tbuckley/cabot-search huggingface dataset:
P01.35 Inhibition of MutT homolog 1 (MTH1) in glioblastoma multiforme results in impaired cell migration and tumor growth
Authors: M. Timmer, S. Kannampuzha
Journal: Neuro-Oncology (2017)

Objective: MutT homolog1 (MTH1) is required for survival of cancer cells. These have irregular redox formations resulting in the production of reactive oxygen species which damage the deoxynucleoside triphosphate pool and subsequent the DNA. MTH1 plays a crucial role by inhibiting the incorporation of oxidized bases into the DNA that avoid apoptosis of cancer cells. Our aim was to analyze the pathophysiological role of MTH1 in glioma. Methods: MTH1 expression was analyzed in human glioma specimens by quantitative RT-PCR, immunohistochemistry and Western Blot. U87 proliferation, cell migration in vitro and tumor growth in an orthotopic rat model was monitored after knock-down of MTH1 by siRNA or inhibition by crizotinib. In addition, progression free- and overall survival of patients was correlated to the MTH1 level using both, own data and the TCGA dataset. Results: Higher expression of MTH1 was observed in glioblastoma than in lower grade astrocytomas and peritumoral tissue, both, on the gene and protein level. Quantitative RT-PCR resulted in a threefold MTH1 mRNA increase in GBM (6.93 ± 1.38) compared to diffuse astrocytoma (2.35 ± 0.27). Immunohistochemistry and Western blot analysis revealed a highly significant grade dependent upregulation of MTH1 in gliomas: control tissue 0.19 ± 0.07; astrocytoma WHO°II 1.42 ± 0.74; astrocytoma WHO°III 2.20 ± 0.55; glioblastoma 5.97 ± 2.68 (p<0.001). MTH1 siRNA transfected U87 cells showed slower migration compared to control U87 cells. Furthermore, treatment with crizotinib, an inhibitor of MTH1, also lowered cell migration (gap distance difference after 24h 994µm±49; p<0.01). In rats, tumor growth was significantly impaired in MTH1 siRNA U87 grafts. Additionally, the data indicate an inverse correlation between the progression free- and overall survival of patients and the expression level of MTH1 (p<0.05). CONCLUSION: These results show that MTH1 plays an essential role in both, malignization of glioma and disease progression in recurrent glioblastoma. Moreover, the MTH1 level in patients seems to influence tumor growth and patient survival and could be targeted by crizotinib indicating a putative role for potential future therapies.
Changing Clinical Laboratories: Better or Worse?
Authors: C. Marwick
Journal: JAMA (1998)

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
Abstract 842: The detection of circulating tumor cells is a negative prognostic factor in colorectal cancer
Authors: Josef Srovnal, Kamil Vyslouzil, Sylwia Jancik, Jiri Drabek, Lenka Radova, Miloslav Duda, Pavel Skalicky, Ivo Klementa, Lubomir Stary, Karel Cwiertka, Jana Straznicka, Vlastimil Sramek, Bohuslav Melichar, Marian Hajduch
Journal: Cancer Research (2010)

Abstract Purpose: We tested the hypothesis that the presence of circulating tumor cells (CTCs) is a negative prognostic factor in patients with stage I-III colorectal cancer (CRC). Patients and methods: This was a prospective study to test for the presence of CTCs in peripheral blood and bone marrow in 182 colorectal cancer patients at the time of surgery and one month after surgery using real-time RT-PCR for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20). Results: Overall, 24 of 147 (16.3%) stage I-III CRC patients developed recurrence/metastasis postoperatively in a mean follow-up period of 22.9 months. There was no correlation between CTCs and conventional clinical pathological features. In total, 51.7% of patients were CTC positive detected in peripheral blood and/or bone marrow at the time of surgery using CEA and/or CK20 and 47% of patients were CTC positive one month after surgery. At surgery, CTC positive patients measured as CEA mRNA copy number in peripheral blood showed significantly poorer disease-free survival (DFS) (p=0.05). One month after surgery, both increased above threshold CEA and/or CK20 mRNA levels in bone marrow and CK20 mRNA level in blood correlated with shorter DFS (p=0.005, resp. p=0.0035). In addition, systemic increase in CEA gene expression, even if the values remained below cut-off threshold also correlated with poorer DFS (p=0.005). Conclusion: Detection of CTCs at surgery and/or one month after surgery is an independent negative prognostic factor for relapsing-free survival in stage I-III colorectal cancer. Acknowledgments of research support: This study was supported by grants MSM 151100001, IGA MZCR NR/7804-5 and IGA MZCR NR/9076. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 842.
Gonorrhea in women
Authors: M. Hart
Journal: JAMA (1971)

