Histology and histopathology Vol.25,nº10 (2010)
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- PublicationOpen AccessLung carcinoma with rhabdoid component. A series of seven cases associated with uncommon types of non-small cell lung carcinomas and alveolar entrapment(Murcia : F. Hernández, 2010) Izquierdo Garcia, Francisco M.; Moreno Mata, Nicolás; Herranz Aladro, María Luisa; Cañizares, Miguel Ángel; Álvarez-Fernández, EmilioRhabdoid tumor, included in the WHO classification among large cell carcinomas of the lung, is an uncommon type of lung carcinoma with poor prognosis. We report a series of 7 cases of lung carcinomas with rhabdoid component in 10% and 80% of the tumor. The associated tumor was adenocarcinoma in 3 cases - one of them with focal micropapillary pattern - large cell carcinoma in 2 cases, squamous cell carcinoma in 1 case and pleomorphic carcinoma in 1 case. Two adenocarcinomas showed a focal spindle cell component. Micropapillary and pleomorphic types had not been reported before as a component associated with rhabdoid carcinomas. All cases were positive for vimentin, and AE1/AE3 cytokeratin and 5 cases for cytokeratin 7. All cases were negative for muscle and endothelial markers and for chromogranin A. Synaptophysin was focally positive only in one case. Alveolar trapping inside the tumor was present in 3 cases - a phenomenon not well studied in lung carcinomas and also not reported in tumors with rhabdoid component. Five patients died because of the tumor within 2 to 31 months after diagnosis, one of myocardial infarction and only one is alive and disease free 123 months after the diagnosis. In summary, we describe 7 new cases of this uncommon lung tumor with aggressive clinical course, associated with infrequent histological types in nonrhabdoid component and with alveolar trapping, a nondescribed finding.
- PublicationOpen AccessPeroxiredoxins in colorectal neoplasms(Murcia : F. Hernández, 2010) Wu, X.Y.; Fu, X.Z.; Wang, X.H.Peroxiredoxins (Prxs) are novel group proteins with efficient antioxidant capacity, and some of them also have effects on cell proliferation, differentiation, apoptosis, and chemotherapy and radiotherapy resistance. Altogether six distinct Prxs expressions were investigated in histological samples of colorectal neoplasm and the distant normal tissues and investigated associatedly with parameters such as clinical stage and lymphnodes metastasis. Normal colorectal tissues were almost negative for Prxs, except Prx4 (15/32). In colorectal cancer tissues, the most prominent reactivity was observed with Prx2 in 23/32 cases, while the corresponding figures for others was 21/32 (Prx1), 18/32 (Prx3, Prx5, Prx6) and 8/32 (Prx4). Prx1 (P=0.023), Prx2 (P=0.012), and Prx5 (P=0.028) were the isoforms that showed significantly increased expression in colorectal cancer patients with stage III or lymphnodes metastasis-positive cases. There was a significant relationship between the expression of Prx1 and Prx2 (rs=0.425, P=0.015) and between Prx3 and Prx4 (rs=0.364, P=0.041). Additionally, 8 cases were studied by western analysis. Prx1, 2, 3, 5 and 6 were particularly elevated in tumors compared to nonmalignant tissue as assessed by immunohistochemistry. It appeared that some Prxs were upexpression in colorectal cancer tissues and may have some prognostic significance; the induction of Prxs could be explained by increased production of reactive oxygen species in carcinomatous tissue.
