tbuckley/cabot-search huggingface dataset:
Sofosbuvir for Hepatitis C Genotype 2 or 3 in Patients without Treatment Options
Authors: Ira M. Jacobson, Stuart C. Gordon, Kris V. Kowdley, Eric M. Yoshida, Maribel Rodriguez-Torres, Mark S. Sulkowski, Mitchell L. Shiffman, Eric Lawitz, Gregory Everson, Michael Bennett, Eugene Schiff, M. Tarek Al-Assi, G. Mani Subramanian, Di An, Ming Lin, John McNally, Diana Brainard, William T. Symonds, John G. McHutchison, Keyur Patel, Jordan Feld, Stephen Pianko, David R. Nelson
Journal: New England Journal of Medicine (2013)

Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection.We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy.Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treatment, as compared with 73% with 16 weeks of treatment (difference, -23 percentage points; 95% CI, -35 to -11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%).In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.).
Assessment of phalangeal bone loss in patients with rheumatoid arthritis by quantitative ultrasound
Authors: P Roben
Journal: Annals of the Rheumatic Diseases (2001)

Periarticular osteopenia is an early radiological sign of rheumatoid arthritis (RA). Quantitative ultrasound (QUS) devices have recently been shown to be useful for assessing osteoporosis. In this study the capability of a transportable and easy to use QUS device to detect skeletal impairment of the finger phalanges in patients with RA was investigated.In a cross sectional study 83 women (30 controls, 29 with glucocorticosteroid (GC) treated RA, and 24 with GC treated vasculitis) were examined. QUS measurements were obtained at the metaphyses of the proximal phalanges II-V and directly at the proximal interphalangeal joints II-IV with a DBM Sonic 1200 (IGEA, Italy) QUS device. Amplitude dependent speed of sound (AD-SoS) was evaluated. In 23 of the patients with RA, hand radiographs were evaluated.Significant differences between patients with RA and the other groups were found for AD-SoS at both measurement sites. Compared with age matched controls, the AD-SoS of patients with RA was lowered by two and three standard deviations at the metaphysis and joint, respectively. Fingers of patients with RA without erosions (Larsen score 0-I) already had significantly decreased QUS values, which deteriorated further with the development of erosions (Larsen II-V).This study indicates that QUS is sensitive to phalangeal periarticular bone loss in RA. QUS is a quick, simple, and inexpensive method free of ionising radiation that appears to be suited to detection of early stages of periarticular bone loss. Its clinical use in the assessment of early RA should be further evaluated in prospective studies.
Cyclooxygenase-2 Overexpression Is Associated with a Poor Outcome in Resected Ampullary Cancer Patients
Authors: Daniele Santini, Bruno Vincenzi, Giuseppe Tonini, Susanna Scarpa, Fortunata Vasaturo, Carolina Malacrino, Fabio Vecchio, Domenico Borzomati, Sergio Valeri, Roberto Coppola, Paolo Magistrelli, Gennaro Nuzzo, Aurelio Picciocchi
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To identify potential prognostic molecular factors in ampullary adenocarcinoma that could be of significant importance. To this end, we examined the possible prognostic significance of cyclooxygenase-2 (Cox-2) and Survivin expression and the apoptotic index in a cohort of uniformly treated patients with ampullary cancer treated with radical surgical excision. Experimental Design: The entry criteria were that the patients have a pathologic diagnosis of ampullary cancer which had been resected. Expression analysis for Cox-2 and Survivin was done by immunohistochemical staining. Apoptotic cells were identified by the terminal deoxyribonucleotidyl transferase–mediated dUTP nick-end labeling (TUNEL) method. Results: Thirty-nine tumor specimens from resected ampullary adenocarcinoma patients were included. By univariate analysis, overall survival was affected by Cox-2 expression and TUNEL staining (respectively, P = 0.0003 and 0.03). Survivin expression did not influence the overall survival in our patient population (P = 0.123). Patients' clinicopathologic features (gender, age, and T and N factors) did not influence outcome. In multivariate Cox regression analysis, Cox-2 expression (relative risk, 4.330; P = 0.005) was the only variable that significantly affected overall survival. Conclusions: The results of the present article provide, for the first time, evidence that Cox-2 expression, but not Survivin expression, may represent a significant prognostic factor after surgical resection in patients affected by cancer of the ampulla of Vater. Further studies are required to determine whether Cox-2 inhibitors may be useful for the therapy or prevention of ampullary carcinoma.
Malignant melanoma occurring at the periphery of a giant congenital naevus previously treated with laser therapy
Authors: S.L. Woodrow, N.P. Burrows
Journal: British Journal of Dermatology (2003)

