tbuckley/cabot-search huggingface dataset:
Abstract 4123: Induction of motility, invasion, and proliferation by wild-type EGFR depends on c-Met in NSCLC
Authors: Austin M. Dulak, Christopher T. Gubish, Jill M. Siegfried
Journal: Cancer Research (2010)

Abstract The complex signaling networks promoting non-small cell lung cancer (NSCLC) progression are currently being dissected to identify novel therapeutic targets or potential drug combinations. One cascade that is at the forefront of drug discovery in NSCLC is the Epidermal Growth Factor Receptor (EGFR) pathway. EGFR is a receptor tyrosine kinase (RTK) that interacts with ligands Epidermal Growth Factor (EGF), Transforming Growth Factor-alpha, and Amphiregulin, to promote invasive growth, a program requiring growth, motility, and invasion. Recently, there has been strong evidence linking c-Met to EGFR tyrosine kinase inhibitor (TKI) resistance. c-Met is a RTK that interacts with its natural ligand Hepatocyte Growth Factor (HGF), also known as Scatter Factor, to activate invasive growth, similar to EGFR, in many cancers including NSCLC. We previously reported an HGF independent mechanism of c-Met activation through EGFR that required c-Src. Here, we demonstrate that c-Met activation is necessary for known EGF-induced phenotypes in 201T and A549 NSCLC cell lines expressing moderate levels of wild-type (wt) EGFR and c-Met. Stimulation with EGF (50 ng/mL) in serum-free media induced cell invasion at 48 h that was inhibited by ∼74% when pretreated with the c-Met TKI, PF2341066 (1 uM) (Pfizer). Motility, initiated through EGFR, was reduced by 47% and 42% in 201T and A549 cells, respectively by PF2341066. Similarly, c-Met inhibition partially abrogated EGF-induced proliferation by 31% in 201T cells and 43% in A549 cells. To confirm these findings, the invasion assay was repeated with c-Met siRNA in 201T cells. Knockdown of c-Met resulted in an 80% reduction in EGF-stimulated invasion. Together, this suggests that EGFR action relies, in part, on activation of c-Met to modulate invasive growth in wt-EGFR NSCLC cell lines. Based on these data, it was addressed whether combined EGFR (gefitinib) and c-Met (PF2341066) targeting in a 3-week 201T xenograft murine model could lead to enhanced anti-tumor effects. PF2341066 (50 mg/kg) alone had no significant effect on inhibiting tumor xenograft growth, whereas gefitinib (150 mg/kg) alone significantly reduced tumor volume by 51%. Combining TKI therapies produced a 66% decrease in tumor volume, a significantly greater effect compared to PF2341066 and gefitinib groups, individually. These findings indicate that EGFR activation of c-Met plays a critical role in lung tumor progression and that combined EGFR and c-Met targeting hold strong therapeutic potential in lung cancer without EGFR and c-Met mutations. 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 4123.
A piece of my mind. Babu
Authors: M. S. Smith
Journal: JAMA (1993)

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
A Phase II study of Viagenpumatucel-l (HS-110) in combination with low-dose Cyclophosphamide versus physician's choice in patients with advanced non-small cell lung cancer
Authors: Roger B Cohen, John Nemunaitis, Nashat Gabrail, Lyudmila Bazhenova, Taylor H Schreiber, Melissa Price
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Viagenpumatucel-L (HS-110) is an allogeneic cell-based therapeutic cancer vaccine for the treatment of advanced NSCLC. The vaccine is composed of a cell line expressing a defined repertoire of tumor antigens (MAGE-A3, NY-ESO-1, LAGE-1, and others) that are chaperoned by a modified
Serum Concentrations of Theophylline in Children Treated with Two Daily Doses of a Sustained‐Release Theophylline Preparation
Authors: B. Sommer, S. E. Pedersen, E. Nathan
Journal: Allergy (1981)

