Histology and histopathology Vol.25, nº3 (2010)

Ir a Estadísticas

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    Angiopoietin-1Tie2 receptor signaling in vascular quiescence and angiogenesis
    (Murcia : F. Hernández, 2010) Fukuhara, Shigetomo; Sako, Keisuke; Noda, Kazuomi; Zhang, Jianghui; Minami, Masayoshi; Mochizuki , Naoki
    Angiopoietin (Ang) 1 is a ligand forendothelium-specific receptor tyrosine kinase Tie-2. Inadult vasculature, Ang1/Tie2 signaling is thought toregulate both maintenance of vascular quiescence andpromotion of angiogenesis. However, it has beenunknown how Tie2 signal regulates these distinctbiological functions. Recently, we and Alitalo’s grouphave clarified that Ang1 assembles distinct Tie2signaling complexes in either presence or absence ofendothelial cell-cell adhesions. Ang1 induces trans-association of Tie2 at cell-cell contacts, whereas Tie2 isanchored to the extracellular matrix (ECM) by Ang1 atthe cell-substratum interface. Trans-associated Tie2 andECM-anchored Tie2 activate distinct signalingpathways. In this review, we discuss how Ang1/Tie2signal regulates both maintenance of vascular quiescenceand promotion of angiogenesis, especially focusing onthe roles of trans-associated Tie2 and ECM-anchoredTie2
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    Histological scoring of articular cartilage alone provides an incomplete picture of osteoarthritic disease progression
    (Murcia : F. Hernández, 2010) Barley, R.D.C.; Bagnal, K.M.; Jomha, N.M.
    Purpose: To ascertain whether molecularsubcategories of disease progression exist withinestablished histological grades of articular cartilage(AC). Methods: Based on H&E and safranin-O stainingof AC sections obtained from 18 knee arthroplastysurgeries, 30 samples ranging from Mankin ScoringSystem grade 1 through 5 were identified. Immuno-histochemical (IHC) analysis for collagen type II andaggrecan was performed on serial sections of theparaffin-embedded AC samples. Six AC samples fromeach of the five Mankin Scoring System grades wereexamined. Results: Significant IHC differences incollagen type II and aggrecan deposition were seenwithin AC samples from all five histological grades. Therange of IHC differences in collagen type II andaggrecan increased with increasing histological grade. Achange in the pattern of collagen type II deposition wasobserved in MG-3 AC that was consistent with a switchin collagen type II metabolism. Conclusions: IHCstaining of collagen type II and aggrecan can identifydifferences within histological grades of AC that areconsistent with the existence of molecular subcategories.These differences were detectable even within the lowesthistological grades; therefore the use of IHC staining canfurther enhance and refine the scoring of ACdeterioration in early osteoarthritis (OA). Furthermore,the changes seen in the deposition pattern for bothaggrecan and collagen type II suggest that they could beused to monitor key molecular events in OAprogression. These findings also underscore the need forthe development of IHC scoring criteria.
