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The Global ETD Search service is a free service for researchers
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Showing 81 to 87 of 87 (0.031 seconds)Spelling suggestions: "subject:"bra"" "subject:"bref""
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Histological and molecular features of serrated colorectal adenocarcinoma and its precursor lesionsVäyrynen, S. (Sara) 16 August 2016 (has links)
Abstract
In the Western world, colorectal cancer (CRC) is one of the most common cancers and causes of cancer deaths. It is estimated that up to a third of CRCs represent a recently defined subtype, serrated adenocarcinoma (SAC), which develops via the serrated pathway and differs from conventional cancer by molecular, histological, and clinicopathological characteristics. The oncogenic mutation of BRAF V600E is characteristic to the serrated pathway lesions, and VE1 is a novel antibody that has been reported to recognize this mutated BRAF protein.
In these studies, two independent cohorts of CRCs and a cohort of 922 colorectal polyps (545 patients) consecutively removed in Oulu University Hospital were utilized to study potential immunohistochemical markers (annexin A10 and VE1) as markers for the serrated pathway lesions, to investigate the presence of ectopic crypt foci (ECF) in different colorectal polyps and CRCs, and to study the network of determinants and the clinical impact of tumor necrosis with special regard to SAC.
VE1 immunohistochemistry was found a sensitive and accurate method in the detection of BRAF V600E mutation with potential applications in the recognition of the BRAF V600E-mutated SACs. Annexin A10 immunohistochemistry was indicated to be a marker with high specificity for the serrated pathway lesions. ECF were found to be frequently encountered in addition to traditional serrated adenomas also in the tubular, tubulovillous and villous adenomas. Tumor necrosis in CRC was associated with high tumor stage and inversely associated with the serrated histology. High tumor necrosis percentage correlated with poor survival in CRC independently of other clinicopathological factors.
In conclusion, these studies add to the knowledge of the molecular and histological features of SAC and its precursors. The results suggest that VE1 and ANXA10 immunohistochemistry may help in the recognition of the serrated pathway lesions. ECF can be found in other colorectal polyps in addition to traditional serrated adenomas. Tumor necrosis represents a relevant histomorphological prognostic indicator in CRC. / Tiivistelmä
Paksu-peräsuolisyöpä on yksi yleisimmistä syövistä länsimaissa. Arviolta kolmasosaa kaikista paksu-peräsuolisyövistä edustava sahalaitainen adenokarsinooma eroaa tavallisesta adenokarsinoomasta molekulaaristen muutostensa sekä histologisten ja kliinispatologisten piirteidensä perusteella. BRAF-onkogeenin V600E-mutaatiota tavataan vain paksu-peräsuolisyövän sahalaitaisen kehittymisreitin muutoksissa ja VE1-immunohistokemian on todettu tunnistavan tämän mutatoituneen BRAF-proteiinin.
Tutkimuksessa käytettiin kahta itsenäistä paksu-peräsuolisyöpäaineistoa sekä polyyppiaineistoa, joka käsitti 922 Oulun yliopistollisessa sairaalassa peräkkäisissä kolonoskopioissa poistettua paksu-peräsuolen polyyppia (545 potilasta). Tutkimuksen tarkoituksena oli selvittää kahden immunohistokemiallisen merkkiaineen (VE1 ja annexin A10) spesifisyyttä sahalaitaiselle adenokarsinoomalle ja sen esiastemuutoksille, ektooppisten kryptafokusten esiintymistä paksu-peräsuolen polyypeissa sekä kasvaimen nekroosiin yhteydessä olevia tekijöitä ja nekroosin ennustevaikutusta.
VE1-immunohistokemia oli sekä sensitiivinen että spesifinen BRAF V600E-mutaation toteamisessa, minkä vuoksi sitä voidaan käyttää BRAF V600E-mutatoituneiden sahalaitaisten adenokarsinoomien tunnistamisessa. Annexin A10-immunohistokemia osoittautui spesifiseksi sahalaitaisen kehittymisreitin muutosten toteamissa. Ektooppisia kryptafokuksia havaittiin traditionaalisen sahalaita-adenooman lisäksi myös tubulaarisissa, tubulovillooseissa ja villooseissa adenoomissa. Kasvaimen nekroosi oli vähäisempää sahalaitaisessa adenokarsinoomassa sekä matalan levinneisyysasteen kasvaimissa. Runsas nekroosin määrä oli kasvaimen levinneisyydestä riippumatta yhteydessä huonompaan ennusteeseen.
