tbuckley/cabot-search huggingface dataset:
Analysis of Liver Tumor-Prone Mouse Models of the Hippo Kinase Scaffold Proteins RASSF1A and SAV1
Authors: Xiaoying Zhang, Cai Guo, Xiwei Wu, Arthur X. Li, Limin Liu, Walter Tsark, Reinhard Dammann, Hui Shen, Steven L. Vonderfecht, Gerd P. Pfeifer
Journal: Cancer Research (2016)

Abstract The tumor suppressor gene RASSF1A is epigenetically silenced in most human cancers. As a binding partner of the kinases MST1 and MST2, the mammalian orthologs of the Drosophila Hippo kinase, RASSF1A is a potential regulator of the Hippo tumor suppressor pathway. RASSF1A shares these properties with the scaffold protein SAV1. The role of this pathway in human cancer has remained enigmatic inasmuch as Hippo pathway components are rarely mutated in tumors. Here we show that Rassf1a homozygous knockout mice develop liver tumors. However, heterozygous deletion of Sav1 or codeletion of Rassf1a and Sav1 produced liver tumors with much higher efficiency than single deletion of Rassf1a. Analysis of RASSF1A-binding partners by mass spectrometry identified the Hippo kinases MST1, MST2, and the oncogenic IκB kinase TBK1 as the most enriched RASSF1A-interacting proteins. The transcriptome of Rassf1a−/− livers was more deregulated than that of Sav1+/− livers, and the transcriptome of Rassf1a−/−, Sav1+/− livers was similar to that of Rassf1a−/− mice. We found that the levels of TBK1 protein were substantially upregulated in livers lacking Rassf1a. Furthermore, transcripts of several β-tubulin isoforms were increased in the Rassf1a-deficient livers presumably reflecting a role of RASSF1A as a microtubule-stabilizing protein. In human liver cancer, RASSF1A frequently undergoes methylation at the promoter but this was not observed for MST1, MST2, or SAV1. Our results suggest a multifactorial role of RASSF1A in suppression of liver carcinogenesis. Cancer Res; 76(9); 2824–35. ©2016 AACR.
Echocardiography Criteria for Structural Heart Disease in Patients With End-Stage Renal Disease Initiating Hemodialysis
Authors: LaTonya J. Hickson, Sara M. Negrotto, Macaulay Onuigbo, Christopher G. Scott, Andrew D. Rule, Suzanne M. Norby, Robert C. Albright, Edward T. Casey, John J. Dillon, Patricia A. Pellikka, Sorin V. Pislaru, Patricia J.M. Best, Hector R. Villarraga, Grace Lin, Amy W. Williams, Vuyisile T. Nkomo
Journal: Journal of the American College of Cardiology (2016)
Lymphoid-Tissue-Resident Commensal Bacteria Promote Members of the IL-10 Cytokine Family to Establish Mutualism
Authors: Thomas C. Fung, Nicholas J. Bessman, Matthew R. Hepworth, Nitin Kumar, Naoko Shibata, Dmytro Kobuley, Kelvin Wang, Carly G.K. Ziegler, Jeremy Goc, Tatsuichiro Shima, Yoshinori Umesaki, R. Balfour Sartor, Kaede V. Sullivan, Trevor D. Lawley, Jun Kunisawa, Hiroshi Kiyono, Gregory F. Sonnenberg
Journal: Immunity (2016)
Biochemical Characterization of Endogenous Carbohydrate-Binding Proteins From Spontaneous Murine Rhabdomyosarcoma, Mammary Adenocarcinoma, and Ovarian Teratoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H J Gabius, R Engelhardt, S Rehm, F Cramer
Journal: JNCI Journal of the National Cancer Institute (1984)

