tbuckley/cabot-search huggingface dataset:
A phase 1b study of the anti-cancer stem cell agent demcizumab (DEM), pemetrexed (PEM) &amp; carboplatin (CARBO) in patients (pts)with 1<sup>st</sup> line non-squamous NSCLC.
Authors: Mark James McKeage, Brett Gordon Maxwell Hughes, Ben Markman, Manuel Hidalgo, Michael Millward, Michael B. Jameson, Dean Laurence Harris, Robert J. Stagg, Ann M. Kapoun, Eric Holmgren, Jakob Dupont, Dusan Kotasek
Journal: Journal of Clinical Oncology (2016)

9023 Background: DEM is a humanized IgG2 anti-DLL4 antibody that inhibits tumor growth, decreases CSC frequency & produces an antiangiogenic effect in human tumor xenograft models by inhibiting the Notch ligand Delta like ligand 4 (DLL4). In addition, inhibition of DLL4 may produce an immunomodulatory effect by reducing the myeloid derived suppressor cells within the tumor. This was a phase 1b study of DEM, PEM & CARBO in pts with 1st line non-squamous NSCLC. Methods: Pts received DEM (2.5 or 5 mg/kg), PEM 500 mg/m2 & CARBO (AUC = 6) induction every 3 wks X 6 cycles followed by maintenance DEM (cohorts 1-4) or truncated DEM (5 or 7.5 mg/kg), PEM 500 mg/m2 & CARBO (AUC = 6) induction every 3 wks X 4 cycles followed by maintenance PEM (cohorts 5 & 6). The objectives were to determine the MTD, safety, efficacy, immunogenicity, pharmacokinetics & biomarkers. Results: Forty-six pts were enrolled; 6 received continuous 2.5 mg/kg, 17 received continuous 5 mg/kg, 6 received 7.5 mg/kg of truncated DEM & 17 received 5 mg/kg of truncated DEM. Related AEs in > 25% of pts were: fatigue (48%), nausea (46%), hypertension (44%) and vomiting (28%). Increased BNP values are an early indicator of the cardiac effects of DEM & mildly elevated values were used to start treatment with a cardioprotective ACE inhibitor or carvedilol. Two pts receiving continuous DEM dosing 5 mg/kg developed reversible related Grade 3 pulmonary hypertension & heart failure on days 167 & 183, respectively. As a result, DEM treatment was limited to 63 days in cohorts 5, 6 & 7. The overall response and disease control rates were 50% and 88%, respectively. The Kaplan Meier estimated median PFS and survival for the truncated demcizumab pts were 5.8 months & 11.6 months, respectively. Eight of 23 (35%) of the truncated demcizumab pts are alive between 12 & 34 months. Conclusions: The truncated DEM regimen was generally well tolerated with fatigue, nausea & hypertension being the most common drug related toxicities. Encouraging activity has been observed. The optimal DEM dose was determined to be a truncated course of 5 mg/kg once every 3 weeks. This regimen is being used in an ongoing randomized Phase 2 study. Final data will be presented. Clinical trial information: NCT01189968.
Gene expression of glucokinase regulatory protein in regenerating rat liver
Authors: J Rosa
Journal: Hepatology (1997)

The activity and messenger RNA (mRNA) levels of glucokinase, and the concentration and mRNA levels of its regulatory protein, were analyzed during liver regeneration. The activity of glucokinase and the concentration of its regulatory protein decreased to 30% and 50%, respectively, after liver resection, remaining low after 1 week. No significant variations in the level of these proteins were found in sham-operated animals. The regulatory protein/glucokinase molar ratio increased during the replicative phase, to a maximum at 48 hours. The mRNA levels of glucokinase and of its regulatory protein decreased rapidly after partial hepatectomy to minimum values at 6 hours (15%) and at 12 hours (4%), respectively, returning to normal values at 24 hours and 168 hours, respectively. Sham-operated animals showed a similar decrease in mRNA levels during the prereplicative phase of liver regeneration, suggesting that the initial effects observed in the gene expression of these proteins were due to surgical stress. During the replicative phase, a specific inhibition of the regulatory protein's gene expression was observed in the regenerating liver. A decrease in the content of regulatory protein and the glucokinase activity, and an increase in the molar ratio of these two proteins correlate with the observed decrease in glycolytic flux, providing further evidence that the phosphorylation of glucose is a control point in the glycolytic/gluconeogenic flux during liver regeneration.
Gemcitabine Combined With Oxaliplatin in Advanced Pancreatic Adenocarcinoma: Final Results of a GERCOR Multicenter Phase II Study
Authors: C. Louvet, T. André, G. Lledo, P. Hammel, H. Bleiberg, C. Bouleuc, E. Gamelin, M. Flesch, E. Cvitkovic, A. de Gramont
Journal: Journal of Clinical Oncology (2002)

