tbuckley/cabot-search huggingface dataset:
P01.10 * METABOLIC CONDITIONS DETERMINE SENSITIVITY OF GLIOMA CELLS AGAINST EPIDERMAL-GROWTH FACTOR RECEPTOR (EGFR)-INHIBITION
Authors: I. A. Hartel, S. Wolking, C. Wanka, M. W. Ronellenfitsch, J. P. Steinbach, J. Rieger
Journal: Neuro-Oncology (2014)

The epidermal growth factor (EGFR) pathway is a frequently activated oncogenic pathway in glioblastoma. Nevertheless, the clinical results using EGFR inhibitors in glioma therapy are disappoiting. The reasons for the failure of these inhibitors are unclear but may involve factors of the tumor microenvironment. In the last years, metabolic processes are increasingly recognized as being highly relevant for tumor biology and therapy resistance. We therefore speculated that metabolic conditions commonly found in human glioma, limited glucose availability and hypoxia, may be responsible for resistance of glioma cells against EGFR inhibitors. We show that both, glucose and oxygen, profoundly influenced the response of glioma cells to EGFR inhibition by PD153035. Specifically, starvation conditions led to resistance against the EGFR inhibitor whereas high glucose amounts and normoxia sensitized glioma cells towards PD153035. As starvation conditions induce activation of the cellular energy sensor AMP-activated kinase (AMPK), we further investigated whether AMPK is involved in the observed modulation of EGFR toxicity by metabolic conditions. Indeed, low glucose and hypoxia stimulated AMPK activation in glioma cells. 2-deoxy-D-glucose (2DG), an inhibitor of glycolysis and AMPK activator, mimicked the effects of low glucose availability. Additionally, activation of AMPK by a specific small molecule inhibitor A769662 also blocked the toxicity of PD153035, whereas inhibition of AMPK by compound C increased cell death induced by the EGFR inhibitor and reverted the protective effect of 2DG and A769662. Similarly, short-hairpin (sh)-mediated suppression of AMPK expression antagonized the inhibitory effects of 2DG and A769662 towards PD153035. In summary, we found that starvation conditions mediate resistance against cell death induced by EGFR inhibition in glioma cells via activation of AMPK. These results provide one explanation for the low activity of EGFR inhibitors in clinical trials and suggest antagonism of AMPK as a promising approach to increase therapeutic efficacy of EGFR inhibitors.
Hemodialysis and Lupus Nephritis in MKSAP VII
Authors: ARNOLD R. EISER
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 October 1987Hemodialysis and Lupus Nephritis in MKSAP VIIARNOLD R. EISER, M.D., MARTIN S. NEFF, M.D., ROBERT F. SLIFKIN, M.D.ARNOLD R. EISER, M.D.Search for more papers by this author, MARTIN S. NEFF, M.D.Search for more papers by this author, ROBERT F. SLIFKIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-107-4-603_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The Medical Knowledge Self-Assessment Program (MKSAP) VII Syllabus (1) in the section on systemic lupus erythematosus on page 117 states that "Hemodialysis has little effect on the overall survival rate of patients with nephritis." Reference 31 (2) is the apparent source of this conclusion. The authors of that reference base this claim on the fact that in the second half of their study (1970 to 1976), when dialysis was generally more available, no decreases in deaths attributed to nephritis were noted. Such a claim from this data is unwarranted. Patients requiring hemodialysis are usually within days to...References1. Medical Knowledge Self-Assessment Program VII: Syllabus and Multiple-Choice Questions, Part 1. Philadelphia: American College of Physicians, 1985:117. Google Scholar2. ROSNERGINZLERDIAMOND SFH. Multicenter study of outcome in systemic lupus erythematosus. II. Causes of death. Arthritis Rheum. 1982;25:612-7. CrossrefMedlineGoogle Scholar3. CHEIGHSTENZELRUBIN JKA. Systemic lupus erythematosus in patients with chronic renal failure. Am J Med. 1983;75:602-6. CrossrefMedlineGoogle Scholar4. WELLERPORTSWARTZFERGUSONWILLIAMSJACOBS JFRCGJ. Analysis of survival of end-stage renal disease patients. Kidney Int. 1982;21:78-83. CrossrefMedlineGoogle Scholar5. HUTCHINSONTHOMASMACGIBBON TDB. Predicting survival in adults with end stage renal disease: an age equivalence index. Ann Intern Med. 1982;96:417-23. LinkGoogle Scholar6. COPLONDISKINPETERSEN NCJ. Long-term clinical course of systemic lupus erythematosus in end-stage renal disease. N Engl J Med. 1983;308:186-90. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ARNOLD R. EISER, M.D.; MARTIN S. NEFF, M.D.; ROBERT F. SLIFKIN, M.D.Affiliations: Mount Sinai Services City Hospital Center at Elmhurst Elmhurst, NY 11373 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1987Volume 107, Issue 4Page: 603-603KeywordsLupus erythematosusLupus nephritisMedical dialysisNephritis ePublished: 1 December 2008 Issue Published: 1 October 1987 PDF downloadLoading ...
Mechanisms of acquired resistance to tyrosine kinase inhibitors
Authors: Yi-fan Chen, Li-wu Fu
Journal: Acta Pharmaceutica Sinica B (2011)

