tbuckley/cabot-search huggingface dataset:
Transfer of Tumor-Specific Immunity With RNA: Demonstration by Immune Cytolysis of Tumor Cells <italic>in Vitro</italic>
Authors: Kenneth P. Ramming, Yosef H. Pilch
Journal: JNCI Journal of the National Cancer Institute (1970)

Extracts rich in RNA were prepared from the spleens of inbred strain-2 guinea pigs that had been immunized with a 3-methylchoI-anthrene-induced, strain-2 liposarcoma (MCA-A). Normal, nonimmune, strain-2 lymphoid cells incubated with these RNA preparations caused specific immune cytolysis of MCA-A cells in vitro. Treatment of the active RNA preparations with ribonuclease resulted in their complete inactivation. RNA from the spleens of guinea pigs not exposed to the tumor was ineffective. Incubation of lymphoid cells with extracts of MCA-A rich in solubilized tumor-specific antigens did not reproduce the immune cytolysis caused by the active RNA preparations. Spleen cells incubated in RNA extracted from strain-2 guinea pigs immunized with MCA-A did not cause significant immune cytolysis when applied to monolayers of MCA-25, a strain-2 sarcoma whose tumor-specific transplantation antigens do not cross-react with MCA-A.
Do health reforms work?
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2016)

The world of health policy isn’t short of opinions, ideas or hunches. But knowing what succeeds isn’t easy. We might examine our health system and decide that it isn’t working, for example, basing our conclusions on quality outcomes, patient satisfaction surveys or process measures. A snapshot of performance, however, tells us little about what works and what doesn’t. When the gold standard for evaluating an intervention is a randomised controlled trial, the dearth of this methodology in analysing health reforms leaves us with insufficient data to act upon.

The reasons for the relative absence of randomised controlled trials in health policy are several and hard to overcome. Health reforms tend to be complex interventions, making it difficult to isolate the intervention, blind the participants and the investigators to the intervention, and find a suitable control group. Importantly, trials take time and do not fit the life cycle of an elected government. Politicians want to make decisions at a time of maximum benefit, and both the timing of trial results and the findings themselves may not suit a political agenda.

Trials are expensive too. Why waste time and money when, a policy maker might argue, a modelling study will provide good enough information? Then the design, analysis and interpretation of trials are themselves controversial and open to disagreement. Which approach do you prefer? Frequentist, Bayesian, or a mixture of the two?1

Yet, these reservations might be more of a hindrance in richer countries with established health systems. Emerging economies around the world are using randomised controlled trials to evaluate health reforms and decide on policy. Mexico is the best example, where the willingness to evaluate is helped by a separation of politics and technical health advice. Brazil, China and India are others attempting rigorous evaluation. Perhaps we have invested so much emotion in health reforms that we are afraid to ask questions? Instead, we drive down a road of incessant innovation, innovation that itself is inadequately evaluated, and, when demonstrably successful, is hard to ‘scale up’.

In the absence of randomised controlled trials, Alice Lale and Jonathan Temple use routinely published data to determine if NHS reforms affect population mortality. Interestingly, or perhaps depressingly, the researchers find that centrally led NHS reorganisation has never had any detectable effect on mortality and should be considered ineffective for this purpose.2 Increased funding, however, may be beneficial.

Rather than focusing on central reforms, the NHS might better serve its population by tackling medicalisation, although the drivers of medicalisation are so strong that it is unlikely to diminish.3 The Choosing Wisely campaign, recently launched in the UK, is one attempt to respond to the challenge of medicalisation. Ahmed Rashid argues that doctors in training, the newest members of each specialty tribe, can be agents of change, which does sound like a hunch worth evaluating.4
Safety and efficacy of AMG 655 in combination with paclitaxel and carboplatin (PC) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: L. Paz-Ares, J. M. Sánchez Torres, I. Diaz-Padilla, M. Links, N. Reguart, M. Boyer, J. Wiezorek, T. Sabin, Y. Pan, J. Van Meerbeeck
Journal: Journal of Clinical Oncology (2009)

