tbuckley/cabot-search huggingface dataset:
Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure
Authors: John R. Teerlink, G. Michael Felker, John J.V. McMurray, Piotr Ponikowski, Marco Metra, Gerasimos S. Filippatos, Justin A. Ezekowitz, Kenneth Dickstein, John G.F. Cleland, Jae B. Kim, Lei Lei, Beat Knusel, Andrew A. Wolff, Fady I. Malik, Scott M. Wasserman
Journal: Journal of the American College of Cardiology (2016)

Omecamtiv mecarbil (OM) is a selective cardiac myosin activator that increases myocardial function in healthy volunteers and in patients with chronic heart failure.This study evaluated the pharmacokinetics, pharmacodynamics, tolerability, safety, and efficacy of OM in patients with acute heart failure (AHF).Patients admitted for AHF with left ventricular ejection fraction ≤40%, dyspnea, and elevated plasma concentrations of natriuretic peptides were randomized to receive a double-blind, 48-h intravenous infusion of placebo or OM in 3 sequential, escalating-dose cohorts.In 606 patients, OM did not improve the primary endpoint of dyspnea relief (3 OM dose groups and pooled placebo: placebo, 41%; OM cohort 1, 42%; cohort 2, 47%; cohort 3, 51%; p = 0.33) or any of the secondary outcomes studied. In supplemental, pre-specified analyses, OM resulted in greater dyspnea relief at 48 h (placebo, 37% vs. OM, 51%; p = 0.034) and through 5 days (p = 0.038) in the high-dose cohort. OM exerted plasma concentration-related increases in left ventricular systolic ejection time (p < 0.0001) and decreases in end-systolic dimension (p < 0.05). The adverse event profile and tolerability of OM were similar to those of placebo, without increases in ventricular or supraventricular tachyarrhythmias. Plasma troponin concentrations were higher in OM-treated patients compared with placebo (median difference at 48 h, 0.004 ng/ml), but with no obvious relationship with OM concentration (p = 0.95).In patients with AHF, intravenous OM did not meet the primary endpoint of dyspnea improvement, but it was generally well tolerated, it increased systolic ejection time, and it may have improved dyspnea in the high-dose group. (Acute Treatment with Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure [ATOMIC-AHF]; NCT01300013).
Abstract 11167: Effects of Conversion to Everolimus With Low-Dose Calcineurin Inhibitors From Mycophenolate Mofetil on Cardiac Allograft Vasculopathy in Maintenance Heart Transplant Recipient: Serial Three-Dimensional Intravascular Ultrasound Analysis at 2 Years
Authors: Takuya Watanabe, Osamu Seguchi, Kunihiro Nishimura, Masanobu Yanase, Takuma Sato, Haruki Sunami, Seiko Nakajima, Eriko Hisamatsu, Takamasa Sato, Kensuke Kuroda, Takashi Kobayashi, Yoko Nakao, MIchikazu Nakai, Misa Takegami, Aya Higashiyama, Makoto Watanabe, Yoshihiro Kokubo, Hiroki Hata, Tomoyuki Fujita, Yoshihiro Miyamoto, Takeshi Nakatani
Journal: Circulation (2014)

Introduction: Everolimus (EVL) has been shown to reduce the severity of CAV in de novo heart transplant (HTx) recipients. However, there is still little knowledge about the effects of conversion from mycophenolate mofetil (MMF) to EVL with reducing calcineurin inhibitor (CNI) dose on cardiac allograft vasculopathy (CAV) in maintenance HTx recipients. To evaluate this hypothesis, we performed a retrospective study. Methods: We examined 63 consecutive HTx recipients who were investigated with three-dimensional intravascular ultrasound (3D-IVUS) analysis every year. 24 recipients were converted to EVL with low-dose CNI from MMF with standard-dose CNI (EVL group) while the others maintained on MMF with standard-dose CNI (MMF group). 3D-IVUS analyses in a year after conversions to EVL with low-dose CNI was compared with those just before the conversions in EVL group, while recent two 3D-IVUS analyses at one year interval were compared in the control group. Results: At the former analyses, plaque volume (PVI) and %plaque volume (%PVI, PVI/vessel volume percent) were significantly greater and lumen volume (LVI) was smaller in the EVL group in comparison with those in the MMF group. %PVI increased (10.37±7.53 versus 12.95±9.83, P=0.008) and LVI (10.57±2.63 versus 9.52±2.42 mm 3 /mm, P&lt;0.001) reduced significantly in the control group but not in the EVL group. The increase in %PVI during one year was suppressed and the decrease in LVI preserved in the EVL group compared with the control group (2.60±0.92 vs -0.66±1.14 %, p=0.031, -1.05±0.26 vs 0.05±0.19 mm 3 /mm, p=0.007, respectively). These effects were sustained at 2 years (p=0.042 and p=0.005). Conclusions: Compared with persistent MMF therapy, EVL conversion with low-dose CNI significantly reduce the severity of luminal narrowing in maintenance HTx recipients.
HER2-positive breast cancer cells percentage and progression to trastuzumab treatment in metastatic patients
Authors: Y. García-García, A. Martínez-Fernández, M. Muñoz Mateu, P. Fernández-Ruiz, X. García-Albéniz, M. Mármol-Casas, J. Domingo-Doménech, E. Pineda-Losada, L. Visa-Turmo, P. Gascón Vilaplana
Journal: Journal of Clinical Oncology (2007)