Over a 3‐month period 22 asthmatic children were treated with a sustained‐release theophylline preparation (Nuelin Retard®, Riker) in twice‐daily doses. During the first 2 weeks of treatment slight side‐effects were observed in 14 children. Over the remaining 10‐week period only four children experienced minor side‐effects. Serum theophylline levels 4 hours after tablet administration were measured three times and serum levels just before tablet administration were measured once during the observation period. The average difference between the serum levels of theophylline just before tablet administration and the corresponding serum value 4 hours afterwards was 4.2 μg/ml. The serum values 4 hours after tablet administration showed an insignificant fall throughout the period and patient compliance was assessed as good. When the average requirements of theophylline in mg/kg found by Wyatt et al. (15) (Table 2) were used as initial doses, few dosage adjustments were necessary and no serum values were greater than 26.2 μg/ml, but in order to avoid serum levels above 20 μg/ml initial doses should be decreased about 10% and final adjustment made with the aid of serum theophylline measurement under steady state conditions. In children, Nuelin Retard given in two daily doses is capable of maintaining a constant therapeutic serum concentration for the whole 24‐hour period.
In the Name of Mental Health: The Social Functions of Psychiatry
Authors: Donald W. Goodwin
Journal: JAMA (1969)

Four years of undergraduate education, four years of medical school, one year of internship, three years of residency: all to be a psychiatrist. The author of this book, himself a psychiatrist, wonders, Why bother? Psychiatrists, he argues, have no business being physicians. Physicians deal with "bodily processes," psychiatrists with "social processes." Physicians are concerned with disease, psychiatrists with "social, moral, political and economic" problems. Physicians correct "undesirable bodily states," usually with the patient's consent; psychiatrists modify behavior that is undesirable to society, often without consent. Why, then, do psychiatrists "disguise" themselves as physicians? Why does society encourage the disguise? Mainly because it promotes society's ends. By "regulating and controlling conduct," psychiatrists protect the community from "certain kinds of deviance." For this, society rewards the psychiatrist with status, income, and laws to maintain his regulatory and coercive function. He performs this function in two ways. First, by labeling such persons as
Utilization Strategies for Intensive Care Units
Authors: Paul E. Kalb
Journal: JAMA (1989)

Critical care resources in the United States are being rationed, that is, not all critical care expected to be beneficial is being provided to all patients who desire it. Although the extent of rationing is uncertain, it is an everyday occurrence in some hospitals and is likely to occur at least some of the time in many hospitals. Substantial evidence suggests that current rationing practices are highly subjective and perhaps inequitable. Critical care is widely believed to be beneficial to many patients, despite a striking dearth of supportive data. Since this type of care is being inequitably denied to some patients, hospitals should either adopt formal rationing guidelines or, alternatively, they should take clear steps to avoid rationing by altering the supply of or the demand for critical care. Reasonable arguments are presented in support of both approaches, as are suggestions for their implementation. (<i>JAMA</i>. 1989;261:2389-2395)
More Medical Students
Authors: John L. Caughey
Journal: JAMA (1966)

It is not easy for the 25th speaker on a program devoted to medical education to add anything which is new or different from what has already been said. But it certainly is appropriate to give some attention to the number and quality of the young people from whom the future members of the medical profession are being created.  Obviously, medical schools select their students from the pool of candidates who make themselves known by submitting applications. In this country, to qualify for consideration by a medical school, the candidate must have completed at least two and usually three years of college study. This is an extremely effective screening device, since a student must perform well in his premedical program if he is to have much chance for acceptance by a medical school. In effect, this means that access to medicine as a career is very greatly affected by the
Functional Imaging of Cancer with Emphasis on Molecular Techniques
Authors: D. A. Torigian, S. S. Huang, M. Houseni, A. Alavi
Journal: CA A Cancer Journal for Clinicians (2007)

A multitude of noninvasive, quantitative, functional imaging techniques are currently in use to study tumor physiology, to probe tumor molecular processes, and to study tumor molecules and metabolites in vitro and in vivo using computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (US), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and optical imaging (OI). Such techniques can be used in conjunction with structural imaging techniques to detect, diagnose, characterize, or monitor tumors before and after therapeutic intervention. These can also be used to study tumor gene expression, to track cells and therapeutic drugs, to optimize individualized treatment planning for patients with tumors, and to foster new oncologic drug development. In this article, we review the rich variety of functional imaging techniques that are available for these purposes, which are becoming increasingly important for optimal individualized patient treatment in this day and age of "personalized medicine."
A Career in Primary Care
Authors: Lawrence L. Hirsch
Journal: JAMA (1977)

