tbuckley/cabot-search huggingface dataset:
<i>TP53</i> germline mutations in young females with early onset breast cancer in a Mexican population.
Authors: Lenny Nadia Gallardo, Teresa Tusie-Luna, Maria Isabel Tusie-Luna, José Díaz-Chávez, Enrique Macario Herrera Medina, Mariana Chavez-Mac Gregor, Enrique Bargallo Rocha, Yayoi Xcchitl Segura Kato, Cynthia Villarreal, Luis Alonso Herrera Montalvo, David Franciso Cantu-de Leon
Journal: Journal of Clinical Oncology (2016)

e13027 Background: Breast cancer in Mexican patients presents in average 10 year earlier compared to other populations. Among patients with TP53 mutations, breast cancer is the most common malignancy. In this study we aim to determine the rate of TP53 mutations among young Mexican breast cancer patients. Methods: Breast cancer patients younger that 45 were retrospectively identified, only patients without BRCA1/2 mutations were included. Clinical records and pedigrees were reviewed. Next generation sequencing test for TP53was performed from blood specimens. All pathogenic mutations were confirmed by Sanger sequencing and verified if were included in the IACR TP53 database. Results: Among the 78 patients younger than 45 yo evaluated and tested with next generation sequencing, we identified 5 patients with a TP53 mutation (6.4%). All were younger than 36 corresponding to a rate of 9.4% of mutations in this group of individuals (n = 53). Two, not previously described, frameshift mutations were found (c.291delC and c.273dupG) and three missense mutations (c.844C > T, c.517G > A, c.604C > T). A VUS c.672G > A that causes a silent mutation in a splicing-donor site was identified. All patients with a TP53 mutation had locally advanced disease and tumors were high grade and Her2 positive. Conclusions: Among Mexican women younger than 45 yo, the rate of TP53 mutations was higher than in other populations where its estimated to be 1%. Among patients younger than 36 the proportion was even higher. All patients had a family history suggestive of Li-Fraumeni syndrome. The VUS found in our series needs a deeper analysis (family segregation, structure and function of the resulting protein). Our results support the international recommendation of performing molecular testing for TP53 in breast cancer patients younger than 35 years. Identification of patients with TP53 mutation has important prognostic, therapeutic and quality of life implications for the proband in addition of the risk reduction strategies and intensive surveillance recommended in their families.
P3-095: Erlotinib in advanced squamous cell carcinoma of the lung
Authors: Dolores Isla, Ulpiano Jimenez, Juan Jose Valverde, Javier Garcia, Jose Alfredo Almenarez, Jose Andres Moreno, Pedro Valero, Reyes Bernabe, Maria Luz Amador, Ares Luis Paz
Journal: Journal of Thoracic Oncology (2007)
Abstract 3053: Knockout of UCP2 suppresses skin carcinogenesis
Authors: Annapoorna Sreedhar, Chunjing Zhang, Yunfeng Zhao
Journal: Cancer Research (2015)

Abstract Mitochondria are important and necessary components of cell organelles. In recent times, mitochondrial metabolism has regained attention due to the growing evidence suggesting that dysfunction of mitochondria could play a major role in cancer. Cancer cells that are actively proliferating have great demand for ATP. This huge demand for ATP is met by glycolysis, which is called the ‘Warburg Effect’. Although the Warburg effect has lately been challenged, dysfunction of the mitochondrial dependent processes is a characteristic feature of almost all tumor cells, which lead to higher oxidative stress, inhibition of apoptosis and enhanced cell proliferation; which are the hallmarks of tumor cells. Mitochondrial uncoupling proteins have gained enormous interest in the field of cancer metabolism due to their impact on mitochondrial dependent processes. Uncoupling proteins are a family of mitochondrial proteins present in the inner mitochondrial membrane whose physiological role is to decrease membrane potential and hence ATP production. One of the most interesting functions of UCPs is to decrease the generation of ROS. However, because of altered mitochondrial dependent processes, cancer cells have elevated levels of ROS production leading to a phenomenon called ‘oxidative stress’. To fight against this oxidative stress, UCP2 (a homologue of UCP family) has shown to be up-regulated in a number of human cancers. However, there is no direct evidence supporting UCP2 contributes to carcinogenesis. Considering this ability of UCP2 to modulate ROS, membrane potential and mitochondrial bioenergetics, an interesting question to us, was whether UCP2 is involved in the progression of cancer. Using UCP2 homozygous knockout mice and UCP2 overexpressed cells; our data have demonstrated that knockout of UCP2 suppressed skin carcinogenesis. Overexpression of UCP2 enhanced skin cell transformation and oncogenic activation. In addition, genipin, a known UCP2 inhibitor, was able to inhibit oncogenic activation during skin cell transformation, even in UCP2 overexpressed cells. Finally, although knockout of UCP2 increased the basal levels of protein oxidation, it did not enhance protein oxidation in mouse skin epidermal tissues during skin carcinogenesis. In summary, our data have provided direct evidence that UCP2 promotes carcinogenesis, and targeting UCP2 may serve as a translational approach for chemoprevention. Citation Format: Annapoorna Sreedhar, Chunjing Zhang, Yunfeng Zhao. Knockout of UCP2 suppresses skin carcinogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3053. doi:10.1158/1538-7445.AM2015-3053
Endoscopic ultrasound-guided transhepatic biliary drainage in altered anatomy: a two-step approach
Authors: Aleksey Novikov, Nikhil Kumta, Benjamin Samstein, Michel Kahaleh
Journal: Endoscopy (2016)

