tbuckley/cabot-search huggingface dataset:
Phase I dose escalation, toxicity and dynamic contrast-enhanced (DCE) MRI imaging biomarker study of first line treatment with imatinib (I) and cisplatin (C) plus docetaxel (D) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: G. Vlahovic, T. L. Foster, C. H. Andrews, J. E. Herndon, T. Sporn, M. J. Kelley, M. W. Dewhirst, Z. Vujaskovic
Journal: Journal of Clinical Oncology (2007)

18056 Background: Imatinib (I) inhibits activated PDGF-Rβ and down-regulates VEGF resulting in decreased angiogenesis and improved blood flow favoring enhanced tumor drug delivery in lung cancer xenoagrafts. Objectives: 1) determine the MTD for the combination of I and C plus D in NSCLC pts, 2) describe non-dose limiting toxicities (non-DLT), 3) evaluate for feasibility and changes in blood flow/permeability measurement by DCE-MRI after treatment with I, and 4) explore the relationship between measured DCE-MRI parameters and proangiogenic plasma tumor markers PDGF-BB, VEGF, PAI1, ANG2, OPN, and MMP1. Methods: Eligibility: NSCLC with tumor expression of p-PDGF-Rβ. DCE-MRI was performed before and after 7 daily doses of I alone (lead-in) followed by C plus D on day 1, every 3 weeks. Once daily I was given with each C plus D cycle, on days -5 to +2. Standardized hemodynamic parameters (Ktrans, Ve, Kep) were acquired from DCE-MRI. Enrolled patients’ plasma was analyzed by ELISA to determine plasma tumor markers’ level. Results: 14 enrolled pts (9 M, 5 F) were evaluable for toxicity and 13 for response. Six pts were treated at dose level 1 (C+D 60/60 mg/m 2 , and I 300 mg); one DLT (febrile neutropenia) was seen; there were no DLTs in cohort 2 (60/60 mg/m 2 and I 400 mg; n=3), and two DLTs were observed in cohort 3 (70/70 mg/m 2 and I 400 mg; n=5) - febrile neutropenia and grade 4 diarrhea. For all cohorts, grade 3 and 4 toxicities were: fatigue (7%), nausea (14%), neutropenia (14%), elevated creatinine (7%), and dispnea (7%). Two pts (15%) had partial response, and 6/13 pts had stable disease as their best response. DCE-MRI demonstrated trend in decrease of Ve after 7-day treatment with I (p=0.088). Exploratory analysis revealed a significant correlation of: both ANG2 and OPN with Ve (p=0.02 and 0.05 respectively), MMP1 with Kep (p=0.03), and VEGF with Ktrans (p=0.02). Conclusions: MTD for I and C plus D in chemo naïve NSCLC pts is 400 mg and 60/60 mg/m 2 , respectively. More, DCE-MRI is feasible in NSCLC pts. Phase II study is open and currently enrolling with continues exploration of DCE-MRI as a predictive imaging biomarker, collectively with tumor proangiogenic markers. No significant financial relationships to disclose.
Abstract 75: Insulin Modulates Cardioprotective Akt Signaling During Ischemia/Reperfusion Attenuating PHLPP-1 Phosphatase
Authors: Yuan Xing, Feng Gao, Heng Ma
Journal: Circulation Research (2012)

Introduction The recently discovered phosphatase PHLPP-1 directly dephosphorylates and inactivates Akt. Whether the suppression of Akt by PHLPP-1 may lead to myocardial ischemia intolerance in aged heart, has never been previously studied. Moreover, we unveiled that the cardioprotective effects of insulin in limiting ischemia/reperfusion(I/R) injury were Akt activation dependent. However,the role of insulin,regulating the endogenous negative regulator of Akt activity, remains largely unknown. In this study, an important role for insulin in intensifying Akt activity through attenuating PHLPP-1 and ameliorating myocardial injury following I/R in the senescent heart has been described. Methods and Results Young (3 M) and aged (20 M) rats were subjected to I (20 min) / R (4 h) in vivo . Insulin treatment during reperfusion significantly increased Akt phosphorylation(2.32 times) response to I/R and decreased the infarct size by 18±3%. Simultaneously, insulin treatment significantly suppressed the PHLPP-1 level by 65±5%. Insulin-induced Akt activation was impaired and the myocardial infarct was larger in I/R aged hearts compared with the young ones. The effect of Insulin attenuating PHLPP-1 to intensify Akt activity was impaired in aged ischemic hearts as compared to young ischemic hearts. In cultured rat ventricular myocytes, the inhibitory effects of insulin on cardiac PHLPP-1 were abolished by the proteasome inhibitor MG132. PHLPP-1 knockdown by small interfering RNA significantly enhances insulin-induced Akt phosphorylation and reduced simulated hypoxia/reoxygenation induced apoptosis. Moreover, swimming training (6 w) incresed insulin sensitivity in the senescent heart. The inhibitory effect of insulin on cardiac PHLPP-1 was partially reversed accompanying enhanced Akt phosphorylation. The tolerance of the aged heart to ischemic damage is also enhanced. Conclusions We conclude that PHLPP-1 may contribute to the aging-associated ischemic intolerance. Insulin acts as a crucial cardioprotective regulator by inhibiting physiological function of PHLPP-1 and thus enchancing Akt activity. For the first time,our results also indicated a new cardioprotective mechanism of insulin modulating ubiquitin-proteasome pathway of PHLPP-1.
Recombinant adenoviral human p53 gene intracavity infusion in treatment of malignant pleural effusions and peritoneal effusions.
Authors: Yi Hu
Journal: Journal of Clinical Oncology (2012)

