tbuckley/cabot-search huggingface dataset:
Metallic vs Plastic Stents for Benign Biliary Strictures—Reply
Authors: Gregory A. Coté
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 810: The CARRIERS consortium: Establishing refined breast cancer risk estimates in known predisposition genes
Authors: Jenna Lilyquist, Peter Kraft, Steven N. Hart, Emily J. Hallberg, Chunling Hu, Raymond Moore, Rohan Gnanaolivu, Susan M. Domchek, Jeffrey N. Weitzel, Katherine L. Nathanson, David E. Goldgar, Fergus J. Couch
Journal: Cancer Research (2016)

Abstract Breast cancer is the most common type of cancer, and has a strong heritable component, with approximately 15 percent of new cases having family history of breast cancer. Genetic panel testing for patients with a family history of breast cancer has become a popular clinical resource. However, the risk of breast cancer associated with inactivating mutations in the predisposition genes is largely undefined, creating critical limitations in the interpretations of the results from panel testing and subsequent medical management. The Cancer Risk Estimates Related to Susceptibility Genes (CARRIERS) consortium was established to determine the risk of cancers associated with truncating mutations in the known predisposition genes and to extend these studies to the clinical classification of variants of uncertain significance (VUS) in the relevant genes. CARRIERS involves screening of approximately 30,000 population-based breast cancer cases and 30,000 study matched controls for mutations in 28 established or proposed breast cancer predisposition genes. Population-based risks for breast cancer associated with mutations in each gene will be estimated. In parallel, 10,000 breast cancer cases from moderate and high-risk breast cancer families will be similarly screened for mutations and the penetrance of the mutations in high-risk families will be estimated. Furthermore, VUS identified by mutation screening will be characterized by functional and family-based studies and models for classification of the clinical relevance of VUS in each gene will be developed. These data are expected to lead to improvements in cancer risk assessment and improved management of patients found to carry mutations or VUS in breast cancer predisposition. Citation Format: Jenna Lilyquist, Peter Kraft, Steven N. Hart, Emily J. Hallberg, Chunling Hu, Raymond Moore, Rohan Gnanaolivu, Susan M. Domchek, Jeffrey N. Weitzel, Katherine L. Nathanson, David E. Goldgar, Fergus J. Couch. The CARRIERS consortium: Establishing refined breast cancer risk estimates in known predisposition genes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 810.
Dual Role of the Adaptive Immune System in Liver Injury and Hepatocellular Carcinoma Development
Authors: Jessica Endig, Laura Elisa Buitrago-Molina, Silke Marhenke, Florian Reisinger, Anna Saborowski, Jutta Schütt, Florian Limbourg, Christian Könecke, Alina Schreder, Alina Michael, Ana Clara Misslitz, Marc Eammonn Healy, Robert Geffers, Thomas Clavel, Dirk Haller, Kristian Unger, Milton Finegold, Achim Weber, Michael P. Manns, Thomas Longerich, Mathias Heikenwälder, Arndt Vogel
Journal: Cancer Cell (2016)
<i>Notes from the Field</i>: Kratom (<i>Mitragyna speciosa</i>) Exposures Reported to Poison Centers — United States, 2010–2015
Authors: Mehruba Anwar, Royal Law, Josh Schier
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Kratom (Mitragyna speciosa) is a plant consumed throughout the world for its stimulant effects and as an opioid substitute (1). It is typically brewed into a tea, chewed, smoked, or ingested in capsules (2). It is also known as Thang, Kakuam, Thom, Ketum, and Biak (3). The Drug Enforcement Administration includes kratom on its Drugs of Concern list (substances that are not currently regulated by the Controlled Substances Act, but that pose risks to persons who abuse them), and the National Institute of Drug Abuse has identified kratom as an emerging drug of abuse (3,4). Published case reports have associated kratom exposure with psychosis, seizures, and deaths (5,6). Because deaths have been attributed to kratom in the United States (7), some jurisdictions have passed or are considering legislation to make kratom use a felony (8). CDC characterized kratom exposures that were reported to poison centers and uploaded to the National Poison Data System (NPDS) during January 2010-December 2015. The NPDS is a national database of information logged by the country's regional poison centers serving all 50 United States, the District of Columbia, and Puerto Rico and is maintained by the American Association of Poison Control Centers. NPDS case records are the result of call reports made by the public and health care providers.
