tbuckley/cabot-search huggingface dataset:
Abstract 4192: Increasing incidence of EBV-related nasopharyngeal carcinoma in the United States
Authors: Ilona Argirion, Katie R. Zarins, Julie J. Ruterbusch, Patravoot Vatanasapt, Hutcha Sriplung, Erlene K. Seymour, Laura S. Rozek
Journal: Cancer Research (2019)

Abstract Purpose: Incidence of nasopharyngeal carcinoma (NPC) is highly geographically variable and historically rare in the US. While etiological factors differ by histological subtype, Epstein-Barr virus (EBV) is generally accepted as the primary risk factor for non-keratinizing NPC. In light of the changing epidemiology of HPV-associated oropharyngeal cancer, it is important to evaluate temporal incidence of NPC in the US. Methods: Incidence and survival data from 1973-2015 were obtained from the Surveillance, Epidemiology and End Results (SEER) Program. Stratified analyses were conducted to assess temporal trends in NPC by histological subtype, sex and race. The data were analyzed using SAS 9.4 and Joinpoint Regression Software to determine age-adjusted incidence rates, trends in annual percent change (APC) as well as calculate 5-year relative survival estimates and Kaplan-Meier curves. Results: Although overall NPC incidence is decreasing in the US, the non-keratinizing differentiated subtype appears to be starkly increasing with an APC of approximately 4% among white males (95%CI: 2.5, 5.2), white females (95%CI: 1.9, 6.2), and black males (95%CI: 2.0, 5.7), 2.7% among black females (95%CI: 0.8, 4.6) and 1.8% among women of other race (95%CI: 0.4, 3.3). When compared to other histological subtypes, patients with keratinizing squamous cell carcinoma had the worst survival (log rank p&amp;lt;0.001). Additional survival disparities were noted, with black males having consistently poorer survival across all histological subtypes, and those individuals in the “other” race category, particularly females, experiencing the highest 5-year relative survival estimates. Conclusions: Although NPC remains relatively rare in the overall US population, there is evidence to suggest that the EBV-related differentiated subtype is increasing across all genders and races. Citation Format: Ilona Argirion, Katie R. Zarins, Julie J. Ruterbusch, Patravoot Vatanasapt, Hutcha Sriplung, Erlene K. Seymour, Laura S. Rozek. Increasing incidence of EBV-related nasopharyngeal carcinoma in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4192.
Cleaner air cut deaths by 8.8% over 40 years, but more progress is needed
Authors: Nigel Hawkes
Journal: BMJ (2019)

Improvements in air quality cut the number of deaths attributable to pollution in the UK sharply between 1970 and 2010, a new analysis has shown.

While in 1970 small particles less than 2.5 µm in diameter (PM2.5) were responsible for 11.8% of deaths, by 2010 that had more than halved, to 5.3%.

Nitrogen dioxide (NO2), the pollutant principally targeted in the current campaign against diesel vehicles, was responsible for 5.3% of deaths in 1970 and 3.0% in 2010, say the team from the Centre for Ecology and Hydrology.1

Emissions of NO2 have fallen by a further 25% since 2010, according to …
Search for new predictive/prognostic biomarkers in potentially resectable pancreatic ductal adenocarcinoma
Authors: I. González Borja, A. Viudez, S. Goñi, J. Pérez Sanz, E. Santamaria, C. López-López, R. Pazo, P. Jimenez Fonseca, S. Arévalo, J. Feliu, J. Fernández Irigoyen
Journal: Annals of Oncology (2019)
FOLFIRINOX versus Nab-paclitaxel plus gemcitabine in the first-line chemotherapy for patients with advanced pancreatic ductal adenocarcinoma: a multivariate analysis of prognostic factors in a national cohort (Comunica-TTD working group)
Authors: F. Longo Muñoz, O. Castillo Trujillo, J. Serrano Domingo, R. Martín Huertas, E. Corral de la Fuente, A. San Juan, J. Portela, J. Cano, P. Reguera Puertas, M. Rodriguez Garrote, M. Izquierdo Manuel, P. Jimenez Fonseca, A. Carrato, E. Aranda
Journal: Annals of Oncology (2019)
N-Myc–mediated epigenetic reprogramming drives lineage plasticity in advanced prostate cancer
Authors: Adeline Berger, Nicholas J. Brady, Rohan Bareja, Brian Robinson, Vincenza Conteduca, Michael A. Augello, Loredana Puca, Adnan Ahmed, Etienne Dardenne, Xiaodong Lu, Inah Hwang, Alyssa M. Bagadion, Andrea Sboner, Olivier Elemento, Jihye Paik, Jindan Yu, Christopher E. Barbieri, Noah Dephoure, Himisha Beltran, David S. Rickman
Journal: Journal of Clinical Investigation (2019)

