bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5763: Incidence and mortality predictors of ill-defined illness (non-diagnosed conditions) as a cause of death in cancer patients: A population-based study
Authors: Elfaituri Muhammed Khaled , Morsy Sara , Huy Nguyen Tien 
Published: September 2020

Abstract
Introduction:
This observational study characterised ill-defined illness (non-diagnosed conditions) mortality risk for multiple cancer sites, with respect to other factors related to the patient's condition and demographic information.
Method: Using the Surveillance, Epidemiology and End Results (SEER) database (1975-2016), complete data on 24378 patients were identified; their death was due to non-diagnosed conditions were identified. Overall survival (OS) was estimated using the Kaplan-Meier method. Cox, the proportional hazards model, were used to produce adjusted hazard ratios (HR). Trend analysis was conducted using joinpoint regression analysis with four join points, and annual percentage change (APC) was calculated.
Results: We found that 24378 cancer patients died due to unknown conditions. The mean age of the patients was 71.22, and most of them were female (50.6%). Most tumours were malignant 92.2% and grade II (n = 6650 (27.3%)). Most patients had surgery, only. White and married patients constituted most of the patients. The most common site associated with the ill-defined condition was GIT (n = 4578) followed by breast (n = 4003) followed by the male genital system (n = 3630). The most common pathology associated with ill-defined conditions was adenoma and adenocarcinoma (n = 9575) followed by ductal and lobular carcinoma (n = 3501) followed by squamous cell carcinoma (n = 2181). There were five trends observed for the mortality due to undiagnosed conditions. The rate of cases increased significantly from 1975 to 2008; then there was a decrease in cases from 2008 till 2015, but it was small and insignificant followed by a significant decrease in the number of cases [-59.4, (95% CI = -71.4; -42.5), p-value &lt;0.001]. The overall average annual percent change was significant increase was 4.8% (95% CI = 4.8; 9.9, p-value &lt; 0.001). Based on the logistic regression analysis, older males had a higher risk for the disease.
Conclusion: Our study finding might serve as a reference for clinicians when evaluating patients with cancer to search for any underlying condition that was not diagnosed during the disease course, as this will help to reduce the mortality associated with these conditions.
Citation Format: Muhammed Khaled Elfaituri, Sara Morsy, Nguyen Tien Huy. Incidence and mortality predictors of ill-defined illness (non-diagnosed conditions) as a cause of death in cancer patients: A population-based study [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 5763.
Abstract 5764: Descriptive epidemiology and clinicopathology of latent versus active JAK2-myeloproliferative neoplasms (MPN)
Authors: Haddad Philip A. , Gallagher Kevin , Hammoud Dalia 
Published: September 2020

Abstract
Splanchnic vein thromboses (SVT) encompass portal, mesenteric, splenic, and hepatic veins thromboses, and often cause Budd-Chiari syndrome (BCS). JAK2-MPNs were found to be the most common cause of SVT and BCS, accounting for up to 50% of all cases. Moreover, endothelial cells harboring JAK2 mutations have been demonstrated in patients with BCS which may contribute to the overall prothrombotic propensity. The aim of this study is to describe the epidemiology and clinicopathology of latent JAK2-MPN (LMPN), where JAK2 mutation is detected without clinical evidence of MPN, versus active JAK2-MPN (AMPN) where JAK2+ MPN is present, in a pooled cohort with SVT and/or BCS. In order to study the demographic characteristics, survival, and prognostic factors, we compiled a pooled database of 90 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinical factors on survival. The cohort consisted of 65% LMPN and 35% AMPN. The median age for patients with SVT/BCS with LMPN and AMPN was 39(15-85) years and 42(24-80) years respectively. The peak incidence of SVT/BCS seems to occur between ages 36 and 48 for LMPN and 24-36 for AMPN. In both groups, females were twice more predominant than males. The AMPN group consisted of 41% Polycythemia Vera (PV), 22% Essential Thrombocythemia (ET), 28% Myelofibrosis (MF), and 3% others. There was no difference in the frequency of particular splanchnic veins' involvement or the number of coexisting acquired or inherited conditions between the two groups. Survival of patients with BCS did not differ by their MPN status or sex. Twenty-four percent of LMPN progressed to AMPN (57% ET, 21.5% PV, and 21.5% MF). The median time to progression was 55 (12-96) months among those that progressed. While the median time to progression was longer for males (63 vs 39 months) this difference did not reach statistical significance. This study describes for the first time the epidemiologic and clinical characteristics of patients with SVT/BSC and LMPN and compares them to those of AMPN. It also reveals that while some SVT/BCS with LMPN progress to active MPN diseases, a sizable proportion of these patients remain latent indicating that its prothrombotic propensity is independent of AMPN phenotype expression.
Citation Format: Philip A. Haddad, Kevin Gallagher, Dalia Hammoud. Descriptive epidemiology and clinicopathology of latent versus active JAK2-myeloproliferative neoplasms (MPN) [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 5764.
Abstract 5768: Peripartum blood transfusions are associated with increased risk of cancer: A national retrospective cohort study
Authors: Chae Young Kwang , Oh Michael S. , Lee Misuk , Cho Sukjoo , Park Jonghanne , Cho Geum Joon 
Published: September 2020