Two hundred thirty-one female patients of private obstetricians and gynecologists were examined for gonorrhea, using cultural techniques. Specimens were taken from the cervix and rectum of all patients and cultured on Thayer-Martin (TM) selective medium. Six, or 2.6%, were found positive. Of these, all were in the 20- to 29-year age group; only one had knowledge of being exposed to gonorrhea; three were pregnant. The frequently asymptomatic nature of gonorrhea in females, combined with a definable incidence of infection in this patient group, suggests that more frequent use of cultural methods employing TM medium would help control this rapidly increasing disease. Cultures are particularly recommended for women under 30 years who are single, pregnant, or manifest acute vaginitis.
New South Wales cracks down on commercial scanning
Journal: BMJ (2003)

lesion.Despite these differences, there is no obvious explanation for the discrepancy.We had few eligibility criteria that would limit the external validity of the study.GPs particularly interested in skin lesions may have been more likely to participate, but the ratios that we observed were similar to that found in an analysis of all excisions sent to a pathology service in Victoria. 5 GPs in Australia practise on a fee for service basis, and excisions of malignant skin lesions attract a higher payment than excisions of benign skin lesions.In conclusion, our results do not show that photography of pigmented skin lesions in general practice in Australia decreases the number of benign lesions excised without compromising sensitivity of the diagnosis of melanoma.
Self-Injury
Authors: Matthew K. Nock
Journal: Annual Review of Clinical Psychology (2010)

People have engaged in self-injury—defined as direct and deliberate bodily harm in the absence of suicidal intent—for thousands of years; however, systematic research on this behavior has been lacking. Recent theoretical and empirical work on self-injury has significantly advanced the understanding of this perplexing behavior. Self-injury is most prevalent among adolescents and young adults, typically involves cutting or carving the skin, and has a consistent presentation cross-nationally. Behavioral, physiological, and self-report data suggest that the behavior serves both an intrapersonal function (i.e., decreases aversive affective/cognitive states or increases desired states) and an interpersonal function (i.e., increases social support or removes undesired social demands). There currently are no evidence-based psychological or pharmacological treatments for self-injury. This review presents an integrated theoretical model of the development and maintenance of self-injury that synthesizes prior empirical findings and proposes several testable hypotheses for future research.
Stereotaxic hypophyseal cryosurgery in acromegaly and other disorders
Authors: A. M. Dashe
Journal: JAMA (1966)

Stereotaxic cryoablation of the sellar contents has been attempted in eight patients with pituitary tumors and in one patient with Cushing's syndrome due to adrenal hyperplasia. All of six patients with acromegaly were greatly improved. Growth hormone assays confirmed the clinical data. Complications of rhinorrhea and diabetes insipidus occurred in one patient. Two patients with pituitary tumors—are with a recurrent chromophobe adenoma and the other with a chromophobe tumor associated with hyperpigmentation following adrenalectomy—had clinical remissions with no loss of pituitary function. The patient with Cushing's syndrome without evidence of pituitary tumor had no beneficial effect from the procedure and required bilateral adrenalectomy at a later date. Stereotaxic cryoablation appears to be a useful procedure in carefully selected cases of pituitary neoplasm.
Methanol Poisoning
Authors: Karl Closs
Journal: JAMA (1970)

A 63-year-old man consumed a nonidentified beverage 18 hours before hospitalization. His symptoms—headache, nausea, vomiting, abdominal pain, drowsiness, and marked dyspnea leading to deep coma—suggested methanol poisoning. Pupillary reaction was impaired, acidois was present, and the urine contained methanol, formic acid, and formaldehyde. Treatment with sodium bicarbonate, saline, and glucose-insulin was immediately instituted. Oliguria was treated with extracorporeal dialysis, and the patient recovered completely except for a thrombosis in the left leg.
Recertification
Authors: RALPH O. WALLERSTEIN
Journal: Annals of Internal Medicine (1975)

Comments and Corrections1 May 1975RecertificationRALPH O. WALLERSTEIN, M.D.RALPH O. WALLERSTEIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-5-718_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I took the Recertification Examination because, with all the talk of recertification in the air, this seemed to be the only concrete thing to do, better than getting various credits for meetings attended. I also wanted to force myself to review the entire field of internal medicine. This worked, illustrating Jung's principle that "need is a better incentive than desire."I read the American College of Physicians' Self-Assessment Syllabus, bought a new Harrison, and checked out a few difficult questions with subspecialist friends. The syllabus is superb and was enjoyable reading. Because of the preliminary announcement that... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 3838 California Street San Francisco, California 94118 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1975Volume 82, Issue 5Page: 718-718KeywordsMotivationSub-specialty care ePublished: 1 December 2008 Issue Published: 1 May 1975 PDF downloadLoading ...
Bronchoscopic appearances
Authors: M. M. Brown
Journal: BMJ (1967)

