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  • 1
  • 2
    Keywords: LUNG-CANCER ; DISEASE ; RISK ; GENES ; GENOME ; SEQUENCE ; MASS-SPECTROMETRY ; NICOTINIC ACETYLCHOLINE-RECEPTORS ; CANCER SUSCEPTIBILITY LOCUS ; 15Q25.1
    Abstract: Genome-wide association studies have highlighted three major lung cancer susceptibility regions at 15q25.1, 5p15.33 and 6p21.33. To gain insight into the possible mechanistic relevance of the genes in these regions, we investigated the regulation of candidate susceptibility gene expression by epigenetic alterations in healthy and lung tumor tissues. For genes up or downregulated in lung tumors, the influence of genetic variants on DNA methylation was investigated and in vitro studies were performed. We analyzed 394 CpG units within 19 CpG islands in the susceptibility regions in a screening set of 34 patients. Significant findings were validated in an independent patient set (n=50) with available DNA and RNA. The most consistent overall DNA methylation difference between tumor and adjacent normal tissue on 15q25 was tumor hypomethylation in the promoter region of CHRNB4 with a median difference of 8% (P〈0.001), which resulted in overexpression of the transcript in tumors (P〈0.001). Confirming previous studies, we also found hypermethylation in CHRNA3 and telomerase reverse transcriptase (TERT) with significant expression changes. Decitabine treatment of H1299 cells resulted in reduced methylation levels in gene promoters, elevated transcript levels of CHRNB4 and CHRNA3, and a slight downregulation of TERT demonstrating epigenetic regulation of lung cancer cells. Single-nucleotide polymorphisms rs421629 on 5p15.33 and rs1948, rs660652, rs8040868 and rs2036527 on 15q25.1, previously identified as lung cancer risk or nicotine-addiction modifiers, were associated with tumor DNA methylation levels in the promoters of TERT and CHRNB4 (P〈0.001), respectively, in two independent sample sets (n=82; n=150). In addition, CHRNB4 knockdown in two different cell lines (A549 and H1299) resulted in reduced proliferation (P(A549)〈0.05;P(H1299)〈0.001) and propensity to form colonies in H1299 cells. These results suggest epigenetic deregulation of nicotinic acetylcholine receptor subunit (nAChR) genes which in the case of CHRNB4 is strongly associated with genetic lung cancer susceptibility variants and a functional impact on tumorigenic potential.Oncogene advance online publication, 3 September 2012; doi:10.1038/onc.2012.344.
    Type of Publication: Journal article published
    PubMed ID: 22945651
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  • 3
    ISSN: 1432-1084
    Keywords: Key words: Granulocyte scintigraphy –111Indium pentetreotide – Kimura's disease –99 mTc-labeled autologous granulocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Uptake of 111In-pentetreotide (OctreoScan) and 99 mTc-labeled autologous granulocytes by the lesions of a 37-year-old female from Thailand with Kimura's disease is described. This is a benign chronic inflammatory condition that is endemic in Asians. It is characterized by adenopathy and subcutaneous nodules mostly affecting the head and neck area or the salivary glands. Although these examinations have previously not been described in Kimura's disease, uptake of the radiopharmaceuticals in the lesions can be expected from their histological appearance. With increasing medical, social and economic interactions with Asia, it is important to recognize this cause of adenopathy, including its appearance at various nuclear medicine examinations.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1084
    Keywords: Key words: Hodgkin's disease ; Positron emission tomography ; Sweat glands ; Fluoro deoxyglucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. A diabetic male with severe autonomic neuropathy and recently discovered Hodgkin's disease demonstrated bilateral uptake of [2-18F]-2-fluoro-2-deoxy-d-glucose (FDG) in the axillary sweat glands during profuse sweating caused by hypoglycaemia at positron emission tomography examination. It is not yet clear whether the sweating interfered with the distribution of the radiopharmaceutical. Regardless of the cause or mechanism for the uptake, the finding is clinically relevant. A bilateral symmetrical accumulation of FDG in the axillae of a tumour patient does not necessarily indicate malignant involvement of the lymph nodes.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1434-9949
    Keywords: Thermography ; Sacro-Iliac Disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The thermographic appearance of the sacro-iliac joints in health and in active inflammation has been established on the basis of 72 thermographic examinations of healthy volunteers and 82 examinations of patients with clinically and radiographically active disease. In the latter group a certain number of cases showed increased heat over the sacro-iliac joints. In addition to the heat patterns described, the main conclusion of the study is a certain variability of the normal thermal pattern, a basic experience of which is necessary for the optimal interpretation of a thermogram in suspected sacro-iliitis. Despite this variability, it is possible to recognize a standard heat pattern from which most heat patterns can be derived with more or less quantitative variations. One factor affecting the thermal pattern in a fairly constant way is the amount of subcutaneous fat.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1619-7089