- PublicationOpen AccessIntermediate conductance Ca2+ activated K+ channels are expressed and functional in breast adenocarcinomas: correlation with tumour grade and metastasis status(Murcia : F. Hernández, 2010) Haren, Nathalie; Khorsi, Hafida; Faouzi, Malika; Ahidouch, Ahmed; Sevestre, Henri; Ouadid-Ahidouch, HalimaK+ channels are key molecules in the progression of several cancer types and are considered to be potential targets for cancer therapy. In this study, we investigated the intermediateconductance Ca2+-activated K+ channels (hKCa3.1) expression in both breast carcinoma (BC) specimens and human breast cancer epithelial primary cell cultures (hBCE) using immuno-histochemistry (60 samples), quantitative Real-Time RT-PCR (30 samples) and Western blot assay (30 samples). We also looked at whether or not the expression of these channels is correlated with breast carcinomas grade tumours and metastasis status. Furthermore, we characterized the hKCa3.1 channel activity in hBCE cells by using the Whole Cell Patch Clamp Technique. We found that hKCa3.1 transcripts and proteins were expressed in both BC samples and hBCE cells. Clinicopathologic evaluation indicated a significant correlation between hKCa3.1-expression and tumour grade. hKCa3.1 mRNA and protein were more highly expressed in grade III tumours than in both grades I and II. However, the hKCa3.1 expression-increase according to grade was only observed in tumours with negative metastasis status. Moreover, the hKCa3.1 channels expressed in hBCE cells are functional. This was attested by patch-clamp recordings showing typical hKCa3.1-mediated currents in these cells. In conclusion, these data suggest that hKCa3.1 might contribute to breast tumour-progression and can serve as a useful prognostic marker for breast cancer
- PublicationOpen AccessComparison of the dysadherin and E-cadherin expression in primary lung cancer and metastatic sites(Murcia : F. Hernández, 2010) Mitselou, Antigony; Batistatou, Anna; Nakanishi, Yukihiro; Hirohashi, Setsuo; Vougiouklakis, Theodoros; Charalabopoulos, KonstantinosDysadherin, a cancer associated cell membrane glycoprotein, has been reported to downregulate E-cadherin. Aberrant expression of Ecadherin has been associated with the development of metastases in patients with cancer. Even though the expression of dysadherin and E-cadherin has been studied in primary non-small cell lung carcinoma, little is known about its expression at the distant metastases sites. We investigate by immunohistochemistry the relationship between E-cadherin and dysadherin in 111 cases of primary lung carcinomas (53 squamous cell carcinomas, 21 adenocarcinomas, 13 large cell carcinomas, and 24 small cell carcinomas), and their distant metastases. The intensity, the expression pattern and the percentage of neoplastic cell staining were recorded and the results were correlated with clinicopathological findings of the subjects. Dysadherin immunostain was expressed in 61 (54.95%) of the cases, and increased dysadherin expression was significantly correlated with tumour size (p=0.003), distant metastases (p=0.0034), and metastasis size (p=0.0008). Reduced Ecadherin expression was noted in 46 (41.45%) of the cases, and was correlated with high-grade tumour (p=0.02), infiltrative growth pattern (p=0.042), and advanced stage (p=0.032). Although the correlation between the expression of dysadherin and E-cadherin was not significant, a group of patients showed reduced E-cadherin expression with dysadherin overexpression. In lung carcinomas dysadherin expression seems to reflect tumour aggressiveness and may be considered a positive marker of poor prognosis when considered alone or/and in combination with down-regulation of Ecadherin.
- PublicationOpen AccessNuclear accumulation of glioma-associated oncogene 2 protein and enhanced expression of forkhead-box transcription factor M1 protein in human hepatocellular carcinoma(Murcia : F. Hernández, 2010) Lin, M.; Guo, Lankai; Liu, H.; Du, J.; Yang, Jilong; Zhang, L.J.; Zhang, B.The hedgehog (Hh) signaling pathway has been reported to be crucial in human carcinogenesis and tumor progression. Glioma-associated oncogenes (Gli), are zinc finger transcription factors which mediate the transcriptional response to Hh signaling. To explore the role of Gli in the development and progression of hepatocellular carcinoma (HCC), we investigated the expression of Gli2 and FoxM1 (forkhead-box transcription factor M1) which is one of the Gli downstream target genes modulating cell cycle progression in 91 specimens of human HCCs with immunohistochemistry. These immunostaining results were compared with various clinicopathologic parameters. Immunoreactivity of Gli2 and FoxM1 was observed respectively in 84.6% (77/91) and 80.2% (73/91) cases of HCC tumor tissues, and this was considerably higher than expression in the peritumoral tissues. Distribution of Gli2 and FoxM1 proteins in tumor cells was nuclear with or without cytoplasmic staining, or cytoplasmic alone. Statistically, increased nuclear immunopositivity of Gli2 protein correlated significantly with poorer tumor differentiation (P<0.05), as well as with portal vein tumor thrombosis (P<0.05). In addition, overexpression of FoxM1 protein was significantly associated with increased tumor grade (P<0.01) and advanced tumor stage (P<0.05). Moreover, there was a significant association between the expressions of Gli2 and FoxM1 proteins in HCC (r=0.464, P=0.000). This is consistent with the concept that in human HCC, the Hh signaling pathway is involved in the differentiation and proliferation of tumor cells, in part through inducing nuclear accumulation of Gli2 protein and subsequent upregulation of FoxM1 protein.
