tbuckley/cabot-search huggingface dataset:
Total androgen-receptor gene expression inhibitor therapy (TARGET): A phase II trial of neoadjuvant SAHA (S) followed prostatectomy for patients (pts) with high-risk prostate cancer (pc).
Authors: S. F. Slovin, S. Fine, P. Nelson, J. Steinbrecher, J. Eastham, J. Coleman, K. A. Touijer, B. S. Carver, V. Laudone, H. I. Scher
Journal: Journal of Clinical Oncology (2010)

e15133 Background: Androgen depletion (ADT) with a gonadotropin releasing hormone (GnRH) analog alone or with an anti- androgen does not ensure complete inhibition of signaling through the androgen receptor (AR). ADT with S (SAHA, suberoylanilide hydroxamic acid), an HDAC, can inhibit HSP90 resulting in loss of HSP90 binding to and degradation of client protein. HDAC inhibitors may reduce AR expression and sensitize pc cells to hormone antagonists. This phase II trial explores whether neoadjuvant ADT with S, can affect signaling through AR, increase the rate of pathologic response (p0), and determine the molecular pathways of response/resistance in pre/posttreatment blood and tissue, respectively, along with testosterone (T), its precursors, and AR target genes. Methods: Pts with newly diagnosed pc of any Gleason score were enrolled as long as they had an abnormal PSA and 1 of 3 or more cores containing ≥ 30% pc. Sixteen of 19 pts were accrued; 11 at MSKCC are reported. Each received S 400mg po daily for 6-8 weeks, bicalutamide 50mg for 4 weeks, and monthly GnRH followed by radical, laparoscopic or robotic prostatectomy. Results: Pretreatment median age was 64yrs, clinical stage T1c 6 pts [T1c-T3], Gleason score 3+4 [7-9], T 343ng/dl [140-521], and PSA 6.36ng/ml [3.87-27.64]. S was well-tolerated; 7 of 11 pts had grade 1 fatigue; 5 had grade 1 diarrhea. Post-surgical median pathologic stage was T2b (5 pts) [1-pT2+; 1-T2c; 2-T3a; 1-T3b; 1-T3bN1]. No pt achieved p0 but 10 of 11 pts achieved a PSA of <0.05 post T recovery with median durability of 87 days [17-379]. Post surgical median time to T recovery in 7 completed pts was 65.1 days [48-167]. Conclusions: The use of neoadjuvant S and a GnRH agonist as proof of concept did not result in a p0 in any of the 11 patients treated to date, however 10 pts had post surgical PSA nadirs of ≤ 0.05 which have been durable. Six additional pts are under treatment at this time. The impact on molecular and biologic markers within postsurgical tissue samples is ongoing. Supported by The Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium, and NCI P50-CA92629 SPORE in Prostate Cancer. No significant financial relationships to disclose.
Abstract P156: Health Care Professionals in Emergency Services and Hospitals Hesitate to Do CPR Because of Fear of Harming The Patient
Authors: Ewa Rosengren, Marja Mäkinen, Sari Ponzer, Jouni Kurola, Christer Axelsson, Lisa Kurland, Solveig Aune, Leila Niemi-Murola, Marja Sopanen, Erika Christensen, silje odegaard, Maaret Castrén
Journal: Circulation (2008)

