bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4712: GPCR panel establishment and application in drug discovery
Authors: Wang Xiaoyan , Sui Ning , Hu Dandan , Zhang Ziwei , Bing Tiejun 
Published: March 2024

Abstract
G protein-coupled receptors (GPCRS) are the largest family of membrane proteins of cell surface receptors. It can be activated by various stimuli and play an important role in various physiological and pathological processes such as cell growth, proliferation, differentiation, metabolism, and homeostasis. Abnormal regulation of GPCR is associated with various human diseases, such as metabolic diseases, cardiovascular diseases, and eye diseases. G protein contains three subunits: α, β, and γ, which form a trimer. When extracellular ligands are bound to GPCRs which activate G protein and GTP phosphorylates Gα subunits, leading to the dissociation of Gα subunits from the trimer and dissociation from the β and γ subunits. In addition, Gα different subtypes of Gαs, Gαi and Gαq have different biological effects after activation, Gas-coupled receptors activate adenylyl cyclase (AC) to increase cAMP. In contrast, Gαi-coupled receptors activated adenylyl cyclase (AC) to inhibit cAMP. Gαq coupled receptors promote phospholipase C (PLC) to produce IP3, and IP3 can increase intracellular Ca2+ concentration. GPCR Panel With high general availability, which provides over 150 GPCR targets, covering wide families like 5-Hydroxytryptamine, adrenoceptors, Acetylcholine, dopamine, glucagon, and opioid receptors and having the selectivity of multiple species. It can conduct similar GPCR poly-link interaction and screening, used to study new GPCR drug development technology, detect the expression properties of GPCR receptors, reveal new GPCR structure and function, and screen GPCR drugs. We also constructed different assay platforms, including cAMP assay, Ca2+ flux assay, IP3 assay, β-arrestin recruitment assay and reporter assay to detect the different second messengers produced by G protein submits and GPCR-mediated multiple signaling pathways. This research constructed stable cell lines expressing GPCRs and provided related assays, which could be used to detect compounds' effects on GPCR targets successfully. In addition, the GPCR panel was applicable to both activating and inhibitory models, and the establishment of this platform provides a powerful tool for drug development of GPCR-related targets.
Citation Format: Xiaoyan Wang, Ning Sui, Dandan Hu, Ziwei Zhang, Tiejun Bing. GPCR panel establishment and application in drug discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4712.
Abstract 4721: Cell death induction via CB2 receptor and TRPV receptor in cannabichromene (CBC) treated human pancreatic cancer cells
Authors: Hwang Yu-Na , Kim Keun-Cheol 
Published: March 2024

Abstract
Cannabichromene (CBC: C21H3O2, M.W.: 314.46g) is one of the most abundant nonpsychotropic phytocannabinoids extracted from Hemp species (Cannabis sativa), and can extract using either a hexane/florisil extraction method. Phytocannabinoids contain Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC), and other compounds. CBC can cause strong anti-inflammatory effects in animal models of edema through non-CB receptor mechanisms, but there is little pharmacological study in cancer disease models. In this study, we investigated the molecular mechanism on anti-cancer activity of CBC treatment in human pancreatic cancer cells. MTT assay was performed to determine concentrations for inducing pharmacological effects of CBC in human pancreatic cancer cells. FACS and Annexin V/PI staining analysis showed the increase dead cells by CBC treatment, and Western blot analysis also showed the changes in expression of cell death related proteins by CBC. Moreover, CBC treatment increased expression of CB2 receptor and TRPV receptor, but the anti-cancer effect was restored by double inhibition with SR144528 for CB2 receptor and capsazepine for TRPV receptor, respectively. mRNA-seq analysis showed that 1206 genes were upregulated and 1145 genes were down-regulated by CBC treatment, indicating that some of ferroptosis related genes (HMOX1, CHAC1, GPX4 and NFE2L2) were regulated by CBC treatment. qPCR analysis showed that those genes are increased by CBC treatment in time dependent manner. It was also confirmed that HMOX1 protein expression was increased using Western blot analysis. Therefore, we suggest that CBC induces multiple cell death mechanism including ferroptosis via CB2 receptor and TRPV receptor in human pancreatic cancer cells.
Citation Format: Yu-Na Hwang, Keun-Cheol Kim. Cell death induction via CB2 receptor and TRPV receptor in cannabichromene (CBC) treated human pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4721.
Abstract 4725: Phenotypic single-cell analysis of nuclear stress responses in drug-treated prostate cancer cells
Authors: Batnasan Enkhzaya , Kärkkäinen Minttu , Koivukoski Sonja , Ruusuvuori Pekka , Latonen Leena 
Published: March 2024

