tbuckley/cabot-search huggingface dataset:
Abstract 262: Anti-tumorigenic effect of ONC201 is enhanced by combination treatment with TRAIL or a DR5 agonist in endometrial cancer in vitro
Authors: Jocelyn Ray, Marie Ralff, David Dicker, Wafik El-Deiry
Journal: Cancer Research (2019)

Abstract ONC201 is a well-tolerated, orally active small molecule in the novel imipridone class that has anti-tumorigenic properties in a number of solid tumors, but not in non-neoplastic cells. ONC201 has demonstrated promising activity as a single agent in patients with advanced endometrial cancer in the first-in-human clinical trial with Phase II trials in endometrial cancer patients now underway. Although the mechanism of action in endometrial cell pathology has not been well studied, ONC201’s anti-tumor effect has been shown in other model systems to be p53-independent and mediated through activation of the integrated stress response (ISR) leading to DR5 activation and through induction of cell death or growth arrest. ONC201 inhibits ERK and AKT leading to upregulation of TRAIL in many systems. We hypothesized that ONC201 upregulation of DR5 could sensitize tumor cells to TRAIL and that TRAIL could convert growth arrest to cell death in ONC201-treated cells. Three endometrial cancer cell lines AN3CA, HEC1A and KLE were treated with ONC201 alone or in combination with TRAIL, or a DR5 agonist. Effects on cell viability were assessed by the Cell Titer-Glo cell viability assay, colony formation assays and cell cycle analysis by propidium iodide staining. QPCR and Western blot analysis were used to evaluate mRNA and protein expression, respectively. Assessment of TRAIL and DR5 cell surface expression was evaluated by surface staining using flow cytometry and FlowJo data analysis. ONC201 decreased the cell viability of all three endometrial cancer cell lines at clinically achievable low micro-molar concentrations. ONC201 activated the ISR and an anti-proliferative effect involving a G1 phase arrest and little cell death as indicated by increased Sub-G1 analysis and PARP cleavage. DR5 mRNA and protein expression at the cell surface were induced by ONC201. All three endometrial cancer cell lines were resistant to TRAIL alone, however, pre-treatment with ONC201 sensitized the AN3CA and KLE to TRAIL and a DR5 agonist, leading to potent cell death induction. The combination of ONC201 plus TRAIL did not cause appreciable cell death in normal human fibroblast. ONC201 decreases cell viability in endometrial cancer cells lines primarily through growth arrest while the combination of ONC201 and TRAIL or a DR5 agonist promotes cell death in AN3CA and KLE cells but not in HEC1A endometrial cancer cells. Our results suggest a novel cancer therapeutic strategy that can be exploited in the clinic. Citation Format: Jocelyn Ray, Marie Ralff, David Dicker, Wafik El-Deiry. Anti-tumorigenic effect of ONC201 is enhanced by combination treatment with TRAIL or a DR5 agonist in endometrial cancer in vitro [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 262.
Autologous Stem Cell Transplantation for Mantle Cell Lymphoma in the Elderly (≥65 Years Of Age): The Mayo Clinic Experience
Authors: Priyanka Pophali, Allison C. Rosenthal, Han Tun, Craig B. Reeder, Ivana N Micallef, Luis Porrata, Stephen M Ansell, Patrick Johnston, David J Inwards
Journal: Blood (2017)
Correction to: Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop
Authors: Davide Bedognetti, Michele Ceccarelli, Lorenzo Galluzzi, Rongze Lu, Karolina Palucka, Josue Samayoa, Stefani Spranger, Sarah Warren, Kwok-Kin Wong, Elad Ziv, Diego Chowell, Lisa M. Coussens, Daniel D. De Carvalho, David G. DeNardo, Jérôme Galon, Howard L. Kaufman, Tomas Kirchhoff, Michael T. Lotze, Jason J. Luke, Andy J. Minn, Katerina Politi, Leonard D. Shultz, Richard Simon, Vésteinn Thórsson, Joanne B. Weidhaas, Maria Libera Ascierto, Paolo Antonio Ascierto, James M. Barnes, Valentin Barsan, Praveen K. Bommareddy, Adrian Bot, Sarah E. Church, Gennaro Ciliberto, Andrea De Maria, Dobrin Draganov, Winson S. Ho, Heather M. McGee, Anne Monette, Joseph F. Murphy, Paola Nisticò, Wungki Park, Maulik Patel, Michael Quigley, Laszlo Radvanyi, Harry Raftopoulos, Nils-Petter Rudqvist, Alexandra Snyder, Randy F. Sweis, Sara Valpione, Roberta Zappasodi, Lisa H. Butterfield, Mary L. Disis, Bernard A. Fox, Alessandra Cesano, Francesco M. Marincola
Journal: Journal for ImmunoTherapy of Cancer (2019)