Abstract 2139: RNA nanoparticles as a two-in-one siRNA delivery carrier synergistically suppress drug-resistance cancer via combination therapy with doxorubicin
Authors: Hyung Jun Ahn
Journal: Cancer Research (2016)

Abstract To overcome multi-drug resistance (MDR) caused by malfunction of genes in chemotherapy, we synthesize RNA nanoparticles (RNA NPs) as a “two-in-one” siRNA delivery system for MDR1 siRNA and BCL2 siRNA by using rolling circle transcription and base-pairing with folate-DNA-cholesterol fragments. The resulting RNA nanoparticles (Dsi RNPs), which contain multiple tandem copies of two siRNA sequences, form the self-assembled structure with about 100 nm of diameter, and simultaneously suppress pump and non-pump phenotypes in the same cancer cells. Using Dsi RNPs, we show that there exists an optimal time point within the window of time at which the synchronous silencing of MDR1 and BCL2 gene markedly enhances the chemosensitivity of MDR cancer cells to doxorubicin. Accordingly, a two-step sequential treatment of MDR cancer cells with Dsi RNPs and doxorubicin leads to the optimal synergistic cancer suppression. Finally, we demonstrate that such a synergism is attributed to the synchronous silencing of both genes, as well as to the precisely controlled timings of drugs and Dsi RNPs treatment. RNA NPs exhibit the folate receptor-specific cellular uptake, lowering the risk of severe adverse side effects. Also, RNA NPs do not induce innate immunostimulatory response and their highly condensed structure reveals the enhanced stability against nuclease attack in bloodstream. Therefore, RNA NPs delivery system provides an alternative tool as a two-in-one siRNA carrier that is suitable for the spatial-temporal synchronization of double gene silencing, and also, Dsi RNPs have great potential as combination chemotherapeutics with traditional anticancer drugs for suppression of MDR cancer. Citation Format: Hyung Jun Ahn. RNA nanoparticles as a two-in-one siRNA delivery carrier synergistically suppress drug-resistance cancer via combination therapy with doxorubicin. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2139.
Abstract 1615: Metastasis suppression by KP54 and non-KP54 kisspeptins
Authors: Kelsey R. Hampton, Keke M. Pounds, Andrew P. Trembath, Danny R. Welch
Journal: Cancer Research (2016)

Abstract The KISS1 metastasis suppressor blocks metastasis by inhibiting colonization at secondary sites. In order to suppress metastasis, KISS1 must be secreted and cleaved by furin into kisspeptins. Kisspeptin-54 (KP54, K67 to F121) binds a G-protein coupled receptor, KISS1R, and the mechanism of metastasis suppression has been assumed to be through KP54 binding with KISS1R. However, since KISS1 is cleaved extracellularly, and since none of the cells tested express KISS1R, an alternate hypothesis is required - another kisspeptin is responsible for suppressing metastasis. To test this hypothesis, we engineered all ten of the possible kisspeptins based upon predicted dibasic cleavage sites (M1-Q145; M1-R56; M1-R67; M1-R124; R56-R66; R67-F121; R56-F121; R56-Q145; R67-Q145; R124-Q145). The (KISS1 Manufactured Peptides, or KMP) each contained the same secretion signal as nascent KISS1 and were designated KMP1 to KMP10 respectively. Each KMP was expressed individually in B16-F10 melanoma cells. Following intravenous injection, experimental lung metastases were quantified. While KP54 expression suppressed metastasis, other KMP lacking the KISS1R binding motif also suppressed metastasis as or more effectively (p&amp;lt;0.05). In vitro, cell lines expressing suppressor KMP inhibited motility, increased mitochondrial biomass, and elevated levels of oxidative phosphorylation (phenotypes previously correlated with KISS1 function). In particular, KMP2 (M1 - R56) completely suppressed metastasis. Collectively, these data demonstrate that the mechanism of action for metastasis suppression by KISS1 does not necessarily require activation of KISS1R, and also suggests the existence of additional receptors. Support: CA134981, Natl Fndn Cancer Res, Komen SAC11037, KS Bioscience Auth, P30-CA168524, Steiner Family Fund for Metastasis Research. Citation Format: Kelsey R. Hampton, Keke M. Pounds, Andrew P. Trembath, Danny R. Welch. Metastasis suppression by KP54 and non-KP54 kisspeptins. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1615.