e19048 Background: AMG 655 is an investigational, fully human IgG1 monoclonal agonist antibody that binds human death receptor 5 (DR5), activates caspases, and induces apoptosis in sensitive tumor cells. The primary objective of this phase 1b study was to determine the maximum tolerated dose (up to a target dose of 15 mg/kg) of AMG 655 that can be safely administered with PC. Methods: Eligibility included: ≥ 18-years old, untreated, advanced NSCLC, and ECOG PS 0 or 1. Patients (pts) were enrolled in sequential dose cohorts of AMG 655 (5 or 15 mg/kg) + P (200 mg/m 2 ) and C (AUC = 6 mg/mL x min) IV every 3 weeks for up to 6 cycles. After completion/discontinuation of PC, pts may continue AMG 655 as monotherapy. Endpoints include: incidence of dose- limiting toxicities (DLT); adverse events (AE); pharmacokinetics (PK); levels of plasma genomic (g)DNA, serum caspase 3/7 activity, and M65 (cell death and apoptosis biomarkers); objective tumor response rate (by RECIST), and progression-free survival (PFS). Results: As of 09/08, 12 pts enrolled and received ≥ 1 dose of AMG 655 + PC. Ten were men; 11 had ECOG 1, and median (range) age = 68.5 (50–83) years. Median (range) time on AMG 655 = 5.2 (0.2–8.3) months; all pts have discontinued treatment. There was 1 DLT: grade 3 hyponatremia (15-mg/kg cohort). Five (42%) pts had grade 3 AE including neutropenia and dyspnea (2 pts each); 3 (25%) had grade 4 AE (2 with neutropenia, 1 with pulmonary embolism). After one 5- or 15-mg/kg dose of AMG 655 + PC, AMG 655 PK values (serum clearance, C max , AUC) were similar to the first-in-human study (LoRusso et al. JCO 2007; 25: abstr 3534) indicating no effect of PC on PK of AMG 655. Data also indicate no effect of AMG 655 on PK of PC. Plasma gDNA, serum caspse 3/7 activity, and serum M65 levels increased significantly from baseline 24 h after administration of AMG 655 + PC. Best overall tumor response: 1 complete response, 3 partial responses, 3 stable disease, and 3 progressive disease (2 pts had no on-treatment tumor assessments). Median (95% CI) PFS = 5.1 months (1.5, 7.0). Conclusions: AMG 655 administered with PC appears to be well tolerated with expected PK properties not altered by PC. A randomized phase 2 trial (AMG 655 ± PC) is ongoing. [Table: see text]
Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial
Authors: Patrick Schöffski, Sant Chawla, Robert G Maki, Antoine Italiano, Hans Gelderblom, Edwin Choy, Giovanni Grignani, Veridiana Camargo, Sebastian Bauer, Sun Young Rha, Jean-Yves Blay, Peter Hohenberger, David D'Adamo, Matthew Guo, Bartosz Chmielowski, Axel Le Cesne, George D Demetri, Shreyaskumar R Patel
Journal: The Lancet (2016)
NA17 and MAGE gene expression in 20 adult sarcoma tumors: Retrospective analysis by semi-quantitative RT-PCR
Authors: S. Piperno-Neumann, O. Lantz, G. De Pinieux, V. Laurence, P. Anract, J. Y. Pierga, A. Babinet, B. Tomeno, P. Pouillart
Journal: Journal of Clinical Oncology (2004)

9053 Background: Expression of the MAGE-A family genes has been found in many types of tumors but not in normal adult tissues with the exception of testicular germ cells. A frequency of 20% MAGE mRNA positive sarcomas has been reported previously (Van den Eynde, Curr Opin Immunol 1997). NA17 is another tumor-associated antigen encoded by an intronal sequence from the N-acetylglucosaminyltransferase-V gene, which is significantly expressed in melanomas. Because NA17 and MAGE gene products are presented by HLA class I molecules and recognized by CD8+ cytolytic T lymphocytes in vivo, they have become promising target antigens for tumor vaccination in melanoma patients. Both are evaluated in ongoing melanoma vaccination trials at the Institut Curie. Methods: In 20 surgically resected bone and soft tissue sarcomas, expression of NA17 and Mage 1, 2, 3, 4, 6 and 10 was measured by semi-quantitative RT-PCR. After RNA extraction with CsCl gradient and reverse transcription, expression was quantified by PCR with comparison to dilutions of reference cell lines. All samples were histologically confirmed to contain tumoral tissue, corresponding to bone sarcomas in 8 and soft tissue sarcomas in 12 cases. Results: Analysis by the multimarker RT-PCR revealed an expression of at least one MAGE gene in 6 of 20 tumors, corresponding to a positivity rate of 30%. Among these 6 cases, MAGE 3 was expressed in 6, MAGE 6 in 4, MAGE 1 and MAGE 2 in 3, MAGE 4 and MAGE 10 in 2. For NA17, 5 of 20 samples exhibited positivity (25%). Overall, 8 of 20 tumors (40%) expressed at least one gene, and 4/20 (20%) expressed 3 or more genes simultaneously. Conclusions: This short series shows that NA17 and MAGE genes are expressed in 4/8 bone sarcomas and 4/12 soft tissue sarcomas. Sarcoma patients showing disease progression after conventional treatment might represent eligible candidates for HLA typing and future sarcoma vaccination trial combining NA17 and MAGE antigen immunization. No significant financial relationships to disclose.
Effect of Inhaled Alpha-Blocker on Airflow Obstruction in Asthma<sup>1</sup>
Authors: John Britton, Jon Ayres, G M Cochrane
Journal: Journal of the Royal Society of Medicine (1981)

