Histology and histopathology Vol.31, nº5 (2016)
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- PublicationOpen AccessFHL2: A scaffold protein of carcinogenesis, tumour-stroma interactions and treatment response(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Verset, Laurine; Feys, Lynn; Trépant, Anne-Laure; De Wever, Olivier; Demetter, PieterFour-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional scaffolding protein regulating signalling cascades and gene transcription. It shuttles between focal adhesions and the nucleus where it signals through direct interaction with a number of proteins including β-catenin. The multiplicity of molecular pathways affected by FHL2 suggests an important role in several physiological and pathological events. The function of FHL2 in cancer is particularly intriguing, since it may act as an oncoprotein or as a tumour suppressor in a tissue-dependent fashion. In this review we present the current knowledge on the role of FHL2 in carcinogenesis, with emphasis on the digestive tract. We discuss the overexpression of FHL2 in colorectal, gastric and pancreatic cancer, the downregulation in hepatocellular carcinoma and the role of FHL2 in epithelial-mesenchymal transition. We briefly look at the potential role of FHL2 in the tumoural microenvironment and discuss how FHL2 expression and function might influence cancer treatment. Before implementation of FHL2 as a biomarker by pathologists, antibody validation should, however, be carried out.
- PublicationOpen AccessChanges in vascular extracellular matrix composition during decidual spiral arteriole remodeling in early human pregnancy(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Smith, Samantha D.; Choudhury, Ruhul H.; Matos, Patricia; Horn, James A.; Lye, Stephen J.; Dunk, Caroline E.; Aplin, John D.; Jones, Rebecca L.; Harris, Lynda KUterine spiral arteriole (SA) remodeling in early pregnancy involves a coordinated series of events including decidual immune cell recruitment, vascular cell disruption and loss, and colonization by placentalderived extravillous trophoblast (EVT). During this process, decidual SA are converted from narrow, muscular vessels into dilated channels lacking vasomotor control. We hypothesized that this extensive alteration in SA architecture must require significant reorganization and/or breakdown of the vascular extracellular matrix (ECM). First trimester decidua basalis (30 specimens) was immunostained to identify spiral arterioles undergoing trophoblast-independent and -dependent phases of remodeling. Serial sections were then immunostained for a panel of ECM markers, to examine changes in vascular ECM during the remodeling process. The initial stages of SA remodeling were characterized by loss of laminin, elastin, fibrillin, collagen types III, IV and VI from the basement membrane, vascular media and/or adventitia, and surrounding decidual stromal cells. Loss of ECM correlated with disruption and disorganization of vascular smooth muscle cells, and the majority of changes occurred prior to extensive colonization of the vessel wall by EVT. The final stages of SA remodeling, characterized by the arrival of EVT, were associated with the increased mural deposition of fibronectin and fibrinoid. This study provides the first detailed analysis of the spatial and temporal loss of ECM from the walls of remodeling decidual SA in early pregnancy.
- PublicationOpen AccessFucosyltransferase 8 expression in breast cancer patients: A high throughput tissue microarray analysis(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Yue, Liling; Han, Cuicui; Li, Zubin; Li, Xin; Liu, Deshui; Liu, Shulin; Yu, HaitaoThe aim of this study was to compare the expression of fucosyltransferase 8 (FUT8) in breast cancer tissue and to investigate the relationship between this marker with tumor progression and its applicability to differential diagnosis. An immunohistochemical study was performed for FUT8 using the tissue microarray technique. In addition, the mRNA and protein levels of FUT8 in the tissue were also tested by real-time PCR and Western blot. There was a significant difference in cytoplasmic expression of FUT8 between breast cancer tissue and matched normal tissue (p<0.001). The percent of FUT8 staining in breast cancer tissues ranging from negative, weak positive, positive and strong positive were 2.7%, 40.2%, 54% and 3.2%, respectively. High FUT8 protein expression correlated with lymphatic metastasis (p=0.008) and with stage status (p=0.039). We detected that reduced FUT8 expression correlated with disease-free survival (p=0.02) and overall survival (p=0.04) of breast cancer patients. Expression of FUT8 can stratify breast cancer tissue and may be considered a prognostic marker for breast cancer patients.
