bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 748: Conjugated primary bile acids as a biomarker for hepatocellular carcinoma risk in two prospective cohorts
Authors: Thomas Claire Elizabeth , Luu Hung , Wang Renwei , Xie Guoxiang , Adams-Haduch Jennifer , Jin Aizhen , Koh Woon-Puay , Jia Wei , Behari Jaideep , Yuan Jian-Min 
Published: July 2021

Abstract
Background: Incidence rates of hepatocellular carcinoma (HCC) has been increasing for several decades in the U.S. Non-alcoholic liver disease (NAFLD) increasingly plays a role in the rising rate of HCC. Experimental data have shown that bile acids, which play key roles in the host-gut microbiota co-metabolism, contribute to the development of NAFLD and HCC. We propose to comprehensively examine the associations of bile acids with risk of HCC in two cohorts.
Methods: Thirty-five bile acids were quantified using the state-of-the-art ultraperformance liquid chromatography triple-quadrupole mass spectrometry assays in serum samples collected, on average, five years prior to diagnosis of 197 HCC and the same number of individually matched controls from the Singapore Chinese Health Study and the Shanghai Cohort Study. Conditional logistic regression was used to assess the associations for major bile acids and their conjugates, and bile acid ratios with the risk of HCC.
Results: Total primary bile acids were significantly elevated whereas the ratio of secondary bile acids over primary bile acids were significantly lower in HCC cases than controls in both cohorts (P's ≤ 0.001). Doubling of tauro- vs. glyco-conjugates of all bile acids, primary bile acids, and specifically chenodeoycholic acid resulted in an increase in HCC risk of 44, 48, and 34% (P = 0.004, &lt;0.001, 0.001) respectively after adjustment for potential confounders.
Conclusion: Primary bile acids, especially tauro-conjugated bile acids were strongly associated with increased risk of HCC risk whereas the secondary vs. primary bile acids ratios were associated with decreased risk of HCC.
Citation Format: Claire Elizabeth Thomas, Hung Luu, Renwei Wang, Guoxiang Xie, Jennifer Adams-Haduch, Aizhen Jin, Woon-Puay Koh, Wei Jia, Jaideep Behari, Jian-Min Yuan. Conjugated primary bile acids as a biomarker for hepatocellular carcinoma risk in two prospective cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 748.
Abstract 768: Predictive role of circulating tumor cells in women with ovarian cancer
Authors: Singh Swarnima , Kumar Uday 
Published: July 2021

Abstract
Background: “Liquid biopsy”, where body fluids is screened for biomarkers is gathering substantial research. We aimed to examine women with suspected ovarian cancer for the presence of circulating tumor cells (CTCs) and study its role in prediction of chemoresistance and survival.
Methods: Magnetic powder labeled monoclonal antibodies for epithelial cell adhesion molecule (EpCAM), Mucin 1 cell surface associated ( MUC1) ,mucin 16, cell surface associated MUC16 or CA125 were prepared according to the manufacturer's protocol. Expression of three ovarian cancer related genes were detected in CTCs using multiplex reverse transcriptase-polymerase chain reaction (Multiplex RT-PCR). CTCs and serum CA125 were measured in 100 patients with suspected ovarian cancer. Correlations with clinicopathological parameters and treatment were analyzed.
Results: CTCs were detected in 18/70 (25.7%) of women with malignancy compared to 0/30 (0.0%) in those with benign gynecologic diseases (p=0.001). The sensitivity and specificity of the CTC test for predicting a malignant histology in pelvic masses was 27.7% (95% CI :16.3%,37.7%) and 100% (95% CI: 85.8%, 100%), respectively. The number of CTCs correlated with stage of ovarian cancer (p=0.030). The presence of EpCAM+CTC at primary diagnosis in ovarian cancer was found to be an independent predictor of a poor progression free survival (PFS) (HR,3.3; 95% CI, 1.3-8.4; p=0.010), overall survival (OS) (HR, 2.6; 95% CI,1.1-5.6; p=0.019) and resistance to chemotherapy (OR 8.6; 95% CI, 1.8-43.7; p=0.009).
Conclusion: Expression of EpCAM in CTC positive patients predicts chemotherapy resistance and prognosis, could aid clinicians in individualizing therapy, saving the patient from unnecessary side effects and systemic toxicity of platinum-based chemotherapy. Also, EpCAM expression can be a strong basis for further investigating anti-EpCAM targeted therapies in ovarian cancer.
Citation Format: Swarnima Singh, Uday Kumar. Predictive role of circulating tumor cells in women with ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 768.
Abstract 79: Crosstalk of PIM and LKB1 kinases in driving growth of prostate cancer cells
Authors: Mung Kwan Long , Eccleshall William , Santio Niina M. , Rivero-Müller Adolfo , Sahlgren Cecilia , Koskinen Päivi J. 
Published: July 2021