Abstract
Background: The effect of blood transfusions on the risk of developing primary cancer remains unclear, especially when administered in the peripartum period.
Methods: We conducted a retrospective cohort study of 270,529 pregnant women who delivered between January 1, 2007 and December 31, 2009, with data obtained from three national databases in South Korea. From this cohort, we identified 4,569 patients who received peripartum blood transfusions. We calculated hazard ratios (HRs) for new diagnoses of cancer, and adjusted them for relevant clinical factors using a Cox proportional hazards model.
Results: During follow-up, patients who received peripartum transfusions had an increased risk of developing cancer, with an adjusted HR of 1.16 (95% confidence interval [CI], 1.01-1.34). This risk was significant only among patients who received 3 or more units of blood, with an adjusted HR of 1.40 (95% CI, 1.10-1.79). Increased risk after transfusions were seen with brain, lung, ovarian, and gallbladder cancers. The difference in cancer risk between the transfusion and no-transfusion groups remained significant during both the first (1.34% vs 1.10%, p &lt; 0.01) and second year (0.78% vs 0.58%, p &lt; 0.01) after delivery.
Conclusion: Receipt of 3 or more blood transfusions in the peripartum period was associated with a significantly increased risk of developing cancer.
Citation Format: Young Kwang Chae, Michael S. Oh, Misuk Lee, Sukjoo Cho, Jonghanne Park, Geum Joon Cho. Peripartum blood transfusions are associated with increased risk of cancer: A national retrospective cohort study [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 5768.
Abstract 5790: An epigenome-wide gene-age interaction analysis reveals opposite effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
Authors: Su Li 
Published: September 2020

Abstract
Introduction: Aging has become a global public health concern. The number of elderly lung cancer patients increased and elderly comprise the majority (81%) of non-small cell lung cancer (NSCLC) patients. DNA methylation is a potential prognostic biomarker for NSCLC, while it is also associated with aging. However, whether the association between DNA methylation and NSCLC survival is modified by aging is not known.
Methods: After quality control procedures, we used a two-stage study design to identify DNA methylation-age interaction that associated with overall survival (OS) for early-stage adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients from four international collaborating study centers. In the discovery phase, we investigated the interaction effect in LUAD and LUSC using Cox proportional hazards model, adjusted for covariates. We confirmed the significant interactions with Bonferroni adjusted P ≤ 0.05 were further confirmed in the validation phase using The Cancer Genome Atlas (TCGA) database.
Results: A total of 1,230 LUAD and LUSC patients were eligible for the study and 311,981 DNA methylation loci were evaluated. There were 613 (NLUAD = 492 and NLUSC = 121) patients in the discovery phase, and 617 (NLUAD = 332 and NLUSC = 285) patients in the validation phase, respectively. We identified one LUAD-specific CpG probe cg14326354PRODH, the effect on OS was significantly modified by age (HRinteraction = 0.989; 95% CI: 0.986-0.994; P = 9.18 × 10−7). The effect of DNA methylation on OS was different in young and elderly patients (young: HR = 2.44; 95% CI: 1.26-4.72; P = 8.34 × 10−3; elderly: HR = 0.58; 95% CI: 0.42-0.82; P = 1.67 × 10−3). Low methylation level benefited elderly LUAD patients. Moreover, there was an antagonistic interaction between low methylation of cg14326354PRODH and elder age (HRinteraction = 0.21; 95% CI: 0.11-0.40; P = 2.20 × 10−6).
Conclusion: Low methylation of cg14326354PRODH may benefit the survival of elderly LUAD patients, providing new insight into only age-specific prediction, but also potential methylation-specific drug targeting.
Citation Format: Li Su. An epigenome-wide gene-age interaction analysis reveals opposite effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients [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 5790.
Abstract 5796: Therapeutic effects of statins against lung adenocarcinoma via mutant p53 mediated apoptosis
Authors: Chou Cheng-wei , Lin Ching-Heng , Hsiao Tzu-Hung , Lo Chia-Chien , Hsieh Chih-Ying , Huang Cheng-Chung , Sher Yuh-Pyng 
Published: September 2020