Introduction: Preliminary studies showed that 41,4 % of nurses in a Finnish hospital hesitate to perform defibrillation because of fear of injuring the patient and 22,9% because the patient might die and the nurse would feel guilty. Of 80 paramedics in Oslo 39 % stated that deep compressions could result in serious patient injury. These attitudes can result in bad quality CPR starting with a delay. Hypothesis: We assessed the hypothesis that it is common among health care professionals to feel that CPR might harm the patient, to hesitate to do compressions and to hesitate to defibrillate. Methods: Valid questionnaires were send to nurses working in Kuopio University hospital in Finland, Uppsala Akademiska sjukhuset, Sahlgrenska hospital, Göteborg and Södersjukhuset, Stockholm in Sweden and to paramedics working in Vantaa and Kuopio in Finland, Århus in Denmark and Gothenburg in Sweden. All together 811 nurses and 216 paramedics answered the questions about background data and attitudes towards resuscitation, defibrillation and guidelines. Results: Of paramedics 60% felt that deep compressions could injure the patient and 32% felt the harm caused is bigger than the benefit of compressions. When arriving to the patient 21.5% prioritize intubation and infusion over everything else. Of the nurses 16% hesitate to start CPR because of anxiety, 26% did not feel competent to defibrillate and 21% hesitate to defibrillate because they fear to harm the patient. Still 54.2% had had CPR training at their hospital during the last six months. Nurses that hesitate to start resuscitation felt significantly more often that only doctors should defibrillate. This will delaye defibrillation and lives will be lost. Conclusion: Major changes has to be done in training programs for CPR to ensure better confidence in performing the different tasks involved in resuscitation. Today too many health care professionals feel that CPR might do more harm than good.
Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the Group d'Etudes de la Greffe de Moelle Osseuse [see comments]
Authors: D Blaise, D Maraninchi, E Archimbaud, J Reiffers, A Devergie, JP Jouet, N Milpied, M Attal, M Michallet, N Ifrah
Journal: Blood (1992)
Frequent BRCA1/2 and BARD1 germline mutations in triple-negative breast cancer patients.
Authors: Jacques De Greve, Sylvia De Brakeleer, Christine Desmedt, Sofie Joris, Christos Sotiriou, Martine J. Piccart-Gebhart, Ingrid Pauwels, Erik Teugels
Journal: Journal of Clinical Oncology (2014)

1107 Background: Triple negative breast cancer (TNBC) accounts for 10-20% of all breast cancers and conventional chemotherapy is the only effective systemic treatment. Germline BRCA1/2 mutations are found in approximately 15% of TNBC patients. PARP inhibitors are being investigated in this subset of patients. In the past we have documented pathogenic mutations in BARD1, a BRCA1 interacting protein, in families at high risk for breast cancer. In the current study we have analyzed the germline DNA from 61 estrogen receptor negative patients included in the TOP trial for the presence of mutations in the BRCA1, BRCA2 and BARD1 gene. Methods: Patients signed a separate informed consent for the current retrospective genetic analysis and were offered oncogenetic counseling. Genetic variants were detected by High Resolution Melting curve Analysis (HRMA) and confirmed by Sanger sequencing. In Silico tools were used to further characterize these variants. Results: Of the 61 ER- patients 42 were TNBC and 19 were HER2-positive. BRCA1/2 mutations were found in 8/42 (19%) TNBC, but none in the ER-/HER2 cohort. We also found four (10%) strong candidate pathogenic mutations in the BARD1 gene, including two protein truncating mutations (p.Gln564X and p.Arg641X), while no such mutations were found in 245 control samples. Only two BARD1 truncating mutations have been reported worldwide earlier in germline DNA from breast cancer patients, including a case we identified in one out of 196 high risk breast cancer families. Our data suggest that TNBC patients are enriched for pathogenic BARD1 mutations as compared to the incidence in control samples and in high breast cancer risk families. Additional clinical-genomic correlations are being investigated. Conclusions: Almost one third of TNBC (29%) have a BRCA pathway mutation. These patients should become eligible for exploring the efficacy of PARP inhibitors.
Modern Trends in Physiology and Biochemistry: Woods Hole Lectures Dedicated to the Memory of Leonor Michaelis
Authors: E. S. Guzman Barron
Journal: JAMA (1952)

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 2778: Lapatinib inhibits CIP2A/PP2A/p-Akt signaling and induces apoptosis in triple negative breast cancer cells
Authors: Ling-Min Tseng, Chun-Yu Liu, Chia-Jung Hsu, Duen-Shian Wang, Jung-Chen Su, Chung-Wai Shiau, Kuen-Feng Chen
Journal: Cancer Research (2014)

