tbuckley/cabot-search huggingface dataset:
Clinical and molecular characteristics of congenital glioblastoma
Authors: M. E. Macy, D. K. Birks, V. N. Barton, M. H. Chan, A. M. Donson, B. K. Kleinschmidt-DeMasters, L. T. Bemis, M. H. Handler, N. K. Foreman
Journal: Neuro-Oncology (2012)

Congenital glioblastoma (cGBM) is an uncommon tumor of infancy with a reported variable but often poor cure rate, even with intensive therapy. Five patients with cGBMs, arising de novo and not in familial tumor predisposition kindreds, were studied for histological and biological features, using Affymetrix microarray. Tumors were large, often associated with hemorrhage, extended into the thalamus, and often bulged into the ventricles. One patient died acutely from bleeding at the time of operation. The 4 surviving patients underwent surgery (1 gross total resection, 3 subtotal resections or biopsies) and moderate intensity chemotherapy without radiation, and remain progression-free at a median time of 36 months (range, 30–110 months). Affymetrix microarrays measured gene expression on the 3 cGBMs from which frozen tissue was available. Unsupervised hierarchical clustering of cGBMs versus 168 other central nervous system tumors demonstrated that cGBMs clustered most closely with other high-grade gliomas. Gene expression profiles of cGBMs were compared with non-congenital pediatric and adult GBMs. cGBMs demonstrated marked similarity to both pediatric and adult GBMs, with only 31 differentially expressed genes identified (false discovery rate, <0.05). Unique molecular features of cGBMs included over-expression of multiple genes involved in glucose metabolism and tissue hypoxia. cGBMs show histological and biological overlap with pediatric and adult GBMs but appear to have a more favorable outcome, with good response to moderate intensity chemotherapy with only subtotal resection or biopsy. Further study may determine whether identified gene expression differences contribute to the improved survival seen in these tumors.
A study of the impact of Sun Awareness Week 1995
Authors: C. FLEMING, J. NEWELL, S. TURNER, R. MACKIE
Journal: British Journal of Dermatology (1997)

We report a questionnaire-based survey of parents of schoolchildren to assess the impact of Sun Awareness Week, organized by the U.K. Skin Cancer Working Party, from 4 to 10 June 1995. A questionnaire was designed, pre-tested and modified. Nine hundred and eighty-nine patients of schoolchildren were approached before and after Sun Awareness Week at eight comprehensive primary schools and a children's clothes shop. Responses to the questionnaires were analysed in the following categories: total knowledge, sunscreen knowledge, melanoma risk factor knowledge, attitude, self-reported behaviour and awareness of the link between childhood sun exposure and cancer (link). A reasonable level of knowledge was demonstrated in the sample population. Significant improvements in attitude and behaviour scores were observed (P < 0.05). Three of the four link questions were significantly improved (P < 0.005). These results were not explained by differences in age, sex, or occupation between the before and after populations. Further national studies are needed to establish long-term benefits of such interventions.
Imaging guided thoracic interventions
Authors: B. Ghaye, R.F. Dondelinger
Journal: European Respiratory Journal (2001)

Interventional Radiology is a technique based medical specialty, using all available imaging modalities (fluoroscopy, ultrasound, computed tomography, magnetic resonance, angiography) for guidance of interventional techniques for diagnostic or therapeutic purposes. Actual, percutaneous transthoracic needle biopsy includes core needle biopsy besides fine needle aspiration. Any pleural, pulmonary or mediastinal fluid or gas collection is amenable to percutaneous pulmonary catheter drainage. Treatment of haemoptysis of the bronchial artery or pulmonary artery origin, transcatheter embolization of pulmonary arteriovenous malformations and pseudoaneurysms, angioplasty and stenting of the superior vena caval system and percutaneous foreign body retrieval are well established routine procedures, precluding unnecessary surgery. These techniques are safe and effective in experienced hands. Computed tomography is helpful in pre- and postoperative imaging of patients being considered for endobronchial stenting. Many procedures can be performed on an outpatient basis, thus increasing the cost-effectiveness of radiologically guided interventions in the thorax.
Immunohistochemical localization of lysyl oxidase in normal human skin
Authors: H. KOBAYASHI, M. ISHII, M. CHANOKI, N. YASHIRO, H. FUSHIDA, K. FUKAI, T. KONO, T. HAMADA, H. WAKASAKI, A. OOSHIMA
Journal: British Journal of Dermatology (1994)