Despite recent therapeutic advances, prostate cancer remains a leading cause of cancer-related death. A subset of castration-resistant prostate cancers become androgen receptor (AR) signaling independent and develop neuroendocrine prostate cancer (NEPC) features through lineage plasticity. These NEPC tumors, associated with aggressive disease and poor prognosis, are driven, in part, by aberrant expression of N-Myc, through mechanisms that remain unclear. Integrative analysis of the N-Myc transcriptome, cistrome, and interactome using in vivo, in vitro, and ex vivo models (including patient-derived organoids) identified a lineage switch towards a neural identity associated with epigenetic reprogramming. N-Myc and known AR cofactors (e.g., FOXA1 and HOXB13) overlapped, independently of AR, at genomic loci implicated in neural lineage specification. Moreover, histone marks specifically associated with lineage-defining genes were reprogrammed by N-Myc. We also demonstrated that the N-Myc–induced molecular program accurately classifies our cohort of patients with advanced prostate cancer. Finally, we revealed the potential for enhancer of zeste homolog 2 (EZH2) inhibition to reverse the N-Myc–induced suppression of epithelial lineage genes. Altogether, our data provide insights into how N-Myc regulates lineage plasticity and epigenetic reprogramming associated with lineage specification. The N-Myc signature we defined could also help predict the evolution of prostate cancer and thus better guide the choice of future therapeutic strategies.
Abstract 5164: Signaling crosstalk within prostate tumor microenvironment mediates castrate resistant disease progression
Authors: Manisha Tripathi, Srinivas Nandana, Jen-Ming Huang, Manabu Kato, Rajeev Mishra, Leland Chung, Li Xin, Neil Bhowmick
Journal: Cancer Research (2019)

Abstract Juxtacrine signaling with the stromal compartment is important to the development of castrate resistance prostate cancer. We found that Notch signaling is upregulated in prostate cancer associated fibroblasts (CAFs) compared with normal tissue associated fibroblasts (NAFs). Further, inhibition of Notch signaling in CAFs resulted in decreased Wnt signaling and decrease in expression of Notch pathway genes. Interestingly, androgen receptor antagonism resulted in increased Notch signaling and the upregulation of downstream Wnts. Further, generation of chimeric tissue recombinant xenografts with human RV1 prostate cancer epithelia with mouse prostate stromal cells with activated Notch signaling that are derived from NICD transgenic mice resulted in increased tumor size compared with wild type control stromal recombinants. Conversely, recombinants derived from prostatic fibroblasts of RBPJ-knockout mice that have a loss of Notch signaling demonstrated diminished tumorigenesis, compared with xenografts with the wild type fibroblasts. In trying to determine the mediator of Wnt-associated paracrine prostate epithelial expansion, we found downstream YAP activation in the RV1 cells. In a reciprocal epithelial-to-fibroblast communication we found that the RV1 cells treated with conditioned media from NICD fibroblasts showed increased IL-6 expression. Conversely, conditioned media from prostate cancer cells caused increased Notch target gene expression in CAFs, which was blocked upon addition of IL-6 neutralizing antibody. Taken together our results suggest that there is a stromal-derived feed-back - feed-forward signaling loop involving Notch and Wnt ligands that activates YAP in the epithelia for paracrine IL-6-dependent Notch activity back in the stromal fibroblasts. Critically, disruption of this cross-talk in the fibroblasts can potentially limit the gain of stem features and castrate resistance of the adjacent epithelia in halting lethal progression of prostate cancer. Citation Format: Manisha Tripathi, Srinivas Nandana, Jen-Ming Huang, Manabu Kato, Rajeev Mishra, Leland Chung, Li Xin, Neil Bhowmick. Signaling crosstalk within prostate tumor microenvironment mediates castrate resistant disease progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5164.
Abstract 4125: Precise and reproducible measurement of tumor mutational burden using panel sequencing: the role of panel size and of mutation types
Authors: Jan Budczies, Eugen Rempel, Michael Allgäuer, Daniel Kazdal, Volker Endris, Peter Schirmacher, Albrecht Stenzinger
Journal: Cancer Research (2019)

