1,721,246 research outputs found
Use of artificial intelligence in endoscopy to analyze tissue biopsies
No full textHintergrund:Innovative Bildgebungstechnologien in Kombination mit künstlicher Intelligenz (KI) und Endoskopie haben das Potenzial, die Entdeckungsrate von Läsionen der Schleimhaut zu erhöhen und Tumorbiopsien besser zu charakterisieren.Ziel der Arbeit:Die Identifizierung von pathologischen Veränderungen während der Endoskopie unter Verwendung von Algorithmen der KI sowie die Bewertung endoskopischer Biopsien mittels moderner hochauflösender bildgebender Verfahren zur Gewinnung von 3D-Informationen über die komplexe Architektur und strukturelle Zusammensetzung von Tumoren soll dargestellt werden.Material und Methoden:Gegenstand der Analyse sind die Entwicklungen und Herausforderungen in den genannten Technologiefeldern und die Bewertung der potenziellen Anwendung neuer Imaging-Biomarker in Kombination mit KI in der Diagnostik von Tumoren.Ergebnisse:Mittels KI können während endoskopischer Untersuchungen Schleimhautveränderungen automatisiert erkannt und in Echtzeit charakterisiert werden. Deep-Learning-Netzwerke erlauben in histopathologischen Standardgewebeschnittbildern prognostische Aussagen zur Tumorentwicklung sowie die Identifizierung neuer Tumor-Imaging-Biomarker zur verbesserten Tumorklassifikation. Neue 3D-bildgebende Verfahren an ungefärbten und intakten Gewebeproben versprechen einen Informationsgewinn zu den morphologischen und molekularen Routineanalysen.Diskussion:Die KI-Algorithmen in Verbindung mit endoskopischen, 2D histopathologischen sowie zerstörungsfreien 3D-Untersuchungen von intakten ungefärbten Tumorbiopsien haben das Potenzial, Diagnose, Behandlung und Forschung im Bereich der Krebserkrankungen zu revolutionieren. Inwieweit die mit KI-Methoden identifizieren Imaging-Biomarker gerade im Zeitalter der Präzisionsmedizin geeignet sind, zusammen mit Daten aus Routineuntersuchungen Tumoren umfassender zu klassifizieren und die Behandlungsergebnisse durch die gezielte Auswahl bestmöglicher Therapieoptionen zu optimieren, ist in größeren klinischen Studien zu evaluieren.Background:Innovative imaging technologies combined with artificial intelligence (AI) and endoscopy have the potential to increase the detection rate of mucosal lesions and better characterize tumor biopsies.Objectives:Identification of pathological changes during endoscopy using AI algorithms and evaluation of intact and unstained endoscopic biopsies using high-resolution imaging techniques to obtain new three-dimensional (3D) information about the complex architecture and structural composition of tumors.Materials and methods:Developments and challenges in the mentioned technological fields, assessment of the potential application of new imaging biomarkers in combination with AI in tumor diagnostics.Results:Using AI, mucosal changes can be automatically detected during endoscopic examinations and characterized in real time. Deep learning networks predict biomarkers of tumor diseases for classification in standard histopathological tissue sections. New 3D imaging methods on unstained and intact tissue samples promise to provide additional information to data from routinely performed morphological and molecular analyses.Conclusion:AI algorithms in conjunction with endoscopy, 2D histopathological data, and nondestructive 3D examinations of intact, unstained tumor biopsies have the potential to revolutionize diagnosis, treatment and research in the field of cancer. The extent to which AI-based imaging biomarkers together with data from routine examinations help to classify tumors more comprehensively, especially in the age of precision medicine, and to optimize treatment results through the selection of the best possible therapy options needs to be evaluated in larger clinical studies
Anatomical and microstructural imaging of angiogenesis
No full textThis article reviews and discusses different options for visualizing the microarchitecture of vessels ex vivo and in vivo with respect to reliability, practicability and availability. The investigation of angiogenesis by standard histological methods, like microvessel density counts, is limited since the three-dimensional (3-D) architecture and the functionality of vessels cannot be considered properly. Coregistration of immunostained images of vessels may be performed but is time consuming and often not sufficiently accurate. Confocal fluorescence microscopy is an alternative, but only enables 3-D stacks of less than 500 nm in thickness. Multiphoton microscopy and other advanced technologies, such as optical coherence tomography and optical frequency domain imaging, provide a deeper view into tissues and allow for in vivo imaging of microvessels, which is a precondition for longitudinal studies. Besides these microscopic techniques, the vascularization in larger tissue samples can be investigated using corrosion casts in combination with scanning electron microscopy, or microcomputed tomography (A mu CT). Furthermore, recent improvements in A mu CT technology open up new perspectives for in vivo scans with high resolution and tolerable X-ray doses. Also 3-D contrast-enhanced high-frequency ultrasound has been shown to be sensitive for angiogenic vessels and even distinguishing between mature and immature vessels appears feasible. Microvessel architecture can also be visualized by MRI. Here, T1-weighted angiography techniques after injection of blood pool contrast agents appear preferable. Optoacoustic tomographic imaging has more recently shown promise for high-resolution in vivo mapping of the microvasculature in rodents using intrinsic haemoglobin-based contrast and exogenous contrast agents
Discoidin domain receptor 1 tyrosine kinase has an essential role in mammary gland development
