bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 471: Attenuation of circulating miR-17-5p, miR-20b-5p, and miR-106a-5p in low-risk prostate cancer patients following proton therapy
Authors: Velasquez Johnny , Bryant Curtis , Mendenhall Nancy , Ricks-Santi Luisel 
Published: March 2024

Abstract
Introduction: Liquid biopsies offer a novel approach to diagnose, predict cancer outcomes, and monitor treatment response by analyzing tumor-derived substances. Circulating cell-free microRNAs (miRNAs) show clinical promise as biomarkers within prostate cancer (PCa) and have been implicated with PCa prognosis and outcomes. However, their potential for monitoring and assessing radiotherapy (RT) treatment response remains understudied. Understanding miRNA expression changes during RT is crucial, as they impact RT efficacy by directly affecting genes and proteins within RT-response pathways.
Aim: This study aimed to profile the expression of three oncogenes, miR-17-5p, miR-20b-5p, and miR-106a-5p and to determine their association with PCa risk groups in patients receiving proton therapy (PT).
Patients and Methods: Plasma was obtained from the University of Florida Health Proton Therapy Institute Outcomes Tracking Protocol biobank. Plasma was collected from men diagnosed with localized PCa without metastatic disease at three time points: prior to PT (PRE-PT), at 4 weeks following the start of PT (4WKSPD1), and at 8 weeks following the start of PT (8WKSPD1). The pilot study consisted of 38 patients, with 23 categorized as low-risk and 15 categorized as high-risk for PCa. MiRNA expression levels were evaluated using reverse transcription-polymerase chain reaction and quantified using the Livak method.
Results: The study revealed a downregulation of miR-17-5p in response to PT, with median gene expression levels decreasing from 0.73 at PRE-PT to 0.587 at 8WKSPD1. Low-risk PCa patients also showed distinct miRNA expression changes with all three miRNAs (miR-17-5p, miR-20b-5p, and miR-106a-5p) downregulated from 0.953, 1.037, and 1.010 at PRE-PT to 0.398, 0.216, and 0.298 at 8WKSPD1, respectively. Statistical analysis using a Kruskal-Wallis test followed by a Dunn's post-hoc test identified significant differences (p=0.035) specifically between PRE-PT and 8WKSPD1 for miR-17-5p.
Conclusion: The study revealed that PT led to a time-dependent reduction in miRNA levels, indicating a higher responsiveness in low-risk compared to high-risk PCa patients. This differential response highlights miR-17-5p, miR-20b-5p, and miR-106a-5p as potential PT response biomarkers, with clinical implications for personalizing PCa treatment. These results underscore the necessity for further validation of these miRNAs to maximize their clinical utility.
Citation Format: Johnny Velasquez, Curtis Bryant, Nancy Mendenhall, Luisel Ricks-Santi. Attenuation of circulating miR-17-5p, miR-20b-5p, and miR-106a-5p in low-risk prostate cancer patients following proton 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 471.
Abstract 4715: Azathioprine and Z36 induced cell death in human colorectal cancer HCT-116 and HCT-15 cells
Authors: Ali Yousuf Tahir , Fatima Mahwish , Ahmed Muhammad Areeb , Siddiqi Hasan Salman , Hussain Azhar , Rehman Mati Ur 
Published: March 2024

Abstract
Rationale and Objectives: Cancer accounts for a huge global health burden and is the third highest cause of death across the globe. Cancer cells are known to have higher basal reactive oxygen species (ROS) levels, owing to their higher metabolism and proliferation. Higher basal ROS in cancer cells made them susceptible to exogenous ROS stimuli that lead to cell death. Therefore, in the present study, we have analyzed the effects of Azathioprine, a glutathione (GSH) inhibitor and an intracellular ROS producer. The effect of Azathioprine was analyzed alone or in combination with a BCL-2 family protein inhibitor Z36, on human colorectal cancer cell lines HCT-116 and HCT-15.
Methods: The effects of the drugs have been investigated using various methods including cell viability assay, DNA fragmentation assay, and Annexin V-FITC/PI apoptosis assay. In addition, morphological changes evident in cell death were detected by Giemsa staining. Combination dosage for drug synergistic effects was computed through the use of CompuSyn software. Western blot was performed to detect changes in the expression of cell death-related proteins following drug treatments.
Results and conclusion: Azathioprine at a dose of 5 µM has been demonstrated to induce cell death in both HCT116 and HCT15 cells in a concentration and time-dependent manner. On the contrary, Z36, a novel BCLXL inhibitor, has demonstrated similar cell viability results at an even lower dose of 2.5 µM. When both drugs were combined at lower doses, no significant effects were observed on the cell viability of either cell line, demonstrating that the combined treatment has no synergistic or additive effects. This suggests that both drugs do not augment each other and might induce cell death via upregulation of ROS using a similar mechanism.
Citation Format: Yousuf Tahir Ali, Mahwish Fatima, Muhammad Areeb Ahmed, Hasan Salman Siddiqi, Azhar Hussain, Mati Ur Rehman. Azathioprine and Z36 induced cell death in human colorectal cancer HCT-116 and HCT-15 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 4715.
Abstract 4719: Modulation of HR-HPV viral protein E7 by SHetA2 in cervical cancer
Authors: Garland Justin , Hussain Showket , Benbrook Doris M. 
Published: March 2024