Reviewsof N. T6rnblom, who thought that it came from the germinal epithelium, seems to have been forgotten.The discussion on the effects of cirrhosis on the plasma testosterone level certainly reached a clinical level.Nevertheless, this is a book for the physio- logist, for whom it is a necessary reading, rather than for, the clinician.RAYMOND GREENE.
CAUTERY HANDLE
Authors: David O'Shea
Journal: JAMA (1925)

The antithermo cautery handle, here illustrated, is aimed to protect the surgeon's hands while doing major cauterization. It is well adapted for the purpose for which it was intended. The handle is bulky. It gives the operator a good hand hold. It is made of cork (which is a nonconductor of heat), in which is embedded the handle part of the cautery. It may be easily sterilized, if necessary, without injury.
The Transmission of Acute Poliomyelitis to Monkeys
Authors: Simon Flexner
Journal: JAMA (1983)

Poliomyelitis or infantile paralysis prevailed in epidemic form along the Atlantic seaboard in the summer of 1907. About that time it appeared in Austria and Germany. In the summer of 1909 the disease reappeared as a focalized epidemic in Greater New York and had, by that time, spread widely throughout the United States and Europe. The cause and mode of dissemination of the disease are unknown; and hence there exists no intelligent means of prevention. While the severity and fatality of the disease fluctuate widely, its effects are always so disastrous as to make it of the highest medical and social importance. In spite of many thorough studies of the spontaneous disease in man, our knowledge of causation and prevention has not been advanced; it may be hoped that it will be advanced by the opportunity for fundamental study opened up by the successful transmission of the disease to lower
PROFESSOR KOCHER ON MODERN PROJECTILES IN WARFARE.
Authors: CHARLES G. CANNADAY
Journal: JAMA (1994)

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
Clinical activity of avapritinib in ≥ fourth-line (4L+) and PDGFRA Exon 18 gastrointestinal stromal tumors (GIST).
Authors: Michael C. Heinrich, Robin L. Jones, Margaret von Mehren, Sebastian Bauer, Yoon-Koo Kang, Patrick Schoffski, Ferry Eskens, Olivier Mir, Philippe Cassier, Cesar Serrano, William D. Tap, Jonathan C. Trent, Piotr Rutkowski, Shreyaskumar Patel, Sant P. Chawla, Eyal Meiri, Teresa Zhou, Maria Roche, Suzanne George
Journal: Journal of Clinical Oncology (2020)

826 Background: Targeting oncogenic KIT and PDGFRA mutations revolutionized treatment of patients (pts) with advanced GIST; however, nearly all pts succumb to resistant disease. Avapritinib is a potent and selective kinase inhibitor with broad activity against oncogenic KIT/PDGFRA mutants, including PDGFRA D842V and other primary or secondary resistance mutations. Results from the phase 1 NAVIGATOR (NCT02508532) study of avapritinib in pts with advanced GIST are presented. Methods: Adult pts with unresectable PDGFRA D842V or other mutant GIST who progressed on imatinib and ≥1 other tyrosine kinase inhibitor (TKI) were treated with oral, daily, continuous avapritinib. Adverse events (AE) and response by mRECIST 1.1 per central radiology were assessed. Overall population safety (30-600 mg starting doses) and efficacy in the response-evaluable 4L+ and PDGFRA Exon 18 (Ex 18) populations treated at the MTD (400 mg)/RP2D (300 mg) were analyzed. Results: As of 16 Nov 2018, 237 pts [172 KIT, 62 PDGFRA Ex 18 [56 D842V, 6 non-D842V), 2 PDGFRA N659K, 1 missing] were enrolled including 111 in the 4L+ population (primarily KIT, median 4 prior TKI) and 43 in the Ex 18 population (median 1 prior TKI). The 4L+ ORR was 22% [1 CR, 23 PR (1 pending)], and 52 SD with mDOR of 10.2 months (95% CI: 7.2–NE). The Ex 18 ORR was 86% [3 CR, 34 PR (1 pending)] and 5 SD; mDOR was not reached (95% CI: 11.3–NE). Most AEs were grade 1–2, most commonly nausea (63%), fatigue (58%), anemia (49%), periorbital edema (42%), diarrhea (40%), vomiting (40%), decreased appetite (38%), increased lacrimation (33%), peripheral edema (33%) and memory impairment (most common cognitive AE, 29%). 10% of pts discontinued due to a related AE. Grade 3–4 related AE ≥ 2% were anemia, fatigue, hypophosphatemia, hyperbilirubinemia, neutropenia, and diarrhea. Conclusions: Avapritinib has important clinical activity in pts with advanced GIST who have no effective therapies. The ORR and DOR of avapritinib in 4L+ exceeds that of approved 2nd and 3rd line therapies and shows impressive activity in D842V and other Ex 18 mutant PDGFRA GIST. Results suggest avapritinib has the potential to change the treatment paradigm of pts with advanced GIST. Clinical trial information: NCT02508532.
"SLEEP"
Authors: Edmund Jacobson
Journal: JAMA (1923)

