tbuckley/cabot-search huggingface dataset:
Animal Models of Human Prostate Cancer: The Consensus Report of the New York Meeting of the Mouse Models of Human Cancers Consortium Prostate Pathology Committee
Authors: Michael Ittmann, Jiaoti Huang, Enrico Radaelli, Philip Martin, Sabina Signoretti, Ruth Sullivan, Brian W. Simons, Jerrold M. Ward, Brian D. Robinson, Gerald C. Chu, Massimo Loda, George Thomas, Alexander Borowsky, Robert D. Cardiff
Journal: Cancer Research (2013)

Animal models, particularly mouse models, play a central role in the study of the etiology, prevention, and treatment of human prostate cancer. While tissue culture models are extremely useful in understanding the biology of prostate cancer, they cannot recapitulate the complex cellular interactions within the tumor microenvironment that play a key role in cancer initiation and progression. The National Cancer Institute (NCI) Mouse Models of Human Cancers Consortium convened a group of human and veterinary pathologists to review the current animal models of prostate cancer and make recommendations about the pathologic analysis of these models. More than 40 different models with 439 samples were reviewed, including genetically engineered mouse models, xenograft, rat, and canine models. Numerous relevant models have been developed over the past 15 years, and each approach has strengths and weaknesses. Analysis of multiple genetically engineered models has shown that reactive stroma formation is present in all the models developing invasive carcinomas. In addition, numerous models with multiple genetic alterations display aggressive phenotypes characterized by sarcomatoid carcinomas and metastases, which is presumably a histologic manifestation of epithelial-mesenchymal transition. The significant progress in development of improved models of prostate cancer has already accelerated our understanding of the complex biology of prostate cancer and promises to enhance development of new approaches to prevention, detection, and treatment of this common malignancy.
Adjuvant chemotherapy with doxorubicin in high-grade soft tissue sarcoma: a randomized trial of the Scandinavian Sarcoma Group.
Authors: T A Alvegård, H Sigurdsson, H Mouridsen, O Solheim, B Unsgaard, U Ringborg, O Dahl, A M Nordentoft, C Blomqvist, A Rydholm
Journal: Journal of Clinical Oncology (1989)

From January 1981 to February 1986, a total of 240 patients with primary, malignancy-grade III or IV soft tissue sarcoma were entered into an adjuvant chemotherapy multicenter trial conducted by the Scandinavian Sarcoma Group (SSG). Of these patients, 181 were evaluable. The tumor was located in the extremities in 155 patients. After radical surgery (wide and compartmental) the patients were randomized to treatment with single-agent doxorubicin 60 mg/m2 administered as an intravenous (IV) bolus once a month for 9 months (group 1, n = 77) or to control (group 2, n = 77). If the surgical procedure was marginal, the patients initially received postoperative radiotherapy, followed by doxorubicin (group 3, n = 16) or control (group 4, n = 11). The control groups did not receive any adjuvant chemotherapy. Adjuvant therapy was initiated within 6 weeks of surgery (group 1) or within 10 weeks of surgery for patients receiving postoperative radiotherapy (group 3). With a median follow-up of 40 months, there was no significant difference between the four treatment groups in overall survival (group 1, 75%; group 2, 70%; group 3, 69%; group 4, 73%), disease-free survival (group 1, 62%; group 2, 56%; group 3, 62%; group 4, 64%), or local tumor control (group 1, 92%; group 2, 92%; group 3, 87%; group 4, 90%). The conclusions were the same whether the total group or evaluable patients only were included in the analysis. The local recurrence rate for patients undergoing radical surgery was 8% and for patients undergoing marginal surgery followed by radiotherapy was 12%. This study indicates that the use of single-agent doxorubicin as postoperative adjuvant chemotherapy has no significant clinical benefit in patients with high-grade soft tissue sarcoma.
Detection of hepatocellular carcinoma in cirrhotic livers with lipiodol-ct
Authors: Carlos Valls, Juan Figueras, S. Bhattacjarya, A. P. Dhillon, B. R. Davidson
Journal: Hepatology (1998)