Abstract Background: Triple-negative breast cancer (TNBC) is a subtype with aggressive behaviors and poor prognosis. Our previous study has shown that CIP2A, cancerous inhibitor of PP2A, may be a novel target in breast cancer cells (Breast Cancer Research 2012). Here, we tested efficacy of lapatinib, a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways, in a panel of TNBC cell lines and examined the drug mechanism. Methods: TNBC cell lines (HCC-1937, MDA-MB-468, MDA-MB-231) were used for in vitro studies. Apoptosis was examined by both flow cytometry and Western blot. Signal transduction pathways in cells were assessed by Western Blot. Quantitative RT-PCR was used for assessing gene transcription. In vivo efficacy of lapatinib was tested in nude mice with breast cancer xenografts. Results: Lapatinib showed anti-proliferative effect in HCC 1937, MDA-MB-468, and MDA-MB-231 cell lines. Lapatinib induced significant apoptosis in dose-dependent and time-dependent manners in the three tested TNBC cell lines. Importantly, lapatinib inhibited CIP2A and p-Akt in a dose-dependent manner in all sensitive TNBC cells. Overexpression of CIP2A protected MDA-MB-468 cells from lapatinib-induced apoptosis. In addition, lapatinib increased PP2A activity (in relation to CIP2A inhibition) in sensitive cells. Moreover, lapatinib-induced apoptosis as well as lapatinib-induced p-Akt downregulation, was attenuated by PP2A antagonist okadaic acid in sensitive cells. Lapatinib downregulated CIP2A mRNA. Importantly, lapatinib showed anti-tumor activity in mice bearing MDA-MB-468 xenograft tumors, and downregulated CIP2A as well as p-Akt in these xenografted tumors. Conclusions: Inhibition of CIP2A determines the effects of lapatinib-induced apoptosis in TNBC cells. Our data suggest that in addition to a dual tyrosine kinase inhibitor of HER2/neu and EGFR, lapatinib can be a novel CIP2A inhibitor and that CIP2A can be a potential target for TNBC. (Supported by Yen Tjing Ling Medical Foundation; NSC 101-2325-B-075-006, NSC-102-2325-B-075-006 and NSC 100-2325-B-010-007; and V100-D-005-4) Citation Format: Ling-Min Tseng, Chun-Yu Liu, Chia-Jung Hsu, Duen-Shian Wang, Jung-Chen Su, Chung-Wai Shiau, Kuen-Feng Chen. Lapatinib inhibits CIP2A/PP2A/p-Akt signaling and induces apoptosis in triple negative breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2778. doi:10.1158/1538-7445.AM2014-2778
Reporter Gene Imaging Following Percutaneous Delivery in Swine
Authors: Martin Rodriguez-Porcel, Todd J. Brinton, Ian Y. Chen, Olivier Gheysens, Jennifer Lyons, Fumiaki Ikeno, Jürgen K. Willmann, Lily Wu, Joseph C. Wu, Alan C. Yeung, Paul Yock, Sanjiv Sam Gambhir
Journal: Journal of the American College of Cardiology (2008)
Differences Between Bilateral Adrenal Incidentalomas and Unilateral Lesions
Authors: Jesse D. Pasternak, Carolyn D. Seib, Natalie Seiser, J. Blake Tyrell, Chienying Liu, Robin M. Cisco, Jessica E. Gosnell, Wen T. Shen, Insoo Suh, Quan-Yang Duh
Journal: JAMA Surgery (2015)

Adrenal incidentalomas are found in 1% to 5% of abdominal cross-sectional imaging studies. Although the workup and management of unilateral lesions are well established, limited information exists for bilateral incidentalomas.To compare the natural history of patients having bilateral incidentalomas with those having unilateral incidentalomas.Retrospective analysis of a prospective database of consecutive patients referred to an academic multidisciplinary adrenal conference. The setting was a tertiary care university hospital among a cohort of 500 patients with adrenal lesions between July 1, 2009, and July 1, 2014.Prevalence, age, imaging characteristics, biochemical workup, any intervention, and final diagnosis.Twenty-three patients with bilateral incidentalomas and 112 patients with unilateral incidentalomas were identified. The mean age at diagnosis of bilateral lesions was 58.7 years. The mean lesion size was 2.4 cm on the right side and 2.8 cm on the left side. Bilateral incidentalomas were associated with a significantly higher prevalence of subclinical Cushing syndrome (21.7% [5 of 23] vs 6.2% [7 of 112]) (P = .009) and a significantly lower prevalence of pheochromocytoma (4.3% [1 of 23] vs 19.6% [22 of 112]) (P = .003) compared with unilateral lesions, while rates of hyperaldosteronism were similar in both groups (4.3% [1 of 23] vs 5.4% [6 of 112]) (P > .99). Only one patient with bilateral incidentalomas underwent unilateral resection. The mean follow-up was 4 years (range, 1.2-13.0 years). There were no occult adrenocortical carcinomas.Bilateral incidentalomas are more likely to be associated with subclinical Cushing syndrome and less likely to be pheochromocytomas. Although patients with bilateral incidentalomas undergo a workup similar to that in patients with unilateral lesions, differences in their natural history warrant a greater index of suspicion for subclinical Cushing syndrome.
Abstract 1762: Phosphodiesterase 10, a novel target for colorectal cancer therapeutics
Authors: Kevin J. Lee, Nan Li, Xi Chen, Bing Zhu, Larry Yet, Gary Piazza
Journal: Cancer Research (2014)