Endoscopic ultrasound (EUS)-guided biliary drainage has been used for more than a decade as an alternative to percutaneous drainage. It offers a minimally invasive option for patients in whom conventional endoscopic retrograde cholangiopancreatography (ERCP) is unfeasible.
Comparison of Three Tests for Confirmation of the Diagnosis of Heparin Induced Thrombocytopenia.
Authors: Harry L. Messmore, Abdul M. Choudhury, Nancy J. Fabbrini, Mary L. Bird, Thomas Moritz, Lizzy Thottapurathu, William H. Wehrmacher, Margaret Prechel, Jeanine M. Walenga, Thelma J. Crosby, Betty C. Love, Courtney A. Zarr, Beth E. Griffin, Sanober S. Balbale
Journal: Blood (2004)
Abstract 4119: Tyrosine phosphorylation of MACC1 is essential and druggable for colorectal cancer metastasis restriction
Authors: Dennis Kobelt, Gunnar Dittmar, Claudia Fleuter, Janice Smith, Mathias Dahlmann, Rebekka Migotti, Peter M. Schlag, Ulrike S. Stein
Journal: Cancer Research (2015)

Abstract We identified the previously undescribed gene Metastasis Associated in Colon Cancer 1 (MACC1). MACC1 is a metastasis inducer and prognostic biomarker for colorectal cancer (CRC). MACC1 has meanwhile been confirmed as decisive driver for tumorigenesis and metastasis for a broad variety of solid cancers. Here we aim to identify the impact of defined tyrosine phosphorylations on the function of the metastasis inducer MACC1. In silico identified MACC1 tyrosine phosphorylation (pY) sites were ranked and most promising positions were site-directed mutated in wildtype (wt) MACC1 constructs. Human CRC cells were transduced with these constructs. Tyrosine phosphorylation was quantified by selected reaction monitoring (SRM)-mass spectrometry. Effects of pY-MACC1 mutants on cell migration, proliferation, dissemination and colony formation were assessed in cell culture as well as on liver metastasis formation in human CRC-xenografted mice. To identify MACC1-phosphorylating kinases the MACC1 interactome was identified using mass spectrometry. Most promising binding partners were validated by immunoprecipitation. Impact of inhibitors targeting kinases phosphorylating MACC1 was assessed on MACC1-induced tumor growth and liver metastasis in human CRC-xenografted mice by in vivo imaging. We report that tyrosine phosphorylation of MACC1 is hierarchical and essential for motility and proliferation in cell culture, as well as for tumor growth and metastasis in mice. We identified kinases for MACC1 phosphorylation. Targeting these kinases using inhibitors employed in clinical trials restricts MACC1-induced tumor growth and metastasis in mice. MACC1 tyrosine phosphorylation is crucial for metastasis and is druggable by small molecule inhibitors. This fundamental finding opens new therapeutic options for inhibition of MACC1-induced cancer metastasis. Citation Format: Dennis Kobelt, Gunnar Dittmar, Claudia Fleuter, Janice Smith, Mathias Dahlmann, Rebekka Migotti, Peter M. Schlag, Ulrike S. Stein. Tyrosine phosphorylation of MACC1 is essential and druggable for colorectal cancer metastasis restriction. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4119. doi:10.1158/1538-7445.AM2015-4119
Taking Care of Our Friends and Neighbors
Authors: Tomasz M. Beer, Vinay Prasad
Journal: JAMA Oncology (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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Oncology journal
Reproductive Aging and Cardiovascular Disease Risk
Authors: Elizabeth McNally
Journal: JAMA Cardiology (2016)