e13521 Background: Malignant pleural or peritoneal effusion adversely affects patients' quality of life. Once the effusions formed it is difficult to control. This report showed intra-cavity infusion of recombinant adenoviral human p53 gene (rAd-p53) was very effective for controlling malignant pleural or peritoneal effusion. Methods: Twenty-seven patients, 15 males and 12 females with a median age of 59 years old , were included this study. The malignant pleural effusions, consisting of 13 patients, were caused by primary lung cancers (12 cases) and breast cancer (1 case), and 14 cases of peritoneal effusions were caused by gastric cancer (5 cases), ovarian cancers (3 cases), primary live cancer (2 cases), pancreatic cancer (2 cases), esophageal cancer (1 case) and bile duct cancer (1 case). The rAd-p53 intra-cavity infusion was given after removing most of fluids. For intra-chest cavity infusion 2×10 12 viral particles (VP) of rAd-p53 diluted into 200 ml of saline solution, and for intra-abdominal cavity infusion 4×10 12 VP of rAd-p53 diluted into 500 ml of saline solution, were given weekly for 3 weeks. Results: A total of 3 cases, 2 with pleural effusion and 1 with peritoneal effusion achieved a complete response (CR), and 10 cases (7 pleural effusions and 3 peritoneal effusions) had a partial response (PR). The overall response rate is 48.1%. The CR was defined as the complete disappearance of pleural or peritoneal fluid and negative cytologic findings for &gt;4 weeks, and the PR is defined as a decrease over 50% of the fluid without the need of drainage and negative cytologic findings for &gt;4 weeks. The fluids in 8 cases with peritoneal effusions decreased by over 30% but less than 50%. The associated symptoms relieved in 23 patients (85.2%). There were no serious side effects observed except for self-limited fever found in all the cases. Conclusions: For some patients with malignant pleural or peritoneal effusions, Intra-cavity infusion of rAd-p53 is effective and safe controlling treatment.
Implementation of multidisciplinary care reduces maternal mortality in women with sickle cell disease living in low‐resource setting
Authors: Eugenia Vicky Asare, Edeghonghon Olayemi, Theodore Boafor, Yvonne Dei‐Adomakoh, Enoch Mensah, Harriet Ghansah, Yvonne Osei‐Bonsu, Selina Crabbe, Latif Musah, Charles Hayfron‐Benjamin, Brittany Covert, Adetola A. Kassim, Andra James, Mark Rodeghier, Michael R. DeBaun, Samuel A. Oppong
Journal: American Journal of Hematology (2017)

Sickle cell disease (SCD) is associated with adverse pregnancy outcome. In women with SCD living in low-resource settings, pregnancy is associated with significantly increased maternal and perinatal mortality rates. We tested the hypothesis that implementing a multidisciplinary obstetric and hematology care team in a low-resource setting would significantly reduce maternal and perinatal mortality rates. We conducted a before-and-after study, at the Korle-Bu Teaching Hospital in Accra, Ghana, to evaluate the effect of a multidisciplinary obstetric-hematology care team for women with SCD in a combined SCD-Obstetric Clinic. The pre-intervention period was assessed through a retrospective chart review to identify every death and the post-intervention period was assessed prospectively. Interventions consisted of joint obstetrician and hematologist outpatient and acute inpatient reviews, close maternal and fetal surveillance, and simple protocols for management of acute chest syndrome and acute pain episodes. Primary outcomes included maternal and perinatal mortality rates before and after the study period. A total of 158 and 90 pregnant women with SCD were evaluated in the pre- and post- intervention periods, respectively. The maternal mortality rate decreased from 10 791 per 100 000 live births at pre-intervention to 1176 per 100 000 at post-intervention, representing a risk reduction of 89.1% (P = 0.007). Perinatal mortality decreased from 60.8 per 1000 total births at pre-intervention to 23.0 per 1000 at post-intervention, representing a risk reduction of 62.2% (P = 0.20). A multidisciplinary obstetric and hematology team approach can dramatically reduce maternal and perinatal mortality in a low-resource setting.
Case 15-2017 — A 27-Year-Old Woman with Anemia, Thrombocytosis, and Skin Lesions after Travel Abroad
Authors: Michael K. Mansour, Alyssa R. Letourneau, Zachary S. Wallace, Florian J. Fintelmann, Ruth K. Foreman
Journal: New England Journal of Medicine (2017)

