tbuckley/cabot-search huggingface dataset:
P11.08 Defining EGFR amplification status for clinical trial inclusion
Authors: P French, M Eoli, J Sepulveda, I de Heer, J M Kros, A Walenkamp, J Frenel, E Franceschi, P Clement, M Weller, P Ansell, J Looman, E Bain, M Morfouace, T Gorlia, M van den Bent
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Precision medicine trials targeting the epidermal growth factor receptor (EGFR) in glioblastoma patients require selection for EGFR-amplified tumors. However, there is currently no golden standard in determining the amplification status of EGFR or EGFRvIII expression. Here, we aimed to determine which technique and which cut-offs are suitable to determine EGFR amplification status. MATERIAL AND METHODS We compared fluorescent in-situ hybridization (FISH) and RT-qPCR data from patients screened for trial inclusion into the Intellance 2 clinical trial, with data from a panel-based next generation sequencing (NGS) platform (both DNA and RNA). RESULTS By using data from &gt;1000 samples, we show which cut-offs are optimal to determine EGFR gene amplification by FISH. Our data also show that gene amplification (as determined by FISH) correlates with EGFR expression levels (as determined by RT-qPCR) with ROC analysis showing an under the curve area of up to 0.902. EGFR expression as assessed by RT-qPCR therefore may function as a surrogate marker for EGFR amplification. Our NGS data shows that EGFR copy numbers can strongly vary between tumors with levels ranging from 2 to more than 100 copies per cell. Levels exceeding 5 gene copies can be used to define EGFR-amplification by NGS; below this level FISH detects very few (if any) EGFR amplified nuclei and none of the samples express EGFRvIII. CONCLUSION Our data from central laboratories and diagnostic sequencing facilities, using material from patients eligible for clinical trial inclusion, help defining the optimal cut-off for various techniques to determine EGFR amplification for diagnostic purposes.
Government Programs To Support Pediatric Research
Journal: JNCI Journal of the National Cancer Institute (2011)

Because cancer rates are so much higher in adults, many more clinical trials of drugs exist for adults than for children.To help prioritize which pediatric drugs are most promising, NCI created the Pediatric Preclinical Testing Program in 2004, which evaluates 12 new cancer agents per year in cell lines and mouse models.The dramatic preclinical results observed in this program for the aurora kinase inhibitor MLN8237, for neuroblastoma, propelled the drug into fast-track status for a phase I trial in children.
The Psychiatrist, the Treatment of Chronic Renal Failure, and the Prolongation of Life: I
Authors: HARRY S. ABRAM
Journal: American Journal of Psychiatry (1968)

The stress of chronic hemodialysis may arouse emotional conflicts in the patient that lead him into open rebellion against the medical regimen upon which his life depends. The author stresses the importance of psychiatric aspects of the selection process and the meaning of the prolongation of life to the patient, including resolution of the conflict between dependency upon the "machine" and the independence inherent in maintaining a "normal" life.
Arsenic: Health Effects, Mechanisms of Actions, and Research Issues
Authors: Charles O. Abernathy, Yung-Pin Liu, David Longfellow, H. Vasken Aposhian, Barbara Beck, Bruce Fowler, Robert Goyer, Robert Menzer, Toby Rossman, Claudia Thompson, Michael Waalkes
Journal: Environmental Health Perspectives (1999)

A meeting on the health effects of arsenic (As), its modes of action, and areas in need of future research was held in Hunt Valley, Maryland, on 22-24 September 1997. Exposure to As in drinking water has been associated with the development of skin and internal cancers and noncarcinogenic effects such as diabetes, peripheral neuropathy, and cardiovascular diseases. There is little data on specific mechanism(s) of action for As, but a great deal of information on possible modes of action. Although arsenite [As(III)] can inhibit more than 200 enzymes, events underlying the induction of the noncarcinogenic effects of As are not understood. With respect to carcinogenicity, As can affect DNA repair, methylation of DNA, and increase radical formation and activation of the protooncogene c-myc, but none of these potential pathways have widespread acceptance as the principal etiologic event. In addition, there are no accepted models for the study of As-induced carcinogenesis. At the final meeting session we considered research needs. Among the most important areas cited were a) As metabolism and its interaction with cellular constituents; b) possible bioaccumulation of As; c) interactions with other metals; d) effects of As on genetic material; e) development of animal models and cell systems to study effects of As; and f) a better characterization of human exposures as related to health risks. Some of the barriers to the advancement of As research included an apparent lack of interest in the United States on As research; lack of relevant animal models; difficulty with adoption of uniform methodologies; lack of accepted biomarkers; and the need for a central storage repository for stored specimens.
Screening tests for HBsAg in transfusion centres of developing countries.
Journal: BMJ (1988)