11510 Background: Immunohistochemistry (IHC) assay for HER2 in breast cancer (BC) identify patients (pts) who are at benefit from Trastuzumab (T) therapy. The percentage (%) of positive cells is not known to have prognostic significance. Methods: We analyze pts that received T as a treatment for metastatic BC in our center, in monotherapy or in combination with other agents, and to ascertain whether the % of her-2 positive cells can be a predictive factor of response to therapy with T. We define HER-2 positive cells according to the Envision method 3+, valuating the percentage of cells with positive result. If the result of the IHC was 2+, we use fluorescence in situ hybridation (FISH). For a total of 36 patients treated, the results of the % were available only for 21 patients. The median of positive cells was 90% (range 30–100%) and it was taken to define low percentage of positive cell tumors (LPPCT) or high percentage of positive cells tumors (HPPCT). We evaluated the initial response (disease progression-stability versus parcial-complete response), the time to progression (TTP) and the overall survival (OS) of pts on T. We used the log-rank test to determinate the TTP and Fisher’s exact text to determinate the initial response and the OS on therapy with T. Results: TTP to T was significantly higher in LPPCT (median 19 months, CI 10–28) than in HPPCT (median 13 months, CI 7–19) (p=0.037). We didn’t find significant differences regarded to baseline characteristics of the patients, response nor OS. Conclusions: We find that the % of HER2-positive cells is significantly correlated with the TTP in patients on T therapy. The percentage of HER2-positive cells can be at clinical interest as a predictive factor of response to her-2 targeted therapy and it must be confirmed with a large number of pts. No significant financial relationships to disclose.
Medical students should be taught to appraise evidence on global health issues
Authors: M. Peel, A. Berlin, J. Piachaud, E. James
Journal: BMJ (1996)

Contemplating a one child worldFundamental rethinking is needed EDITOR,-A one child world' may just be possible in China, a country of coercion, abortion, and neglect of orphans; it may also be achievable soon in Catholic Italy and Ireland.For most countries, though, the switch from demographic transition (average families of 2-1 children) to ecological transition (a one child world) is at least a generation away, and in countries threatened by or already experiencing demographic entrapment this will take much longer.The resurgence of nationalism also complicates this objective, as many ethnic groups will insist that a one child family should not apply to them.If human survival on a global level is possible, families urgently need to adopt not only a one child world but one in which the destructive ecological effect of each person is as small as possible.2'The issues of demographic and ecological entrapment must become central to the debate over scientific and public health policy; the taboos that hamper this must be dropped.Fundamental rethinking is needed.This is especially true in the industrialised countries in the North, where the ecological effect of one person easily outweighs that of 50 in the non-industrialised South.Improved surveillance of, and response to, the catastrophic public health threats that the North now faces is not an adequate solution.4The explosion of the consumption bomb threatens populations in both the North and the South.5To defuse it, fundamental rethinking is needed; along with the nuclear and population bombs this is the greatest threat to public health that we currently face.
The bent twig: psychiatry and medical education
Authors: H Klein, E Mumford
Journal: American Journal of Psychiatry (1978)