In recent years, structural and functional studies reveal that tyrosine kinases (TKs) act as the essential components of signal transduction pathways that regulate cancer cell proliferation, apoptosis and angiogenesis, and therefore become potential targets for anticancer therapy. Most of TK inhibitors (TKIs) are small molecular and hydrophobic compounds, thus they can rapidly reach their specific intracellular targets and inhibit the activation of the related TKs. Unfortunately, accompanied with patients who gain great benefit of TKIs therapy, increasing evidences of acquired resistance to these agents have been documented. The unveiling point mutations within the kinase domain, gene amplification or overexpression, or modification of signaling pathway have been implicated in drug resistance. Additionally, overexpression of ABC transporters is likely to set stage for resistant development. In this review, we focus on the discussion of the molecular mechanisms of acquired resistance to TKIs therapy. The mechanistic understanding may help to put forward new hypotheses on drug development and design better therapies to overcome TKIs resistance.
Organized Premedical Education
Authors: E. GREY DIMOND
Journal: Annals of Internal Medicine (1968)

ExcerptPremedical education may be an overlooked key to several problems involving medicine.There are probably 60,000 premedical students in the United States. That is, at any one time, allowing for the usual 3 years of premedical work, there are 60,000 men and women who have at least declared their hope or have dreamed of entering medical school. Beyond these 60,000 are the unknown numbers who do not even dream of a career in the health field because it is unknown and even forbidding.These 3 years of premedicine are remarkably removed from medical education itself, and the contact between student...
Consolidation Radiation After Complete Remission in Hodgkin's Disease Following Six Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine Chemotherapy: Is There a Need?
Authors: S. Laskar, T. Gupta, S. Vimal, M.A. Muckaden, T.K. Saikia, S.K. Pai, K.N. Naresh, K.A. Dinshaw
Journal: Journal of Clinical Oncology (2003)

Combined modality treatment using multidrug chemotherapy (CTh) and radiotherapy (RT) is currently considered the standard of care in early stage Hodgkin's disease. Its role in advanced stages, however, continues to be debated. This study was aimed at evaluating the role of consolidation radiation in patients achieving a complete remission after six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy using event-free survival (EFS) and overall survival (OS) as primary end points.Two hundred and fifty-one patients with Hodgkin's disease attending the lymphoma clinic at the Tata Memorial Hospital (Mumbai, India) from 1993 to 1996 received induction chemotherapy with six cycles of ABVD after initial staging evaluation. A total of 179 of 251 patients (71%) achieved a complete remission after six cycles of ABVD chemotherapy and constituted the randomized population. Patients were randomly assigned to receive either consolidation radiation or no further therapy.With a median follow-up of 63 months, the 8-year EFS and OS in the CTh-alone arm were 76% and 89%, respectively, as compared with 88% and 100% in the CTh+RT arm (P =.01; P =.002). Addition of RT improved EFS and OS in patients with age < 15 years (P =.02; P =.04), B symptoms (P =.03; P =.006), advanced stage (P =.03; P =.006), and bulky disease (P =.04; P =.19).Our study suggests that the addition of consolidation radiation helps improve the EFS and OS in patients achieving a complete remission after six cycles of ABVD chemotherapy, particularly in the younger age group and in patients with B symptoms and bulky and advanced disease.
Abstract 1319: Establishment and characterization of fresh primary human colorectal tumor implants
Authors: Alexei Miagkov, Rajneesh Uzgare, Shaobin Zhong, Lisa Leary, Janine Ondrus, Thomas Hundley, Malathi Sathyamoorthy, Dhanrajan Tiruchinapalli, Nicole Todaro, Christina Griffin, Rao Mulpuri, Damon Hostin, Jeffery Otto, Hao Chen
Journal: Cancer Research (2012)

