Histology and histopathology Vol.22, nº 9 (2007)

Ir a Estadísticas

Permanent URI for this collection

http://hdl.handle.net/10201/177350

Browse

Recent Submissions

Now showing 1 - 5 of 12
  • Thumbnail Image
    Publication
    Open Access
    Prostate stem cells and cancer
    (Murcia : F. Hernández, 2007) Nikitin, Alexander Y.; Matoso, A.; Roy-Burman, P.
    Properties shared by neoplastic and stem cells indicate a possibility that somatic stem cells or transit-amplifying cells that have reacquired stem cell properties, particularly the ability for self-renewal, represent favorable targets for malignant transformation. In this review we discuss significance of the stem cell model for understanding prostate cancer pathogenesis and describe relevant studies in animals. It is proposed that dissemination of rare cancer stem cells may lead to metastatic disease and that resistance of such cells to multiple drugs and androgen ablation make them responsible for failure of current treatments. Thus further understanding of the cancer stem cell biology is needed for development of efficient rationally designed therapy permitting better targeting and better treatment outcomes for patients with prostate neoplasms
  • Thumbnail Image
    Publication
    Open Access
    ß-Galactosidase staining on bone marrow. The osteoclast pitfall
    (Murcia : F. Hernández, 2007) Kopp, H.G.; Hooper, A.T.; Shmelkov, S.V.; Rafii, S.
    The enzyme ß-galactosidase, encoded by the bacterial gene lac-Z, is commonly used as a histochemical reporter to track transplanted cells in vivo or to analyze temporospatial gene expression patterns by coupling expression of specific target genes to ßgalactosidase activity. Previously, endogenous ßgalactosidase activity has been recognized as a confounding factor in the study of different soft tissues, but there is no description of the typical background on bone marrow sections when using the chromogenic substrate 5-Bromo-4-chloro-3-indolyl ß-D-Galactoside (X-Gal). In this report, we show that osteoclasts in bone marrow sections specifically and robustly stain blue with X-Gal. This leads to a typical background when bone marrow is examined that is present from the first day post partum throughout the adult life of experimental mice and can be confused with transgenic, bacterial ßgalactosidase expressing hematopoietic or stromal cells. Experimental variations in the X-Gal staining procedure, such as pH and time of exposure to substrate, were not sufficient to avoid this background. Therefore, these data demonstrate the need for strenuous controls when evaluating ß-galactosidase positive bone marrow cells. Verifiable bacterial ß-galactosidase positive bone marrow cells should be further identified using immunohistological or other approaches. Specifically, ßgalactosidase positive hematopoietic or stromal cells should be proven specifically not to be osteoclasts by costaining or staining adjacent sections for specific markers of hematopoietic and stromal cells.
  • Thumbnail Image
    Publication
    Open Access
    Altered expression of urokinase-type plasminogen activator and plasminogen activator inhibitor in high-risk soft tissue sarcomas
    (Murcia : F. Hernández, 2007) Benassi, M.S.; Ponticelli, F.; Azzoni, E.; Gamberi, G.; Pazzaglia, L.; Chiechi, A.; Conti, A.; Spessotto, P.; Scapolan, M.; Pignotti, E.; Bacchini, P.; Picci, P.
    In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant upregulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered. In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant upregulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered.
  • Thumbnail Image
    Publication
    Open Access
    Causal probabilistic modeling for malignancy grading in pathology with explanations of dependency to the related histological features
    (Murcia : F. Hernández, 2007) Weidl, G.; Iglesias-Rozas, J.R.; Roehrl, N.
    This work demonstrates that histological grading of brain tumors and astrocytomas can be accurately predicted and causally explained with the help of causal probabilistic models, also known as Bayesian networks (BN). Although created statistically, this allows individual identification of the grade of malignancy as an internal cause that has enabled the development of the histological features to their observed state. The BN models are built from data representing 794 cases of astrocytomas with their malignant grading and corresponding histological features. The computerized learning process is improved when pre-specified knowledge (from the pathologist) about simple dependency relations to the histological features is taken into account. We use the BN models for both grading and causal analysis. In addition, the BN models provide a causal explanation of dependency between the histological features and the grading. This can offer the biggest potential for choice of an efficient treatment, since it concentrates on the malignancy grade as the cause of pathological observations. The causal analysis shows that all ten histological features are important for the grading. The histological features are causally ordered, implying that features of first order are of higher priority, e.g. for the choice of treatment in order not to allow the malignancy to progress to a higher degree. Due to the explanations of feature relations, the complement to any malignancy classification tool and allows reproducible comparison of malignancy grading.
  • Thumbnail Image
    Publication
    Open Access
    The S100 proteins for screening and prognostic grading of bladder cancer
    (Murcia : F. Hernández, 2007) Yao, R.; Davidson, D.D.; López Beltrán, A.; MacLennan, G.T.; Montironi, R.; Cheng, L.
    The S100 gene family, which is composed of at least 24 members carrying the Ca2+ binding EF-hand motif, has been implicated in both intracellular and extracellular functions, including enzyme activities, immune responses, cytoskeleton dynamics, Ca2+ homeostasis, cell growth and cell differentiation. Altered S100 protein levels are associated with a broad range of diseases, including cardiomyopathy, inflammatory and immune disorders, neurodegenerative disorders and cancer. Although the precise role of S100 protein in carcinogenesis is poorly understood, it seems that formation of homo- and hetero-dimers, binding of Ca2+ and interaction with effector molecules are essential for the development and progression of many cancers. Several studies have suggested that S100 proteins promote cancer progression and metastasis through cell survival and apoptosis pathways. In animal models of bladder cancer, several S100 proteins are differentially expressed in bladder tumors relative to normal urothelium. In human bladder cancer, overexpression of S100A4, S100A8 or S100A11 are associated with stage progression, invasion, metastasis and poor survival. This review summarizes these findings and evaluates their implications for human bladder cancer management