tbuckley/cabot-search huggingface dataset:
p14ARF Protein Expression Is a Predictor of Both Relapse and Survival in Squamous Cell Carcinoma of the Anterior Tongue
Authors: Rhonda A. Kwong, Larry H. Kalish, Tuan V. Nguyen, James G. Kench, Ronaldo J. Bova, Ian E. Cole, Elizabeth A. Musgrove, Robert L. Sutherland
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The INK4A-ARF locus at chromosome 9p21 is frequently altered in head and neck squamous cell carcinoma (SCC) and encodes two distinct tumor suppressors, p16INK4A and p14ARF. This study addressed the role of p14ARF as a potential prognostic marker in this disease. Experimental Design: p14ARF protein expression was assessed by immunohistochemistry in a cohort of 140 patients with SCC of the anterior tongue. Using univariate and multivariate Cox's proportional hazards models, the outcomes examined were time to disease recurrence or death, with or without clinicopathologic covariates, including nodal status, disease stage, treatment status, Ki-67 staining, and molecular markers with known functional or genetic relationships with p14ARF (p16INK4A, p53, pRb, p21WAF1/CIP1, E2F-1). Results: On multivariate analysis, p14ARF positivity (nucleolar p14ARF staining and/or nuclear p14ARF staining in ≥30% of tumor cells) was an independent predictor of improved disease-free survival (DFS; P = 0.002) and overall survival (OS; P = 0.002). This was further enhanced when p14ARF positivity was cosegregated with positive (≥1%) p16INK4A staining (DFS, P &amp;lt; 0.001; OS, P &amp;lt; 0.001). Patients whose cancers were p14ARF negative and p53 positive (&amp;gt;50%) had the poorest outcome (DFS, P &amp;lt; 0.001; OS, P &amp;lt; 0.001) of any patient subgroup analyzed. Conclusions: These data show that in patients with SCC of the tongue, combined nuclear and nucleolar expression of p14ARF protein predicts for improved DFS and OS independent of established prognostic markers.
Gene expression in human chondrocytes in late osteoarthritis is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy
Authors: C J Brew, P D Clegg, R P Boot-Handford, J G Andrew, T Hardingham
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: To investigate changes in gene expression in fibrillated and intact human osteoarthritis (OA) cartilage for evidence of an altered chondrocyte phenotype and hypertrophy. Methods: Paired osteochondral samples were taken from a high-load site and a low-load site from 25 OA joints and were compared with eight similar paired samples from age-matched controls. Gene expression of key matrix and regulatory genes was analysed by quantitative real-time reverse transcription-polymerase chain reaction on total RNA extracted from the cartilage. Results: There was a major change in chondrocyte gene expression in OA cartilage. SOX9 (38-fold) and aggrecan (4-fold) gene expression were both lower in OA (p&lt;0.001), and collagen I (17-fold) and II (2.5-fold) gene expression were each increased in a subset of OA samples. The major changes in gene expression were similar at the fibrillated high-loaded site and the intact low-loaded site. There was no evidence of a generalised change in OA to proliferative or hypertrophic phenotype as seen in the growth plate, as genes associated with either stage of differentiation were unchanged (PTHrPR), or significantly downregulated (collagen X (14-fold, p&lt;0.002), VEGF (23-fold, p&lt;0.02), BCL-2 (5.6-fold, p&lt;0.001), matrilin-1 (6.5-fold, p&lt;0.001)). In contrast MMP-13 was significantly upregulated in the OA cartilage samples (5.3-fold, p&lt;0.003). Conclusions: The expression of key chondrocyte genes, including aggrecan and SOX9, was decreased in OA cartilage and the changes were similar in both fibrillated high-loaded and intact low-loaded cartilage on the same joint. However, there was no significant upregulation of type X collagen, and other genes associated with chondrocyte further differentiation and hypertrophy.
Part 8: Education, Implementation, and Teams
Authors: Farhan Bhanji, Judith C. Finn, Andrew Lockey, Koenraad Monsieurs, Robert Frengley, Taku Iwami, Eddy Lang, Matthew Huei-Ming Ma, Mary E. Mancini, Mary Ann McNeil, Robert Greif, John E. Billi, Vinay M. Nadkarni, Blair Bigham, Janet E. Bray, Jan Breckwoldt, Steven C. Brooks, Adam Cheng, Aaron J. Donoghue, Jonathan P. Duff, Dana P. Edelson, Henrik Fischer, Elaine Gilfoyle, Ming-Ju Hsieh, David A. Kloeck, Patrick Ko, Marion Leary, Theresa M. Olasveengen, Jon C. Rittenberger, Robert D. Schultz, Dion Stub, Zuzana Triska, Traci A. Wolbrink, Chih-Wei Yang, Joyce Yeung
Journal: Circulation (2015)
Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa
Authors: G. Kelly, R. Hughes, T. McGarry, M. Born, K. Adamzik, R. Fitzgerald, C. Lawlor, A.M. Tobin, C.M. Sweeney, B. Kirby
Journal: British Journal of Dermatology (2015)