Journal Article Malignant melanoma occurring at the periphery of a giant congenital naevus previously treated with laser therapy Get access S.L. Woodrow, S.L. Woodrow Department of Dermatology, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, U.K. E‐mail: woodrow.smith@btopenworld.com Search for other works by this author on: Oxford Academic Google Scholar N.P. Burrows N.P. Burrows Department of Dermatology, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, U.K. E‐mail: woodrow.smith@btopenworld.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 4, 1 October 2003, Pages 886–888, https://doi.org/10.1046/j.1365-2133.2003.05591.x Published: 01 October 2003
<i>CMTM5</i> Exhibits Tumor Suppressor Activities and Is Frequently Silenced by Methylation in Carcinoma Cell Lines
Authors: Luning Shao, Yan Cui, Hongyu Li, Yanan Liu, Hongshan Zhao, Yu Wang, Yingmei Zhang, Ka Man Ng, Wenling Han, Dalong Ma, Qian Tao
Journal: Clinical Cancer Research (2007)

Abstract Purpose: CMTM5 (CKLF-like MARVEL transmembrane domain containing member 5) is located at 14q11.2, a locus associated with multiple cancers. It has six RNA splicing variants with CMTM5-v1 as the major one. We explored its expression pattern in normal tissues and tumor cell lines, as well as its functions in carcinoma cells. Experimental Design: We evaluated CMTM5 expression by semiquantitative reverse transcription-PCR (RT-PCR) in normal tissues and carcinoma cell lines of cervical, breast, nasopharyngeal, lung, hepatocellular, esophageal, gastric, colon, and prostate. We further examined CMTM5 promoter methylation in these cell lines. We also analyzed CMTM5 expression after 5-aza-2′-deoxycytidine treatment and genetic demethylation and the functional consequences of restoring CMTM5 in HeLa and PC-3 cells. Results: CMTM5-v1 is broadly expressed in human normal adult and fetal tissues, but undetectable or down-regulated in most carcinoma cell lines. Its promoter methylation was detected in virtually all the silenced or down-regulated cell lines. The silencing of CMTM5 could be reversed by pharmacologic demethylation or genetic double-knockout of DNMT1 and DNMT3B, indicating methylation-mediated mechanism. Restoration of CMTM5-v1 suppressed carcinoma cell proliferation, migration, and invasion. Conclusions: These results indicate that CMTM5 exhibits tumor suppressor activities, but with frequent epigenetic inactivation in carcinoma cell lines.
Validity of a Set of Clinical Criteria to Rule Out Injury to the Cervical Spine in Patients with Blunt Trauma
Authors: Jerome R. Hoffman, William R. Mower, Allan B. Wolfson, Knox H. Todd, Michael I. Zucker
Journal: New England Journal of Medicine (2000)

Because clinicians fear missing occult cervical-spine injuries, they obtain cervical radiographs for nearly all patients who present with blunt trauma. Previous research suggests that a set of clinical criteria (decision instrument) can identify patients who have an extremely low probability of injury and who consequently have no need for imaging studies.
Fatty acid synthase as a novel target for meningioma therapy
Authors: Daniela Haase, Stefan Schmidl, Christian Ewald, Rolf Kalff, Christian Huebner, Raimund Firsching, Gerburg Keilhoff, Matthias Evert, Werner Paulus, David H. Gutmann, Anita Lal, Christian Mawrin
Journal: Neuro-Oncology (2010)

