bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1947: Clinical and genomic correlates with genetic ancestry in lung squamous cell carcinoma
Authors: Jain Sejal , Yao Alexandria G. , Allen-Gipson Diane , Momen-Heravi Fatemeh , Taylor Alison M. 
Published: April 2023

Abstract
Many translational studies suggest racial and ethnic survival disparities in lung squamous cell carcinoma (LSCC), with self-identified African-Americans showing significantly lower overall survival and progression-free survival than self-identified Caucasians. However, potential clinical and genomic factors contributing to this disparity have yet to be elucidated. Using clinically annotated genomic data from 501 LSCC tumor samples in the Cancer Genome Atlas (TCGA), we compared clinical data, gene expression profiles, mutations, and focal and arm-level copy number changes from tumors across ancestral groups to identify significantly differential events. Within this dataset, patients of AFR ancestry had worse survival and progression-free survival then patients of EUR ancestry. We applied the Cox Proportional Hazards model to predict overall and progression-free survival as functions of genetic ancestry alongside other genetic, molecular, and clinical variables. We found a significant difference in metastatic stage between tumors from patients of African (AFR) and European (EUR) ancestry, which was significant in predicting survival. Compared to tumors from EUR patients, tumors from AFR patients featured increased chromosome arm 8q gain and more frequent amplification of genetic locus chr8q24, which contains proto-oncogene MYC. Expression of MYC target genes was also significantly increased in AFR samples relative to EUR samples. These findings may suggest a role for the MYC pathway in differential cancer progression. We found more frequent amplification of genetic loci chr22q11 and chr16p11 in AFR samples compared to EUR samples. We identified top differentially mutated genes between groups, of which SPRR3, PDGFA, FRS3, and C21orf62 correlate with survival. We also found immune signaling gene sets enriched in the EUR group by gene set expression analysis (GSEA). These results suggest potential genetic and clinical factors implicated in racial survival disparities. Further studies and more diverse sampling of cancer patient populations are required to validate these differences and elucidate patient-specific treatment modalities.
Citation Format: Sejal Jain, Alexandria G. Yao, Diane Allen-Gipson, Fatemeh Momen-Heravi, Alison M. Taylor. Clinical and genomic correlates with genetic ancestry in lung squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1947.
Abstract 1948: Novel insights into lung cancer & chronic obstructive pulmonary disease racial disparities
Authors: Thaiparambil Jose Thomas , Yin Zheng , El-Zein Randa 
Published: April 2023

Abstract
Introduction: Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) result from the dual effects of smoking/pollution exposure and genetic susceptibility. Blacks/African Americans (B/AA) have higher tobacco-related morbidity and mortality than Whites/European Americans (W/EA), despite smoking fewer cigarettes and starting later in life. COPD is a well-established risk factor for LC and B/AA develop COPD with less cumulative smoking and at younger ages. We will test the hypothesis that NRF2 and Focal Adhesion-PI3K-Akt-mTOR-signaling pathways play a significant role in the disparities observed between B/AA and W/EA with LC and COPD and that account for worsened outcomes in B/AA.
Methods: RNAseq analysis was conducted on tissues from 30 LC patients and 29 COPD patients undergoing lung transplantation. We compared both LC and COPD RNAseq data to identify common and unique transcripts associated with each disease.
Results: A total of 153 genes were significantly upregulated in COPD compared to LC adeno carcinoma and 174 LC squamous cell carcinoma. Ingenuity pathway analysis revealed the involvement of top regulator networks with the activation of EPSA1, CTNNB1, EP300, IKBKB and IL1B which are seen in both LC and COPD and may be involved in COPD progression to LC. We further analyzed the transcriptome of COPD between B/AA and W/EA and identified 141 significantly upregulated genes in B/AAs. We further validated our findings in TCGA B/AA LC patients to determine the extent of overlap between COPD and LC. Among these, 42 (29.8%) and 13 (9.2%) genes were significantly upregulated in TCGA LC adenocarcinoma (58 B/AA patients vs 527 from other races) and LC squamous cell carcinoma cohorts (32 B/AA patients vs 518 from other races), respectively. Survival analysis using the upregulated genes from the TCGA LC B/AA cohorts showed a higher expression of three LC adenocarcinoma (TOMM5, CEP-152 and HGS) and two LC squamous cell carcinoma specific genes (PYROXD2 and USP43) significantly associated with overall survival.
Conclusion: Our data provide novel insight on the overlap between COPD and LC and identified potential pathways that may be contributing to the significant health care disparity among B/AAs. Future studies are warranted to identify early-stage COPD markers that could be used for identification of high-risk individuals that would benefit from therapeutic interventions.
Citation Format: Jose Thomas Thaiparambil, Zheng Yin, Randa El-Zein. Novel insights into lung cancer & chronic obstructive pulmonary disease racial disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1948.
Abstract 197: Novel 3D bioprinted pancreatic tumor models for anti-cancer drug assessment
Authors: Gaikwad Shreyas Ramchandra , Srivastava Sanjay K. 
Published: April 2023

