Browsing by Subject "HIF-1α"

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    Comprehensive insights into the understanding of hypoxia in ameloblastoma
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Bologna Molina, Ronell; Schuch, Lauren; Niklander, Sven Eric
    Hypoxia is characterized by a disparity between supply and demand of oxygen. The association between hypoxia and head and neck tumors is a topic of significant interest. Tumors frequently encounter areas with inadequate oxygen supply, resulting in a hypoxic microenvironment. Ameloblastoma is one of the most common benign odontogenic tumors of the maxillofacial region. It is a slow-growing but locally invasive tumor with a high recurrence rate. The literature has demonstrated the correlation between hypoxia and ameloblastoma, revealing a discernible link between the heightened expression of hypoxic markers in low oxygen conditions. This association is intricately tied to the tumoral potential for invasion, progression, and malignant transformation. Hypoxia profoundly influences the molecular and cellular landscape within ameloblastic lesions. The present review sheds light on the mechanisms, implications, and emerging perspectives in understanding this intriguing association to clarify the dynamic relationship between hypoxia and ameloblastoma.
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    Differential expression of HIF-1α and its hypoxia-related inducers in the spleens of plateau yaks and plain yellow cattle
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Zhou, Manlin; Dong, Shihui; Wang, Jun; Luo, Xuehui; Li, Rui; Zhang, Yiyang; Ding, Haie; Tan, Xiao; Qiao, Zilin; Yang, Kun; Chen, Weiji
    The present study aims to investigate the distribution and expression characteristics of HIF-1α, VEGF, VEGFR-2, VCAM-1, and IL-4 in the spleen of plateau yaks and plain yellow cattle and to speculate the possible regulatory role of HIF-1α and its related hypoxia-inducible factors in the adaptation of the yak spleen to the plateau hypoxic environment. Histological features were observed using H&E and PAS stains. Immunohistochemical staining and optical density analysis were applied to investigate the distribution and differences in the expression of HIF-1α, VEGF, VEGFR-2, VCAM-1, and IL-4 in the spleen of yaks and cattle. The results showed that the area of splenic trabeculae and splenic nodules was significantly larger in the yak than in yellow cattle (P<0.05). Glycogen was mainly distributed in splenic arterial endothelial cells, vascular smooth muscle cells, splenic blood sinusoidal endothelial cells, and fibroblasts, and the distribution was significantly higher in the spleen of yaks than in cattle (P<0.05). HIF-1α, VEGF, VEGFR-2, VCAM-1, and IL-4 were mainly expressed in lymphocytes, arterial endothelial cells, vascular smooth muscle cells, splenic blood sinusoidal endothelial cells, and fibroblast cytoplasm, with higher expression in yak spleen (P<0.05). In conclusion, combining the differences in spleen tissue structure, glycogen distribution, and expression distribution of several hypoxia-related factors between yaks and cattle, we suggest that HIF-1α, VEGF, VEGFR-2, VCAM-1, and IL-4 may be important factors in the adaptation of yak spleen to the plateau environment, which provides a theoretical basis for further exploring the adaptation mechanism of plateau hypoxia in yaks.
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    Immunoexpression patterns for Hypoxia-inducible Factor-1α and von Hippel-Lindau protein, in relation to Hsp90, of human brain tumors
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Assimakopoulou, Martha; Androutsopoulou, Christina; Zolota, Vassiliki; Matsoukas, John
    The pathogenesis of many tumors, including brain tumors, has been associated with hypoxia, which induces the transcriptional activity of Ηypoxia-inducible Factor-1α (HIF-1α). HIF-1α is normally degradated by the von Hippel-Lindau protein (pVHL) but, in hypoxia, pVHL/HIF-1α interaction is inhibited resulting in the nuclear accumulation of HIF-1α. Hsp90 (Heat shock protein 90), as a chaperone protein, plays a critical role for both stabilization of HIF-1α and degradation of pVHL. The aim of this study was to estimate immunohistochemically the expression levels of HIF-1α and pVHL, in relation to Hsp90, in different types of human brain tumors (42 gliomas, 9 medulloblastomas, and 38 meningiomas) using specific antibodies. The tumors were further divided into two groups according to the age of patients (≥19 years old or <19 years old). Nuclear, for HIF-1α, and cytoplasmic, for pVHL and Hsp90, localization was detected in a high percentage of tumor cells in the majority of tumors. In astrocytomas, a significant, grade-dependent relationship for HIF-1α immunoexpression was observed (p<0.05). Furthermore, there was a significant correlation between pVHL and Hsp90 immunoexpression (p<0.01). The group of ≥19 years old patients with glioblastomas (WHO grade IV) demonstrated significantly increased immunoexpression for HIF-1α compared to pVHL (p<0.0001) and Hsp90 expression (p<0.01). In medulloblastomas, a significant correlation of HIF-1α with Hsp90 immunoexpression (p<0.05) was found. In meningiomas, no significant correlation for the expression of the three proteins was detected (p≥0.05). These results indicate that HIF1α/pVHL/Hsp90 interactions may be implicated in biology of different types of brain tumors through different signaling mechanisms.
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    Spatial transcriptomic analysis of tumour with high and low CAIX expression in TNBC tissue samples using GeoMx™ RNA assay
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Shamis, Suad A.K.; Savioli, Francesca; Ammar, Aula; Al Badran, Sara S.F.; Hatthakarnkul, Phimmada; Leslie, Holly; Mallon, Elizabeth E.A.; Jamieson, Nigel B.; McMillan, Donald C; Edwards, Joanne
    Purpose. Prognostic significance and gene signatures associated with carbonic anhydrase IX (CAIX) was investigated in triple negative breast cancer (TNBC) patients. Methods. Immunohistochemistry (IHC) for CAIX was performed in tissue microarrays (TMAs) of 136 TNBC patients. In a subset of 52 patients Digital Spatial Profiler (DSP) was performed in tumour (pancytokeratin+) and stroma (pan-cytokeratin-). Differentially expressed genes (DEGs) with P<0.05 and log2 fold change (FC)>(±0.25 and ±0.3, for tumour and stromal compartment, respectively) were identified. Four genes were validated at the protein level. Result. Cytoplasmic CAIX expression was independently associated with poor recurrence free survival in TNBC patients [hazard ratio (HR)=6.59, 95% confidence interval (CI): 1.47-29.58, P=0.014]. DEG analysis identified 4 up-regulated genes (CD68, HIF1A, pan-melanocyte, and VSIR) in the tumour region and 9 down-regulated genes in the stromal region (CD86, CD3E, MS4A1, BCL2, CCL5, NKG7, PTPRC, CD27, and FAS) when low versus high CAIX expression was explored. Employing IHC, high CD68 and HIF-1α was associated with poorer prognosis and high BCL2 and CD3 was associated with good prognosis. Conclusions. DSP technology identified DEGs in TNBC. Selected genes validated by IHC showed involvement of CD3 and BCL2 expression within stroma and HIF-1α, and CD68 expression within tumour. However, further functional analysis is warranted