Abstract
Chemotherapy with anti-cancer drugs aims to stop the growth of cancer cells either by killing them or by stopping them from dividing. The different specificities in inducing cellular damage responses are incompletely understood currently and may underlie the preferential effectiveness of anti-cancer drugs against different types of cancer cells. Better understanding and tools to measure drug-induced phenotypes in vitro may aid in assessing cellular heterogeneity of responses, determining potential effectiveness, estimating amount and types of adverse effects, and predicting likelihood of surviving populations for residual disease. To measure the types and extent of nuclear stress responses to cancer drugs, we studied nuclear organelle, namely nucleolar and Cajal body, phenotypes to drug-induced stress in prostate cancer cells. We utilized organelle-specific markers NPM, Fibrillarin, Coilin, and SMN1 in immunofluorescence staining to determine suitable markers for nuclear organelle stress. We used three different prostate cancer cells lines representing different biological types of advanced prostate cancer (AR positive, AR negative, and expressing AR transcript variant). Based on initial assessments, NPM and coilin immunostaining were selected for automated phenotypic analysis screening for drug effects. Using AI-assisted nuclear segmentation and feature-based single-cell phenotypic analysis, we demonstrated quantitative effects on nuclear morphology, nucleoli, and Cajal bodies with drug treatments. A proof-of-principle study with platinum-based chemotherapeutic agents in clinical use demonstrated heterologous responses to the platinum drugs that are associated with prostate cancer cell types with different AR status. Further, we have defined the corresponding quantitative responses for androgen deprivation therapy (ADT) drugs enzalutamide and bicalutamide in AR-positive prostate cancer cells. Our findings evidence variability of prostate cancer cells’ response to chemotherapy and have implications in future therapy regimen considerations. Furthermore, we have developed a fluorescence light microscopy-based method to assess nuclear stress response phenotypes in prostate cancer cells that can be used for high throughput drug screening.
Citation Format: Enkhzaya Batnasan, Minttu Kärkkäinen, Sonja Koivukoski, Pekka Ruusuvuori, Leena Latonen. Phenotypic single-cell analysis of nuclear stress responses in drug-treated prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4725.
Abstract 4737: The combination of the BET inhibitor JQ1 and gemcitabine induces regressions in gemcitabine resistant patient-derived xenograft models of pancreatic cancer
Authors: Miller Aubrey L. , Fehling Samuel C. , Brown Eric Josh , Heard Eric O. , Gamblin Tracy L. , Vance Rebecca B. , Yoon Karina J. 
Published: March 2024

Abstract
Efforts to develop targeted therapies for drug resistant tumors have been relatively unsuccessful. The 5-year survival for patients with advanced pancreatic cancer is ~3%. Gemcitabine is usually combined with nab-paclitaxel as a standard of care for treatment of locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). However, no chemotherapeutic regimens thus far evaluated have been curative. We developed the first PDAC patient-derived xenograft (PDX) models in which resistance against gemcitabine was acquired in vivo. We used RNA-seq and ingenuity pathway analysis to compare expression profiles of paired parent vs gemcitabine resistant PDX models. This comparison suggested a previously unreported mechanism for gemcitabine resistance, involving aberrations of cholesterol biosynthesis and lipid metabolism pathways. We also made the unexpected observation that gemcitabine-resistant PDAC models derived from primary tumors have high levels of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), an enzyme essential to cholesterol biosynthesis and rate limiting in ketogenesis. Notably, the BET bromodomain inhibitor JQ1 decreases HMGCS2 levels; and BET inhibitors + gemcitabine exert synergistic cytotoxicity in gemcitabine-resistant PDAC cells. We determined that the BET bromodomain inhibitor JQ1 + gemcitabine induces regressions of two in vivo gemcitabine-resistant tumor models which we developed directly from primary human tumor tissue. These mechanism-based studies suggest that inhibiting HMGCS2 represents a novel approach to therapy for PDAC. We propose that combining gemcitabine with agents that decrease levels of HMGCS2 comprises effective treatment for patients with drug resistant PDAC.
Citation Format: Aubrey L. Miller, Samuel C. Fehling, Eric Josh Brown, Eric O. Heard, Tracy L. Gamblin, Rebecca B. Vance, Karina J. Yoon. The combination of the BET inhibitor JQ1 and gemcitabine induces regressions in gemcitabine resistant patient-derived xenograft models of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4737.
Abstract 4758: Targeting cellular pH as a novel therapeutic strategy in CDK4/6 inhibitor resistant breast cancer
Authors: Scheidemann Erin R. , Demas Diane M. , Shajahan-Haq Ayesha N. 
Published: March 2024