Abstract A personalized approach towards the therapy of colorectal carcinoma is critical for a successful outcome. In recent years, direct transfer xenograft models (or the “tumor graft”) have proven to be highly predictive and are being adapted in clinical practice. However, direct drug evaluation in tumor graft models for each individual patient is not feasible due to time and cost constraints. Predictive biomarker discovery is an extremely promising application of the tumor graft model, since the discovered biomarker signatures will direct therapy choice in a much broader patient population. In collaboration with the Catholic Health Initiatives Center for Translational Research we at Caliper Life Sciences have established a collection of tumor graft samples of primary human colorectal carcinomas. All samples were collected fresh from consenting patients following an IRB-approved protocol and implanted in vivo on the day of surgical tumor resection. Tumors were grafted either orthotopically or subcutaneously in female NIH-III mice. We present here the results of a comparative study of gene and protein expression profiles for the primary tumor (clinical samples) and the direct transfer xenografts. These data will be correlated with drug sensitivity profiles generated by using the same samples. The resulting data sets will be used to characterize predictive biomarker signatures that will be a valuable tool for selection of the most effective therapy tailored to the individual patient. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1319. doi:1538-7445.AM2012-1319
Cell calcium, cell injury and cell death.
Authors: B F Trump, I K Berezesky, T Sato, K U Laiho, P C Phelps, N DeClaris
Journal: Environmental Health Perspectives (1984)

The role of calcium in cell injury has been the subject of much recent investigation. The movement and redistribution of this cation from extra to intracellular compartments and the calcium shifts between intracellular compartments may well play a determinate role in the cell's reaction to injury. Therefore, data of such shifts and their correlation with morphological, biochemical and cytoskeletal studies will provide a better understanding of these processes. To study the effects of calcium regulation on acute lethal anoxic injury and the effects of inhibition of respiration with cyanide, three experimental systems were utilized: Ehrlich ascites tumor cells, isolated rabbit proximal tubule segments and suspended or cultured rat proximal tubule cells. Although our data showed no correlation between total cell calcium and cell death except in highly selected cell systems, they did indicate that calcium can be an important control variable. Therefore, massive increases in total cell calcium, as seen in Ca3(PO4)2 precipitation in mitochondria, must be a secondary event and represent the modern day equivalent of the classical dystrophic calcification seen by pathologists in the past. Although the involvement of extracellular calcium in cell death may well be significant in some cell types, redistribution of calcium within the intracellular compartments may play an even more important role.
CLINICAL BENEFIT AND COST-EFFECTIVENESS OF CARDIOVASCULAR DISEASE SCREENING IN HIV-INFECTED PATIENTS
Authors: Alexander Goehler, Julia Nolte, Anja Neumann, Sarah Mostardt, Jennifer M. Manne, Suhny Abbara, Thomas J. Brady, Udo Hoffmann, G. Scott Gazelle, Juergen Wasem, Till Neumann
Journal: Journal of the American College of Cardiology (2011)
THE TREATMENT OF PLACENTA PRAEVIA
Authors: M. PIERCE RUCKER
Journal: JAMA (1931)

Foster Kellogg<sup>1</sup>recently reviewed the changes that have taken place at the Boston Lying-In Hospital with reference to the treatment of placenta praevia. From 1895 to 1915 the method of treatment was version and immediate extraction. The maternal mortality was 19 per cent. From 1915 to 1919, when conservative delivery, bags or Braxton Hicks version and slow delivery had considerably displaced the older method, the mortality dropped to 6 per cent. In 1926, after five years more in which conservative methods had increased from 60 per cent to 76 per cent of the total cases, Kellogg came to the conclusion that all cases of central and partial placenta praevia are best treated by low classic cesarean section, regardless of the condition of the baby; that marginal placenta praevia is best treated by the Voorhees bag; that moribund or very sick patients with placenta praevia should be rested and quieted
Abstract PD6-7: The prognostic relevance of disseminated tumor cells (DTC) form the bone marrow (BM) in different molecular subtypes of primary breast cancer (PBC) patients
Authors: AD Hartkopf, F-A Taran, S Brucker, M Hahn, D Wallwiener, S Becker, E-F Solomayer, M Wallwiener, T Fehm
Journal: Cancer Research (2013)

