bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4349: Comparison of Psychosocial Wellbeing among African American and Caucasian Metastatic Cancer Survivors
Authors: Caffey Jayla M. , Bail Jennifer 
Published: September 2020

Abstract
Introduction:
Approximately 5 million Americans are living with metastatic cancer and are at an increased risk for psychosocial distress (e.g., hopelessness). Hope is vital to life and is essential for effectively coping with illness. Among early-stage cancer survivors, previous studies indicate that African Americans (AA) experience greater cancer burden than Caucasians (CAU). The aim of this study was to compare psychosocial wellbeing between AA and CAU MCS residing in the Deep South.
Methods:
MCS were identified via UAB Cancer Registry and I2B2.Using a modified Dilman's method, eligible MCS (&gt;21 years and physician permission to contact) were mailed a survey. Psychosocial wellbeing (i.e. physical and mental wellbeing, anxiety, depression, social isolation, emotional support, and hopefulness) of MCS were assessed via PROMIS® measures. Returned surveys were double-key entered into REDCap®. Data were analyzed using Excel. Descriptive statistics were used to characterize the study sample and instrument scores. Between group difference, between AA and CAU MCS, was examined via independent-samples t-test.
Results:
To date, 100 surveys have been returned (AA=18; CAU=82; Mage=67 years; Msurvivorship=3 years) with a broad representation of primary cancer sites (breast=23%; prostate=10%; gynecological=16%; colorectal=13%; lung=10%; kidney=11%; other=17%). Mean instrument scores were similar between AA and CAU MCS for physical wellbeing (44.57 vs 44.81), mental wellbeing (48.1 vs 48.46), anxiety (45.76 vs 48.45), depression (44.85 vs 46.77), social isolation (39.96 vs 40.89), and emotional support (39.96 vs 40.89). However, AA MCS reported significantly better feelings of hopefulness than CAU MCS (61.34 vs 55.39, p&gt;0.01, d=0.73).
Discussion:
Findings suggest that AA MCS may be more hopeful than CAU MCS. These preliminary findings warrant further analysis after data collection is complete (an additional 300 returned surveys are anticipated).
Citation Format: Jayla M. Caffey, Jennifer Bail. Comparison of Psychosocial Wellbeing among African American and Caucasian Metastatic Cancer Survivors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4349.
Abstract 4355: Different strategies for peritoneal lavage cytology testing in the staging of gastric cancer: A cost-effectiveness analysis
Authors: He Qifei , Zhu Jinyi , Wang Anqiang , Li Xia , Bu Zhaode , Ji Jiafu 
Published: September 2020

Abstract
Background & Aims: The positive peritoneal cytology (PCY) indicates metastasis disease in patients with gastric cancer (GC); thus, the cytology testing is directly related to subsequent treatments, patients' prognoses, and medical costs. However, the cost-effectiveness of PCY testing remains unclear. We aim to evaluate the cost-effectiveness of PCY testing by comparing two active testing strategies of a guideline-recommended intraoperative laparoscopic peritoneal lavage (ILPL) and a newly proposed preoperative percutaneous peritoneal lavage (PPPL), and a third strategy of exploratory laparotomy with no cytology testing (ELNC) among GC patients.
Methods: We developed a decision-analytic Markov model to compare the cost-effectiveness of the above three strategies for a hypothetical cohort of GC patients with curative intent after initial imaging, from the perspective of Chinese society. Quality-adjusted life-years (QALYs), transition probabilities and costs were modeled using data mainly from published literature. We performed base case analysis and measured incremental cost-effectiveness ratios (ICERs) for various strategies, which were compared to a willingness-to-pay (WTP) threshold that was set to a three-fold of Chinese gross domestic product (GDP) per capita, $29,313/QALY gained. Furthermore, we conducted both one-way and probabilistic sensitivity analyses to investigate the model's robustness.