No full textVarious types of collagen have been identified as potential ligands for the two mammalian discoidin domain receptor tyrosine kinases, DDR1 and DDR2. Here, we used a recombinant fusion protein between the extracellular domain of DDR1 and alkaline phosphatase to detect specific receptor binding sites during mouse development, Major sites of DDR1-binding activity, indicative of ligand expression, were found in skeletal bones, the skin, and the urogenital tract. Ligand expression in the uterus during implantation and in the mammary gland during pregnancy colocalized with the expression of the DDR1 receptor, The generation of DDR1-null mice by gene targeting yielded homozygous mutant animals that were viable but smaller in size than control littermates, The majority of mutant females were unable to bear offspring due to a lack of proper blastocyst implantation into the uterine wall, When implantation did occur, the mutant females were unable to lactate. Histological analysis showed that the alveolar epithelium failed to secrete milk proteins into the lumen of the mammary gland. The lactational defect appears to be caused by hyperproliferation and abnormal branching of mammary ducts. These results suggest that DDR1 is a key mediator of the stromal-epithelial interaction during ductal morphogenesis in the mammary gland
Differential cellular expression of the human MSH2 protein in normal and myelodysplastic haematopoiesis
No full textLoss of human MSH2 (hMSH2) protein might be involved in the multistep pathogenesis of haematological malignancies associated with genetic instability. Here, we examine cellular hMSH2 expression in bone marrow samples from 10 haematopoietically normal individuals in comparison with nine patients with myelodysplastic syndrome (MDS) [one refractory anaemia (RA), two RA with ringed sideroblasts (RARS), four RA with excess blasts (RAEB) and two RAEB in transformation (RAEB-T)]. HMSH2 protein was predominantly expressed in myeloblasts and promyelocytes. Blast cells from three patients with RAEB and one with RAEB-T displayed absent or very low hMSH2 expression. As no correlation between hMSH2 expression and chromosomal aberrations was observed, further genetic events seem to be required to induce karyotype instability
Genetic instability in myelodysplastic syndrome: detection of microsatellite instability and loss of heterozygosity in bone marrow samples with karyotype alterations
No full textUsing a polymerase chain reaction (PCR)-based approach, we examined the prevalence of loss of heterozygosity (LOH) and microsatellite instability (MSI) in relation to chromosomal imbalances in myelodysplastic syndrome (MDS). Two of 26 patients displayed MSI (8%), one of them at five loci. LOH was detected in six out of 26 cases (23%), predominantly involving markers IRF1 [5q31] and WT1 [11p]. Two patients displayed a corresponding chromosomal deletion by conventional cytogenetics. Supporting the mutator phenotype hypothesis, a significant coincidence of LOH, MSI and chromosome abnormalities was observed (P < 0.025). Moreover, our data suggest that LOH represents an initial rather than a secondary genetic event in MDS, promoting genetic instability in a subset of patients
Increased peripheral stem cell pool in MDS: an indication of disease progression?
No full textThe colony-forming capacity of the peripheral blood stem/progenitor cells (PBSC) in different forms of myelodysplastic syndrome (MDS) was investigated. In most cases of refractory anemia (RA) the colony growth of PBSC was definitely reduced as compared to the controls. However, in RA with unfavorable chromosomal aberrations, in refractory anemia with ringed sideroblasts (RARS) and in advanced stages of MDS such as refractory anemia with excess blasts (RAEB) and refractory anemia in transformation (RAEB-t), the number of myeloid progenitor cells increased up to 100-fold. In chronic myelomonocytic leukemia (CMML), the increase was even more marked, up to 350-fold. Although the number of PBSC was strongly elevated, these cells were not able to restore hematopoiesis in vivo. In conclusion, the increase of circulating colony-forming cells (CFC) seems to be associated with disease progression, and thus, the evaluation of PBSC could be an important parameter in the diagnosis of MDS. (C) 2001 Elsevier Science Ltd. All rights reserved
Organoid-Immune Cell Co-culture for Stable Live Imaging
No full textPatient-derived organoids (PDOs) have emerged as a promising model for personalized drug testing. Generated from human tumor samples, PDOs effectively recapitulate the genetic and phenotypic heterogeneity of patient tumors, making them an ideal ex vivo platform for studying therapeutic responses, particularly to chemotherapies. However, their lack of components of the immune system limits their use in immunotherapy testing. The following protocol facilitates the co-culture of PDOs from tumor tissue with HLA-matched peripheral blood mononuclear cells (PBMCs) in a fixed Z-plane for stable live-cell imaging. This three-dimensional co-culture method represents a significant advancement in enabling real-time assessment of immunotherapeutic effects on tumor-derived PDOs by live cell imaging
Tumor blood vessel visualization
No full textSignificant advances have been made in understanding the role of tumor angiogenesis and its influence on tumor progression in cancer. Based on this knowledge, a series of inhibitors of angiogenesis have been developed and evaluated in preclinical and clinical trials. Since detailed information of tumor progression in response to therapy is important to assess the efficacy of antitumor treatment in vivo, noninvasive imaging techniques emerge more and more as important tools to monitor alterations in tumor growth and vessel recruitment, as well as metastatic spread over time. So far, remarkable efforts have been made to improve the technical capability of these imaging modalities based on better resolution, as well as to implement multimodal approaches combining molecular with anatomical information. Advanced imaging techniques not only allow the detection and monitoring of tumor development, but also facilitate a broad understanding of the cellular and molecular events that propagate tumor angiogenesis, as well as those occurring in response to therapy.This review provides an overview of different imaging techniques in preclinical settings of oncological research and discusses their potential impact on clinical translation. Imaging modalities will be presented that have been implemented to address key biological issues by exploring tumor angiogenic processes and evaluating antiangiogenic therapy.Deutsche Forschungsgemeinschaft [AL336/5-1, SPP1190
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