counterimmunoelectrophoresis.The benefit of reverse passive haemagglutination and ELISA over counterimmunoelectrophoresis is therefore 2 8- fold and 9-4-fold respectively (not 2-5 and 7 7 as stated).And the cost of detecting each unit of infected blood by counterimmunoelectrophoresis is $62.50 (not $6.25).The figures for hepatitis B markers among the potential recipients suggested there was no overlap between hepatitis B surface antigen, antibody to the core antigen, and antibody to surface antigen groups (99+108+39+254=500).I find this rather surprising.
Total and cancer-attributable phase-based costs for adolescent cancer care: A population–based study in British Columbia, Canada.
Authors: Mary L McBride, Ross Duncan, Karen Bremner, Claire De Oliveira, Ning Liu, Paul C. Nathan, Paul C. Rogers, Stuart Peacock, Murray Dale Krahn
Journal: Journal of Clinical Oncology (2017)

12 Background: Cancer among adolescents presents unique issues regarding diagnosis, treatment, late effects, and survival; but little is known about their healthcare costs, which are useful for economic evaluations and planning care. This study estimates total and cancer-attributable (net) medical costs for a population-based adolescent cancer cohort in British Columbia, Canada, by phase of care. Methods: Patients diagnosed with cancer aged 15 to 19 years from 1995 to 2009 were identified from the British Columbia Cancer Registry, and followed to December 31 st 2010. Data were linked with clinical and provincial administrative healthcare databases covering all medically-necessary costs. Total resource-specific costs (Canadian $ 2012) by phase of care were estimated for all patients and specific common cancers. Net costs were calculated by subtracting healthcare costs for propensity-score-matched provincial samples of adolescents without cancer from cancer patient costs. Results: Of the 750 cases, approximately 26% had lymphoma, 17% germ cell, 14% bone and soft tissue sarcomas, 12% central nervous system (CNS), and 11% leukemia; 94% survived &gt; = 1 year. Total mean pre-diagnosis costs per patient were $3657, of which $3554 was attributable to the cancer. First-year mean costs were $60,531 ($59,826). Continuing phase mean costs were $8,413 ($7,708). Final year of life mean costs were $224,243 ($221,018). Cancer types with highest costs were CNS (pre-diagnosis), leukemia (first-year); bone and soft tissue (continuing), and leukemia (end-of-life). Virtually all inpatient hospitalizations were cancer-related, representing ~40% of pre-diagnosis, ~62% of first-year, ~56%of continuing, and ~72%of end-of-life costs respectively. Conclusions: Management of adolescent cancer is costly, but is lower than for childhood cancer in all phases of care. Total costs, cancer-attributable costs, and inpatient activity were highest in the end-of-life period. Hospitalizations were the largest driver of costs in all post-diagnosis phases of care. Costs in the continuing phase, including surveillance and care for late effects, were 14% of first-year phase costs.
Respirators in Respiratory Failure
Authors: W. H. Kelleher
Journal: BMJ (1969)

BRnTnS 369 raises the point that the presence of the prune-belly syndrome in an older child should be unacceptable because it represents failure to apply early preventive treatment.In addition to the psychological and cos- metic benefit it might well be that the stronger abdominal wall would also be a positive advantage in the child's urinary dynamics.-Iam, etc.,
Host-Directed Therapy for AIDS
Authors: Michael M. Lederman
Journal: Annals of Internal Medicine (1995)