Abstract Background: The presence of disseminated tumor cells (DTC) in the bone marrow (BM) of primary breast cancer (PBC) patients is associated with a worsened prognosis. This is the largest single-center study that determines the impact of DTC on disease free (DFS) and overall survival and compares it to predefined molecular subtypes of PBC. Methods: BM aspirates were collected from patients that underwent surgery for PBC at Tuebingen University Hospital, Germany between 01/2001 and 01/2013. DTC were identified by immunocytochemistry (pancytokeratin antibody A45/B3) and cytomorphology. Patients were divided into three subgroups based on immunohistochemical staining of the primary tumor: (1) hormone receptor-positive/HER2-negative (HR+/HER2-), (2) HER2-positive (HER2+), and (3) HR-negative/HER2-negative (HR-/HER2-) patients. The DTC-status was compared to other prognostic factors by use of the chi-squared test and survival was analyzed in an univariate (log-rank test) and multivariate analysis (cox regression). Results: 3,141 patients were available for this retrospective analysis. Of these 803 (26%) were DTC-positive. DTC-positivity was associated with larger tumors (p&amp;lt;0.001), positive lymph nodes (p = 0.001), ER-negative (p = 0.016) and PR-negative (p&amp;lt;0.001) patients. DTC-positive patients were at an increased risk of death (median OS of DTC- vs. DTC+ patients: n. r. (not reached) vs. 115 (95% CI: 113-118) months, p = 0.004) and disease relapse (median DFS was n. r. in either groups, p&amp;lt;0.001). Independent factors for OS / DFS were DTC-status, menopausal-status, tumor size, nodal-status, ER-status and PR-status / DTC-status, tumor size, nodal-status and ER-status. In the subgroup analysis (median OS was n. r. in either groups), the DTC-status had a significant impact on OS only within the HR+/HER2- subgroup (p = 0.004) and on DFS in the HR+/HER2- (p = 0.005) and the HER2+ subgroup (p&amp;lt;0.001). Conclusion: This study confirms the strong and independent prognostic value of DTC-determination in primary breast cancer patients. With respect to analysis of different molecular subtypes, the DTC-status was found to be of prognostic significance especially in HR+/HER2- patients. The DTC-status might help to identify HR+/HER2- patients that are at an increased risk of death or disease relapse and thus in need for an aggressive adjuvant treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD6-7.
Osteoporosis Treatment and Fracture Outcomes
Authors: Robert Lindsay
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
266. Gene Modification of T Antigen Presenting Cells for the Induction of Antitumor Immunity
Authors: Aaron E. Foster, Ann M. Leen, Timothy Lee, Juan Vera, Gianpietro Dotti, Cliona M. Rooney
Journal: Molecular Therapy (2006)

Introduction: Activated T cells proliferate rapidly, upregulate molecules important for antigen-presentation including CD80 and CD86 and can readily be modified to express neo-antigens by retrovirus transduction suggesting that T cells might be useful in immunotherapy protocols including cancer vaccines and adoptive T cell transfer. Here, we assess whether T antigen presenting cells (T- APC) are capable of inducing antitumor immune responses against two common tumor associated antigens, MAGE-3 and MART-1.
Critical Care Obstetrics
Authors: Stanley H. Tischler
Journal: JAMA (1991)

This book is written for all of us, the obstetrician, the gynecologist, the resident, the student, and yes, even the internist. It fits into that area between the textbook and the responsible individual who has to treat the pregnant patient, whether it be the attending or the resident. Our training today has made it possible for the obstetrician to manage many more of our high-risk patients. It has also taught us to know when to refer. It is necessary for the physician to be thoroughly familiar with all the cardiological, respiratory, and vascular changes that take place. It is absolutely necessary to understand and treat those physiological, pathological reactions that take place in our pregnant patients. It is also necessary to be aware of all the new approaches. In his foreword Dr Edwin Quilligan states that "this book will give you all the facts to be a good obstetrician. All
Sickle Cell Trait in The Nonblack Population
Authors: C. J. McGrew
Journal: JAMA (1975)

