tbuckley/cabot-search huggingface dataset:
Prognostic Role of the Ratio between Cyclooxygenase-2 in Tumor and Stroma Compartments in Cervical Cancer
Authors: Gabriella Ferrandina, Franco Oreste Ranelletti, Francesco Legge, Marco Gessi, Vanda Salutari, Maria Grazia Distefano, Libero Lauriola, Gian Franco Zannoni, Enrica Martinelli, Giovanni Scambia
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The aim of this study was to analyze the clinical role of cyclooxygenase (COX)-2 in a large series of 175 cervical cancer patients. Experimental Design: Immunohistochemistry was performed on paraffin-embedded sections by using rabbit antiserum against COX-2. The tumor:stroma (T/S) ratio of COX-2 expression was used to define the overall COX-2 content in the tumor. Results: The T/S COX-2 ratio values ranged from 0.03 to 48.2 (mean ± SE, 3.7 ± 0.5). A total of 95 of 175 patients (54.3%) were scored as having a high (&amp;gt;1) T/S COX-2 ratio. In locally advanced cervical cancer patients who underwent neoadjuvant treatment, the percentage of cases showing a high T/S COX-2 ratio was greater in patients who did not respond to treatment (26 of 29 patients, 89.7%) than in patients with a partial (32 of 50 patients, 64.0%) or complete (19 of 44 patients, 43.2%) response (P = 0.0003). When logistic regression was applied, International Federation of Gynecologists and Obstetricians (FIGO) stage (χ2 = 11.3; P = 0.0008) and T/S COX-2 ratio (χ2 = 5.3; P = 0.021) retained an independent role in predicting a poor chance of response. Cases with a high T/S COX-2 ratio had a shorter overall survival (OS) [2-year OS, 61%(95% confidence interval 750–83)] than cases with a low T/S COX-2 ratio (2-year OS, 90%; 95% confidence interval, 81–99; P = 0.0001). In multivariate analysis, the status of T/S COX-2 IDV ratio, together with advanced stage, retained an independent negative prognostic role for OS. Conclusions: The assessment of COX-2 status in both tumor and stroma compartment could provide valuable information to identify cervical cancer patients endowed with a very poor chance of response to neoadjuvant treatment and unfavorable prognosis.
(29) Lupoid sycosis
Authors: J. Klrby, D.D. Munro
Journal: British Journal of Dermatology (2006)

Journal Article (29) Lupoid sycosis Get access J. Klrby, J. Klrby St Bartholomew's Hospital, London Search for other works by this author on: Oxford Academic Google Scholar D.D. Munro D.D. Munro St Bartholomew's Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 95, Issue s14, 1 December 1976, Pages 59–60, https://doi.org/10.1111/j.1365-2133.1976.tb07917.x Published: 01 December 1976
Phase 1 study of interleukin-12 in combination with rituximab in patients with B-cell non-Hodgkin lymphoma
Authors: Stephen M. Ansell, Thomas E. Witzig, Paul J. Kurtin, Jeff A. Sloan, Diane F. Jelinek, Kyle G. Howell, Svetomir N. Markovic, Thomas M. Habermann, George G. Klee, Pamela J. Atherton, Charles Erlichman
Journal: Blood (2002)
Androgen Receptor (AR) Coregulators: An Overview
Authors: Cynthia A. Heinlein, Chawnshang Chang
Journal: Endocrine Reviews (2002)

The biological action of androgens is mediated through the androgen receptor (AR). Androgen-bound AR functions as a transcription factor to regulate genes involved in an array of physiological processes, most notably male sexual differentiation and maturation, and the maintenance of spermatogenesis. The transcriptional activity of AR is affected by coregulators that influence a number of functional properties of AR, including ligand selectivity and DNA binding capacity. As the promoter of target genes, coregulators participate in DNA modification, either directly through modification of histones or indirectly by the recruitment of chromatin-modifying complexes, as well as functioning in the recruitment of the basal transcriptional machinery. Aberrant coregulator activity due to mutation or altered expression levels may be a contributing factor in the progression of diseases related to AR activity, such as prostate cancer. AR demonstrates distinct differences in its interaction with coregulators from other steroid receptors due to differences in the functional interaction between AR domains, possibly resulting in alterations in the dynamic interactions between coregulator complexes.
Campus Disorders: A Problem of Adult Leadership
Authors: ARMAND M. NICHOLI
Journal: American Journal of Psychiatry (1970)