Abstract
The oncogenic PIM kinases and the tumor-suppressive LKB1 kinase have been linked to regulation of cell growth and proliferation. Here we have investigated their potential interactions as well as their relative impacts on tumorigenic growth of prostate cancer cells. The cellular functions of PIM and LKB1 kinases were evaluated using either pan-PIM inhibitors or CRISPR/Cas9-based genomic editing, with which all three PIM family members and/or LKB1 were knocked out from PC3 prostate cancer cells. In addition to cell-based 2D proliferation assays, we examined tumor growth using the chick embryo chorioallantoic membrane (CAM) xenograft model. In this report, we show that inhibition of PIM expression or activity results in increased phosphorylation of AMPK at Thr172 in an LKB1-dependent fashion. With in vitro kinase assays, we demonstrate that LKB1 is a novel direct substrate for PIM kinases and that Ser334 is one of the PIM target sites in LKB1. Accordingly, wild-type LKB1, but not the phosphodeficient S334A mutant can restore PIM inhibitor-induced AMPK phosphorylation in LKB1 knock-out cells. Whereas loss of LKB1 exaggerates formation of PC3-based tumors in the CAM xenograft model, co-deletion of PIM kinases attenuates it. The impairment of cell proliferation and tumor growth in cells lacking both PIM and LKB1 kinases not only underscores the potential crosstalk in signaling between these kinases, but also suggest that PIM inhibitors could be used to restrain growth of LKB1-deficient tumors.
Citation Format: Kwan Long Mung, William Eccleshall, Niina M. Santio, Adolfo Rivero-Müller, Cecilia Sahlgren, Päivi J. Koskinen. Crosstalk of PIM and LKB1 kinases in driving growth of prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 79.
Abstract 791: Incidence rates of digestive cancers among US military servicemen: Comparison with the rates in the general US population
Authors: Bytnar Julie A. , Shriver Craig D. , Zhu Kangmin 
Published: July 2021

Abstract
Background: Digestive cancers greatly contribute to the cancer burden in the United States. These cancers are more common among men and some are increasing among adults under age 50. Military population, which is dominantly male and young, and general populations differ in exposure to risk factors for these cancers. However, no studies have systematically investigated whether the incidence rates of these cancers differ between the two populations. This study aimed to compare incidence rates and trends of select digestive cancers between active-duty military and general populations.
Methods: Data were from the Department of Defenses' Automated Central Tumor Registry (ACTUR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results 9 (SEER-9) registries. Age-adjusted incidence rates of colorectal, stomach, liver, and pancreatic cancers among men aged 20-59 years during 1990-2013 were compared between the two populations. Stratified analyses were done for colorectal and stomach cancers.
Results: The age-adjusted incidence rates of colorectal, stomach, liver, and pancreatic cancers were overall lower among active-duty than SEER (IRR=0.86, 95% CI=0.81-0.92; IRR=0.65, 95% CI=0.55-0.76; IRR=0.39, 95% CI=0.30-0.49; IRR=0.51, 95% CI=0.41-0.62, respectively). This was observed in the subgroups stratified by age for colorectal and stomach cancers except that among men aged 40-59 with colorectal cancer. The incidence rate of colorectal cancer was decreased the latest period (2010-2013) in ACTUR.
Conclusion: The incidence rates for selected digestive cancers overall were lower in the active-duty military population than the U.S. general population. This study highlights the need for more research enhancing our understanding of variations in these cancers between the two populations.
Citation Format: Julie A. Bytnar, Craig D. Shriver, Kangmin Zhu. Incidence rates of digestive cancers among US military servicemen: Comparison with the rates in the general US population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 791.
Abstract 831: State of medical and surgical oncology training in India: An infrastructural challenge to delivering high-quality cancer care
Authors: Ozair Ahmad , Rahman Faique , Singh Kaushal K. 
Published: July 2021

