tbuckley/cabot-search huggingface dataset:
In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission.
Authors: A S Stein, M R O'Donnell, A Chai, G M Schmidt, A Nademanee, P M Parker, E P Smith, D S Snyder, A Molina, D E Stepan, R Spielberger, G Somlo, K A Margolin, N Vora, J Lipsett, J Lee, J Niland, S J Forman
Journal: Journal of Clinical Oncology (1996)

PURPOSE To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.
Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial
Authors: Louis Fehrenbacher, Alexander Spira, Marcus Ballinger, Marcin Kowanetz, Johan Vansteenkiste, Julien Mazieres, Keunchil Park, David Smith, Angel Artal-Cortes, Conrad Lewanski, Fadi Braiteh, Daniel Waterkamp, Pei He, Wei Zou, Daniel S Chen, Jing Yi, Alan Sandler, Achim Rittmeyer
Journal: The Lancet (2016)
Frequent dosing and GPNMB expression with CDX-011 (CR011-vcMMAE), an antibody-drug conjugate (ADC), in patients with advanced melanoma.
Authors: O. Hamid, M. Sznol, A. C. Pavlick, H. M. Kluger, K. B. Kim, P. D. Boasberg, R. Simantov, T. A. Davis, E. Crowley, P. Hwu
Journal: Journal of Clinical Oncology (2010)

8525 Background: CDX-011 is an ADC consisting of the potent cellular toxin MMAE conjugated to a fully human monoclonal antibody (CR011) to GPNMB, a novel glycoprotein frequently expressed in melanoma. CDX-011 potently inhibits the growth of a variety of melanoma cell lines in vitro and shows significant antitumor activity in melanoma xenograft mouse models. Methods: This phase I/II study in patients with unresectable, stage III/IV melanoma evaluated CDX-011, given once every 3 weeks (q3w), in a standard 3+3 dose-escalation (DE) and a phase II expansion at the maximum tolerated dose (MTD) with primary activity endpoint of overall response rate (ORR) (P0 = ≤5%; P1 = ≥20%; α = β = 0.10). Subsequently, more frequent dosing schedules (once weekly for two of three weeks [q2/3w] and weekly [qw]) were evaluated. Results: Enrollment is complete (n = 117; male = 64%; median age = 62y; stage IV = 89%; M1c = 50%). For q3w, q2/3w, and qw schedules, respectively, MTDs were 1.88, 1.5, and 1.0 mg/kg. At the MTDs, the most frequent treatment-related adverse events included rash, fatigue, alopecia, pruritus, diarrhea, and neuropathy. 33/40 (83%) with tumor sample analyzed by immunohistochemistry to date were positive for GPNMB expression. Data for MTDs are shown in the Table. Conclusions: CDX-011, dosed either q3w, q2/3w or qw, is active in patients with advanced melanoma. The primary activity endpoint has been met; ORR of 15%-20% is promising. GPNMB was frequently expressed; preliminary data suggest increased PFS in patients with high GPNMB expression. Further development of CDX-011 in melanoma is warranted. N Karnofsky performance status = 100% M1c disease ORR PR + SD ≥ 12 weeks Median PFS (months) q3w (phase II) 36 72% 56% 5/34 (15%)* 20/34 (59%) 3.9 qw and q2/3w 21 38% 76% 4/21 (19%)** 7/21 (33%) 1.4*** Strongly positive (3+, ≥90%) GPNMB expression (q3w, q2/3w, and qw) 7 57% 71% 1/7 (14%) 6/7 (86%) 7.7**** * Including 1 unconfirmed PR (96% tumor reduction). ** Including 1 unconfirmed PR. *** 2 patients ongoing. **** Mean PFS is displayed. Median PFS of 11.7 months was not considered representative due to small sample size. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celldex Therapeutics Bristol-Myers Squibb, Celldex Therapeutics Celldex Therapeutics Bristol-Myers Squibb Bristol-Myers Squibb, Celldex Therapeutics
Clinicopathological and Survival Analysis of Japanese Patients with Resected Non-Small-Cell Lung Cancer Harboring NKX2-1, SETDB1, MET, HER2, SOX2, FGFR1, or PIK3CA Gene Amplification
Authors: Yusuke Inoue, Shun Matsuura, Nobuya Kurabe, Tomoaki Kahyo, Hiroki Mori, Akikazu Kawase, Masato Karayama, Naoki Inui, Kazuhito Funai, Kazuya Shinmura, Takafumi Suda, Haruhiko Sugimura
Journal: Journal of Thoracic Oncology (2015)
Health effects of outdoor air pollution. Part 2. Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society.
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Although sources of airborne lead have been reduced over the last decade, particularly with the use of lead-free gasoline, there are still relatively high levels of lead contamination in soils and the residential housing stock built before the 1970s, which pose a risk for continued direct exposure through ingestion or airborne exposure if resuspended. Neurobehavioral effects, particularly as a result of early childhood exposures, have been documented, and, because of the way lead is stored in the body, late effects can become manifest during periods of high bone turnover (e.g., pregnancy, lactation, or hyperthyroidism). Late consequences not only relate to lead excretion affecting the fetus or newborn but also appear to be associated with hypertension in adults. Control of exposure in early life is an important component of appropriate preventive action.
Annals On Being a Doctor Story Slam - Shackled But Not Silenced
Authors: Charmaine S. Wright
Journal: Annals of Internal Medicine (2016)

