tbuckley/cabot-search huggingface dataset:
PD-0018 Phase I/II Study of Tivantinib (ARQ 197) Irinotecan, and Cetuximab in Patients with Kras Wildtype, Previously Treated, Metastatic Colorectal Cancer
Authors: Cathy Eng, Bessudo Alberto, Nashat Gabrail, Taina Lopez, Hamim Zahir, Reinhard von Roemeling, Johanna Bendell
Journal: Annals of Oncology (2012)
SNO-MLP (S-Nitrosylation of Muscle LIM Protein) Facilitates Myocardial Hypertrophy Through TLR3 (Toll-Like Receptor 3)–Mediated RIP3 (Receptor-Interacting Protein Kinase 3) and NLRP3 (NOD-Like Receptor Pyrin Domain Containing 3) Inflammasome Activation
Authors: Xin Tang, Lihong Pan, Shuang Zhao, Feiyue Dai, Menglin Chao, Hong Jiang, Xuesong Li, Zhe Lin, Zhengrong Huang, Guoliang Meng, Chun Wang, Chan Chen, Jin Liu, Xin Wang, Albert Ferro, Hong Wang, Hongshan Chen, Yuanqing Gao, Qiulun Lu, Liping Xie, Yi Han, Yong Ji
Journal: Circulation (2020)

S-nitrosylation (SNO), a prototypic redox-based posttranslational modification, is involved in the pathogenesis of cardiovascular disease. The aim of this study was to determine the role of SNO of MLP (muscle LIM protein) in myocardial hypertrophy, as well as the mechanism by which SNO-MLP modulates hypertrophic growth in response to pressure overload.Myocardial samples from patients and animal models exhibiting myocardial hypertrophy were examined for SNO-MLP level using biotin-switch methods. SNO sites were further identified through liquid chromatography-tandem mass spectrometry. Denitrosylation of MLP by the mutation of nitrosylation sites or overexpression of S-nitrosoglutathione reductase was used to analyze the contribution of SNO-MLP in myocardial hypertrophy. Downstream effectors of SNO-MLP were screened through mass spectrometry and confirmed by coimmunoprecipitation. Recruitment of TLR3 (Toll-like receptor 3) by SNO-MLP in myocardial hypertrophy was examined in TLR3 small interfering RNA-transfected neonatal rat cardiomyocytes and in a TLR3 knockout mouse model.SNO-MLP level was significantly higher in hypertrophic myocardium from patients and in spontaneously hypertensive rats and mice subjected to transverse aortic constriction. The level of SNO-MLP also increased in angiotensin II- or phenylephrine-treated neonatal rat cardiomyocytes. S-nitrosylated site of MLP at cysteine 79 was identified by liquid chromatography-tandem mass spectrometry and confirmed in neonatal rat cardiomyocytes. Mutation of cysteine 79 significantly reduced hypertrophic growth in angiotensin II- or phenylephrine-treated neonatal rat cardiomyocytes and transverse aortic constriction mice. Reducing SNO-MLP level by overexpression of S-nitrosoglutathione reductase greatly attenuated myocardial hypertrophy. Mechanistically, SNO-MLP stimulated TLR3 binding to MLP in response to hypertrophic stimuli, and disrupted this interaction by downregulating TLR3-attenuated myocardial hypertrophy. SNO-MLP also increased the complex formation between TLR3 and RIP3 (receptor-interacting protein kinase 3). This interaction in turn induced NLRP3 (nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3) inflammasome activation, thereby promoting the development of myocardial hypertrophy.Our findings revealed a key role of SNO-MLP in myocardial hypertrophy and demonstrated TLR3-mediated RIP3 and NLRP3 inflammasome activation as the downstream signaling pathway, which may represent a therapeutic target for myocardial hypertrophy and heart failure.
Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses
Authors: Patricia R. Souza, Raquel M. Marques, Esteban A. Gomez, Romain A. Colas, Roberta De Matteis, Anne Zak, Mital Patel, David J. Collier, Jesmond Dalli
Journal: Circulation Research (2019)