Following publication of the original article [1], the author reported that an author name, Roberta Zappasodi, was missed in the authorship list. Davide Bedognetti, Rongze Lu, Josue Samayoa, Stefani Spranger and Sarah Warren contributed equally to this work. The original article can be found online at 10.1186/s40425-019-0602-4
Abstract 14337: Relationship Between Long-Term Bleeding Risk and Choice Between Drug-Eluting and Bare Metal Stents: Insights From the PRISM Study
Authors: Ali Shafiq, Kensey Gosch, John A Spertus, Adam C Salisbury
Journal: Circulation (2016)

Introduction: In patients at high risk for long-term bleeding after PCI, bare metal stents (BMS) may be preferable to drug-eluting stents (DES) given a significantly shorter requirement for mandato...
Bevacizumab (BV) maintenance after first-line chemotherapy plus BV for metastatic colorectal cancer patients: a meta-analysis of individual patients data from 3 phase III studies
Authors: L. Salvatore, E. Bria, I. Sperduti, A. Hinke, S. Hegewisch-Becker, T. Aparicio, K. Le Malicot, V. Boige, D. Koeberle, D. Baertschi, D. Dietrich, G. Tortora, D. Arnold
Journal: Annals of Oncology (2019)
Seroprevalence and demographic factors associated with hepatitis B, hepatitis C and HIV infection from a hospital emergency department testing programme, London, United Kingdom, 2015 to 2016
Authors: Nick Bundle, Sooria Balasegaram, Sarah Parry, Sadna Ullah, Ross J Harris, Karim Ahmad, Graham R Foster, Cheuk YW Tong, Chloe Orkin
Journal: Eurosurveillance (2019)

Background Progress towards HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) elimination requires local prevalence estimates and linkage to care (LTC) of undiagnosed or disengaged cases. Aim We aimed to estimate seroprevalence, factors associated with positive blood-borne virus (BBV) serology and numbers needed to screen (NNS) to detect a new BBV diagnosis and achieve full LTC from emergency department (ED) BBV testing. Methods During a 9-month programme in an ED in east London, England, testing was offered to adult attendees having a full blood count (FBC). We estimated factors associated with positive BBV serology using logistic regression and NNS as the inverse of seroprevalence. Estimates were weighted to the age, sex and ethnicity of the FBC population. Results Of 6,211 FBC patients tested, 217 (3.5%) were positive for at least one BBV. Weighted BBV seroprevalence was 4.2% (95% confidence interval (CI): 3.6–4.9). Adjusted odds ratios (aOR) of positive BBV serology were elevated among patients that were: male (aOR: 2.7; 95% CI: 1.9–3.9), 40–59 years old (aOR: 1.9; 95% CI: 1.4–2.7), of Black British/Black other ethnicity (aOR: 1.8; 95% CI: 1.2–2.8) or had no fixed address (aOR: 2.9; 95% CI: 1.5–5.5). NNS to detect a new BBV diagnosis was 154 (95% CI: 103–233) and 135 (95% CI: 93–200) to achieve LTC. Conclusions The low NNS suggests routine BBV screening in EDs may be worthwhile. Those considering similar programmes should use our findings to inform their assessments of anticipated public health benefits.
Abstract 3357: The fibrolamellar registry: A model for the study of rare diseases
Authors: Michelle Desmond, Julie Latone, Siobhan Lett, Rachael D. Migler, Elana P. Simon, Sanford M. Simon
Journal: Cancer Research (2019)