Some Cryptic IssuesTo the Editor: Hepatitis B virus (HBV) is an infection with highest prevalences in Asia and sub-Saharan regions of the world where temperatures may vary widely, and where cold storage is not readily available.These are also regions where universal vaccination against HBV infection is essential to break the long-standing cycle of mother-to-infant transmission of this virus.HBV vaccine is a heat-labile product that must be stored between 2°C to 8°C in single-or multidose vials.Any potential deterioration in its potency during exposure to adverse conditions has been tested by prolonged exposure to high temperatures.The recombinant yeast-derived HBV vaccine, Engerix-B, was exposed to temperatures of 45°C for 1 week or to temperatures of 37°C for 1 month.One hundred thirty-eight volunteers were immunized with these exposed lots, and high rates of protective immunity achieved, without adverse reactions, 1 indicated that the immunogenicity of the vaccine would be preserved even in suboptimal environmental conditions.Such reports of the stability of HBV vaccine in potentially adverse environments are misleading.They underestimate the ground realities of environmental hazards that are encountered in the field.Moreover, assessment of adequate immunogenicity may be inaccurate, because vaccine failures are often not apparent until many years after immunization.HBV infection in infants and preschool-aged children are typically subclinical without clinical manifestations of an episode of acute viral hepatitis. 2Thus, vaccine failures would not be evident either at the time of initial vaccination or even at the completion of several vaccine doses.Many decades would need to elapse before inadvertent failure would become clinically apparent with symptoms of chronic hepatitis, cirrhosis, or primary hepatocellular carcinoma.Quantification of the potency lots of HBV vaccine is a complex procedure.Unlike live measles or poliomyelitis vaccines that are quantified by inoculations of cell cultures in vitro, validation of HBV vaccine lots requires inoculation in human volunteers or experimental animals in vivo.The lack of an in vitro assay greatly limits our ability to measure the potency of a large number of HBV vaccine lots that have been exposed to ''field conditions.''Frequent assessment of potency will not be practical until simple in vitro assays are routinely available.To optimize immunogenicity, vaccine manufacturers should be aware of variations in temperature, humidity, air velocity,
Improved Survival and Renal Prognosis of Patients With Type 2 Diabetes and Nephropathy With Improved Control of Risk Factors
Authors: Gudbjörg Andrésdóttir, Majken L. Jensen, Bendix Carstensen, Hans-Henrik Parving, Kasper Rossing, Tine W. Hansen, Peter Rossing
Journal: Diabetes Care (2014)

To evaluate long-term survival, development of renal end points, and decline in glomerular filtration rate (GFR) in patients with type 2 diabetes and diabetic nephropathy (DN) after renin-angiotensin system (RAS) inhibition and multifactorial treatment of cardiovascular risk factors have become standard of care.All patients with type 2 diabetes and DN (n = 543) at the Steno Diabetes Center were followed during 2000-2010. GFR was measured yearly with 51Cr-EDTA plasma clearance. Annual decline in GFR was determined in patients with at least three measurements over a minimum of 3 years (∆GFR cohort, n = 286). Results were compared with historical data, obtained using identical criteria at our hospital, before implementation of current treatment guidelines.Baseline mean (SD) GFR was 74 (32) mL/min/1.73 m2. More than 93% received RAS inhibition. During median 7.8 (interquartile range 5.7-9.8) years, mean (SE) annual GFR decline was 4.4 (0.24) compared with previously 5.2 (0.27) mL/min/1.73 m2/year (P = 0.04). Doubling of plasma creatinine or end-stage renal disease (ESRD) developed in 19%, and 37% died during 5.7 (3.3-8.8) years. Mortality from onset of DN in the ∆GFR cohort was compared with that of our prior ∆GFR cohort from 1983 to 2003 (n = 227). Crude mortality risk was reduced by 42% and after age adjustment by 50% (P < 0.001 for both). In a multistate model accounting for competing risks of ESRD and death, prior cardiovascular disease and lower GFR were predictors of mortality, whereas albuminuria, HbA1c, and low GFR predicted ESRD.Overall prognosis has improved considerably with current multifactorial treatment of DN in type 2 diabetes, including long-term RAS inhibition.
Effect of stellectomy and vagotomy on ventricular refractoriness in dogs.
Authors: P J Schwartz, R L Verrier, B Lown
Journal: Circulation Research (1977)