Specialized pro-resolving mediators (SPM-lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acids docosahexaenoic acid and n-3 docosapentaenoic acid. These mediators exert potent leukocyte directed actions and control vascular inflammation. Supplementation of animals and humans with essential fatty acids, in particular omega-3 fatty acids, exerts protective actions reducing vascular and systemic inflammation. Of note, the mechanism(s) activated by these supplements in exerting their protective actions remain poorly understood.Given that essential fatty acids are precursors in the biosynthesises of SPM, the aim of the present study was to establish the relationship between supplementation and peripheral SPM concentrations. We also investigated the relationship between changes in plasma SPM concentrations and peripheral blood platelet and leukocyte responses.Healthy volunteers were enrolled in a double-blinded, placebo-controlled, crossover study, and peripheral blood was collected at baseline, 2, 4, 6, and 24 hours post administration of placebo or one of 3 doses of an enriched marine oil supplement. Assessment of plasma SPM concentrations using lipid mediator profiling demonstrated a time- and dose-dependent increase in peripheral blood SPM concentration. Supplementation also led to a regulation of peripheral blood cell responses. Here we found a dose-dependent increase in neutrophil and monocyte phagocytosis of bacteria and a decrease in the diurnal activation of leukocytes and platelets, as measured by a reduction in adhesion molecule expression. In addition, transcriptomic analysis of peripheral blood cells demonstrated a marked change in transcript levels of immune and metabolic genes 24 hours post supplementation when compared with placebo.Together, these findings demonstrate that supplementation with an enriched marine oil leads to an increase in peripheral blood SPM concentrations and reprograms peripheral blood cells, indicating a role for SPM in mediating the immune-directed actions of this supplement.URL: http://www.clinicaltrials.gov. Unique identifier: NCT03347006.
Clinical Outcome of Radioimmunotherapy with ASCT (Z-Leed) for Relapsed and Refractory B-Cell Lymphoma
Authors: Y. Tatsumi, S. Rai, Y. Kanai, C. Hirase, T. Yamaguchi, Y. Morita, H. Tanaka, T. Simada, K. Kawanishi, J. Miyaktake, T. Ashida, I. Matsumura
Journal: Annals of Oncology (2012)
Sequential Androgen Deprivation and Chemotherapy in Metastatic Prostate Cancer: Discordant Responses in Pilot Study Suggest an Opportunity for Individualized Therapy
Authors: R. Tang, C. Piatek, J. Pinski, F. Acosta, C. Korn, D. Raghavan, T.B. Dorff, D.I. Quinn
Journal: Annals of Oncology (2012)
Patterns of Clinical Management and Resource Utilization for Postmenopausal Hormone-Receptor–Positive HER2-Negative (HR+ HER2–) Advanced Breast Cancer (ABC) in Europe
Authors: G. Jerusalem, N. Marinsek, J. Ricci, J. Etchberger, R. Degun, G. Benelli, S. Saletan, F. André
Journal: Annals of Oncology (2012)
The NLRP3 inflammasome pathway is activated in sarcoidosis and involved in granuloma formation
Authors: Christine Huppertz, Benedikt Jäger, Grazyna Wieczorek, Peggy Engelhard, Stephen J. Oliver, Franz-Georg Bauernfeind, Amanda Littlewood-Evans, Tobias Welte, Veit Hornung, Antje Prasse
Journal: European Respiratory Journal (2020)