The psychological determinants of campus disorders can in part be understood in terms of unresponsive and inaccessible adult leaders—in the home, the university, and government. A fundamental problem centers around the failure of these adult leaders to listen to youth, to spend sufficient time with them, and thus to recognize and affirm their worth as human beings. The author discusses various levels of emotional response evoked in students by the remote leader and, based on this formulation, offers eight specific recommendations for working effectively with youth.
Enzyme inhibitory autoantibodies to pyruvate dehydrogenase complex in primary biliary cirrhosis: Applications of a semiautomated assay
Authors: Khay-Lin Teoh, Merrill J. Rowley, Helen Zafirakis, Rolland E. Dickson, Russell H. Wiesner, Eric M. Gershwin, Ian R. Mackay
Journal: Hepatology (1994)

Sera from patients with primary biliary cirrhosis inhibit the activity of the mitochondrial pyruvate dehydrogenase complex. We utilized this effect to develop a simple, miniaturized, semiautomated spectrophotometric assay as a diagnostic aid. The sera studied were from 71 patients with primary biliary cirrhosis and 62 other subjects. The assays included enzyme inhibition, immunofluorescence on HEp-2 cells, enzyme-linked immunosorbent assay using recombinant pyruvate dehydrogenase complex-E2 and immunoblotting on bovine heart mitochondria. With the 71 primary biliary cirrhosis sera, on which M2 antibody was detected by immunofluorescence in 64 (90%), antibodies against pyruvate dehydrogenase complex were detected in 53 (83%) by means of enzyme inhibition, in 57 (89%) by means of enzyme-linked immunosorbent assay and in 60 (94%) by means of immunoblotting. Of the 64 sera positive by immunofluorescence, 60 reacted with pyruvate dehydrogenase complex-E2 on immunoblotting, and the miniaturized enzyme inhibition assay was positive in 53 of these. The enzyme inhibition assay and enzyme-linked immunosorbent assay were calibrated to give a specificity of 100%. At this level, the sensitivities for detection of pyruvate dehydrogenase complex antibody were 83% and 87%, respectively. We found no significant changes in levels of reactivity with the enzyme inhibition assay or enzyme-linked immunosorbent assay according to disease stage. Treatment with cyclosporine was accompanied by a significant decrease in levels of antibody to pyruvate dehydrogenase complex-E2 that matched improved indexes of biochemical liver function.(ABSTRACT TRUNCATED AT 250 WORDS)
A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed small-cell lung cancer: a CALGB and NCCTG study
Authors: G.K. Dy, A.A. Miller, S.J. Mandrekar, M.-C. Aubry, R.M. Langdon, R.F. Morton, S.E. Schild, J.R. Jett, A.A. Adjei
Journal: Annals of Oncology (2005)
Abstract 910: Selective inhibition of Rac1 and Cdc42 in ovarian cancer using the R-enantiomer of ketorolac
Authors: Shelby R. Kenney, Tudor Oprea, Oleg Ursu, Larry Sklar, Lesley Lomo, Carolyn Muller, Yuna Gao, Angela Wandinger-Ness, Laurie Hudson
Journal: Cancer Research (2012)