Abstract 751: Secreted anterior gradient-2 is a potential tumor-microenvironment-related therapeutic target
Authors: Hao Guo, Qi Zhu, Zhenghua Wu, Hitesh B. Mangukiya, Xiaoyan Yu, Dawei Li
Journal: Cancer Research (2016)

Abstract The secreted anterior gradient-2 (AGR2) orthologs in amphibians are critical signaling proteins in anterior specification and limb regeneration. It is also overexpressed in diverse human cancers especially adenocarcinomas. Although tumor-related functions of intracellular AGR2 have been intensively investigated and several AGR2-related signaling pathways have been identified, the full scope of secreted AGR2 functions, especially the exact mechanism of actions, remain insufficiently explored. Here we report that AGR2 induction after SKOV3 xenograft inoculation is tumor microenvironment (TME) dependent. This phenomenon can be mimic in vitro through serum deprivation but not hypoxia treatment. In addition, the secreted AGR2 may in turn influence the development of TME. It scatters the tumor cells and guides the nearby vascular endothelial cells and fibroblasts toward the source of AGR2 through various degrees of crosstalk with VEGF and bFGF pathways. Blocking the AGR2 inhibits the tumor growth and decreases the blood vessel density in SKOV3 xenograft model. Our results show that exogenous AGR2 binds specifically with VEGF and bFGF, and promotes their dimerization. This binding enhances the phosphorylation signals, such as ERK phosphorylation, induced by VEGF and bFGF, and promotes the VEGF- and bFGF- dependent angiogenesis. We also find that heparin may reverse the binding between bFGF and AGR2, indicating that dimerized bFGF that promoted by AGR2 would be released when it is close to the cell surface where heparin sulfate is abundant. Taken together, the present results suggest that tumor-secreted AGR2 may activate the specific growth factors surrounding the tumor cells to promote the angiogenesis and tumor growth, and also act as a short-range chemoattractant to guide surrounding vascular endothelial cells and fibroblasts toward tumor cells in building the TME. This mechanism of action directly links the secreted AGR2 with the cell signaling networks well-known in building TME. This may help to further explain how tumor cells interact with and attract nearby fibroblasts and blood vessel cells to form their microenvironment and support their growth, suggesting a potential anti-TME target. Citation Format: Hao Guo, Qi Zhu, Zhenghua Wu, Hitesh B. Mangukiya, Xiaoyan Yu, Dawei Li. Secreted anterior gradient-2 is a potential tumor-microenvironment-related therapeutic target. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 751.