Sarcoidosis is a disease characterised by granuloma formation. There is an unmet need for new treatment strategies beyond corticosteroids. The NLRP3 inflammasome pathway is expressed in innate immune cells and senses danger signals to elicit inflammatory interleukin (IL)-1β; it has recently become a druggable target. This prompted us to test the role of the NLRP3 inflammasome and IL-1β pathway in granuloma formation and sarcoidosis.19 sarcoid patients and 19 healthy volunteers were recruited into this pilot study. NLRP3 inflammasome activity was measured in bronchoalveolar lavage (BAL) cells and lung and skin biopsies using immunohistochemistry, Western blot, reverse-transcriptase PCR and ELISA. For in vivo experiments we used the trehalose 6,6'-dimycolate-granuloma mouse model and evaluated lung granuloma burden in miR-223 knockout and NLRP3 knockout mice, as well as the treatment effects of MCC950 and anti-IL-1β antibody therapy.We found strong upregulation of the NLRP3 inflammasome pathway, evidenced by expression of activated NLRP3 inflammasome components, including cleaved caspase-1 and IL-1β in lung granuloma, and increased IL-1β release of BAL cells from sarcoid patients compared to healthy volunteers (p=0.006). mRNA levels of miR-223, a micro-RNA downregulating NLRP3, were decreased and NLRP3 mRNA correspondingly increased in alveolar macrophages from sarcoid patients (p<0.005). NLRP3 knockout mice showed decreased and miR-223 knockout mice increased granuloma formation compared to wild-type mice. Pharmacological interference using NLRP3 pathway inhibitor MCC950 or an anti-IL-1β antibody resulted in reduced granuloma formation (p<0.02).In conclusion, our data provide evidence of upregulated inflammasome and IL-1β pathway activation in sarcoidosis and suggest both as valid therapeutic targets.
A Study of Illness in a Group of Cleveland Families
Authors: Kenneth S. Warren, John H. Dingle
Journal: New England Journal of Medicine (1966)

ANTIBODIES to Toxoplasma gondii are widespread throughout the human population of the United States of America, and yet the epidemiologic behavior of toxoplasmosis, including the mode of transmission, has not been clearly defined.1 Although several large-scale cross-sectional surveys have been made1 2 3 only a few, relatively circumscribed, longitudinal surveys in which a given population has been observed over a specified period have been reported. One longitudinal survey consisted of a study of 2 serum specimens collected seven months apart from each of 359 college students4; the other encompassed an average of 3 serum specimens collected from each of 272 obstetric . . .
Atlas of the human intestine
Authors: Xi C. He, Linheng Li
Journal: The Journal of Experimental Medicine (2020)

In this issue of JEM, Wang et al. (https://doi.org/10.1084/jem.20191130), using a single-cell RNA-seq approach, establish an atlas of human colon, rectum, and ileum epithelial cells. Their study reveals that different regions have specialized nutrient absorption preferences, microbe defenses, and endocrine function. They also identify new markers for a variety of cell types.
Genetic variants in toll‐like receptor 4 are associated with lack of steroid‐responsiveness in pediatric ITP patients
Authors: Taylor Olmsted Kim, Jonathan M. Flanagan, Ali Habibi, Abinaya Arulselvan, Michele P. Lambert, Rachael F. Grace, Jenny M. Despotovic
Journal: American Journal of Hematology (2020)