<h3>To the Editor:</h3> —In the editorial on sleep and its relation to complete muscular relaxation (The Journal, October 20, p. 1366) you stated that "we have failed, heretofore, to realize the extent to which the impulses pouring into the brain come from the muscles, tendons and joints, proprioceptive impulses as they are often termed, in addition to the visual, auditory and tactile sensations that usually play on the sensorium." Observations have been made and recorded that have formed the nucleus of interest in the work of my associates and myself for many years. Relaxation has been studied in connection with sleep, insomnia and nervous states (Use of Relaxation in Hypertensive States,<i>New York M. J.</i><b>111</b>:419 [March 6] 1920; Reduction of Nervous Irritability and Excitement by Progressive Relaxation,<i>Tr. Sect. Nerv. &amp; Ment. Dis. A. M. A.</i>, 1920, p. 17; Treatment of Nervous Irritability and Excitement,<i>Illinois M. J.</i>
REPORTS OF SOCIETIES
Journal: BMJ (1940)

In this the most remote of your affiliated Branches the British Medical Jourtnal has ever been a strong and important link between us and the parent body.We welcome this opportunity of acknowledging our debt of grati- tude to those who maintain its standard of scientific excellence and to those who keep us so well informed on professional and political matters.In these great and difficult times we follow the work of the medical profession in the United Kingdom with increased interest, and the articles on the special problems of the war which have appeared over the past year are of the greatest value to us in New Zealand
Left ventricular mass and risk of stroke in an elderly cohort. The Framingham Heart Study
Authors: M. Bikkina
Journal: JAMA (1994)

<h3>Objective.</h3> —To evaluate the association of echocardiographically determined left ventricular mass (LVM) with incidence of stroke or transient ischemic attack in an elderly cohort. <h3>Design.</h3> —Cohort study with a follow-up period of 8 years. <h3>Setting.</h3> —Population-based sample. <h3>Subjects.</h3> —Elderly original cohort subjects of the Framingham Heart Study who were free of cerebrovascular disease and atrial fibrillation at the 16th biennial examination and who had adequate echocardiograms. This group consisted of 447 men (mean age, 67.8 years; range, 60 to 90 years) and 783 women (mean age, 69.2 years; range 59 to 90 years). <h3>Main Outcome Measures.</h3> —Age-adjusted 8-year incidence of stroke was examined as a function of baseline quartiles of LVM-to-height ratio. Proportional hazards regression was used in multivariate analyses to assess risk of stroke as a function of LVM-to-height ratio quartile, adjusting for age, sex, systolic blood pressure, hypertension treatment, diabetes, cigarette smoking, and blood lipid levels. <h3>Results.</h3> —Among the 1230 subjects eligible, 89 cerebrovascular disease events (62 strokes and 27 transient ischemic attacks) occurred during follow-up. In men, 8-year age-adjusted incidence of cerebrovascular events was 18.4% in the highest quartile of LVM-to-height ratio and 5.2% in the lowest quartile. Corresponding values in women were 12.2% and 2.9%. The hazard ratio for cerebrovascular events comparing highest to lowest quartile of LVM-to-height ratio was 2.72 (95% confidence interval [CI], 1.39 to 5.36) after adjusting for age, sex, systolic blood pressure, hypertension treatment, diabetes, cigarette smoking, and the ratio of total cholesterol to high-density lipoprotein cholesterol. After adjusting for age, sex, and cardiovascular disease risk factors, the hazard ratio for cerebrovascular events was 1.45 (95% CI, 1.17 to 1.80) for each quartile increment of LVM-to-height ratio. <h3>Conclusions.</h3> —Echocardiographically determined LVM-to-height ratio offers prognostic information beyond that provided by traditional cerebrovascular disease risk factors. Echocardiography provides information that facilitates identification of individuals at high risk for stroke and transient ischemic attack. (<i>JAMA</i>. 1994;272:33-36)
A MODIFICATION OF HARRISON'S TREATMENT FOR RINGWORM OF THE NAIL
Journal: JAMA (1920)

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
PLoS Medicine Issue Image | Vol. 4(8) August 2007
Journal: PLoS Medicine (2007)

A recent PLoS Medicine systematic review of qualitative research on adherence to tuberculosis treatment (Munro et al.) shows there is a need to listen more carefully to patients' own accounts of their treatment experiences. This review has prompted the writing of an editorial (PLoS Medicine Editors) on the importance of qualitative research. Image Credit: "Statue of Liberty Ear" by Eddie-S at Flickr.com