- PublicationOpen AccessRole of an endothelin type A receptor antagonist in regulating torsion-induced testicular apoptosis in rats(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Cayli, Sevil; Ocakli, Seda; Senel, Ufuk; Karaca, Zafer; Erdemir, Fikret; Delibasi, TuncayTesticular torsion is a well-known medical emergency that can lead to pathological changes in the testicular tissues and male infertility. This investigation was undertaken to gain insight into the effects of an endothelin type A receptor antagonist (BQ123) on torsion-induced germ cell loss. Twenty-eight male Wistar albino rats were divided into four groups. In group I (control group), a sham operation to the left testis was performed. In group II (I/R injury), I/R injury was created by rotating the left testis 720° in a clockwise direction for 2 h and detorsing the testis after 2 h. In group III (I/R injury+BQ123), the rats were subjected to I/R injury and BQ123 injection (1 mg/kg, intravenous). In group IV (control+BQ123), the sham operated rats were subjected to BQ123. The testes of the rats were removed in all groups. Torsion-induced apoptosis and the effects of BQ123 were examined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) technique, immunohistochemistry and western blotting. In group II, the number of TUNEL-positive cells increased after testicular torsion. Immunohistochemistry and western blotting showed that apoptotic proteins (active caspase 3 and Bax) were upregulated, and the anti-apoptotic protein Bcl2 was downregulated in I/R injury. The administration of BQ123 caused a significant decrease in the number of apoptotic cells and the expression of apoptotic proteins (p<0.05) when compared with the I/R injury group. No significant effect of BQ123 was observed in the testicular cells of group IV. This animal study provides evidence of the regulatory effects of BQ123 on torsion-induced testicular apoptosis.
- PublicationOpen AccessNew insights on hormones and factors that modulate Sertoli cell metabolism(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Rato, Luís; Meneses, Maria João; Silva, Branca M.; Sousa, Mário; Alves, Marco G.; Oliveira, Pedro F.Sertoli cells (SCs) play a key role in spermatogenesis by providing the physical support for developing germ cells and ensuring them the appropriate nutrients, energy sources, hormones, and growth factors. The control of SCs metabolism has been in the spotlight for reproductive biologists, since it may be crucial to determine germ cells’ fate. Indeed, the maintenance of spermatogenesis is highly dependent on the metabolic cooperation established between SCs and germ cells, though this event has been overlooked. It depends on the orchestration of various metabolic pathways and an intricate network of signals. Several factors and/or hormones modulate the metabolic activity of SCs, which are major targets for the hormonal signalling that regulates spermatogenesis. Any alteration in the regulation of these cells’ metabolic behaviour may compromise the normal development of spermatogenesis and consequently, male fertility. In this context, SC metabolism arises as a key regulation point for spermatogenesis. Herein, we present an up-to-date overview on the impact of hormones and factors that modulate SC metabolism, with special focus on glycolytic metabolism, highlighting their relevance in determining male reproductive potential.
- PublicationOpen AccessRadiofrequency preserves histoarchitecture and enhances collagen synthesis in experimental tendon injury(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Akamatsu, Flavia Emi; Saleh, Samir Omar; Hojaij, Flávio; Real Martinez, Carlos Augusto; Andrade, Mauro; Teodoro, Walcy Rosolia; Jacomo, Alfredo LuizWe investigated the action of radiofrequency (RF) on the healing process after inducing experimental lesions of the Achilles tendon in rats. Wistar rats were surgically subjected to bilateral partial transverse sectioning of the Achilles tendon. The right tendon was treated with radiofrequency (RFT), whereas the left tendon served as a control (CT). On the third postoperative day, the rats were divided into three experimental groups consisting of ten rats each, which were treated with monopolar radiofrequency (Tonederm™) until they were sacrificed on the 7th, 14th or 28th days. The histological specimens were studied for inflammatory cell content, collagen types I and III, immunostaining and morphometry. Total collagen were biochemically analyzed and to evalute fibroblast and myofibroblast proliferation by vimentin and α-actin smooth muscle immunohistochemistry methods. Statistical analysis was performed using the Student's ttest, the sign test and the Kruskal-Wallis test to compare tendons treated with radiofrequency with the non-treated tendons (α=5%; α=10%). Larger amounts of collagen I with hydroxyproline content and myofibroblast cells were clearly evident within 7 days (p<0.05). No difference was observed in the inflammatory cell content between the groups. We found better collagen arrangement with RF administration across the entire time studied. Radiofrequency administration preserves histoarchitecture and enhances collagen synthesis during the initial phases of cicatrization, suggesting that the treatment can provide improved stiffness during the most vulnerable phases of tendon healing. Clinical studies may include RF among the therapeutic tools in tendinous lesion management.
