tbuckley/cabot-search huggingface dataset:
Influence of statins on survival outcomes in men with metastatic castration resistant prostate cancer treated with abiraterone.
Authors: Martin Boegemann, Julie Steinestel, Ann-Kathrin Fischer, Katrin Schlack, Laura-Maria Krabbe
Journal: Journal of Clinical Oncology (2016)

e16573 Background: Statins are normally used for treatment of hypercholesterolemia (HCL). There is growing evidence that statins can prolong overall survival (OS) in cancer in general and especially in prostate cancer (PCa). Part of this is caused by improved cardiovascular-specific survival. In addition, in PCa, statins competitively inhibit the solute carrier transporter (SLC) and hinder dehydroepiandrosterone (DHEAS) from entering the tumor cell. DHEAS is a precursor of androgens which are thus diminished by blockade of the SLC. Knowledge of this in the public domain leads to increasing use of statins even in men with no HCL at all. Abiraterone (AA) inhibits CYP17A1 and thus the synthesis of androgens, amongst these DHEAS. Therefore, the efficacy of statins for prolonging OS in men with metastatic castration resistant PCa (mCRPC) can be questioned when treated with AA. In this study we investigated the effect of statins on survival outcomes in men with mCRPC treated with AA. Methods: Between 03/2012 and 07/2015 108 men with mCRPC under AA therapy with or without concomitant statin therapy were studied. Progression-free survival (PFS) and OS were analyzed using Kaplan Meier analysis and Cox regression analysis. Best clinical benefit was analyzed using bivariate logistic regression. Results: Twenty one men with and 87 without concomitant statin use were treated with AA. A decline of prostate specific antigen (PSA) ≥ 50% was not different in both groups. (57 vs. 53%; p = 0,73). Median PFS of men with statin use was 9 months vs. 10 months without statins (hazard ratio (HR): 1.0 (95% confidence interval (CI): 0.6-1.7); p = 0.97). For OS, equally, no difference of median survival was found (14 vs. 18 months (HR: 1.1 (CI: 0.6-1.9); p = 0.77). No improved clinical benefit was seen with concomitant statin treatment (odds ratio: 1.2 (CI: 0.4-4.2); p = 0.76). Conclusions: Concomitant use of statins next to AA treatment results in no improvement of survival outcomes or clinical benefit in men with mCRPC. Overdosing of statins and interaction with other medication can lead to severe side effects. Therefore, statins should not be used in patients with mCRPC treated with AA without accompanying HCL.
Phase I Trial of the Human Double Minute 2 Inhibitor MK-8242 in Patients With Advanced Solid Tumors
Authors: Andrew J. Wagner, Udai Banerji, Amit Mahipal, Neeta Somaiah, Heather Hirsch, Craig Fancourt, Amy O. Johnson-Levonas, Raymond Lam, Amy K. Meister, Giuseppe Russo, Clayton D. Knox, Shelonitda Rose, David S. Hong
Journal: Journal of Clinical Oncology (2017)

Purpose To evaluate MK-8242 in patients with wild-type TP53 advanced solid tumors. Patients and Methods MK-8242 was administered orally twice a day on days 1 to 7 in 21-day cycles. The recommended phase II dose (RP2D) was determined on the basis of safety, tolerability, pharmacokinetics (PK), and by mRNA expression of the p53 target gene pleckstrin homology-like domain, family A, member 3 ( PHLDA3). Other objectives were to characterize the PK/pharmacodynamic (PD) relationship, correlate biomarkers with response, and assess tumor response. Results Forty-seven patients received MK-8242 across eight doses that ranged from 60 to 500 mg. Initially, six patients developed dose-limiting toxicities (DLTs): grade (G) 2 nausea at 120 mg; G3 fatigue at 250 mg; G2 nausea and G4 thrombocytopenia at 350 mg; and G3 vomiting and G3 diarrhea at 500 mg. DLT criteria were revised to permit management of GI toxicities. Dosing was resumed at 400 mg, and four additional DLTs were observed: G4 neutropenia and G4 thrombocytopenia at 400 mg and G4 thrombocytopenia (two patients) at 500 mg. Other drug-related G3 and G4 events included anemia, leukopenia, pancytopenia, nausea, hyperbilirubinemia, hypophosphatemia, and anorexia. On the basis of safety, tolerability, PK, and PD, the RP2D was established at 400 mg (15 evaluable patients experienced two DLTs). PK for 400 mg (day 7) showed Cmax 3.07 μM, Tmax 3.0 hours, t1/2 (half-life) 6.6 hours, CL/F (apparent clearance) 28.9 L/h, and Vd/F (apparent volume) 274 L. Blood PHLDA3 mRNA expression correlated with drug exposure ( R2 = 0.68; P < .001). In 41 patients with postbaseline scans, three patients with liposarcoma achieved a partial response (at 250, 400, and 500 mg), 31 showed stable disease, and eight had progressive disease. In total, 27 patients with liposarcoma had a median progression-free survival of 237 days. Conclusion At the RP2D of 400 mg twice a day, MK-8242 activated the p53 pathway with an acceptable safety and tolerability profile. The observed clinical activity (partial response and prolonged progression-free survival) provides an impetus for further study of HDM2 inhibitors in liposarcoma.
Incremental Innovation and Progress in Advanced Squamous Cell Lung Cancer: Current Status and Future Impact of Treatment
Authors: Corey J. Langer, Coleman Obasaju, Paul Bunn, Philip Bonomi, David Gandara, Fred R. Hirsch, Edward S. Kim, Ronald B. Natale, Silvia Novello, Luis Paz-Ares, Maurice Pérol, Martin Reck, Suresh S. Ramalingam, Craig H. Reynolds, Mark A. Socinski, David R. Spigel, Heather Wakelee, Carlos Mayo, Nick Thatcher
Journal: Journal of Thoracic Oncology (2016)
Local Release of Paclitaxel from Aligned, Electrospun Microfibers Promotes Axonal Extension
Authors: Jose A. Roman, Ian Reucroft, Russell A. Martin, Andres Hurtado, Hai‐Quan Mao
Journal: Advanced Healthcare Materials (2016)