The influence of tonic sympathetic and parasympathetic nervous system activity on ventricular refractory period duration was studied in 13 mongrel dogs. Strength-interval curves were obtained from the apex of the right ventricular endocardium with a transvenous bipolar catheter. The effects of sympathetic activity were assessed by unilateral and bilateral stellectomies and tonic vagal effects were studied by inducing cholinergic blockade with atropine (0.2 mg/kg) and by sectioning the cervical vagi bilaterally. Right stellectomy shifted the strength-interval curve 3-5 msec earlier (P less than 0.005). In contrast, left stellectomy shifted the strength-interval curve 4-7 msec later (P less than 0.001). Thus, right and left unilateral stellectomy produced opposite effects. However, when the contralateral ganglion was removed, right and left stellectomy produced qualitatively similar effects, increasing refractoriness. The net effect of bilateral stellectomy was to shift the strength-interval curve 8-10 msec later (P less than 0.001) and this was primarily dependent on left stellectomy. Blockade of vagal efferent activity with atropine shifted the strength-interval curve 3-6 msec earlier (P = .001). Removal of vagal afferent activity by vagotomy during atropine blockade shifted the strength-interval curve 2-3 msec earlier (P = 0.03). It is concluded that both stellate ganglia exert qualitatively similar effects on cardiac refractoriness; however, the left ganglion dominates and unilateral right stellectomy produces a paradoxical decrease in refractoriness. The sympathetic effects are tonically antagonized by vagal activity.
CCK-related peptides stimulation of the Na+/H+ antiport in pancreatic acinar cells leads to cytoplasmic alkalinisation.
Authors: M J Bastie, M Dufresne, M Delvaux, N Vaysse, A Ribet
Journal: Gut (1987)

Caerulein, gastrin and pentagastrin stimulation of the Na+/H+ exchange leads to intracellular alkalinisation in pancreatic acinar cells. Activation of protein kinase-C is the more probable mechanism involved in the effect of caerulein.
Diagnostic pitfalls in sports related laryngeal injury.
Authors: S D Rejali, J D Bennett, T Upile, M P Rothera
Journal: British Journal of Sports Medicine (1998)

The serious nature of laryngeal trauma sustained during sporting activity can be easily overlooked. Concomitant injury should not distract from the diagnosis of potential airway problems. The effects of head and neck trauma on the airway may be delayed. The assessment and management of a patient with suspected laryngeal injury should be carried out by experienced medical practitioners.
Combination of Docetaxel and Recombinant Vaccine Enhances T-Cell Responses and Antitumor Activity: Effects of Docetaxel on Immune Enhancement
Authors: Charlie T. Garnett, Jeffrey Schlom, James W. Hodge
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Taxanes comprise some of the most widely used cancer chemotherapeutic agents. Members of this drug family, including docetaxel, are commonly used to treat breast, prostate, and lung cancers, among others. This study was designed to determine if this taxane has the ability to modulate components of the immune system independent of antitumor activity and to investigate the potential synergistic activities of the combination of docetaxel and vaccine therapy. Experimental Design: We examined the in vivo effects of docetaxel on immune-cell subsets and on the function of CD4+, CD8+, and regulatory T-cell (Treg) populations in response to antigen-specific vaccination. We also examined the antitumor effects of the combination of docetaxel and vaccine in a preclinical model in which docetaxel has no observable effect on tumor growth. Results: These studies show for the first time that (a) docetaxel modulates CD4+, CD8+, CD19+, natural killer cell, and Treg populations in non–tumor-bearing mice; (b) unlike cyclophosphamide, docetaxel does not inhibit the function of Tregs; (c) docetaxel enhances CD8+ but not CD4+ response to CD3 cross-linking; (d) docetaxel given after vaccination provides optimal enhancement of immune response to recombinant viral vaccines; (e) docetaxel combined with recombinant viral vaccine is superior to either agent alone at reducing tumor burden; and (f) docetaxel plus vaccine increases antigen-specific T-cell responses to antigen in the vaccine, as well as to cascade antigens derived from the tumor. Conclusions: These findings suggest potential clinical benefit for the combined use of docetaxel and recombinant cancer vaccines.
Genetic analyses of chromosome 12 loci in Crohn's disease
Authors: S Lesage
Journal: Gut (2000)

Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease, both of which are multifactorial diseases involving the interaction of genetic and environmental factors. A region on chromosome 12 centred around the marker locus D12S83 has previously been associated with IBD predisposition. The aim of the study was to investigate this genetic region in an independent panel of European families affected by Crohn's disease.A sample of 95 families with two or more affected relatives and 75 simplex nuclear families were genotyped for 19 microsatellite loci located on chromosome 12. A search for linkage and linkage disequilibrium was performed using non-parametric two point and multipoint analyses with the Analyze and Genehunter packages.No evidence of linkage or linkage disequilibrium was observed for any of the marker loci, including D12S83 (p=0.35 for the two point linkage test). Multipoint linkage analysis also failed to reveal positive linkage on chromosome 12. Power calculations allowed us to reject the hypothesis that the genetic region of chromosome 12 centred on D12S83 contains a susceptibility locus with a relative risk (lambda(s)) equal to or greater than 2.0 in these families.Failure to detect linkage or linkage disequilibrium in these families suggests that the chromosome 12 locus previously reported to be associated with genetic predisposition to IBD does not play a role in all European family samples. This observation is compatible with heterogeneity in the genetic basis of susceptibility to the disease and/or exposure to various environmental factors among Caucasian families.
Superantigen binding to a T cell receptor beta chain of known three-dimensional structure.
Authors: E L Malchiodi, E Eisenstein, B A Fields, D H Ohlendorf, P M Schlievert, K Karjalainen, R A Mariuzza
Journal: The Journal of Experimental Medicine (1995)

The three-dimensional structure of an unglycosylated T cell antigen receptor (TCR) beta chain has recently been determined to 1.7 A resolution. To investigate whether this soluble beta chain (murine V beta 8.2J beta 2.1C beta 1) retains superantigen (SAG)-binding activity, we measured its affinity for various bacterial SAGs in the absence of MHC class II molecules. Dissociation constants (KDs) were determined using two independent techniques: surface plasmon resonance detection and sedimentation equilibrium. Specific binding was demonstrated to staphylococcal enterotoxins (SEs) B, C1, C2, and C3 and to streptococcal pyrogenic exotoxin A (SPEA), consistent with the known proliferative effects of these SAGs on T cells expressing V beta 8.2. In contrast, SEA, which does not stimulate V beta 8.2-bearing cells, does not bind the recombinant beta chain. Binding of the beta chain to SAGs was characterized by extremely fast dissociation rates (&amp;gt; 0.1 s-1), similar to those reported for certain leukocyte adhesion molecules. Whereas the beta chain bound SEC1, 2, and 3 with KDs of 0.9-2.5 microM, the corresponding value for SEB was approximately 140 microM. The much weaker binding to SEB than to SEC1, 2, or 3 was surprising, especially since SEB was found to actually be 3- to 10-fold more effective, on a molar basis, than the other toxins in stimulating the parental T cell hybridoma. We interpret these results in terms of the ability of SEC to activate T cells independently of MHC, in contrast to SEB. We have also measured SE binding to the glycosylated form of the beta chain and found that carbohydrate apparently does not contribute to recognition, even though the N-linked glycosylation sites at V beta 8.2 residues Asn24 and Asn74 are at or near the putative SAG-binding site. This result, along with the structural basis for the V beta specificity of SEs, are discussed in relation to the crystal structure of the unglycosylated beta chain.
Differential expression of apoptotic genes PDIA3 and MAP3K5 distinguishes between low- and high-risk prostate cancer
Authors: Nicole Chui Pressinotti, Helmut Klocker, Georg Schäfer, Van-Duc Luu, Markus Ruschhaupt, Ruprecht Kuner, Eberhard Steiner, Annemarie Poustka, Georg Bartsch, Holger Sültmann
Journal: Molecular Cancer (2009)