    Keywords: Key words: Chemotherapy ; Osteosarcoma ; Technetium-99m hexakis-2-methoxyisobutylisonitrile ; Therapy evaluation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The use of gamma camera scintigraphy with technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) for assessment of the response of high-grade osteosarcoma to preoperative chemotherapy was evaluated. Twelve patients with osteosarcoma of the extremities underwent planar examination with 99mTc-MIBI before and after preoperative chemotherapy according to the recommendations of the Scandinavian Sarcoma Group. After calculating a quotient for the tumour and the average activity of both extremities and correcting for background activity, the change in uptake between the two examinations was assessed. This was compared with histological examination of the ultimately resected specimen in 11 patients and progressive clinical disease in one. All the 11 tumours undergoing histological examination showed cellular necrosis of between 50% and 100% as well as a reduced uptake of 99mTc-MIBI, while the single progressive tumour showed an increased uptake. There was a correlation between the reduction of radiopharmaceutical uptake and the histological response in the entire series, while the variation was too large to allow conclusions in individual patients. This variation may have biological reasons or may be due to the planar imaging technique, which only allows semiquantitative evaluation. The technique reflects response to therapy but is not yet clinically applicable for the identification of poor responders, which would serve as a basis for alteration of the chemotherapy regimen. In order to evaluate whether such a role could be fulfilled, further studies using single-photon emission tomography with correction for attenuation and scattering of photons are necessary.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1619-7089
    Keywords: Chemotherapy ; Osteosarcoma ; Technetium-99m hexakis-2-methoxyisobutylisonitrile ; Therapy evaluation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use of gamma camera scintigraphy with technetium-99m hexakis-2-methcxyisobutylisonitrile (99mTc-MIBI) for assessment of the response of high-grade osteosarcoma to preoperative chemotherapy was evaluated. Twelve patients with osteosarcoma of the extremities underwent planar examination with99mTc-MIBI before and after preoperative chemotherapy according to the recommendations of the Scandinavian Sarcoma Group. After calculating a quotient for the tumour and the average activity of both extremities and correcting for background activity, the change in uptake between the two examinations was assessed. This was compared with histological examination of the ultimately resected specimen in 11 patients and progressive clinical disease in one. All the 11 tumours undergoing histological examination showed cellular necrosis of between 50% and 100% as well as a reduced uptake of99mTc-MIBI, while the single progressive tumour showed an increased uptake. There was a correlation between the reduction of radiopharmaceutical uptake and the histological response in the entire series, while the variation was too large to allow conclusions in individual patients. This variation may have biological reasons or may be due to the planar imaging technique, which only allows semi quantitative evaluation. The technique reflects response to therapy but is not yet clinically applicable for the identification of poor responders, which would serve as a basis for alteration of the chemotherapy regimen. In order to evaluate whether such a role could be fulfilled, further studies using single-photon emission tomography with correction for attenuation and scattering of photons are necessary.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 88 (2000), S. 1407-1411 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The sublimation epitaxy growth process has been studied. The structural quality of the grown layers improves compared with the substrate mainly due to a diminished domain structure misorientation. Optical microscopy shows that the as-grown surfaces are free of typical defects appearing in silicon carbice (SiC) epitaxy, whereas atomic force microcopy measurements show macrosteps. As a possible technique to produce high-quality 4H–SiC, sublimation epitaxy was performed on substrates containing a layer grown by liquid phase epitaxy which is a growth process for closing micropipes in the initial substrate. In spite of the initial surface roughness of the liquid phase epitaxy layer, the surface morphology of the sublimation grown epilayers remained smooth and the structural quality improvement was maintained. This does not occur if the initial surfaces are too rough. A suggestion for roughness reduction is presented. The growth conditions (growth rate ramp up, growth temperature, temperature gradient, source to substrate distance, and substrate surface orientation) leading to the results are presented. A model for the mechanism for structural improvement is outlined and supporting experimental observations are given. © 2000 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The mixed lymphocyte culture (MLC) response of lymphocytes from CBA mice against C3H cells was studied after injection of spleen cells from C3H mice or C3H hybrids. Intravenous infusion of C3H cells resulted in a strongly suppressed specific MLC response, but this was not the case when cells from H-2-incompatible hybrids of C3H mice were injected. However, when mixtures of cells from the two parental strains-C3H cells and H-2-incompatible cells-were injected into CBA mice, there was a strongly suppressed MLC response to C3H cells. Mice that were hybrids between CBA and an H-2-disparate strain showed a depressed MLC response against C3H after injection of cells from hybrids between C3H and the same H-2-disparate strain. The results may indicate that a suppression of the MLC response to the strongly stimulatory non-H-2 antigen on C3H lymphocytes develops only when the immunizing cells can survive in the host for long periods, thus exhausting the pool of specifically responsive cells. The presence of another foreign transplantation antigen, such as H-2, on the same cells shortens the survival of the cells in the recipient.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Injection of CBA mice with H-2-compatible lymphoid cells from C3H hybrids induces a specific reduction of the mixed lymphocyte culture (MLC) response of their lymphoytes. This is not the case after injection of H-2-disparate C3H-hybrid cells, presumably because they are rapidly eliminated due to the immune response of the host. This investigation shows that CBA mice injected with CBA × C57B1 cells (H-2-disparate) at an age of 0–3 days, but not older, develop a specifically reduced MLC response after infusion of C3H × C57B1 cells as adults, indicating that they were tolerant to the C57B1-determined antigens. However, lymphocytes from such mice showed a normal reactivity against C57B1 as assessed by MLC, graft-versus-host tests, and capacity to produce specific antibodies.
    Type of Medium: Electronic Resource
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