Traumatic spinal cord injuries ultimately result in an inhibitory environment that prevents axonal regeneration from occurring. A low concentration administration of paclitaxel has been previously shown to promote axonal extension and attenuate the upregulation of inhibitory molecules after a spinal cord injury. In this study, paclitaxel is incorporated into electrospun poly( l ‐lactic acid) (PLA) microfibers, and it is established that a local release of paclitaxel from aligned, electrospun microfibers promotes neurite extension in a growth‐conducive and inhibitory environment. Isolated dorsal root ganglion cells are cultured for 5 d directly on tissue culture polystyrene surface, PLA film, random, or aligned electrospun PLA microfibers (1.44 ± 0.03 μm) with paclitaxel incorporated at various concentrations (0%–5.0% w/w in reference to fiber weight). To determine the effect of a local release of paclitaxel, paclitaxel‐loaded microfibers are placed in CellCrown inserts above cultured neurons. Average neurite extension rate is quantified for each sample. A local release of paclitaxel maintains neuronal survival and neurite extension in a concentration‐dependent manner when coupled with aligned microfibers when cultured on laminin or an inhibitory surface of aggrecan. The findings provide a targeted approach to improve axonal extension across the inhibitory environment present after a traumatic injury in the spinal cord.
Do smokers in Europe think all cigarettes are equally harmful
Authors: Abraham Brown, Ann McNeill, Ute Mons, Romain Guignard
Journal: European Respiratory Journal (2012)

Despite the ban on misleading descriptors such as light or mild cigarettes in Europe, there are still widespread misperceptions of the relative harmfulness of different brands of cigarettes among smokers. This study examined the extent to which smokers in three European countries believed that some cigarette brands are less harmful and why, using data from the International Tobacco Control (ITC) Europe surveys. Cross-sectional analyses were completed among nationally representative samples of 4,956 current smokers (aged ≥ 18) from Germany (n = 1,515), France (n = 1,735) and the United Kingdom (n = 1,706) conducted between September 2006 and November 2007. Logistic regression models examined whether outcomes, including beliefs that some cigarettes could be less harmful than others, varied by socio-demographic and country of residence. Around a quarter of smokers in the UK and France, and a third in Germany believed some cigarettes are less harmful than others. Overall, of smokers who falsely believed that some cigarettes are less harmful, 86.3% thought that tar/nicotine yields, 48.7% taste, and 40.4% terms on packs such as 9smooth9 or 9ultra9 indicated less harmful brands. About a fifth of smokers across all countries chose their brand based on health reasons, and a similar proportion gave tar yields as a reason for choosing brands. Our research suggests that the current European Tobacco Products Directive is inadequate in eliminating misperceptions about the relative risk of brand descriptors on cigarettes. There is therefore an urgent need to protect smokers in Europe from these misperceptions via stronger measures such as plain packaging regulations.
The Combined Safety and Tolerability Profile of Vorinostat-Based Therapy for Solid or Hematologic Malignancies.
Authors: David Siegel, Pamela N Munster, Eric Rubin, Marian Iwamoto, Simon van Belle, Mohamad Hussein, Chandra P Belani, Francisco Robert, Evanthia Galanis, James Hardwick, Syed Rizvi
Journal: Blood (2009)
Cellular Barcoding Links B-1a B Cell Potential to a Fetal Hematopoietic Stem Cell State at the Single-Cell Level
Authors: Trine A. Kristiansen, Elin Jaensson Gyllenbäck, Alya Zriwil, Tomas Björklund, Jeremy A. Daniel, Ewa Sitnicka, Shamit Soneji, David Bryder, Joan Yuan
Journal: Immunity (2016)
Introduction Of Universal Leucodepletion Associated With a Reduction In New Renal Failure, But Not Infection Or Mortality, In Cardiac Surgery Patients: Results From a Before and After Study
Authors: Zoe K. McQuilten, Nick Andrianopoulos, Leo Van De Watering, Louise E. Phillips, Merrole Faye Cole-Sinclair, Christopher Reid, Peter A. Cameron, John J. McNeil, Erica M. Wood
Journal: Blood (2013)
Review: Aspirin reduces colorectal cancer incidence and mortality in patients at average risk
Authors: Robert H. Fletcher
Journal: Annals of Internal Medicine (2016)