High levels of fatty acid synthase (FAS) expression have been reported in hormone receptor-positive tumors, including prostate, breast, and ovarian cancers, and its inhibition reduces tumor growth in vitro and in vivo.Similar to other hormone receptor-positive tumor types, meningiomas are progesterone receptor-and estrogen receptor-immunoreactive brain tumors.To define the role of FAS in human meningioma growth control, we first analyzed the FAS expression using a tissue microarray containing 38 meningiomas and showed increased FAS expression in 70% of atypical WHO grade II and anaplastic WHO grade III meningiomas compared with 10% of benign WHO grade I tumors.We next confirmed this finding by real-time PCR and Western blotting.Second, we demonstrated that treatment with the FAS inhibitor, cerulenin (Cer), significantly decreased meningioma cell survival in vitro.Third, we showed that Cer treatment reduced FAS expression by modulating Akt phosphorylation (activation).Fourth, we demonstrated that Cer treatment of mice bearing meningioma xenografts resulted in significantly reduced tumor volumes associated with increased meningioma cell death.Collectively, our data suggest that the increased FAS expression in human meningiomas represents a novel therapeutic target for the treatment of unresectable or malignant meningioma.
Improved relapse-free survival after autologous stem cell transplantation does not translate into better quality of life in chronic lymphocytic leukemia: Lessons from the randomized European Society for Blood and Marrow Transplantation-Intergroup study
Authors: Liesbeth C. de Wreede, Maggie Watson, Marleen van Os, Donald Milligan, Michel van Gelder, Mauricette Michallet, Peter Dreger, Claire E. Dearden, Janis Homewood, Jehan Dupuis, Michel Leporrier, Michal Karas, Bernadette Corront, Gabriela M. Baerlocher, Wolfgang Herr, Sylvain Choquet, Dietger W. Niederwieser, Laurent Sutton, Nicolaus Kröger, Theo M. de Witte, Johannes Schetelig
Journal: American Journal of Hematology (2013)

In chronic lymphocytic leukemia (CLL) medical progress is driven by clinical studies with relapse-free survival (RFS) as the primary endpoint. The randomized EBMT-Intergroup trial compared high-dose therapy and autologous stem cell transplantation (ASCT) to observation and demonstrated a substantial improvement of RFS without showing improved overall survival for the transplant arm. Here we report quality of life (QoL) information of the first 3 years following randomization from that study. The main objective was to assess the impact of treatment on QoL over time. Two secondary analyses were performed to further investigate the impact of ASCT and relapse on QoL. In the primary analysis, we demonstrate an adverse impact of ASCT on QoL which was largest at 4 months and continued throughout the first year after randomization. Further, we demonstrated a sustained adverse impact of relapse on QoL which worsened over time. Despite better disease control by ASCT the side effects thus turned the net effect towards inferior QoL in the first year and comparable QoL in the following 2 years after randomization. This study emphasizes the importance of information concerning QoL impacts when patients are counseled about treatments aimed at improving RFS in the absence of a survival benefit.
Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury—outcomes at 6 months
Authors: Phil Edwards, Miguel Arango, Laura Balica, Rowland Cottingham, Hesham El-Sayed, Barbara Farrell, Janice Fernandes, Tamar Gogichaisvili, Nyoman Golden, Bennie Hartzenberg, Mazhar Husain, Mario Izurieta Ulloa, Zouheir Jerbi, Hussein Khamis, Edward Komolafe, Véronique Laloë, Gabrielle Lomas, Silke Ludwig, Guy Mazairac, Maria de los Angeles Muñoz Sanchéz, Luis Nasi, Fatos Olldashi, Patrick Plunkett, Ian Roberts, Peter Sandercock, Haleema Shakur, Caridad Soler, Reto Stocker, Petr Svoboda, Stefan Trenkler, N K Venkataramana, Jonathan Wasserberg, David Yates, Surakrant Yutthakasemsunt
Journal: The Lancet (2005)
Combination Trastuzumab and Chemotherapy May Have a Role in Women With Small, Node-Negative, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: Heather L. McArthur, Patrick G. Morris, Clifford A. Hudis
Journal: Journal of Clinical Oncology (2014)