The stated objective of the authors is to "propose a new approach to medical education in the primary and continuing care of ambulatory patients." In developing this concept, there is a large amount of historical, analytic, and normative material presented— sometimes not clearly differentiated. The plan consists of six distinct phases or steps: (1) career choice and commitment on graduating from high school, (2) selection on the bases of interest, aptitude, and personality, (3) two years of collegiate and some clinical "environments," (4) four years of a primary care track in medical school, including brief periods on hospital wards, (5) one year in an internship following graduation, and (6) continuing education. On completing this course of study, a person would be qualified to participate in a group or association of those involved with all levels of care. The area of specialization of the primary care physician would be that of
Vulnerable Subjects and Civic Professionalism: Would Six-Sigma Research and Research Ethics Consultation Solve the Vulnerability Problem?
Authors: Mary Faith Marshall
Journal: The American Journal of Bioethics (2004)

"Vulnerable Subjects and Civic Professionalism: Would Six-Sigma Research and Research Ethics Consultation Solve the Vulnerability Problem?." The American Journal of Bioethics, 4(3), pp. 54–55
THE DENTITION OF MAMMALS WITH REFERENCE TO THAT OF MAN.
Authors: H. W. MARETT TIMS
Journal: JAMA (1905)

In response to the kind invitation of your president, I have ventured to bring before you some of the results of recent researches into the tooth-genesis in mammals including that of man. Though my work on primate dentitions is still incomplete, I shall endeavor to summarize some of the problems to which I am paying particular attention, in the hope that an appreciation of the gaps in our present knowledge may suggest lines of investigation to other workers. Before homologies and methods of tooth replacement can be adequately interpreted it is necessary to have a clear idea of the number of dentitions represented in the<i>Mammalia.</i>The introduction by Owen of the terms "monophyodont" and "diphyodont" indicated the state of knowledge in his day, but with the application of histologic methods to the problems of comparative odontology, the words lost much of their original significance. The marsupials, regarded by Owen
Platelet Activation in Obese Women
Authors: Giovanni Davì, Maria Teresa Guagnano, Giovanni Ciabattoni, Stefania Basili, Angela Falco, Marina Marinopiccoli, Michele Nutini, Sergio Sensi, Carlo Patrono
Journal: JAMA (2002)

ContextObesity, in particular abdominal adiposity, is associated with increased cardiovascular morbidity and mortality through mechanisms possibly linking the metabolic disorder to platelet and vascular abnormalities.ObjectiveTo investigate the clinical and biochemical determinants of lipid peroxidation and platelet activation in obese women.Design, Setting, and ParticipantsCross-sectional comparison, conducted between September 1999 and September 2001, of urinary 8-iso prostaglandin F2α (8-iso PGF2α) and 11-dehydrothromboxane B2 (11-dehyhdro-TxB2) excretion levels in 93 women: 44 with a body mass index (BMI) higher than 28 and a waist-to-hip ratio (WHR) of 0.86 or higher, android obesity; 25 with a BMI higher than 28 and a WHR lower than 0.86, gynoid obesity; and 24 nonobese women with a BMI lower than 25. An additional study was conducted to determine the short-term effects of weight loss in 20 of the 44 women with android obesity.InterventionDuring a 12-week period, 20 women with android obesity followed a weight loss program to reduce caloric intake to about 1200 kcal/d.Main Outcome MeasuresPlasma C-reactive protein, insulin and leptin levels, and urinary 8-iso PGF2α (marker of in vivo lipid peroxidation) and 11-dehyhdro-TxB2 (marker of in vivo platelet activation) excretion. Weight loss was defined as successful when the initial body weight decreased by at least 5 kg after a 12-week period of caloric restriction.ResultsWomen with android obesity had higher levels of 8-iso PGF2α (median [interquartile range {IQR}] 523 [393-685] vs 187 [140-225] pg/mg creatinine) and 11-dehyhdro-TxB2 (median [IQR], 948 [729-1296] vs 215 [184-253] pg/mg creatinine) than nonobese women (P&lt;.001). Both 8-iso PGF2αand 11-dehyhdro-TxB2 were higher in women with android obesity than women with gynoid obesity (P&lt;.001). Based on multiple regression analysis, C-reactive protein levels and WHRs of 0.86 or higher predicted the rate of 8-iso PGF2α excretion independently of insulin and leptin levels. Of 20 women with android obesity, 11 achieved successful weight loss, which was associated with statistically significant reductions in C-reactive protein (median change, 23%; P&lt;.05), 8-iso PGF2α (median change, 32%; P = .04) and 11-dehydro-TxB2 (median change, 54%; P = .005).ConclusionsAndroid obesity is associated with enhanced lipid peroxidation and persistent platelet activation. These abnormalities are driven by inflammatory triggers related to the degree of abdominal adiposity and are, at least in part, reversible with a successful weight-loss program.
Health effects of hexachlorobenzene and the TEF approach.
Authors: J G Vos
Journal: Environmental Health Perspectives (2000)