Abstract Background Despite recent progress in the identification of genetic and molecular alterations in prostate cancer, markers associated with tumor progression are scarce. Therefore precise diagnosis of patients and prognosis of the disease remain difficult. This study investigated novel molecular markers discriminating between low and highly aggressive types of prostate cancer. Results Using 52 microdissected cell populations of low- and high-risk prostate tumors, we identified via global cDNA microarrays analysis almost 1200 genes being differentially expressed among these groups. These genes were analyzed by statistical, pathway and gene enrichment methods. Twenty selected candidate genes were verified by quantitative real time PCR and immunohistochemistry. In concordance with the mRNA levels, two genes MAP3K5 and PDIA3 exposed differential protein expression. Functional characterization of PDIA3 revealed a pro-apoptotic role of this gene in PC3 prostate cancer cells. Conclusions Our analyses provide deeper insights into the molecular changes occurring during prostate cancer progression. The genes MAP3K5 and PDIA3 are associated with malignant stages of prostate cancer and therefore provide novel potential biomarkers.
Macrophage-lymphocyte clustering in rheumatoid arthritis.
Authors: F W Webb, M Baker, R Weisbart, R Bluestone, L Goldberg
Journal: Annals of the Rheumatic Diseases (1975)

The cells in synovial fluid from patients with rheumatoid arthritis contain a small percentage of macrophages. Such macrophages were isolated and cultured alone and with homologous and heterologous lymphocytes for 24 hours, in an attempt to identify possible contact between living lymphocytes and macrophages. Such contact was found, with clustering of lymphocytes around macrophages, and was particularly well shown by scanning electron microscopy.
Investigation of physicochemical properties and in-vitro in-vivo evaluation of agomelatine polymorphs
Authors: Wei Du, Yuefang Zhou, Yafei Gong, Chunshun Zhao
Journal: Asian Journal of Pharmaceutical Sciences (2013)

In the present study, Form I, Form II and Form III of agomelatine were prepared to investigate the variability of polymorphs, then the in-vitro in-vivo correlation were established. The presence of three polymorphs of agomelatine was corroborated through studies by XRPD, TGA and DSC. All the forms obtained were then subjected to the powder and intrinsic dissolution tests. The IDR ranked in the order of Form III > Form I > Form II. Form I and Form III both underwent solvent-mediated phase transformation (SMPT) to Form II during dissolution and the transition points were 62 and 45 min, respectively. Pharmacokinetic profiles were acquired after oral administration of tablets, showing that the ka and AUC0–12 h of Form I, Form II, Form III were 0.58 ± 0.11, 0.34 ± 0.05, 0.74 ± 0.07 h−1 and 296.25 ± 49.39, 186.05 ± 45.93, 331.16 ± 54.74 ng*h/ml, respectively. Good linearities between IDR and ka, IDR and AUC were established, suggesting that the agomelatine polymorphic forms with faster dissolution rates in-vitro would increase the rate and extent of oral absorption in-vivo. These results demonstrated that IDR was predictive in estimating the relative bioavailability of agomelatine polymorphic forms.
Heart Failure Gene Therapy
Authors: Sven T. Pleger, Henriette Brinks, Julia Ritterhoff, Philip Raake, Walter J. Koch, Hugo A. Katus, Patrick Most
Journal: Circulation Research (2013)

Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses formulations of DNA and RNA, whose products determine the therapeutic classification through their biological actions. Among resident cardiac cells, cardiomyocytes have been the therapeutic target of numerous attempts to regenerate systolic and diastolic performance, to reverse remodeling and restore electric stability and metabolism. Although the concept to intervene directly within the genetic and molecular foundation of cardiac cells is simple and elegant, the path to clinical reality has been arduous because of the challenge on delivery technologies and vectors, expression regulation, and complex mechanisms of action of therapeutic gene products. Nonetheless, since the first demonstration of in vivo gene transfer into myocardium, there have been a series of advancements that have driven the evolution of heart failure gene therapy from an experimental tool to the threshold of becoming a viable clinical option. The objective of this review is to discuss the current state of the art in the field and point out inevitable innovations on which the future evolution of heart failure gene therapy into an effective and safe clinical treatment relies.