Neural Crest Stem Cells in Juvenile Angiofibromas

The etiology of juvenile angiofibroma (JA) has been a controversial topic for more than 160 years. Numerous theories have been proposed to explain this rare benign neoplasm arising predominately in adolescent males, focusing mainly on either the vascular or fibrous component. To assess our hypothesis of JA’s being a malformation arising from neural crest cells/remnants of the first branchial arch plexus, we performed immunohistochemical analyses of neural crest stem cells (NCSC) and epithelial-mesenchymal transition (EMT) candidates. Immunoexpression of the NCSC marker CD271p75 was observed in all investigated JA’s (n = 22), mainly around the pathological vessels. Close to CD271p75-positive cells, high MMP3-staining was also observed. Additionally, from one JA with sufficient material, RT-qPCR identified differences in the expression pattern of PDGFRβ, MMP2 and MMP3 in MACS®-separated CD271p75positive vs. CD271p75 negative cell fractions. Our results, together with the consideration of the literature, provide evidence that JA’s represent a malformation within the first branchial arch artery/plexus remnants deriving from NCSC. This theory would explain the typical site of tumor origin as well as the characteristic tumor blood supply, whereas the process of EMT provides an explanation for the vascular and fibrous tumor component

Comparison of optical sensors discrimination ability using spectral libraries

In remote sensing, the ability to discriminate different land covers or material types is directly linked with the spectral resolution and sampling provided by the optical sensor. Previous studies showed that the spectral resolution is a critical issue, especially in complex environment. In spite of the increasing availability of hyperspectral data, multispectral optical sensors onboard various satellites are acquiring everyday a massive amount of data with a relatively poor spectral resolution (i.e. usually about 4 to 7 spectral bands). These remotely sensed data are intensively used for Earth observation regardless of their limited spectral resolution. In this paper, we studied seven of these optical sensors: Pleiades, QuickBird, SPOT5, Ikonos, Landsat TM, Formosat and Meris. This study focuses on the ability of each sensor to discriminate different materials according to its spectral resolution. We used four different spectral libraries which contains around 2500 spectra of materials and land covers with a fine spectral resolution. These spectra were convolved with the Relative Spectral Responses (RSR) of each sensor to create spectra at the sensors’ resolutions. Then, these reduced spectra were compared using separability indexes (Divergence, Transformed divergence, Bhattacharyya, Jeffreys-Matusita) and machine learning tools. In the experiments, we highlighted that the spectral bands configuration could lead to important differences in classification accuracy according to the context of application (e.g. urban area)

Crowdsourcing of Histological Image Labeling and Object Delineation by Medical Students

Crowdsourcing in pathology has been performed on tasks that are assumed to be manageable by nonexperts. Demand remains high for annotations of more complex elements in digital microscopic images, such as anatomical structures. Therefore, this work investigates conditions to enable crowdsourced annotations of high-level image objects, a complex task considered to require expert knowledge. 76 medical students without specific domain knowledge who voluntarily participated in three experiments solved two relevant annotation tasks on histopathological images: (1) Labeling of images showing tissue regions, and (2) delineation of morphologically defined image objects. We focus on methods to ensure sufficient annotation quality including several tests on the required number of participants and on the correlation of participants' performance between tasks. In a set up simulating annotation of images with limited ground truth, we validated the feasibility of a confidence score using full ground truth. For this, we computed a majority vote using weighting factors based on individual assessment of contributors against scattered gold standard annotated by pathologists. In conclusion, we provide guidance for task design and quality control to enable a crowdsourced approach to obtain accurate annotations required in the era of digital pathology

Immunohistochemistry Reveals TRPC Channels in the Human Hearing Organ : A Novel CT-Guided Approach to the Cochlea

TRPC channels are critical players in cochlear hair cells and sensory neurons, as demonstrated in animal experiments. However, evidence for TRPC expression in the human cochlea is still lacking. This reflects the logistic and practical difficulties in obtaining human cochleae. The purpose of this study was to detect TRPC6, TRPC5 and TRPC3 in the human cochlea. Temporal bone pairs were excised from ten body donors, and the inner ear was first assessed based on computed tomography scans. Decalcification was then performed using 20% EDTA solutions. Immunohistochemistry with knockout-tested antibodies followed. The organ of Corti, the stria vascularis, the spiral lamina, spiral ganglion neurons and cochlear nerves were specifically stained. This unique report of TRPC channels in the human cochlea supports the hypothesis of the potentially critical role of TRPC channels in human cochlear health and disease which has been suggested in previous rodent experiments

Extraction de détecteurs d'objets urbains à partir d'une ontologie

National audienceAfin de parvenir à une méthode d'interprétation automatique d'im-ages de télédétection à très haute résolution spatiale, il est nécessaire d'exploiter autant que possible les connaissances du domaine. Pour détecter différents types d'objet comme la route ou le bâti, des méthodes très spécifiques ont été dévelop-pées pour obtenir de très bons résultats. Ces méthodes utilisent des connais-sances du domaine sans les formaliser. Dans cet article, nous proposons tout d'abord de modéliser la connaissance du domaine de manière explicite au sein d'une ontologie. Ensuite, nous introduisons un algorithme pour construire des détecteurs spécifiques utilisant les connaissances de cette ontologie. La sépara-tion nette entre modélisation des connaissances et construction des détecteurs rend plus lisible le processus d'interprétation. Ce découplage permet également d'utiliser l'algorithme de construction de détecteurs dans un autre domaine d'ap-plication, ou de modifier l'algorithme de construction de détecteurs sans modi-fier l'ontologie

