bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A047: Modeling the role of the fallopian tube in the prevention and spread of high grade serous cancer using a multi-organ platform
Authors: Burdette Joanna 
Published: March 2024

Abstract
It is now recognized that a large percentage of high grade serous ovarian cancers arise in the fallopian tube and colonize the ovary as the primary metastatic step. One of the risk factors associated with ovarian cancer is the lifetime number of ovulations. Few models are currently available that allow the process of ovulation and the development of ovarian cancer to be studied. To address this gap, our team developed a microphysiological platform called PREDICT-multi-organ-system (MOS). PREDICT-MOS contains 30 wells for culturing organs and 60 pumps with precisely controlled flow rates. Human fallopian tube tissue can be grown in an air-liquid interface, while murine ovaries can be engineered to ovulate while producing and secreting physiological concentrations of hormones and proteins over the entire process of ovulation. Importantly, these secreted factors are contained in the device within the media and can therefore precisely model local concentration gradients and temporal exposure of the human fallopian tube tissues. First, we uncovered that the ovary secretes versican during the cycle to enhance ovarian migration, adhesion, and expansion within the ovarian microenvironment. We revealed that fallopian tube tumor cells stimulate the ovary to produce testosterone, which enhanced fallopian tube invasion and stem cell marker expression. Next, we profiled the expression of secreted extracellular vesicles that are produced by the fallopian tube on the platform. Extracellular vesicles may provide a new form of liquid biopsy, but understanding the cargo expressed from normal cells is critical for understanding the importance of cancer EV’s during progression. Finally, we have engineered the platform to allow for real-time invasion using an insert technology and a modified pump that allows for interaction between the organs. Overall, the integration of organ-on-chip technology with key human tissues allows for the in-depth analysis of the role of ovulation in the onset and spread of high-grade serous cancer from the fallopian tube.
Citation Format: Joanna Burdette. Modeling the role of the fallopian tube in the prevention and spread of high grade serous cancer using a multi-organ platform [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 A047.
Abstract B032: Probing the molecular crosstalk between ovarian cancer and omentum
Authors: Haughan Monica A. , Lusk Hannah , Bergsten Tova M. , Levy Sarah E. , Klingelhutz Aloysius J. , Sanchez Laura M. , Burdette Joanna E. 
Published: March 2024

Abstract
Ovarian cancer (OC) is the 5th leading cause of cancer death in women despite being considered rare, highlighting the critical need to better understand the mechanisms of pathogenesis and progression. High grade serous OC, the most prevalent OC subtype, frequently metastasizes to the omentum. Building off previous work using an imaging mass spectrometry (IMS) co-culture system to uncover metabolomic changes in primary metastasis, we are now probing the molecular crosstalk between the omentum and OC cells. Our IMS co-culture system identifies molecules produced in co-culture of tumorigenic MOE PTENshRNA or vector control MOE PTENSCR cells and explants. IMS revealed multiple signals, including epinephrine (EPI), unique to the MOE PTENshRNA + omentum condition. Clinical data shows stress and increased expression of ADRβ2, an EPI receptor, are correlated with poorer survival. However, no significant changes were observed in EPI (10mM) treated MOE PTENshRNA invasiveness investigated via Boyden chamber assay. EPI signaling through ADRβ2 can induce lipolysis and propranolol treatment, antagonizing ADRβ2, has shown partial deactivation of OC stimulated lipolysis. We hypothesize EPI may be an autocrine signal produced by the omentum liberating fatty acids and driving tumor progression. To test this, we began examining an immortalized, human pre-adipocyte line (VNPAD 30315) for mechanistic studies. VNPAD 30315 can be differentiated into adipocytes and forms spheroids more accurately simulating in vivo fatty tissues compared to 2D culture. Successfully differentiated spheroids have been generated and spheroid conditioned media (CM) increases invasion like omentum CM. Preliminary results suggest spheroids produce results similar to murine and human omentum explants in IMS co-culture. Currently we are exploring the effects of EPI on the spheroids and adipocyte CM on tumorigenic models. Overall, we are working to identify signals in omental metastasis with our IMS co-culture system and to determine their mechanisms in vitro with a 3D adipocyte model.
Citation Format: Monica A. Haughan, Hannah Lusk, Tova M. Bergsten, Sarah E. Levy, Aloysius J. Klingelhutz, Laura M. Sanchez, Joanna E. Burdette. Probing the molecular crosstalk between ovarian cancer and omentum [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 B032.
Abstract B055: Identifying compounds to promote apoptotic cell death in clear cell ovarian cancer
Authors: Shay Brendan , Handly-Santana Abram , Qin Xingping , Choniere Jonathan , Sarosiek Kristopher , Brugge Joan S. , Stover Elizabeth H. 
Published: March 2024