Abstract Ovarian cancer is the 5th leading cause of cancer death for women in the United States and is frequently diagnosed at late stage with multiple secondary metastases. Ras-homologous (Rho) family GTPases contribute to metastatic dissemination through regulation of actin reorganization, cell motility, cell-cell and cell-extracellular matrix adhesion. Rho GTPases are altered in a number of human cancers and our work provides the first evidence for dysregulation of Rac1 and Cdc42 in ovarian cancer. These findings suggest that Rac1 and Cdc42 inhibitors represent potential therapeutics for ovarian cancer. Using high throughput screening we identified the R-enantiomers of ketorolac and naproxen as novel inhibitors of Rac1 and Cdc42. Although it has been noted that R-enantiomers of nonsteroidal anti-inflammatory drugs are poor inhibitors of cyclooxygenase (COX) activity, little is known about the pharmacologic activities or targets of the R-enantiomers. The objective of this study was to investigate the effects of R-ketorolac on ovarian cancer. The effects of racemic, R- and S-ketorolac were investigated using SKOV3ip ovarian cancer cells. The compounds NSC23766 and MLS0000693334 were used as positive controls for Rac1 and Cdc42 respectively. An in vitro G-LISA assay indicated R-ketorolac, and not S-ketorolac, inhibits Rac1 and Cdc42 activity. In cells, R-Ketorolac, not S-ketorolac, inhibits cell:cell adhesion and cell migration. An intra-peritoneal xenograft model of tumor implantation was used to determine the effects of drugs in vivo. Racemic ketorolac decreased the number of implanted tumors by 70%. To elucidate the mechanism of GTPase inhibition by R-ketorolac, a targeted microarray analysis was performed. Preliminary results show an alteration to the gene expression profile of human cytoskeletal regulators in response to ketorolac treatment. These effects may be due to inhibition of Rac1 and Cdc42 directly or through upstream or downstream inhibition. This analysis also provides biomarkers that can be used to analyze tumor tissues from primary patients and animal studies. Together, these findings indicate that R-ketorolac is a novel inhibitor of Rac1 and/or Cdc42, and inhibit cellular processes necessary for ovarian cancer metastasis. The mechanism behind ketorolac inhibition will require further investigation. In the future, this drug may offer benefit to ovarian cancer patients through inhibition of these GTPase targets Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 910. doi:1538-7445.AM2012-910
Prebiotics for obesity: a small light on the horizon?
Authors: Herbert Tilg, Antonio Gasbarrini
Journal: Gut (2013)

The gastrointestinal tract holds a very complex and diverse microbial community which is predominantly bacterial. This human gut microbiota is believed to consist of at least 1014 bacteria, composed of more than 1000 species. Their microbial inhabitants play a major role in metabolic processes, for example, energy extraction from food, and can nowadays be considered as probably the major environmental factor linking dietary factors with the host.1 The association between the microbiota and metabolic inflammation as observed in obesity, non-alcoholic fatty liver disease, cardiovascular disease and type 2 diabetes is becoming clearer and increasingly also supported by clinical evidence.2 ,3 Prebiotics are non-digestible food ingredients that when consumed in sufficient amounts selectively modulate growth and activity of certain members of the microbiota.4 Certain prebiotics such as inulin or trans-galacto-oligosaccharides which are resistant to gastric digestion and hydrolysis are able to positively affect the microbiota. Most effects of prebiotics on metabolic functions have so far been gained from various animal studies.5

Targeting the gut microbiota may be a promising treatment concept in obesity and metabolic syndrome. Dewulf and colleagues address such an aspect by studying the prebiotic composition dietary inulin-type fructans (ITF) …
Left-ventricle leiomyosarcoma: imaging by multislices computed tomography with retrospective electrocardiogram-gated reconstruction
Authors: C P M Jayle, L P Christiaens, P Ardilouze, S Franco, P J Corbi
Journal: Thorax (2007)