There is a dearth of information on the precise pathogenesis of hidradenitis suppurativa (HS), but immune dysregulation is implicated.To determine the nature of the immune response in HS.Skin biopsies - lesional, perilesional (2 cm away) and uninvolved (10 cm away) - were obtained from patients with HS and healthy controls. The expression of various cytokines was determined by enzyme-linked immunosorbent assay, flow cytometry and real-time polymerase chain reaction.The expression of the inflammatory cytokines interleukin (IL)-17, IL-1β and tumour necrosis factor-α was enhanced in lesional skin of patients with HS. In addition, IL17A and IL1B mRNA were enhanced in clinically normal perilesional skin. CD4(+) T cells produced IL-17 in HS, while CD11c(+) CD1a(-) CD14(+) cells were sources of IL-1β. Activated caspase-1 was detected in HS skin and was associated with enhanced expression of NLRP3 and IL18. Inhibition of caspase-1 decreased IL-1β and IL-18 production, suggesting that the caspase-1 pathway participates in IL-1β and IL-18 expression in HS. Abnormal cytokine expression was detected in perilesional and uninvolved skin, which may suggest that subclinical inflammation is present in HS skin prior to the formation of an active lesion.This study demonstrates that CD4(+) T cells produce IL-17 in HS and that the IL-17 pathway may be important in HS pathogenesis. CD11c(+) CD1a(-) CD14(+) cells are a source of IL-1β in HS, the production of which was shown to be mediated, in part, via a caspase-1-dependent pathway. These results suggest that IL-17 and the caspase-1-associated cytokines IL-1β and IL-18 may play a role in the pathogenesis of HS.
Clinical Efficacy, Tolerability, and Safety of SAM486A, a Novel Polyamine Biosynthesis Inhibitor, in Patients with Relapsed or Refractory Non-Hodgkin’s Lymphoma
Authors: Miklos Pless, Karim Belhadj, Hans D. Menssen, Wolfgang Kern, Bertrand Coiffier, Jürgen Wolf, Richard Herrmann, Eckhard Thiel, Doug Bootle, Ivo Sklenar, Christian Müller, Les Choi, Carl Porter, Renaud Capdeville
Journal: Clinical Cancer Research (2004)

Abstract Purpose: SAM486A is a new inhibitor of S-adenosyl-methionine-decarboxylase, a key enzyme for polyamine biosynthesis. It is more potent than the first generation S-adenosyl-methionine-decarboxylase inhibitor methylglyoxal bis-guanylhydrazone. This Phase IIa study reports the findings of SAM486A monotherapy in patients with refractory or relapsed non-Hodgkin’s lymphoma (NHL). Patients and Methods: Forty-one previously treated patients with either diffuse large cell, follicular, or peripheral T-cell NHL were treated i.v. with 100 mg/m2 SAM486A as a daily 1-h infusion for 5 days repeated every 3 weeks. Treatment was continued for a total of eight cycles or until disease progression. Results: Two patients, both with large B-cell lymphoma, showed a complete response at cycle 3 that was maintained for ≥13 and ≥28 months. Five patients had a partial response, and 3 had stable disease at last follow-up. The overall response rate (complete response plus partial response) was 18.9% for evaluable patients (7 patients). Anemia was the primary hematological toxicity and observed in 7 (17.1%) patients. Five patients experienced grade 3/4 anemia. Four patients (9.8%) experienced grade 3/4 febrile neutropenia and grade 3/4 thrombocytopenia, respectively. Nonhematological toxicities were mild to moderate in intensity. The most frequent side effects were nausea (39%), vomiting (22%), diarrhea (19.5%), asthenia (17.1%), abdominal pain (14.6%), and flushing (9.8%). Conclusion: SAM486A has a promising clinical activity in patients with poor prognosis NHL and manageable safety profile. To further define the role of SAM486A, in the treatment of NHL, additional studies are warranted.
Prognostic Impact of Minimal Pleural Effusion in Non–Small-Cell Lung Cancer
Authors: Jeong-Seon Ryu, Hyo Jin Ryu, Si-Nae Lee, Azra Memon, Seul-Ki Lee, Hae-Seong Nam, Hyun-Jung Kim, Kyung-Hee Lee, Jae-Hwa Cho, Seung-Sik Hwang
Journal: Journal of Clinical Oncology (2014)