Abstract Phosphodiesterase 10 (PDE10) is a newly characterized PDE isozyme that is expressed in regions of the brain affecting cognition and psychomotor activity. Inhibitors are currently being developed for the treatment of schizophrenia and Huntington's disease, one of which, Pf-2545920 (MP-10), is in clinical trials. Although PDE10 is not expressed in most peripheral tissues, we recently found high levels in colon tumor cells compared with normal colonocytes and that genetic silencing by siRNA selectively suppressed colon tumor cell growth. These observations suggest that PDE10 may represent a novel anticancer target. Pf-2545920 was found to selectively inhibit colon tumor cell growth. Here we show that PDE10 knockdown reduced the sensitivity of colon tumor cells to Pf-2545920. Consistent with the ability of PDE10 to degrade cGMP and cAMP, Pf-2545920 activated both PKG and PKA as determined using site-specific phospho-VASP antibodies. Treatment of colon tumor cells with Pf-2545920 induced caspase activation as well as cytotoxicity. A novel PDE10 inhibitor, MCI-030, was found to potently inhibit colon tumor cell lines with IC50 values in the 0.3μM range without significantly affecting the growth of normal colonocytes. MCI-030 appears to exhibit selectivity for cGMP PDE10 signaling over cAMP shown by the activation of PKG but not PKA at doses that match those which inhibit growth. PDE10 knockdown cells were appreciably less sensitive to MCI-030 as well. These findings support a novel role of PDE10 as a therapeutic target for the treatment or prevention of colorectal cancer. Citation Format: Kevin J. Lee, Nan Li, Xi Chen, Bing Zhu, Larry Yet, Gary Piazza. Phosphodiesterase 10, a novel target for colorectal cancer therapeutics. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1762. doi:10.1158/1538-7445.AM2014-1762
Neutrophilic-chronic myeloid leukemia: a distinct disease with a specific molecular marker (BCR/ABL with C3/A2 junction) [see comments]
Authors: F Pane, F Frigeri, M Sindona, L Luciano, F Ferrara, R Cimino, G Meloni, G Saglio, F Salvatore, B Rotoli
Journal: Blood (1996)
Abstract 17013: Post-traumatic Stress Disorder is Associated with Adverse Non-Linear Heart Rate Variability in Veteran Twins
Authors: Danesh K Kella, Rachel Lampert, Forrester Lee, Jack Goldberg, Douglas Bremner, Viola Vaccarino, Amit J Shah
Journal: Circulation (2014)