Based on preclinical in vitro synergy data, this study evaluated the activity and toxicity of a gemcitabine/oxaliplatin combination in patients with metastatic and locally advanced pancreatic adenocarcinoma.Previously untreated metastatic and locally advanced unresectable pancreatic adenocarcinoma patients were enrolled onto this multicenter phase II study. Patients received gemcitabine 1,000 mg/m(2) as a 10-mg/m(2)/min infusion on day 1 and oxaliplatin 100 mg/m(2) as a 2-hour infusion on day 2 every 2 weeks. Patients with metastatic disease were treated until evidence of progressive disease, whereas patients with locally advanced disease received six cycles in the absence of progression, followed when appropriate by concomitant radiochemotherapy.Among 64 eligible patients included in eight centers, 30 had locally advanced and 34 had metastatic disease. Response rate for the 62 patients with measurable disease was 30.6% (95% confidence interval, 19.7% to 42.3%), 31.0% for locally advanced and 30.3% for metastatic patients. Among 58 assessable patients, 40% had clinical benefit. Median progression-free survival and median overall survival (OS) were 5.3 and 9.2 months, respectively, with 36% of patients alive at 1 year. Median OS for patients with metastatic disease and locally advanced disease were 8.7 and 11.5 months, respectively. With 574 treatment cycles (median per patient, nine; range, zero to 27), grade 3/4 toxicity per patient was 11% for neutropenia and thrombocytopenia, 14% for nausea or vomiting, 6.2% for diarrhea, and 11% for peripheral neuropathy, with no toxic deaths.Palliative effects, response rate, and survival observed with this well-tolerated gemcitabine/oxaliplatin combination deserve additional evaluation. A comparative study of combination therapy versus gemcitabine alone is ongoing.
The clinical safety of H<sub>1</sub>-receptor antagonists: An EAACI position paper
Authors: G. Passalacqua, J. Bousquet, C. Bachert, M. K. Church, C. Bindslev-Jensen, L. Nagy, P. Szemere, R. J. Davies, S. R. Durham, F. Horak, K. Kontou-Fili, H.-J. Malling, P. Cauwenberge, G. W. Canonica
Journal: Allergy (1996)
Correction
Journal: Circulation (1968)

On page 985 (vol. 36, 1967) of the "Recommendations for Human Blood Pressure Determinations by Sphygmomanometers" it is stated "To measure blood pressure by the flush method, a suitable cuff is placed on the forearm or calf...." This is in error and should read "To measure blood pressure by the flush method, a suitable cuff is placed on the wrist or ankle...."
Abstract 3812: Overcoming de novo and acquired modes of cetuximab resistance by broad-spectrum receptor tyrosine kinase inhibitors
Authors: Bhuminder Singh, Ramona Graves-Deal, Galina Bogatcheva, Robert J. Coffey
Journal: Cancer Research (2019)

Abstract MEK inhibition has been shown to delay emergence of cetuximab resistance in colorectal cancer (CRC) (Nat Commun 22;6:8305, 2015). By exploiting a novel 3D culture system, we herein show that three broad-spectrum tyrosine kinase inhibitors overcome de novo and acquired resistance to cetuximab. By culturing a CRC cell line, HCA-7 in 3D in type I collagen, we previously identified two novel modes of cetuximab resistance. In 3D culture, HCA-7-derived CC are sensitive to cetuximab, while SC exhibit de novo cetuximab resistance (PNAS 114:E2852-E2861, 2017). Continuous exposure of CC to cetuximab resulted in colonies that acquired resistance to cetuximab, designated CC-CR, which was dependent in part on increased levels of lncRNA MIR100HG that leads to increased WNT signaling (Nat Med 23:1331-1341, 2017). We previously showed increased MET and RON tyrosine phosphorylation in SC cells and that MET/RON inhibitor, crizotinib overcomes SC cetuximab resistance. We now show that crizotinib also overcomes acquired cetuximab resistance in CC-CR. A phospho-RTK array showed increased phosphorylation of several RTKs, including MET and RON, in SC and CC-CR cells compared to cetuximab-sensitive CC counterparts. Furthermore, other multi-RTK inhibitors cabozantinib and BMS-777607 helped overcome cetuximab resistance, as measured by 3D colony growth and activation state of key signaling molecules. Conversely, addition of RTK ligands HGF and NRG1 induced cetuximab resistance in CC cells, which could be blocked by addition of crizotinib and this was associated with disorganized spindle positioning during cell division, leading to multi-layering of CC cultures. By FACS analysis, we observed increased cell cycle arrest in G1 phase in SC and CC-CR cultures treated with cetuximab and crizotinib. Furthermore, we show that crizotinib overcomes cetuximab resistance in vivo in SC nude mice xenografts. Finally, in a direct comparison between vertical suppression (EGFR/MEK inhibition) and parallel inhibition (EGFR/multi-RTK inhibition), we observed a higher degree of synergy with the latter strategy. The non-overlapping toxicities of cetuximab and crizotinib warrants consideration for its clinical deployment. Note: This abstract was not presented at the meeting. Citation Format: Bhuminder Singh, Ramona Graves-Deal, Galina Bogatcheva, Robert J. Coffey. Overcoming de novo and acquired modes of cetuximab resistance by broad-spectrum receptor tyrosine kinase inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3812.
Mercuric Cataphoresis.
Authors: G. Betton Massey
Journal: JAMA (1903)