Minimal (< 10 mm thick) pleural effusion (PE) may represent an early phase of malignant PE, but its clinical relevance has rarely been studied. Therefore, we examined the proportion of minimal PE in patients with non-small-cell lung cancer (NSCLC) and its impact on survival. We also considered possible accumulation mechanisms in our data set.On the basis of PE status from chest computed tomography scans at diagnosis, 2,061 patients were classified into three groups: no PE, minimal PE, and malignant PE. Twenty-one variables associated with four factors-patient, stage migration, tumor, and treatment-were investigated for correlation with survival.Minimal PE presented in 272 patients (13.2%). Of 2,061 patients, the proportion of each stage was the following: 5.2% stage I, 10.9% stage II, 13.2% stage IIIA, 23.8% stage IIIB, and 13.9% stage IV. Minimal PE correlated significantly with shorter survival time than did no PE (median survival time, 7.7 v 17.7 months; log-rank P < .001), even after full adjustment with all variables (adjusted hazard ratio, 1.40; 95% CI, 1.21 to 1.62). Prognostic impact of minimal PE was higher in early versus advanced stages (Pinteraction = .001). In 237 patients (87.8%) with minimal PE, pleural invasion or attachment as a direct mechanism was observed, and it was an independent factor predicting worse survival (P = .03).Minimal PE is a commonly encountered clinical concern in staging NSCLCs. Its presence is an important prognostic factor of worse survival, especially in early-stage disease.
Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: meta-analysis of randomised controlled
Authors: A Messori
Journal: BMJ (2000)

<h3>Aim</h3> Comparing outcomes after combined phacoemulsification, two iStents insertion and endocyclophotocoagulation (ECP) versus phacoemulsification-iStents alone. <h3>Methods</h3> This is a longitudinal retrospective 12 months study in eyes with ocular hypertension or early-to-moderate open angle glaucoma. Level of disease, intraocular pressure (IOP) and tolerance of glaucoma medication were considered before planning surgery. Best-corrected visual acuity (BCVA-logMAR), IOP (mm Hg), number of medications were assessed at baseline, week 1, week 5, month 3, 6, 12 postop. Main outcome: percentage (%) in IOP reduction at 12 months vs medicated baseline. Secondary outcomes: absolute values of IOP/medication reduction, BCVA and postop complications. <h3>Results</h3> The ICE2 (two iStents-cataract extraction-ECP) group included 63 eyes and Phaco-iStent group included 46 eyes. Baseline IOP was higher in the ICE2 than phaco-iStent group (19.97±4.31 mm Hg vs 17.63±3.86 mm Hg, p=0.004) and mean deviation was lower (−7.20±2.58 dB vs −4.94±4.51 dB, p=0.037). Number of medications were comparable at baseline: 2.22±1.06 (ICE2) vs 2.07±1.02 (phaco-iStent), p=0.442. At month 12 postop, IOP in the ICE2 group decreased 35% from baseline vs 21% in the phaco-iStent group (p=0.03); absolute IOP reduction was significantly lower than baseline in each group (p&lt;0.001), yet final IOP was lower in the ICE2 group than phaco-iStent group (13.05±2.18 mm Hg vs 14.09±1.86 mm Hg, p=0.01). Similar results were found for glaucoma medication (1.24±1.05 in ICE2 group vs 1.39±1.03 in phaco-iStent group, p=0.01). Final BCVA was 0.11±0.18 (phaco-iStent group) vs 0.08±0.08 (ICE2 group), p=0.309. Safety outcomes were comparable between groups. <h3>Conclusion</h3> ICE2 procedure offers better results in IOP/medication reduction at 12 months than phacoemulsification-iStents alone.
Alterations of the Tumor Suppressor Gene <b> <i>Parkin</i> </b> in Non-Small Cell Lung Cancer
Authors: Maria Cristina Picchio, Eric Santos Martin, Rossano Cesari, George Adrian Calin, Sai Yendamuri, Tamotsu Kuroki, Francesca Pentimalli, Manuela Sarti, Kristine Yoder, Larry R. Kaiser, Richard Fishel, Carlo Maria Croce
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Parkin, a gene mutated in autosomal recessive juvenile Parkinsonism and mapped to the common fragile site FRA6E on human chromosome 6q25-q27, is associated with a frequent loss of heterozygosity and altered expression in breast and ovarian carcinomas. In addition, homozygous deletions of exon 2 creating deleterious truncations of the Parkin transcript were observed in the lung adenocarcinoma cell lines Calu-3 and H-1573, suggesting that the loss of this locus and the resulting changes in its expression are involved in the development of these tumors. Experimental Design: We examined 20 paired normal and non-small cell lung cancer samples for the presence of Parkin alterations in the coding sequence and changes in gene expression. We also restored gene expression in the Parkin-deficient lung carcinoma cell line H460 by use of a recombinant lentivirus containing the wild-type Parkin cDNA. Results: Loss of heterozygosity analysis identified a common region of loss in the Parkin/FRA6E locus with the highest frequency for the intragenic marker D6S1599 (45%), and semi-quantitative reverse transcription-PCR revealed reduced expression in 3 of 9 (33%) lung tumors. Although we did not observe any in vitro changes in cell proliferation or cell cycle, ectopic Parkin expression had the ability to reduce in vivo tumorigenicity in nude mice. Conclusion: These data suggest that Parkin is a tumor suppressor gene whose inactivation may play an important role in non-small cell lung cancer tumorigenesis.
Place of Routine Examinations in Promotion of Health Among Industrial Executives
Authors: O. B. Schreuder
Journal: BMJ (1958)