The authors note that an increase in psychiatry's involvement in the selection and education of medical school students, which historically has been limited and problematic, would benefit both the discipline and the profession in general. There is evidence indicating the need to pay attention to personal attributes in medical education, particularly in light of the incidence of problems in physicians (e.g., addiction, alcoholism, and suicide) that fall within psychiatry's area of expertise. Active participation by psychiatry in medical education might also help combat the cynicism that seems to develop during training and might contribute to consideration of ethical issues and to the fostering of emotional maturity.
Abstract 280: Delta-24-RGDOX: making cancer more “visible” to the immune system
Authors: Hong Jiang, Xuejun Fan, Karen Clise-Dwyer, Laura Bover, Joy Gumin, Kathryn E. Ruisaard, Farah J. Mukheef, Frederick F. Lang, Candelaria Gomez-Manzano, Juan Fueyo
Journal: Cancer Research (2015)

Abstract Emerging evidence indicates that host immunity is critical for successful cancer virotherapy. We found that oncolytic adenovirus Delta-24-RGD elicited antiglioma immunity in an immunocompetent murine model. Recent studies suggested that the therapeutic efficacy of immune checkpoint blockade in cancer patients could be enhanced by strategies inducing tumor inflammation. We hypothesized that highly immunogenic adenovirus combined with targeting immune co-stimulator would result in better anti-tumor efficiency. Thus, we used the backbone of Delta-24-RGD to express the mouse OX40 ligand to increase the recognition of tumor-associated antigens by immune cells. The resulting Delta-24-RGDOX adenovirus maintained the oncolytic potency of Delta-24-RGD and efficiently expressed OX40 ligand on infected cells. More importantly, compared to Delta-24-RGD, Delta-24-RGDOX induced higher antiglioma activity in immunocompetent glioma models but not in an immunodeficient model, and accordingly mediated greater lymphocyte infiltration at tumor sites and stronger lymphocyte antitumor activity. While blocking or stimulating immune checkpoints with antibodies currently dominates the clinical applications, our data demonstrate that intratumoral injection of oncolyticviruses carrying immune co-stimulatory ligands may constitute a powerful alternative to the use of antibodies and other strategies targeting immune checkpoints in cancer therapy. Note: This abstract was not presented at the meeting. Citation Format: Hong Jiang, Xuejun Fan, Karen Clise-Dwyer, Laura Bover, Joy Gumin, Kathryn E. Ruisaard, Farah J. Mukheef, Frederick F. Lang, Candelaria Gomez-Manzano, Juan Fueyo. Delta-24-RGDOX: making cancer more “visible” to the immune system. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 280. doi:10.1158/1538-7445.AM2015-280
Association of response to programmed death receptor 1 (PD-1) blockade with pembrolizumab (MK-3475) with an interferon-inflammatory immune gene signature.
Authors: Antoni Ribas, Caroline Robert, F. Stephen Hodi, Jedd D. Wolchok, Anthony M Joshua, Wen-Jen Hwu, Jeffrey S. Weber, Hassane M. Zarour, Richard Kefford, Andrey Loboda, Andrew Albright, Soonmo Peter Kang, Scot Ebbinghaus, Jennifer Yearley, Erin Murphy, Michael Nebozhyn, Jared K. Lunceford, Terri McClanahan, Mark Ayers, Adil Daud
Journal: Journal of Clinical Oncology (2015)

3001 Background: Immunotherapy with anti–PD-1 monoclonal antibodies such as pembrolizumab shows robust, durable antitumor activity in patients with advanced melanoma. Examining gene expression related to the immune response within the tumor may provide new insights into the molecular features associated with clinical response to these agents. We evaluated immune-related gene expression patterns in patients with melanoma enrolled in the phase Ib KEYNOTE-001 study. Methods: Baseline tumor biopsy samples from 19 patients with melanoma enrolled in KEYNOTE-001 were used as a discovery set. Results were validated using samples from 62 additional patients from KEYNOTE-001, of whom 51 were evaluable for response per RECIST v1.1 by central review. RNA was extracted from formalin-fixed paraffin-embedded tissue sections and analyzed using the NanoString nCounter. Two signatures, the "Interferon-gamma [IFNγ] 10-gene" and the "Expanded-immune 28-gene," were pre-specified prior to linking NanoString data to clinical outcomes. Results: The overall response rate (ORR) was 47% in the validation cohort. Both the IFNγ and the expanded-immune signatures showed statistically significant associations with ORR (P = 0.047 and 0.027, respectively) and progression-free survival (P = 0.016 and 0.015). Analysis of top-ranked genes on the platform led to the discovery of two new signatures, "TCR-signaling" and "Denovo" that were enriched in T-cell markers and MHC Class I and II genes. Conclusions: Measuring immune-related biomarkers, including T-cell specific, antigen presentation–related, and IFNγ signaling–related genes, may allow for improved selection of patients likely to respond to anti–PD-1 therapy with pembrolizumab. Results are consistent with the hypothesis that clinical responses to PD-1 blockade occur in patients with a preexisting interferon-mediated adaptive immune response. Further confirmation of these new signatures in melanoma is required. Clinical trial information: NCT01295827.
Cytogenetic Studies of Lymphoma Cells From an American Patient With a Tumor Similar to Burkitt's Tumors in African Children
Authors: Elizabeth W. Chu, Jacqueline J. K. Whang, Alan S. Rabson
Journal: JNCI Journal of the National Cancer Institute (1966)