A controlled study of the effect on airflow obstruction of 30 mg of the alpha-blocker thymoxamine given by inhalation is reported in 10 patients with chronic stable asthma. No significant change in peak expiratory flow rate was seen with either thymoxamine or placebo in any patient. Alpha-adrenergic receptors are therefore unlikely to contribute significantly to resting bronchomotor tone in chronic stable asthma.
Tumor size and prognosis in aggressively treated osteosarcoma.
Authors: N Jaffe, D M Jaffe
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.8.2399 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8708733 Tumor size and prognosis in aggressively treated osteosarcoma. N JaffexN JaffeSearch for articles by this author , D M JaffexD M JaffeSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.8.2399 PDF "Tumor size and prognosis in aggressively treated osteosarcoma.." Journal of Clinical Oncology, 14(8), pp. 2399–2400© 1996 by American Society of Clinical Oncology
A new model of early supportive care and symptoms management: The experience of Pisa medical oncology.
Authors: Andrea Antonuzzo, Enrico Vasile, Maurizio Lucchesi, Laura Ginocchi, Luca Galli, Isa Maura Brunetti, Sergio Ricci, Alfredo Falcone
Journal: Journal of Clinical Oncology (2013)

e20711 Background: Recent advances in medical oncology research and new possibilities of care create a growing number of treatment-related complications. Due to these clinical relevant toxicities a significative number of patients have to admit to our hospital emergency rooms in the recent years. Data from different institutions in Italy suggest that an integrated model of supportive care dedicated to symptoms management and not only, is more effective for cancer patient’s care. Methods: In the last seven months of 2012 we started the “supportive care-team” activity giving a dedicated-room inside the day hospital offering to the patients a direct and early management of chemotherapy toxicities (mucositis, febrile neutropenia, etc.) and “new drugs” induced toxicities (cutaneous, hypertension/cardiovascular, infective, etc.). The medical and nurse team does receive the patient without appointment, based on the severity of clinical problems and give a mobile phone consult all days in the morning. Patients receive symptomatic therapy, i.v. fluid infusions, collecting of blood samples, corrections of medical therapies (e.g. pain therapy), venous accesses management for one-day or more until resolution and physicians are able to organize further specialists evaluations. Moreover, there are strictly linked specialists such as anesthesiology involved in all cases of severe drugs adverse reactions. Other two ancillary support activities the for patients are offered by the psychologist and chaplain daily inside the day hospital. Results: During all 2012 we have delivered 13.365 courses of anticancer therapies in 1,358 patients. All these were outpatients. During the last 7 months of 2012 we have made 761 unplanned visits (median number/day 6, range 0-13) and the team did respond to 1,138 phone calls (median number/day 9, range 2-24). Conclusions: These analysis does attempt to answer to the main question of reducing hospitalizations and their related costs. Our new organizative model prompt to maintain much more the management of oncologic patients inside the oncologic department and to increase the feasibility of patient’s continuos care, improving symptoms control and patient’s quality of life.
Abstract 12044: Absence of Coronary Artery Disease by Coronary Computed Tomographic Angiography and the Warranty Period Associated With All-Cause Mortality: Findings From the CONFIRM Long-Term Follow-Up Registry
Authors: Iksung Cho, Bríain ó Hartaigh, Heidi Gransar, Joshua Schulman-Marcus, Valentina Valenti, Daniel S Berman, Matthew J Budoff, Stephan Achenbach, Mouaz Al-Mallah, Daniele Andreini, Filippo Cademartiri, Tracy Q Callister, Hyuk-Jae Chang, Kavitha Chinnaiyan, Ricardo Cury, Augustin Delago, Millie Gomez, Martin Hadamitzky, Joerg Hausleiter, Niree Hindoyan, Gudrun Feuchtner, Yong-Jin Kim, Philipp A Kaufmann, Jonathon Leipsic, Fay Y Lin, Erica Maffei, Gianluca Pontone, Gilbert Raff, Leslee J Shaw, Todd C Villines, Allison Dunning, James K Min
Journal: Circulation (2014)

