Histology and histopathology Vol.27, nº 6 (2012)
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- PublicationOpen AccessPeroxisome morphology in pathology(F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Ribeiro, Daniela; Castro, Inês; Fahimi, H. Dariush; Schrader, MichaelSummary. Peroxisomes are remarkably dynamic and versatile organelles that are essential for human health and development. They respond to physiological changes in the cellular environment by adapting their morphology, number, enzyme content and metabolic functions accordingly. With the discovery of the first key peroxisomal morphology proteins, the investigation of peroxisomal shape, distribution and dynamics has become an exciting new field in cell biology and biomedical sciences because of its relation to organelle functionality and its impact on developmental and physiological processes. In this review, we summarize recent findings on peroxisome biology, dynamics and the modulation of peroxisome morphology, especially in mammals. Furthermore, we discuss the roles of peroxisome dynamics and morphology in cell pathology and present recent examples for alterations in peroxisome morphology under disease conditions. Besides defects in the peroxisomal morphology machinery, we also address peroxisome biogenesis disorders, alterations of peroxisome number during carcinogenesis and liver cirrhosis, and morphological alterations of peroxisomes during viral infection.
- PublicationOpen AccessHistological study of the protective effect of melatonin on neural cells after neonatal hypoxia-ischemia(F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Alonso-Alconada, Daniel; Álvarez, Antonia; Lacalle, J.; Hilario, EnriqueTo minimize as much as possible the neurological consequences from hypoxic-ischemic (HI) brain injury, neuroprotective strategies are urgently required. In this sense, there is growing interest in the neuroprotective potential of melatonin after perinatal asphyxia, due to its high efficacy, low toxicity and ready cross through the blood-brain barrier. Twenty six Wistar rats at postnatal day 7 were randomly assigned to: two hypoxic-ischemic groups: pups with the left common carotid artery ligated and then submitted to hypoxia (HI group) and animals that received a dose of 15 mg/kg melatonin just after the hypoxic-ischemic event and repeated twice with an interval of 24 hours (HI+MEL group). Pups without ischemia or hypoxia were used as controls (Sham group). Seven days after surgery, brains were collected and coronal sections Nissl-stained, TUNEL-labeled, or MBP- and GFAP-immunolabeled prior to determining brain infarct area, quantify surviving neurons and evaluate oligodendroglial injury and reactive astrogliosis. The number of surviving neurons showing a well preserved architecture in HI+MEL group was similar to that observed in the Sham group. Moreover, TUNEL-positive cells only appeared in the HI group. The ratio of left-to-right hemispheric MBP immunostaining showed a significant decrease in the HI group in comparison with Sham pups, which was restored after melatonin administration. Melatonin also reduced reactive gliosis. Thus, our results suggest that treatment with melatonin after neonatal hypoxia-ischemia led to a neuroprotective effect reducing cell death, white matter demyelination and reactive astrogliosis.
- PublicationOpen AccessMolecular characterization of EGFR and EGFR-downstream pathways in triple negative breast carcinomas with basal like features(F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Martin, Vittoria; Botta, Francesca; Zanellato, Elena; Molinari, Francesca; Crippa, Stefano; Mazzucchelli, Luca; Frattini, MiloAims: Triple negative breast cancer with basal like features (TN-BCBL) do not benefit from hormonal and anti-HER2 therapies. As a considerable fraction of TN-BCBLs shows EGFR deregulation, EGFR-targeted therapies have been proposed as an option. The characterization of EGFR and EGFR-downstream members may therefore provide important predictive information. Methods and results: Based on morphological and immunophenotypic features, we identified 38 TN-BCBLs that were subsequently investigated for alterations in EGFR signaling pathways. EGFR and PTEN protein levels were studied by immunohistochemistry, EGFR gene status by FISH, EGFR, H-Ras, K-Ras, N-Ras, BRAF and PIK3CA gene mutations by direct sequencing. EGFR overexpression and loss of PTEN expression characterized the majority of TN-BCBLs (76% and 74% of patients, respectively). EGFR gene copy number gain (FISH+) was identified in 51% of analyzable patients. PIK3CA gene mutations were detected in three cases (8%), whereas EGFR, H-Ras, K-Ras, N-Ras and BRAF genes showed no mutations. Overall, out of 17 patients classified as FISH+, 12 cases (70%) showed a concomitant alteration in PI3K/PTEN pathway. Conclusions: These results provide evidence that the efficacy of anti-EGFR drugs in TN-BCBL patients could be impaired by frequent alterations in the PI3K/PTEN axis, and suggest that TN-BCBLs could benefit from tailored treatments against this axis.