Three entirely different tumor types were investigated biochemically for the presence and characteristics of endogenous carbohydrate-binding proteins in an inbred Brown Norway rat, an outbred Sprague-Dawley rat, and an outbred Han:NMRI mouse. The patterns under investigation included specificities for alpha- and beta-galactosyl, alpha-mannosyl, and alpha-fucosyl moieties, respectively, and specificities for heparin, analyzed by affinity chromatography on resins with immobilized sugars or glycoproteins and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The patterns were divided into categories according to dependence of the binding activity on the presence of Ca2+ and dependence on extraction conditions. Rhabdomyosarcoma revealed only Ca2+-independent activities, i.e., activities with specificity for beta-galactosides at a molecular weight of 12,000, with specificity for alpha-galactosides at molecular weights of 29,000, 43,000, and 45,000, with specificity for heparin at molecular weights of 13,000 and 16,000, and with specificities for mannose and fucose at molecular weights ranging from 62,000 to 70,000. For the spontaneous mammary adenocarcinoma the pattern was entirely different and more diverse, including species with the Ca2+ requirement. Extracts with the use of 0.2 M NaCl (salt) and 2% Triton X-100 (detergent) from teratoma contained at least nine different carbohydrate-binding proteins. The only similarities between the pattern of endogenous carbohydrate-binding proteins from teratoma and from mammary adenocarcinoma were beta-galactoside-binding proteins, one with a Ca2+ requirement and one without a Ca2+ requirement, and the heparin-binding proteins. These heparin-binding proteins were the only types of carbohydrate-binding proteins common to all three tumor types. The analysis indicates that certain bands represented newly identified proteins capable of binding to galactose-, mannose- or fucose-containing glycoconjugates, respectively. When assayed with rabbit erythrocytes, the different fractions showed agglutination activity. They can thus be termed "endogenous lectins." The use of endogenous lectin patterns as potential diagnostic markers in addition to the corresponding changes in the glycoconjugate composition is proposed.
Concurrent Surgery and Informed Consent
Authors: Alexander Langerman
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Sentinel Lymph Node Procedure in Squamous Cell Carcinoma of the Vulva
Authors: Blake Cady
Journal: Journal of Clinical Oncology (2000)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.15.2795 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10920125 Sentinel Lymph Node Procedure in Squamous Cell Carcinoma of the Vulva Blake Cady, MDxBlake CadySearch for articles by this author Show More Brown University School of Medicine, Women and Infants Hospital, Providence, RI https://doi.org/10.1200/JCO.2000.18.15.2795 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
A phase II study of cetuximab (Cetuximab) with cisplatin and capecitabine (Xeloda) as 1st line treatment in advanced gastric cancer
Authors: X. Zhang, J. Xu, L. Shen, J. Wang, J. Liang, N. Xu, Y. Bai, J. Wang
Journal: Journal of Clinical Oncology (2008)

15663 Background: The epidermal growth factor receptor (EGFR) commonly appears in 40–90% of gastric cancer, and preliminary data has shown the EGFR monoclonal antibody Cetuximab(C) might be an effective agent in advanced gastric cancer. The aim of this single arm, open, multicenter phase II study is to observe the efficacy and safety of Cetuximab combined with XP(cisplatin plus capecitabine) in advanced gastric cancer as the first line therapy. Methods: All patients with measurable disease had KPS≥60, normal bone marrow, hepatic and renal function. Patients received cisplatin(80mg/m2, triweekly), capecitabine(2000mg/m2,d1–14, triweekly),and Cetuximab weekly (initially at 400 mg/m2, then subsequent doses at 250 mg/m2). Tumor assessment by imaging was done every 6 weeks. Primary endpoint is response rate, and secondary endpoints are time to progression(TTP), overall survival(OS), safety, and the relationship of K-ras, b-raf, p53 gene mutation, EGFR gene copy number with tumor response. Using Simon's 2-stage design, the sample size was calculated to be 41cases. Results: 38 patients were enrolled from 04/07 to 12/07, including 2 screen failures, 2 withdraw for personal willing, 1 withdraw of adverse event, and 8 patients were too early to evaluate. Of the remaining 25 pts, there were 10 responses (40.0%), including 1CR and 9 PRs. There are additional 13 SD, so disease control rate is 92%. All secondary endpoints are not reached after a median follow-up of 13 weeks. Toxicities included Grade 3/4: neutropenia (14.2%),nausea/vomiting(11.1%) rash/desquamation (10.7%), fatigue (11.1%), diarrhea (6.3%), Hand-Foot syndrome(2.8%), abdominal pain (6%), infection with < Grade 2 ANC (2.8%%). Conclusions: Treatment with XP+C is well-tolerated and met the pre-specified criteria for objective response and disease Control. Further analysis of this study will allow more detailed assessment of this new therapy. No significant financial relationships to disclose.
What do you think is a non-disease?
Authors: S. Wessely
Journal: BMJ (2002)