Abstract Advances in genomics and proteomics have enabled more precise characterizations of tumors with the consequence that many cancers are being segregated into smaller categories. With this larger number of categories, more cancers are being categorized as rare. The downside to such categorizations is that the reduced numbers of patients in each category makes it difficult to gather enough information about each cancer. We are a group of patients and caregivers who have joined together to form a repository for patient-shared data and reports in an IRB-approved, non-profit medical registry for the rare and usually lethal childhood liver cancer, fibrolamellar hepatocellular carcinoma (FLC). Since the Fibrolamellar Registry is patient-run and patient-owned, we have the trust of the patient community that the records will not be sold for profit. This has enabled us, in our first two years, to gather detailed medical records, scans and tests from over 140 patients. With input from scientists and clinicians who study FLC, we have written 600 questions of specific interest to this disease. Most of our patients have also opted to allow these medical records to be shared with a tissue FLC repository that already has samples from 110 patients. We have initiated two different collaborations with the clinical-research community to explore the records and our patients have been answering additional questions when pertinent to a particular study. Our ability to gather so many records for what is a rare cancer comes from our ability to involve patients from across institutions and across the globe. We are working with other patient groups and we feel that the Fibrolamellar Registry could be a model for gathering and organizing data for many rare diseases. Citation Format: Michelle Desmond, Julie Latone, Siobhan Lett, Rachael D. Migler, Elana P. Simon, Sanford M. Simon. The fibrolamellar registry: A model for the study of rare diseases [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 3357.
Dual Antiplatelet Therapy
Authors: Khaled M. Ziada, David J. Moliterno
Journal: JAMA (2019)

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Abstract 544: Glycogen Synthase Kinase-3α Regulates Cardiac Growth and Attenuates Pressure Overload-induced Cardiac Hypertrophy in Transgenic Mice
Authors: Peiyong Zhai, Shumin Gao, Junichi Sadoshima
Journal: Circulation (2006)

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase having multiple functions including growth, death and metabolism. Two isoforms of GSK-3, GSK-3α and GSK-3β, have been identified in m...
Abstract 3458: Investigation of oxidative stress-related gene signature in cancer-associated cachexia
Authors: Sumeet Jain, Surendra K. Shukla, Aneesha Dasgupta, Pankaj K. Singh
Journal: Cancer Research (2019)

Abstract About eighty percent of pancreatic cancer patients demonstrate excessive loss of skeletal muscles with or without loss of adipose deposits, a condition known as cancer-associated cachexia. Severe complexities related to cancer-associated cachexia contribute to mortality in one-third of pancreatic cancer patients. Multiple factors, including loss of appetite, systemic inflammation, digestive enzymes, and hormonal imbalance may contribute to the development of cancer-associated cachexia. Poor understanding of the molecular mechanism is the key challenge for targeting cancer-associated cachexia. Hence, to facilitate the identification of new targets for ameliorating cancer-induced muscle loss, we undertook genomic studies. We evaluated differentially expressed gene signatures in muscle tissues of cachectic and non-cachectic human pancreatic cancer patients. To better model the mechanisms of cancer cachexia, we also compared the identified gene signatures to that of orthotopic and spontaneous mice models of pancreatic cancer cachexia. We observed significant alterations in multiple genes related to oxidative stress in muscle tissues from human patients with cachexia and mice cachexia models. We targeted oxidative stress regulatory genes by genetic manipulations or targeted oxidative stress with pharmacological approaches to evaluate the impact of oxidative stress in skeletal muscles on cancer-associated cachexia. Our results suggest that targeting the oxidative stress pathway prevents/reverts cancer-associated cachexia. Moreover, inhibition of oxidative stress also abolished cancer cell-conditioned medium-induced atrophy in C2C12-derived myotubes and diminished the expression of atrophy markers. Overall, our studies revealed the potential role of oxidative stress induced by cancer cells in muscle wasting. Future studies to target tumor-induced oxidative stress in muscle fibers may provide new therapeutic approaches to prevent cancer-associated cachexia. Citation Format: Sumeet Jain, Surendra K. Shukla, Aneesha Dasgupta, Pankaj K. Singh. Investigation of oxidative stress-related gene signature in cancer-associated cachexia [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 3458.
Abstract 82: Transforming of human osteoblasts with the combination of hTERT (T), SV40Tag (S) and c-Myc: Changes in phenotype and tumorigenesis capability
Authors: Zhongting Zhang, Yifei Wang, Wendong Zhang, Michael Roth, Jonathan Benjamin Gill, Zhaohui Xu, Xiangjun Tian, Jing Wang, Richard Gorlick
Journal: Cancer Research (2019)