Abstract
Clear cell ovarian cancer is a rare subtype of ovarian cancer with a poor prognosis in advanced-stage disease and increased resistance to standard-of-care treatments including platinum chemotherapy. Previously, we found that multiple clear cell ovarian cancer cell lines are sensitive to inhibition of BCL-XL, a pro-survival member of the BCL-2 family of proteins that control mitochondrial apoptosis. Adding a BCL-XL inhibitor also enhances cell death in clear cell ovarian cancer cell lines treated with standard-of-care drugs including cisplatin, paclitaxel, and poly(ADP-ribose) polymerase (PARP) inhibitor olaparib. To more broadly identify compounds that affect the viability of clear cell ovarian cancer cell lines, either alone or in combination with BCL-XL inhibition, we applied a chemical screening approach. We designed an anchor screen strategy in which a chemical library of clinically relevant compounds (Selleck bioactive compound library; 1,902 compounds) was screened against clear cell ovarian cancer cell lines in two sets: library compounds only, or library compounds combined with BCL-XL inhibitor A1331852 at a fixed concentration (IC25 for each cell line). Fold-change in cell number compared to controls and Z-scores were calculated to identify compounds with single-agent activity in clear cell ovarian cancer and/or with enhanced activity in the presence of A1331852. Initial screening data from JHOC5 and OVISE cell lines identified compounds with targets such as SYK and other tyrosine kinases, PI3K/AKT, and BCL2, as well as chemotherapies, which demonstrated increased activity in the presence of BCL-XL inhibition. Screening of additional cell lines and validation of candidate hits is ongoing to identify agents that are active alone or in combination with BCL-XL inhibition against clear cell ovarian cancer.
Citation Format: Brendan Shay, Abram Handly-Santana, Xingping Qin, Jonathan Choniere, Kristopher Sarosiek, Joan S. Brugge, Elizabeth H. Stover. Identifying compounds to promote apoptotic cell death in clear cell 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 B055.
Abstract B076: Targeting cancer glycomes sensitizes ovarian tumors to immunotherapy
Authors: Nie Hao , Saini Pratima , Liu Heng , Zhou Wei , Wang Chen , Claiborne Daniel , Zhang Nan , Abdel-Mohsen Mohamed , Zhang Rugang 
Published: March 2024

Abstract
Aberrant glycans on tumor cell surface contribute to immune escape. The purpose of this study is to establish novel immunotherapeutic strategies for HGSOC tumors by targeting glycans-mediated immune escape in high-grade serous ovarian cancer (HGSOC). Here, we performed in vivo screens targeting 96 glycan structures among a series of mouse HGSOC tumors with different genotypes. We identified β1, 6-GlcNAc branched N-glycan as a major determinant of immune escape in a homologous recombination (HR)-proficiency dependent manner in HGSOCs. Mechanistically, BRCA1/2 transcriptionally suppresses the expression of MGAT5 that produces β1, 6-GlcNAc branched glycans. Using in vitro T cell killing assay, we observed that removal of β1, 6-GlcNAc branched glycans by a small molecule inhibitor or genetically knocking down MGAT5, sensitizes HR-proficient human HGSOC cells to T cells assault. Consistently, using orthotopic syngeneic mouse models, we observed that inhibition of β1, 6-GlcNAc branched glycans sensitizes and synergizes with anti-PD-L1 in HR-proficient, but not HR-deficient HGSOCs. In summary, we identified β1, 6-GlcNAc branched N-glycan as a key mediator of immune escape in HR-proficient HGSOCs. Our findings indicate that MGAT5 represents a therapeutic target to overcome immune escape in a HR-status dependent manner and inhibition of β1, 6-GlcNAc branched glycans sensitizes HR-proficient HGSOCs to immune checkpoint blockades.
Citation Format: Hao Nie, Pratima Saini, Heng Liu, Wei Zhou, Chen Wang, Daniel Claiborne, Nan Zhang, Mohamed Abdel-Mohsen, Rugang Zhang. Targeting cancer glycomes sensitizes ovarian tumors to immunotherapy [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 B076.
Abstract IA007: Tumor heterogeneity in ovarian clear cell carcinoma
Authors: Huang Ruby Yun-Ju 
Published: March 2024