- PublicationOpen AccessClinical significance of Src expression and activity in human neoplasia(2012) Chatzizacharias, Nikolaos A.; Kouraklis, Gregory P.; Giaginis, constantinos; Theocharis, Stamatios E.Src, a 60 kDa non-receptor tyrosine kinase, is the product of normal c-src of the human genome and member of the Src protein tyrosine kinases family (SFK). As described by Martin and Rous, a genetic recombination between c-src and the RSV oncogene of Rous sarcoma virus results in a modified Src protein, with increased intrinsic activity and transforming potential in animal and human tissues. Several in vitro and in vivo studies supported this theory providing insight in the signalling pathways involved. Accumulating evidence from studies on clinical samples supported the role of Src in the process of carcinogenesis and disease progression in several human malignancies. Some studies have further reinforced the significance of the kinase in malignacy by correlating its expression and/or activity with important clinicopathological parameters, such as tumour stage, histopathological grade, proliferative capacity and most importantly patient’s survival. This review is a comprehensive report of the published evidence on the expression and clinical significance of Src in human malignancy, which constitutes the background of the current studies and clinical trials on the use of Src inhibitors as novel potent antineoplastic strategy.
- PublicationOpen AccessThe clinicopathological significance of REIC expression in colorectal carcinomas(F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Wang, Wei; Zhu, Wan; Xu, Xiao-yan; Nie, Xiao-cui; Yang, Xue; Xing, Ya-nan; Yu, Miao; Liu, Yun-peng; Takano, Yasuo; Zheng, Hua-chuanREIC is down-regulated in immortalized cell lines compared with the parental normal counterparts, and could inhibit colony formation, tumor growth and induce apoptosis. Here, its expression was examined by immunohistochemistry on tissue microarray containing colorectal non-neoplastic mucosa (NNM), adenoma and adenocarcinoma. Colorectal carcinoma tissue and cell lines were studied for REIC expression or its secretory level by Western blot, RT-PCR or enzyme-linked immunosorbent assay (ELISA). The results demonstrated that REIC was differentially expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM-12, SW480, SW620, and WiDr with its secretion concentration less than 300 pg/mL. Carcinomas showed statistically lower REIC expression than matched NNM with no difference for protein content. Immunohistochemically, REIC expression was significantly decreased from NNM, adenoma to adenocarcinoma (p<0.05). REIC expression was negatively correlated with depth of invasion, TNM staging, dedifferentiation, Capase-3 and nuclear inhibitor of growth 5 (ING5) expression (p<0.05), while not with age, sex, tumor size, lymphatic or venous invasion, or lymph node metastasis (p>0.05). Kaplan-Meier analysis indicated that REIC expression was not associated with the prognosis of colorectal carcinomas (p>0.05). Cox’s analysis demonstrated that lymphatic and venous invasion, lymph node metastasis, and UICC staging were independent prognostic factors for carcinoma (p<0.05). Our study indicated that down- regulated REIC expression might play an important role in colorectal adenoma-adenocarcinoma sequence and subsequent progression. Aberrant REIC expression might be employed as a good marker of pathogenesis and development of colorectal carcinomas.
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