Results: In the base case analysis, we found that ELNC was dominated (i.e., more expensive and less effective) by PPPL and ILPL. ILPL was the most cost-effective method, with an ICER of US $16,673/QALY compared to PPPL. One-way sensitivity analyses demonstrated that the exploratory laparotomy mortality following ILPL and the peritoneal cytology prevalence were the only two influential parameters within their plausible range when assessing the cost-effectiveness of PPPL and ILPL. In the probabilistic sensitivity analyses, the probability of ILPL being cost-effective was 71.3% at the WTP threshold of $29,313/QALY; however, PPPL was more likely to be cost-effective when the willing-to-pay (WTP) threshold was below $17,020/QALY gained.
Conclusion: Cytology testing for GC staging through either ILPL or PPPL dominated ELNC in patients with curative intent. Moreover, ILPL was the most cost-effective modality at the current WTP threshold, while PPPL could potentially be cost-effective in lower-income areas.
Citation Format: Qifei He, Jinyi Zhu, Anqiang Wang, Xia Li, Zhaode Bu, Jiafu Ji. Different strategies for peritoneal lavage cytology testing in the staging of gastric cancer: A cost-effectiveness analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4355.
Abstract 4362: Combination of conventional therapies and antiandrogenic treatments as a succesful tool for triple negative breast cancer (TNBC) treatment
Authors: Caceres Sara , Diez Angela Alonso , Silvan Gema , Illera Maria J. , Illera Juan C. 
Published: September 2020

Abstract
Triple negative breast cancer (TNBC) patients do not benefit from conventional hormonal therapies due to the loss of expression of ER, PR, and HER2. Therefore, the usual adjuvant treatments for breast cancer, are not applied to TNBC. Recently, it has been found that approximately one third of TNBC tumours express androgen receptor (AR) and it is associated with better response to endocrine therapies. However, the prognostic value of AR expression in TNBC is still unclear. Therefore, in this preliminary study we evaluate the effectiveness of an anti-androgen treatment (bicalutamide) respect to conventional treatments (doxorubicin and lapatinib) in TNBC human cell lines and their corresponding xenografts. Briefly, SUM149, SUM159 and MDAMB231 TNBC cell lines were cultured in supplemented medium. Cells were plated in 96-well plates and a serial dilution of Doxorubicin, Lapatinib, Bicatulamide and respective combinations were added. In addition, 106 cells were implanted subcutaneosly into five female mice (Balb/C SCID). When tumors developed, mice were treated with doxorubicin, bicalutamide, doxorubicin + bicalutamide and doxorubicin + bicalutamide + lapatinib. Every treatment was perfomed every 3 days during 15 days and tumor reduction and appearance of metastases were evaluated. Results from cell culture showed that neoplasic cells from each cell line were high sensitive to bicalutamide treatment (SUM149 EC50: 9,860e009; MDAMB231 EC50: 9,454e009; SUM159 EC50: 2,170e009). Also, viability decreased when we added an anti-androgen (bicalutamide) to the conventional treatments (doxorubicin + lapatinib). In vivo experiments revealed a greater percentage of tumour reduction (around 70%) in mice treated with combination of treatments and a lower appearance of metastasis was observed in this group respect to control group (SUM149: 40% vs 60%; MDA-MB-231: 20% vs 75%; SUM159: 20% vs 60%). Therefore, our preliminary findings suggest that the addition of an anti-androgenic agent to treatments currently in use can reduce the tumour considerably, defining anti-androgenic treatments as a novel effective therapeutic target.
Citation Format: Sara Caceres, Angela Alonso Diez, Gema Silvan, Maria J. Illera, Juan C. Illera. Combination of conventional therapies and antiandrogenic treatments as a succesful tool for triple negative breast cancer (TNBC) treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4362.