Abstract
Introduction The p53 gene is well known as an important tumor suppressor gene. Mutant p53 genes account for about half of all lung cancer cases. There is increasing evidence for the anti-tumor effects of statins via inhibition of the mevalonate pathway. However, the cancer prevention and protection effects of statinsin population-based studies are controversial. Previous population-based studies have shown protective effects of statins in advanced lung cancer patients; however, the effects in early lung cancer patients are unclear.
Methods We investigated the correlation between statin use and lung cancer prognosis using the Taiwanese National Health Insurance Research Database retrospectively, mainly focusing on early-stage lung cancer. Cell viability, lipid raft changes, and motile activity from simvastatin-treated cell lines were examined to determine the effect of simvastatin under different p53 mutations. Apoptotic pathways and autophagy in lung cancer cells treated with simvastatin were analyzed using a western blot assay.
Results Statin treatments reduced the 5-year mortality (odds ratio, 0.43; 95% confidence interval [CI], 0.37-0.49;P&lt; 0.001) in this population-based study. Simvastatin inhibited cell growth, especially in mutant p53 lung cancer cell lines. Significantly higher levels of cellular apoptosis and decreased lipid rafts were shown in mutant p53 lung cancer cells treated with simvastatin. Further, simvastatin increased activity of the caspase-dependent apoptotic pathway in lung cancer cells containing mutant p53. In addition, simvastatin reduced migration in cells with a mutated p53 gene.
Conclusion This study reports the protective effects of statin use in early-stage lung cancer patients regardless of chemotherapy. Simvastatin induced cellular apoptosis and regulated lipid raft content; further, motile activity was reduced in lung cancer cells with p53 missense mutations. These data suggest that statin use in selected lung cancer patients may have clinical benefits.
Citation Format: Cheng-wei Chou, Ching-Heng Lin, Tzu-Hung Hsiao, Chia-Chien Lo, Chih-Ying Hsieh, Cheng-Chung Huang, Yuh-Pyng Sher. Therapeutic effects of statins against lung adenocarcinoma via mutant p53 mediated apoptosis [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 5796.
Abstract 5837: Exploring integrated stress response pathway to target MYC-amplified medulloblastoma
Authors: Langman Sofya , Sorensen Poul H. 
Published: September 2020

Abstract
Medulloblastoma (MB) accounts for 20% of diagnosed brain tumors in children. The Group 3 (G3) MB subtype is found to be especially malignant. Current G3 MB treatment regimens provide for 50% 5-year survival rates and are associated with severe side effects, including hearing loss and neurocognitive deficits. G3 MB is characterized by MYC overexpression, which drives elevated protein translation in tumor cells. High expression levels of PERK correlate with poor survival outcome in G3 MB, and knockdown of PERK combined with hypoxic stress induces apoptosis in MB cells. PERK is an eIF2α kinase that responds to ER stress and is one of the key mediators of unfolded protein response. When ER stress is detected, PERK phosphorylates eIF2α to shut down global translation and to initiate integrated stress response. However, there are 3 other eIF2α kinases that work alongside PERK to help cells respond to various stresses. ISRIB is in an integrated stress response inhibitor that blocks P-eIF2α attenuation by eIF2B, thus maintaining high translation levels under stress. Combining ISRIB with stress such as hypoxia induces apoptosis in MB cells. In addition, combination of ISRIB and hypoxia is correlated with increased levels of oxidative stress. Apart from restoring global translation levels, ISRIB can prevent stress granules (SGs) from being formed. High expression of SG proteins such as G3BP1 and YB1 also correlates with poor survival outcome in G3 MB patients. When SG formation is inhibited by knocking down expression of G3BP1 and G3BP2, MB cells undergo higher levels of apoptosis under vincristine induced stress. We show that preventing G3 MB cells from undergoing integrated stress response and inhibiting formation of stress granules induces higher levels of cancer cell death. Overall, combining ISRIB with conventional chemotherapy may enhance the effects of the latter, which is increasingly relevant for patients suffering from G3 MB.
Citation Format: Sofya Langman, Poul H. Sorensen. Exploring integrated stress response pathway to target MYC-amplified medulloblastoma [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 5837.
Abstract 5849: Association between annexin-A6 expression and metabolic vulnerabilities of TNBC cells and their response to EGFR-tyrosine kinase inhibitors
Authors: Williams Stephen D. , Sakwe Amos M. 
Published: September 2020

