BACKGROUND/AIM: Spontaneous regression (SR) of tumours is a rare phenomenon not yet fully understood. The aim of this study was to investigate immune cells infiltrating progressive and SR tumours in a Lewis rat sarcoma model. MATERIALS AND METHODS: Rats were subcutaneously inoculated with rat sarcoma R5-28 (clone C4) cells. Developing tumours were obtained on day 42 and cryosections were immunohistochemically processed for detection of immune cells. RESULTS: A high density of granulocytes was found in the necrotic areas of both progressive and SR tumours. CD4+ cells and CD8+ cells were rare and sparsely dispersed in the tumour tissue without clear difference between the two types of tumours. On the contrary, CD161+ cells were abundant and evenly distributed in SR tumours, but these cells were very rare in progressive tumours. CONCLUSION: Based on the differences in number and distribution of the immune cell subpopulations, we believe that natural killer (CD161+) cells play a major role in the destruction of cancer cells during SR of tumours in this Lewis rat model.

• Klíčová slova
• CD161, CD4, CD8, Tumour, immunohistochemistry, spontaneous regression,
• MeSH
• buňky NK patologie   MeSH
• CD4-pozitivní T-lymfocyty patologie   MeSH
• CD8-pozitivní T-lymfocyty patologie   MeSH
• imunohistochemie MeSH
• krysa rodu Rattus MeSH
• lektinové receptory NK-buněk - podrodina B genetika   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• potkani inbrední LEW MeSH
• regulace genové exprese u nádorů MeSH
• sarkom genetika   patologie   MeSH
• spontánní regrese nádoru genetika   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lektinové receptory NK-buněk - podrodina B MeSH

Farber disease (FD) is a debilitating lysosomal storage disorder (LSD) caused by a deficiency of acid ceramidase (ACDase) activity due to mutations in the gene ASAH1. Patients with ACDase deficiency may develop a spectrum of clinical phenotypes. Severe cases of FD are frequently associated with neurological involvement, failure to thrive, and respiratory complications. Mice homozygous ( Asah1P361R/P361R) for an orthologous patient mutation in Asah1 recapitulate human FD. In this study, we show significant impairment in lung function, including low compliance and increased airway resistance in a mouse model of ACDase deficiency. Impaired lung mechanics in Farber mice resulted in decreased blood oxygenation and increased red blood cell production. Inflammatory cells were recruited to both perivascular and peribronchial areas of the lung. We observed large vacuolated foamy histiocytes that were full of storage material. An increase in vascular permeability led to protein leakage, edema, and impacted surfactant homeostasis in the lungs of Asah1P361R/P361R mice. Bronchial alveolar lavage fluid (BALF) extraction and analysis revealed accumulation of a highly turbid lipoprotein-like substance that was composed in part of surfactants, phospholipids, and ceramides. The phospholipid composition of BALF from Asah1P361R/P361R mice was severely altered, with an increase in both phosphatidylethanolamine (PE) and sphingomyelin (SM). Ceramides were also found at significantly higher levels in both BALF and lung tissue from Asah1P361R/P361R mice when compared with levels from wild-type animals. We demonstrate that a deficiency in ACDase leads to sphingolipid and phospholipid imbalance, chronic lung injury caused by significant inflammation, and increased vascular permeability, leading to impaired lung function.

• MeSH
• bronchoalveolární lavážní tekutina MeSH
• ceramidy metabolismus   MeSH
• fenotyp MeSH
• fosfolipidy metabolismus   MeSH
• homozygot MeSH
• kyselá ceramidasa fyziologie   MeSH
• modely nemocí na zvířatech * MeSH
• myši knockoutované MeSH
• myši MeSH
• plíce metabolismus   patologie   MeSH
• poškození plic etiologie   metabolismus   patologie   MeSH
• respirační funkční testy MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Asah1 protein, mouse MeSH Prohlížeč
• ceramidy MeSH
• fosfolipidy MeSH
• kyselá ceramidasa MeSH

Establishment of new animal models using selected cell lines with different behaviour is very important for cancer investigations. In this study, we describe three morphologically distinct rat sarcoma clones-C4, C7 and D6-isolated from the R5-28 cell line. Cells of all clones expressed vimentin, fibronectin, laminin, collagen IV and matrix metalloproteinases 2 and 9. However, desmin, cytokeratins 8 and 18, ZO-1 and desmoplakins I and II were not detected. Significant proliferative capacity was documented by proliferating cell nuclear antigen expression and BrdU positivity. Karyotype of the C4, C7 and D6 cells greatly differed from diploid chromosome number of normal rat somatic cells. High expression of three cytokines-monocyte chemoattractant protein 1, tissue inhibitor of metalloproteinases 1 and vascular endothelial growth factor-was observed in all three clones. However, they varied in concentration of chemokines associated with neutrophil migration and activation-cytokine induced neutrophil chemoattractant 2 and lipopolysaccharide induced CXC chemokine. The C4 clone showed spontaneous tumour regression in vivo that was associated with significant changes in lymphocyte subpopulations.

• MeSH
• buněčné klony * MeSH
• extracelulární matrix - proteiny metabolismus   MeSH
• karyotypizace MeSH
• krysa rodu Rattus MeSH
• nádorové buněčné linie MeSH
• sarkom genetika   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• extracelulární matrix - proteiny MeSH