Massive acute gases intoxication: Clinical presentation and outcomes
Authors: María Sánchez-Carpintero Abad, Ana Belén Alcaide, Aranzazu Campo, Jorge Zagaceta, Felipe Lucena, Manuel Landecho, Félix Alegre, Luis Seijo, Juan Pablo de Torres, Javier Zulueta
Journal: European Respiratory Journal (2011)

On Oct 30th, 2008, a car bomb exploded on the University of Navarre (UN) campus, causing serious damages and several fires. On Nov 5th, during the repairing works, gases retained inside the false ceiling were released, causing intoxication by inhalation in about 300 people.  A longitudinal observational study was performed to assess the presentation and outcomes of 230 patients assisted at the Emergency Room (ER) of the UN Hospital.  Employees and students were affected: 104 men and 126 women, with mean age 31±12 y, 23% smokers and 13% with previous respiratory disease. 65% of patients got to the ER on Nov 5th. At the first 6 h commonest complaints were cough (80%), dyspnea (51%), sore throat (38%), and chest tightness (32%). People coming after 6 h had more frequently fever (31%), headache (30%), nausea (25%), asthenia (18%), dizziness (16%), and vomiting (7%). Chest xray (n=218) showed infiltrates in 17.5% and chest CT (n=19) interstitial/alveolar infiltrates in 68%. Blood analysis (n=101) revealed leukocytosis in 65%, and high CRP in 85%. 80 patients were hospitalised (34.8%) with a median length of stay of 1 day (max 5 d). At the ER, patients received bronchodilators (62%) and steroids (54%). Upon discharge, bronchodilators (82%), steroids (30%) and N-acetyl cysteine (82%) were prescribed.  One month after discharge, 206 patients were re-evaluated: 41 (20%) had symptoms, consisting in dyspnea (12%) and cough (11%). Chest xray (n=162) was normal in all the cases. Chest CT (n=36) showed alveolar-interstitial infiltrates in 5 patients. Spirometry (n=193) was normal in all the cases. We describe the clinical features of an acute intoxication by unknown gases, with a biphasic presentation of symptoms and short clinical resolution.
Abstract 3608: Detection of somatic structural variants using nanopore sequencing
Authors: Alexis L. Norris, Rachael E. Workman, Yunfan Fan, James R. Eshleman, Winston Timp
Journal: Cancer Research (2016)

Abstract Structural variants (SVs) are a hallmark of human cancer, but remain difficult to reliably and accurately detect with next generation sequencing (NGS). This is in part due to the difficult in mapping NGS's short reads (&amp;lt;300bp) to repetitive elements, which often flank the genomic rearrangements of SVs. Nanopore sequencing, a 3rd generation sequencing technology, offers long sequencing reads (up to 20kb), that should allow for more reliable mapping of SVs. Nanopore sequencing relies on a similar concept to a Coulter counter, reading the DNA sequence from the change in electrical current resulting from a DNA strand being forced through a nanometer-sized pore embedded in a membrane. Here, we have tested the ability of nanopore sequencing to detect a series of well-characterized SVs (including large deletions, inversions, and translocations), that inactivate the CDKN2A/p16 and SMAD4/DPC4 tumor suppressor genes in pancreatic cancer. Using PCR amplicon mixes, we show that nanopore sequencing on the MinION platform can detect large deletions, translocations, and inversions at dilutions as low as 1:100. Given the speed, small footprint (USB size), and low capital cost, nanopore sequencing could become the ideal tool for the low-level detection of somatic SVs, with clinical applications of molecular relapse, early detection, or therapeutic monitoring. Citation Format: Alexis L. Norris, Rachael E. Workman, Yunfan Fan, James R. Eshleman, Winston Timp. Detection of somatic structural variants using nanopore sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3608.
A population-based study of racial/ethnic disparities in cancer survival among adolescents and young adults.