Abstract
PURPOSE: Triple-negative breast cancer (TNBC), and the basal-like TNBC subtype, accounts for ~20% of all breast cancer (BC) cases, and is particularly prevalent in younger patients of African-American and Hispanic descent. The importance of annexin A6 (AnxA6) as a tumor suppressor in various cancers has been widely investigated, but the mechanisms by which AnxA6-induced basal-like triple negative breast cancer progression remain largely unknown. Physiological changes such as hypoxia, metabolic acidosis, and oxidative stress in the tumor microenvironment (TME) during cancer progression endow cancer cells with malignant properties, ultimately leading to metastatic dissemination that remains the major cause of death in cancer patients. By linking the altered expression status of AnxA6, with changes in metabolic output of the tumor cells and the efficacy of the otherwise ineffective epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), these metabolic vulnerabilities can be targeted to attenuate the growth and/or motility of this hard-to-treat breast cancer subtype. DESIGN METHODS: AnxA6-high (BT-549) and AnxA6-low (MDA-468) TNBC cell lines were cultured in hypoxic conditions (94%N2; 1%O2; 5%CO2; 37°C) using a Bactrox Hypoxia Chamber (Terra Universal Inc., Fullerton, CA). TNBC cells were treated with EGFR-TKI Lapatinib (Biovision Inc., Milpitas, CA).
RESULTS: We demonstrate that exposure of AnxA6-high (BT-549) and AnxA6-low (MDA-468) TNBC cell lines to acute hypoxia (1% O2; ≤24 hrs.) is associated with down-regulation of AnxA6 while chronic hypoxia (1% O2; &gt;24 hrs.) led to a consistent up-regulation of AnxA6. AnxA6, FABP4, and HIF-1α downstream genes GLUT1 and PGK-1, mRNA levels were upregulated in chronic hypoxic conditions. AnxA6 metabolic studies reveal that contrary to AnxA6-high, down regulation of AnxA6 in TNBC cells increased lactate production, glucose consumption, and ATP-synthesis and lipid metabolism under hypoxia. In addition, chronic hypoxia sensitized TNBC cells to EGFR-TKIs. CONCLUSION: These data suggest that the transition from AnxA6-high to AnxA6-low may be dependent on hypoxia in the TME and consequently, TNBC cell survival and resistance to EGFR-targeted therapies.
Supported by NIH/NIGMS 1SC1CA211030 (AMS)
Citation Format: Stephen D. Williams, Amos M. Sakwe. Association between annexin-A6 expression and metabolic vulnerabilities of TNBC cells and their response to EGFR-tyrosine kinase inhibitors [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 5849.
Abstract 5910: Single-cell multiomic analysis of SNV, CNV, and protein expression
Authors: Ooi Aik , Mendez Pedro , Dhingra Dalia , Beard Nigel , Ruff David 
Published: September 2020

