scholarly journals Chronic Occupational Exposure to Ionizing Radiation Induces Alterations in the Structure and Metabolism of the Heart: A Proteomic Analysis of Human Formalin-Fixed Paraffin-Embedded (FFPE) Cardiac Tissue

2020 ◽  
Vol 21 (18) ◽  
pp. 6832
Author(s):  
Omid Azimzadeh ◽  
Tamara Azizova ◽  
Juliane Merl-Pham ◽  
Andreas Blutke ◽  
Maria Moseeva ◽  
...  

Epidemiological studies on workers employed at the Mayak plutonium enrichment plant have demonstrated an association between external gamma ray exposure and an elevated risk of ischemic heart disease (IHD). In a previous study using fresh-frozen post mortem samples of the cardiac left ventricle of Mayak workers and non-irradiated controls, we observed radiation-induced alterations in the heart proteome, mainly downregulation of mitochondrial and structural proteins. As the control group available at that time was younger than the irradiated group, we could not exclude age as a confounding factor. To address this issue, we have now expanded our study to investigate additional samples using archival formalin-fixed paraffin-embedded (FFPE) tissue. Importantly, the control group studied here is older than the occupationally exposed (>500 mGy) group. Label-free quantitative proteomics analysis showed that proteins involved in the lipid metabolism, sirtuin signaling, mitochondrial function, cytoskeletal organization, and antioxidant defense were the most affected. A histopathological analysis elucidated large foci of fibrotic tissue, myocardial lipomatosis and lymphocytic infiltrations in the irradiated samples. These data highlight the suitability of FFPE material for proteomics analysis. The study confirms the previous results emphasizing the role of adverse metabolic changes in the radiation-associated IHD. Most importantly, it excludes age at the time of death as a confounding factor.

2021 ◽  
Vol 4 (1) ◽  
pp. 61-65
Author(s):  
Elahe Esmaeili ◽  
◽  
Sara Ghaffarpour ◽  
Alireza Sadeghipour ◽  
Tooba Ghazanfari ◽  
...  

Background: Finding a sample of healthy tissue is a critical challenge in research studies. Non-pathological Tissue adjacent to the tumor (NAT) specimens is usually used as the control in several studies. However, little is known about the similarity of NAT to healthy tissues. Here, we compared the expression of Matrix Metalloproteinase 2 (MMP-2) and its inhibitor, Tissue Inhibitors of MMP (TIMP)-1 as extracellular matrix remodeling factors in NAT and autopsy lung tissue. Materials and Methods: RNA of 7 NAT and 6 Formalin-Fixed Paraffin-Embedded (FFPE) lung autopsies from healthy people as the control group was extracted, and cDNA was synthesized. The gene expression levels of MMP-2 and TIMP-1 were evaluated by real-time PCR. Results: There were no significant differences in the expression of MMP-2, TIMP-1, or their ratio between the two groups. Conclusion: The results showed that NAT could be used as healthy controls in lung tissue studies for MMP-2 and TIMP-1.


2019 ◽  
Vol 19 (7) ◽  
pp. 2631-2642 ◽  
Author(s):  
Anna Mantsiou ◽  
Manousos Makridakis ◽  
Konstantinos Fasoulakis ◽  
Ioannis Katafigiotis ◽  
Constantinos A. Constantinides ◽  
...  

2020 ◽  
Vol 26 (4) ◽  
pp. 2801-2807
Author(s):  
Andras Burian ◽  
Laszlo Lujber ◽  
Imre Gerlinger ◽  
Tamas Jarai ◽  
Eva Orosz ◽  
...  

Abstract Squamous cell carcinoma (SCC) of the head and neck region is the sixth most frequent malignancy with high mortality rate. Due to its poor prognosis it is considered a growing public health problem worldwide inspite of existing treatment modalities. Thus, early diagnosis of new diseases and recurrences is emerging on one hand, but on the other hand troublesome in the lack of reliable tumor markers in this field. The rapid development of proteomics has opened new perspectives in tumor marker discovery. Liquid chromatography/mass spectrometry (LC/MS) as the gold standard in proteomics enables the semi-quantitative analysis of proteins within various tissues. Abundance differences between tumor and normal tissue also can be interpreted as tumor specific changes. The aim of this study was to identify potential tumor markers of laryngeal/hypopharyngeal SCC by revealing abundance changes between cancerous and the surrounding phenotypically healthy tissue. After separating the phenotypically cancerous and healthy parts of formalin-fixed paraffin-embedded tissues, each sample underwent protein recovery process and tryptic digestion for label-free semi-quantitative LC/MS analysis. Eight proteins showed significantly higher abundance in tumor including tenascin, transmembrane emp24 domain-containing protein 2, cytoplasmic dynein light chain 1, coactosin-like protein, small proline-rich protein 2D, nucleolin, U5 small nuclear RNP 200-kDa helicase and fatty aldehyde dehydrogenase. Desmoglein-1 and keratin type I cytoskeletal 9 were down-regulated in tumor. Using Ingenuity Pathway Analysis we mapped the signaling pathways these proteins play role in regarding other tumors. Based on these findings these proteins may serve as promising biomarkers in the fight against laryngeal/hypopharyngeal SCCs.


2016 ◽  
Vol 96 (10) ◽  
pp. 1116-1127 ◽  
Author(s):  
Joon-Yong Chung ◽  
Jiyeon Choi ◽  
John D Sears ◽  
Kris Ylaya ◽  
Candice Perry ◽  
...  

2012 ◽  
Vol 19 (3) ◽  
pp. 201-206 ◽  
Author(s):  
Shirin Karimi ◽  
Forouzan Mohammadi ◽  
Kian Khodadad ◽  
Makan Sadr ◽  
Leila Seyfollahi ◽  
...  

OBJECTIVE: To better understand the characteristic morphology of angiogenic squamous dysplasia (ASD) and its association with different types of common bronchogenic carcinomas using routine white light bronchoscopy.METHODS: Using a case-control design, 186 formalin-fixed paraffin-embedded blocks of bronchial tissue (136 cases, 50 controls) obtained from patients who underwent routine nonfluorescence bronchoscopy between 2004 and 2005 were studied.RESULTS: ASD occurred at a higher frequency in patients with neoplastic lesions compared with those without neoplastic lesions (28 of 136 versus one of 50). ASD was also more prevalent in patients with squamous cell carcinoma compared with other neoplasms. Seventy six per cent of the ASD patients (22 of 29) smoked cigarettes. The morphology of ASD on hematoxylin and eosin- and CD31-stained sections was characterized by prominent microvasculature and capillary projections closely juxtaposed to variable degrees of dysplasia in all of the bronchogenic carcinoma specimens, and to metaplasia in one case in the control group.CONCLUSION: ASD is a unique morphological entity that should be considered by pathologists even on bronchoscopic biopsies from patients who undergo white light bronchoscopy. The presence of ASD may represent a risk biomarker of bronchogenic carcinoma in screening programs and in chemoprevention of lung cancer.


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