89 research outputs found
Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators by oligonucleotide microarray analysis
<p>Abstract</p> <p>Background</p> <p>The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling.</p> <p>Methods</p> <p>The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Patients (n=20) from which there were available tumor and matched normal mucosa were grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, <it>GLUT3</it>, <it>HSAL2</it>, and <it>PACE4</it>, were selected for their potential biological significance in a larger cohort of 49 patients via quantitative real-time RT-PCR.</p> <p>Results</p> <p>Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, <it>MMP-1</it> encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of <it>GLUT3</it>, <it>HSAL2</it> and <it>PACE4</it>, respectively. Univariate analyses demonstrated that <it>GLUT3</it> over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). <it>HSAL2</it> was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.047). In survival studies, only <it>GLUT3</it> showed a prognostic value with disease-free (P=0.049), relapse-free (P=0.002) and overall survival (P=0.003). <it>PACE4</it> mRNA expression failed to show correlation with any of the relevant parameters. </p> <p>Conclusion</p> <p>The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma.</p
Impaired Vascular Contractility and Aortic Wall Degeneration in Fibulin-4 Deficient Mice: Effect of Angiotensin II Type 1 (AT1) Receptor Blockade
Medial degeneration is a key feature of aneurysm disease and aortic dissection. In a murine aneurysm model we investigated the structural and functional characteristics of aortic wall degeneration in adult fibulin-4 deficient mice and the potential therapeutic role of the angiotensin (Ang) II type 1 (AT1) receptor antagonist losartan in preventing aortic media degeneration. Adult mice with 2-fold (heterozygous Fibulin-4+/R) and 4-fold (homozygous Fibulin-4R/R) reduced expression of fibulin-4 displayed the histological features of cystic media degeneration as found in patients with aneurysm or dissection, including elastin fiber fragmentation, loss of smooth muscle cells, and deposition of ground substance in the extracellular matrix of the aortic media. The aortic contractile capacity, determined by isometric force measurements, was diminished, and was associated with dysregulation of contractile genes as shown by aortic transcriptome analysis. These structural and functional alterations were accompanied by upregulation of TGF-β signaling in aortas from fibulin-4 deficient mice, as identified by genome-scaled network analysis as well as by immunohistochemical staining for phosphorylated Smad2, an intracellular mediator of TGF-β. Tissue levels of Ang II, a regulator of TGF-β signaling, were increased. Prenatal treatment with the AT1 receptor antagonist losartan, which blunts TGF-β signaling, prevented elastic fiber fragmentation in the aortic media of newborn Fibulin-4R/R mice. Postnatal losartan treatment reduced haemodynamic stress and improved lifespan of homozygous knockdown fibulin-4 animals, but did not affect aortic vessel wall structure. In conclusion, the AT1 receptor blocker losartan can prevent aortic media degeneration in a non-Marfan syndrome aneurysm mouse model. In established aortic aneurysms, losartan does not affect aortic architecture, but does improve survival. These findings may extend the potential therapeutic application of inhibitors of the renin-angiotensin system to the preventive treatment of aneurysm disease
A quantitative synthesis of the medicinal ethnobotany of the Malinké of Mali and the Asháninka of Peru, with a new theoretical framework
<p>Abstract</p> <p>Background</p> <p>Although ethnomedically and taxonomically guided searches for new medicinal plants can improve the percentage of plants found containing active compounds when compared to random sampling, ethnobotany has fulfilled little of its promise in the last few decades to deliver a bounty of new, laboratory-proven medicinal plants and compounds. It is quite difficult to test, isolate, and elucidate the structure and mechanism of compounds from the plethora of new medicinal plant uses described each year with limited laboratory time and resources and the high cost of clinical trials of new drug candidates.