Abstract
The advent of bioprinting as a technology has greatly advanced the field of tissue engineering. Currently, it is being explored as a means to create complex disease models, specifically to create 3D tissue environments. Such complex models allow incorporation of dynamic microenvironments during in vitro studies. In terms of cancer drug development, the tumor microenvironment plays a significant role in cancer progression. The use of conventional 2D models in the preliminary stages of anti-cancer screening reduces the probability of successful translation towards clinical trials. In the current study, we have utilized bioprinting to create pancreatic tumor model which specifically mimics the human pancreatic tissue in terms of the biological and chemical makeup. We developed and optimized a novel bioink to create the tumor tissue. The bioink specifically mimics the pancreatic tumor microenvironment making it unique and novel as compared to the currently used bioinks which are mainly derived from animal tissues. The bioprinted tumors were then characterized for various important hallmarks of cancer such as tissue stiffness, hypoxia, and immunomodulation. We also analyzed the expression of various oncoproteins in comparison to 2D cultures to explore the role of 3D microenvironments on cancer cells. Additionally, we evaluated the efficacy of standard chemotherapies, radiotherapy and immunotherapy on the tumors as compared to 2D monolayer cultures. The bioprinted pancreatic tumors serve as a bridge between conventional assays and animal models. We observed a stark difference in the characteristics of cancer cells in monolayer cultures versus bioprinted tumors. Since a bioprinter can be programmed to control the geometry of the tissue, these models serve as the most accurate means to mimic the in vivo tumor microenvironment.
Citation Format: Shreyas Ramchandra Gaikwad, Sanjay K. Srivastava. Novel 3D bioprinted pancreatic tumor models for anti-cancer drug assessment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 197.
Abstract 1971: Understanding the perspectives of Latino smokers on physical activity: A qualitative study
Authors: Cartujano-Barrera Francisco , Alaniz-Cantu Edgar , Rojas Maria Valeria Bautista , Hernández-Torres Ruthmarie , McIntosh Scott , Ossip Deborah J. , Cupertino Ana Paula 
Published: April 2023