Abstract 440: Dual role of epithelial MyD88 inApc-mutant intestinal tumors
Authors: Kajino-Sakamoto Rie , Fujishita Teruaki , Taketo Makoto Mark , Aoki Masahiro 
Published: September 2020

Abstract
Mutational activation of the Wnt/β-catenin signaling plays essential roles in initiating the adenoma-carcinoma sequence for the majority of colorectal cancers (CRCs) as well as in maintaining the transformed phenotypes of progressed CRCs. However, the Wnt/β-catenin signaling itself is not easy to target for therapy. Here we addressed the roles of MyD88, a critical adaptor protein in the interleukin (IL)-1β and Toll-like receptor (TLR) pathways, in intestinal epithelial cells (IECs) during intestinal tumor formation in Apc+/Δ716 mice, a mouse model of familial adenomatous polyposis as well as the early-stage spontaneous colorectal cancer. Conditional knockout of MyD88 in IECs significantly reduced the number of intestinal tumors in Apc+/Δ716 mice. Although suppression of tumor formation in Apc mutant mice by IEC-specific knockout of MyD88 was previously reported by others, our mechanistic studies uncovered the downstream molecular pathways of MyD88 involved in tumor formation. (1) IEC-specific MyD88 loss induced inactivation of the JNK/mTORC1 signaling, a pathway we previously demonstrated to be essential in the growth of Apc+/Δ716 tumors, leading to decreased proliferation of tumor cells in vivo. (2) IEC-specific MyD88 loss reduced the level of NF-κB p65 and attenuated the Wnt/β-catenin signaling, leading to apoptosis of intestinal tumor cells in vivo. (3) Induction of MyD88 deletion in the intestinal tumor-derived organoids, but not in the normal IEC-derived organoids, caused apoptotic cell death and suppressed their growth in vitro. (4) Knockdown of MYD88 in colorectal cancer cell lines harboring mutations in the Wnt/β-catenin signaling reduced their proliferation and induced apoptosis. These results demonstrate a novel mechanism by which epithelial MyD88 contributes to intestinal tumorigenesis, and also suggest synthetic lethality between MyD88 deficiency and mutations in the Wnt/β-catenin signaling in CRCs.
Citation Format: Rie Kajino-Sakamoto, Teruaki Fujishita, Makoto Mark Taketo, Masahiro Aoki. Dual role of epithelial MyD88 inApc-mutant intestinal tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 440.
Abstract 4401: GABA system expression level changes persist across cancers of many organ systems
Authors: Knott Erika Lynn , Leidenheimer Nancy J. 
Published: September 2020

Abstract
The gamma-aminobutyric acid (GABA) system is evolutionarily conserved and, in mammals, is comprised of 30 genes encoding 4 enzymes, 21 receptor subunits, and 5 transporters. The GABA system has primarily been studied for its role in inhibitory neurotransmission in the brain; however, the physiological importance of this system in peripheral tissues is less well-recognized. Although a few GABA system components have been linked to cancer progression, this information is disparate, limited, and largely unsupervised. Here, we undertook a systematic bioinformatics investigation. To this end, we accessed RNA-seq / microarray transcript data and mass spectrometry / immunohistochemistry protein data from patient tumor datasets within The Cancer Genome Atlas (TCGA), NCBI's Gene Expression Omnibus (GEO), and the NCI's Clinical Proteomic Tumor Analysis Consortium (CPTAC). In order to visualize / analyze data, bioinformatics user-interface platforms were used, including cBioPortal, the Human Protein Atlas, UALCAN, and KM-Plotter. Kaplan-Meier survival curves, differential gene expression between tumor vs. normal samples (across cancer subtypes and stages), and targeted gene set enrichment / correlations were assessed. Several GABA system genes - such as ABAT, GABRP, and GABBR1 - were commonly altered across the &gt;13 cancer types examined (including reproductive, digestive, and secretory and solid organ tumors). Unexpectedly, other transcripts such as ALDH5A1 were highly expressed across all cancers (RNA-seq log2 RSEM median value ~9). Based on Kaplan-Meier survival curve analysis, 11 GABA system genes were identified as prognostic markers for at least one type of cancer (log-rank P value &lt; 0.001 when analyzed using optimized cutoff values; average FKPM &gt; 1). Furthermore, 19 of the 30 investigated genes showed significant alterations in transcript levels between normal adjacent vs. tumor tissues (p &lt; 0.05; minimum median expression = 1 TPM) in at least one cancer type. Interestingly, unique transcript expression patterns of GABA system genes were found among cancer subtypes, such as between triple-negative vs. ER+ breast cancers. Our efforts seek both to identify cancers that leverage the GABA system for their progression, and also to provide a basis for subsequent hypothesis-driven experimentation. Additionally, the data analyzed herein may reveal opportunities to repurpose drugs for cancer treatment, as there are a variety of GABA system-targeting therapeutic agents used to treat neurological and psychiatric disorders.