Abstract
Introduction: Cancer care delivery in low- and middle-income countries (LMICs) is significantly influenced by the number and distribution of oncologists, which are products of the state of oncology training in those LMICs. In LMICs like India, where the number of trained oncologists is low, cancer care is often delivered by generalists, resulting in poorer outcomes. India, with a population of 1.38 billion people, was projected to have needed over 5000 oncologists in 2020. But, the Global Survey of Clinical Oncology Workforce reported only 1500 clinical oncologists here in 2018. Therefore, we sought to systematically determine and describe the current state of accredited oncology training in India.
Methods: We searched, in October 2020, the databases of two major accrediting bodies, the National Medical Council (NMC) and the National Board of Examinations (NBE) to determine the total number of programs and the positions therein for the fields of medical, surgical, and gynecological oncology. We correlated our search with the current regulations from NMC and NBE.
Results: Both the NMC and NBE currently offer training for 3-year specialty oncology training after 3-years of medical or surgical residency. We found India currently has a total of 166, 139, and 22 training positions for surgical, medical, and gynecological oncology respectively (Table 1). Significant variation in the number of positions exists, with a few institutions providing training to over 10 fellows, leading to concerns about the volume of training and exposure to cases. There is a clustering of training programs in major metropolitan cities.
Discussion: India is currently training a highly insufficient number of clinical oncologists for its increasing cancer burden. Clustering of training programs in metropolitan cities results in a greater likelihood of trained physicians practicing in the same location. Both of these may cause greater disparities in cancer care delivery.
Table 1.State of accredited oncology training programs and positions in India.SubspecialtyMCI-accredited trainingNBE-accredited trainingNumber of training programsTotal number of positionsMedian (IQR) number of positions per programNumber of training programsTotal number of positionsMean number of positions per programSurgical oncology23983 (2.5)36682Medical Oncology18762 (4)30632Gynecologic Oncology8152 (0.5)472
Citation Format: Ahmad Ozair, Faique Rahman, Kaushal K. Singh. State of medical and surgical oncology training in India: An infrastructural challenge to delivering high-quality cancer care [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 831.
Abstract 834: Association between ABO and Duffy blood types and circulating chemokines and cytokines
Authors: Van Alsten Sarah C. , Aversa John , Santo Loredana , Camargo M. Constanza , Huang Wen-Yi , Kemp Troy , Liu Jia , Samspon Joshua , Rabkin Charles S. 
Published: July 2021

Abstract
Background: Blood group antigens may play a role in immune and inflammatory processes. The aim of this analysis was to identify specific inflammatory pathways associated with blood group antigens.
Methods: We investigated associations between blood type and circulating inflammatory markers in data for 3,537 non-Hispanic white participants selected from previous case-control studies nested in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. Whole genome scans were used to infer blood types for twelve common antigen systems (ABO, Duffy, Lewis, RhE, Kidd, Kell, Secretor, Lutheran, Colton, Dombrock, Auberger, and Knops) based on well-characterized single nucleotide polymorphisms. Circulating levels of 96 immune- and inflammation-related biomarkers were measured on multiplex fluorescent bead-based panels. We estimated associations between blood type and markers using design-weighted linear or logistic regression adjusted for age, sex, smoking status, and principal components of population substructure, and using a Bonferroni correction to control for multiple comparisons.
Results: Among the 1,152 blood type-biomarker associations tested, we identified 10 which were significant after correction for multiple comparisons. ABO subtype was associated with levels of sVEGFR2, sVEGFR3, and sGP130, and Duffy subtype was associated with levels of CXCL6/GCP2, CXCL5/ENA78, CCL11/EOTAXIN, CXCL1/GRO, CCL2/MCP1, CCL13/MCP4, and CCL17/TARC. Post-hoc pairwise t-tests showed that individuals with type A blood had lower levels of all ABO-associated markers than individuals with type O or B blood, while individuals with type Fy(a+b-) had lower levels of all Duffy-associated markers than individuals with type Fy(a+b+) or Fy(a-b+).
Conclusion: ABO blood type is associated with levels of three circulating angiogenic markers, while Duffy blood type is associated with eight chemokines. Additional work to understand the clinical implications of these differences is needed.
Citation Format: Sarah C. Van Alsten, John Aversa, Loredana Santo, M. Constanza Camargo, Wen-Yi Huang, Troy Kemp, Jia Liu, Joshua Samspon, Charles S. Rabkin. Association between ABO and Duffy blood types and circulating chemokines and cytokines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 834.
Abstract 835: T-cell abundance, clonality and disease specific survival in colorectal cancer
Authors: Bonner Joseph , Schmit Sephanie L. , Lindsey Sidney S. , Tsai Ya-Yu , Sanz-Pamplona Rebeca , Alonso M. Henar , Melas Marilena , Rennert Hedy S. , McDonnell Kevin J. , Idos Gregory , Walker Christopher P. , Kast W. Martin , Da Silva Diane , Robins Harlan S. , Greenson Joel K. , Moreno Victor , Rennert Gad , Gruber Stephen B. 
Published: July 2021