Abstract
Introduction: Smoking and sedentarism frequently co-occur among Latinos. Evidence suggests that moderate to vigorous physical activity (MVPA) may enhance smoking cessation rates. However, this synergistic phenomenon has not been studied among Latinos, the largest minority group in the U.S.
Objective: To understand the perspectives of Latino smokers on physical activity.
Methods: Participants were recruited using community-based recruitment strategies. Semi-structured interviews were conducted in English and Spanish with Latino smokers. The Health Belief Model was used as a framework for qualitative theoretical analysis.
Results: At baseline, participants’ mean age was 54.9 years old (SD 12.1), 50% of the participants were female, and 85% self-identified as heterosexual or straight. Eight participants (40%) indicated their language of preference as “Only Spanish” and 50% were born in Cuba and the Dominican Republic (25% for each country). Most participants (70%) were light smokers (1-10 cigarettes per day), 35% smoked their first cigarettes within five minutes after waking up, and 50% used menthol cigarettes. We identified perceived benefits (e.g., mood management, weight loss, strategy to quit smoking), susceptibility (e.g., risk of cardiovascular diseases and physical impairment, susceptibility to weight gain), and barriers (e.g., lack of social support, health constraints, and low financial resources) of being physically active. Moreover, we identified cues to action to do physical activity (e.g., being a role model: “⋯I’m going to do it [physical activity] so she [the daughter] can do it too⋯”; spending time with family and friends: “Well, since I have some little nephews and some little nieces... I go with them to the playground⋯”; being outdoors: “⋯go to the parks a lot or go nature walking⋯ being out in the woods⋯ taking all of nature⋯ I would go down to [local towns in New York] on my bicycle⋯”).
Conclusion: Multiple perceived factors of being physically active were identified among Latino smokers. These factors provide concrete operational strategies to address smoking cessation and physical activity among Latinos. Further research is needed on how best to integrate these perspectives into smoking cessation interventions.
Citation Format: Francisco Cartujano-Barrera, Edgar Alaniz-Cantu, Maria Valeria Bautista Rojas, Ruthmarie Hernández-Torres, Scott McIntosh, Deborah J. Ossip, Ana Paula Cupertino. Understanding the perspectives of Latino smokers on physical activity: A qualitative study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1971.
Abstract 2085: Structural principles of kinase-selectivity drug design
Authors: Zhang Mingzhen , Liu Yonglan , Jang Hyunbum , Nussinov Ruth 
Published: April 2023

Abstract
Kinase drug selectivity is one of the main challenges in cancer research. The kinases encoded byhuman genome share the highly similar catalytic kinase domains. As a result, the drug that isdesigned to target one kinase frequently binds to another, leading to the off-target toxicity. Despitethe high structural similarity, the kinase drug pockets at the atomic level are not completelyidentical. We ask that whether there are some inhibitor-accessible geometric features in the kinasepockets that only exist in one kinase but not in all others. To target these unique features in thekinase pockets may help design the kinase drugs with the kinome-wide selectivity. In this work,we describe a transformation invariant protocol (binary network with unsupervised clustering) andperform the kinome-wide structural bioinformatic analysis by integrating the experimental andartificial intelligence (AI)-based kinase structures. The results show that ~ 66.8 % kinases containthe unique features that may distinguish them from all others and the geometric features shared byless than seven other kinases can be found in all the analyzed kinases. We apply the binary networkto EGFR tyrosine kinase and AKT1 serine/threonine kinases, illustrating the potential structuralstrategies to design the high-selectivity kinase drugs. Finally, we develop a cross-platformsoftware, named as KDS (Kinase Drug Selectivity), to achieve the customized real-timevisualization and mutation analysis of the binary networks in the human kinome.
Citation Format: Mingzhen Zhang, Yonglan Liu, Hyunbum Jang, Ruth Nussinov. Structural principles of kinase-selectivity drug design [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2085.
Abstract 2154: Differential expression of the PI3K-Akt signaling pathway pre and post chemotherapy in relation to hormonal profile in African women
Authors: Kengni Hurette Junie Chansi 
Published: April 2023