Abstract
Recent advancements in precision medicine, while highly promising, presents a major technical challenge to researchers due to disease heterogeneity. The emergence of single-cell technologies has greatly refined the resolution in which sample diversity can be investigated, enhancing the efficiency of selecting appropriate molecular targets. Additionally, applying multiomic analysis on single cells would further improve the understanding of cell-to-cell heterogeneity by providing unique insights on cellular and genetic composition. Using a two-step droplet microfluidic technology, the Mission Bio Tapestri Platform enables multiplex-PCR based high-throughput targeted DNA sequencing in single cells to obtain single-nucleotide variation (SNV) and copy number variation (CNV) information. By leveraging this technology, a new workflow is developed to detect protein expression in addition to DNA genotype in the same single cells. In this approach, cells are labeled with a pool of oligonucleotide-conjugated antibodies prior to loading the cells into the Tapestri Instrument for targeted DNA analysis. Sequencing libraries are then prepared from both antibody oligonucleotides and the amplified DNA sequences, followed by identification of single-cell DNA genotypes and protein signatures from the sequencing readout. In a mixed population of four cell lines, single-cell SNV and CNV information from 127 targeted amplicons and the protein data from 10 antibodies independently classified the cells into appropriate clusters. This method has been successfully performed on clinical samples with myeloid malignancies. In an acute myeloid leukemia (AML) sample, combined single-cell SNV, CNV, and protein expression data illustrated the heterogeneity within the sample. The data clearly identified CD3+ T cells and CD19+ B cells without pathogenic SNVs and CNVs. CD34hiCD11blo and CD34loCD11bhi subpopulations were also identified within the cells carrying the same pathogenic SNVs and CNVs. We believe that this novel multiomic technology will enable new discoveries in the complex relationship between genotype and phenotype, leading to a better understanding of disease biology, and subsequently better design of diagnostics and therapies.
Citation Format: Aik Ooi, Pedro Mendez, Dalia Dhingra, Nigel Beard, David Ruff. Single-cell multiomic analysis of SNV, CNV, and protein expression [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 5910.
Abstract 5956: New molecular mechanisms of small cell lung cancer growth
Authors: Alam Sk. Kayum , Wang Li , Ren Yanan , Hernandez Christina E. , Kosari Farhad , Roden Anja C. , Yang Rendong , Hoeppner Luke H. 
Published: September 2020

Abstract
Lung cancer is the leading cause of cancer death among both men and women in the United States. Small cell lung cancer (SCLC) results in over 30,000 deaths of Americans annually and comprises 15-17% incidences of lung cancer. SCLC is the most aggressive form of lung cancer due to its rapid doubling time and early widespread metastasis. Most SCLC patients present with advanced disease, respond to initial systemic chemotherapy, and then treatment refractory progression usually occurs within one year due to acquired drug resistance. Consequently, the median survival time of SCLC patients is only 9 to 20 months and merely 7% of SCLC patients survive beyond five years. A better molecular understanding of SCLC is necessary to develop much needed new treatment strategies. For the first time, we demonstrate that dopamine and cAMP-regulated phosphoprotein, Mr 32000 (DARPP-32) and its splice variant t-DARPP stimulate tumors of neuroendocrine origin, and we show DARPP-32 proteins are aberrantly overexpressed in human SCLC. Upregulation of t-DARPP protein in a subset of SCLC patients positively correlates with overexpression of genes associated with Notch signaling, including achaete-scute homologue 1 (ASCL1). We reveal that DARPP-32 isoforms are transcriptionally activated by ASCL1 in human SCLC cells. To determine whether DARPP-32 drives SCLC growth in vivo, we utilized an orthotopic lung cancer xenograft mouse model. Mice challenged with DARPP-32-ablated DMS-53 cells show a substantial decrease in lung tumor growth relative to controls. Correspondingly, we demonstrate increased tumor growth in mice harboring lung tumors formed by administration of DMS-53 or H1048 cells overexpressing DARPP-32 and t-DARPP proteins. Mechanistically, we describe how DARPP-32 isoforms promote SCLC growth through increased proliferation, Akt/Erk-mediated survival, and anti-apoptotic signaling. Taken together, we define new regulatory mechanisms of SCLC oncogenesis that suggest DARPP-32 isoforms may represent a negative prognostic indicator for SCLC and serve as a potential target for the development of new therapies.
Citation Format: Sk. Kayum Alam, Li Wang, Yanan Ren, Christina E. Hernandez, Farhad Kosari, Anja C. Roden, Rendong Yang, Luke H. Hoeppner. New molecular mechanisms of small cell lung cancer growth [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 5956.