Letters15 September 1995Host-Directed Therapy for AIDSMichael M. Lederman, MDMichael M. Lederman, MDCase Western Reserve University; Cleveland, OH 44106Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-6-199509150-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Stricker and Goldberg suggest that DNCB is used by thousands of HIV-infected patients around the world at a cost of pennies a week [1]. Although the cash outlay for DNCB is modest, the actual cost of this therapy may be substantially greater. The clinical value of DNCB is currently uncertain. Several uncontrolled studies have suggested that some patients treated with DNCB may experience increases in the number of circulating CD8+ lymphocytes; in some instances, increases in the number of CD56+ lymphocytes (cells with a natural killer phenotype) were also seen [2, 3]. These observations must be confirmed by ...References1. Stricker RB, Elswood BF, Goldberg B, Henry J, et al. Clinical and immunologic monitoring of HIV-infected patients treated with topical dinitrochlorobenzene (DNCB) [Abstract]. Int Conf AIDS. 1994; 10:216. Google Scholar2. Traub A. Use of DNCB as an immune modulator in HIV-positive patients-a pilot study [Abstract]. Int Conf AIDS. 1994; 10:219. Google Scholar Author, Article, and Disclosure InformationAffiliations: Case Western Reserve University; Cleveland, OH 44106 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1995Volume 123, Issue 6Page: 472KeywordsAIDSCellsClinical trialsLymphocytesNatural killer cellsPhenotypesResearch laboratories Issue Published: 15 September 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Abstract 4847: Investigating the impact of astrocytes on targeted therapy of melanoma brain metastases
Authors: Joshua Parris, Subhasree Basu, Thibaut Barnoud, Yongkang Zhao, Peter Somboonsong, Qing Chen, Maureen Murphy
Journal: Cancer Research (2019)

Abstract Metastatic melanoma is a devastating disease that leads to the development of brain metastases (MBMs) in 40-60% of patients. Upon diagnosis of brain metastases, patient overall survival is less than 6 months. Poor patient survival is believed to be due to resistance driven by the brain microenvironment. Collectively, these findings underscore the need for novel therapeutic strategies to improve the survival of patients with MBMs. Development of effective therapies relies on an understanding of the interaction between MBMs and different cell types within the brain microenvironment. Astrocytes are the most abundant cell type within the brain and interact with MBMs through direct and indirect mechanisms. Astrocyte interaction with MBMs alters MBM gene expression and promotes metastatic outgrowth and resistance to cytotoxic chemotherapies. Exactly how astrocytes alter MBM response to MAPK inhibition remains unclear. Using conditioned media from primary astrocytes, as well as co-culture of primary astrocytes with either the MBM cell line WM4265-2 or the primary melanoma cell line WM983B, we found that the interaction of melanoma cells with astrocytes increased melanoma sensitivity to MEK inhibition (MEKi). RNA sequencing of WM4265-2 and WM983B cell lines treated with the MEK inhibitor PD0325901 (PD901) showed significant up-regulation of the transcriptional regulator ID3, which is known to play a role in the resistance of melanoma to MAPK inhibition. Interestingly, astrocyte conditioned media prevented the upregulation of ID3. To validate this finding, we silenced ID3 in WM4265-2 and WM983B cell lines, and showed that knockdown of ID3 caused increased sensitivity to MEKi. These combined data support the premise that the increased response to PD901 in MBMs exposed to astrocytes is due to ID3 down-regulation. How ID3 modulates resistance to MAPK inhibition remains unclear. Elucidating the mechanism of ID3 mediated resistance to MEKi may uncover new avenues for improving the treatment of melanoma brain metastases. Citation Format: Joshua Parris, Subhasree Basu, Thibaut Barnoud, Yongkang Zhao, Peter Somboonsong, Qing Chen, Maureen Murphy. Investigating the impact of astrocytes on targeted therapy of melanoma brain metastases [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 4847.
Abstract 802: Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism
Authors: Jiyoung Lee
Journal: Cancer Research (2019)