A 27-year-old woman presented with skin lesions that had developed after international travel. Biopsy of a skin lesion revealed granulomatous dermatitis. Fatigue, weakness, and pulselessness developed in the left arm. A diagnosis was made.
Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part IX. Ensuring effectiveness of communitywide emergency cardiac care
Journal: JAMA (1992)

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
CONTACT DEEMATITIS XVIII.
Authors: D.S. Wilkinson
Journal: British Journal of Dermatology (1972)

Journal Article CONTACT DEEMATITIS XVIII: Ancillary Aids in Elucidation of Causes of Contact Dermatitis Get access D.S. Wilkinson D.S. Wilkinson General Hospital High Wycombe Buckinghamshire Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 86, Issue 4, 1 April 1972, Page 445, https://doi.org/10.1111/j.1365-2133.1972.tb05067.x Published: 01 April 1972
Aptamer-mediated gene therapy enhanced antitumor activity against human hepatocellular carcinoma in vitro and in vivo
Authors: Shuangli Xiao, Zhongbing Liu, Ruolan Deng, Chunhong Li, Shaozhi Fu, Guilan Chen, Xiaoqin Zhang, Famin Ke, Siyun Ke, Xin Yu, Shurong Wang, Zhirong Zhong
Journal: Journal of Controlled Release (2017)
Easi-CRISPR: a robust method for one-step generation of mice carrying conditional and insertion alleles using long ssDNA donors and CRISPR ribonucleoproteins
Authors: Rolen M. Quadros, Hiromi Miura, Donald W. Harms, Hisako Akatsuka, Takehito Sato, Tomomi Aida, Ronald Redder, Guy P. Richardson, Yutaka Inagaki, Daisuke Sakai, Shannon M. Buckley, Parthasarathy Seshacharyulu, Surinder K. Batra, Mark A. Behlke, Sarah A. Zeiner, Ashley M. Jacobi, Yayoi Izu, Wallace B. Thoreson, Lisa D. Urness, Suzanne L. Mansour, Masato Ohtsuka, Channabasavaiah B. Gurumurthy
Journal: Genome biology (2017)

Conditional knockout mice and transgenic mice expressing recombinases, reporters, and inducible transcriptional activators are key for many genetic studies and comprise over 90% of mouse models created. Conditional knockout mice are generated using labor-intensive methods of homologous recombination in embryonic stem cells and are available for only ~25% of all mouse genes. Transgenic mice generated by random genomic insertion approaches pose problems of unreliable expression, and thus there is a need for targeted-insertion models. Although CRISPR-based strategies were reported to create conditional and targeted-insertion alleles via one-step delivery of targeting components directly to zygotes, these strategies are quite inefficient.
Immunologic Release of Chemical Mediators from Human Nasal Polyps
Authors: Michael Kaliner, Stephen I. Wasserman, K. Frank Austen
Journal: New England Journal of Medicine (1973)

Human nasal polyps from three ragweed-sensitive atopic patients released three chemical mediators: histamine, slow reacting substance of anaphylaxis, and eosinophil chemotactic factor of anaphylaxis on challenge with ragweed antigen. Polyps from four non-ragweed-sensitive subjects passively sensitized in vitro released the same chemical mediators. In a patient with chronic sinusitis and one with cystic fibrosis, dibutyryl cyclic adenosine 3′,5′-monophosphate and the beta adrenergic agent isoproterenol both produced dose-dependent suppression of the immunologic release of mediators. Cholera toxin after a 30-minute lag period induced a marked increase in the tissue concentrations of cyclic adenosine monophosphate in a patient with chronic sinusitis and at the same time suppressed the immunologic release of mediators; each of these effects persisted through three hours of incubation. Alpha-adrenergic stimulation as achieved by combining phenylephrine with propranolol and cholinergic stimulation with carbachol enhanced the antigen-induced release of histamine and slow reacting substance in two patients with chronic sinusitis. Thus, the antigen-activated release of mediators from nasal polyps is modulated by agents affecting the intracellular concentrations of cyclic nucleotides. (N Engl J Med 289:277–281, 1973)
A phase II biomarker trial of everolimus in patients with advanced renal cell carcinoma (08-313).
Authors: Anasuya Gunturi, Jonathan Chipman, Toni K. Choueiri, Deborah Ann Bradley, Michael B. Atkins, James Walter Mier, Sabina Signoretti, David F. McDermott, Rupal Satish Bhatt
Journal: Journal of Clinical Oncology (2014)