Editor—The BMJ 's decision to extend participatory democracy to the question of disease is important not so much for the results but because it happened at all.1

To a previous generation the idea of asking consumers to decide on these matters would have been incomprehensible. Doctors decided which conditions were legitimate and which should be consigned to the outer darkness. In the debate about the nature of neurasthenia at the end of the 19th century all protagonists were in the medical profession and their debates were published in journals. The views of a few well educated and well heeled patients may be inferred from diaries and fiction, but their voices were largely unheard and unheeded.

Now of course medical authority is in retreat everywhere and the final arbiter of “non-disease” is fast becoming the patient.

All this is well and good, so why the outrage of so many respondents?1 I suspect it comes from a failure to recognise the different concepts of illness and disease.

Taking chronic fatigue syndrome as an example from the debate,1 few could now question that it is indeed an illness. It has a nosological status and is clearly associated with suffering, ill health, and disability. The patient's voice must be and is paramount. But is it a disease—that is, has a specific pathological process been identified to account for the above? Chronic fatigue syndrome is not yet a disease because no unambiguous evidence has yet been presented that has commanded widespread acceptance by the scientific community, which remains the arbiter.

Of course, the syndrome may plausibly make the transition from illness to disease like many other illnesses have done. Or it may not. The traffic is not entirely one way in which illness entities inevitably receive the stamp of scientific approval, usually after a period of being falsely labelled as psychological. Previously apparently sound entities have lost their disease status under the cold light of scientific scrutiny.

The concept of labelling also generated a lot of heat in this debate. People behave according to the labels that are ascribed to them, a process seen as largely negative. Some respondents rightly echo this, citing examples in which the act of labelling distress as something medical (pathological) carries with it a host of adverse consequences.1 w1-w8

But more commonly the act of giving a name to symptoms and disability brings relief.w9-15 The acknowledgement by the medical profession that a patient's condition has a name and is a legitimate illness is immensely reassuring and enabling. It also ends the battle of diagnosis—“If you have to prove you are ill you can't get well.”w16

Giving a condition a name is an intervention in itself with costs and benefits.w17 Crudely handled, medicalisation can perpetuate disability and exclusion. But used constructively and appropriately it is the first step towards recovery.
Outcomes for Older Patients in Stratus (MM-010), a Single-Arm, and Phase 3b Study of Pomalidomide + Low-Dose Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma
Authors: Antonio Palumbo, Meletios A. Dimopoulos, Katja Weisel, Michele Cavo, Enrique M. Ocio, Paolo Corradini, Michel Delforge, Albert Oriol, Hartmut Goldschmidt, Maria Jesus Blanchard, Concetta Conticello, Angelo Vacca, Markus Hansson, Ana Slaughter, Mathew Simcock, Jennifer Herring, Teresa Peluso, Lars Sternas, Mohamed H. Zaki, Philippe Moreau
Journal: Blood (2014)
Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial
Authors: Joel E Gallant, Eric S Daar, François Raffi, Cynthia Brinson, Peter Ruane, Edwin DeJesus, Margaret Johnson, Nathan Clumeck, Olayemi Osiyemi, Doug Ward, Javier Morales-Ramirez, Mingjin Yan, Michael E Abram, Andrew Plummer, Andrew K Cheng, Martin S Rhee
Journal: The Lancet HIV (2016)
Does the Country of Origin Matter in Health Care Innovation Diffusion?
Authors: Matthew Harris, Yasser Bhatti, Ara Darzi
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
Association of the AA genotype of the regulatory <i>BCL2</i> promoter polymorphism (-938C&gt;A) with 5-year survival in oropharynx carcinoma patients
Authors: W. Siffert, G. Lehnerdt, A. Bankfalvi, H. Nückel, S. Grehl, S. Lang, K. W. Schmid, H. S. Bachmann
Journal: Journal of Clinical Oncology (2008)