Taulant Muka, MD, PhD; Clare Oliver-Williams, PhD; Setor Kunutsor, MD, PhD; Joop S. E. Laven, MD, PhD; Bart C. J. M. Fauser, MD, PhD; Rajiv Chowdhury, MD, PhD; Maryam Kavousi, MD, PhD; Oscar H. Franco, MD, PhD
Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study
Authors: Susan O'Brien, Jeffrey A Jones, Steven E Coutre, Anthony R Mato, Peter Hillmen, Constantine Tam, Anders Österborg, Tanya Siddiqi, Michael J Thirman, Richard R Furman, Osman Ilhan, Michael J Keating, Timothy G Call, Jennifer R Brown, Michelle Stevens-Brogan, Yunfeng Li, Fong Clow, Danelle F James, Alvina D Chu, Michael Hallek, Stephan Stilgenbauer
Journal: The Lancet Oncology (2016)
Combination of Lenalidomide and R-DHAP for Treatment of Relapsed and Refractory Aggressive B-NHL
Authors: Bertram Glass, Anke Goerlitz, Sebastian Pfeiffer, Maike Nickelsen, Andreas Huettmann, Justin Hasenkamp, Lorenz H. Truemper, Martin Dreyling, Michael G Kiehl, Hans Salwender, Norbert Schmitz
Journal: Blood (2014)
The modulation of stem cell behaviors by functionalized nanoceramic coatings on Ti-based implants
Authors: Xiangmei Liu, Man Li, Yizhou Zhu, K.W.K. Yeung, Paul K. Chu, Shuilin Wu
Journal: Bioactive Materials (2016)

Nanoceramic coating on the surface of Ti-based metallic implants is a clinical potential option in orthopedic surgery. Stem cells have been found to have osteogenic capabilities. It is necessary to study the influences of functionalized nanoceramic coatings on the differentiation and proliferation of stem cells in vitro or in vivo. In this paper, we summarized the recent advance on the modulation of stem cells behaviors through controlling the properties of nanoceramic coatings, including surface chemistry, surface roughness and microporosity. In addition, mechanotransduction pathways have also been discussed to reveal the interaction mechanisms between the stem cells and ceramic coatings on Ti-based metals. In the final part, the osteoinduction and osteoconduction of ceramic coating have been also presented when it was used as carrier of BMPs in new bone formation.
Do Patients with Post-Essential Thrombocythemia and Post-Polycythemia Vera Differ from Patients with Primary Myelofibrosis?
Authors: Lucia Masarova, Naval Daver, Naveen Pemmaraju, Prithviraj Bose, Sherry Pierce, Taghi Manshouri, Jorge E. Cortes, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Blood (2015)
Analysis of clonality by HUMARA PCR in high risk MDS patients before and after intensive anti-leukemic treatment
Authors: J Van Dijk, M Aivado, Michel Delforge, R Van Soest, G Catalano, B Johansson, I Tigaud, M Jotterand-Bellomo, J Cermak, Anne Hagemeijer-Hausman, S Suciu, B Van Der Reijden, J Jansen, P Muus, T de Witte
Journal: Blood (2001)
Five-Year Survival After Endosonography vs Mediastinoscopy for Mediastinal Nodal Staging of Lung Cancer
Authors: Jolanda C. Kuijvenhoven, Daniël A. Korevaar, Kurt G. Tournoy, Thomas L. A. Malfait, Christophe Dooms, Robert C. Rintoul, Jouke T. Annema
Journal: JAMA (2016)
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
Authors: Steven P. Marso, Stephen C. Bain, Agostino Consoli, Freddy G. Eliaschewitz, Esteban Jódar, Lawrence A. Leiter, Ildiko Lingvay, Julio Rosenstock, Jochen Seufert, Mark L. Warren, Vincent Woo, Oluf Hansen, Anders G. Holst, Jonas Pettersson, Tina Vilsbøll
Journal: New England Journal of Medicine (2016)

Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown.We randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. We hypothesized that semaglutide would be noninferior to placebo for the primary outcome. The noninferiority margin was 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio.At baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both. The primary outcome occurred in 108 of 1648 patients (6.6%) in the semaglutide group and in 146 of 1649 patients (8.9%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.58 to 0.95; P<0.001 for noninferiority). Nonfatal myocardial infarction occurred in 2.9% of the patients receiving semaglutide and in 3.9% of those receiving placebo (hazard ratio, 0.74; 95% CI, 0.51 to 1.08; P=0.12); nonfatal stroke occurred in 1.6% and 2.7%, respectively (hazard ratio, 0.61; 95% CI, 0.38 to 0.99; P=0.04). Rates of death from cardiovascular causes were similar in the two groups. Rates of new or worsening nephropathy were lower in the semaglutide group, but rates of retinopathy complications (vitreous hemorrhage, blindness, or conditions requiring treatment with an intravitreal agent or photocoagulation) were significantly higher (hazard ratio, 1.76; 95% CI, 1.11 to 2.78; P=0.02). Fewer serious adverse events occurred in the semaglutide group, although more patients discontinued treatment because of adverse events, mainly gastrointestinal.In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide. (Funded by Novo Nordisk; SUSTAIN-6 ClinicalTrials.gov number, NCT01720446 .).
World Rugby's erroneous and misleading representation of Australian sports' injury statistics
Authors: Joe Piggin, Allyson Pollock
Journal: British Journal of Sports Medicine (2016)

The goals of World Rugby's strategic plan, 2010 are to ‘Protect and promote Rugby, its values, spirit and ethos’ and to ‘Drive player welfare best practice’. These values are under question with the publication of misleading data on injury risks in its SportsWise Survey.

In response to calls earlier this year to the UK government for a ban on tackle and contact in the school game,1 World Rugby has published a report in which it states that ‘Compared with other sports and activities, rugby has a relatively low injury rate despite being known for its physicality’.2 The statement is misleading and should be changed.

World Rugby's report draws on data taken from a report published by the Australian Government and Flinders University, ‘Australian sports injury hospitalisations 2011–12’.3 World Rugby produced two charts to support their …
Novel technique to relax the lower esophageal sphincter during challenging peroral endoscopic myotomy (POEM)
Authors: Majidah Bukhari, Vivek Kumbhari, Yamile Haito-Chavez, Yen-I Chen, Saowanee Ngamruengphong, Payal Saxena, Mouen Khashab
Journal: Endoscopy (2016)

Amyl nitrite is easily administered and is a potent short-acting smooth muscle relaxant. Therefore, it can be used to relax the lower esophageal sphincter (LES) during submucosal tunneling in peroral endoscopic myotomy (POEM) ([Fig. 1]) [1] [2]. One study demonstrated that the diameter of the LES increased by > 3 mm in patients with idiopathic achalasia in response to amyl nitrite [3]. POEM involves the creation of a submucosal tunnel, for which dissection of fibers should be carried out close to the muscle layer to avoid mucosal injury. When the LES is tight, this dissection of the fibers can be challenging to perform safely without risking mucosal injury. [Video 1] demonstrates the use of amyl nitrite inhalation to relax the LES and facilitate submucosal tunneling in two patients.
Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin Activity in Human Atrial Fibrillation
Authors: Javier Barallobre-Barreiro, Shashi K. Gupta, Anna Zoccarato, Rika Kitazume-Taneike, Marika Fava, Xiaoke Yin, Tessa Werner, Marc N. Hirt, Anna Zampetaki, Alessandro Viviano, Mei Chong, Marshall Bern, Antonios Kourliouros, Nieves Domenech, Peter Willeit, Ajay M. Shah, Marjan Jahangiri, Liliana Schaefer, Jens W. Fischer, Renato V. Iozzo, Rosa Viner, Thomas Thum, Joerg Heineke, Antoine Kichler, Kinya Otsu, Manuel Mayr
Journal: Circulation (2016)