Web Exclusives19 January 2016Annals On Being a Doctor Story Slam - Shackled But Not SilencedFREECharmaine S. Wright, MD, MSHPCharmaine S. Wright, MD, MSHPFrom University of Pennsylvania, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/V15-0016 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals On Being a Doctor Story Slam - Shackled Not Silenced This story, “Shackled Not Silenced," by Dr. Charmaine S. Wright, is from the Annals On Being a Doctor Story Slam held on 18 November 2015 in Philadelphia, with support from the Josiah Macy Jr. Foundation. (Duration 6:24)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals On Being a Doctor Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From University of Pennsylvania, Philadelphia, Pennsylvania.Note: This story is from the Annals On Being a Doctor Story Slam held on 18 November 2015 in Philadelphia, with support from the Josiah Macy Jr. Foundation.Corresponding Author: Charmaine S. Wright, MD, MSHP, University of Pennsylvania, 23 Guardian Drive, Blockley Hall, Philadelphia, PA 19104; e-mail, [email protected]med.upenn.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 January 2016Volume 164, Issue 2Page: SS5 ePublished: 19 January 2016 Issue Published: 19 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.Loading ...
Growth inhibitory effect of anti PAR antibodies on PAR-overexpressing tumor cells
Authors: O. Platica, S. Gasic, E. Ivan, A. Ionescu, J. F. Holland, M. Platica
Journal: Journal of Clinical Oncology (2005)

2559 Background: PAR (Prostate Androgen Regulated) is a gene expressed in all normal tissues and is overexpressed in most tumors studied compared to their normal counterparts. The gene is located on chromosome 1 in Epidermal Differentiation Complex. It encodes a 146 aminoacid (aa) transmembrane protein. PAR gene behaves like a protooncogene as revealed by transfection of gene encoding sequence in sense and antisense orientation in NIH3T3 and DU145 cells, respectively. The PAR cellular function is not fully understood but preliminary data suggest that the gene is involved in cell cycle. Methods: A polyclonal antibody (Ab) was raised against a 20 aa peptide (P1) selected from the amino terminal region of deduced PAR sequence. The antibody was affinity purified. The effect of anti PAR antibody on the proliferation of MCF7 breast cancer cell line and DU145 androgen resistant prostate cancer cell line was studied in vitro by cell counts and MTT assay, and in vivo, on the growth of DU145 tumors in SCID mice, treated intraperitoneal twice a week with 50ug Ab, for 17 days. Apoptosis was assessed by flow cytometry using Annexin V-FITC. BCL2, BAX and caspase 3 expression levels were determined by Western blots. Results: Anti PAR Ab is a highly specific antibody which reacted only with the peptide P1, the PAR recombinant protein prepared in E coli, and with lysates from various cell lines. The Ab activity was completely blocked by treatment with the peptide P1. Anti PAR Ab inhibited the proliferation of DU145 and MCF7 tumor cells in vitro in a dose and time dependent manner. At concentration of 9ug Ab/ml only about 10% of the cells were still alive after 5 days, in comparison with controls treated with IgG from normal rabbits. The Ab did not have any effect on MCF10F normal breast cells treated in a similar way. The anti PAR Ab also inhibited significantly the growth of DU145 tumor grafted in CB17 SCID mice. The mechanism of this inhibition involves apoptosis associated with Bcl 2 down regulation and caspase 3 over expression. Conclusions: the data presented here suggest that the anti PAR Ab maybe a potential treatment for breast and prostate cancers. No significant financial relationships to disclose.
Abstract 15269: Automated Quantification of Mitral Regurgitation by 3D PISA Using Real Time Three Dimensional Volume Echocardiography: Comparisons with 2D PISA and Magnetic Resonance Imaging
Authors: Ran Heo, Hyuk-Jae Chang, Jin-Kyung Lee, Ran-Young Song, Hee-Jung Jung, Young-Jin Kim, Chi Young Shim, Saurabh Datta, Geu-Ru Hong, Jong-Won Ha, Namsik Chung
Journal: Circulation (2012)

