MENX is a recessive multiple endocrine neoplasia-like syndrome in the rat. The tumor spectrum overlaps those of human neoplasia (MEN) types 1 and 2. We mapped MenX locus to distal part rat chromosome 4, excluding homologs genes responsible for MEN syndromes ( RET MEN1 ) with an component VHL NF1 ). report fine mapping disease identification homozygous frameshift mutation Cdkn1b , encoding cyclin-dependent kinase inhibitor p27 Kip1 . As consequence mutation, MENX-affected rats show dramatic...

In BriefO'Leary et al. find a long non-coding RNA called PARTICLE that is overexpressed following irradiation.PARTICLE represses tumor suppressor MAT2A via triplex formation and interaction with the polycomb repressor complex.PARTICLE also acts as cytosolic scaffold for in preparation exosomal transport from cell.

Exosomes are nanometer-sized extracellular vesicles that believed to function as intercellular communicators. Here, we report exosomes able modify the radiation response of head and neck cancer cell lines BHY FaDu. were isolated from conditioned medium irradiated well non-irradiated cells by serial centrifugation. Quantification using NanoSight technology indicated an increased exosome release compared 24 hours after treatment. To test whether released influence other transferred recipient...

Backround Radiation therapy treatment of breast cancer, Hodgkin's disease or childhood cancers expose the heart to high local radiation doses, causing an increased risk cardiovascular in survivors decades after treatment. The mechanisms that underlie damage remain poorly understood so far. Previous data show impairment mitochondrial oxidative metabolism is directly linked development disease. Methodology/Principal findings In this study, radiation-induced vivo effects on cardiac proteome and...

Radiation is a highly efficient therapy in squamous head and neck carcinoma (HNSCC) treatment. However, local recurrence metastasis are common complications. Recent evidence shows that cancer-cell-derived exosomes modify tumour cell movement metastasis. In this study, we link radiation-induced changes of to their ability promote migration recipient HNSCC cells. We demonstrate isolated from irradiated donor cells boost the motility BHY FaDu. Molecular data identified enhanced AKT-signalling,...

Chronic low-dose ionizing radiation induces cardiovascular disease in human populations but the mechanism is largely unknown. We suggested that chronic exposure may induce endothelial cell senescence associated with vascular damage vivo. investigated whether causing a change onset of cells vitro. Indeed, when exposed to continuous rate gamma (4.1 mGy/h), primary umbilical vein (HUVECs) initiated much earlier than nonirradiated control cells. changes protein expression HUVECs before and...

There is evidence that the extent of G2/M arrest following irradiation correlated with tumour cell survival and hence therapeutic success. We studied regulation cellular response to radiation treatment by miR-21-mediated modulation cycle progression in breast cancer cells analysed miR-21 expression tissue samples long-term follow up. The levels were quantified (qRT-PCR) a panel 86 cases invasive carcinomas relation metastasis free survival. radiosensitivity human after was determined...

Epidemiological data from radiotherapy patients show the damaging effect of ionizing radiation on heart and vasculature. The endothelium is main target damage contributes essentially to development cardiac injury. However, molecular mechanisms behind radiation-induced endothelial dysfunction are not fully understood. In present study, 10-week-old C57Bl/6 mice received local X-ray doses 8 or 16 Gy were sacrificed after weeks; controls sham-irradiated. microvascular cells isolated tissue using...

In rat osteoblast-like cells, a time-dependent sequence of growth and differentiation-dependent genes has been identified model osteoblast differentiation in culture suggested. We investigated the expression bone matrix-associated proteins osteonectin procollagen I cell phenotype-related alkaline phosphatase osteocalcin during primary human like cells. Primary explant cultures from nine young healthy donors were established under highly standardized conditions. Cells second passage analyzed...

Abstract Loss-of-function mutations in Patched (Ptch1) are implicated constitutive activation of the Sonic hedgehog pathway human basal cell carcinomas (BCCs), and inherited Ptch1 underlie nevus syndrome which a typical feature is multiple BCC occurring with greater incidence portals radiotherapy. Mice one copy inactivated show increased susceptibility to spontaneous tumor development hypersensitivity radiation-induced tumorigenesis, providing an ideal vivo model study pathologies associated...