Abstract
Background: Breast cancer (BC) is the most common cancer in US and Canadian women. Despite therapeutic advances, it remains the second leading cause of female cancer mortality. Aggressive breast cancers are represented as a clinical (inflammatory BC or locally advanced BC) or as a biopathological form (triple negative BC or HER2+ BC). These aggressive forms have a poor prognosis. In the US, African Americans have a 41% higher BC death rate than Caucasians women. As observed in the US, in African Gabon women, a more aggressive and cases of triple negative BC are found. Aggressive BC are mainly associated with African women. At this stage, chemotherapy is the main therapeutic treatment but chemoresistance is the major hurdle. One solution to chemoresistance would be to found candidates biomarkers that predict therapeutic responses. The goal of our study was to establish an RNA signature that could differentiate chemosensitive from chemoresistant patients in BC African women.
Methods: RNA sequencing technique was used to establish expression profiling in African women before and after chemotherapy using three groups of aggressive BC patients treated with: Doxorubicin, 5-Fluorouracil or Navelbine. We first isolated RNA from tissues fixed in paraffin and sequenced it via the Nextseq 2000 system. A tximport (v1.20.0) and DESeq2 (v1.26.0) analysis then identified significantly and differentially expressed transcripts between the different groups.
Results: In the doxorubicin group, post-chemotherapy patients had 962 significant genes out of the 46461 transcripts compared to pre-chemotherapy patients. The post-chemotherapy 5-FluoroUracil group had 3723 significant genes out of 43821 transcripts compared to pre-chemotherapy Fluorouracil group and the post-chemotherapy Navelbine group had 980 significant genes out of 44689 transcripts compared to pre-chemotherapy Navelbine group. Relevant overexpressed genes were selected for validation by immunohistochemistry
(IHC). We found an enrichment in the KEGG and PI-3K/Akt pathways and observed that Akt downstream substrates were express differently between pre- and post-chemotherapy patients.
Conclusion: Our study suggests that some of the overexpressed post chemotherapy genes could serve as biomarkers of aggressive BC. This is the first study in Canada to investigate Doxorubicin, Flurouracile and Navelbine chemoresistance-related genes in African women and could lead to the discovery of diagnostic markers and therapeutic targets.
Citation Format: Hurette Junie Chansi Kengni. Differential expression of the PI3K-Akt signaling pathway pre and post chemotherapy in relation to hormonal profile in African women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2154.
Abstract 2169: NAD(P)H: quinone oxidoreductase 1 (NQO1)- A viable biomarker in colorectal cancer
Authors: Ganji Chaithanya , Lakkakula Bhaskar VK , Behera Santosh Kumar , El-Rayes Bassel F. 
Published: April 2023

Abstract
Background/Objective: Colorectal cancer (CRC) is aggressive and widespread (3rd among malignancies) in the United States. NAD(P)H: Quinone Oxidoreductase 1 (NQO1) is an enzyme that contributes to chemoprotection for CRC. The aim of this meta-analysis is to test the connection between NQO1 C609T polymorphisms and CRC risk. Furthermore, the study explores the binding capacity and efficacy of BBI 608 against NQO1 in CRC through molecular docking. The inhibitor will then be tested in vitro.
Methods: PubMed, Web of Science, and Google Scholar were used in bibliographic searches. For the NQO1 C609T analysis, a total of 18 studies were used. Data was gathered and subsequently calculated using the pooled odds ratio (OR) (95% confidence interval, CI). Molecular docking, Western Blot and QRT-PCR were used to determine the molecular function of BBI 608 and NQO1.
Results: The relation between NQO1 polymorphism and CRC risk (TT + CT vs. CC: OR=1.19, 95% CI =1.06-1.34, p&lt;0.001) was significant. Furthermore, stratified investigation based on ethnicity indicated significant association between NQO1 polymorphism and CRC risk (TT + CT vs. CC: OR=1.17, 95% CI =1.08-1.27, p&lt;0.001). This study indicates that the C609T polymorphism of NQO1 is linked with CRC risk in Asians and Caucasians. To observe the molecular properties of BBI 608 (NQO1 inhibitor) and to analyze the exact mechanism of NQO1 on CRC, computational approaches were applied. This investigation provides a detailed understanding of the interaction between NQO1 and BBI 608 and its implication in CRC therapy. To support this computational analysis, in vitro studies were performed. BBI 608 creates higher cytotoxicity in a dose dependent manner in CRC cell lines. BBI 608 treatment significantly (p&lt;0.001) reduced the NQO1 expression at protein and messenger levels in both CRC (HCT 116 and RKO) cell lines.
Conclusion: Based on meta-analysis and computational approach, NQO1 is a viable biomarker and targeted molecule in CRC. In vitro results showed that inhibiting NQO1 with the drug BBI 608 decreased cell proliferation in both CRC cell lines. Knockout or overexpression or site directed mutagenesis is essential for a better understanding about BBI 608 targeted NQO1 and its amino acids.
Citation Format: Chaithanya Ganji, Bhaskar VK Lakkakula, Santosh Kumar Behera, Bassel F. El-Rayes. NAD(P)H: quinone oxidoreductase 1 (NQO1)- A viable biomarker in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2169.
Abstract 2243: Cyproheptadine exhibits anti-tumor activity by reversing the epigenetic silencing of IRF6 in urothelial carcinoma
Authors: Chen Pie-Che , Lin Guan-Ling , Lin Hon-Yi , Huang Wan-Hong , Chuang Yu-Ming , Lin Ru-Inn , Wu Shu-Fen , Shen Cheng-Huang , Chan Michael W.Y. 
Published: April 2023