11051 Background: Expression of the anti-apoptotic and anti-proliferative protein Bcl-2 has been repeatedly shown to be associated with clinical outcome in head and neck cancer. Although results were partially conflicting, especially in the subgroup of squamous oropharyngeal carcinomas, Bcl-2 Expression was associated with better locoregional control and patients’ survival, respectively. We recently described a novel regulatory (-938C>A) single nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generating significantly different BCL2 promoter activities. Additionally, this SNP was associated with survival of patients with different malignancies, e.g. breast cancer and B-CLL. Methods: Paraffin-embedded neoplastic and non-neoplastic tissues from 133 patients with primary squamous oropharyngeal carcinoma were retrospectively investigated. Bcl-2 expression of tumor cells was demonstrated by immunohistochemistry; non-neoplastic tissues were used for genotyping. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients’ survival. Results: Kaplan-Meier curves revealed a significant association of the AA genotype with increased survival (p = 0.024) in oropharyngeal cancer patients. Five-year survival rates were 60.0% for the AA genotype, 47.7% for the AC, and 34.2% for the CC genotype. Multivariable Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for cancer related death in squamous oropharyngeal carcinoma patients (HR 1.99, p = 0.042). Immunohistochemical Bcl-2 expression was significantly associated with the clinical outcome. The (-938C>A) SNP was both significantly related with the immunohistochemically determined level of Bcl-2 expression and the survival of patients with Bcl-2 expressing carcinomas. Conclusions: These results suggest the (-938C>A) polymorphism to be a survival prognosticator as well as indicator of a high risk group for patients with squamous oropharyngeal carcinoma. No significant financial relationships to disclose.
Clonal Dynamics In Vivo of Virus Integration Sites of T Cells Expressing a Safety Switch
Authors: Edmund C Chang, Hao Liu, John A West, Xiaoou Zhou, Olga Dakhova, David A Wheeler, Helen E Heslop, Malcolm K Brenner, Gianpietro Dotti
Journal: Molecular Therapy (2015)

Safety switches are becoming relevant for the clinical translation of T-cell-based immunotherapies. In patients receiving an allogeneic hematopoietic stem cell transplant, the inducible caspase-9 gene (iC9) safety switch expressed by donor-derived T lymphocytes efficiently controls acute graft versus host disease (GvHD). However, in vivo elimination of iC9-T cells by the chemical inducer of dimerization (CID) that activates the iC9 protein is incomplete. To study this effect, we characterized the clonal diversity and dynamics of vector insertion sites (VIS) in iC9-T cells pre- and post-CID administration in four patients who developed GvHD. We identified 3,203 VIS among four patients and followed their in vivo clonal dynamics up to 161 days post-CID. VIS were categorized by their proximity to host genome elements, gene associations, and cis-modulatory relationship to mapped promoters. We found that VIS are preferentially located near open chromatin and promoter regions; furthermore, there was no evidence for selection bias among VIS surviving the CID treatment. The majority of iC9-T cells with high normalized VIS copy number at the time of GvHD onset were eliminated by CID, while iC9-T cells detectable post-CID generally have low normalized VIS copy number. We propose that suboptimal iC9 transgene expression is responsible for the incomplete elimination of iC9-T cells and illustrate here by simple model how cis-modulatory influences of local genome context and T-cell receptor activation status at time of CID treatment contribute to stochastic sparing of iC9-T cells.
18FDG-PET in the management of malignant peritoneal mesothelioma: A retrospective review of 145 scans in 37 patients
Authors: T. Uldrick, M. Hesdorffer, M. J. Rasiej, J. H. Austin, R. N. Taub
Journal: Journal of Clinical Oncology (2007)