Health Effects of Hexachlorobenzene and the TEF ApproachIn her paper, van Birgelen (1) argued that hexachlorobenzene (HCB) should be dassified as a dioxin-like compound, with a toxic equiva- lency factor (TEF) value of 0.0001.By doing this, HCB could add 10-60% to the total toxic equivalents (TEQs) in human milk samples in most countries.To indude a compound in the TEF concept, the following criteria are used: a) the compound must show a structural relation- ship to polychlorinated dibenzo-p-dioxins or polychlorinated dibenzofurans; b) the com- pound must bind to the aryl hydrocarbon (Ah) receptor; c) the compound must elicit Ah receptor-mediated biochemical and toxic responses; and d) the compound must be per- sistent and accumulate in the food chain (2).van Birgelen (1) also referred to these criteria.In respect to the toxic responses, one can question the validity of using a TEF approach for HCB, because the most basic assumption for this concept is that the com- bined effects are dose or concentration addi- tive (3).The dioxin-like effects for HCB mentioned by van Birgelen (1) are reduction in reproduction, splenomegaly, increase in mortality, neurologic alterations, teratologic effects, and immunotoxic effects.Although TCDD and HCB share target organs of toxi- city, the effects produced in these systems or organs do differ: * Laboratory animals that are lethally exposed to TCDD die following a wasting disease that is not seen in HCB poisoning * Neurotoxic effects such as tremors are typical after HCB exposure in rodents and birds (4) but are not observed after TCDD poisoning (5) *Thymic atrophy and suppression of thymus-dependent immunity is a hallmark of TCDD toxicity observed in all species investigated (6), whereas the immunotoxici- ty of HCB is species-dependent: this is characterized in rats and in humans by splenomegaly, enlarged lymph nodes, and enhancement of parameters of specific immunity, and in the mouse by suppression of most immune responses (4) *Target organs for the carcinogenic actions of HCB and TCDD are different; only the liver and thyroid are target organs for both compounds (5,7) * Edema formation, not mentioned by van Birgelen (1), is a pathology typically caused by TCDD in some species, which includes subcutaneous edema, ascites, and hydropericardium in the chicken (5) * Chloracne is a specifically characteristic skin disease attributed to human exposure to TCDD-like compounds, whereas the cuta- neous lesions caused by HCB poisoning are hirsutism and bullous lesions, usually in sun-exposed skin areas; these skin lesions in victims of HCB poisoning have been attrib- uted to the porphyrogenic activity of HCB (4,4.Furthermore, for the toxic effects of HCB mentioned above (which differ largely from those induced by TCDD, although in the same target organs), there are no available data that show these effects to be Ah receptor mediated.These considerations do not justify the TEF approach as defined by Ahlborg et al.(2) for HCB.
Impaired Marrow Granulocyte Reserve and Leukocyte Mobilization in Leukemic Reticuloendotheliosis
Authors: LUNG T. YAM
Journal: Annals of Internal Medicine (1977)