Although occupational medicine has been well recog nized and well implemented in industry in the United States for a number of years, it is only during the past eight to ten years that the executive health phase of this programme has been stressed to any great extent. That industrial medicine has progressed rather rapidly during the past several years in the United States is shown by its recognition as a specialty under the American Board of Preventive Medicine, other subspecialties under this board being public health and aviation medicine.
Antibiotic Therapy of Acute Exacerbations of Chronic Bronchitis
Authors: M. BROOKE NICOTRA
Journal: Annals of Internal Medicine (1982)

We conducted a double-blind, randomized, placebocontrolled trial in 40 patients to evaluate the need for antibiotics in acute exacerbations of chronic bronchitis. All patients were sufficiently ill to require hospitalization although none needed ventilatory support; the presence of pneumonia was excluded. Treatment consisted of bronchodilators, corticosteroids, and either tetracycline, 500 mg, or placebo by mouth every 6 hours for 1 week. Arterial blood gases, Spirometrie tests, bacteriologic evaluation of sputum, and patient and physician evaluation of the severity of illness were assessed at the beginning and end of the study. All patients improved both symptomatically and by objective measures of lung function. At the end of the study period there were no differences between those patients receiving tetracycline and those receiving placebo. We conclude that antibiotic therapy is not needed in moderately ill patients with exacerbations of chronic bronchitis.
Remembering the “Pan” in “Pandemic”: Considering the Impact of Global Resource Disparity on a Duty to Treat
Authors: Alison Reiheld
Journal: The American Journal of Bioethics (2008)

While Malm and colleagues (2008) do a fine job of considering the limits and merits of a duty to treat in the face of pandemic disease, they do so in the developed-world context. Developing world h...
Multicenter, Phase II Study of Decitabine for the First-Line Treatment of Older Patients With Acute Myeloid Leukemia
Authors: Amanda F. Cashen, Gary J. Schiller, Margaret R. O'Donnell, John F. DiPersio
Journal: Journal of Clinical Oncology (2009)

Older patients with acute myeloid leukemia (AML) have limited treatment options because of the lack of effectiveness and the toxicity of available therapies. We investigated the efficacy and toxicity of the hypomethylating agent decitabine as initial therapy in older patients with AML.In this multicenter, phase II study, patients older than 60 years who had AML (ie, > 20% bone marrow blasts) and no prior therapy for AML were treated with decitabine 20 mg/m(2) intravenously for 5 consecutive days of a 4-week cycle. Response was assessed by weekly CBC and bone marrow biopsy after cycle 2 and after each subsequent cycle. Patients continued to receive decitabine until disease progression or an unacceptable adverse event occurred.Fifty-five patients (mean age, 74 years) were enrolled and were treated with a median of three cycles (range, one to 25 cycles) of decitabine. The expert-reviewed overall response rate was 25% (complete response rate, 24%). The response rate was consistent across subgroups, including in patients with poor-risk cytogenetics and in those with a history of myelodysplastic syndrome. The overall median survival was 7.7 months, and the 30-day mortality rate was 7%. The most common toxicities were myelosuppression, febrile neutropenia, and fatigue.Decitabine given in a low-dose, 5-day regimen has activity as upfront therapy in older patients with AML, and it has acceptable toxicity and 30-day mortality.
Visual Event-Related Potentials in Subjects With Alexithymia: Modified Processing of Emotional Aversive Information?
Authors: Matthias Franz, Ralf Schaefer, Christine Schneider, Wolfgang Sitte, Jessica Bachor
Journal: American Journal of Psychiatry (2004)