Philadelphia, Nov. 25, 1903. <h3>To the Editor:</h3> —I wish to correct a mistake which I allowed to remain when correcting the report of my remarks on the papers of Drs. Dunning and Bovée. This discussion appeared inThe Journal, November 14, page 1194. I was reported as speaking of a method of diffusion of mercury through the "abdominal wall" for chronic inflammation of the uterine appendages. It should have been "vaginal wall." The method referred to is described in a paper inThe Journal, Aug. 30, 1902, and I will be glad to send reprints to those who wish them.
Childhood Poisoning
Authors: Regine Aronow
Journal: JAMA (1972)

Accidental ingestion of methadone hydrochloride by 18 children less than seven years of age occurred during a nine-month period. In each situation, someone in the environment was taking methadone for heroin addiction. Although the lethal dose for children has not been established, even a small amount may threaten life and result in a varying clinical course for 48 hours. Therapy to maintain adequate respiration should include nalorphine hydrochloride and precise supportive care.
Successful liver transplantation in older patients raises new hopes, challenges, ethics questions
Authors: T. Randall
Journal: JAMA (1990)

BEING in one's 60s or even 70s is no longer reason enough to be denied orthotopic liver transplantation, two new studies suggest. The latest findings indicate that patients in their seventh or eighth decades of life do as well as younger adults. Moreover, similar success has been recorded with elderly kidney recipients in the last several years (<i>Transplantation</i>. 1989;47:259 and 1989;48:689,<i>Am J Kidney Dis</i>. 1988;12:516,<i>Transplant Proc</i>. 1989;21:2018, 2020, 2024). While donor organ shortages unfortunately persist, the positive results recorded for older recipients of livers are likely to confound even more the decision as to who should receive a liver transplant. That is, when both young and older adults face similar chances for success, who should receive the scarce organs? "Our data make the debate even more difficult," says John Pirsch, MD, assistant professor of medicine and transplant physician at the University of Wisconsin Hospital and Clinics, Madison. "It's
Emotional Maturity
Authors: Donald Oken
Journal: JAMA (1961)

This book will fan sparks of happy memories for many psychiatrists of the post—World War II generation, for whom the first edition served as an inspiration and tonic. At that time, the air was full of enthusiasm, challenge, and promise of things to come. This new edition revives that feeling. It is an exciting book, full of vitality and intensity, coupled with strong underlying optimism. Saul is deeply concerned about the social consequences of psychopathology, and he stresses the necessity for prompt and effective application of rational psychodynamic principles to deal with these problems, believing that with energy and earnest understanding solutions will be found. The objectives of this book are to present the motivational dynamics of personality and the unfolding of these forces over the course of development. The author's approach grows out of his psychoanalytic background, but his book is no mere rehash of analytic theory. The discussion
Abstract 903: Real-time imaging of cellular senescence in living animals
Authors: Lina Cui
Journal: Cancer Research (2019)

Abstract Senescence, a cellular stage that halts proliferation, plays a critical role in cellular processes such as tumor suppression, tumorigenesis and aging. Monitoring of senescence in real-time in living objects not only holds value in basic biological studies, it can also benefit treatments of various diseases such as cancer and age-related conditions. Our lab has developed a series of small molecule based agents for non-invasive imaging of cellular senescence in real-time. We have demonstrated their applications in tumor models receiving chemo- or radiotherapy, as well as aging mice models. These probes will be useful for treatment response monitoring, therapeutic regimen optimization, as well as imaging-guided removal of aged cells. Citation Format: Lina Cui. Real-time imaging of cellular senescence in living animals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 903.
Canad Anaesthetists' Society Journal, Toronto
Journal: JAMA (1966)