TO THE EDITOR: In their recent editorial, Reeder-Hayes and Carey 1 address two important questions for patients with small ( 1.0 cm), node-negative (N0), breast cancer that overexpress human epidermal growth factor receptor 2 (HER2). First, what is the risk of distant metastases for these women? Second, what is the optimum approach to adjuvant therapy? With respect to the first issue, we agree that accurate risk-benefit analyses are critical to guide adjuvant systemic therapy. Risk stratification is particularly challenging when traditional assessment tools (tumor size, nodal status, and so on) estimate that the absolute risks of developing metastases are relatively low, but our understanding of tumor biology (eg, HER2-positive disease) suggests a more aggressive phenotype. In the articles accompanying the editorial, data from two cohort studies suggest that these patients do indeed have a relatively low risk of metastases. First, Fehrenbacher et al 2 report that with 5 years of follow-up, the distant recurrence-free interval was 99% (95% CI, 93.0% to 99.9%) for patients with T1aN0M0 HER2-positive breast cancer and 97.0% (95% CI, 88.6 to 99.2) for those with T1bN0M0 tumors. Similar results were seen in a second study by Vaz-Luis et al, 3 which included data from 257 women with T1a/bN0M0 HER2-positive breast cancer. Although these risks of distant metastases appear low, we agree with ReederHayes and Carey 1 that patient loss to follow-up may have underesti
Phenotypic switching of Cryptococcus neoformans occurs in vivo and influences the outcome of infection
Authors: Bettina C. Fries, Carlos P. Taborda, Evan Serfass, Arturo Casadevall
Journal: Journal of Clinical Investigation (2001)

Phenotypic switching has been linked to the virulence of many pathogens, including fungi. However, it has not been conclusively shown to occur in vivo or to influence the outcome of infection. Cryptococcus neoformans undergoes phenotypic switching in vitro to colony types that differ in their virulence in mice. In this study, we asked whether C. neoformans undergoes phenotypic switching in vivo and whether this phenomenon contributes to virulence. By using a small inoculum to preclude the introduction of variants that had already switched during in vitro propagation, we demonstrated that in vivo switching to a mucoid phenotype occurred in two mice strains and was associated with a lethal outcome. Phenotypic switching resulted in changes of the capsular polysaccharide that inhibited phagocytosis by alveolar macrophages. This promoted a more vigorous inflammatory response and rapid demise. These data document in vivo switching in a fungus and associate this phenomenon with enhanced virulence and a lethal outcome. The importance of this finding is underscored by the increased likelihood of phenotypic switching in chronic cryptococcosis; thus this mechanism may account for the inability to eradicate the organism in immunocompromised hosts.
The role of alpha 1- and alpha 2-adrenergic receptors in mediation of coronary vasoconstriction in hypoperfused ischemic myocardium during exercise.
Authors: D D Laxson, X Z Dai, D C Homans, R J Bache
Journal: Circulation Research (1989)

This study was carried out to test the hypothesis that adrenergic coronary vasoconstriction limits blood flow to hypoperfused regions of myocardium during exercise. The vasoconstrictor influence of alpha-adrenergic receptor subtypes was assessed by use of selective adrenergic blocking agents. Dogs chronically instrumented with a circumflex coronary artery hydraulic occluder and an intra-arterial catheter underwent treadmill exercise in the presence of a coronary stenosis that decreased distal perfusion pressure to 40 mm Hg. Myocardial blood flow was measured with radioactive microspheres (15 microns) before and during selective alpha 1- or alpha 2-adrenergic receptor blockade produced by intracoronary infusion of prazosin (1 microgram/kg/min x 10 min) or idazoxan (1 microgram/kg/min x 10 min), respectively. Coronary perfusion pressure was held equal before and during receptor blockade with the hydraulic occluder. Compared with control exercise, subendocardial blood flow increased during alpha 1-receptor blockade with prazosin from 0.60 +/- 0.14 to 1.12 +/- 0.17 ml/min/g (p less than 0.05), and mean transmural flow increased from 1.07 +/- 0.19 to 1.60 +/- 0.22 ml/min/g (p less than 0.05). In contrast, subendocardial and mean transmural blood flow were not different from control during selective alpha 2-adrenergic receptor blockade with idazoxan (0.48 +/- 0.10 vs. 0.67 +/- 0.14 ml/min/g, p = 0.33, and 0.82 +/- 0.15 vs. 1.02 +/- 0.20 ml/min/g, p = 0.45, respectively). These data indicate that even in the presence of a coronary stenosis that causes substantial myocardial underperfusion during exercise, residual coronary vasoconstrictor tone is present in ischemic myocardium, and this vasoconstriction is mediated predominantly by the alpha 1-adrenergic receptor.
Mitochondrial oxidative activity in human rheumatoid synovial lining cells.
Authors: B Henderson, L Bitensky, J Chayen
Journal: Annals of the Rheumatic Diseases (1978)