Source Citation Chubak J, Whitlock EP, Williams SB, et al. Aspirin for the prevention of cancer incidence and mortality: systematic evidence reviews for the U.S. Preventive Services Task Force. Ann Intern Med. 2016;164:814-25. 27064482
Study of the Subclonal Mutations in Primary Diffuse Large B-Cell Lymphoma
Authors: Yan Asmann, Vivekananda Sarangi, Chen Wang, Matthew J Maurer, Stephen Ansell, Andrew L Feldman, Grzegorz S. Nowakowski, Thomas M. Habermann, Anne J. Novak, Susan L. Slager, Brian K Link, James Cerhan
Journal: Blood (2015)
Paternal Mitochondrial Transmission in Intra-Species<i>Caenorhabditis briggsae</i>Hybrids: Table 1
Authors: Joseph A Ross, Dana K Howe, Anna Coleman-Hulbert, Dee R Denver, Suzanne Estes
Journal: Molecular Biology and Evolution (2016)

To study mitochondrial-nuclear genetic interactions in the nematode Caenorhabditis briggsae, our three laboratories independently created 38 intra-species cytoplasmic-nuclear hybrid (cybrid) lines. Although the cross design combines maternal mitotypes with paternal nuclear genotypes, eight lines (21%) unexpectedly contained paternal mitotypes. All eight share in common ancestry of one of two genetically related strains. This unexpected parallel observation of paternal mitochondrial transmission, undesirable given our intent of creating cybrids, provides a serendipitous experimental model and framework to study the molecular and evolutionary basis of uniparental mitochondrial inheritance.
Immune-related gene expression signatures as predictive biomarkers for outcome after concurrent chemoradiation in patients with locally advanced oropharyngeal carcinomas.
Authors: Inge Tinhofer, Anne-Katrin Hess, Korinna Jöhrens, Ulrich Keilholz, Damian Tobias Rieke, Wilko Weichert, Panagiotis Balermpas, Claus Roedel, Fabian Dominik Mairinger, Michael Hummel, Petra Augstein, Volker Budach
Journal: Journal of Clinical Oncology (2016)

6056 Background: Immune-related gene expression signatures as candidate predictive biomarkers for cisplatin (CDDP)- and mitomycin C (MMC)-based chemoradiation (CRTX) were established in oropharyngeal carcinoma (OPC) patients from the ARO04-01 phase III trial. Potential overlap between the immune signatures of CRTX efficacy and the previously reported ‘inflamed’ signature of pembrolizumab activity was determined. Methods: Archival tumor specimens from OPC patients treated within the ARO04-01 study with concurrent MMC-CTRX (N = 24) or CDDP-CTRX (N = 23) were included. FFPE-extracted RNA was analyzed using the PanCancer Immune Profiling Panel on the NanoString nCounter system. Gene expression signatures predictive for 3yr-OS were established by Spearman Rank correlation and hierarchical cluster analysis. Survival estimates according to the immune signatures were determined by Kaplan-Meier analysis. The potential interference with the HPV status was evaluated in multivariate Cox regression models. Results: Signature 1 was associated with OS (P< 0.001) and PFS (P= 0.006) after CDDP-CRTX but not MMC-CRTX. Its positive predictive value for 3yr-OS was 87.5%, and the negative predictive value was 100%; AUC = 0.97 [95% CI, 0.89-1.0]. Signature 1 was enriched for genes of the adaptive immune system, mainly affecting T-cell receptor and PD-1 signaling. A partial overlap with genes from the ‘inflamed’ pembrolizumab signature was observed. In contrast, signature 2 which showed a significant association with outcome for both CRTX regimens was enriched for genes of the innate immune system, regulating Toll-like receptor, TNF receptor and NFkB signaling. Despite a higher prevalence of signature 1 in HPV+ tumors, its predictive value for OS and PFS after CDDP-CRTX was independent of the HPV status. Conclusions: We demonstrate for the first time an impact of adaptive immunity and PD-1 signaling on the efficacy of CDDP-CRTX which may be important for inclusion of PD-1/PD-L1 inhibitors into curative treatment settings. The NanoString technology for immune gene expression analysis should provide a useful tool for patient stratification.
Prognosis of Transient Neurological Attacks
Authors: J. Gert van Dijk
Journal: JAMA (2008)