Abstract
Introduction: The purpose of this study is to determine the effect of the chemotherapeutic sulfur heteroarotinoid A2 (SHetA2) on high-risk human papillomavirus (HR-HPV) proteins and the modulation of cell survival and proliferation in cervical cancer. Cervical cancer is caused by persistent HR-HPV infection. HR-HPV tumorigenesis is driven by its early 6 and 7 (E6, E7) oncoproteins, which increase cell proliferation and survival. Cellular pathways regulated by E6 and E7 are counter-regulated by the investigational new drug SHetA2, which is currently in phase 1 clinical trial for advanced and recurrent cancers. SHetA2 disrupts complexes of 70-kDa heat shock protein (HSP70) family members, hsc70, GRP78, and mortalin, with their client proteins. We hypothesized that SHetA2 reduces E6 and E7 levels and their binding to HSP70 chaperones in association with the reduction of cervical cancer cells and tumor growth.
Methods: SHetA2 effects on specific genes and proteins in HR-HPV-positive cervical cancer cell lines and xenograft tumors were assessed by western blot, quantitative polymerase chain reaction, immunofluorescence ligation assays, and coimmunoprecipitation assays.
Results: SHetA2 significantly reduced E6 and E7 mRNA, and protein levels of E7 and the E7-regulated p16, but not E6 in cervical cancer cells and xenograft tumors. MG132 inhibition of proteasome function attenuated the E7 reduction. HSP70/hsc70 proteins bound E7 and SHetA2 disrupted these complexes.
Conclusions/Implications: SHetA2 reduces E7 proteins in cervical cancer cells through a mechanism that involves proteasomal degradation in association with disruption of HSP70/E7 complexes, p16 reduction, and decreased cell and tumor growth. This is the first demonstration of HSP70/E7 complexes. SHetA2-induced release of E7 from HSP70s could be causing increased susceptibility of E7 to proteasomal degradation. This data supports the development of SHetA2 and HSP70 inhibitors for cervical cancer.
Citation Format: Justin Garland, Showket Hussain, Doris M. Benbrook. Modulation of HR-HPV viral protein E7 by SHetA2 in cervical 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 4719.
Abstract 4746: PIM kinase inhibition synergizes with a MERTK inhibitor to treat osimertinib resistant EGFR-mutant non-small cell lung cancer
Authors: Yan Dan , Wang Xiaodong , Frye Stephen V. , Earp H. Shelton , DeRyckere Deborah , Graham Douglas K. 
Published: March 2024

Abstract
There is an unmet need for effective treatment in the setting of acquired osimertinib resistance in EGFR-mutant non-small cell lung cancer (NSCLC) patients and MERTK tyrosine kinase is a potential therapeutic target in this context. Treatment with the MERTK inhibitor MRX-2843 was sufficient to abrogate downstream PI3K-AKT and MAPK-ERK signaling, cell expansion, and colony formation in osimertinib-resistant EGFR-mutant NSCLC cell lines, suggesting dependence on MERTK signaling for tumor cell proliferation/survival. Further, two structurally distinct PIM kinase inhibitors, SGI-1776 and PIM447, provided synergistic inhibition of cell expansion and colony formation in osimertinib-resistant cell line cultures when combined with MRX-2843 treatment. Mechanistically, treatment with MRX-2843 in combination with either PIM kinase inhibitor decreased downstream PI3K-AKT and MAPK-ERK signaling more effectively than single agents. Furthermore, knockdown of PIM kinases (PIM1, 2, 3) using nine sets of siRNAs led to various changes in expression of TAM receptor family members (TYRO3, AXL, MERTK), indicating a role for PIM kinases in regulation of TAM kinase expression. These studies suggest a novel treatment strategy for osimertinib-resistant EGFR-mutant NSCLC using a first-in-class MERTK kinase inhibitor that is currently under evaluation in multiple Phase I clinical trials.
Citation Format: Dan Yan, Xiaodong Wang, Stephen V. Frye, H. Shelton Earp, Deborah DeRyckere, Douglas K. Graham. PIM kinase inhibition synergizes with a MERTK inhibitor to treat osimertinib resistant EGFR-mutant non-small cell lung 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 4746.
Abstract 4748: Aronia berry overcomes gemcitabine resistance by regulating the MYD88/NF-kB/P-glycoprotein pathway in pancreatic ductal adenocarcinoma
Authors: Li Yuan , Xu Caiming , Han Haiyong , Goel Ajay 
Published: March 2024

Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is lethal, which is partly due to the limited efficacy of Gemcitabine (Gem)-based chemotherapy, resulting from the development of acquired resistance to this regimen. Aronia berry extract (ABE) is a natural source of phenolic compounds known for its anti-cancer properties. Previous research has highlighted the ability of ABE to help overcome chemoresistance to conventional chemotherapies in various cancers. In this study, we interrogated the ability of ABE to overcome Gem-resistance (Gem-R) in PDAC and identify specific pathway(s) responsible for this anti-cancer efficacy. Methods: We performed a series of in-vitro experiments in Gem-R cells to evaluate the synergistic effect of combined treatment with Gem and ABE. Furthermore, we conducted a genomewide transcriptomic analysis to identify the critical regulatory pathways associated with chemoresistance and potential therapeutic targets of ABE in Gem-R PDAC cells. The cell culture findings were validated in patient-derived 3D organoids. Results: The combined treatment with ABE and Gem in Gem-R cells exhibited significant synergistic anticancer effects on cell viability, proliferation, migration, and invasion. The transcriptomic analysis revealed that the NF-κB signaling pathway was associated with Gem-R (p&lt;0.05), with a significant upregulation of MYD88. Additionally, MYD88 was significantly associated with overall survival in PDAC patients in the TCGA cohort (HR=1.58, P=0.045). The MYD88/NF-κB signaling is associated with chemoresistance as it can upregulate the efflux transporters like P-glycoprotein (P-gp). Our results confirmed that combined treatment inhibited the NF-κB signaling pathway by suppressing MYD88 and downregulating P-gp expression to overcome Gem-R. Finally, the combined treatment demonstrated superior anti-cancer activity in 3D organoids by reducing both their number and size (P&lt;0.05). Conclusion: We provide novel insights into the potential of ABE in overcoming Gem-R in PDAC cells by targeting the MYD88/NF-κb/P-gp axis, which offers a safe and inexpensive approach for improving therapeutic outcomes in this fatal malignancy.
Citation Format: Yuan Li, Caiming Xu, Haiyong Han, Ajay Goel. Aronia berry overcomes gemcitabine resistance by regulating the MYD88/NF-kB/P-glycoprotein pathway in pancreatic ductal adenocarcinoma [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 4748.
Abstract 4765: Tumor, serum and plasma metabolome in patients with high-grade bladder cancer
Authors: Tsamouri Maria-Malvina , Karthikeyan Akshaya , Lucchesi Christopher A. , Durbin-Johnson Blythe P. , Dall'Era Marc A. , Ghosh Paramita M. 
Published: March 2024

Abstract
Introduction: Bladder cancer (BlCa) ranks as the sixth most prevalent cancer in the world. A number of urine based BlCa detection tests have recently been approved for clinical use, including the NMP22 tests and the bladder tumor antigen (BTA) tests for both detection and monitoring of patients with known bladder cancer. The FDA have approved them both for surveillance in BlCa only in conjunction with cystoscopy. Unfortunately, the sensitivity and specificity of these tests are poor, and cannot distinguish between aggressive and non-aggressive tumors. This project aims to identify alternate markers that can overcome these drawbacks.
Methods: We characterized the global metabolome of 47 bladder tumors retrieved by radical cystectomy (RC) or TURBT, including 14 specimens with matching plasma and serum samples. All specimens were subjected to untargeted metabolomic approaches with gas chromatography- time-of-flight mass spectrometry (GC-TOF MS) to profile primary metabolites, hydrophilic interaction liquid chromatography MS (HILIC-QTOF MS) to profile biogenic amines, and liquid chromatography charged surface hybrid MS (LC-CSH-QTOF MS) to characterize complex lipids. Differentially expressed metabolites were analyzed with respect to grade, stage, metastases, and the use of neoadjuvant chemotherapy. For selected metabolites, area under the ROC curve (AUC) is calculated as % sensitivity vs. 100% specificity. Expression of highly discriminatory metabolites were then validated in the plasma and serum samples to determine which forum would provide greater specificity.
Results: We first assembled a discovery cohort of 33 patients who did not have matching blood specimen for primary metabolites, biogenic amines and complex lipids. Comparison of high vs low grade tumors yielded two lipids, a sphingomyelin (SM (d38) and a phosphatidylcholine PC(p-38), that were significantly different (adjusted p-value&lt;0.05, log2fold change&gt;2.5). These results were validated in the 14-sample cohort with matching plasma and serum of which the latter showed significant correlation between tumor and plasma (Spearman R=0.872, adj p=0.03).
Conclusions: Our results indicate that certain sphingomyelins and phosphatidylcholines may be useful as plasma markers of high grade BlCa. Further analyses are required to evaluate whether these markers are more discriminatory compared to existing urinary markers.
Citation Format: Maria-Malvina Tsamouri, Akshaya Karthikeyan, Christopher A. Lucchesi, Blythe P. Durbin-Johnson, Marc A. Dall'Era, Paramita M. Ghosh. Tumor, serum and plasma metabolome in patients with high-grade bladder 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 4765.
Abstract 4790: Hospitalization as an opportunity to improve lung cancer screening in high-risk patients
Authors: Nielsen Ellen M. , Zhang Jingwen , Marsden Justin , Bays Chloe , Moran William P. , Mauldin Patrick D. , Lenert Leslie A. , Toll Benjamin A. , Schreiner Andrew D. , Heincelman Marc 
Published: March 2024