We thank the LSU Health School of Graduate Studies and Feist-Weiller Cancer Center for support.
Citation Format: Erika Lynn Knott, Nancy J. Leidenheimer. GABA system expression level changes persist across cancers of many organ systems [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4401.
Abstract 4421: Development of a clinical-genomic database to study tumor evolution and molecular biomarkers of drug resistance in a real-world setting
Authors: Kumar Naveen , Kucharlapati Rajesh , Hardin Aaron , Raymond Victoria M. , Fairclough Stephen , Lang Kathryn 
Published: September 2020

Abstract
Background: Real-world evidence (RWE), specifically the integration of clinical and molecular data, plays an increasingly important role in elucidating the molecular landscape of advanced solid tumors, at diagnosis and at progression, and furthering precision oncology research. However, reliance on tissue genomic testing results within these RWE databases significantly limits our understanding of tumor evolution as tissue profiles are typically limited to a single time point, generally at diagnosis, and biopsies are not routinely completed at progression. Circulating tumor DNA (ctDNA) analysis at diagnosis and progression is an alternative to serial tissue testing. Studying the real-world data derived from ctDNA testing results can provide additional information, specifically around tumor evolution and mechanisms of innate and acquired resistance in response to intervening therapies (targeted and non-targeted).
Methods: Anonymized results from patients consecutively tested with Guardant360®, a CLIA-certified, CAP-accredited, NYSDOH-approved ctDNA test indicated for patients with advanced and metastatic solid tumor cancers (Guardant Health, Redwood City, California) were analyzed. Using a secure and HIPAA-compliant methodology, these results were then linked to a de-identified encounters database containing medical and pharmacy claims to provide a longitudinal view of patients' journeys, including diagnosis, treatments, and real-world outcomes.
Results: Of 85,874 patients, the disease groups most highly represented were lung, breast, colorectal, prostate, and pancreas cancers. 48,317 patients (56.3%) had a record of treatment with an antineoplastic treatment (i.e. chemo, hormonal, small molecule, or immuno-therapy). Of patients with a record of therapy, 14,608 (30.2%) had a record of therapy following, but none prior to, the Guardant360 test date, 14,493 (30.0%) had a record of therapy prior to, but not following theGuardant360 test date, and 19,216 (39.8%) had a record of therapy both before and after Guardant360 test date.
Conclusions: In a cohort of patients who underwent ctDNA testing and for whom treatment information was available, post-therapy molecular results were available in 69.8%. The availability of genomic information following systemic therapy suggest that this dataset is a viable resource to study drug resistance and tumor evolution in the real-world setting.
Citation Format: Naveen Kumar, Rajesh Kucharlapati, Aaron Hardin, Victoria M. Raymond, Stephen Fairclough, Kathryn Lang. Development of a clinical-genomic database to study tumor evolution and molecular biomarkers of drug resistance in a real-world setting [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4421.