e15565 Background: Mammalian target of rapamycin inhibitors (mTORi) are currently FDA approved in the second-line for treatment of advanced RCC. Concurrent with the development of these therapies h...
Lamotrigine for Generalized Seizures Associated with the Lennox–Gastaut Syndrome
Authors: Jacques Motte, Edwin Trevathan, Jan F.V. Arvidsson, Manuel Nieto Barrera, E. Lynette Mullens, Penelope Manasco
Journal: New England Journal of Medicine (1997)

The Lennox–Gastaut syndrome, a severe form of epilepsy that usually begins in early childhood, is difficult to treat. Dose-related drug toxicity is common.
Hypophysectomy in Breast Cancer
Authors: R. D. Bulbrook, F. C. Greenwood, G. J. Hadfield, E. F. Scowen
Journal: BMJ (1958)

IBRmOL 15Conversely, progression of the disease might take place in spite of the fact that no oestrogen could be detected in the urine.In general, continued oestrogen excretion was found more often in cases in relapse than in remis- sion.We are grateful to the surgical staff and the staft of the radio- therapy department of St. Bartholomew's Hospital for allowing us to investigate patients under their care, and partdcularly to Professor Sir James Paterson Ross, who has also been most help- ful with his advice and criticism.
Call for GP training to be extended to four years
Authors: Gareth Iacobucci
Journal: BMJ (2017)

All general practice training schemes starting within the next 12 months should be at least four years in length and include a minimum of 24 months spent within general practice to help tackle the workforce crisis, local GP leaders have said.

A motion passed at the annual conference of local medical committees (LMCs) also called for all foundation programmes starting in the next year to include a dedicated general practice …
Urging Europe to put non-adherence to inhaled respiratory medication higher on the policy agenda: a report from the First European Congress on Adherence to Therapy
Authors: Job F.M. van Boven, Federico Lavorini, P.N. Richard Dekhuijzen, Francesco Blasi, David B. Price, Giovanni Viegi
Journal: European Respiratory Journal (2017)

"Drugs don't work in patients that don't take them" are the by now almost legendary words of former US Surgeon General C. Everett Koop. Arguably worse than "just not working", for the European Union (EU), it has been estimated that non-adherence to medication is associated with almost 200 000 deaths and an excess cost of EUR80–125 billion [1]. Realising that 1) non-adherence affects about 50% of chronic medication users [2], of which the large majority elderly, and 2) tackling non-adherence requires a joint effort, the Senior International Health Association took the initiative to bring together seniors, clinical and adherence experts, and European Parliament members. On November 18 and 19, 2016, all these key stakeholders met at the First European Congress on Adherence to Therapy in Rimini, Italy, passionately chaired by Giovanni La Via, President of the Environment, Public Health and Food Safety Committee of the European Parliament. Notably, there were representatives from several major European scientific societies, i.e. those of pulmonology (ERS), atherosclerosis (EAS), urology (EAU), heart rhythm (EHRA), psychiatry (EPA), cardiology (ESC) and hypertension (ESH). The overall goal of the congress was to identify unmet needs in adherence research, funding and policy by specifying the roles of patients, healthcare providers, societies, funding bodies and governments. In this report, we present the main conclusions and recommendations following the congress, in particular those of interest for healthcare policy regarding inhaled medication non-adherence in patients with obstructive airway diseases ( i.e. asthma and/or chronic obstructive pulmonary disease (COPD)). Huge impact, but little attention: time to put respiratory non-adherence higher on Europe's policy agenda! <http://ow.ly/vVDj309Yblz> The authors thank Stefano Nardini (Pulmonary and TB Unit, Vittorio Veneto General Hospital, Vittorio Veneto, Italy) for moderating the respiratory session and all discussants for their input. A full report from the First European Congress on Adherence to Therapy is available ([www.seniorinternationalhealthassociation.org/events/european-congress-on-adherence-to-therapy/][1]). The views and opinions expressed here are those of the authors only. [1]: http://www.seniorinternationalhealthassociation.org/events/european-congress-on-adherence-to-therapy/
Gene Expression Profiling of Large Cell Lung Cancer Links Transcriptional Phenotypes to the New Histological WHO 2015 Classification
Authors: Anna Karlsson, Hans Brunnström, Patrick Micke, Srinivas Veerla, Johanna Mattsson, Linnea La Fleur, Johan Botling, Mats Jönsson, Christel Reuterswärd, Maria Planck, Johan Staaf
Journal: Journal of Thoracic Oncology (2017)