- PublicationOpen AccessPhysiological and pathological significance of the molecular cross-talk between autophagy and apoptosis(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Oral, Ozlem; Akkoc, Yunus; Bayraktar, Oznur; Gozuacik, Devrimy. Autophagy and apoptosis are two important molecular mechanisms that maintain cellular homeostasis under stress conditions. Autophagy represents an intracellular mechanism responsible for turnover of organelles and long-lived proteins through a lysosome-dependent degradation pathway. Cell death signals or sustained stress might trigger programmed cell death pathways, and among them, apoptosis is the most extensively studied one. Recent studies indicate the presence of a complex interplay between autophagy and apoptosis. Physiological relevance of autophagyapoptosis crosstalk was mainly shown in vitro. However, in vivo consequences possibly exist both during health and disease. In this review, we will summarize the current knowledge about molecular mechanisms connecting autophagy and apoptosis, and about the significance of this crosstalk for human health.
- PublicationOpen AccessImmunoexpression 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, JohnThe 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.
- PublicationOpen AccessControversies on electromagnetic field exposure and the nervous systems of children(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Warille, Aymen A.; Onger, M. Emin; Turkmen, A. Pınar; Deniz, Ö. Gülsüm; Altun, Gamze; Yurt, K. Kubra; Altunkaynak, B. Zuhal; Kaplan, SüleymanThis paper reviewed possible health effects from exposure to low levels of electromagnetic field (EMF) in children, arising from electrical power sources and mobile phones. Overall, the information about effects on developmental processes and cognitive functions is insufficient and further research on children and adolescents is critically needed. New research approaches are required focused on the effects on the developmental processes of children exposed to electromagnetic fields, using consistent protocols. When the current data were considered in detail, it was noted that children's unique vulnerabilities make them more sensitive to EMFs emitted by electronics and wireless devices, as compared to adults. Some experimental research shows a neurological impact and exposure in humans may lead to the cognitive and behavioral impairments. Because of the proliferation of wireless devices, public awareness of these dangers now is important to safeguard children’s future healthy brain development.
- PublicationOpen AccessThe role of extracellular and intracellular proteolytic systems in aneurysms of the ascending aorta(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Werner, Isabella; Schack, Stephanie; Richter, Manfred; Stock, Ulrich A.; El-Sayed Ahmad, Ali; Moritz, Anton; Beiras-Fernandez, Andres
- PublicationOpen AccessDevelopment of germ cell neoplasia in situ in chinchilla rabbits(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Vigueras-Villaseñor, Rosa María; Montelongo Solís, Paola; Chávez-Saldaña, Margarita; Gutiérrez-Pérez, Oscar; Cortés Trujillo, Lucero; Rojas-Castañeda, Julio CésarThe present study was designed to describe the development of germ cell neoplasia in situ in Chinchilla rabbit by administration of estradiol. The study was performed in rabbits distributed into two groups: control and 17 β-estradiol. The determination of histological alterations and POU5F1 and c-kit proteins employed as biomarkers for the diagnosis of this neoplasia was carried out. Testicular descent and complete spermatogenesis were observed in the control group. The protein biomarkers were negative. However, in the rabbits treated with estradiol, the testes remained undescended with the gonocytes undifferentiated to spermatogonia. There were histological lesions owing to germ cell neoplasia in situ and positive to POU5F1 and c-kit proteins. These findings indicate that the chinchilla rabbit is an ideal model to study this neoplasia in which the histological characteristics and biomarkers of the disease could be clearly observed. Using this model we suggested that the persisting gonocytes could be responsible for the development of germ cell neoplasia in situ.