Abstract
Immune responses to colorectal cancer (CRC) are important prognostic factors as measured by either tumor infiltrating lymphocytes per high powered field or the presence of Crohn's like lymphoid reaction. New technologies to quantify specific features of immune responses include immunoSeq (Adaptive Biotechnologies), which accurately quantifies T-cell receptor (TCR) abundance and T-cell receptor clonality. Here we measured the independent contributions of TCR abundance and TCR clonality to 5-year CRC-specific survival in the Molecular Epidemiology of Colorectal Cancer (MECC) study. The MECC study consented, interviewed, and followed 6,006 incident cases of CRC diagnosed between March 31, 1998 and July 1, 2017 (median follow-up time = 6.9 years). Archived paraffin blocks were retrieved, and 2,750 cases had sufficient tissue and adequate DNA extraction to perform the immunoSeq assay. Analyses were restricted to 1,625 samples with more than 100 T-cells to permit accurate quantification of TCR abundance and TCR clonality as measured by Simpson Clonality Index. TCR abundance was log2 transformed for analyses, and Simpson Clonality Index was log2-transformed and z-scale normalized separately by assay version. In unadjusted models, dichotomized log2 transformed TCR abundance (Hazard Ratio (HR) = 0.57, 95% confidence interval (CI) 0.47-0.71, p=9.77E-08) and dichotomized TCR clonality (HR = 0.77, 95% CI 0.63-0.94, p=0.01) were each statistically significantly associated with 5-year CRC-specific survival. In a model with adjustment for age, sex, microsatellite instability, stage and assay version, both dichotomized log2 transformed TCR abundance (HR = 0.61, 95% CI, 0.49-0.75, p=3.03E-06), and dichotomized TCR clonality (HR = 0.81, 95% CI, 0.66-0.99, p=0.048) were associated with improved 5-year disease-specific survival.
Conclusion: TCR abundance and TCR clonality are independent prognostic indicators in CRC.
Citation Format: Joseph Bonner, Sephanie L. Schmit, Sidney S. Lindsey, Ya-Yu Tsai, Rebeca Sanz-Pamplona, M. Henar Alonso, Marilena Melas, Hedy S. Rennert, Kevin J. McDonnell, Gregory Idos, Christopher P. Walker, W. Martin Kast, Diane Da Silva, Harlan S. Robins, Joel K. Greenson, Victor Moreno, Gad Rennert, Stephen B. Gruber. T-cell abundance, clonality and disease specific survival in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 835.
Abstract 836: Immunologic markers and the progression of liver disease in HCV-positive individuals
Authors: Argirion Ilona , Pfeiffer Ruth M. , Liu Zhiwei , Hildesheim Allan , Pinto Ligia , McGlynn Katherine A. , Petrick Jessica L. , Lam Tram Kim , O'Brien Thomas R. , Yu Kelly , Chen Chien-jen , Yang Hwai-I , Lee Mei-Hsuan , Koshiol Jill 
Published: July 2021

