephew Kenneth P. , Carpenter Richard 
Published: March 2024

Abstract
Ovarian cancer is a disease that afflicts 1 in 78 women. This disease only has a 5-year relative survival rate of 49% due to the fact that the first line chemotherapy for this disease, platinum-based chemotherapy with taxanes, has an 80% recurrence rate. To improve the treatment for this disease, it would be wise to find biomarkers of sensitivity to other drugs. Using publicly available data from The Cancer Genome Project, our lab has shown that 36% of High Grade Serous Ovarian Cancers (HGSOC) have gene amplifications for both Cellular Myelocytomatosis (MYC) and Heat Shock Factor 1 (HSF1) genes. These genes encode for transcription factors and are known to contribute to malignant disease in multiple cancer types, including ovarian cancer. Evidence indicates that MYC and HSF1 are both essential to HGSOC cells with co-amplification of these genes, that MYC and HSF1 transcriptional activities are highly correlated in patient tumors, and the two transcription factors have a protein-protein interaction, all suggesting these two transcription factors cooperate to drive this subset of HGSOC tumors. Many drugs have been developed to inhibit MYC or HSF1 though they have not shown success in clinical development. We aimed to decrease the activity of these proteins by targeting polo-like kinase 1 (PLK1), a kinase that phosphorylates and regulates both MYC and HSF1 proteins. Active PLK1 levels were highly correlated with MYC and HSF1 protein levels and inhibition of PLK1 with volasertib reduced MYC and HSF1 protein levels and transcriptional activity. Furthermore, volasertib was found to have 155-fold greater potency in HGSOC cells with MYC-HSF1 co-amplification compared to cells without these genes amplified. The increased potency of volasertib in MYC-HSF1 co-amplified cells were also observed in clonogenic growth and spheroid models. Together, these data indicate that MYC and HSF1 cooperate in HGSOC when these genes are amplified and targeting a common kinase between them in PLK1 disrupts this cooperation. Furthermore, MYC and HSF1 co-amplification may serve as a biomarker for volasertib through a personalized medicine approach to treat HGSOC patients.
Citation Format: Matthew O'Malley, Imade W. Williams, Bobby Walker, Haimanti Ray, Kenneth P. Nephew, Richard Carpenter. The PLK1 inhibitor Volasertib as a treatment for HSF1 and MYC coamplified ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B031.
Abstract B042: Feasibility of an electronic medical records based ovarian cancer symptom screening patient questionnaire
Authors: Behbakht Kian , Nguyen Cam , Rotholz Stephen , Guntupalli Saketh , Goff Barbara , Bitler Benjamin 
Published: March 2024

Abstract
Objectives: Symptoms occur in 75% of women with early-stage ovarian cancer and are also common in the absence of cancer. We report the feasibility and results of a prospective four-question symptom screen applied to a gynecology preventive care visit. Methods: Starting February 2021, a patient-facing questionnaire was added to the electronic medical records for women requesting routine gynecology visit. The question asks patients if they have had any of the following symptoms for more than two weeks duration in the prior year: bloating, difficulty eating or feeling full soon after eating, pelvic or abdominal pain, or trouble with urination. In September 2021, the response “No symptoms” was added. Questionnaire responses, medical history and work up performed +/- 3 months of the preventive gynecologic visit were extracted from electronic medical records, compiled in REDCap, and analyzed using R. Results: Between February 2021 and November 2022, a total of 498 patients completed the questionnaire (72.7% White, 10.2% Black, 7.0% Asian/Pacific Islander, 9.8% Other, and 0.2% not stated). The median age was 50 years (range: 40-86). Nearly half (47.2%) reported at least one symptom. The most common isolated single symptom was urinary urgency or frequency (22.9%); 12.3% of these patients had a urinary tract infection. The least common single symptom was early satiety (8.8%). 12 patients (2.4%) reported all four symptoms, and most had explanatory existing diagnoses such as endometriosis, adenomyosis or chronic pelvic pain. No cancers have been diagnosed to date. Conclusions: Ovarian cancer symptom-based screening using electronic medical records is feasible, but alone may not be clinically beneficial. Patients reporting three or more symptoms were 6.6% of the respondents and may represent an ideal group for focused ovarian cancer screening efforts and selective enrolment to novel imaging/tumor marker and proximate fluid analyses.
Citation Format: Kian Behbakht, Cam Nguyen, Stephen Rotholz, Saketh Guntupalli, Barbara Goff, Benjamin Bitler. Feasibility of an electronic medical records based ovarian cancer symptom screening patient questionnaire [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B042.
Abstract B043: Feasibility of a traceback approach to facilitate genetic testing in the Genetic Risk Analysis in Ovarian Cancer (GRACE) study
Authors: White Larissa L. , Prado Yolanda K. , Reyes Ana A. , Zepp Jamilyn M. , Sawyer Jennifer , Maiyani Mahesh , Zucker Rachel , Vertrees Sarah , Rope Alan F. , Weinmann Sheila , Caruncho Mika , Lee Sandra Soo-Jin , Henrikson Nora B. , Feigelson Heather Spencer , Hunter Jessica Ezzell 
Published: March 2024