Abstract The etiology of osteosarcoma (OS), the most common primary malignant bone cancer in pediatric patients, still remains unknown. It is not clear where tat which point he osteosarcoma is originated from the osteogenic lineagein the osteogenic osteosarcoma arises., some consider Potential candidates in the literature include the human mesenchymal cells (hMSC) as the cell of origin in OS, whereas others believe theand osteoblast (OB) to be the most likely cell of origin. To understand the origin and molecular pathogenesis of osteosarcoma, we have transformed hMSCs and OBs differentiated from the same MSC with oncogenes hTERT (T), SV40Tag (S) and H-RAS (R) in series to check evaluate for spindle cell tumor formation in mice. Transformed MSC did not form osteoid, whereas OB-TSR tumor showed only scant production of osteoid, suggesting MSC may not be the origin of OS and the hTERT, SV40Tag and h-Ras may not be sufficient for osteoblast to form OS. C-Myc is one of the genes that play a major role in oncogenic transformation of normal cells. It has been shown that c-Myc is overexpressed in OS cells and more than 10% OS patients carry c-Myc amplification mutations. We further decide to look intoThis served as the basis to examine the role of c-Myc in OS formation in the background of cells transformed by hTERT and SV40. OB transformed with hTERT and SV40Tag cells were further transfected with a retrovirus containing human c-Myc to obtain stable cell lines. Quantitative PCR and western blots assays detected both gene and protein expression patterns of c-Myc, respectively, in the transformed cell lines. Transformed cell lines were analyzed for proliferation, invasion, migration, and spheroid formation to determine the tumorigenic capacity capability. TThe tumorigenesis capability is found to be correlated with the level of c-Myc expression level based onby RT-PCR data. Furthermore, we used RNA-seq to analyze gene expression profiles of the transformed cell lines, compared with those forin comparison to primary OS cell lines and patient derived xenografts (PDXs). In -vivo tumorigenic assays, histological examination for osteoid production and chromosome analysis are still under way. Our study using an osteosarcoma model with transformed human cells may provide new insights on the cell origin of OS. Citation Format: Zhongting Zhang, Yifei Wang, Wendong Zhang, Michael Roth, Jonathan Benjamin Gill, Zhaohui Xu, Xiangjun Tian, Jing Wang, Richard Gorlick. Transforming of human osteoblasts with the combination of hTERT (T), SV40Tag (S) and c-Myc: Changes in phenotype and tumorigenesis capability [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 82.
Does PICC side matter? The experience at our hospital
Authors: A. Gil Torralvo, A. López Ladrón, J. Rodríguez Hernández, S. Garcia Rodríguez, A. Sánchez Vegas, M. Rodríguez de la Borbolla, C. Robles Barraza, E. Fernández-Parra, J. Fuentes PRadera, P. Jimenez-Vilches, G. Lourenzo Aguilera, I. Beltrán Guerra, J. Acosta Contento, P. López Álvarez, M. Chaves
Journal: Annals of Oncology (2019)
Abstract 2748: The role of TMPRSS2_ERG fusions in modulating tumor microenvironment in prostate cancer
Authors: Hubert Pakula, Caroline F. Ribeiro, Giuseppe N. Fanelli, Rory Kirchner, Sudeepa Syamala, Basudev Chowdhury, Giorgia Zadra, Paolo Chetta, Zhe Li, Massimo Loda
Journal: Cancer Research (2019)