Abstract
Background: Lung cancer screening with annual low-dose computed tomography (LDCT) in high-risk patients with exposure to smoking reduces lung cancer-related mortality, yet the screening rate of eligible adults is low. As hospitalization is a critical moment to engage patients in their overall health, it may be an opportunity to improve rates of lung cancer screening. Prior to implementing a hospital-based lung cancer screening referral program, this study assesses the association between hospitalization and completion of lung cancer screening.
Methods: A retrospective cohort study of evaluated completion of at least one LDCT from 2014-2021 using electronic health record data using hospitalization as the primary exposure. Patients aged 55-80 who received care from a university-based internal medicine clinic and reported cigarette use were included. Univariate analysis and logistic regression models evaluated the association of hospitalization and completion of LDCT. The secondary outcome was completion of any CT of the chest.
Results: Of the 1,935 current smokers identified, 47% had at least one hospitalization, and 21% completed a LDCT during the study period. While a higher proportion of patients with a hospitalization had a LDCT (24%) compared to patients without a hospitalization (18%, p&lt;0.001), there was no association between hospitalization and completion of a LDCT after adjusting for potentially confounding covariates (95%CI 0.680 - 1.149). Of cohort patients, 38% completed any CT of the chest and hospitalization was associated with increased odds of receiving chest CT imaging in the adjusted model (OR 1.72; 95%CI 1.37 - 2.17).
Conclusions: In a cohort of patients at risk for lung cancer, only 1 in 5 completed lung cancer screening with LDCT and hospitalization events were not associated with LDCT completion. A hospitalist driven lung cancer screening program has the potential to increase the suboptimal rates of lung cancer screening in high-risk patients.
Citation Format: Ellen M. Nielsen, Jingwen Zhang, Justin Marsden, Chloe Bays, William P. Moran, Patrick D. Mauldin, Leslie A. Lenert, Benjamin A. Toll, Andrew D. Schreiner, Marc Heincelman. Hospitalization as an opportunity to improve lung cancer screening in high-risk patients [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 4790.
Abstract 4840: Creating a culturally sensitive manual to increase clinical trial participation among African Americans and African Nationals
Authors: Aristizabal Carolina , Ibarra Eduardo , Baezconde-Garbanati Lourdes A. 
Published: March 2024

Abstract
Background: Racial and ethnic minorities are immensely underrepresented in clinical trial studies in the United States. Black/African Americans, Latinos/as, Asians, American Indians, and Pacific Islanders make up roughly 30% of all clinical trials (CT) participation across all race groups. Being inclusive of all populations in CT ensures that everyone has access to modern medicines and treatments, but also, that these latest treatments work and react well to all people.
Methods: We developed a manual on clinical trials with a target focus to African Americans and African Nationals. We hosted two focus groups with Blacks/African Americans in which we found they are more comfortable getting cancer related information through trusted community services, such as coming from churches. We have connected with over 80 Pastors who agreed to collaborate in clinical trials education.
Results: Through outreach and engagement to African American churches in Los Angeles County, we have distributed a copy of this clinical trials educational manual to 90 churches to be disseminated during their services. Our office of Community Outreach and Engagement (COE) regularly attend community health and resource events and provide hard copies of the clinical trials manual at tables/booths designated for our participation. We have attended 50 community events and have disseminated about 1,900 copies of the CT manual so far this year 2023. This manual is also available for free download on our cancer center’s website, in which over 100 toolkits have been downloaded within the last year.
Conclusions: By creating a culturally sensitive and adapted educational manual and partnering with trusted services in the community such as faith-based organizations, we can begin to break down barriers to clinical trials participation among all race and ethnic minority groups.
Citation Format: Carolina Aristizabal, Eduardo Ibarra, Lourdes A. Baezconde-Garbanati. Creating a culturally sensitive manual to increase clinical trial participation among African Americans and African Nationals [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 4840.