Abstract
Current guidelines state that genetic testing is clinically indicated for all individuals diagnosed with ovarian cancer (OC). Individuals with a prior diagnosis of OC who have not received genetic testing represent missed opportunities to identify individuals and their families with inherited variants that put them at a higher risk for cancer. The Genetic Risk Analysis in Ovarian Cancer (GRACE) study aims to address this significant healthcare gap using a “traceback testing” approach to identify individuals with a prior diagnosis of OC and to offer genetic risk information to them and their family members. Tumor registry data at two integrated health care systems (Kaiser Permanente Northwest and Colorado) identified cases of OC diagnosed 1998-2020 with no prior genetic testing or testing limited to BRCA1/2. The study aimed to provide genetic risk information to OC survivors as well as family members of patients who were deceased by leveraging stored pathology specimens for germline testing. Comprehensive genetic testing using a panel of 60 cancer risk genes was offered; genetic testing of the familial variant was offered to first- and second-degree relatives if a pathogenic or likely pathogenic variant was detected. A total of 317 eligible OC survivors were identified from tumor registry and medical record review; 79 (25%) consented for testing. Sixteen (21%) were found to carry a pathogenic or likely pathogenic variant in a cancer risk gene. Genes with pathogenic variants included BRCA1/2, BARD1, PMS2, DICER1, MUTYH, APC, and SDHB. Of 73 relatives eligible for cascade testing, 24 consented (≈ 33% uptake) and 9 were found to carry the familial variant. The uptake of testing by OC survivors and their relatives reflects a strong interest in genetic risk information. However, practical barriers must be addressed to provide genetic risk information to relatives of individuals who are deceased. The GRACE study can inform broad implementation of future traceback programs, providing information to prevent and mitigate the burden of ovarian and other hereditary cancers.
Citation Format: Larissa L. White, Yolanda K. Prado, Ana A. Reyes, Jamilyn M. Zepp, Jennifer Sawyer, Mahesh Maiyani, Rachel Zucker, Sarah Vertrees, Alan F. Rope, Sheila Weinmann, Mika Caruncho, Sandra Soo-Jin Lee, Nora B. Henrikson, Heather Spencer Feigelson, Jessica Ezzell Hunter. Feasibility of a traceback approach to facilitate genetic testing in the Genetic Risk Analysis in Ovarian Cancer (GRACE) study [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B043.
Abstract B056: The unconfounded effect of bevacizumab on advanced ovarian clear cell carcinoma: a systematic review, traditional meta-analysis, and network meta-analysis
Authors: Huang Fisher Kuan-Ju 
Published: March 2024