Large cell lung cancer (LCLC) and large cell neuroendocrine carcinoma (LCNEC) constitute a small proportion of NSCLC. The WHO 2015 classification guidelines changed the definition of the debated histological subtype LCLC to be based on immunomarkers for adenocarcinoma and squamous cancer. We sought to determine whether these new guidelines also translate into the transcriptional landscape of lung cancer, and LCLC specifically.Gene expression profiling was performed by using Illumina V4 HT12 microarrays (Illumina, San Diego, CA) on samples from 159 cases (comprising all histological subtypes, including 10 classified as LCLC WHO 2015 and 14 classified as LCNEC according to the WHO 2015 guidelines), with complimentary mutational and immunohistochemical data. Derived transcriptional phenotypes were validated in 199 independent tumors, including six WHO 2015 LCLCs and five LCNECs.Unsupervised analysis of gene expression data identified a phenotype comprising 90% of WHO 2015 LCLC tumors, with characteristics of poorly differentiated proliferative cancer, a 90% tumor protein p53 gene (TP53) mutation rate, and lack of well-known NSCLC oncogene driver alterations. Validation in independent data confirmed aggregation of WHO 2015 LCLCs in the specific phenotype. For LCNEC tumors, the unsupervised gene expression analysis suggested two different transcriptional patterns corresponding to a proposed genetic division of LCNEC tumors into SCLC-like and NSCLC-like cancer on the basis of TP53 and retinoblastoma 1 gene (RB1) alteration patterns.Refined classification of LCLC has implications for diagnosis, prognostics, and therapy decisions. Our molecular analyses support the WHO 2015 classification of LCLC and LCNEC tumors, which herein follow different tumorigenic paths and can accordingly be stratified into different transcriptional subgroups, thus linking diagnostic immunohistochemical staining-driven classification with the transcriptional landscape of lung cancer.
Taxane‐Grafted Metal‐Oxide Nanoparticles as a New Theranostic Tool against Cancer: The Promising Example of Docetaxel‐Functionalized Titanate Nanotubes on Prostate Tumors
Authors: Alexis Loiseau, Julien Boudon, Céline Mirjolet, Gilles Créhange, Nadine Millot
Journal: Advanced Healthcare Materials (2017)

The combination of anticancer drugs and metal oxide nanoparticles is of great interest in cancer nanomedicine. Here, the development of a new nanohybrid, titanate nanotube-docetaxel (TiONts-DTX) is reported, the two parts of which are conjugated by covalent linkages. Unlike most nanoparticles currently being developed for biomedical purposes, TiONts present a needle-shaped morphology. The surface of TiONts is linked with 3-aminopropyl triethoxysilane and with a hetero-bifunctional polymer (polyethylene glycol) to create well-dispersed and biocompatible nanovectors. The prefunctionalized surface of this scaffold has valuable attachments to graft therapeutic agents (DTX in our case) as well as chelating agents (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) to monitor the nanohybrids. To evaluate drug efficacy, in vitro tests have demonstrated that the association between TiONts and DTX shows cytotoxic activity against a hormone-refractory prostate cancer cell line (22Rv1) whereas TiONts without DTX do not. Finally, the first in vivo tests with intratumoral injections show that more than 70% of TiONts nanovectors are retained within the tumor for at least 7 d. Moreover, tumor growth in mice receiving TiONts-DTX is significantly slower than that in mice receiving free DTX. This nanohybrid can thus become a promising new tool in biomedicine to fight against prostate cancer.
The novel point shear-wave elastography method ElastPQ ® is accurate for non-invasive evaluation of liver fibrosis and portal hypertension
Authors: T. Bucsics, B. Grasl, P. Schwabl, M. Mandorfer, J. Dmitrieva, M. Peck-Radosavljevic, M. Trauner, W. Sieghart, A. Ferlitsch, T. Reiberger
Journal: Journal of Hepatology (2017)