Abstract Although the most common front‐line therapies for immune thrombocytopenia (ITP) have been in use for decades, it is still not possible to predict an individual patient's clinical course and response to therapy. Patients are managed with a trial‐and‐error approach and often suffer side effects of therapies which could have been avoided if response prediction were possible. Corticosteroids are the most frequently used upfront therapy for adults and children with ITP. Our group performed whole exome sequencing on a cohort of pediatric ITP patients, and identified two missense single nucleotide variants (SNV) in Toll‐like receptor 4 ( TLR4 ). These coding variants in TLR4 had an increased frequency in Caucasian patients with poor response to upfront steroid therapy. Both TLR4 (D299G; rs4986790) and TLR4 (T399I; rs4986791) had a minor allele frequency (MAF) of 20.7% in those patients unresponsive to steroids, but were present at lower allele frequencies of 2.3% and 3.4% in responders respectively ( P &lt; .001). These findings were consistent with the trend identified in an independent cohort of pediatric ITP patients treated with corticosteroids who underwent direct genotyping for both SNVs. This study identified two candidate genetic variants in two unique cohorts of ITP patients which may contribute to steroid response and have prognostic implications for treatment response in ITP.
Platinum Combination Chemotherapy Versus Platinum Monotherapy in Platinum-Sensitive Recurrent Ovarian Cancer: A Meta-Analysis of Randomised Trials Using Individual Patient Data (IPD)
Authors: F.A. Raja, N. Counsell, N. Colombo, M.K. Parmar, J. Pfisterer, I.B. Vergote, A. Gonzalez Martin, D. Alberts, M. Plante, J.A. Ledermann
Journal: Annals of Oncology (2012)
Host Wnt5a Potentiates Microenvironmental Regulation of Ovarian Cancer Metastasis
Authors: Marwa Asem, Allison M. Young, Carlysa Oyama, Alejandro Claure De La Zerda, Yueying Liu, Jing Yang, Tyvette S. Hilliard, Jeffery Johnson, Elizabeth I. Harper, Ian Guldner, Siyuan Zhang, Toni Page-Mayberry, William J. Kaliney, M. Sharon Stack
Journal: Cancer Research (2020)

The noncanonical Wnt ligand Wnt5a is found in high concentrations in ascites of women with ovarian cancer. In this study, we elucidated the role of Wnt5a in ovarian cancer metastasis. Wnt5a promoted ovarian tumor cell adhesion to peritoneal mesothelial cells as well as migration and invasion, leading to colonization of peritoneal explants. Host components of the ovarian tumor microenvironment, notably peritoneal mesothelial cells and visceral adipose, secreted Wnt5a. Conditional knockout of host WNT5A significantly reduced peritoneal metastatic tumor burden. Tumors formed in WNT5A knockout mice had elevated cytotoxic T cells, increased M1 macrophages, and decreased M2 macrophages, indicating that host Wnt5a promotes an immunosuppressive microenvironment. The Src family kinase Fgr was identified as a downstream effector of Wnt5a. These results highlight a previously unreported role for host-expressed Wnt5a in ovarian cancer metastasis and suggest Fgr as a novel target for inhibition of ovarian cancer metastatic progression.Significance: This study establishes host-derived Wnt5a, expressed by peritoneal mesothelial cells and adipocytes, as a primary regulator of ovarian cancer intraperitoneal metastatic dissemination and identifies Fgr kinase as novel target for inhibition of metastasis.
P-0264 Carboxy-Terminal Telopeptide of Type I Collagene and Tartrate-Resistant Acid Posphatase Measurement in Patients with Colorectal Cancer and Bone Metastases
Authors: Franco Lumachi, Davide Santeufemia, Salvatore Tumolo, Paolo Doretto, Renato Tozzoli, Giordano Chiara, Stefano Basso
Journal: Annals of Oncology (2012)
Immunotherapy using tumor-specific cytotoxic T lymphocytes (CTLs) for PTEN knock-out spontaneous prostate cancer model
Authors: Atsushi Tomioka, Kazunori Haga, Chun-Peng Liao, Takahiro Kimura, Christpher Logg, Hiroshi Matsumoto, Izumi Ohno, Kip Hermann, Motoyoshi Tanaka, Hirotsugu Uemura, Yoshihiko Hirao, Pradip Roy-Burman, Noriyuki Kasahara
Journal: Cancer Research (2008)