Tutkimus lisää tietoa sahalaitaisesta adenokarsinoomasta ja sen esiastemuutoksista. Tulokset osoittavat, että VE1 ja annexin A10 -immuno¬histokemia auttaa sahalaitaisen kehittymisreitin muutosten tunnistamisessa; ektooppisia kryptafokuksia voidaan nähdä traditionaalisten sahalaita-adenoomien lisäksi myös muissa paksu-peräsuolen polyypeissa; lisäksi todettiin, että kasvaimen nekroosin määrällä on vaikutusta paksu-peräsuolisyövän ennusteen arvioinnissa.
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| 82 |
Vývoj a validace nové metodiky pro obohacení a detekci cirkulující nádorové DNA u onkologických pacientů / Development and validation of a new method for enrichment and detection of circulating tumor DNA in cancer patientsPláničková, Lenka January 2017 (has links)
Tumors are one of the leading causes of death worldwide. Generally, the prognosis is better if the treatment begins at an early stage. Nowadays, the conventional chemotherapy treatment of cancer, known for its limited efficacy and side effects, is being gradually replaced by targeted biological treatment, which is used when specific genetic mutations are found. A part of the treatment is a detection of a potential progression, which is mainly based on the tumor biomarkers monitoring. Currently, further investigation of a so-called liquid biopsy method are ongoing, on which this thesis is focused. The main aim of this work was the experimental development and validation of the method for detection of the ctDNA in the plasma samples based on the somatic mutations presence. For the development and optimization of the system on the principle of denaturation capillary electrophoresis, the samples of cancer patients with KRAS mutation were used. Subsequently, a clinical part of the research was performed on a pilot set of 21 plasma samples. Finally, the method was optimized for the detection of BRAF and EGFR markers. A partial objective was to improve the detection sensitivity and increase the capture of the ctDNA in patients with advanced stage of the disease. The results of this work suggest the...
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Molekulární testování nádorů hlavy a krku asociovaných s HPV infekcí / Molecular analysis of head and neck carcinomas associated with HPV infectionGlendová, Kristýna January 2018 (has links)
Head and neck cancers (HNSCC) are highly heterogeneous disease, results from two major carcinogens - tobacco and/or alcohol, or HR HPV infection. This thesis was based on 60 biopsies of head and neck tumours embedded into paraffin after histological verification. HPV infection, including particular types was monitored in different HNSCC regions by multiplex qPCR. Subsequent IHC demonstrated expression of p16INK4A and p53 as a possible diagnostic biomarker. Based on the information, patients with HNSCC can benefit from antiEGFR therapy by Cetuximab, but so far without defined predictors, the analysis of point mutations of Ras gene family (Kras, Nras) and Braf gene was performed. These mutations were monitored as potential predictive biomarkers, in correlation with gender, age and other risk factors. For all statistical processing the Chi-x2 test was used. Key words: Head and neck cancers, biopsy, HPV types, PCR, p16INK4A, p53, molecular predictors, Kras, Nras, Braf
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A NOVEL BRAF SIGNALING CASCADE THROUGH p-21 ACTIVATED KINASES REGULATES THYROID CANCER CELL MOTILITYMcCarty, Samantha Keiko 06 August 2013 (has links)
No description available.