Abstract Mitochondrial metabolism is an attractive target for cancer therapy. Reprogramming metabolic pathways could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options like triple negative breast cancer (TNBC). Here we show that BACH1 (BTB and CNC homology1), a heme-binding transcription factor whose expression is enriched in TNBC patients, targets mitochondrial metabolism. BACH1 decreases glucose utilization in the TCA cycle and negatively regulates transcription of electron transport chain (ETC) genes. BACH1 depletion by shRNA or degradation by hemin sensitizes cells to ETC inhibitors such as metformin, suppressing growth of both cell line and patient-derived tumor xenografts. Expression of a heme-resistant BACH1 mutant in shBACH1 cells rescues the BACH1 phenotype and restores metformin resistance in hemin-treated cells and tumors. Finally, BACH1 gene expression inversely correlates with ETC gene expression in breast cancer patients as well as other tumor types, highlighting the clinical relevance. This study demonstrates that mitochondrial metabolism can be exploited through targeting BACH1 to sensitize breast cancer and potentially other tumor tissues to mitochondrial inhibitors. Citation Format: Jiyoung Lee. Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism [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 802.
This Week in&lt;EMPH TYPE="ITAL"&gt;JAMA&lt;/EMPH&gt;
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
Prospective study of estrogen replacement therapy and risk of breast cancer in postmenopausal women
Authors: G. A. Colditz
Journal: JAMA (1990)

We prospectively examined the use of estrogen replacement therapy in relation to breast cancer incidence in a cohort of women 30 to 55 years of age in 1976. During 367 187 person-years of follow-up among postmenopausal women, 722 incident cases of breast cancer were documented. Overall, past users of replacement estrogen were not at increased risk (relative risk, 0.98; 95% confidence interval, 0.81 to 1.18), including even those with more than 10 years of use (relative risk after adjustment for established risk factors, 0.70; 95% confidence interval, 0.45 to 1.10). However, the risk of breast cancer was significantly elevated among current users (relative risk, 1.36; 95% confidence interval, 1.11 to 1.67). Among current users, a stronger relationship was observed with increasing age but not with increasing duration of use. These data suggest that long-term past use of estrogen replacement therapy is not related to risk of breast cancer but that current use may modestly increase risk. (<i>JAMA</i>. 1990;264:2648-2653)
Effects of biphasic positive airway pressure in patients with chronic obstructive pulmonary disease
Authors: E. Katz-Papatheophilou, W. Heindl, H Gelbmann, P Hollaus, M Neumann
Journal: European Respiratory Journal (2000)

Biphasic positive airway pressure (BiPAP) is a ventilatory mode in which two pressure levels (higher (Phigh) and lower (Plow)) acting as continuous positive airway pressure (CPAP) alternate at preset time intervals. BiPAP combines pressure-controlled ventilation with unrestricted spontaneous breathing. BiPAP has not yet been evaluated in patients with chronic obstructive pulmonary disease (COPD). Therefore, the effects of BiPAP (15 cmH2O Phigh and 5 cmH2O Plow) pressure support (PS; 15 cmH2O and positive end-expiratory pressure (PEEP) 5 cmH2O) and CPAP (5 cmH2O) on respiratory mechanics in COPD patients were compared. Twenty-one COPD patients were supported in randomized order with BiPAP, PS and CPAP. Pressure-time product (PTP), work of breathing (WOB), change in oesophageal pressure (deltaPoes), mouth occlusion pressure (P0.1), intrinsic PEEP (PEEPi), tension time index (TTI), respiratory frequency, and tidal volume (VT) were measured. During BiPAP, the COPD patients showed a significantly higher PTP, WOB, deltaPoes, P0.1, TTI and PEEPi than during PS. Comparing the Plow phases of BiPAP and CPAP, the breaths during the Plow phases of BiPAP had a lower VT and a greater WOB and PTP due to a higher PEEPi than on CPAP alone. In conclusion, biphasic positive airway pressure carries the risk of increased work of breathing in spontaneously breathing chronic obstructive pulmonary disease patients. Pressure support is superior for reducing their respiratory muscle effort.
DR. MARTIN WARE-NEW EDITOR OF THE BRITISH MEDICAL JOURNAL
Journal: JAMA (1965)

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
THE PROGRESS OF PURE FOOD LAWS.
Journal: JAMA (1905)

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
ASPECTS OF THE TUBERCULOSIS PROBLEM
Journal: JAMA (1922)

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