Lysyl oxidase (EC 1.4.3.13), a copper‐dependent enzyme which catalyses the formation of aldehyde cross‐links, and acts primarily on collagen and elastin, is known to be increased during wound healing and in fibrotic disorders including liver cirrhosis and atherosclerosis, and to be decreased in some hereditary connective tissue diseases and in malignant cell lines. A recent study showed that lysyl oxidase might possess tumour suppressor activity as an antioncogene for ras. Little is known about the localization of this enzyme in human skin. In this study, we determined immunohistochemically the localization of lysyl oxidase in normal skin of young and elderly subjects obtained from sun‐exposed and unexposed regions of the body. All skin samples tested had similar distributions of lysyl oxidase. The enzyme was present both extracellularly and intracellularly. Extracellularly, a few granular aggregates of immunoreactants were observed along collagen and elastic fibres. These granules were more common in the adventitial portion of the dermis than in the reticular portion. Of all sun‐exposed and unexposed regions studied, the skin of the face displayed the greatest amount of extracellular immunoreactants. Immunopositive granules were observed intracellularly in fibroblasts, vascular endothelial cells, sweat glands, sebaceous glands, arrector pili muscles and some keratinocytes. These findings provide evidence that, as suggested in recent reports, lysyl oxidase may have a variety of intracellular functions.
Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial
Authors: Thomas A Rasmussen, Martin Tolstrup, Christel R Brinkmann, Rikke Olesen, Christian Erikstrup, Ajantha Solomon, Anni Winckelmann, Sarah Palmer, Charles Dinarello, Maria Buzon, Mathias Lichterfeld, Sharon R Lewin, Lars Østergaard, Ole S Søgaard
Journal: The Lancet HIV (2014)
Selective Degradation of Basement Membrane Macromolecules by Metastatic Melanoma Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R H Kramer, K G Vogel
Journal: JNCI Journal of the National Cancer Institute (1984)

The extracellular matrix deposited in culture by the mouse endodermal cell line (PF HR9) was used as an experimental model to study the interactions between basement membranes and several tumorigenic and nontumorigenic cell lines, including the metastatic B16 melanoma cell sublines. Analysis by biochemical and immunologic methods indicated that the isolated HR9 extracellular matrix was composed of laminin, type IV collagen, entactin, and heparan sulfate proteoglycans--all basement membrane-specific macromolecules. Ultrastructurally, the extracellular matrix elaborated by the HR9 cells appears as a meshwork of finely fibrillar material. B16 melanoma cells were found to adhere rapidly to the isolated HR9 matrix, but significant penetration into the structure was not observed. However, the melanoma cells did induce an extensive solubilization of 35S-sulfate-labeled heparan sulfate to fragments that were approximately one-third the size of the intact heparan sulfate chains. Only the B16 melanoma sublines exhibited this unique pattern of proteoglycan degradation, which suggests that they possess an endoglycosidase specific for heparan sulfate chains. B16 melanoma cells seeded onto HR9 matrices labeled with [1H]leucine or [3H]proline caused no detectable increase in matrix protein solubilization compared to controls. The results indicate that the metastatic tumor cells degrade the proteoglycans in the HR9 matrix more readily than the other matrix proteins.
Liver microRNA-21 is overexpressed in non-alcoholic steatohepatitis and contributes to the disease in experimental models by inhibiting PPARα expression
Authors: Xavier Loyer, Valérie Paradis, Carole Hénique, Anne-Clémence Vion, Nathalie Colnot, Coralie L Guerin, Cécile Devue, Sissi On, Jérémy Scetbun, Mélissa Romain, Jean-Louis Paul, Marc E Rothenberg, Patrick Marcellin, François Durand, Pierre Bedossa, Carina Prip-Buus, Eric Baugé, Bart Staels, Chantal M Boulanger, Alain Tedgui, Pierre-Emmanuel Rautou
Journal: Gut (2015)