Abstract The control region of TMPRSS2 fuses with ETS transcription factor family members, particularly ERG. This occurs in ~20-50% of human prostate cancers depending on the ethnicity. TMPRSS2-ERG (T2E) fusions, however, do not display a notable phenotype in genetically engineered mouse models (GEMM) recapitulating the fusion expression and T2E also has no prognostic significance in humans, despite its high incidence. Wnt signaling has been implicated in prostate cancer. Here, we report a discovery of a role for T2E fusion that impacts the prostate stroma in pre-clinical models. The composition of stromal cells within the microenvironment in T2E mice was studied by single cell RNAseq analysis. We identified stromal cell clusters in T2E mice that differed from wild type mice in the expression of Pdgfrβ, Pdgfrα and Col1a1. Interestingly, these clusters showed an increase of expression of Wnt receptors such as Lgr5 and Fzd7 as well as Wnt ligands such as Sfrp2, Wnt2 and Wnt6. T2E GEMMs also exhibited upregulation of the Wnt-secretion regulator porcupine (PORCN-Protein-serine O-palmitoleoyltransferase) in the stroma adjacent to the T2E-expression prostate epithelial cells. Furthermore, lineage-tracing with the Wnt reporter and epithelial stem cell marker Lgr5 showed that Wnt-active cells were increased in prostatic intraepithelial neoplasia (PIN) lesions in T2E;Pten+/- mice. Strikingly, Lgr5+ cells were also found in the prostate stroma surrounding these PINs. Since, TMPRSS2/ERG fusions represent an early event in prostate tumorigenesis, here we provide a mechanism whereby induction of Wnt signaling in the stroma by T2E-expressing prostate epithelial cells increases the stem cell compartments in both epithelial and stromal cells. These data suggest that aberrant ERG-expressing prostate epithelial cells activate upregulation of Wnt signaling in stromal cells, which provides a possible route for enhancing prostate carcinogenesis. Citation Format: Hubert Pakula, Caroline F. Ribeiro, Giuseppe N. Fanelli, Rory Kirchner, Sudeepa Syamala, Basudev Chowdhury, Giorgia Zadra, Paolo Chetta, Zhe Li, Massimo Loda. The role of TMPRSS2_ERG fusions in modulating tumor microenvironment in prostate cancer [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 2748.
Abstract 3138: <i>SMARCA4</i> mutations in <i>KRAS</i>-mutant lung adenocarcinoma: A multi-cohort analysis
Authors: LIANG LIU, Tamjeed Ahmed, Willam Jeffrey Petty, Stefan Grant, Jimmy Ruiz, Thomas W. Lycan, Umit Topaloglu, Ping-Chieh Chou, Lance D. Miller, Gregory A. Hawkins, Martha A. Alexander-Miller, Stacey S. O’Neill, Bayard L. Powell, Ralph B. D’Agostino, Reginald F. Munden, Boris Pasche, Wei Zhang
Journal: Cancer Research (2019)

Abstract KRAS is a key oncogenic driver in lung adenocarcinoma (LUAD). Chromatin-remodeling gene SMARCA4 was co-mutated with KRAS in LUAD; however, the impact of SMARCA4 mutations on clinical outcome has not been adequately established. This study sought to shed light on the clinical significance of SMARCA4mutations in LUAD. The association of SMARCA4 mutations with survival outcomes was interrogated in 4 independent cohorts totaling 564 patients: KRAS-mutant patients with LUAD who received non-immunotherapy treatment from 1) The Cancer Genome Atlas (TCGA) and 2) the MSK-IMPACT Clinical Sequencing (MSK-CT) cohorts; and KRAS-mutant patients with LUAD who received immune checkpoint inhibitor-based immunotherapy treatment from 3) the MSK-IMPACT (MSK-IO) and 4) the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) immunotherapy cohorts. Of the patients receiving non-immunotherapy treatment, in the TCGA cohort (n=155), KRAS-mutant patients harboring SMARCA4 mutations (KS) showed poorer clinical outcome (P=6e-04 for disease-free survival (DFS) and .031 for overall survival (OS), respectively), compared to KRAS-TP53 co-mutant (KP) and KRAS-only mutant (K) patients; in the MSK-CT cohort (n=314), KS patients also exhibited shorter OS than KP (P=.03) or K (P=.022) patients. Of patients receiving immunotherapy, KS patients consistently exhibited the shortest progression-free survival (PFS; P=.0091) in the MSK-IO (n=77), and the shortest PFS (P=.0026) and OS (P=0.0014) in the WFBCCC (n=18) cohorts, respectively. Therefore, mutations of SMARCA4 represent a genetic factor that lead to adverse clinical outcome in lung adenocarcinoma treated by either non-immunotherapy or immunotherapy. Citation Format: LIANG LIU, Tamjeed Ahmed, Willam Jeffrey Petty, Stefan Grant, Jimmy Ruiz, Thomas W. Lycan, Umit Topaloglu, Ping-Chieh Chou, Lance D. Miller, Gregory A. Hawkins, Martha A. Alexander-Miller, Stacey S. O’Neill, Bayard L. Powell, Ralph B. D’Agostino, Reginald F. Munden, Boris Pasche, Wei Zhang. SMARCA4 mutations in KRAS-mutant lung adenocarcinoma: A multi-cohort 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 3138.