<h3>To the Editor.—</h3> Considerable interest continues, in the literature, on sickle cell trait in the nonblack population.<sup>1</sup>In a previous communication (224: 1762, 1973), I briefly summarized our experience in identifying sickle cell trait in nonblack Naval recruits. We have been screening all recruits (mainly from the eastern half of the United States) for sickle cell trait during the past 36 months (227:1405, 1974), and records have been reviewed for a 24-month interval. A total of 65,751 male and female recruits of all races were screened and those with positive screening tests for hemoglobin S were confirmed to be hemoglobin S-positive by hemoglobin electrophoresis. The incidence of the sickle cell trait among 7,986 black recruits remained at 8% with no significant difference between men and women. A total of 57,665 nonblack recruits (45,500 men and 12,165 women) were screened. Twenty-seven nonblack recruits (25 men and two women have been
Aberrant DNA Methylation Links Cancer Susceptibility Locus 15q25.1 to Apoptotic Regulation and Lung Cancer
Authors: Anupam Paliwal, Thomas Vaissière, Annette Krais, Cyrille Cuenin, Marie-Pierre Cros, David Zaridze, Anush Moukeria, Paolo Boffetta, Pierre Hainaut, Paul Brennan, Zdenko Herceg
Journal: Cancer Research (2010)

Nicotinic acetylcholine receptor (nAChR) genes form a highly conserved gene cluster at the lung cancer susceptibility locus 15q25.1. In this study, we show that the CHRNalpha3 gene encoding the nAChRalpha3 subunit is a frequent target of aberrant DNA hypermethylation and silencing in lung cancer, whereas the adjacent CHRNbeta4 and CHRNalpha5 genes exhibit moderate and no methylation, respectively. Treatment of cancer cells exhibiting CHRNalpha3 hypermethylation with DNA methylation inhibitors caused demethylation of the CHRNalpha3 promoter and gene reactivation. Restoring CHRNalpha3 levels through ectopic expression induced apoptotic cell death. Small hairpin RNA-mediated depletion of nAChRalpha3 in CHRNalpha3-expressing lung cancer cells elicited a dramatic Ca(2+) influx response in the presence of nicotine, followed by activation of the Akt survival pathway. CHRNalpha3-depleted cells were resistant to apoptosis-inducing agents, underscoring the importance of epigenetic silencing of the CHRNalpha3 gene in human cancer. In defining a mechanism of epigenetic control of nAChR expression in nonneuronal tissues, our findings offer a functional link between susceptibility locus 15q25.1 and lung cancer, and suggest nAChRs to be theranostic targets for cancer detection and chemoprevention.
TRANSCATHETER AORTIC VALVE IN VALVE REPLACEMENT FOR DEGENERATIVE AORTIC BIOPROSTHESIS: INITIAL RESULTS FROM THE STS/ACC TRANSCATHETER VALVE THERAPY REGISTRY
Authors: E. Murat Tuzcu, J. Matthew Brennan, Ralph Brindis, John Carroll, Fred Edwards, Frederick Grover, David Shahian, Eric Peterson, John Rumsfeld, David Holmes, Michael Mack
Journal: Journal of the American College of Cardiology (2014)
Efficacy and Safety of Budesonide and Formoterol in One Pressurized Metered-Dose Inhaler in Patients with Moderate to Very Severe Chronic Obstructive Pulmonary Disease
Authors: Donald P Tashkin, Stephen I Rennard, Paula Martin, Sulabha Ramachandran, Ubaldo J Martin, Philip E Silkoff, Mitchell Goldman
Journal: Drugs (2008)
Models for Delivering Survivorship Care
Authors: Kevin C. Oeffinger, Mary S. McCabe
Journal: Journal of Clinical Oncology (2006)

Survivors of adult cancer face lifetime health risks that are dependent on their cancer, cancer treatment exposures, comorbid health conditions, genetic predispositions, and lifestyle behaviors. Content, intensity, and frequency of health care that addresses these risks vary from survivor to survivor. The aims of this article are to provide a rationale for survivor health care and to articulate a taxonomy of models of survivor care that is applicable to both community practices and academic institutions.