Histology and histopathology Vol.33, nº9 (2018)
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- PublicationOpen AccessHuman skin model for mimic dermal studies in pathology with a clinical implication in pressure ulcers(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Cristóbal, Lara; Ortega, Miguel A.; Asúnsolo, Ángel; Romero, Beatriz; Álvarez Mon, Melchor; Buján, Julia; Maldonado, Andrés A.; García Honduvilla, NatalioDespite advances in regenerative medicine and tissue engineering, human skin substitutes remain a clear goal to achieve. Autografts remain the principal clinical option. The long-term changes in dermis, as well as its response after injuries, are not well known. Research in this field has been hindered by a lack of experimental animal models. This study analyzes the architectural dermal scaffold (collagen and elastin fibers plus fibrillin-microfibrils) changes in a model of human skin pressure ulcers in mice. Immunosuppressed NOD/Scid mice (n=10) were engrafted with human skin of dimensions 4x3 cm. After 60 days as a permanent graft, a pressure ulcer (PU) was created in the human skin using a compression device. Three study groups were established: full-thickness skin graft before (hFTSG) and after applying mechanical pressure (hFTSG-PU). Native human skin was used as control group. Evaluations were conducted with visual and histological assessment. Scaffold components from each group were compared by immunohistochemical staining (tropoelastin, collagen I and III, metalloproteins (MMP), fibulins, and lysil oxidases (LOX) among others). The long-term engrafted skin showed a certain degradative state of dermis scaffold, as noticed by the active expression of MMPs and tropoelastin compared to native skin. However, a great reparative response after pressure ulcer onto the engrafted skin was observed. A significant increase of fibrillin microfibrils components (TGF-β, MAGP-1 and fibrillin-1), and matrix suprastructures of collagen I, III and LOX lead to an active restructuration of dermal tissue. Our human skin model in mice revealed the important role of the dermal scaffold component to reach skin stability and its capability to react to mechanical pressure injuries. These results showed the important role of dermal scaffold to support the histoarchitecture and mechanosensation of the human skin.
- PublicationOpen AccessUnderstanding the roles of negative immune regulator TIPE2 in different diseases and tumourigenesis(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Li, Zequn; Jia, Wenyu; Niu, Jun; Zhang, LiningTumour necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a novel identified negative regulator of both innate and adaptive immunity, which participates in immune homeostasis. TIPE2 is expressed in both immune tissues and nonimmune tissues. It is significantly down-regulated in patients with infectious and autoimmune diseases, and the depletion of TIPE2 causes severe inflammatory disease. In recent years, accumulating evidence has shown that TIPE2 serves as an ideal biomarker and as a tumour suppressor in several tumour types. In this review, we summarized the roles and corresponding mechanisms of TIPE2 in immune regulation and different diseases, especially in tumourigenesis.
- PublicationOpen AccessExpression of plakophilin 3 in diffuse malignant pleural mesothelioma(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Mašić, Silvija; Brčić, Luka; Krušlin, Božo; Pigac, Biserka; Stančić Rokotov, Dinko; Jakopović, Marko; Seiwerth, SvenDiffuse malignant pleural mesothelioma (DMPM) is the most common primary malignant pleural neoplasm still posing major diagnostic, prognostic and therapeutic challenges. Plakophilins are structural proteins considered to be important for cell stability and adhesion in both tumor and normal tissues. Plakophilin 3 is a protein present in desmosomes of stratified and simple epithelia of normal tissues with presence in malignant cells of various tumors where it participates in the process of tumorigenesis. The aim of this study was to investigate the expression of plakophilin 3 protein in DMPM, but also to study its prognostic significance and relation to histologically accessible parameters of aggressive growth. Archival samples of tissue with established diagnosis of DMPM and samples of normal pleural tissue were used. Tumor samples were classified into three histological types of DMPM (epithelioid, sarcomatoid and biphasic). Additional subclassification of epithelioid mesotheliomas into nine patterns based on the prevalent histological component of the tumor was then performed. After immunohistochemical staining, cytoplasmic and membrane immunopositivity of tumor cells was assesed by scoring the intensity of the staining from 0 (no staining) to 4 (very strong staining). Prognostic value and expression of plakophilin 3 with consideration to histologically estimated aggression in tumor growth were then statistically analyzed using nonparametric tests. The results demonstrated higher level of plakophilin 3 expression in tumor samples with histologically more aggressive tumor growth, but no significant prognostic value. According to our study, plakophilin 3 appears to be involved in tumor invasion in malignant mesothelioma.