Authors: Meryl Colton, Adam L. Green
Journal: Journal of Clinical Oncology (2016)

6557 Background: Disparities in cancer survival have been demonstrated between racial and ethnic groups. Several mechanisms could be involved, including differences in stage at presentation, treatment differences, and biological variation. Racial/ethnic disparities have not been comprehensively evaluated in adolescents and young adults (AYA) (age 15-29), a population at particular risk for disparities in socioeconomic status (SES) and delayed diagnosis. Methods: We utilized the Surveillance, Epidemiologic and End Results (SEER) 18 database to calculate hazard ratios (HR) of death within two years of diagnosis for Hispanic White (HW), Non-Hispanic Black (NHB), and Hispanic Black (HB) compared to Non-Hispanic White (NHW) individuals between the ages of 15 and 29 for each ICCC group. We then compared crude HR and HR adjusted for insurance status and/or stage at diagnosis to explore the influence of these factors. Results: HW, NHB and/or HB AYA were found to have significantly higher risk of death than NHW AYA for several cancer types. These associations were only partially attenuated after controlling for insurance status and stage at diagnosis (Table). Conclusions: Racial and ethnic disparities in survival exist among AYA in many cancer types. These differences are partially, but not fully, explained by insurance status and stage at presentation, suggesting influences of both biology and SES on the diagnostic and treatment processes. Further work should explore the mechanisms of these disparities. Hazard ratios (HR) and 95% confidence intervals (95%CI) of HW and NHB AYA versus reference (NHW). HR 95%CI Leukemia HW 1.15 (1.03, 1.29) NHB 1.05 (0.88, 1.25) Lymphoma HW 1.28 (1.16, 1.40) NHB 1.07 (0.96, 1.2) Brain tumors HW 1.26 (1.09, 1.46) NHB 0.91 (0.73, 1.13) Renal tumors HW 0.92 (0.67, 1.28) NHB 1.43 (1.06, 1.94) Hepatic tumors HW 1.77 (1.13, 2.76) NHB 1.76 (1.08, 2.87) Bone tumors HW 0.92 (0.73, 1.16) NHB 0.61 (0.44, 0.86) Soft tissue sarcomas HW 1.19 (1.03, 1.38) NHB 1.23 (1.11, 1.51) Germ cell tumors HW 1.27 (1.17, 1.39) NHB 1.16 (0.96, 1.41) Other malignant epithelial neoplasms HW 1.15 (1.08, 1.23) NHB 1.13 (1.04, 1.23) Model adjusted for stage at presentation and insurance status.
Bioenergetic Insufficiencies Due to Metabolic Alterations Regulated by the Inhibitory Receptor PD-1 Are an Early Driver of CD8 + T Cell Exhaustion
Authors: Bertram Bengsch, Andy L. Johnson, Makoto Kurachi, Pamela M. Odorizzi, Kristen E. Pauken, John Attanasio, Erietta Stelekati, Laura M. McLane, Michael A. Paley, Greg M. Delgoffe, E. John Wherry
Journal: Immunity (2016)
Abstract 2413: Cell type-specific deconvolution of heterogeneous tumor samples with immune infiltration using expression data
Authors: Zeya Wang, Jeffrey S. Morris, Chris C. Holmes, Jaeil Ahn, Bo Li, Wei Lu, Ximing Tang, Ignacio I. Wistuba, Wenyi Wang
Journal: Cancer Research (2016)

Abstract Tumor tissue samples comprise a mixture of cancerous and surrounding stromal cells. Understanding tumor heterogeneity is crucial to analyzing gene signatures associated with cancer prognosis and treatment decisions. Compared with the experimental approach of using laser micro-dissection to isolate different tissue components, in silico dissection of mixed cell samples is faster and cheaper. Numerous computational approaches previously developed have limited ability to deconvolute heterogeneous tumor samples. We have developed a deconvolution model, DeMix-T, that can explicitly account for a third component such as infiltrating immune cells, and address this challenging problem when the observed signals are assumed to come from a mixture of three cell compartments, infiltrating immune cells, the tumor microenvironment and cancerous tissues. The optimization-based algorithm for DeMix-T finds a local optimum for our estimation problem and is computationally feasible when it needs to compute high-dimensional integrals. DeMix-T therefore involves a novel two-stage filtering method that yields accurate estimates of cell purities and compartment-specific expression profiles. Simulations and real data analyses have demonstrated the good performance of our method. Compared with other deconvolution tools, DeMix-T can be applied more widely and provides deeper insight for cancer biomarker studies. It allows for a further understanding of immune cell infiltration in cancer and assists in the development of novel prognostic markers and therapeutic strategies. Citation Format: Zeya Wang, Jeffrey S. Morris, Chris C. Holmes, Jaeil Ahn, Bo Li, Wei Lu, Ximing Tang, Ignacio I. Wistuba, Wenyi Wang. Cell type-specific deconvolution of heterogeneous tumor samples with immune infiltration using expression data. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2413.