Left-ventricle leiomyosarcoma: imaging by multislices computed tomography with retrospective electrocardiogram-gated reconstruction A 49-year-old man was referred for dizziness and malaise.Echocardiogram showed a 362.5 cm mass within the left ventricle.A contrast-enhanced 16-row multislice computed tomography (MSCT) scan with retrospective ECG-gated reconstruction confirmed the mass, without infiltration of the left ventricular wall or marked coronary artery stenosis (fig 1).Surgical resection of the mass was performed, and 6 days later, the patient was discharged from hospital without radiotherapy or chemotherapy.On pathological examination, the gross appearance was that of a soft, tan-yellow mass with smooth contours.Haemorrhagic areas were noted.The cells exhibited marked pleiomorphism and abundant mitotic figures.The tumour cells were positive for muscle cell antigen/CD34 and smooth muscle actin.Immunohistochemical stains were diffusely positive for vimentin and focally positive for desmin and CD68.These findings are consistent with the diagnosis of primary heart leiomyosarcoma.After 18 months, a heart MSCT examination showed absence of recurrence of the tumour (fig 2).After 3 years, the patient is doing well with a normal echocardiogram and MSCT.Primary cardiac tumours are uncommon, with an incidence ranging from 0.001% to 0.03%. 1 Leiomyosarcomas are about 9% of primary malignant cardiac tumours, and are highly aggressive and locally invasive.Leiomyosarcomas are uncommon malignancies of soft tissue associated with a poor prognosis owing to local and metastatic disease.Extra cardiac localisations are in the retroperitoneum, gastrointestinal tract, uterus, skin and vessels.Chemotherapy or radiotherapy gives poor results and are controversial. 1 2 Surgical treatment offers the best chance of cure.Echocardiograms are mainly used in the diagnosis of cardiac tumours.Our reported case illustrates the value of MSCT imaging in providing an excellent anatomical definition of the tumour, the screening of all cardiac chambers and the depiction of coronary artery vessels.
Gemtuzumab ozogamicin with or without interleukin 11 in patients 65 years of age or older with untreated acute myeloid leukemia and high-risk myelodysplastic syndrome: comparison with idarubicin plus continuous-infusion, high-dose cytosine arabinoside
Authors: Elihu H. Estey, Peter F. Thall, Francis J. Giles, Xue-Mei Wang, Jorge E. Cortes, Miloslav Beran, Sherry A. Pierce, Deborah A. Thomas, Hagop M. Kantarjian
Journal: Blood (2002)
Role of type 1 versus type 2 immune responses in liver during the onset of chronic woodchuck hepatitis virus infection
Authors: Yun Wang, Stephan Menne, James R. Jacob, Bud C. Tennant, John L. Gerin, Paul J. Cote
Journal: Hepatology (2003)

Immune response messenger RNAs (mRNA) were compared in liver during self-limited (resolved) and chronic neonatal woodchuck hepatitis virus (WHV) infection. At week 14 postinfection (mid-acute phase), mRNAs for leukocyte markers (CD3, CD4, CD8), type 1 cytokines and related transcription factors (IFN-gamma, TNF-alpha, STAT4, T-bet), and IL-10 were increased in livers from resolving infections, but mRNAs of other type 1 (IL-2) and type 2 (IL-4, STAT6, and GATA3 markers remained at baseline levels. Increased coexpression of IFN-gamma and TNF-alpha mRNAs correlated in most cases with lower levels of intrahepatic WHV covalently closed circular DNA (cccDNA). At the same time point postinfection, livers from woodchucks that eventually progressed to chronic infection had baseline or slightly elevated levels of CD and type 1 mRNAs, which were significantly lower (or elevated less frequently) compared with resolving woodchucks. Earlier, at week 8, there were no differences between the two outcome settings. During these early time points and at a later stage in chronic infection (15 months), type 2 mRNAs in carrier liver remained at baseline levels or, when elevated, were never in excess of those in resolving woodchucks. In conclusion, the onset and maintenance of neonatal chronic WHV infection are not associated with antagonistic type 2 immunoregulation of type 1 responses in liver. Accordingly, chronicity develops in association with a primary deficiency in the intrahepatic CD responses, especially involving CD8(+) T lymphocytes, and in both extracellular (cytokine) and intracellular (transcriptional) type 1 response mediators. This has relevant implications for future treatment of chronic hepatitis B virus (HBV) infection in humans.
Genetic Analysis of the -Tubulin Gene, TUBB, in Non-Small-Cell Lung Cancer
Authors: M J Kelley, S Li, D H Harpole
Journal: JNCI Journal of the National Cancer Institute (2001)