- PublicationOpen AccessThe role of neurotrophins related to stress in saliva and salivary glands(Murcia : F. Hernández, 2010) Saruta, Juri; Sato, Sadao; Tsukinoki, KeiichiNerve growth factor (NGF) and brainderived neurotrophic factor (BDNF) are well-studied neurotrophins involved in neurogenesis, differentiation, growth, and maintenance of selected peripheral and central populations of neuronal cells during development and adulthood. Neurotrophins, in concert with the hypothalamic-pituitary-adrenal (HPA) axis, play key roles in modulating brain plasticity and behavioral coping, especially during ontogenetic critical periods, when the developing brain is particularly sensitive to external stimuli. Early life events, such as psychophysical stress, affect NGF and BDNF levels and induce dysregulation of the HPA axis, thereby affecting brain development and contributing to inter-individual differences in vulnerability to stress or psychiatric disorders. Immobilization stress modifies BDNF mRNA expression in some organs. We studied the effect of immobilization stress on BDNF and its receptor tyrosine receptor kinase B (TrkB) in rat submandibular glands, and found increased BDNF expression in duct cells under immobilization stress. Upon further investigation on the influence of salivary glands on plasma BDNF using an acute immobilization stress model, we found that acute immobilization stress lasting 60 min significantly increases the plasma BDNF level. However, plasma BDNF elevation is markedly suppressed in bilaterally sialoadenectomized rats. This suggests that salivary glands may be the primary source of plasma BDNF under acute immobilization stress. This report reviews the structure of salivary glands, the role of neurotrophins in salivary glands, and the significance of BDNF in saliva and salivary glands, followed by a summary of the evidence that indicates the relationship between immobilization stress and BDNF expression within salivary glands.
- PublicationOpen AccessUltrastructural morphology of equine adipose-derived mesenchymal stem cells(Murcia : F. Hernández, 2010) Pascucci, Luisa; Mercati, Francesca; Marini, Carla; Ceccarelli, Piero; Dall’Aglio, C.; Pedini, Vera; Gargiulo, Anna MaríaMesenchymal stem cells are a virtually ubiquitous population of adult stem cells, able to differentiate into various tissue lineages. As they are multipotent and easy to grow in culture, they are at present considered very attractive candidates for tissue repair and gene therapy. With the exception of a few reports, mesenchymal stem cell morphology has been widely disregarded in the past years. In this paper we discuss the establishment of mesenchymal stem cell cultures from equine adipose tissue and describe their fine structure by transmission electron microscopy. The cultured cells revealed a fibroblastoid appearance and were characterized by an eccentric nucleus with multiple nucleoli, dense cytoplasm rich in ribosomes, a rough endoplasmic reticulum with dilated cisternae, elongated mitochondria and heterogeneous vacuolar inclusions. In addition, they were often interconnected by adhesion structures located on the cell body and on cytoplasmic processes contacting other cells. The features observed are evocative of an undifferentiated cellular phenotype and of an intense synthetic and metabolic activity.
- PublicationOpen AccessThe cellular expression of GABAA receptor a1 subunit during spermatogenesis in the mouse testis(Murcia : F. Hernández, 2010) Kanbara, Kiyoto; Okamoto, Keiko; Nomura, Sakashi; Kaneko, Takeshi; Watanabe, Masahito; Otsuki, YoshinoriGABAA receptors are pentamers in structure and are mainly composed of α, ß and γ subunits. These receptors are known to function as chloride channels. We observed α5, ß1 and γ3 subunit immunoreactivity in the mouse testes, specifically in the cytoplasm surrounding the nucleus in the spermatocytes and spermatids. In the current study, α1 subunit immunoreactivity was located in the nucleus of spermatogonia, spermatocytes and round spermatids. Immunoelectron microscopy revealed that the α1 subunit was localized within the nucleus of pachytene and diplotene spermatocytes in the area of condensed chromatin rather than extended chromatin. Protein sequence analysis revealed that the α1 subunit included DM DNA binding domains that were related to transcription factors involved in testicular differentiation in adult mice. These findings suggest that the α1 subunit may undertake a gene transcription function during the maturation of germ cells. α1 immunoreactivity was also detected within the mitochondria of spermatocytes and in the acrosome of round and elongated spermatids. Although the precise physiological role of the GABAA receptor α1 subunit in mitochondria remains unknown, we hypothesize that its function in the acrosome may be related to the acrosome reaction during fertilization or during spermatogenesis.
- PublicationOpen AccessComparison of ultrastructure and lectin histochemistry on the anterior medial gland of nasal septum in rat and gerbil(Murcia : F. Hernández, 2010) Chang, Chi-Fen; Chau, Yat-Pang; Lu, Kuo-ShyanThe anterior medial gland (AMG), located in the submucosa of rodent nasal septum, is suggested to provide fluid for humidification of inspired air. Tremendous variation of the environmental air humidity, on which rats and gerbils depend to live, leads us to expect a multiplicity on ultrastructure and various subcellular glycoconjugate distribution within the AMG acinar cells between these two species. Electron microscopy revealed that: (1) The nucleus of AMG acinar cells in rat was irregular-shaped, but that in gerbil was round or elliptical; (2) Secretory granules in rat AMG acinar cells contained homogenous content with various electron density. However, two types of secretory granules in gerbil AMG acinar cells were found: one with lamellated-structure and high electron density, while the others had particulate materials; (3) Myoepithelial cells were present in the acinus of medial and posterior regions in rat AMG, but absent in gerbil; and (4) Nerve terminals were present only in the medial and posterior rat AMG, but in all three regions of the gerbil AMG. Lectin histochemistry demonstrated that: (1) Rat and gerbil AMG acinar cells expressed strong affinity toward Con A and WGA, but neither showed any reactivity toward UEA and PNA; and (2) Varying degrees of reactivity toward different lectins, including DBA, PNA, SBA and EBL, were recognized in rat and gerbil AMG acinar cells. We confirm the species variation on the ultrastructure and lectin histochemistry of AMG in rats and gerbils, and speculate that these variations may be due to the different living environment.