Abstract
Urothelial carcinoma (UC) is the second most common malignancy of the urinary system with high rate of recurrence, UC patients therefore needed to be treated with surgery followed by chemotherapy. Development of novel therapeutics with minimal side-effect is an urgent issue. Our previous study showed that cyproheptadine (CPH), an anti-histamine, exhibited antitumor activity in UC in vitro and in an xenograft model. In this study, we performed RNA-Seq to examine genes that are differentially expressed after treatment with CPH in UC cells. Our result showed that several genes, including IRF6, were upregulated after treatment with CPH in BFTC905 UC cells. Further experiments found that treatment of CPH could restore the expression of IRF6 in several other UC cell lines, which is due to promoter hypomethylation and enrichment of H3K27 acetylation, as well as H3K4 mono-methylation. Importantly, treatment of CPH can inhibit tumor growth in a syngeneic mouse tumor model. The tumor growth can be further inhibited by combination treatment of CPH and immune checkpoint blockade. Flow cytometric analysis of the tumor found that NK cells are significantly enriched in the CPH treatment group, as compared to DMSO control. Co-culture experiments confirmed that UC cells pretreated with CPH showed an increased NK-92-mediated cytotoxicity. In conclusion, these results suggested that treatment of CPH can inhibit tumor growth, by epigenetic priming of IRF6 in UC. The role of CPH in eliciting anti-tumor innate immune response deserves further investigation.
Citation Format: Pie-Che Chen, Guan-Ling Lin, Hon-Yi Lin, Wan-Hong Huang, Yu-Ming Chuang, Ru-Inn Lin, Shu-Fen Wu, Cheng-Huang Shen, Michael W.Y. Chan. Cyproheptadine exhibits anti-tumor activity by reversing the epigenetic silencing of IRF6 in urothelial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2243.
Abstract 2279: Tumor treating fields induce immune modulation in non-small cell lung cancer
Authors: Wang Suhe , Baker James R. , Chen Jesse , Cao Zhengyi , Cannon Jayme 
Published: April 2023

Abstract
Non-small cell lung cancer (NSCLC) is one of most common lung cancers in the general population. KRAS mutations occur in 15-30% of NSCLC. The mutation results in continuous activation of KRAS, triggering multiple kinase signaling pathways. The oncogenic features of KRAS mutations are in line with clinical observations that NSCLC patients with KRAS mutations have a worse prognosis with less benefit from chemotherapies. Although the targeted inhibition of KRAS G12C mutation in NSCLC has achieved remarkable success, the inhibition of KRAS G12D has not yet been successful. It has been reported that KRAS mutations can facilitate the development of immunosuppressive properties of the tumor microenvironment. Specifically, KRAS mutations can up-regulate regulatory T cell (Treg) population. Tumor Treating Fields (TTFields) are a cancer therapy based on noninvasive delivery of electric fields. Our current in vitro study was performed in peripheral blood mononuclear cells (PBMC) from a transgenic mouse lung cancer model with a KRAS G12D mutation. Our data showed that TTFields treatment decreased CD4+CD25+ Foxp3+ T cells intensity prepared from PBMC compared to untreated cells by flow cytometric determination. In addition, CD4+ T cells prepared from TTFields treated PBMC have enhanced IFN-γ expression levels compared to untreated PBMC. These results suggest TTFields treatment appear to correct the immunosuppressive properties created by KRAS mutations. Therefore, in vivo treatment for the inducible lung cancer with KRAS activating mutations is needed to confirm the in vitro results. In conclusion, TTFields are a potential therapeutic tool for NSCLC with KRAS G12D mutation.
Citation Format: Suhe Wang, James R. Baker, Jesse Chen, Zhengyi Cao, Jayme Cannon. Tumor treating fields induce immune modulation in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2279.