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    Survivin overexpression in HCC and liver cirrhosis differentially correlates with p-STAT3 and E-cadherin
    (Murcia : F. Hernández, 2010) Peroukides, Stavros; Bravou, Vasiliki; Alexopoulos, Alexandros; Varakis, John; Kalofonos, Haralabos; Papadaki, Helen
    Survivin, a member of the family of inhibitorof apoptosis proteins, functions as a key regulator ofapoptosis and cell proliferation. Overexpression ofsurvivin has been implicated in several human cancers,including human hepatocellular carcinoma (HCC).Although several factors have been shown in vitrotoupregulate survivin expression in cancer cells, the invivoregulators of survivin in human hepato-carcinogenesis are largely unknown. We studied byimmunohistochemistry the protein expression ofsurvivin in relation to cyclin D1, phosphorylated signaltransducer and activator of transcription 3 (p-STAT3), ß-catenin, E-cadherin and phosphorylated-Akt (p-Akt) in69 cases of HCC and adjacent liver cirrhosis. Survivinwas expressed in 63/69 (91.3%) cases of HCC and in40/47 (85.1%) cases of liver cirrhosis. Survivinlocalization in HCC was exclusively nuclear, whileintense cytoplasmic and low nuclear expression ofsurvivin was observed in cases of cirrhosis. Survivinexpression in HCC correlated significantly with lowgrade tumors, expression of cyclin D1 and p-STAT3.Expression of survivin in liver cirrhosis correlated withdownregulation of E-cadherin expression. There was nosignificant correlation of survivin with ß-catenin or p-Akt in HCC or liver cirrhosis. In conclusion, we showedan association of nuclear survivin with welldifferentiated HCC, as well as with the expression of thecell cycle regulator cyclin D1. Activation of STAT3 andloss of E-cadherin but not ß-catenin or Akt pathwaysseem to be implicated in survivin upregulation in HCCand liver cirrhosis.
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    MCM proteins as diagnostic and prognostic tumor markers in the clinical setting
    (Murcia : F. Hernández, 2010) Giaginis, constantinos; Vgenopoulou, Stephanie; Vielh, Philippe; Theocharis, Stamatios
    Minichromosome maintenance (MCM)proteins are essential for the process of DNA replication,functioning as license components for the S-phase ofcell-cycle initiation and further exerting weak helicaseactivity to unwind DNA from its supercoiled state atreplication forks. The requirement for MCM proteins incycling cells and their absence in quiescent onessupports evidence for their potential clinical applicationas cell proliferation markers. In the last few years, asidefrom their utility as cell proliferation markers, theassessment of MCM expression levels in diverse humanmalignancies has been the focus of extensive research inan aim to facilitate tumor diagnosis and prognosis inclinical settings. The present article aims to review theavailable data so far concerning the clinical significanceof MCM protein expression in human neoplasia incomparison to conventional proliferative markers. Areview of the literature revealed that MCM expression isassociated with important clinicopathological parametersfor patient management and also exhibits significantdiagnostic and prognostic value in several malignancies.MCMs are characterized by higher specificity andsensitivity than the conventional proliferative markers,such as Ki-67 and PCNA, and are thus considered asdiagnostic and prognostic tools of greater clinicalsignificance in several types of human malignancy.
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    Stem cells in human breast cancer
    (Murcia : F. Hernández, 2010) Roberto Oliveira, Lucinei; Jeffrey, Stefanie S.; Ribeiro Silva, Alfredo
    Increasing data support cancer as a stem cell-based disease. Cancer stem cells (CSCs) have beenfound in different human cancers, and recent evidenceindicates that breast cancer originates from and ismaintained by its own CSCs, as well as the normalmammary gland. Mammary stem cells and breast CSCshave been identified and purified in in vitroculturesystems, transplantation assays and/or by cell surfaceantigen identification. Cell surface markers enable thefunctional isolation of stem cells that can initiate andpropagate tumorigenesis in mammary gland. Theseobservations have dramatic biological and clinicalsignificance due to increasing evidence suggesting thatthe recurrence of human cancer and treatment failuremay reflect the intrinsic quiescence and drug resistanceof CSCs. Thus, the CSC hypothesis providesfundamental implications for understanding breastcarcinogenesis and for developing new strategies forbreast cancer prevention and therapy for advanceddisease. Further strategies to isolate breast CSCs, to findadditional trustworthy surface markers, and to comparegene expression pathways profiles with their normalstem cells counterparts are necessary to more accuratelydefine putative breast cell-lineage markers for thedifferent cell types present in the mature mammarygland and to identify potential therapeutical targets inbreast cancer. This review discusses the currentknowledge about stem cells and CSCs, focusing onmammary stem cells and breast CSCs, and theirconsequences for breast tumorigenesis and implicationsfor breast cancer susceptibility, prognosis, and treatment.