Histology and histopathology Vol.22, nº10 (2007)
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- PublicationOpen AccessMüllerianosis(Murcia : F. Hernández, 2007) Batt, R.E; Smith, R.A.; Buck Louis, G.M.; Martin, D.C.; Chapron, C.; Koninckx, P.R.; Yeh, J.Müllerianosis may be defined as an organoid structure of embryonic origin; a choristoma composed of müllerian rests - normal endometrium, normal endosalpinx, and normal endocervix - singly or in combination, incorporated within other normal organs during organogenesis. A choristoma is a mass of histologically normal tissue that is “not normally found in the organ or structure in which it is located” (Choristoma, 2006). Müllerian choristomas are a subset of non-müllerian choristomas found throughout the body. Histologically, endometrial-müllerianosis and endometriosis are both composed of endometrial glands and stroma, but there the similarity ends. Their pathogenesis is different. Sampson faced the same difficulty with pathogenesis and nomenclature when he wrote: “The nomenclature of misplaced endometrial or müllerian lesions is a difficult one to decide upon.” “The term müllerian would be inclusive and correct, but unfortunately it suggests an embryonic origin.” Sampson then divided “misplaced endometrial or müllerian tissue” into “four or possibly five groups, according to the manner in which this tissue reached its ectopic location” (Sampson, 1925). Sampson’s classification of heterotopic or misplaced endometrial tissue is based on pathogenesis: 1) “direct or primary endometriosis” [adenomyosis]; “a similar condition occurs in the wall of the tube from its invasion by the tubal mucosa” [endosalpingiosis]; 2) “peritoneal or implantation endometriosis;” 3) “transplantation endometriosis;” 4) “metastatic endometriosis;” and 5) “developmentally misplaced endometrial tissue. (I admit the possibility of such a condition, but have never been able to appreciate it.)” (Sampson, 1925). It is precisely this condition “developmentally misplaced endometrial tissue,” [müllerianosis] that is the subject of this review.
- PublicationOpen AccessBone morphogenetic proteins and their receptor signaling in prostate cancer(Murcia : F. Hernández, 2007) Ye, L.; Lewis-Russell, J.M.; Kynaston, H.G.; Jiang, W.G.Bone morphogenetic proteins (BMPs) belong to the TGF-ß superfamily and are vital bone inductive factors. BMPs also play important roles during embryonic development and the postnatal homeostasis of various organs and tissues, by controlling cellular differentiation, proliferation and apoptosis. Prostate cancer is the most common cancer in men in Western countries, with a high incidence of bone metastasis. Once bony metastasis developed, the condition is incurable, and contributes significant disease specific morbidity and mortality. However, the mechanisms underlying the development of bone metastasis remain unclear. BMPs have been implicated in the development of both primary and secondary tumors, particularly skeletal metastasis. Aberrations in BMPs signaling have also been identified in various neoplasms. Recently studies have also suggested a pivotal role in bone metastasis for Noggin, which is a BMP antagonist. In this review, we discuss the current knowledge of BMPs signaling, abnormalities which have been identified and their involvement in tumour progression, and particularly in the development of bone metastasis in prostate cancer.
- PublicationOpen AccessIncreased expression of 5-lipoxygenase is common in clear cell renal cell carcinoma(Murcia : F. Hernández, 2007) Faronato, M.; Muzzonigro, G.; Milanese, G.; Menna, C.; Bonfigli, A.R.; Catalano, A.; Procopio, A.The clinical behaviour of Clear Cell Renal Cell Carcinoma (CC-RCC) is often unpredictable. To fully understand the signaling pathways involved in CCRCC development, we examined whether the 5- Lipoxygenase (5-LO), which catalyzes the biosynthesis of proinflammatory leukotrienes, is involved in renal tumorigenesis. By analyzing 46 snap-frozen primary renal cell carcinomas and their corresponding normal renal cortex biopsies, 5-LO protein levels were found to be significantly increased in the majority of CC-RCCs (P<0.001). Quantitative 5-LO mRNA expression analysis revealed up to 3-fold increased expression in the tumor tissues. There was no association between 5-LO and gender, grade or vein invasion. In contrast, increased 5-LO protein and mRNA correlated with large tumor size (>4 cm) and age of patients (P<0.001). 5-LO was frequently overexpressed in von Hippel-Lindau protein (pVHL)–reduced tumors and in Vascular Endothelial Growth Factor (VEGF)-positive tumors, which represent two frequent alterations in CC-RCC. Cell culture experiments demonstrated that VEGF expression was strongly inducible by 5-LO metabolites in RCC cell lines. The loss of pVHL expression led to high basal 5- LO and VEGF expression, which were markedly reduced by transfection with 5-LO small interfering RNA (siRNA). These results suggest that 5-LO upregulation is an important step in renal cancer progression.