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
Gammopathy of undetermined significance: Identification of prognostic factors and survival
Authors: F. Sackmann Massa, C. Corrado, I. Fernandez, P. Mountford, A. Pavlovsky, G. Remaggi, D. Intile, M. Alejandre, M. Pizzolato, S. Pavlovsky
Journal: Journal of Clinical Oncology (2008)

19512 Background: MGUS has a prevalence of 1 to 3%. Although it has an indolent evolution, some patients (pts) will develop a malignant neoplasm. Thus, factors that identify pts who will progress are important. Methods: We performed a retrospective analysis of 343 pts with MGUS in order to asses the value for malignant transformation of simple hematological or biochemical parameters detected at diagnosis. Rate of transformation, progression free survival (PFS) and overall survival (OS) will also be calculated. PFS and OS were calculated using the Kaplan Meier method and the curves were compared with the log-rank test. The identification of prognostic factors was made using Cox models. Results: Median (md) monoclonal component (MC) was 0.6 gr/dl (range 0.1 - 2.8). In 70% of the cases it was IgG, 16% IgA, 13% IgM and 1% biclonal. The light chain was Kappa in 63% of the pts. Bence Jones was detected in only 12%. Uninvolved immunoglobulins (UI) were reduced in 21% of the pts. Bone marrow analysis were performed in 73 pts (22%) and md plasma cell infiltration was 3 (range 0 - 10). Erythrocyte sedimentation rate (ESR) was normal in 42%. With a median follow up of 63 months (range 6 - 378), 25 pts (7.7%) evolved to a malignancy (17 multiple myeloma, 7 NHL, and 1 amyloidosis) and 14 (4%) died (2 related to progressive disease, 9 related to non hematological malignancy or cardiovascular disorder and 3 of unknown cause. PFS and OS at 10 years were 90% and 92%, respectively. MC concentration (p = 0.003, HR 3.88, CI 1.6 - 9.6), reduction of UI (p = 0.009, HR 2.9, CI 1.3 - 6.5) and ESR (p = 0.02, HR 3.1, CI 1.2 - 8) had prognostic value for progression. Conclusions: MC concentration, UI level and ESR at diagnosis identify a subgroup of pts with higher risk of transformation. No significant financial relationships to disclose.
Fat-free mass at admission predicts 28-day mortality in intensive care unit patients: the international prospective observational study Phase Angle Project
Authors: Ronan Thibault, Anne-Marie Makhlouf, Aurélien Mulliez, M. Cristina Gonzalez, Gintautas Kekstas, Nada Rotovnik Kozjek, Jean-Charles Preiser, Isabel Ceniceros Rozalen, Sylvain Dadet, Zeljko Krznaric, Kinga Kupczyk, Fabienne Tamion, Noël Cano, Claude Pichard, Séverine Graf, Claudia P. Heidegger, Marcio Guerreiro, Silvana Orlandi, Andrius Klimasauskas, Gintare Sostakaite, Kristina Gorjup, Katja Kogovšek, Katja Kopriva Pirtovšek, Michelle Norrenberg, Karen Rizkallah, François Wéry, Ali Ait Hssain, Bruno Pereira, Bertrand Souweine, Steven Grange, Antoine Marchalot, Pauline Bernier-Enguerrand, Marlena Jakubczyk, Aleksandra Różowicz, Stanisław Kłęk, Ana Kunovic
Journal: Intensive Care Medicine (2016)
Trends in Use and Outcomes of Women Undergoing Hysterectomy With Electric Power Morcellation
Authors: Jason D. Wright, Ling Chen, William M. Burke, June Y. Hou, Ana I. Tergas, Cande V. Ananth, Dawn L. Hershman
Journal: JAMA (2016)