Abstract Purpose: Osteosarcoma, the most common primary malignant tumor of bone, is characterized by complex karyotypes with numerous structural and numerical alterations. Despite attempts to establish molecular prognostic markers at time diagnosis, accepted predictive factor remains histologic evaluation necrosis after neoadjuvant chemotherapy. The present approach was carried out search for genome-wide recurrent loss heterozygosity copy number variations that could have therapeutic impact...

Circulating microRNAs (miRNAs) are easily accessible and have already proven to be useful as prognostic markers in cancer patients. However, their origin function the circulation is still under discussion. In present study we analyzed changes miRNAs blood plasma of head neck squamous cell carcinoma (HNSCC) patients response radiochemotherapy compared them a culture model primary HNSCC cells undergoing simulated anti-cancer therapy. MiRNA-profiles were by qRT-PCR arrays paired samples before...

Accidental nuclear scenarios lead to environmental contamination of unknown level. Immediate radiation-induced biological responses that trigger processes leading adverse health effects decades later are not well understood. A comprehensive proteomic analysis provides a promising means identify and quantify the initial damage after radiation exposure. Early changes in cardiac tissue C57BL/6 mice exposed total body irradiation were studied, using dose relevant both intentional accidental...

Epidemiological evidence suggests that low doses of ionising radiation (≤1.0 Gy) produce persistent alterations in cognition if the exposure occurs at a young age. The mechanisms underlying such are unknown. We investigated long-term effects total body gamma on neonatally exposed NMRI mice molecular and cellular level to elucidate neurodegeneration. Significant spontaneous behaviour were observed 2 4 months following single 0.5 or 1.0 Gy exposure. Alterations brain proteome, transcriptome,...

The etiology of radiation-induced cardiovascular disease (CVD) after chronic exposure to low doses ionizing radiation is only marginally understood. We have previously shown that a low-dose rate (4.1 mGy/h) causes human umbilical vein endothelial cells (HUVECs) prematurely senesce. now show dose 2.4 mGy/h also able trigger premature senescence in HUVECs, primarily indicated by loss growth potential and the appearance senescence-associated markers ß-galactosidase (SA-ß-gal) p21. In contrast,...

Formalin-fixed paraffin-embedded (FFPE) tissue has recently gained interest as an alternative to fresh/frozen for retrospective protein biomarker discovery. However, during the fixation process, proteins undergo degradation and cross-linking, making conventional analysis technologies problematic. In this study, we have compared several extraction separation methods of in FFPE tissues. Incubation sections at high temperature with a novel buffer (20 mM Tris-HCl, pH 8.8, 2% SDS, 1%...

Multiple cell types secrete exosome-like extracellular vesicles (ELVs) to the environment. Pathological conditions can produce characteristic changes vesicle cargo. We investigated if ionizing radiation is capable of inducing in protein and microRNA (miRNA) cargo ELVs.Whole blood samples from healthy donors were irradiated with 2 Gy gamma rays then peripheral mononuclear cells plasma separated residual co-cultivated for 24 h. The released ELVs collected by differential ultracentrifugation...

Extracellular vesicles (EVs) are cell-derived membrane-bound organelles that have generated interest as they reflect the physiological condition of their source. Mass spectrometric (MS) analyses protein cargo EVs may lead to discovery biomarkers for diseases. However, a comprehensive MS-based proteomics analysis, an optimal lysis is required. Six methods extraction from secreted by head and neck cell line BHY were compared. Commercial radioimmunoprecipitation assay (RIPA) buffer outperformed...

The antibody response to H. influenzae type b (Hib) is pauciclonal, and dominated by antibodies using the VkappaA2 gene. Navajos have a 5-10-fold increased incidence of Hib disease compared with control populations. We hypothesized that polymorphism in one genes this oligoclonal may lead susceptibility. Since predominant A2+ anti-Hib high avidity for can be unmutated, A2 Vkappa gene was analyzed. Over half studied, but only individual, had new allele A2, termed A2b, three changes from...

Journal Article Exon skipping in the E-cadherin gene transcript metastatic human gastric carcinomas Get access Karl-F. Becker, Becker * 1GSF-Forschungszentrum für Umwelt und Gesundheit, Institut PathologieIngolstädter Landstraβe 1,8042 Neuherberg b. München To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael J. Atkinson, Atkinson Ulrike Reich, Reich Hsuan-H. Huang, Huang 2Institut Pathologie, Technische...