Myocardial fibrosis is a feature of many cardiac diseases. We used proteomics to profile glycoproteins in the human cardiac extracellular matrix (ECM).Atrial specimens were analyzed by mass spectrometry after extraction of ECM proteins and enrichment for glycoproteins or glycopeptides.ECM-related glycoproteins were identified in left and right atrial appendages from the same patients. Several known glycosylation sites were confirmed. In addition, putative and novel glycosylation sites were detected. On enrichment for glycoproteins, peptides of the small leucine-rich proteoglycan decorin were identified consistently in the flowthrough. Of all ECM proteins identified, decorin was found to be the most fragmented. Within its protein core, 18 different cleavage sites were identified. In contrast, less cleavage was observed for biglycan, the most closely related proteoglycan. Decorin processing differed between human ventricles and atria and was altered in disease. The C-terminus of decorin, important for the interaction with connective tissue growth factor, was detected predominantly in ventricles in comparison with atria. In contrast, atrial appendages from patients in persistent atrial fibrillation had greater levels of full-length decorin but also harbored a cleavage site that was not found in atrial appendages from patients in sinus rhythm. This cleavage site preceded the N-terminal domain of decorin that controls muscle growth by altering the binding capacity for myostatin. Myostatin expression was decreased in atrial appendages of patients with persistent atrial fibrillation and hearts of decorin null mice. A synthetic peptide corresponding to this decorin region dose-dependently inhibited the response to myostatin in cardiomyocytes and in perfused mouse hearts.This proteomics study is the first to analyze the human cardiac ECM. Novel processed forms of decorin protein core, uncovered in human atrial appendages, can regulate the local bioavailability of antihypertrophic and profibrotic growth factors.
P3-033: Serum biomarkers predict response to combination celecoxib and erlotinib therapy in advanced non-small cell lung cancer
Authors: Karen L. Reckamp, Brian K. Gardner, David Elashoff, Robert A. Figlin, Kostyantyn Krysan, Mariam Dohadwala, Landon Inge, Ayyappan Rajasekaran, Steven M. Dubinett
Journal: Journal of Thoracic Oncology (2007)
Is Surgical Resection Justified for Advanced Intrahepatic Cholangiocarcinoma?
Authors: Tomoaki Yoh, Etsuro Hatano, Kenya Yamanaka, Takahiro Nishio, Satoru Seo, Kojiro Taura, Kentaro Yasuchika, Hideaki Okajima, Toshimi Kaido, Shinji Uemoto
Journal: Liver Cancer (2016)

&lt;b&gt;&lt;i&gt;Backgrounds: &lt;/i&gt;&lt;/b&gt;Prognosis for patients with advanced intrahepatic cholangiocarcinoma (ICC) with intrahepatic metastasis (IM), vascular invasion (VI), or regional lymph node metastasis (LM) remains poor. The aim of this study was to clarify the indications for surgical resection for advanced ICC. &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;We retrospectively divided 213 ICC patients treated at Kyoto University Hospital between 1993 and 2013 into a resection (n=164) group and a non-resection (n=49) group. Overall survival was assessed after stratification for the presence of IM, VI, or LM. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;Overall median survival times (MSTs) for the resection and non-resection groups were 26.0 and 7.1 months, respectively (p&lt;0.001). After stratification, MSTs in the resection and non-resection groups, respectively, were 18.7 vs. 7.0 months for patients with IM (p&lt;0.001), 23.4 vs. 5.7 months for those with VI (p&lt;0.001), and 12.8 vs. 5.5 months for those with LM (p&lt;0.001). &lt;b&gt;&lt;i&gt;Conclusion: &lt;/i&gt;&lt;/b&gt;When macroscopic curative resection is possible, surgical resection can be justified for some advanced ICC patients with IM, VI, or LM.
RN-1, a Potent and Selective LSD1 Inhibitor, Induces High Levels of Fetal Hemoglobin (HbF) in Anemic Baboons (P. anubis)
Authors: Angela Rivers, Kestis Vaitkus, Maria Armila Ruiz, Vinzon Ibanez, Tatiana Kouznetsova, Joseph DeSimone, Donald Lavelle
Journal: Blood (2014)
Author response: Unfounded criticisms
Authors: Chris G Maher, Mark J Hancock, Daniel Steffens
Journal: British Journal of Sports Medicine (2016)

Dr Shiri1 criticises our back pain prevention review2 that was summarised as a PEDro synthesis in BJSM .3 None of the criticisms are valid.

The claim that we missed studies is incorrect, as the five studies cited by Dr Shiri were found in our search but excluded as they were …
Dysfunction of Somatostatin-Positive Interneurons Associated with Memory Deficits in an Alzheimer’s Disease Model
Authors: Lena C. Schmid, Manuel Mittag, Stefanie Poll, Julia Steffen, Jens Wagner, Hans-Rüdiger Geis, Inna Schwarz, Boris Schmidt, Martin K. Schwarz, Stefan Remy, Martin Fuhrmann
Journal: Neuron (2016)