Abstract Tumor mutational burden (TMB) is an emerging biomarker for patient stratification for immune checkpoint inhibition. Implementing TMB measurement by panel sequencing, experimental setup and bioinformatics pipelines need to be optimized to minimize sources of error and variance. To gain insight into contributors to TMB variance, combinatorial calculations were performed based on the hypothesis that each base in the coding sequence was mutated with the same probability. Simulations of sequencing panels in the TCGA data were performed to check for additional contributors to the variance. A narrow definition of TMB including only missense mutations was compared to a broader definition additionally including other mutation types. The quantity under investigation was TMB measured in relatively to the size of the panel (per Mbp). The combinatorial contribution to the coefficient of variation (CV) of TMB turned out to be inversely proportional to the square root of the panel size and inversely proportional to the square root of the TMB. For a tumor with TMB of 10 muts/Mbp, the combinatorial CV increased drastically for panels sizes smaller than 1.5 Mbp. The combinatorial variance represents a persistent contribution to the error of TMB calculation that cannot be avoided. Simulations in WES data confirmed the combinatorial variance as main contributor to the imprecision of TMB estimation. In many instances, the fold change between the number of all mutations in the coding sequence and the number of missense mutations was similar for tumors of the same cancer type. However, the fold changes were different in specific cancer types for example significantly higher in melanoma (1.66) compared lung adenocarcinoma (1.48). In particular, the former tumors were observed to include a higher proportion of synonymous mutations than the latter. The combinatorial source of error implies that a panel of least 1.5 Mbp is needed to precisely determine TMB for tumors ranging around typical currently used diagnostic thresholds (10 muts/Mbp). Additional sources of error might even favor larger panel sizes such as 3 Mbp. The combinatorial error can be reduced by including all mutations types instead of only missense mutations and simultaneously adjusting TMB with a cancer type specific factor. Citation Format: Jan Budczies, Eugen Rempel, Michael Allgäuer, Daniel Kazdal, Volker Endris, Peter Schirmacher, Albrecht Stenzinger. Precise and reproducible measurement of tumor mutational burden using panel sequencing: the role of panel size and of mutation types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4125.
Abstract 15745: Low Income Predicts Mortality Independently From the Presence of Type 2 Diabetes and Pre-Existing Coronary Artery Disease
Authors: Christoph H Saely, Alexander Vonbank, Christine Heinzle, Daniela Zanolin, Barbara Larcher, Arthur Mader, Andreas Leiherer, Axel Muendlein, Heinz Drexel
Journal: Circulation (2018)

Introduction: A low socioeconomic status has been associated with increased mortality. Hypothesis: We tested the hypothesis that low income predicts mortality risk independently from the presence o...
Mechanism of tea catechin and caffeine in inhibition of lung tumor progression induced by 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mouse
Authors: Gang Lu, Jie Liao, Guangyu Yang, Cs Yang
Journal: Cancer Research (2006)