</p> <p>Methods</p> <p>A new quantitative theoretical framework of mathematical formulas called "relational efficacy" is proposed that should narrow down this search for new plant-derived medicines based on the hypothesis that closely related plants used to treat closely related diseases in distantly related cultures have a higher probability of being effective because they are more likely to be independent discoveries of similar plant compounds and disease mechanisms. A prerequisite to this hypothesis, the idea that empirical testing in traditional medicine will lead to choosing similar medicinal plants and therefore the medicinal flora of two distant cultures will prove to be more similar than their general flora, is tested using resampling statistics on cross-cultural field data of the plants used by the MalinkĂ© of Mali and the Asháninka of Peru to treat the diseases malaria, African sleeping sickness, Chagas' disease, leishmaniasis, diabetes, eczema, asthma, and uterine fibroids.</p> <p>Results</p> <p>In this case, the similarity of the medicinal floras is found to be significantly greater than the similarity of the general floras, but only when the diseases in question are grouped into the categories of parasitic and autoimmune diseases.</p> <p>Conclusion</p> <p>If the central theoretical framework of this hypothesis is shown to be true, it will allow the synthesis of medicinal plant information from around the world to pinpoint the species with the highest potential efficacy to take into the laboratory and analyze further, ultimately saving much field and laboratory time and resources.</p> <p><b>Spanish abstract</b></p> <p>Las bĂşsquedas que utilizan la etnomedicina y la taxonomĂa para descubrir nuevas plantas medicinales, pueden aumentar la probabilidad de Ă©xito de encontrar compuestos quĂmicos activos en plantas, en comparaciĂłn con las bĂşsquedas aleatorias. A pesar de lo anterior, en las Ăşltimas dĂ©cadas, la etnobotánica no ha cumplido con las expectativas de proveer numerosas plantas medicinales y quĂmicos nuevos una vez examinados en el laboratorio. Cada año se describen una plĂ©tora de plantas medicinales y sus usos, sin embargo las limitaciones de tiempo y recursos en los laboratorios, unidos al alto coste de los ensayos clĂnicos de las drogas potenciales, hacen muy difĂcil probar, aislar, y elucidar la estructura y el mecanismo de los compuestos de estas plantas. Se propone un nuevo marco teĂłrico cuantitativo cuyo fin es focalizar la bĂşsqueda de nueva plantas medicinales. Este marco teĂłrico está basado en la hipĂłtesis que las plantas cercanamente relacionadas, usadas para tratar enfermedades cercanamente relacionadas en culturas distantemente relacionadas, tienen una eficacia potencial más alta, debido a que es más probable que estos hallazgos sean descubrimientos independientes de compuestos quĂmicos similares. Parte de esta hipĂłtesis, que las escogencias racionales se hacen para elegir plantas medicinales similares y que la flora medicinal de dos culturas distantes es más similar que su flora general, se probĂł usando mĂ©todos estadĂsticos de remuestreo con datos de campo de la comunidad MalinkĂ© de MalĂ y de la Asháninka de PerĂş, y las enfermedades de paludismo, enfermedad africana del sueño, enfermedad de Chagas, leishmania, diabetes, eczema, asma, y fibromas uterinos. Se encontrĂł, en este caso, que la similitud de las floras medicinales es significativamente mayor a la similitud de las floras generales, solamente cuando las enfermedades analizadas se agruparon en las categorĂas de enfermedades parasitarias y enfermedades autoinmunes. Si se demostrara que las otras partes de esta hipĂłtesis son ciertas, se podrĂa sintetizar la informaciĂłn sobre plantas medicinales alrededor del mundo, para establecer asĂ las plantas potencialmente más eficaces para llevarlas al laboratorio y analizarlas más profundamente.</p> <p><b>French abstract</b></p> <p>Par rapport aux recherches menĂ©es de façon alĂ©atoire, les recherches effectuĂ©es par des critères ethnobotaniques et taxonomiques ont de meilleures chances Ă dĂ©couvrir de nouvelles plantes mĂ©dicinales Ă produit chimique actifs. Pendant les dernières dĂ©cennies pourtant, l'ethnobotanique a rĂ©alisĂ© peu de ces promesses Ă rĂ©vĂ©ler un grand nombre de plantes mĂ©dicinales et de nouveaux produits chimiques, testĂ©s au laboratoire. Avec les ressources limitĂ©es pour la recherche au laboratoire et le coĂ»t Ă©levĂ© des Ă©preuves cliniques pour trouver de nouveaux candidats aux mĂ©dicaments, il est difficile d'Ă©tudier, d'isoler et d'Ă©lucider la structure et le mĂ©canisme des produits chimiques de chacune des nombreuses plantes mĂ©dicinales (et les utilisations de ces plantes) dĂ©crites chaque annĂ©e. Nous proposons une nouvelle technique thĂ©orique et quantitative pour prĂ©ciser la recherche de nouvelles plantes mĂ©dicinales; elle est basĂ©e sur l'hypothèse que les plantes Ă©troitement apparentĂ©es, employĂ©es pour traiter les maladies Ă©troitement apparentĂ©es