4480  Introduction and Objective: The tumor suppressor gene MMAC/PTEN located on chromosome 10q23.3 is frequently inactivated in a variety of tumors such as prostate cancer and has a dual phosphatase activity in the phosphatidylinositol 39-kinase signal pathway and inhibits Akt activation, serine-threonine kinase, which is involved in proliferative and anti-apoptotic pathway. We have now generated the treatment of PTEN deleted prostate cancer by using tumor-specific CTLs (cytotoxic T lymphocytes) which are sensitized to tumors and also traffic through tissue and can act directly as cytolytic effector cells.  Methods: We injected subcutaneously irradiated PTEN-Cap8 cells which are isogenic, androgen receptor-positive prostate epithelial lines from intact conditional PTEN knock-out mice and extracted tumor-specific CTLs from spleen. In vitro the effect of tumor-specific CTLs was examined with cell proliferation assay. In vivo tumor trafficking effect of CTLs and cytotoxicity of locally administered CTLs were examined by live imaging of luciferase. To determine the treatment effect, we followed the PTEN-CaP8 subcutaneous tumor size and luciferase expression after injection of tumor-specific CTLs.  Results: CTLs killed the mouse prostate cancer cells dose-dependently invitro. The effect of tumor-specific CTLs was tracked by in vivo image. Tumor size showed significant reduction of the tumor after treated with CTLs.  Conclusions: Treatment with tumor-specific CTLs is effective for PTEN deleted mouse prostate cancer.
Prognostic Role of ERCC1, Bax and TP53 in Advanced Colorectal Cancer (CRC) PTS Randomly Assigned to First-Line UFT/Leucovorin (LV) Plus Irinotecan (Tegafiri) Versus UFT/LV Plus Oxaliplatin (Tegafox)
Authors: F. Pietrantonio, P. Biondani, M. Milione, F. Perrone, F.G.M. De Braud, G. Bertarelli, L. Mariani, F. Melotti, G. Montemurro, M. Di Bartolomeo
Journal: Annals of Oncology (2012)
Predictive Factors of no Response During Neoadjuvant Chemotherapy in Breast Cancer
Authors: J. Jo, C. Yoo, J.-E. Kim, J.-H. Ahn, S.-B. Kim, H.-H. Kim, J.H. Cha, H.J. Shin, S.-H. Ahn, B.H. Son, J.W. Lee, H.J. Kim, G. Gong, K.H. Jung
Journal: Annals of Oncology (2012)
P-0126 Gastrointestinal Tumor Board: An Evolving Experience in Tehran Cancer Institute
Authors: Peiman Haddad, Mohammad-Reza Mir, Masoud Jamali, Afshin Abdirad, Afsaneh Alikhasi, Farshid Farhan, Freydoon Memari, Sanambar Sadighi, Farhad Shahi
Journal: Annals of Oncology (2012)
Retroviral Insertional Mutagenesis in Humans: Evidence for Four Genetic Mechanisms Promoting Expansion of Cell Clones
Authors: Frederic D. Bushman
Journal: Molecular Therapy (2020)

Integration of new DNA into a cellular chromosome can alter the activity of nearby genes, sometimes affecting subsequent cell growth. A potent form of insertional mutagenesis involves integration of retroviral DNA produced by reverse transcription, a required step in the replication of retroviruses. In recent years retroviral replication has been adapted to allow new gene addition by retroviral vectors. Early in the history of retrovirus research, analysis of insertional mutagenesis in laboratory animals was found at times to result in transformation, leading to the discovery of cellular proto-oncogenes. In-depth analysis of the genetic consequences showed that integration of retroviral DNA could alter the gene activity in a variety of ways. Mechanisms of retroviral insertional mutagenesis in humans are much less well documented. However, recent work from the gene therapy and HIV fields now specify four genetic mechanisms of retroviral insertional mutagenesis in humans: (1) gene activation by integration of an enhancer sequence encoded in a retroviral vector (enhancer insertion), (2) gene activation by promoter insertion, (3) gene inactivation by insertional disruption, and (4) gene activation by mRNA 3' end substitution. In each example, integration in patients was associated with clonal expansion or frank transformation.
Incidence, Trends, and Outcomes of Type 2 Myocardial Infarction in a Community Cohort
Authors: Claire E. Raphael, Véronique L. Roger, Yader Sandoval, Mandeep Singh, Malcolm Bell, Amir Lerman, Charanjit S. Rihal, Bernard J. Gersh, Bradley Lewis, Ryan J. Lennon, Allan S. Jaffe, Rajiv Gulati
Journal: Circulation (2020)