A modified autonomous response (e.g., electrodermal activity) in subjects with alexithymia (a reduced ability to identify and communicate emotions) while processing emotional information is well known. However, the functional and neurobiological bases of this impairment are unclear. Do subjects with alexithymia suffer from a primary lack of perception ("emotional blindness"), or is alexithymia based on incomplete information processing due to immature undifferentiated cognitive schemes? The study investigates if subjects with alexithymia show a modified central response as a correlate of classifying emotional aversive stimuli.Twenty subjects with high alexithymia and 20 with low alexithymia (selected by the 20-item Toronto Alexithymia Scale) were investigated within a modified odd-ball paradigm. Three different stimulus categories were presented: aversive (probes) and affective neutral pictures (nontargets and instructed targets). Visual event-related EEG potentials and subjective data were recorded.All subjects showed elevated positive amplitudes or mean activity after probe presentation in the latency range: 150-260, 280-450, and 600-1500 msec. Subjects with alexithymia displayed increased positive components (especially P2) of visual event-related potentials after probe presentation than subjects without alexithymia. Subjects without alexithymia more frequently verbalized the emotional impact of these aversive pictures than subjects with alexithymia.These findings do not support the assumption of a primary lack of perception in alexithymia. Subjects with alexithymia show central correlates of perception and classification of aversive pictures. They may need more effort and cognitive recourses to process emotional information. Nevertheless, spontaneous verbal reference to emotional stimulus aspects is reduced.
The miR-15a–miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities
Authors: Désirée Bonci, Valeria Coppola, Maria Musumeci, Antonio Addario, Raffaella Giuffrida, Lorenzo Memeo, Leonardo D'Urso, Alfredo Pagliuca, Mauro Biffoni, Catherine Labbaye, Monica Bartucci, Giovanni Muto, Cesare Peschle, Ruggero De Maria
Journal: Nature Medicine (2008)
Interferon-α, but not the ABL-kinase inhibitor imatinib (STI571), induces expression of myeloblastin and a specific T-cell response in chronic myeloid leukemia
Authors: Andreas Burchert, Stefan Wölfl, Manuel Schmidt, Cornelia Brendel, Barbara Denecke, Dali Cai, Larissa Odyvanova, Tanja Lahaye, Martin C. Müller, Thomas Berg, Harald Gschaidmeier, Burghardt Wittig, Rüdiger Hehlmann, Andreas Hochhaus, Andreas Neubauer
Journal: Blood (2002)
Primary Tumor Standardized Uptake Value Measured on F18-Fluorodeoxyglucose Positron Emission Tomography Is of Prediction Value for Survival and Local Control in Non–Small-Cell Lung Cancer Receiving Radiotherapy: Meta-Analysis
Authors: Feifei Na, Jingwen Wang, Cong Li, Lei Deng, Jianxin Xue, You Lu
Journal: Journal of Thoracic Oncology (2014)

The 2-[18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) has become an imaging tool for clinical assessment of tumor, node, metastasis in non-small-cell lung cancer (NSCLC). Primary tumor maximum standardized uptake value (SUV(max)) on (18)F-FDG PET/CT before and after radiation therapy (RT) has been studied as a potential prognostic factor for NSCLC patients receiving radiotherapy. However, the sample sizes of most studies were small, and the results of the prediction value of SUV(max) remained undetermined, which lead us to perform a meta-analysis to improve the precision in estimating its effect.
Molecular Pathways: Targeting the Kinase Effectors of RHO-Family GTPases
Authors: Tatiana Y. Prudnikova, Sonali J. Rawat, Jonathan Chernoff
Journal: Clinical Cancer Research (2014)

RHO GTPases, members of the RAS superfamily of small GTPases, are adhesion and growth factor-activated molecular switches that play important roles in tumor development and progression. When activated, RHO-family GTPases such as RAC1, CDC42, and RHOA, transmit signals by recruiting a variety of effector proteins, including the protein kinases PAK, ACK, MLK, MRCK, and ROCK. Genetically induced loss of RHO function impedes transformation by a number of oncogenic stimuli, leading to an interest in developing small-molecule inhibitors that either target RHO GTPases directly, or that target their downstream protein kinase effectors. Although inhibitors of RHO GTPases and their downstream signaling kinases have not yet been widely adopted for clinical use, their potential value as cancer therapeutics continues to facilitate pharmaceutical research and development and is a promising therapeutic strategy.