The activities of two mitochondrial enzymes, succinate dehydrogenase and cytochrome oxidase, have been measured by quantitative cytochemistry and microdensitometry in the synoviocytes of rheumatoid and non-rheumatoid synovial lining cells. Although both tended to be higher in the former, there was no statistically significant difference in the activities of either enzyme in these tissues. However, when cytochrome oxidase activity was measured without exogenous cytochrome c, the activity in the rheumatoid synoviocytes was highly significantly elevated. It is suggested that these findings may indicate only that the cytochrome c-cytochrome oxidase complex in the rheumatoid cells is more stable, possibly because of the increased availability of phospholipids in these cells.
Muscarinic M3 receptor stimulation increases cigarette smoke-induced IL-8 secretion by human airway smooth muscle cells
Authors: R. Gosens, D. Rieks, H. Meurs, D. K. Ninaber, K. F. Rabe, J. Nanninga, S. Kolahian, A. J. Halayko, P. S. Hiemstra, S. Zuyderduyn
Journal: European Respiratory Journal (2009)

Acetylcholine is the primary parasympathetic neurotransmitter in the airways and is known to cause bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine also regulates aspects of remodelling and inflammation through its action on muscarinic receptors. In the present study, we aimed to determine the effects of muscarinic receptor stimulation on cytokine production by human airway smooth muscle cells (primary and immortalised cell lines). The muscarinic receptor agonists carbachol and methacholine both induced modest effects on basal interleukin (IL)-8 and -6 secretion, whereas the secretion of RANTES, eotaxin, vascular endothelial growth factor-A and monocyte chemoattractant protein-1 was not affected. Secretion of IL-8 and -6 was only observed in immortalised airway smooth muscle cells that express muscarinic M3 receptors. In these cells, methacholine also significantly augmented IL-8 secretion in combination with cigarette smoke extract in a synergistic manner, whereas synergistic effects on IL-6 secretion were not significant. Muscarinic M3 receptors were the primary subtype involved in augmenting cigarette smoke extract-induced IL-8 secretion, as only tiotropium bromide and muscarinic M3 receptor subtype selective antagonists abrogated the effects of methacholine. Collectively, these results indicate that muscarinic M3 receptor stimulation augments cigarette smoke extract-induced cytokine production by airway smooth muscle. This interaction could be of importance in patients with chronic obstructive pulmonary disease.
ABO Blood Groups and Multiple Cancers
Authors: H. A. Fadhli
Journal: JAMA (1963)

A statistically significant excess of blood group A has been found in a sample of 123 white patients with multiple primary cancers. This sample represents 2.4% of all patients with cancer in a 20-year survey. In 54% of the patients, the first and last diagnosis of cancer occurred within 3 years of one another. The relative frequency of sites of these cancers, taken individually, does not differ essentially from that of single cancers. No statistically significant difference was found between male and female with respect to the ABO system. If the excess of multiple primary cancers in patients with group A blood can be established in larger series and in different geographical locations, it will mean that the probability of another primary cancer developing is greater in the patients of blood group A.