- PublicationOpen AccessPiecemeal degranulation in human eosinophils: a distinct secretion mechanism underlying inflammatory responses(Murcia : F. Hernández, 2010) Melo, Rossana C.N.; Weller, Peter F.Secretion is a fundamental cell process underlying different physiological and pathological events. In cells from the human immune system such as eosinophils, secretion of mediators generally occurs by means of piecemeal degranulation, an unconventional secretory pathway characterized by vesicular transport of small packets of materials from the cytoplasmic secretory granules to the cell surface. During piecemeal degranulation in eosinophils, a distinct transport vesicle system, which includes large, pleiomorphic vesiculotubular carriers is mobilized and enables regulated release of granule-stored proteins such as cytokines and major basic protein. Piecemeal degranulation underlies distinct functions of eosinophils as effector and immunoregulatory cells. This review focuses on the structural and functional advances that have been made over the last years concerning the intracellular trafficking and secretion of eosinophil proteins by piecemeal degranulation during inflammatory responses.
- PublicationOpen AccessHuR, a key post-transcriptional regulator, and its implication in progression of breast cancer(Murcia : F. Hernández, 2010) Yuan, Zhu; Sanders, Andrew J.; Ye, Lin; Jiang, Wen G.HuR, an ubiquitously expressed member of the Hu family, selectively binds and stabilizes AREcontaining mRNAs encoding proto-oncogenes, cell cycle regulators, cytokines and growth factors. The mechanism of HuR stabilization on target mRNAs is believed to be mediated through competition with destabilizing ARE-BPs. HuR is mainly localized within the cell nucleus and the nucleo-cytoplasmic shuttling of HuR is generally assumed as the initial and critical step of its stabilizing effects. A number of signaling pathways are believed to be involved in HuR shuttling. Due to the pivotal role played by HuR in stabilizing the mRNA of key factors or cytokines involved in carcinogenesis and subsequent progression, its implication and therapeutic potential in cancer have been investigated intensively since its discovery in 1996. This review discusses the role of HuR in the stabilization of key mRNAs and it’s the nucleo-cytoplasmic shuttling. The review also covers the current knowledge of HuR’s role in carcinogenesis, particularly its involvement in breast cancer, and the feasibility of using HuR as a therapeutic target for the treatment of breast cancer.
- PublicationOpen AccessAngiogenesis index CD105 (Endoglin)-CD31 (PECAM-1) as a predictive factor for invasion and proliferation in intraductal papillary mucinous neoplasm (IPMN) of the pancreas(Murcia : F. Hernández, 2010) Tachezy, Michael; Reichelt, Uta; Melenberg, Tanja; Gebauer, Florian; Izbicki, Jacob R.; Kaifi, Jussuf T.Background: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is an increasingly diagnosed entity since its definition by the World Health Organization in 1996. It has a broad clinical spectrum ranging from benign to malignant tumors. Optimum treatment is controversial and a better understanding of the development of IPMN of the pancreas and identification of potential prognostic factors will help to address this. Angiogenesis plays an elementary role in the development of malignant tumors and may well also be important in the development of IPMN of the pancreas. Therefore we investigated endothelial cell marker CD31 (PECAM-1) and angiogenesis associated marker CD105 (Endoglin) by immunohistochemistry. Methods: Thirty-two cases of surgically resected IPMN were chosen retrospectively and clinical data were obtained. Specimens were stained for proliferation marker (Ki-67), CD31 and CD105 by immunohistochemistry. A CD105/CD31 Angiogenesis ratio (AR) was established to determine the proliferating fraction of endothelial cells. Results: The AR is significantly elevated in invasive IPMN of the pancreas (Mann-Whitney-U Test, p<0.05) and is associated with the Ki-67-labelling-index, demonstrating synergy between tumor-growth and neovascularisation. Invasive IPMN of the pancreas is associated with significantly lower recurrence-free and overall survival. Conclusions: Neovascularisation plays an important role in the tumorigenesis of invasive IPMN of the pancreas, and therefore angiogenesis-associated molecules like CD105 and CD31 might be useful tools as prognostic markers. Furthermore, the results indicate a potential role for adjuvant anti-angiogenic therapies in selected patients with recurring and/or invasive IPMN of the pancreas.