Type 2 myocardial infarction (T2MI) occurs because of an acute imbalance in myocardial oxygen supply and demand in the absence of atherothrombosis. Despite being frequently encountered in clinical practice, the population-based incidence and trends remain unknown, and the long-term outcomes are incompletely characterized.
Moving beyond Fine Particle Mass: High-Spatial Resolution Exposure to Source-Resolved Atmospheric Particle Number and Chemical Mixing State
Authors: Qing Ye, Hugh Z. Li, Peishi Gu, Ellis S. Robinson, Joshua S. Apte, Ryan C. Sullivan, Allen L. Robinson, Neil M. Donahue, Albert A. Presto
Journal: Environmental Health Perspectives (2020)

Background: Most epidemiological studies address health effects of atmospheric particulate matter (PM) using mass-based measurements as exposure surrogates. However, this approach ignores many critical physiochemical properties of individual atmospheric particles. These properties control the deposition of particles in the human lung and likely their toxicity; in addition, they likely have larger spatial variability than PM mass. Objectives: This study was designed to quantify the spatial variability in number, size, source, and chemical mixing state of individual particles in a populous urban area. We quantified the population exposure to these detailed particle properties and compared them to mass-based exposures. Methods: We performed mobile sampling using an advanced single-particle mass spectrometer to measure the spatial variability of number concentration of source-resolved 50–1,000 nm particles and particle mixing state in Pittsburgh, Pennsylvania. We built land-use regression (LUR) models to estimate their spatial patterns and coupled them with demographic data to estimate population exposure. Results: Particle number concentration had a much larger spatial variability than mass concentration within the city. Freshly emitted particles from traffic and cooking drive the variability in particle number, but mass concentrations are dominated by aged background particles composed of secondary materials. In addition, people exposed to elevated number concentrations of atmospheric particles are also exposed to more externally mixed particles. Conclusions: Our advanced measurement technique provides a new exposure picture that resolves the large intra-city spatial heterogeneity in traffic and cooking particle number concentrations in the populous urban area. Our results provide a complementary and more detailed perspective compared with bulk measurements of composition. In addition, given the influence of particle mixing state on properties such as particle deposition in the lung, the large spatial gradients of chemical mixing state may significantly influence the health effects of fine PM. https://doi.org/10.1289/EHP5311
Assessment of the Predictive/ Prognostic Value of the Myeloid-Derived Suppressor Cells (MDSC) and Regulatory T Cells (TREGS) in Non-Small Cell Lung Cancer (NSCLC). Preliminary Results
Authors: E.K. Vetsika, E. Skalidaki, A. Koutoulaki, D. Mavroudis, V. Georgoulias, A. Kotsakis
Journal: Annals of Oncology (2012)
P2.19 Aaptamine, Demethyloxyaaptamine, and Isoaaptamine: A Proteomic-Based Screening of Protein Targets in Cisplatin-Resistant Tumor Cells
Authors: S.A. Dyshlovoy, I. Naeth, S. Venz, S.N. Fedorov, L.K. Shubina, V.A. Stonik, S. Balabanov, F. Honecker
Journal: Annals of Oncology (2012)
Proton Pump Inhibitors vs Histamine-2 Receptor Blockers for Stress Ulcer Prophylaxis in Critically Ill Patients
Authors: Todd W. Rice, Sunil Kripalani, Christopher J. Lindsell
Journal: JAMA (2020)

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Comparison in 1323 Patients of Preoperative Imaging Staging and Pathological Examination of Resected Pancreatic Head Adenocarcinoma: Series of the Association Française De Chirurgie
Authors: M. Gilabert, J.M. Boher, J.L. Raoul, O. Turrini, F. Paye, P. Bachellier, J. Delpero, G. Afc
Journal: Annals of Oncology (2012)