Introduction: Coronary computed tomographic angiography (CCTA) is widely utilized for the detection of coronary artery disease (CAD). Foremost, the very low risk associated with normal CCTA is an important component for the purpose of cardiovascular risk stratification. To date, however, data that accounts for long-term prognosis of normal CCTA is sparse. Purpose: Using data from a multi-center, global observational CCTA registry, we sought to determine the potential warranty period of normal CCTA. Methods: Among 12,086 patients who underwent CCTA, 7,651 patients without history of previous CAD, aged between 30-74 years, were included in the current analysis and followed consecutively over 5 years. Normal CCTA was defined as the absence of any plaque in the coronary arteries. Annual mortality was calculated and compared with overall patients. The primary event in this study was all-cause mortality (ACM). Results: During a median follow-up of 5.8 years (IQR, 5.3-6.3 years), 120 of all-cause deaths occurred among 3,051 patients with normal CAD. Mean age of the study population was 52±11 years, and 45% were men. Annual mortality rate was 0.68% (95% confidence interval (CI), 0.57~0.82), while annual mortality of overall patients was 1.31% (95% CI, 1.20~1.42) ( p &lt;0.001). When we defined warranty period as a follow-up duration until the estimated mortality reached the threshold of 5% using a Kaplan Meier curve, the warranty period of normal CCTA for ACM was 7.2 years. In subgroup analysis, according to a baseline risk factor profile using Framingham risk scores (FRS), annual mortality rate was 1.31% (95% CI, 0.85~2.03) among patients with high FRS and 0.62% (95% CI, 0.51~0.76) among those with low to intermediate FRS. Conclusion: Absence of CAD by CCTA demonstrates a favorable survival rate with a minimum warranty period of at least 7 years. Persons presenting with a high cardiovascular risk profile displayed a relatively higher mortality, which is similar to overall population. Therefore, they should be considered a distinct group of individuals at-risk by physicians and researchers alike.
Abstract 15168: Interleukin-18 Enhances Mitochondrial Function in Pressure Overload through AMP-activated Protein Kinase Activation
Authors: Toshihiro Iwasaku, Shinichi Hirotani, Akiyo Eguchi, Yoshitaka Okuhara, Daisuke Morisawa, Makiko Oboshi, Hisashi Sawada, Yoshiro Naito, Toshiaki Mano, Tohru Masuyama
Journal: Circulation (2014)

Introduction: We have reported that serum Interleukin-18 (IL-18) concentrations increased according to worsening heart failure (HF) functional class. However, the pathological roles of serum IL-18 elevation in HF have not been fully elucidated. The purpose of this study was to elucidate the role of IL-18 in adaptation to pressure overload in IL-18 null mice. Hypothesis: We hypothesized that IL-18 plays a key role in pressure overload-induced hypertrophic responses by enhancing mitochondrial function. Methods: Ten-week-old male C57BL6/J-background wild type (WT) mice and C57BL6/J-background IL-18 null (IL-18-/-) were subjected to transaortic constriction (TAC). Cardiac function was assessed by transthoracic echocardiography every week. Two weeks after TAC, myocardial samples were obtained. Detection of cardiac gene expressions by q-RT PCR and quantification of phospho-proteins by western blot were performed. An AMPK activator (AICAR 100mg/kg,) was given intraperitoneally everyday after TAC procedure. Resul...
The neuropsychological signature of schizophrenia: generalized or differential deficit?
Authors: J J Blanchard, J M Neale
Journal: American Journal of Psychiatry (1994)

The aim of this study was to provide a comprehensive assessment of neuropsychological functioning in schizophrenia so as to evaluate hypotheses of lateralized or differential cognitive impairment in this disorder. Furthermore, the study sought to address the potentially confounding factors of medication side effects and relevant demographic variables such as age, education, gender, and handedness.The neuropsychological functioning of 28 schizophrenic patients whose medication had been withdrawn for research purposes and 15 demographically matched normal subjects was evaluated. A comprehensive battery of tasks was used to determine whether performance patterns of schizophrenic patients were consistent with models of lateralized or localized neuropsychological impairment in schizophrenia. To facilitate comparison with results of other studies, several analytic strategies were used, including comparisons of group performance on individual tests, composite function scores, and evaluation of performance based on "clinical" criteria of impairment.In contrast to the normal subjects, the schizophrenic patients displayed impairment across measures of motor, sensory, and perceptual functioning, verbal and nonverbal memory, and indexes of frontal lobe functioning. This pattern of generalized dysfunction was evident regardless of the method of analysis used to assess performance.These findings fail to support conjectures regarding differential neurocognitive deficits in schizophrenia. However, the psychometric limitations of currently available neuropsychological measures may obscure the finding of differential impairment and must be considered in interpreting the results of this study as well as those of any investigation using such instruments.
Abstract 19103: Revascularization Improves the Myopathy, Hemodynamics and Function of the Limbs of Patients With Peripheral Arterial Disease
Authors: Evlampia Papoutsi, George P Casale, Panagiotis Koutakis, Sara Myers, Jonathan R Thompson, Duy Ha, Stanley A Swanson, Zhen Zhu, Kyung-Soo Kim, Shane Wurdeman, Jason M Johanning, Rodney D McComb, Iraklis I Pipinos
Journal: Circulation (2013)