P35. Intratumoral patterns of clonal evolution in meningiomas

Núm. a Art Públic: 1815Digitalitzat per Tecnodo

Segmentation par ligne de partage des eaux basée sur des connaissances texturales

La segmentation d'une image a pour but de créer des régions homogènes selon un critère défini en fonction de l'application considérée. Le critère peut être, par exemple, les valeurs des pixels de l'image ou des indices de texture. Une fois la segmentation obtenue, une classification des régions peut être effectuée afin d'associer une sémantique aux objets présents dans l'image. L'hypothèse d'homogénéité entre des pixels d'un même objet doit permettre la construction de régions correspondant aux objets de l'image. Dans le cas d'images complexes comme les images satellites à très haute résolution spatiale, l'homogénéité classique des pixels d'un même objet n'est pas valide, réduisant la qualité des segmentations obtenues. Dans cet article, nous proposons d'intégrer au processus de segmentation par ligne de partage des eaux des connaissances sous forme d'exemples étiquetés par l'utilisateur. Nous introduisons ainsi un critère d'homogénéité de plus haut niveau basé sur des connaissances texturales

Prognostic genetic markers in malignant gliomas

Glioblastomas are the most frequent and malignant brain tumors in adults. Surgical cure is virtually impossible and despite of radiation and chemotherapy the clinical course is very poor. Epigenetic silencing of MGMT has been associated with a better response to temozolomide-chemotherapy. We previously showed that temozolomide increases the median survival time of patients with tumors harbouring deletions on 9p within the region for p15(INK4b), p16(INK4a), and 10q (MGMT). The aim of this study was to investigate the methylation status of p15, p16, 14ARF and MGMT in glioblastomas and to correlate the results with the clinical data.Only patients with KPS > 70, radical tumor resection, radiation and temozolomide-chemotherapy after recurrence were included. We observed promoter methylation of MGMT in 56% (15/27) and of p15 in 37% (10/27) of the tumors, whereas methylation of p16 and p14ARF were rare. Interestingly, methylation of p15 emerged as a significant predictor of shorter overall survival (16.9 vs. 23.8 months, p=0.025), whereas MGMT promoter methylation had no significant effect on median overall survival under this treatment regimen (22.5 vs. 22.1 months, p=0.49). In the presence of other clinically relevant factors, p15 methylation remains the only significant predictor (p=0.021; Cox regression).Although these results need to be confirmed in larger series and under different treatment conditions, our retrospective study shows clear evidence that p15 methylation can act as an additional prognostic factor for survival and underlines that this tumor suppressor, involved in cell cycle control, can act as an attractive candidate for therapeutic approaches in glioblastomas

Antagonizing Sec62 function in intracellular Ca2+ homeostasis represents a novel therapeutic strategy for head and neck cancer

Various cancer types including head and neck squamous cell carcinomas (HNSCC) show a frequent amplification of chromosomal region 3q26 that encodes, among others, for the SEC62 gene. Located in the ER membrane, this translocation protein is known to play a critical role as a potential driver oncogene in cancer development. High SEC62 expression levels were observed in various cancer entities and were associated with a poor outcome and increased metastatic burden. Because of its intracellular localization the SEC62 protein is poorly accessible for therapeutic antibodies, therefore a functional SEC62 knockdown represents the most promising mechanism of a potential antineoplastic targeted therapy. By stimulating the Ca2+ efflux from the ER lumen and thereby increasing cellular stress levels, a functional inhibition of SEC62 bears the potential to limit tumor growth and metastasis formation. In this study, two potential anti-metastatic and -proliferative agents that counteract SEC62 function were investigated in functional in vitro assays by utilizing an immortalized human hypopharyngeal cancer cell line as well as a newly established orthotopic murine in vivo model. Additionally, a CRISPR/ Cas9 based SEC62 knockout HNSCC cell line was generated and functionally characterized for its relevance in HNSCC cell proliferation and migration as well as sensitivity to SEC62 targeted therapy in vitro

Inhibition of CK2 Reduces NG2 Expression in Juvenile Angiofibroma

Juvenile angiofibroma (JA) is a rare fibrovascular neoplasm predominately found within the posterior nasal cavity of adolescent males. JA expresses the proteoglycan nerve–glial antigen (NG)2, which crucially determines the migratory capacity of distinct cancer cells. Moreover, it is known that the protein kinase CK2 regulates NG2 gene expression. Therefore, in the present study, we analyzed whether the inhibition of CK2 suppresses NG2-dependent JA cell proliferation and migration. For this purpose, we assessed the expression of NG2 and CK2 in patient-derived JA tissue samples, as well as in patient-derived JA cell cultures by Western blot, immunohistochemistry, flow cytometry and quantitative real-time PCR. The mitochondrial activity, proliferation and migratory capacity of the JA cells were determined by water-soluble tetrazolium (WST)-1, 5-bromo-20 -deoxyuridine (BrdU) and collagen sprouting assays. We found that NG2 and CK2 were expressed in both the JA tissue samples and cell cultures. The treatment of the JA cells with the two CK2 inhibitors, CX-4945 and SGC-CK2-1, significantly reduced NG2 gene and protein expression when compared to the vehicle-treated cells. In addition, the loss of CK2 activity suppressed the JA cell proliferation and migration. These findings indicate that the inhibition of CK2 may represent a promising therapeutic approach for the treatment of NG2-expressing JA