Abstract
Cyclin dependent kinase 4 and 6 inhibitors (CDK4/6i) are part of standard of care therapy in combination with antiestrogens for the treatment of metastatic estrogen receptor positive (ER+) breast cancer. Of the three major CDK4/6i, only ribociclib and abemaciclib, but not palbociclib, have shown significant improvement in overall survival in the clinic. However, resistance to CDK4/6i is prevalent and advanced metastatic ER+ breast cancer remains incurable. Other studies have focused on cell cycle or growth factor alterations in resistant tumors but targeting these pathways have not been clinically validated. Beside inhibiting the cell cycle, CDK4/6i are known to induce lysosomes in sensitive cells but the role of lysosomes in CDK4/6i resistance remains elusive. Recently, we have shown that CDK4/6i resistant breast cancer cells gain metastatic potential relative to sensitive cells and this is potentially due to deregulated lysosomes, which can be targeted with lysosome destabilizers. Here we show that all three CDK4/6i induce rapid lysosomal acidification in sensitive cells, which suggests a role of cellular pH in CDK4/6i-mediated cell death. However, in resistant cells, lysosomal acidification following CDK4/6i treatment was diminished. Therefore, we hypothesize that cellular pH is tightly regulated in CDK4/6i resistant cells and this pathway can be targeted to inhibit cell viability. Interestingly, protein levels of carbonic anhydrase IX (CA9), an important regulator of cellular pH, is significantly elevated in resistant cells. Increased CA9 levels correlate with impaired overall survival in breast and other cancers. Small molecule inhibitor of CA9, S4 or clinical-grade SLC-0111, inhibits growth of resistant cells when combined with CDK4/6i plus antiestrogens. Thus, our study highlights the role of pH changes in CDK4/6i resistant breast cancer and offer therapeutic strategies to treat this incurable disease.
Citation Format: Erin R. Scheidemann, Diane M. Demas, Ayesha N. Shajahan-Haq. Targeting cellular pH as a novel therapeutic strategy in CDK4/6 inhibitor resistant breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4758.
Abstract 482: Advancing treatment for metastatic triple negative breast cancer: Liposomal oncolytic adenovirus as a novel neoadjuvant therapy
Authors: Shah Jaimin R. , Dong Tao , Phung Abraham , Blair Sarah L. , Aisagbonhi Omonigho , Trogler William C. , Kummel Andrew C. 
Published: March 2024

Abstract
Introduction: Adenovirus type-5 (Ad) is considered a prominent viral vector in cancer therapy due to its modifiability for the selective lysis of cancer cells. However, challenges are posed in Ad delivery to cancers lacking coxsackievirus and adenovirus receptors (CARs). In response to this limitation, Ad-encapsulated DOTAP-folate liposomes were developed, which improved Ad delivery and heightened therapeutic efficacy through membrane fusion and folate receptor-mediated endocytosis.
Methods: The 4T1 mammary carcinoma model, a CAR-negative triple-negative breast cancer (TNBC) cell line (ER-, PR-, HER2-), resistant to adenoviral infection, was utilized for studying the comparative in vitro transduction of green fluorescent protein (GFP)-expressing Ad (Ad-GFP). The study assessed Ad-GFP with and without DOTAP-folate liposomal encapsulation at a multiplicity of infection (MOI) of 50. Additionally, an oncolytic adenovirus, Ad-hTERT, with a human telomerase promoter, underwent liposomal encapsulation. CAR-negative 4T1 GFP-expressing cells and CAR-positive MDA-MB-231-GFP human breast adenocarcinoma TNBC cells were transduced in vitro at MOI 100 with Ad-hTERT, both with and without DOTAP-folate liposomal encapsulation.
Results: CAR-negative 4T1 cells exhibited superior Ad-GFP transduction when encapsulated in DOTAP-folate liposomes, compared to the unencapsulated form (p &lt; 0.001). For oncolytic adenovirus Ad-hTERT, encapsulation resulted in 100% cell lysis within 24 hours in 4T1-GFP cells, contrasting with 13% with unencapsulated Ad-hTERT (P &lt; 0.0001). In CAR-positive MDA-MB-231-GFP TNBC cells, encapsulated Ad-hTERT showed enhanced efficacy, resulting in 100% cell lysis within 24 hours compared to 75% with unencapsulated Ad-hTERT (P &lt; 0.001).
Discussion: DOTAP-folate liposomal encapsulation enhances the efficacy of oncolytic Ad-hTERT in both CAR-negative and CAR-positive TNBC cells, establishing it as an optimal therapy for tumors with CAR heterogeneity. Ongoing in vivo studies with Balb/C immune-competent mice and the 4T1 tumor model will assess the effectiveness of encapsulation through intratumoral administration. This approach may extend the recurrence-free period post-surgical tumor removal.
Citation Format: Jaimin R. Shah, Tao Dong, Abraham Phung, Sarah L. Blair, Omonigho Aisagbonhi, William C. Trogler, Andrew C. Kummel. Advancing treatment for metastatic triple negative breast cancer: Liposomal oncolytic adenovirus as a novel neoadjuvant therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 482.
Abstract 4848: An analysis of black women in the Deep South with triple negative breast cancer and the social determinants of health
Authors: Evans Lauren K. , Jubilee Ivan T. , Lemieux KiTani Parker 
Published: March 2024