Cytogenetic studies were done on lymphoma cells from ascitic fluid of an American woman with a tumor similar to Burkitt's tumors in African children and on the established cell culture line (AL-2) derived from the ascites cells, More than 90% of the metaphases in direct preparations of the ascitic fluid contained an extra submedium chromosome, larger than pair #1, and lacked one chromosome from this #1 pair. The AL-2 line had a chromosome number distribution ranging from 42–86 with a modal number of 46, and the cells with 46 chromosomes had an apparently normal female karyotype. None of the AL-2 cells showed any marker chromosomes. The cultural conditions apparently favored the growth of those cells without the marker chromosome.
Peripheral Causes of Cognitive Motor Dissociation in Patients With Vegetative or Minimally Conscious State—Reply
Authors: Davinia Fernández-Espejo, Adrian M. Owen
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
Elotuzumab in combination with bortezomib in patients with relapsed/refractory multiple myeloma: A phase I study.
Authors: A. J. Jakubowiak, D. M. Benson, W. Bensinger, D. S. Siegel, T. M. Zimmerman, A. Mohrbacher, P. G. Richardson, D. Afar, A. K. Singhal, K. C. Anderson
Journal: Journal of Clinical Oncology (2010)

8003 Background: Elotuzumab is a humanized antibody against a cell surface glycoprotein, CS1, which is highly expressed in multiple myeloma (MM). This phase I study was designed to determine MTD, safety, PK and response of elotuzumab in combination with bortezomib in relapsed/refractory MM patients (pts) following 1-3 prior therapies. Methods: Four escalating doses of elotuzumab (2.5 mg/kg to 20 mg/kg) were administered on D 1 and 11 and bortezomib (1.3 mg/m2) on D 1, 4, 8 and 11 of a 21-day cycle. Pts with ≥ stable disease after 4 cycles continued treatment until progression. Key entry criteria included age ≥ 18 years; confirmed MM diagnosis with 1 to 3 prior therapies including prior bortezomib and refractory MM; measurable M-protein in serum and/or urine. Results: In this fully enrolled study, 28 MM pts were treated; 3 each at 2.5, 5 and 10 mg/kg and 19 at 20 mg/kg elotuzumab. The 26 pts with completed analysis had a median of 3.4 years from initial MM diagnosis and a median of 2 prior lines of therapy. Eight pts (31%) had previously been treated with bortezomib and nine (35%) were refractory to the last MM therapy. No DLT was observed during the first treatment cycle and the MTD was not reached. Twelve SAEs were reported in 9 pts; two G3 events, chest pain and gastroenteritis, were assessed as elotuzumab- related. Unrelated SAEs included G4 hypercalcemia, G3 myocardial infarction, sepsis, vomiting, pneumonia (2 pts), G2 dehydration, G1 ileus and G1 incoherence. Most common AEs included fatigue, diarrhea, nausea, thrombocytopenia, constipation, anemia, peripheral neuropathy, lymphopenia, neutropenia, and leukopenia. Best response (≥ MR) by combined EBMT and uniform criteria in 20 evaluable pts with ≥ 2 treatment cycles was 60% including 40% ≥ PR. Median time to progression (TTP) is currently 9.6 months. Preliminary analysis of bone marrow plasma cells indicated that ≥ PR correlate well with complete or near complete saturation of CS1 sites by elotuzumab. Conclusions: The combination of elotuzumab with bortezomib has a manageable safety profile and shows encouraging activity in relapsed and refractory MM with ≥MR in 60% pts and a median TTP of 9.6 months. Updated safety and efficacy data will be presented at the meeting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Facet Biotech Bristol-Myers Squibb, Celgene, Centocor Ortho Biotech, Exelixis, Millennium, Novartis, PDL BioPharma Facet Biotech Bristol-Myers Squibb, Celgene, Centocor Ortho Biotech, Exelixis, Millennium Celgene, Facet Biotech, Millennium, Novartis
Effect of simultaneous inhibition of MEK and PI3K/Akt pathways on paclitaxel sensitivity in ovarian cancer
Authors: J. Kigawa, W. Kawaguchi, H. Itamochi, Y. Kanamori, T. Oishi, M. Shimada, S. Sato, S. Sato, N. Terakawa
Journal: Journal of Clinical Oncology (2007)