This surgical epidemiology examines trends in the type of hysterectomy, use of electric power morcellators, and prevalence of abnormal pathology before and after the US Food and Drug Administration's 2014 guidance recommending against use of electric morcellation.
Final results of a randomized, double-blind, phase II study of gemcitabine plus vandetanib or plus placebo in the treatment of advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC) elderly patients (ZELIG study NCT00753714).
Authors: Cesare Gridelli, Silvia Novello, Nicoletta Zilembo, Paolo Foa, Adolfo G. Favaretto, Filippo De Marinis, Giovenzio Genestreti, Lucio Crinò, Francesco Grossi, Orazio Caffo, Francesco Ferraù, Giorgio Cruciani, Alba Ariela Brandes, Domenico Galetta, Sandro Barni, Gianpiero Fasola, Salvatore Siena, Ettore Mari, Claudio Iannacone, Fortunato Ciardiello
Journal: Journal of Clinical Oncology (2012)

7550 Background: Vandetanib (V) is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. Single-agent gemcitabine (G) is a standard of care option for unselected patients (pts) unfit for doublet platinum based chemotherapy. This study assessed the progression-free survival (PFS) benefit of G+V compared to G plus placebo (P) in pts with advanced NSCLC aged ≥ 70 years. Methods: Eligible pts (stage IIIB/IV NSCLC; WHO PS 0-2; all histologies; chemonaïve, aged ≥70) were randomized 1:1 to receive G 1200 mg/m2 i.v. day 1 and 8 of each 21-day cycle, up to 6 cycles plus V 100 mg/day or plus P until progression/toxicity. The primary objective was PFS (80% power to detect a hazard ratio [HR] ≤ 0.667). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Between Oct 2008-May 2010, 124 pts (median age 75 yrs (70-84); 72.6% male; 57.2% WHO PS 0-1; 74.2% past/never-smoker; 58.1% adenocarcinoma; 89.5% stage IV) were randomized to G+V (n = 61) or G+P (n = 63). Baseline characteristics were similar in both arms. At data cut-off (Apr11), 87.9% pts progressed and 73.4% pts had died. PFS was significantly prolonged for G+V (HR=0.729; 95% CI 0.484-1.096; p=0.0417), median PFS G+V=6.0 months, G+P=5.5 months. No differences were seen in ORR (14.8% and 12.7%; p = 0.74), DCR (72.1% and 66.7%; p =0.51), OS (HR=1.024 [95% CI 0.667-1.571] p=0.8960), proportion of pts alive at 1-year G+V=31.1% and G+P=30.2% (p=0.90). Adverse events (AEs) observed for V 100 mg were generally consistent with previous NSCLC studies of V 100 mg. Common AEs (any grade) occurring with a greater frequency in the G+V arm included skin toxicity (34.4% vs 15.9%) and hypertension (9.8% vs 3.2%). Diarrhea and neutropenia were similar in both arms (14.8% and 14.3%; 19.7% and 19.0%). Conclusions: Despite a marginally statistically significant improvement in PFS the study did not met the primary and secondary end points. The combination G+V was well tolerated in this clinical setting.
A T2* MRI Prospective Survey on Pancreatic Iron in Thalassemia Major Patients Treated with Deferasirox, Deferiprone and Desferrioxamine
Authors: Antonella Meloni, Cristina Paci, Giuseppe Serra, Stefania Vacquer, Roberto Giugno, Aurelio Maggio, Silvia Macchi, Maria Giovanna Neri, Vincenzo Positano, Patrizia Toia, Gennaro Restaino, Massimiliano Missere, Cristina Salvatori, Alessia Pepe
Journal: Blood (2014)
Lysyl oxidase activity in human skin is increased by chronic ultraviolet radiation exposure and smoking
Authors: A.K. Langton, E. Tsoureli-Nikita, C.E.M. Griffiths, A. Katsambas, C. Antoniou, A. Stratigos, M.J. Sherratt, R.E.B. Watson
Journal: British Journal of Dermatology (2016)

Lifestyle choices, such as tobacco smoking and sunbathing can lead to premature skin ageing1. These extrinsic accelerators of the ageing process cause profound changes to the abundance and arrangement of the elastic fibres and fibrillar collagens of the dermal extracellular matrix (ECM).

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Extracorporeal membrane oxygenation in burn patients with refractory acute respiratory distress syndrome leads to 28 % 90-day survival
Authors: Sabri Soussi, Pauline Gallais, Levon Kachatryan, Mourad Benyamina, Axelle Ferry, Alexandru Cupaciu, Maïté Chaussard, Véronique Maurel, Marc Chaouat, Maurice Mimoun, Alexandre Mebazza, Matthieu Legrand
Journal: Intensive Care Medicine (2016)