Abstract
Ovarian clear cell carcinoma (OCCC) is a gynecologic cancer showing high incidence in East Asia with critical unmet needs for novel therapeutic options. It is a histological subtype with distinct pathological features, molecular profiles, and biological functions. At the bulk transcriptomic level, there are distinct epithelial (EpiCC) and mesenchymal (MesCC) subtypes and immune-related gene expression signatures (irGES) in OCCC tumors. The MesCC subtype or Immune-Hot features are shown to associate with worse clinical outcomes across several cohort studies. During disease progression from early to advanced OCCC, there is a switch from EpiCC to MesCC subtypes and Immune-Cold to Immune-Hot features. Therefore, the landscapes of tumor heterogeneity in early versus advanced OCCC are different. Bulk and spatial profiling revealed that most early OCCC tumors exhibited Immune-Cold features associated with a non-CTLA4 irGES subtype, no tumor infiltrating immune cells (TIIs), and non-immune mimic tumor cells. A subset of early OCCC tumors acquired Immune-Hot features that were associated with a CTLA4 irGES subtype, and TIIs situated adjacent to immune mimic tumor cells. Two translational studies TGOG-4001 and TGOG-4002 have been launched to validate clinical assays for the stratification of Immune-Hot tumors. In advanced OCCC, certain metastatic sites showed high degrees of heterogeneity in spatial transcriptomics with subregions close to the tumor periphery or invasion fronts at the tumor-stromal interface showing inflammatory and EMT-like signals. The primary sites with subregions situated at the tumor core predominantly showed oxidative phosphorylation and low EMT signals. Collectively, OCCC is an ovarian cancer with immense degree of tumor heterogeneity. Comprehensive and in-depth multi-dimensional analysis could facilitate the design of better patient stratification strategies.
Citation Format: Ruby Yun-Ju Huang. Tumor heterogeneity in ovarian clear cell carcinoma [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 IA007.
Abstract IA021: Mutational processes as determinants of immune evasion in ovarian cancer
Authors: Shah Sohrab P. 
Published: March 2024

Abstract
High-grade serous ovarian cancer (HGSOC) is an archetypal cancer of genomic instability patterned by distinct mutational processes, tumor heterogeneity and intraperitoneal spread. Immunotherapies have had limited efficacy in HGSOC, highlighting an unmet need to assess how mutational processes and the anatomical sites of tumor foci determine the immunological states of the tumor microenvironment. Here we carried out an integrative analysis of whole-genome sequencing, single-cell RNA sequencing, digital histopathology and multiplexed immunofluorescence of 160 tumor sites from 42 treatment-naive patients with HGSOC. Homologous recombination-deficient HRD-Dup (BRCA1 mutant-like) and HRD-Del (BRCA2 mutant-like) tumors harbored inflammatory signaling and ongoing immunoediting, reflected in loss of HLA diversity and tumor infiltration with highly differentiated dysfunctional CD8+ T cells. By contrast, foldback-inversion-bearing tumors exhibited elevated immunosuppressive TGFβ signaling and immune exclusion, with predominantly naive/stem-like and memory T cells. Phenotypic state associations were specific to anatomical sites, highlighting compositional, topological and functional differences between adnexal tumors and distal peritoneal foci. Our findings implicate anatomical sites and mutational processes as determinants of evolutionary phenotypic divergence and immune resistance mechanisms in HGSOC. Our study provides a multi-omic cellular phenotype data substrate from which to develop and interpret future personalized immunotherapeutic approaches and early detection research.
Citation Format: Sohrab P. Shah. Mutational processes as determinants of immune evasion 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 IA021.
Torsemide Versus Furosemide After Discharge in Patients Hospitalized With Heart Failure Across the Spectrum of Ejection Fraction: Findings From TRANSFORM-HF
Authors: Kapelios Chris J. , Greene Stephen J. , Mentz Robert J. , Ikeaba Uchechukwu , Wojdyla Daniel , Anstrom Kevin J. , Eisenstein Eric L. , Pitt Bertram , Velazquez Eric J. , Fang James C. ,   TRANSFORM-HF Investigators
Published: March 2024