<h3>Objective</h3> Previous studies suggested that microRNA-21 may be upregulated in the liver in non-alcoholic steatohepatitis (NASH), but its role in the development of this disease remains unknown. This study aimed to determine the role of microRNA-21 in NASH. <h3>Design</h3> We inhibited or suppressed microRNA-21 in different mouse models of NASH: (a) low-density lipoprotein receptor-deficient (<i>Ldlr</i><sup>−/−</sup>) mice fed a high-fat diet and treated with antagomir-21 or antagomir control; (b) microRNA-21-deficient and wild-type mice fed a methionine-choline-deficient (MCD) diet; (c) peroxisome proliferation-activator receptor α (PPARα)-deficient mice fed an MCD diet and treated with antagomir-21 or antagomir control. We assessed features of NASH and determined liver microRNA-21 levels and cell localisation. MicroRNA-21 levels were also quantified in the liver of patients with NASH, bland steatosis or normal liver and localisation was determined. <h3>Results</h3> Inhibiting or suppressing liver microRNA-21 expression reduced liver cell injury, inflammation and fibrogenesis without affecting liver lipid accumulation in <i>Ldlr</i><sup>−/−</sup> fed a high-fat diet and in wild-type mice fed an MCD diet. Liver microRNA-21 was overexpressed, primarily in biliary and inflammatory cells, in mouse models as well as in patients with NASH, but not in patients with bland steatosis. PPARα, a known microRNA-21 target, implicated in NASH, was decreased in the liver of mice with NASH and restored following microRNA-21 inhibition or suppression. The effect of antagomir-21 was lost in PPARα-deficient mice. <h3>Conclusions</h3> MicroRNA-21 inhibition or suppression decreases liver injury, inflammation and fibrosis, by restoring PPARα expression. Antagomir-21 might be a future therapeutic strategy for NASH.
Osteopontin induces ductular reaction contributing to liver fibrosis
Authors: Xiaodong Wang, Aritz Lopategi, Xiaodong Ge, Yongke Lu, Naoto Kitamura, Raquel Urtasun, Tung-Ming Leung, Maria Isabel Fiel, Natalia Nieto
Journal: Gut (2014)

Objective In human chronic liver disease, there is association between ductular reaction (DR) and fibrosis; yet, the mechanism triggering its onset and its role in scar formation remains unknown. Since we previously showed that osteopontin (OPN) is highly induced during drug-induced liver fibrosis, we hypothesised that OPN could drive oval cells (OC) expansion and DR and signal to hepatic stellate cells (HSC) to promote scarring. Results In vivo studies demonstrated increased OPN expression in biliary epithelial cells (BEC) and in OC in thioacetamide (TAA)-treated mice. OPN ablation protected mice from TAA and bile duct ligation-induced liver injury, DR and scarring. This was associated with greater hepatocyte proliferation, lower OC expansion and DR along with less fibrosis, suggesting that OPN could activate the OC compartment to differentiate into BEC, which could then signal to HSC to enhance scarring. Since TAA-treated wild-type mice and cirrhotic patients showed TGF-β + BEC, which were lacking in TAA-treated Opn −/− mice and in healthy human explants, this suggested that OPN could regulate TGF-β, a profibrogenic factor. In vitro experiments confirmed that recombinant OPN (rOPN) decreases hepatocyte proliferation and increases OC and BEC proliferation. To evaluate how BEC regulate collagen-I production in HSC, co-cultures were established. Co-cultured BEC upregulated OPN and TGF-β expression and enhanced collagen-I synthesis by HSC. Lastly, recombinant TGF-β (rTGFβ) and rOPN promoted BEC proliferation and neutralisation of OPN and TGF-β reduced collagen-I expression in co-cultured HSC. Conclusions OPN emerges as a key matricellular protein driving DR and contributing to scarring and liver fibrosis via TGF-β.
The utility and safety evaluation of ultrasonography guided transthoracic biopsy
Authors: Yoshikazu Yamaji, Kazunori Tobino, Mina Asaji, Yuichiro Yasuda, Keisuke Anan, Kosuke Tsuruno, Yosuke Mukasa, Noriyuki Ebi
Journal: European Respiratory Journal (2014)

Rationale: Percutaneous transthoracic biopsy under computed tomography (CT) guidance has been well accepted as a useful technique to obtain tissue for histologic diagnosis of thoracic lesions that are not readily accessible with bronchoscopy. On the other hand, in the chest, the role of ultrasonography (US) has been limited to evaluation for pleural effusion and guidance for thoracentesis, although its role in the diagnosis of pulmonary, pleural, and mediastinal masses has been emphasized.  Aims: To examine the utility and safety evaluation of ultrasonography guided transthoracic biopsy at our institution.  Methods: From May 1, 2011 to October 31, 2013, US-guided transthoracic biopsies were performed in 42 consecutive patients at our institution. CT imaging characteristics of mass, histologic diagnosis, and complications were recorded.  Results: The location of the 42 lesions included 27 lung parenchymal, two pleural, six chest wall, and seven mediastinal. The mean mass diameter was 65.5 mm. A histologic diagnosis was achieved in 39 (92.8%) of 42 patients, including 31 primary or secondary carcinoma (74%); five lung abscess (12%), one empyema (2%), two non-specific inflammatory change (5%). CT scan demonstrated homogeneous or heterogeneous low attenuation in 21 lesions. There were nine (21.4%) procedure-related complications: three pneumothoraces, three pleuritis, and one hypotension due to vasovagal reflex, one disseminated to subcutaneous tissue, and one death.  Conclusions: US-guided thoracic biopsy is a safe, easy and reliable method with a high diagnostic yield in thoracic lesions.
Increasing CD44+/CD24- tumor stem cells, and upregulation of COX-2 and HDAC6, as major functions of HER2 in breast tumorigenesis
Authors: Kai-Hung Wang, An-Pei Kao, Chia-Cheng Chang, Jau-Nan Lee, Ming-Feng Hou, Cheng-Yu Long, Hung-Sheng Chen, Eing-Mei Tsai
Journal: Molecular Cancer (2010)