dans les cultures très Ă©loignĂ©es les unes des autres, ont une potentialitĂ© d'efficacitĂ© supĂ©rieure parce qu'elles reprĂ©sentent la dĂ©couverte indĂ©pendante des propriĂ©tĂ©s chimiques semblables des plantes. Une partie de cette hypothèse-qui dĂ©montre que la sĂ©lection des plantes mĂ©dicinales semblables est un choix rationnel et qu'il y a davantage de ressemblance dans la flore mĂ©dicinale de deux cultures Ă©loignĂ©es que dans leur flore gĂ©nĂ©rale-est examinĂ©e par un re-Ă©chantillonnage des donnĂ©es de recherches effectuĂ©es parmi les MalinkĂ© au Mali et les Asháninka au PĂ©rou, en particulier sur la malaria, la maladie africaine du sommeil, la maladie de Chagas, la leishmania, le diabète, l'eczĂ©ma, l'asthme et les fibromes utĂ©rins. Dans ces cas prĂ©cis, la similitude de la flore mĂ©dicinale s'avère sensiblement plus grande que la similitude de la flore gĂ©nĂ©rale, mais seulement quand les maladies en question sont regroupĂ©es ensemble comme maladies parasitaires et auto-immunitaires. Si cette hypothèse est prouvĂ©e, elle permettra la synthèse des informations recueillies sur les plantes mĂ©dicinales du monde entier pour en sĂ©lectionner de façon plus prĂ©cise celles qui sont les plus efficaces et qui mĂ©ritent analyse plus approfondie au laboratoire.</p> <p><b>Asháninka abstract</b></p> <p>Aayiantyarori iròpero aavintane, ontzimatye ancovacovatero ayotero ovaqueraripaye incashi iyoyetziri ashaninka, ayotzityaro aajatzi iyotane viracocha paitachari "quimica" ancantero aaca oshintsinka inchashipaye. Atziri yotacotzirori cametsa, ishtoriajacotzirori iyotane ashaninkapaye te iroñà rantero maaroni ocaratzi yamenacotaqueri laboratorioki. Aaviantyarori cametsa, ayotacotero aavintarontsiyetatsiri osamani antzimaventero ishtoriatacotaro, aajatzi osheki opinata ampinaventero aparopaye inchashi, acoviriqui ayotacotero, osaretsikipaye. Tzimatsi ovaquerari quenquishiriantsitatsiri ero opinata osheki ashitoriatacotero aparopaye inchashi, asampiyetatyrey pashinipaye atziri saicatsiri intaina puitarika inchasshi yavintari, ajatzirica oshiyaro ayotzi aaca, quemetachari atziri saikatsiri nampitsiki malinke aajatzi ishiyari ashaninka saicatsiri peruki, tzimatsi inchashi aajatzi yaavintari osheki okamètsatzi aririka anteri mantsiyarentsi icantaitziri ompetarentsi catsirentsi, pochokirentsi, patsarontsi(matatsi) ashipetate maaroni, ampochavathate, ancainikentsite, oncatsithakite tsinani. Aririka añaker aajatzi ahiyaro inchashi yaavintayetari pashinipaye atziri intainasatzi irdotake ahitoriatacoperoteri anĂ ashityard aavintarontsi ovamairiri shithanentsi, onĂ shitaavintarontsi tzicaacoventairi ero antane mantsiyarentsi. Omanperotatyarica iròperotzi avintarontsi, oshitovake laboratorioki aritaque iyoitanaquero maaroni quipatsiki iroperori avintarontsi.</p
Relationship Between [18F]FDOPA PET Uptake, Apparent Diffusion Coefficient (ADC), and Proliferation Rate in Recurrent Malignant Gliomas
Purpose: Diffusion magnetic resonance imaging (MRI) and 6-[18F]fluoro-l-dopa ([18F]FDOPA) positron emission tomography (PET) are used to interrogate malignant tumor microenvironment. It remains unclear whether there is a relationship between [18F]FDOPA uptake, diffusion MRI estimates of apparent diffusion coefficient (ADC), and mitotic activity in the context of recurrent malignant gliomas, where the tumor may be confounded by the effects of therapy. The purpose of the current study is to determine whether there is a correlation between these imaging techniques and mitotic activity in malignant gliomas.Procedures: We retrospectively examined 29 patients with recurrent malignant gliomas who underwent structural MRI, diffusion MRI, and [18F]FDOPA PET prior to surgical resection. Qualitative associations were noted, and quantitative voxel-wise and median measurement correlations between [18F]FDOPA PET, ADC, and mitotic index were performed.Results: Areas of high [18F]FDOPA uptake exhibited low ADC and areas of hyperintensity T2/fluid-attenuated inversion recovery (FLAIR) with low [18F]FDOPA uptake exhibited high ADC. There was a significant inverse voxel-wise correlation between [18F]FDOPA and ADC for all patients. Median [18F]FDOPA uptake and median ADC also showed a significant inverse correlation. Median [18F]FDOPA uptake was positively correlated, and median ADC was inversely correlated with mitotic index from resected tumor tissue.Conclusions: A significant association may exist between [18F]FDOPA uptake, diffusion MRI, and mitotic activity in recurrent malignant gliomas
Expression of HLA-2 antigen in human melanoma cell lines and its role in T-cell recognition
(IF 2007: 7.672
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