- PublicationOpen AccessExpression of EMT inducers integrin-linked kinase (ILK) and ZEB1 in phyllodes breast tumors is associated with aggressive phenotype(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Akrida, Ioanna; Nikou, Sofia; Gyftopoulos, Konstantinos; Argentou, Marianna; Kounelis, Sofia; Zolota, Vassiliki; Bravou, Vasiliki; Papadaki, HelenPhyllodes tumors (PTs) of the breast constitute an uncommon group of mammary fibroepithelial lesions with ambiguous biologic behavior. Recent evidence suggests that epithelial mesenchymal transition (EMT), a driving force of cancer progression is implicated in PTs pathogenesis. Integrin-linked kinase (ILK), a focal adhesion kinase, has been implicated in cancer and EMT and represents a novel cancer therapeutic target. In this study, we aimed to investigate ILK and EMT markers expression in phyllodes breast tumors in relation to tumor grade. Expression of ILK and EMT markers E-cadherin, β-catenin, Ν-cadherin, vimentin, Snail, ZEB1 and Twist was evaluated by immunohistochemistry in paraffin-embedded tissue sections from 96 human phyllodes breast tumors (48 benign, 27 borderline, 21 malignant). Cytoplasmic and nuclear immunopositivity of ILK were observed in both the epithelial and the stromal component of phyllodes breast tumors and were significantly higher with increasing tumor grade. An EMT-related expression profile consisting of decreased membranous and increased nuclear/cytoplasmic immunoreactivity of Ecadherin and β-catenin and increased expression of Ncadherin, vimentin, Snail, ZEB1 and Twist was observed in tumor epithelial and stromal component and was significantly associated with malignant phyllodes breast tumor histopathology. Interestingly, there was a significant correlation of ILK expression with all of the EMT markers examined. Our results suggest that EMT significantly contributes to phyllodes tumor pathogenesis and originally implicate ILK and ZEB1 in phyllodes tumors malignant phenotype.
- PublicationOpen AccessSPHK2 protein expression, Ki-67 index and infiltration of tumor-associated macrophages (TAMs) in human glioma(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Liu, J.; Zhou, Q.; Wu, C.P.; Xu, Y.W.; Liu, W.L.; Zhao, H.F.; Li, W.P.Introduction. Sphingosine kinases (SPHKs), the Ki-67 index and tumor-associated macrophages (TAMs) are associated with diverse human malignancies, including glioma. SPHK2, a subtype of SPHKs, has not been assessed in glioma or correlated with the Ki-67 index or TAM infiltration. We tested the hypothesis that expression of SPHK2 correlates with the Ki-67 index and TAM infiltration in patients with glioma. Materials and method. Western blot analysis was performed on protein lysates prepared from human astrocyte (HA) and glioma cell lines. Immunofluorescence was used to determine the subcellular location of SPHK2 protein in glioma cells. Next, immunohistochemistry was employed to analyze the correlations among SPHK2, Ki-67, CD68, and CD206 in 11 non-neoplastic brain tissues and 60 glioma tissues. All slides were evaluated under ×400 magnification, and the ratio of positively stained cells to the total number of cells was calculated for analysis. Results. SPHK2, CD68 and CD206 were all increased in glioma tissues compared to non-neoplastic brain tissues, but there were no differences between WHO grades of glioma. Ki-67 was highest in WHO grade IV tumors and lowest in non-neoplastic brain tissues, and all between-group differences were statistically significant. Moreover, SPHK2 expression was positively correlated with the Ki-67, CD68 and CD206 indexes. Finally, the CD68 and CD206 indexes were both associated with the Ki-67 index. Conclusion. SPHK2 protein expression, the Ki-67 index and TAM infiltration in human glioma tissue were reported in this study for the first time. SPHK2 was positively associated with TAM infiltration and glioma proliferation. Mechanistically, SPHK2 may promote glioma growth by stimulating TAMs to polarize M2-type macrophages.
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