Tubulin, the cellular target for the taxane chemotherapeutic agents, is composed of heterodimers. There are at least six human genes encoding different tubulin subunits (1). In most epithelial tumor cells, the most highly expressed isoform of -tubulin is 5, which is encoded by the TUBB gene, also referred to as M40 (2). Chinese hamster ovary cells (3) and an ovarian tumor cell line (4) adapted for growth in vitro in the presence of the taxane paclitaxel have been found to have mutations in TUBB. Monzo et al. (5) reported TUBB mutations in 16 (33%) of 49 tumor samples from previously untreated patients with advanced non-small-cell lung cancer (NSCLC). All of the mutations, except two, were located in exon 4, which encodes more than half of the -tubulin protein and includes the adenosine triphosphate-binding site composed of the ribose-, phosphate-, and base-binding regions. There was also a statistically significant association between the presence of TUBB mutations and both poor treatment response to paclitaxel-containing chemotherapy and shortened overall survival (5). These associations led to the proposal to use the presence of TUBB mutations as a basis for selecting initial chemotherapy for patients with advanced NSCLC (6). To better study the association between TUBB mutations and tumor cell growth and taxane resistance in patients with NSCLC, we selected 25 tumor cell lines (supplementary Table 1, available at the Journal’s Web site http://jnci. oupjournals.org) that differed in their in vitro sensitivity to paclitaxel (7). Genomic DNA was isolated from these cell lines, from normal human peripheral blood leukocytes, and from 20 NSCLC primary tumor samples by proteinase K digestion and phenol–chloroform extraction. Patients providing a tumor sample gave written informed consent to use their tumor under an institutional review board-approved human study. Oligonucleotides for polymerase chain reaction (PCR) amplification of the coding regions of TUBB were designed on the basis of the genomic sequence of TUBB from the Human Genome Project (GenBank accession number AC006165) with the use of GeneWorks version 2.45 (IntelliGenetics, Mountain View, CA). At least one oligonucleotide was required to be within an intronic sequence. Oligonucleotides used in the amplification and sequencing reactions were as follows: Exon 1—1F, 5 -CCCATA-
The Predictive Capacity of Personal Genome Sequencing
Authors: Nicholas J. Roberts, Joshua T. Vogelstein, Giovanni Parmigiani, Kenneth W. Kinzler, Bert Vogelstein, Victor E. Velculescu
Journal: Science Translational Medicine (2012)

New DNA sequencing methods will soon make it possible to identify all germline variants in any individual at a reasonable cost. However, the ability of whole-genome sequencing to predict predisposition to common diseases in the general population is unknown. To estimate this predictive capacity, we use the concept of a "genometype." A specific genometype represents the genomes in the population conferring a specific level of genetic risk for a specified disease. Using this concept, we estimated the maximum capacity of whole-genome sequencing to identify individuals at clinically significant risk for 24 different diseases. Our estimates were derived from the analysis of large numbers of monozygotic twin pairs; twins of a pair share the same genometype and therefore identical genetic risk factors. Our analyses indicate that (i) for 23 of the 24 diseases, most of the individuals will receive negative test results; (ii) these negative test results will, in general, not be very informative, because the risk of developing 19 of the 24 diseases in those who test negative will still be, at minimum, 50 to 80% of that in the general population; and (iii) on the positive side, in the best-case scenario, more than 90% of tested individuals might be alerted to a clinically significant predisposition to at least one disease. These results have important implications for the valuation of genetic testing by industry, health insurance companies, public policy-makers, and consumers.
Randomised controlled trial of weightlifting exercise in patients with chronic airflow limitation.
Authors: K Simpson, K Killian, N McCartney, D G Stubbing, N L Jones
Journal: Thorax (1992)

BACKGROUND PATIENTS: with chronic airflow obstruction are often limited by muscle fatigue and weakness. As exercise rehabilitation programmes have produced modest improvements at best a study was designed to determine whether specific muscle training techniques are helpful. METHODS: Thirty four patients with chronic airflow limitation (forced expiratory volume in one second (FEV1) 38% of predicted values) were stratified for FEV1 to vital capacity (VC) ratio less than 40% and arterial oxygen desaturation during exercise and randomised to a control or weightlifting training group. In the experimental group training was prescribed for upper and lower limb muscles as a percentage of the maximum weight that could be lifted once only. It was carried out three times a week for eight weeks. RESULTS: Three subjects dropped out of each group; results in the remaining 14 patients in each group were analysed. Adherence in the training group was 90%. In the trained subjects muscle strength and endurance time during cycling at 80% of maximum power output increased by 73% from 518 (SE69) to 898 (95) s, with control subjects showing no change (506 (86) s before training and 479 (89) s after training). No significant changes in maximum cycle ergometer exercise capacity or distance walked in six minutes were found in either group. Responses to a chronic respiratory questionnaire showed significant improvements in dyspnoea and mastery of daily living activities in the trained group. CONCLUSIONS: Weightlifting training may be successfully used in patients with chronic airflow limitation, with benefits in muscle strength, exercise endurance, and subjective responses to some of the demands of daily living.