1914  Chemoprevention is considered as a promising weapon to fight against cancers. The present study investigated the inhibitory effects of Polyphenon E (a standardized green tea polyphenol preparation containing 65% EGCG) and caffeine on lung tumor progression from adenoma to adenocarcinoma in 4-(methylnitrosaminao)-1-(3-pyridyl)-1-butanone (NNK) model. Female A/J mice were treated with a single dose of NNK (103 mg/kg b.w., ip), and by Week 20, the mice developed lung adenoma. The mice were then given 0.5% Polyphenon E or 0.044% caffeine as the sole source of drinking fluid until Week 52. Polyphenon E administration significantly reduced the incidence (by 52%) and multiplicity (by 63%) of lung adenocarcinoma. Caffeine also showed inhibitory effects, but the results were not statistically significant. Markers of cell proliferation, apoptosis, and cellular signal pathways were studied by immunohistochemistry. Labeling index and staining intensity were quantified by Image-Pro system. Polyphenon E and caffeine treatment inhibited cell proliferation (by 57% and 50%, respectively in adenocarcinomas) and enhanced apoptosis in the adenomas (both by 2.5 folds) and adenocarcinomas (by 2.6 and 4 folds, respectively), but both agents had no significant effect on apoptosis in the normal tissues. The cancer preventive effects of Polyphenon E and caffeine were associated with lower levels of Erk and c-Jun phosphorylation. Furthermore, a two-week treatment (0.32% EGCG or 0.044% caffeine) on mice, that have developed adenoma at 20 weeks after NNK injection, showed increased apoptotic index (by 130% and 140%, respectively) in the adenomas. Caffeine administration reduced Erk and c-Jun phosphorylation levels (38% and 72%, respectively; P
Abstract 2047: Identification of endometrial cancer specific immuno-therapeutic targets by comprehensive In Silico analysis
Authors: Yuji Ikeda
Journal: Cancer Research (2019)

Abstract Background; Immune-therapeutic targets specific to endometrial cancer has been unclarified. In term of HLA allele type, about 60% and 40% of Japanese has HLA-A*24 and -A*02,respectively. Development of new immune-therapeutics taking account of these types is required. We herein aimed to identify immune-therapeutic targets specific to endometrial cancer and commonly available for Japanese patients using in Silico analysis, which can search comprehensively peptides binding to HLA molecule in an allele-specific manner. Methods; mRNA sequencing data obtained from 582 samples of endometrial cancer and 53 control samples from 31 normal organs were extracted from cancer genome atlas (TCGA) database and Genotype-Tissue Expression project, respectively. After filtering of protein coding genes, 8 to 12 peptides with high binding affinity to HLA-A*24 and -A*02 alleles were identified by an artificial neural network soft trained for peptide-MHC class I binding. Results; Based on mRNA sequencing data, we identified 71 genes that are expressed in endometrial cancer but not in control organs. Of them, top ten genes with high mRNA levels in the cancer are selected. Analysis of binding affinity revealed that 21 and 146 peptides derived-from ten genes of interest showed high binding affinity to HLA-A*24 and -A*02, respectively. Especially, one target gene showed the highest expression levels in endometrial cancer, and possessed 15 and 58 candidate peptides in HLA-A*24 and -A*02, respectively. Conclusion; By comprehensive analysis using mRNA data, we identified reliable candidates target of immune-therapeutics for HLA-A*02 and -A*24 patient with endometrial cancer. Citation Format: Yuji Ikeda. Identification of endometrial cancer specific immuno-therapeutic targets by comprehensive In Silico analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2047.
Serious-Illness Care 2.0 — Meeting the Needs of Patients with Heart Failure
Authors: Haider J. Warraich, Diane E. Meier
Journal: New England Journal of Medicine (2019)

Palliative and hospice care remain underused for patients with heart failure. In the next phase of serious-illness care, care delivery innovations can help providers integrate approaches to improving functioning and quality of life into the care of such patients.
Abstract 1577: Telomerase reverse transcriptase (<i>TERT</i>) promoter mutations in cancers derived from multiple organ sites among Middle Eastern population
Authors: Rong Bu, Abdul K. Siraj, Kaleem Iqbal, Sandeep Parvathareddy, Mark Diaz, Dionne Rala, Ingrid G. Victoria, Khadija Al-Obaisi, Wael Al-Haqawi, Nabil Siraj, Allianah Benito, Khawla S. Al-Kuraya
Journal: Cancer Research (2019)

