Search results for "Mutation"
showing 10 items of 2830 documents
Quantitative Imaging of D-2-Hydroxyglutarate in Selected Histological Tissue Areas by a Novel Bioluminescence Technique
2016
Abstract Patients with malignant gliomas have a poor prognosis with average survival of less than one year. Whereas in other tumor entities the characteristics of tumor metabolism are successfully used for therapeutic approaches, such developments are very rare in brain tumors, notably in gliomas. One metabolic feature characteristic of gliomas, in particular diffuse astrocytomas and oligodendroglial tumors, is the variable content of D-2-hydroxyglutarate (D2HG), a metabolite, which was discovered first in this tumor entity. D2HG is generated in large amounts due to various “gain-of–function” mutations in the isocitrate dehydrogenases IDH-1 and IDH-2. Meanwhile, D2HG has been detected in se…
Frequency and prognostic impact of ALK amplifications and mutations in the European Neuroblastoma Study Group (SIOPEN) high-risk neuroblastoma trial …
2021
Purpose: In neuroblastoma (NB), the ALK receptor tyrosine kinase can be constitutively activated through activating point mutations or genomic amplification. We studied ALK genetic alterations in high-risk (HR) patients on the HR-NBL1/SIOPEN trial to determine their frequency, correlation with clinical parameters, and prognostic impact. Materials and methods: Diagnostic tumor samples were available from 1,092 HR-NBL1/SIOPEN patients to determine ALK amplification status (n = 330), ALK mutational profile (n = 191), or both (n = 571). Results: Genomic ALK amplification (ALKa) was detected in 4.5% of cases (41 out of 901), all except one with MYCN amplification (MNA). ALKa was associated with …
HDAC1 and HDAC2 integrate the expression of p53 mutants in pancreatic cancer.
2015
Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels. We fur…
The tumour microenvironment as an integrated framework to understand cancer biology
2019
Cancer cells all share the feature of being immersed in a complex environment with altered cell-cell/cell-extracellular element communication, physicochemical information, and tissue functions. The so-called tumour microenvironment (TME) is becoming recognised as a key factor in the genesis, progression and treatment of cancer lesions. Beyond genetic mutations, the existence of a malignant microenvironment forms the basis for a new perspective in cancer biology where connections at the system level are fundamental. From this standpoint, different aspects of tumour lesions such as morphology, aggressiveness, prognosis and treatment response can be considered under an integrated vision, givin…
Molecular pathway activation – New type of biomarkers for tumor morphology and personalized selection of target drugs
2018
Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in cancer development and progression, being deeply implicated in intracellular signaling pathways. To date, hundreds of different ATDs were approved for clinical use in the different countries. Compared to previous chemotherapy treatments, ATDs often demonstrate reduced side effects and increased efficiency, but also have higher costs. However, the efficiency of ATDs for the advanced stage tumors is still insufficient. Different ATDs have different mechanisms of action and are effective in different cohorts of patients. Personalized approaches are therefore needed to select the best ATD…
Molecular subtyping of colon cancer (CC) based on mutational status of RAS, BRAF, and DNA mismatch repair (MMR) proteins. Prognostic value.
2016
e15094Background: CC is a heterogeneuous disease with clinical, pathological and biological variability. Molecular classification could indentify prognostic subtypes. Methods: 105 patients with sta...
Abstract IA06: Targeting the mutanome for individualized cancer immunotherapy
2016
Abstract Mutations are regarded as ideal targets for cancer immunotherapy. As neo-epitopes with strict lack of expression in any healthy tissue, they are expected to be safe. The systematic use of mutations for vaccine approaches, however, is hampered by the uniqueness of the repertoire of mutations (the mutanome) in every patient's tumor. We have recently proposed a personalized immunotherapy approach targeting the spectrum of individual mutations. Preclinically we could show in three independent murine tumor models that a considerable fraction of non-synonymous cancer mutations is immunogenic and that unexpectedly the immunogenic mutanome is pre-dominantly recognized by CD4+ T cells (the …
Follow up analysis by exosomal miRNAs in EGFR mutated non-small cell lung cancer (NSCLC) patients during osimertinib (AZD9291) treatment: A potential…
2016
e23035Background: NSCLC patients harboring EGFR mutations are able to receive approved tyrosine kinase inhibitors (TKIs) but to better assess the treatment responses new tools are needed. Liquid bi...
Molecular Basis of Mismatch Repair Protein Deficiency in Tumors from Lynch Suspected Cases with Negative Germline Test Results
2020
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Cumulative visual impact of two coagulability disorders: A case report.
2020
Cumulative visual impact of two coagulability disorders were reviewed by presenting a case of a young female patient with a spontaneous abortion and two thromboembolic events in 8 years, whose visual function was severely affected. The particularities of her genetic constellation regarding the retinal circulation are also discussed. The patient developed a central retinal artery occlusion in the right eye during pregnancy in 2010, which led to an extended hematological workup that revealed presence of MTHFR C677T and MTHFR A1298C heterozygote mutations. The screening for myeloproliferative disorders showed JAK2 V617F gene mutation. Test results confirmed the diagnosis of thrombophilia and e…