BACKGROUND:
The TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) found no significant difference in all-cause mortality or hospitalization among patients randomized to a strategy of torsemide versus furosemide following a heart failure (HF) hospitalization. However, outcomes and responses to some therapies differ by left ventricular ejection fraction (LVEF). Thus, we sought to explore the effect of torsemide versus furosemide by baseline LVEF and to assess outcomes across LVEF groups.

METHODS:
We compared baseline patient characteristics and randomized treatment effects for various end points in TRANSFORM-HF stratified by LVEF: HF with reduced LVEF, ≤40% versus HF with mildly reduced LVEF, 41% to 49% versus HF with preserved LVEF, ≥50%. We also evaluated associations between LVEF and clinical outcomes. Study end points were all-cause mortality or hospitalization at 30 days and 12 months, total hospitalizations at 12 months, and change from baseline in Kansas City Cardiomyopathy Questionnaire clinical summary score.

RESULTS:

Overall, 2635 patients (median 64 years, 36% female, 34% Black) had LVEF data. Compared with HF with reduced LVEF, patients with HF with mildly reduced LVEF and HF with preserved LVEF had a higher prevalence of comorbidities. After adjusting for covariates, there was no significant difference in risk of clinical outcomes across the LVEF groups (adjusted hazard ratio for 12-month all-cause mortality, 0.91 [95% CI, 0.59–1.39] for HF with mildly reduced LVEF versus HF with reduced LVEF and 0.91 [95% CI, 0.70–1.17] for HF with preserved LVEF versus HF with reduced LVEF;
P
=0.73). In addition, there was no significant difference between torsemide and furosemide (1) for mortality and hospitalization outcomes, irrespective of LVEF group and (2) in changes in Kansas City Cardiomyopathy Questionnaire clinical summary score in any LVEF subgroup.

CONCLUSIONS:
Despite baseline demographic and clinical differences between LVEF cohorts in TRANSFORM-HF, there were no significant differences in the clinical end points with torsemide versus furosemide across the LVEF spectrum. There was a substantial risk for all-cause mortality and subsequent hospitalization independent of baseline LVEF.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03296813.
Optimising the sensitivity of optically-pumped magnetometer magnetoencephalography to gamma band electrophysiological activity
Authors: Hill Ryan M. , Schofield Holly , Boto Elena , Rier Lukas , Osborne James , Doyle Cody , Worcester Frank , Hayward Tyler , Holmes Niall , Bowtell Richard , Shah Vishal , Brookes Matthew J. 
Published: March 2024

Abstract
The measurement of electrophysiology is of critical importance to our understanding of brain function. However, current non-invasive measurements—electroencephalography (EEG) and magnetoencephalography (MEG)—have limited sensitivity, particularly compared to invasive recordings. Optically-Pumped Magnetometers (OPMs) are a new type of magnetic field sensor which ostensibly promise MEG systems with higher sensitivity; however, the noise floor of current OPMs remains high compared to cryogenic instrumentation and this limits the achievable signal-to-noise ratio of OPM-MEG recordings. Here, we investigate how sensor array design affects sensitivity, and whether judicious sensor placement could compensate for the higher noise floor. Through theoretical analyses, simulations, and experiments, we use a beamformer framework to show that increasing the total signal measured by an OPM array—either by increasing the number of sensors and channels, or by optimising the placement of those sensors—affords a linearly proportional increase in signal-to-noise ratio (SNR) following beamformer reconstruction. Our experimental measurements confirm this finding, showing that by changing sensor locations in a 90-channel array, we could increase the SNR of visual gamma oscillations from 4.8 to 10.5. Using a 180-channel optimised OPM-array, we capture broadband gamma oscillations induced by a naturalistic visual paradigm, with an SNR of 3; a value that compares favourably to similar measures made using conventional MEG. Our findings show how an OPM-MEG array can be optimised to measure brain electrophysiology with the highest possible sensitivity. This is important for the design of future OPM-based instrumentation.
TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells
Authors: Song Hee Ju , Kim Young Hwan , Choi Han Na , Kim Taehee , Kim Soo Jin , Kang Min Woong , Lee Sang Do 
Published: March 2024