Introduction: Peripheral arterial disease (PAD), is characterized by myopathy, reduced hemodynamics and dysfunction of the ischemic legs. Two key characteristics of the myopathy of PAD limbs are myofiber degeneration and oxidative damage. We hypothesize that revascularization operations improve the myopathy of PAD limbs in association with improvements of hemodynamics and function. Methods: We recruited PAD patients undergoing open or endovascular revascularization of their ischemic legs. The gastrocnemius of these patients was biopsied, and limb hemodynamics (Ankle-Brachial Index, ABI) and function (six-minute walking distance and treadmill claudication walking times) were assessed before and six months after revascularization. Slide mounted specimens of the gastrocnemius biopsies were analyzed for biomarkers of myofiber oxidative damage (carbonyl groups and 4-hydroxy-2-nonenal adducts) and morphology (myofiber cross-sectional area, major axis, minor axis and equivalent diameter) by quantitative fluorescence microscopy. Results: Thirty claudicating patients underwent revascularization operations (21 open and 9 endovascular operations). Revascularization reduced oxidative damage observed as decreased carbonyl groups (13.4%, p&lt;0.001) and 4-hydroxy-2-nonenal adducts (29.6%, p&lt;0.001). Myofiber morphology improved as determined by increased cross-sectional area (18.1%, p&lt;0.001), major axis (5.3%, p&lt;0.05), minor axis (4.6%, p&lt;0.05) and equivalent diameter (6.3%, p&lt;0.01). ABI increased from 0.50±0.03 to 0.86±0.03 (p&lt;0.001) and limb function improved as determined by increases of six-minute walking distance (25.9%, p&lt;0.05), onset of claudication time (101.4%, p=0.001) and maximum walking time (236.3%, p=0.01). Conclusions: Revascularization operations improved the myopathy of PAD limbs in association with improvements in both hemodynamics and function.
Prognostic factors for clinical benefit after epidermal growth factor receptor (EGFR) directed therapy in squamous cell carcinomas of the head and neck (SCCHN)
Authors: A. B. Halpern, K. Kasza, M. Kocherginsky, G. Clark, E. E. Vokes, R. Williams, E. E. Cohen
Journal: Journal of Clinical Oncology (2007)

6025 Background: Single agent EGFR tyrosine kinase inhibitors (TKI) have demonstrated reproducible response rates of 5–15% in treatment of SCCHN. The subset of patients that benefits most from these agents remains unknown. We undertook a review of data from 5 clinical trials administering EGFR TKI in order to determine if there are clinical characteristics that are associated with response or benefit. Methods: We reviewed individual patient data from 5 clinical trials of erlotinib, lapatinib, or gefitinib. The primary endpoint was association of clinical variables with clinical benefit, defined as response (CR or PR) and stable disease (SD) &gt;4 months. Secondary correlative endpoints included progression-free survival (PFS) and overall survival (OS). Logistic regression and Cox proportional hazard models were used to conduct univariate and multivariate analysis. Results: 319 subjects were included in the analysis with a median age of 59 years, 79% male. Disease status at start of therapy was local only in 43%, metastatic only in 29%, and both in 27%. Performance status (PS) was 0 in 25%, 1 in 62%, and 2 in 13%. Observed responses were: 1% CR, 6% PR, 24% SD &gt;4 mo, 18 % SD3 in 6%) and diarrhea (grade 1 in 30%, grade 2 in 10%, grade 3 in 5%). Lower PS (p=0.06, OR (0/2)=3.1), age 70+ (p=0.02, OR= 2.1), and development of rash (p&lt;0.01, OR=3.6), and diarrhea (p=0.03, OR=1.8) were associated with higher response rates. These variables were also associated with longer OS and PFS. Conclusions: Clinical parameters that appear to predict response to EGFR TKI include PS and age. EGFR mechanistic toxicities that develop during therapy are highly associated with benefit and suggest a relationship between drug exposure and outcome. No significant financial relationships to disclose.