Abstract
Background Ovarian clear cell carcinoma (OCCC) accounts for 5-20% of all epithelail ovarian cancers, and is associated high recurrence rate and chemoresistance. There are some new therapies available in recent years, including bevacizumab, an anti-VEGF monoclonal antibody, and the poly ADP-ribose polymerase (PARP) inhibitors. Previous research and current support the use of both medication in OCCC. However, most of the studies reported results for all subtypes collectively in which OCCC only accounted for a small proportion of the study cohort. Besides, dislike the high-grade serous subtype, only around 10% of OCCC respond to poly ADP-ribose polymerase (PARP) inhibitor. In the subgroup analysis from ICON7, Bevacizumab had limited role in OCCC patients, in which OCCC of any stage were included. On the other hand, another 2 multi-center studies evaluated Bevacizumab as the front-line or salvage therapy revealed positive results. However, the results could be biased due to unadjusted confounders. Objective: To find the real effect of Bevacizumab on advanced stage OCCC. Materials and Methods: A systematic review via searching the Pubmed with "ovarian clear cell carcinoma" and "bevacizumab" was performed. Any comparative study met the inclusion criteria. The data were extracted, evaluated and classified by their combination of potential confounders. Primary data from National Taiwan University Hospital (NTUH) Database were collected and incorporated into the traditional meta-analysis, and the network meta-analysis. The potential confounders for analysis include "residual tumor", "FIGO stage", and "functional status". Results: There were 3 retrospective studies, including one single-center study from Japan (N=28), one multi-center study from Japan (N=145), and one multi-center study from Korea (N=138). There were 64 patients identified from NTUH database between 2011 and 2020. By traditional meta-analysis, it revealed Bevacizumab is associated with improved progression-free survival (HR 0.62, 95% C.I. 0.44 - 0.87, common effect model, I2= 50%). After adjusted for confonders and analyzed by network meta-analysis, however, only "no residual tumor" is associated with improved progression-free survival (HR 0.37, 95% C.I. 0.14 - 0.97). The role of Bevacizumab on OCCC is limited (HR 1.20, 95% C.I. 0.51 - 2.83). Conclusion: By adjusting for possible confounders in published studies, it reveals that Bevacizumab may not improve progression-free survival in advanced-stage OCCC from a network meta-analysis.
Citation Format: Fisher Kuan-Ju Huang. The unconfounded effect of bevacizumab on advanced ovarian clear cell carcinoma: a systematic review, traditional meta-analysis, and network meta-analysis [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B056.
Abstract B089: Intratumoral expression analysis of mast cells in high grade serous ovarian cancer
Authors: McAdams Julia , Ebott Jasmine , De La Cruz Payton , James Nicole E. 
Published: March 2024

Abstract
Objective: The goal of this study is to examine intratumoral expression and phenotypic changes in mast cells following neoadjuvant chemotherapy (NACT) exposure in high grade serous ovarian cancer (HGSOC). Methods: 37 HGSOC matched pre-and post-NACT patient tumors were stained with a commercially available mast cell hemotoxic-based kit and both intratumoral and stromal mast cells were quantified. Immunohistochemistry was employed to stain for histamine in 19 matched HGSOC patient tumors and mean intensity and integrated optical density was quantified using Image J. Kaplan Meier curve analysis was employed to determine the relationship between mast cells levels and progression-free survival (PFS). Immortalized human mast cells, LUVA were treated with carboplatin and paclitaxel and specific genomic changes were measured by quantitative PCR (qPCR). Results. Mast cells were more prominently expressed in intraepithelial regions compared to stromal cells, however both populations were significantly (p&lt;0.05) increased following NACT. Total mast cells stratified by upper and lower quartile demonstrated that higher levels were significantly (p&lt;0.05) associated with improved PFS. Furthermore, histamine, a marker of mast cell degranulation was significantly (p&lt;0.05) increased in HGSOC tumors post-NACT and significantly correlated (r=0.553, p=0.013) with the change in total mast cells. Following chemotherapy treatment LUVA cells demonstrated an over 7-fold increase in amphiregulin (AREG) expression (p&lt;0.01), a key marker of mast cell activation. Interestingly, angiogenic and pro-tumorigenic factors IL-10, IL-8, and VEGFA exhibited no significant differences in expression following chemotherapy exposure. Conclusions: Overall, our findings suggest a correlation in NACT exposure and intratumoral mast cell recruitment, degranulation, and activation. Further studies include investigating differences in specific tumorigenic genes and cell signaling pathways in mast cells pre- and post- NACT, as well as determining if mast cells can impact HGSOC chemotherapy response.
Citation Format: Julia McAdams, Jasmine Ebott, Payton De La Cruz, Nicole E. James. Intratumoral expression analysis of mast cells in high grade serous ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B089.