Abstract Background Cancer cells are believed to arise primarily from stem cells. CD44 + /CD24 - have been identified as markers for human breast cancer stem cells. Although, HER2 is a well known breast cancer oncogene, the mechanisms of action of this gene are not completely understood. Previously, we have derived immortal (M13SV1), weakly tumorigenic (M13SV1R2) and highly tumorigenic (M13SV1R2N1) cell lines from a breast epithelial cell type with stem cell phenotypes after successive SV40 large T-antigen transfection, X-ray irradiation and ectopic expression of HER2/C-erbB2/neu. Recently, we found that M13SV1R2 cells became non-tumorigenic after growing in a growth factor/hormone-deprived medium (R2d cells). Results In this study, we developed M13SV1R2N1 under the same growth factor/hormone-deprived condition (R2N1d cells). This provides an opportunity to analyze HER2 effect on gene expression associated with tumorigenesis by comparative study of R2d and R2N1d cells with homogeneous genetic background except HER2 expression. The results reveal distinct characters of R2N1d cells that can be ascribed to HER2: 1) development of fast-growing tumors; 2) high frequency of CD44 + /CD24 - cells (~50% for R2N1d vs. ~10% for R2d); 3) enhanced expression of COX-2, HDAC6 mediated, respectively, by MAPK and PI3K/Akt pathways, and many genes associated with inflammation, metastasis, and angiogenesis. Furthermore, HER2 expression can be down regulated in non-adhering R2N1d cells. These cells showed longer latent period and lower rate of tumor development compared with adhering cells. Conclusions HER2 may induce breast cancer by increasing the frequency of tumor stem cells and upregulating the expression of COX-2 and HDAC6 that play pivotal roles in tumor progression.
Distribution of Potassium, Sodium, and Chloride in Canine Purkinje and Ventricular Tissues
Authors: ROBERT L. VICK, CARLTON F. HAZLEWOOD, BUFORD L. NICHOLS
Journal: Circulation Research (1970)

Cellular resting and action potentials and total tissue concentrations of K + , Na + , and Cl - were measured in canine myocardial and Purkinje tissues. The results with myocardium were consistent with those of others: the total tissue concentration of K + was greater than that of Na + of Cl - In Purkinje tissue, the total tissue concentration of K + was relatively low, while that of Na + and of Cl - was high. Extracellular space was calculated on the basis of four different assumptions about the intracellular concentration of one of the ions: (1) the intracellular concentrations of Cl - is zero; (2) the electrochemical equilibrium potential of Cl - equals the cellular resting potential; (3) the electrochemical equilibrium potential of K + equals the cellular maximum diastolic potential; (4) the electrochemical equilibrium potential of Na + equals the reversal of the cellular action potential. In the myocardium, the lowest estimate of extracellular space was 14±2%, and the highest was 18±2%. In the Purkinje tissue, the minimum extracellular space: (1) permitting adequate intracellular K + to account for the maximum diastolic potential was 45±3%; (2) consistent with passive distribution of Cl - was 61±4%; (3) yielding low enough intracellular concentration of Na + to account for the reversal of the action potential was 63±10%. These results suggest that in cardiac Purkinje tissue: (1) the extracellular space is unusually large with respect to that of myocardium and skeletal muscle; (2) intracellular activities of ions do not necessarily equal concentrations; or (3) intracellular space is not necessarily a single compartment.
Distilling the essence of breathlessness: the first vital symptom
Authors: David C. Currow, Miriam J. Johnson
Journal: European Respiratory Journal (2015)