Abstract
Background
Macrophages promote angiogenesis, metastasis, and drug resistance in several cancers. Similarly, TonEBP/NFAT5 induces metastasis in renal carcinoma and colon cancer cells. However, the role of this transcription factor and that of macrophages in lung cancer cells remains unclear. Therefore, this study investigated the effects of macrophages and TonEBP/NFAT5 expression on cisplatin resistance and migration in A549 lung adenocarcinoma cells.

Results
A549 cells were cultured alone or indirectly co-cultured with THP-1-derived macrophages using a transwell culture chamber. Cisplatin-induced cell death was markedly decreased and migration increased in co-cultured A549 cells. Macrophage-conditioned media (CM) showed a similar effect on drug resistance and migration. Cisplatin-induced apoptosis, DNA fragmentation, and cleaved apoptotic proteins PARP and caspase-3 were markedly reduced in macrophage CM-induced A549 cells. Here, ERK, p38, JNK, and NF-κB activities were increased by macrophage CM. Furthermore, the proteins involved in cisplatin resistance and cancer cell migration were identified using specific inhibitors of each protein. ERK and NF-κB inhibition considerably reduced cisplatin resistance. The increase in macrophage CM-induced migration was partially reduced by treatment with ERK, JNK, and NF-κB inhibitors. TonEBP/NFAT5 expression was increased by macrophages, resulting in increased cisplatin resistance, cell migration, and invasion. Moreover, RNAi-mediated knockdown of TonEBP/NFAT5 reduced cisplatin resistance, migration, and invasion in macrophage CM-induced A549 cells.

Conclusions
These findings demonstrate that paracrine factors secreted from macrophages can change A549 cells, resulting in the induction of drug resistance against cisplatin and migration. In addition, the TonEBP/NFAT5 ratio, increased by macrophages, is an important regulator of the malignant transformation of cells.
Genome-wide identification, expression profiling, and protein interaction analysis of the CCoAOMT gene family in the tea plant (Camellia sinensis)
Authors: Wang Yiqing , Wang Tao , Qi Siyu , Zhao Jiamin , Kong Jiumei , Xue Zhihui , Sun Weijiang , Zeng Wen 
Published: March 2024

Abstract
Background
The caffeoyl-CoA-O methyltransferase (CCoAOMT) family plays a crucial role in the oxidative methylation of phenolic substances and is involved in various plant processes, including growth, development, and stress response. However, there is a limited understanding of the interactions among CCoAOMT protein members in tea plants.

Results
In this study, we identified 10 members of the CsCCoAOMT family in the genome of Camellia sinensis (cultivar ‘HuangDan’), characterized by conserved gene structures and motifs. These CsCCoAOMT members were located on six different chromosomes (1, 2, 3, 4, 6, and 14). Based on phylogenetic analysis, CsCCoAOMT can be divided into two groups: I and II. Notably, the CsCCoAOMT members of group Ia are likely to be candidate genes involved in lignin biosynthesis. Moreover, through the yeast two-hybrid (Y2H) assay, we established protein interaction networks for the CsCCoAOMT family, revealing 9 pairs of members with interaction relationships.

Conclusions
We identified the CCoAOMT gene family in Camellia sinensis and conducted a comprehensive analysis of their classifications, phylogenetic and synteny relationships, gene structures, protein interactions, tissue-specific expression patterns, and responses to various stresses. Our findings shed light on the evolution and composition of CsCCoAOMT. Notably, the observed interaction among CCoAOMT proteins suggests the potential formation of the O-methyltransferase (OMT) complex during the methylation modification process, expanding our understanding of the functional roles of this gene family in diverse biological processes.