Cytotoxic chemotherapy often induces sustained, severe granulocytopenia in patients with leukemic reticuloendotheliosis. Many of the patients so treated subsequently develop serious infections. Poor marrow reserve has been implicated but lacks supporting evidence as the cause of the granulocytopenia. In six patients we studied with leukemic reticuloendotheliosis, bone marrow showed severe granulocytopenia, blood neutrophil response after intravenous hydrocortisone injection was poor, and leukocyte migration to the site of inflammation showed suboptimal neutrophilia and poor or no mononuclear response. Splenic hypersequestration and pooling were probably not important factors in causing neutropenia, since similar results were seen in patients without spleens. These findings suggest that in this disease the marrow granulocyte reserve and leukocyte mobilization are impaired and the neutropenia is due to poor granulocyte production and not to increased migration of leukocytes to tissues. Cytotoxic chemotherapy should be used with caution in patients with this disease.
At-Home Treatment of Patients with Acute Attacks of Hereditary Angioedema with the Bradykinin B2 Receptor-Antagonist Icatibant
Authors: H. Farkas, D. Csuka, Z. Zotter, L. Varga, Z. Böröcz, G. Temesszentandrási, I. Karádi
Journal: Journal of Allergy and Clinical Immunology (2011)
Abstract 4813: Aberrant promoter methylation of TMS1 gene in patients with colorectal carcinoma in Saudi Arabia
Authors: Shahab Uddin, Abdul K. Siraj, Maha Al-Rasheed, Azhar Husain, Prashant Bavi, Nasser Al-Sanea, Alaa Abduljabbar, Samar Al Homoud, Luai Ashari, Fouad Al Dayel, Khawla S. Al-Kuraya
Journal: Cancer Research (2011)

Abstract Gene silencing associated with aberrant methylation of promoter region CpG islands is an acquired epigenetic alteration. It serves as an alternative to genetic defects in the inactivation of tumor suppressor and other genes in human cancers. Several genes have been shown to be epigenetically inactivated in a wide range of tumors. TMS1 is a tumor suppressor gene which encodes for a CARD (caspase recruitment domain) containing regulatory protein and has been shown to be hyper-methylated in various cancers. Therefore, we studied the methylation status of TMS1 using a panel of colorectal cell lines and 15 CRC cases. Methylation status of the promoter region of TMS1 gene was determined using methylation specific PCR in colorectal cancer cell lines. Seven out of 13 colorectal cell lines showed to be methylated for TMS1 gene (54%). Initial analyses with 15 clinical colorectal cases demonstrated 53% methylation. Real time PCR and western bolt analysis was employed to assess the expression levels. 5-AZA-2′-deoxycytidine was used to demethylate colorectal cancer cell lines. Four out of 7 methylated colorectal cell lines were completely methylated and 3 out of 7 showed partial methylation for TMS1 gene resulting in loss of TMS1 expression. Treating methylated colorectal cell lines with the methyltransferase inhibitor, 5-aza-2’ deoxycytidine alone resulted in partial demethylation and re-expression of TMS1 gene, suggesting the role of methylation in silencing the gene. TMS1 gene has shown tumor suppressive effects after demethylation in thyroid cancer cell. Additionally the oncogenic role of TMS1 has been demonstrated in different cancers. We will further evaluate the role of TMS1 gene after demethylation for apoptosis. After demethylation of TMS1 gene with 5-aza-2’ deoxycytidine we will treat our colorectal cancer cell lines with increasing doses of TRAIL and will evaluate its response by Annexin/PI dual staining and western blot analysis. Our results demonstrated that TMSI gene is methylated in colorectal cancer cells and repression of methylation by 5-Aza-2′-deoxycytidine restored the expression of TMS1 gene. In conclusion, methylation of TMS1 may prove to be a useful prognostic marker and/or predictor of patient survival in colorectal and can be utilized for targeted therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4813. doi:10.1158/1538-7445.AM2011-4813
SULFONYLUREA-METFORMIN COMBINATION THERAPIES IN TYPE II DIABETES AND ASSOCIATED MORTALITY AND CARDIOVASCULAR RISK: A NATIONWIDE STUDY
Authors: Ulrik Madvig Mogensen, Charlotte Andersson, Emil Loldrup Fosbøl, Tina Kenn Schramm, Allan Vaag, Nicolai Scheller, Christian Torp-Pedersen, Gunnar Gislason, Lars Kober
Journal: Journal of the American College of Cardiology (2013)