A physician is obligated to consider more than a diseased organ, more even than the whole man – he must view the man in his world Assessing and adequately treating refractory breathlessness is an explicit responsibility of every clinician <http://ow.ly/LolmT>
Anabolic steroids and Norwegian weightlifters.
Authors: S. Solberg
Journal: British Journal of Sports Medicine (1982)

The mean bodyweight, in kilograms, and mean weightlifting result, in points, for the ten best weightlifters at the annual Norwegian championships 1962-82 have been studied. During the 21 years, the mean bodyweight for these ten increased by 18 kg, probably due to the effect of androgens. The weightlifting results improved rapidly from 1968 onwards, probably reflecting an increasingly widespread use of anabolic steroids by Norwegian weightlifters. In 1977 doping tests were introduced, and from then on, rate of improvement has increased much more slowly. The annual sale of anabolic steroids 1963-81 and testosterone 1974-81, in Norway have been recorded. The sale of anabolic steroids increased irregularly until 1974-75, and has since shown a 42% decrease. The sale of testosterone 1974-81 showed a slight reduction, thus giving no support to the suggestion that doping tests for anabolic steroids would lead to a transfer to testosterone abuse.
Repetitive Cycles of High-Dose Cytarabine Benefit Patients With Acute Myeloid Leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): Results from CALGB 8461
Authors: John C. Byrd, Amy S. Ruppert, Krzysztof Mrózek, Andrew J. Carroll, Colin G. Edwards, Diane C. Arthur, Mark J. Pettenati, Judith Stamberg, Prasad R.K. Koduru, Joseph O. Moore, Robert J. Mayer, Frederick R. Davey, Richard A. Larson, Clara D. Bloomfield
Journal: Journal of Clinical Oncology (2004)

To study the impact of repetitive (three to four courses) versus a single course of high-dose cytarabine (HDAC) consolidation therapy on outcome of patients with acute myeloid leukemia (AML) and inv(16)(p13q22) or t(16;16)(p13;q22).We examined the cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS) for 48 adults younger than 60 years with inv(16)/t(16;16) who had attained a complete remission on one of four consecutive clinical trials and were assigned to receive HDAC consolidation therapy. Twenty-eight patients were assigned to either three or four courses of HDAC, and 20 patients were assigned to one course of HDAC followed by alternative intensive consolidation therapy.Pretreatment features were similar for the two groups. The CIR was significantly decreased in patients assigned to receive three to four cycles of HDAC compared with patients assigned to one course (P=.03; 5-year CIR, 43% v 70%, respectively). The difference in RFS also approached statistical significance (P=.06). In a multivariable analysis that adjusted for potential confounding covariates, only treatment assignment (three to four cycles of HDAC) predicted for superior RFS (P=.02). The OS of both groups was similar (P=.93; 5-year OS, 75% for the three to four cycles of HDAC group v 70% for the one cycle of HDAC group), reflecting a high success rate with stem-cell transplantation salvage treatment administered among patients in both treatment groups.We conclude that, in AML patients with inv(16)/t(16;16), repetitive HDAC therapy decreases the likelihood of relapse compared with consolidation regimens including less HDAC.
Rapid Clearance of Human Papillomavirus and Implications for Clinical Focus on Persistent Infections
Authors: A. C. Rodriguez, M. Schiffman, R. Herrero, S. Wacholder, A. Hildesheim, P. E. Castle, D. Solomon, R. Burk
Journal: JNCI Journal of the National Cancer Institute (2008)

Health professionals and the public need to understand the natural history of human papillomavirus (HPV) infections of the cervix to best use the information provided by new molecular screening tests. We investigated outcomes of 800 carcinogenic HPV infections detected in 599 women at enrollment into a population-based cohort (Guanacaste, Costa Rica). For individual infections, we calculated cumulative proportions of three outcomes (viral clearance, persistence without cervical intraepithelial neoplasia grade 2 or worse [CIN2+], or persistence with new diagnosis of CIN2+) at successive 6-month time points for the first 30 months of follow-up. Cervical specimens were tested for carcinogenic HPV genotypes using an L1 degenerate-primer polymerase chain reaction method. Infections typically cleared rapidly, with 67% (95% confidence interval [CI] = 63% to 70%) clearing by 12 months. However, among infections that persisted at least 12 months, the risk of CIN2+ diagnosis by 30 months was 21% (95% CI = 15% to 28%). The risk of CIN2+ diagnosis was highest among women younger than 30 years with HPV-16 infections that persisted for at least 12 months (53%; 95% CI = 29% to 76%). These findings suggest that the medical community should emphasize persistence of cervical HPV infection, not single-time detection of HPV, in management strategies and health messages.