Background: Accurate assessment of mitral regurgitation (MR) severity is the key for the clinical decision-making to optimize patient outcomes. Recent advances in real-time 3D echocardiography prov...
Parkinson disease and multiple sclerosis are not associated with autoantibodies against structural proteins of the dermal-epidermal junction
Authors: A. Recke, A. Oei, F. Hübner, K. Fechner, J. Graf, J. Hagenah, C. May, D. Woitalla, A. Salmen, D. Zillikens, R. Gold, W. Schlumberger, E. Schmidt
Journal: British Journal of Dermatology (2016)
Coronary Flow Reserve and Microcirculatory Resistance in Patients With Intermediate Coronary Stenosis
Authors: Joo Myung Lee, Ji-Hyun Jung, Doyeon Hwang, Jonghanne Park, Yongzhen Fan, Sang-Hoon Na, Joon-Hyung Doh, Chang-Wook Nam, Eun-Seok Shin, Bon-Kwon Koo
Journal: Journal of the American College of Cardiology (2016)
Darzi calls for overhaul of safety incident reporting
Authors: Jacqui Wise
Journal: BMJ (2016)

The systems for reporting safety incidents in the NHS need to be overhauled, according to two reports led by former health minister Ari Darzi.1 2

The report Patient Safety 2030 said that as little as 5% of patient safety incidents are reported. It calls on healthcare providers to cultivate an open and transparent culture, as staff are often put off reporting errors for fear of being blamed.

The report, written by researchers from Imperial College London, said that a demographic shift towards an older …
Antibodies to infliximab in Remicade-treated rheumatic patients show identical reactivity towards biosimilars
Authors: M Begoña Ruiz-Argüello, Ainara Maguregui, Ainhoa Ruiz del Agua, Dora Pascual-Salcedo, Ana Martínez-Feito, Teresa Jurado, Chamaida Plasencia, Alejandro Balsa, Francisca Llinares-Tello, José Rosas, Nerea Torres, Antonio Martínez, Daniel Nagore
Journal: Annals of the Rheumatic Diseases (2016)

The aim of this study was to determine whether antibodies to infliximab (IFX) in Remicade-treated patients cross-react with the biosimilar CT-P13.250 consecutive patients with rheumatic diseases under Remicade and 77 controls were retrospectively selected for the study. Anti-IFX antibodies at drug through levels were measured in parallel with three different bridging ELISA assays: Promonitor-ANTI-IFX kit, which uses Remicade to detect antibodies, and two more assays that use either Inflectra or Remsima with the same format. Correlation and association between each assay was studied.50.4% of patients were tested positive with Promonitor-ANTI-IFX. All were antibodies to IFX (ATI)-positive when either Inflectra or Remsima assays were used. In all comparisons positive and negative percentage agreements were 100%, and correlation coefficients were ≥0.995. No differences between rheumatoid arthritis and spondyloarthritis, or between concomitant immunosuppressives, were observed.Anti-IFX antibodies of Remicade-treated patients cross-react with either Inflectra or Remsima. Although additional epitopes may be present in the biosimilar, results suggest that epitopes influencing the immune response to IFX are also present in the biosimilar. Antibody-positive patients treated with Remicade should not be switched to the biosimilar, since antibodies will interact with the new drug and potentially lead to loss of response. This finding supports the utility for therapeutic drug monitoring before a switching strategy is considered.
TOXIC DRUGS AND ACCIDENTS
Journal: JAMA (1949)

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
Mutant p53 Promotes Epithelial Ovarian Cancer by Regulating Tumor Differentiation, Metastasis, and Responsiveness to Steroid Hormones
Authors: Yi A. Ren, Lisa K. Mullany, Zhilin Liu, Alan J. Herron, Kwong-Kwok Wong, JoAnne S. Richards
Journal: Cancer Research (2016)