20519 Background: Malignant peritoneal mesothelioma is a rare tumor best managed by an interdisciplinary approach. The role of 18 FDG-PET scans in monitoring patients with peritoneal mesothelioma has not been defined. Methods: Patients with peritoneal mesothelioma treated at Columbia University (October, 1997 - October, 2006) who had a PET scan were reviewed. Data were gathered on modes of therapy, imaging, and clinical outcome. The frequency with which PET scans led to a change in management, defined as scans that led to a biopsy or initiation of chemotherapy, was evaluated. Results: 37 patients, 21 women (57%) and 16 men (43%), were reviewed. The median age was 50 (range 14 - 79) years. All patients underwent surgery, 35 (95%) intraperitoneal chemotherapy, 15 (41%) external beam radiation, and 17 (46%) intravenous chemotherapy. At 43 (range 8.5 - 127) months median follow-up, 27 (73 %) are alive. Among 145 PET scans, 66 (46%) were PET/CT scans, 52 (26%) were PET scans with a CT scan performed within one month, and 27 (19%) were PET scans only. 8 (6%) of PET scans were for initial staging, and 137 (95%) for monitoring. A change in management based on findings in PET imaging occurred in 11 (30%) patients and 14 (10%) scans. Two patients were started on salvage chemotherapy without further evaluation. Two were diagnosed with peritoneal recurrence, 1 with lung metastasis, 1 with lymph node metastasis, 1 with a second malignancy, and 3 with colon polyps. One had a false positive scan, proven by negative surgical biopsy. PET provided early detection of disease progression in 6 (16%) of patients evaluated. One patient (3%) had biopsy proven progressive disease despite no 18 FDG uptake on PET scan. Conclusions: 18 FDG-PET findings changed management in 30% of patients with peritoneal mesothelioma undergoing multimodality therapy, and provided early detection of recurrence in 16% of patients. Further evaluation of test characteristics and prognostic value of 18 FDG-PET in the setting of peritoneal mesothelioma is warranted. No significant financial relationships to disclose.
PWE-223 Investigating biofilm formation in the lumen of sterile nasogastric tubes
Authors: M Baker Moffatt, S Wilks, S Green
Journal: Gut (2015)

<h3>Introduction</h3> Fine bore nasogastric tube (NGT) blockages can result in delays in nutrient provision and poor patient experience. Biofilm development on the internal lumen wall of the tube has the potential to initiate such blockages, but has been little investigated. <h3>Method</h3> The study aimed to investigate the rate of biofilm formation in sterile NGTs <i><i>in vitro</i></i>. Short sections of new sterile NGTs were placed in a 6-well microtiter plate and immersed in a standard commercial enteral feed to which an inoculum was added. This was incubated at 37°C. The inocula used in the study were prepared from strains of<i>Escherichia coli</i>and <i>Pseudomonas aeruginosa.</i>The NGT sections were removed after 0, 15, 30, 60, 120, 240 and 1440 min. Culturable cells were quantified by colony forming units (CFU), and bacterial viability was measured by cell elongation (CE). In addition, the sections were examined directly using episcopic differential interference contrast (EDIC) microscopy. <h3>Results</h3> Results from 3 sections at each time point from 11 NGTs for the <i>E. coli</i>inoculum and 3 NGTs for the <i>P. aeruginosa</i>inoculum are presented. Mean CE and CFU counts for both the <i>E. coli</i>and <i>P. aeruginosa</i>inocula increase from 0 to 1440 min. This demonstrates bacteria attach to the NGT within 15 min of introduction, with generally increasing colonisation over the subsequent time measured, and retain viability. EDIC microscopy was successfully used to directly examine the NGT surface, showing evidence of extensive biofilm formation. <h3>Conclusion</h3> The study has demonstrated the development of bacterial biofilms (evidenced by CE, CFU and microscopy) on NGT lumen walls over a 24 h period in the laboratory setting. The presence of biofilms may have the potential to interrupt flow through the lumen and contribute to blockage development. Further studies plan to examine the effect of flushing with water on biofilm development, in particular considering the use of sterile and tap water flushes, and to investigate biofilm presence in used NGTs retrieved from adult patients in the course of their normal clinical care. <h3>Disclosure of interest</h3> None Declared.