Abstract
Background: Host immune response and chronic inflammation associated with chronic hepatitis C virus (HCV) infection play a key role in the progression of liver disease from cirrhosis to hepatocellular carcinoma (HCC). We evaluated a large panel of circulating immunologic markers to better understand the natural history of HCV-related liver disease.
Methods: We sampled 94 HCC, 68 cirrhotic and 100 non-cirrhotic controls from a Taiwanese prospective cohort study of chronically HCV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis as compared to controls and those who developed HCC. P-values for individual markers were corrected for multiple testing using a false discovery rate of 10%; a p-value&lt;0.05 was used to determine significance in CDA. Receiver operating characteristic curves were used to compare the predictive ability of marker groups from both analyses.
Results: After adjusting for age, sex, years of follow-up, serum alanine aminotransferase level, alcohol and smoking, DEFA-1 (p-trend: &lt;0.0001), ITGAM (p-trend: &lt;0.0001), CCL18 (p-trend: 0.002) and ARTN (p-trend: 0.003) were all found to be positively associated with the development of cirrhosis when compared to non-cirrhotic controls; the same four markers were shown to be associated with HCC when compared to cirrhotic participants. Taken together, these four markers predicted cirrhosis and HCC development with 79% and 88% accuracy, respectively in adjusted models. CDA models isolated a twelve-marker signature that included DEFA1, CCL18, and ARTN, improving predictability of cirrhosis development to 91% accuracy in adjusted models. Using the same methods, a fourteen-marker signature that included DEFA-1, ITGAM, CCL18 and ARTN was found to predict HCC development with 97% accuracy when compared to cirrhotic individuals in adjusted models.
Conclusion: To our knowledge, this is the first prospective study to assess immunologic markers in relation to liver disease progression in individuals chronically infected with HCV. While further validation is required, these findings highlight the importance of immunologic processes in HCV-related disease.
Citation Format: Ilona Argirion, Ruth M. Pfeiffer, Zhiwei Liu, Allan Hildesheim, Ligia Pinto, Katherine A. McGlynn, Jessica L. Petrick, Tram Kim Lam, Thomas R. O'Brien, Kelly Yu, Chien-jen Chen, Hwai-I Yang, Mei-Hsuan Lee, Jill Koshiol. Immunologic markers and the progression of liver disease in HCV-positive individuals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 836.
Abstract 84: Characterization of oncogenic KRAS A59 alleles and their cooperation with the MAPK signaling pathway
Authors: Johnson Christian W. , Terrell Elizabeth M. , Burd Christin E. , Morrison Deborah , Haigis Kevin M. 
Published: July 2021

Abstract
The Kirsten rat sarcoma (KRAS) proto-oncogene regulates signaling pathways that control proliferation (e.g. MAPK pathway), metabolism and survival (e.g. AKT pathway), and apoptosis (e.g. Hippo pathway). Mutations in KRAS are found in 40% of colorectal cancers (CRC). However, there are no FDA-approved drugs for CRC that target this oncogene. One reason why developing drugs against KRAS is difficult is because a number of different oncogenic alleles have been identified. Thus, an allele-specific approach to target KRAS is necessary. In turn, this approach requires a detailed understanding of their structure and function to drive cell transformation and tissue dysregulation. Our goal is to characterize the function of KRAS A59T in CRC. These alleles are interesting for a number of reasons. First, A59T discriminates retroviral homologues of mammalian RAS from their cellular counterparts. Second, unlike other oncogenic alleles, the KRAS A59T protein undergoes autophosphorylation, the biological function of which is unknown. Third, patient data show that A59 alleles of KRAS frequently co-occur with other genetic alterations in the MAPK signaling pathway, which is uncommon for other KRAS alleles. We hypothesize that KRAS autophosphorylation promotes CRC in a manner that is independent, but cooperative, with the MAPK signaling pathway. To test this hypothesis, we first characterized the function of KRAS A59T and its phosphomimetic A59E using in silico and biochemical techniques, along with classic assays of cell transformation. Next, we generated a new genetically engineered mouse model, K-Ras+/LSL-A59E, in order to test how KRAS autophosphorylation cooperates with other oncogenic mechanisms of MAPK pathway activation to alter colon homeostasis and model colon tumorigenesis. Consistent with our hypothesis, KRAS autophosphorylation and A59E inhibit KRAS-effector interactions that activate the MAPK, AKT, and Hippo signaling pathways. How this change in function alters the ability of K-RasA59E, versus K-RasG12D, to promote hyperproliferation and tumor development in combination with N-RasQ61K and Apc loss in the mouse colon, is currently underway. Ultimately, these studies bring us closer to discovering allele-specific vulnerabilities of KRAS and provide a means to test less understood aspects of oncogenic KRAS signaling.
Citation Format: Christian W. Johnson, Elizabeth M. Terrell, Christin E. Burd, Deborah Morrison, Kevin M. Haigis. Characterization of oncogenic KRAS A59 alleles and their cooperation with the MAPK signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 84.