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
Subdural haematoma as a complication of spinal anaesthetic
Authors: P. Newrick, D. Read
Journal: BMJ (1982)

High incidence of amiodaroneinduced photosensitivity in North-west England Amiodarone is a potent cardiac antiarrhythmic agent which has been used in Europe for more than a decade but which has only recently become available in Britain.Facial pigmentation and photosensitivity are well recognised side effects,'-4 but their incidence is disputed.We report the incidence of photosensitivity in a large group of patients receiving amiodarone at a regional cardiothoracic centre.
Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice
Authors: Takuya Kobayashi, Yoshio Tahara, Mayumi Matsumoto, Masako Iguchi, Hideto Sano, Toshinori Murayama, Hidenori Arai, Hiroji Oida, Takami Yurugi-Kobayashi, Jun K. Yamashita, Hiroyuki Katagiri, Masataka Majima, Masayuki Yokode, Toru Kita, Shuh Narumiya
Journal: Journal of Clinical Investigation (2004)

Production of thromboxane (TX) A2 and PG I2/prostacyclin (PGI2) is increased in patients with atherosclerosis. However, their roles in atherogenesis have not been critically defined. To examine this issue, we cross-bred atherosclerosis-prone apoE-deficient mice with mice deficient in either the TXA receptor (TP) or the PGI receptor (IP). Although they showed levels of serum cholesterol and triglyceride similar to those of apoE-deficient mice, apoE-/-TP-/- mice exhibited a significant delay in atherogenesis, and apoE-/-IP-/- mice exhibited a significant acceleration in atherogenesis compared with mice deficient in apoE alone. The plaques in apoE-/-IP-/- mice showed partial endothelial disruption and exhibited enhanced expression of ICAM-1 and decreased expression of platelet endothelial cell adhesion molecule 1 (PECAM-1) in the overlying endothelial cells compared with those of apoE-/-TP-/- mice. Platelet activation with thrombin ex vivo revealed higher and lower sensitivity for surface P-selectin expression in platelets of apoE-/-IP-/- and apoE-/-TP-/- mice, respectively, than in those of apoE-/- mice. Intravital microscopy of the common carotid artery revealed a significantly greater number of leukocytes rolling on the vessel walls in apoE-/-IP-/- mice than in either apoE-/-TP-/- or apoE-/- mice. We conclude that TXA2 promotes and PGI2 prevents the initiation and progression of atherogenesis through control of platelet activation and leukocyte-endothelial cell interaction.
The Art of Anæsthesia.
Journal: JAMA (1928)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Busulphan lung
Authors: W. A. Littler, J. M. Kay, P. S. Hasleton, D. Heath
Journal: Thorax (1969)

A 61-year-old man with chronic myeloid leukaemia was treated with busulphan (Myleran). After receiving 1 g. of this drug over a period of 20 months he became dyspnoeic and developed crepitations in the lungs. Two months later radiographs of the chest revealed peri-hilar infiltrates and subsequently diffuse mottling throughout both lungs. Lung function tests showed a gross impairment of the transfer factor to a quarter of the predicted normal. At necropsy the lungs showed a striking proliferation of granular pneumocytes, many of which had disintegrated to produce intra-alveolar debris, some of which showed organization by fibrous tissue. There was associated interstitial pulmonary fibrosis. Electron microscopy confirmed the desquamated alveolar cells to be type II (granular) pneumocytes containing characteristic lamellar bodies. Many of these osmiophilic bodies, believed to be the source of pulmonary surfactant, had been liberated into the alveolar spaces, with the formation of phospholipid myelin figures and lattices. We think that the basic pathology of busulphan lung is a chemically induced alveolitis with proliferation of granular pneumocytes followed by fibrosis of alveolar walls and intra-alveolar contents.
Thyroxine replacement therapy: prescribing patterns and problems in 2710 patients. Scottish Automated Follow-up Register Group.
Authors: K Graham, C Kesson, B Kennedy
Journal: BMJ (1980)

The use of thyroxine replacement therapy was studied in 2710 patients with a previous diagnosis of either thyrotoxicosis or primary hypothyroidism. The patients, who were treated in five centres, were followed-up continuously using an automated register. Seventy per cent of patients had been prescribed daily doses of thyroxine of 200 microgram or more. The estimated 10-year cumulative incidence of detected undertreatment was 13 . 2% (95% confidence limits 10 . 9-15 .6%). The median cumulative incidence of recognised overtreatment was 6 . 2%. Improved patient education and the dissemination of guidelines to doctors on the use of thyroxine replacement may reduce the incidence of undertreatment or overtreatment.