BACKGROUND: Veterans with post-traumatic stress disorder (PTSD) have higher risk of coronary heart disease (CHD) incidence and mortality. Psychological conditions may have an adverse effect on the autonomic nervous system, and may in part have genetic origins. Novel non-linear measures of heart rate variability (HRV), such as fractal dimension (FD) and power law slope have been associated with mortality and may signify autonomic dysfunction. We hypothesized that PTSD is associated with reduced FD and increased power law slope, suggesting higher mortality risk. METHODS: FD and power law slope were measured from 24-hour Holter recordings in 416 predominantly healthy middle-aged male twins from the Vietnam Era Twin Registry. Current (symptoms within the past month) and remitted (past history of) PTSD were measured using the Structured Clinical Interview for Psychiatry Disorders. Mixed-effect regression models were used to adjust for twin clustering and account for genetic/familial influences. RESULTS: The mean age was 56 ± 3 years, 35 had current PTSD, and 46 had remitted PTSD. In models that analyzed twins as individuals, current PTSD was significantly associated with 22% reduced FD and 18% increased power law slope. This association persisted for power law slope after adjustment for traditional risk factors, lifestyle factors, depression, and anti-depressant medication use (table). After controlling for genetic/familial factors by comparing twin brothers discordant for current PTSD within pairs (20 pairs), both measures remained significantly associated with current PTSD. Remitted PTSD did not influence HRV measures. No interaction by zygosity was found. CONCLUSIONS: Vietnam era veterans with PTSD have reduced FD and increased power law slope persisting after multivariable adjustment. This suggests that autonomic mechanisms, independent of genetic and familial effects, may contribute to increased CHD and mortality in veterans with PTSD.
ON MISTAKING OTHER DISEASES FOR ACUTE CORONARY THROMBOSIS
Authors: James B. Herrick
Journal: Annals of Internal Medicine (1938)

Article1 June 1938ON MISTAKING OTHER DISEASES FOR ACUTE CORONARY THROMBOSISJAMES B. HERRICK, M.D., F.A.C.P.JAMES B. HERRICK, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-11-12-2079 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWhen a previously misunderstood or overlooked disease has been shown to be common, when its symptoms are first described, for a time it is likely to be a front page medical news item. It is a best seller. A good illustration is afforded by appendicitis. The classic paper of Reginald Fitz in 1886 stirred surgeons and internists to a more accurate understanding of this condition, its frequency, diagnosis and—after some prolonged and lively discussion—its essentially surgical character from the standpoint of treatment. For a time there was a tendency to regard too readily nearly every acute pain in the abdomen...Bibliography1. BARNES AR: Electrocardiographic pattern observed following acute coronary occlusion complicated by pericarditis, Am. Heart Jr., 1934, ii, 734-741. CrossrefGoogle Scholar2. WOOD P: Changes of a T2 pattern in pericardial lesions and in stab wounds of the heart, Lancet, October 2, 1937. CrossrefGoogle Scholar3. WHITE PD: The acute cor pulmonale, ANN. INT. MED., 1935, ii, 115-122. Google Scholar4. BARNES AR: Pulmonary embolism Jr. Am. Med. Assoc., 1937, cix, 1347-1353. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Chicago, Illinois*Read before the American College of Physicians, New York, N. Y., April 5, 1938. Nextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDie Coronarerkrankungen. Coronarinsuffizienz, Angina pectoris und HerzinfarktTHE INDUSTRIAL ASPECTS OF CARDIAC INFARCTION*G. F. STRONG, M.D., F.A.C.P., F.R.C.P. (C)An intimate account of my early experience with coronary thrombosisCentral nervous system manifestations in acute myocardial infarction 1 June 1938Volume 11, Issue 12Page: 2079-2085KeywordsAbdominal painAppendicitisSurgeonsThrombosis ePublished: 1 December 2008 Issue Published: 1 June 1938 Copyright & PermissionsCopyright, 1938, by The American College of PhysiciansPDF downloadLoading ...
Abstract 17100: CaMKII Activity Modulates Basal Sarcoplasmic Reticulum Ca2+ Cycling to Drive Normal Automaticity of Sinoatrial Node Cells
Authors: Tatiana M Vinogradova, Syevda Sirenko, Yue Li, Harold Spurgeon, Edward G Lakatta
Journal: Circulation (2011)

Spontaneous beating of rabbit sinoatrial node cells (SANC) is linked to rhythmic, sarcoplasmic reticulum (SR) generated, submembrane local Ca2+ releases (LCR) during diastolic depolarization (DD). ...
An anti-CD19 antibody inhibits the interaction between P-glycoprotein (P-gp) and CD19, causes P-gp to translocate out of lipid rafts, and chemosensitizes a multidrug-resistant (MDR) lymphoma cell line
Authors: Maria-Ana Ghetie, Radu Marches, Stephanie Kufert, Ellen S. Vitetta
Journal: Blood (2004)
Spring Landscape in Deer Grove
Authors: M. Therese Southgate
Journal: JAMA (1999)

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