- PublicationOpen AccessOccurrence of two NOS isoforms in the developing gut of sea bass Dicentrarchus labrax (L.)(Murcia : F. Hernández, 2007) Pederzoli, A.; Conte, A.; Tagliazucchi, D.; Gambarelli, A.; Mola, L.In this work we have examined the appearance and distribution of nitric oxide synthase (NOS), with histochemical, immunohistochemical and biochemical methods, during development of the sea bass (Dicentrarchus labrax) gut. The data showed that both the calcium-calmodulin dependent neuronal isoform (nNOS) and calciumindependent inducible isoform (iNOS) are present in the larval gut of sea bass. The nNOS-immunoreactivity was present in the epithelial cells and enteric nerve cells of gut both in the 8-day-old specimens and in the 24-dayold- larvae. In the adult nNOS-immunoreactivity disappeared from epithelial cells, remaining in the wall intramural neurons and fibers. The iNOSimmunoreactivity was present in the epithelial cells of 24-day-old-larvae and was not detectable in the adult gut. Western blot analysis and determination of NOS activity also demonstrated the presence of the two NOS isoforms, nNOS and iNOS, in the gut of 24-day-old specimens. The presumably different roles played by the two isoforms of enzyme are discussed. The presence of nNOS isoform in the gut enteric neurons of the same larval stages of D. labrax in which we previously demonstrated the presence of substance P and Vasoactive Intestinal Polypeptide (VIP), may suggest that all these three components of the motility control system are already present in the larval phase. Nitric oxide (NO) may be also involved in the early immune response. The present results on the occurrence of iNOS isoform in epithelial gut cells of the same regions in which the gut-associated lymphoid tissue (GALT) will differentiate, may suggest for NO a role in early defence mechanisms, before the establishment of immune responses in GALT. Finally, the developmental and regional differences in nNOS and iNOS expession also suggest a regulatory role in development and differentiation of the sea bass gut.
- PublicationOpen AccessCurrent concepts in human prion protein (Prp) misfolding, Prnp gene polymorphisms and their contribution to Creutzfeldt-Jakob Disease (CJD)(Murcia : F. Hernández, 2007) Michalczyk, K.; Ziman, M.Transmissible spongiform encephalopathies are a group of neural degenerative diseases that may be infectious, sporadic, or hereditary and are associated with an abnormally folded prion protein. Unfortunately at the current time it is not at all clear what the normal structure of the prion protein actually is or how it is toxic to cells. Extensive research on prion diseases has led to a dramatic increase in understanding of the pathogenesis of prion disorders, which will hopefully lead to the development of effective treatments. The inability to detect the disease in blood using current technology has made screening difficult. While fortunately there has been a decline in the number of clinical cases of transmissible variant CJD, evidence indicates that very long incubation periods can occur in humans so there may be a long slow, gradual epidemic. In particular, clinical cases in genotypes other than those homozygous for methionine at codon 129 of PRNP have not yet occurred, but such cases might be expected to have longer incubation periods and show differences in pathology to those seen to date. proportion of infected animals develop sub-clinical disease. Moreover, results from a large prevalence study in humans show that several cases test positive but do not develop clinical disease. It is possible therefore that further cases of secondary transmission could occur by iatrogenic spread, which could result in vCJD persisting in the UK at low levels for many years, highlighting the importance of continued vigilance.
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