Abstract
Background: Triple negative breast cancer (TNBC) has a higher incidence both of diagnosis and mortality among Black women. This research aims to identify specific social determinants of health among African American women in the Deep South with breast cancer. The biological presentation of disease accounts for approximately forty percent of the Experience with the health care providers, access to greenspace, and the quality of infrastructure, such as sidewalks and streetlights evaluate environmental trends associated with the outcomes of Black women in the Deep South who have been diagnosed with TNBC.
Methods: Survey data was derived from the All of Us Research Program Database with inclusion criteria of Black women from Alabama, Georgia, Mississippi, and Louisiana who are 18 or older, born a female, and have been diagnosed with TNBC. Selected questions from the SDoH survey examined infrastructure, interactions with healthcare providers, and perceptions of community dynamics. Participants were identified via the cohort selection tool and further subdivided based on zip codes within the target states. Python was used in Jupyter Notebook to analyze the data the AoURP Workbench, responses were organized according to their corresponding survey questions. Participant responses were then extracted and quantified, facilitating the interpretation of respondents’ answers on a larger scale.
Results: Three hundred and twenty women met the criteria of being born female, being black, being diagnosed with TNBC, and living in the Deep South. Of the topics examined, infrastructure was the area where participants’ feedback indicated the largest socioeconomic deficit. Forty-eight and 49%, respectively. Indicated that did not have access to greenspace nor did not live within 10-15-minute walking distance of a transit stop. Thirty percent reported that their doctor or nurse does not listen to what they are saying.
Conclusion: Quality of life and interaction with members of the health care team associated with poorer health outcomes for Black women in the Deep South. These preliminary results indicate that those diagnosed with TNBC are impacted by the social determinants of health, specifically, proximity to public transportation, quality healthcare, recreational facilities, and infrastructure which suggests that basic needs are not met.
Citation Format: Lauren K. Evans, Ivan T. Jubilee, KiTani Parker Lemieux. An analysis of black women in the Deep South with triple negative breast cancer and the social determinants of health [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4848.
Abstract 4861: Incidence rates of bladder and kidney cancers among U.S. military servicemen: Comparison with the rates in the general U.S. population
Authors: Bytnar Julie A. , McGlynn Katherine A. , Kern Sean Q. , Shriver Craig D. , Zhu Kangmin 
Published: March 2024

Abstract
Background: The military population may differ from the general population in factors related to the incidence of bladder and kidney cancers. However, incidence rates of these cancers have not been systematically compared between the two populations. This study compared incidence rates of bladder and kidney cancers and their trends between active-duty servicemen and men in the general U.S. population.
Methods: Data were obtained from the Department of Defense’s (DoD) Automated Central Tumor Registry (ACTUR) and the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database. Patients were active-duty servicemen in ACTUR and men in SEER who were diagnosed with malignant bladder and kidney cancers and 18-59 years at diagnosis from 1990-2013. Age-adjusted rates, incidence rate ratios (IRR), and their 95% confidence intervals (95% CI) were compared between the two populations by age, race, and cancer stage. Trends in the incidence were also compared.
Results: Incidence rates were lower in ACTUR than SEER for bladder cancer overall (IRR=0.55, 95% CI=0.48-0.62) and by age, race, or tumor stage. However, for 50-59-year-old men, the rates did not differ between the populations. Trend analysis showed bladder cancer incidence decreased more in ACTUR than SEER over the study period. Kidney cancer incidence rates were marginally lower overall (IRR=0.92, 95% CI=0.84-1.00) and significantly lower for 30-49-year-old Black men in the military than the general population. For kidney cancer, the trends were similar between the two populations with increased incidence from 1999 to 2013.
Conclusion: Lower bladder and kidney cancer incidence in ACTUR, notably in younger individuals, may be primarily associated with healthier status and better health care. The lack of differences in bladder or kidney cancer incidence among 50-59-year-old men between the populations might result from more cumulative military-related exposures in this age group, which effects were offset by healthier status and better medical care. Disclaimer: The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views, opinions or policies of NCI, USUHS, HJF, the DoD or the Departments of the Army, Navy or Air Force. Mention of trade names, commercial products or organizations does not imply endorsement by the US Government.
Citation Format: Julie A. Bytnar, Katherine A. McGlynn, Sean Q. Kern, Craig D. Shriver, Kangmin Zhu. Incidence rates of bladder and kidney cancers among U.S. military servicemen: Comparison with the rates in the general U.S. population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4861.