Abstract Activation of telomerase induced by telomerase reverse transcriptase (TERT) promoter mutations has been implicated in human carcinogenesis. The two mutations termed C228T and C250T in TERT promoter region have been reported in various human tumor entities with different frequencies in Western populations. However, the contribution of these mutations to cancer progression in the Middle Eastern region remains poorly understood. In this study we investigated the frequency of TERT promoter mutations and TERT protein expression with their association to clinicopathological characteristics in 2113 samples from 13 different types of cancers. The TERT promoter mutations were most frequently present in bladder cancers (68.6%), followed by anaplastic thyroid cancers (50%), Hurthle cell carcinomas (40%), central nervous system (CNS) tumors (28.7%) and follicular thyroid cancers (19%). The low frequency of these mutations was found in medullary thyroid cancers (10%), prostate cancers (9.3%), endometrial carcinomas (3.7%), rhabdomyosarcomas (1.4%), colorectal cancers (CRC) (1%), epithelial ovarian carcinomas (EOC) (0.7%) and breast cancers (0.7%). No mutations were observed in gastric cancers, lung cancers, diffuse large B-cell lymphomas (DLBCL) and acute lymphoblastic leukemias (ALL). In CNS tumors the TERT promoter mutations were significantly associated with older age (p&amp;lt;0.0001), histological subtype (p&amp;lt;0.0001), high grade (p&amp;lt;0.0001) and poor 5 years overall survival (p&amp;lt;0.0001). In gliomas, TERT promoter mutations were more frequently present in cases with old age (p=0.003), high grade (p&amp;lt;0.0001) and poor 5 years overall survival (p&amp;lt;0.0001). Furthermore it was also revealed that co-occurrence of TERT promoter mutations and IDH1 wildtype predicted worst survival (p=0.0001) in gliomas. Our results demonstrate that mutations in TERT promoter is a frequently occurring event in several types of cancers and may be utilized for prognostic prediction in CNS tumors from Middle Eastern Region. Citation Format: Rong Bu, Abdul K. Siraj, Kaleem Iqbal, Sandeep Parvathareddy, Mark Diaz, Dionne Rala, Ingrid G. Victoria, Khadija Al-Obaisi, Wael Al-Haqawi, Nabil Siraj, Allianah Benito, Khawla S. Al-Kuraya. Telomerase reverse transcriptase (TERT) promoter mutations in cancers derived from multiple organ sites among Middle Eastern population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1577.
Abstract 3677: Downregulation of FOXO3a by DNMT1 promotes breast cancer stem cell properties and tumorigenesis
Authors: Zhimin He, Hao Liu, Ying Song, Guopei Zheng
Journal: Cancer Research (2019)

Abstract Breast cancer stem cells (BCSCs) are tumor initiating cells that can self-renew and are highly tumorigenic and chemoresistant. Recent evidence indicated that FOXO3a plays an important role in regulating CSCs properties. However, the biologic function and detailed molecular mechanism of FOXO3a in BCSCs remains largely elusive. Here, we demonstrated that FOXO3a was hypermethylated and downregulated in breast cancer cells and tissues. Overexpression of FOXO3a potently attenuated the BCSCs properties in vitro and inhibited tumorigenesis in vivo, whereas knockdown of FOXO3a increased these properties. Further mechanistic investigation revealed that FOXO3a was functionally linked to the inhibition of the FOXM1/SOX2 pathway. Moreover, we found that SOX2 directly transactivated DNMT1 gene expression and then feedback inhibited FOXO3a expression. Clinically, we observed a significant inverse correlation between FOXO3a and FOXM1 or SOX2 expression levels. Loss of FOXO3a expression also predicted poor prognosis in breast cancer. In addition, we demonstrated that inhibition of DNMT activity suppressed tumor growth via regulating of FOXO3a/FOXM1/SOX2 signaling in breast cancer. Our findings suggest an important role of DNMT1/FOXO3a/FOXM1/SOX2 pathway in regulating BCSCs properties, identifying potential therapeutic targets for breast cancer. Keywords: breast cancer, cancer stem cell, FOXO3a, DNMT Note: This abstract was not presented at the meeting. Citation Format: Zhimin He, Hao Liu, Ying Song, Guopei Zheng. Downregulation of FOXO3a by DNMT1 promotes breast cancer stem cell properties and tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3677.