16046 Background: Paclitaxel (PTX) is one of the key drugs for ovarian cancer treatment. PTX activates the Raf-mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3’-kinase (PI3K) pathways that lead to cell survival pathways. The purpose of this study was to clarify whether and how the inhibitors of MEK and/or PI3K affect the sensitivity to PTX in ovarian cancer cells. Methods: We treated five ovarian cancer cell lines in combination with PTX and MEK- [PD98059 (PD)] and/or PI3K-inhibitor [LY294002 (LY)] and assessed cell viability, apoptosis, and the expression of phosphorylated (p) MEK and pAkt. The sensitivity of the cell lines to PTX was determined by 3-(4,5- dimethylthiazol-2-yl) -2,5-dyphenyltetrazolium bromide (MTT) assay. The level of protein expression was analyzed by western blot analysis. The drug-induced apoptosis was assessed by Annexin V-FITC staining. Additionally, KOC-2S was injected to intraperitoneal cavity of nude mouse. The effect of combined treatment on the survival in xenograft model was investigated. Results: The levels of pMEK and pAkt protein expression were higher in PTX resistant cell lines (KOC-2S and KFTx) than that in sensitive cell lines (KF, SHIN-3, SK-OV-3). Treatment of PTX induced MEK activation in all five ovarian cancer cell lines. The combination of PTX with either PD or LY led to additive effect on cell growth inhibition. In contrast, synergistic effect was observed in the combination of PTX with PD and LY. Furthermore, apoptotic cells were significantly increased after exposure to PTX and both inhibitors in comparison with other treatment conditions, such as PTX alone, PTX with either PD or LY. The level of pMEK induced by PTX was down-regulated by PD. Interestingly, the level of pAkt was up-regulated by the combination of PTX with PD, which was reduced by LY. Treatment with PTX, PD, and LY prolonged survival in an ovarian cancer xenograft model (p &lt; 0.01). Conclusions: The present study suggests that simultaneous inhibition of MEK and PI3K/Akt pathways enhances the sensitivity to PTX in ovarian cancer. The combination of PTX with MEK- and PI3K-inhibitor may be a new treatment strategy for ovarian cancer. No significant financial relationships to disclose.
Some Observations on Nuclear Budding and Nuclear Extrusions in a Chinese Hamster Cell Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Longwell, Arlene Crosby, Yerganian, George
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Some Observations on Nuclear Budding and Nuclear Extrusions in a Chinese Hamster Cell Culture Get access Arlene Crosby Longwell, Arlene Crosby Longwell The Children's Cancer Research Foundation and the Department of Pathology, Harvard Medical School, at The Children's Hospital, Boston, Massachusetts 3Postdoctoral fellow (PF73) of the American Cancer Society, Inc., during part of this study. Search for other works by this author on: Oxford Academic PubMed Google Scholar George Yerganian George Yerganian The Children's Cancer Research Foundation and the Department of Pathology, Harvard Medical School, at The Children's Hospital, Boston, Massachusetts 4We wish to thank Dr. Agnes Russfield for assistance in the final preparation of the manuscript. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 34, Issue 1, January 1965, Pages 53–69, https://doi.org/10.1093/jnci/34.1.53 Published: 01 January 1965 Article history Received: 08 May 1964 Published: 01 January 1965
Positively selected autologous blood CD34+ cells and unseparated peripheral blood progenitor cells mediate identical hematopoietic engraftment after high-dose VP16, ifosfamide, carboplatin, and epirubicin
Authors: W Brugger, R Henschler, S Heimfeld, RJ Berenson, R Mertelsmann, L Kanz
Journal: Blood (1994)