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| 85 |
Cell type-dependent differential activation of ERK by oncogenic KRAS or BRAF in the mouse intestinal epitheliumBrandt, Raphael 10 March 2023 (has links)
Kolorektale Karzinome (CRC) zeigen eine heterogene Ätiologie. Die Progression prämaligner Vorläufer zu CRC unterscheidet (U) sich in Morphologie, molekularen Veränderungen und Interaktion mit der Tumorumgebung. CRC weisen oft onkogene Mutationen in KRAS und BRAF auf. Diese steigern die MAPK Signalwegaktivität (Mpa). Obwohl sie im selben Signalweg wirken, sind KRAS und BRAF auf die CRC-Entitäten U verteilt. Dabei ist KRAS häufiger im sogenannten konventionellen und BRAF im serratierten Weg zu CRC mutiert. In dieser Studie nutzte ich murine intestinale Organoide (iO), die induzierbare (Ind) KRAS oder BRAF Onkogene exprimieren. Große U zwischen KRAS und BRAF zeigten sich sowohl in Signaltransduktion (ST) als auch im Phänotyp. Phosphoprotein-, ERK-Reporter-, scRNA-Seq und EM-Analysen ergaben eine starke Mpa durch BRAF, die zu hoher Expression von MAPK-Zielgenen und Verlust der epithelialen Integrität führte. iO nach KRAS-Ind blieben intakt, korrelierend mit moderater, zelltypspezifischer (ZS) Mpa in sekretorischen und undifferenzierten Zellen. Die meisten Enterozyten waren Mpa-negativ. ERK-Reporter zeigten: Das ZS Muster der Mpa ist nicht nur gegenüber KRAS, sondern auch dem Entzug von Wachstumsfaktoren stabil. Dies spricht für eine intrinsische, robuste Regulierung der Mpa. BRAF-Ind Mpa setzte die ZS Regulierung der MAPK außer Kraft und schädigte das Gewebe, im Einklang mit einer oberen Grenze tolerabler Mpa. Die ZS Mpa wurde in CRC-Zelllinien bestätigt, deren Mpa durch KRAS aber nicht BRAF U ausfiel. Ferner, nutzte ich iO mit bCatenin+KRAS-Ind, um den konventionellen Weg zu CRC zu modellieren. Die Kombination führte zu synergistischen Effekten, die sich in EGFR-unabhängigem Wachstum und der
Aufhebung der ZS Mpa-Blockade äußerten, die durch eine Verschiebung der Differenzierung zu mehr Progenitorzellen bewirkt wurde. Zusammenfassend konnte ich U in der Mpa durch KRAS oder BRAF im Darmepithel feststellen, was dazu beiträgt, deren Rollen in der CRC-Genese zu bestimmen. / Colorectal cancer (CRC) is a disease with heterogeneous etiology. Premalignant lesions
follow distinct routes of progression to carcinoma reflected by differences in morphology,
molecular alterations and the tumor environment. Mutant KRAS and BRAF are frequent,
leading to MAPK pathway activation (Mpa), which is relevant for CRC therapy. Despite
acting in the same pathway, mutant KRAS and BRAF segregate to different entities, as KRAS
is more frequent in the conventional- and BRAF being specific for the serrated route to
CRC. I used murine intestinal organoids (iO) expressing inducible oncogenic KRAS or BRAF
to study the impact of oncogenes in primary cells. I found marked differences in signal
transduction and phenotype. Phospho-protein, ERK-reporter, scRNA-seq and EM data showed
strong Mpa upon BRAF induction followed by ERK-target gene expression leading to tissue
disruption. In contrast, KRAS left the tissue intact resulting in less and cell
type-dependent Mpa limited to secretory cells, a subset of late-stage enterocytes and
undifferentiated crypt cells. Most enterocytes were irresponsive to KRAS. The pattern of
Mpa was robust towards KRAS or growth factor depletion arguing in favor of intrinsic,
resilient MAPK regulation. In iO, BRAF-induced Mpa could break this cell type-specific
regulation, indicating an upper limit of tolerable Mpa. I validated these findings in CRC
cell lines that differed in Mpa in response to oncogenic KRAS but not BRAF. Finally, I
used iO expressing an inducible form of stabilized bCatenin in combination with KRAS to
mimic events frequently found in the conventional pathway to CRC. Expression of KRAS and
bCatenin synergized in driving EGFR independent growth and breaking the villus-specific
block of Mpa by altering differentiation towards progenitor cell types. In summary, this
study emphasizes differences between Mpa induced by oncogenic KRAS or BRAF which helps
clarifying their nature in different etiological routes to CRC genesis.
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| 86 |
MT1-MMP: TARGETING THE CENTER OF MELANOMA METASTASIS, GROWTH AND TREATMENT RESISTANCEMarusak, Charles 23 May 2019 (has links)
No description available.
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| 87 |
Modulation of Sodium Iodide Symporter-mediated Thyroidal Radioiodide Uptake by Small Molecule Inhibitors, Natural Plant-based Products and microRNAsLakshmanan, Aparna 27 May 2015 (has links)
No description available.
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