Abstract 4432: scMAGeCK links genotypes with multiple phenotypes in single-cell CRISPR screens
Authors: Yang Lin , Zhu Yuqing , Yu Hua , Cheng Xiaolong , Chen Sitong , Chu Yulan , Huang He , Zhang Jin , Li Wei 
Published: September 2020

Abstract
We present scMAGeCK, a computational framework to identify genomic elements associated with multiple expression-based phenotypes in CRISPR/Cas9 functional screening that uses single-cell RNA-seq as readout. scMAGeCK outperforms existing methods, identifies genes and enhancers with known and novel functions in cell proliferation, and enables an unbiased construction of genotype-phenotype network. Single-cell CRISPR screening on mouse embryonic stem cells identifies key genes associated with different pluripotency states. Applying scMAGeCK on multiple datasets, we identify key factors that improve the power of single-cell CRISPR screening. Collectively, scMAGeCK is a novel tool to study genotype-phenotype relationships at a single-cell level.
Citation Format: Lin Yang, Yuqing Zhu, Hua Yu, Xiaolong Cheng, Sitong Chen, Yulan Chu, He Huang, Jin Zhang, Wei Li. scMAGeCK links genotypes with multiple phenotypes in single-cell CRISPR screens [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4432.
Abstract 4436: Combination therapy with an antibody specific for transferrin receptor 1 (ch128.1/IgG1) and bortezomib or lenalidomide results in increased survival in an in vivo model of human multiple myeloma
Authors: Candelaria Pierre V. , Nava Miguel , Martinez-Maza Otoniel , Daniels-Wells Tracy R. , Penichet Manuel L. 
Published: September 2020

Abstract
Multiple myeloma (MM) is a B-cell proliferative disorder of monoclonal malignant plasma cells. It is the second most common hematologic malignancy in the United States, after non-Hodgkin lymphoma (NHL). Clinical manifestations of MM include osteolytic bone lesions, hypercalcemia, renal failure, anemia, recurrent infections, and neuropathy. Standard treatments for MM include the proteasome inhibitor bortezomib, as well as lenalidomide, a thalidomide analog with immunomodulatory and antiangiogenic properties. Although the use of these two agents in combination with other therapies have significantly improved MM survival, the disease remains incurable. We previously developed a mouse/human chimeric antibody (ch128.1/IgG1) specific for human transferrin receptor 1 (TfR1). TfR1, also known as CD71, is a meaningful target for antibody-based cancer therapy, given its high expression on malignant cells and relevant role in cancer cell pathology. We have reported that treatment of SCID-Beige mice bearing disseminated human KMS-11, MM.1S, or MM.1R myeloma tumors with ch128.1/IgG1 results in significant antitumor activity in early and late disease stages. The mechanism of antitumor activity is Fc-mediated in which macrophages are considered to play a relevant role. Since combining multiple treatments with differing mechanisms of action is an effective antitumor strategy, and given the relevance of bortezomib and lenalidomide in MM therapy, we decided to explore, for the first time, the combination of these two agents with ch128.1/IgG1. We found that treatment with a single dose of ch128.1/IgG1, or multiple doses of bortezomib or lenalidomide used as single agents, results in significant antitumor activity in SCID-Beige mice bearing late stage disseminated human MM.1S tumors. However, this antitumor activity is superior when ch128.1/IgG1 was combined with bortezomib or lenalidomide, showing significantly longer survival compared to each therapy used alone. These results suggest that the addition of a ch128.1/IgG1 therapy arm in a combinatorial treatment regimen involving bortezomib and/or lenalidomide is a promising strategy against human B-cell malignancies such as MM.
Citation Format: Pierre V. Candelaria, Miguel Nava, Otoniel Martinez-Maza, Tracy R. Daniels-Wells, Manuel L. Penichet. Combination therapy with an antibody specific for transferrin receptor 1 (ch128.1/IgG1) and bortezomib or lenalidomide results in increased survival in an in vivo model of human multiple myeloma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4436.