Mutations in the tumor protein p53 (TP53) are the most frequently occurring genetic events in high-grade ovarian cancers, especially the prevalence of the Trp53(R172H)-mutant allele. In this study, we investigated the impact of the Trp53(R172H)-mutant allele on epithelial ovarian cancer (EOC) in vivo We used the Pten/Kras(G12D)-mutant mouse strain that develops serous EOC with 100% penetrance to introduce the mutant Trp53(R172H) allele (homolog for human Trp53(R172H)). We demonstrate that the Trp53(R172H) mutation promoted EOC but had differential effects on disease features and progression depending on the presence or absence of the wild-type (WT) TP53 allele. Heterozygous WT/Trp53(R172H) alleles facilitated invasion into the ovarian stroma, accelerated intraperitoneal metastasis, and reduced TP53 transactivation activity but retained responsiveness to nutlin-3a, an activator of WT TP53. Moreover, high levels of estrogen receptor α in these tumors enhanced the growth of both primary and metastatic tumors in response to estradiol. Ovarian tumors homozygous for Trp53(R172H) mutation were undifferentiated and highly metastatic, exhibited minimal TP53 transactivation activity, and expressed genes with potential regulatory functions in EOC development. Notably, heterozygous WT/Trp53(R172H) mice also presented mucinous cystadenocarcinomas at 12 weeks of age, recapitulating human mucinous ovarian tumors, which also exhibit heterozygous TP53 mutations (∼50%-60%) and KRAS mutations. Therefore, we present the first mouse model of mucinous tumor formation from ovarian cells and supporting evidence that mutant TP53 is a key regulator of EOC progression, differentiation, and responsiveness to steroid hormones. Cancer Res; 76(8); 2206-18. ©2016 AACR.
Vitamin D During Pregnancy and Multiple Sclerosis
Authors: Benjamin M. Greenberg
Journal: JAMA Neurology (2016)

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 Neurology 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 Neurology journal
The changing landscape of biosimilars in rheumatology
Authors: Thomas Dörner, Vibeke Strand, Paul Cornes, João Gonçalves, László Gulácsi, Jonathan Kay, Tore K Kvien, Josef Smolen, Yoshiya Tanaka, Gerd R Burmester
Journal: Annals of the Rheumatic Diseases (2016)

Biosimilars remain a hot topic in rheumatology, and some physicians are cautious about their application in the real world. With many products coming to market and a wealth of guidelines and recommendations concerning their use, there is a need to understand the changing landscape and the real clinical and health-economic potential offered by these agents. Notably, rheumatologists will be at the forefront of the use of biosimilar monoclonal antibodies/soluble receptors. Biosimilars offer cost savings and health gains for our patients and will play an important role in treating rheumatic diseases. We hope that these lower costs will compensate for inequities in access to therapy based on economic differences across countries. Since approved biosimilars have already demonstrated highly similar efficacy, it will be most important to establish pharmacovigilance databases across countries that are adequate to monitor long-term safety after marketing approval.
Abstract 14201: Vasopressin Type 1a Receptor Deficiency Prevents the Onset of Heart Failure: Possible Link with Myocardial Fibrosis
Authors: Toru Takase, Yoshitaka Iwanaga, Yodo Tamaki, Hanako Morooka, Fujiki Hiroyuki, Taka-aki Koshimizu, Gozoh Tsujimoto, Shunichi Miyazaki
Journal: Circulation (2010)

Background: Plasma arginine vasopressin (AVP) levels are increased and correlated with adverse outcome in heart failure (HF). Among the three distinct receptor subtypes: V1a, V1b, and V2 receptors,...
Long-term neurotoxicity in patients treated with cisplatin, vinblastine, and bleomycin for metastatic germ cell cancer.
Authors: S W Hansen, S Helweg-Larsen, W Trojaborg
Journal: Journal of Clinical Oncology (1989)

Thirty patients treated for germ cell cancer with six cycles of cisplatin, vinblastine, and bleomycin participated in a follow-up examination of neurotoxicity 49 to 106 months after treatment. Of these, 22 patients (73%) had sensory loss; half of them complained of paresthesias. The vibration perception threshold was increased in 24 patients (80%). Auditory stimulation revealed a normal latency of the first component of the brain stem-evoked potentials Pl but an increased interpeak interval between this and Pv; reflecting a central conduction defect. Motor conduction velocity (CV) along the peroneal nerve was normal. The average sural nerve CV was decreased (P less than .01) and the sensory action potential amplitude was reduced (P less than .01). Warm perception threshold was increased in 10 patients (33%). Cortical-evoked potentials after tibial nerve stimulation had increased latencies in 29 patients (97%). The peripheral CV along the tibial nerve was slowed (P less than .01) in 19 patients, and the central conduction time from Th12 to cortex was prolonged in 15 patients (P less than .01). The changes in conduction along peripheral and central pathways after tibial nerve stimulation are compatible with a toxic effect on the sensory root ganglia causing a "dying back" axonal degeneration of central and peripheral nerve fibers.