Histology and histopathology Vol.22, nº 3 (2007)

Ir a Estadísticas

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http://hdl.handle.net/10201/177633

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Open Access
Expression of TGF-ß signaling proteins in normal placenta and gestational trophoblastic disease
(Murcia : F. Hernández, 2007) Xuan, Y.H.; Choi, Y.L.; Shin, Y.K.; Ahn, G.H.; Kim, Kyung Hee; Kim, W.J.; Lee, H.C.; Kim, S.H.
The transforming growth factor ß (TGF-ß) is a vital regulator of placental development and functions. TGF-ß exerts several modulatory effects on trophoblast cells, such as inhibition of proliferation and invasiveness, and stimulation of differentiation by inducing multinucleated cell formation. In this study, we determine the expression patterns of TGF-ß signaling molecules in normal trophoblast, various hydatidiform mole types and choriocarcinoma. A total of 132 cases, including 51 normal placenta (20 first trimester, 11 second trimester, and 20 third trimester) and 81 gestational trophoblastic diseases (17 choriocarcinoma, and 64 hydatidiform moles: 39 complete, 6 partial, and 19 invasive) were immunohistochemically analyzed with anti-TGF ß1/2, TGF-ß receptor type I (TßRI), TßRII, Smad 2/3, and Smad 4 antibodies on paraffin blocks. In the case of normal placenta, maximal levels of all TGF-ß signaling molecules were observed in villous trophoblast in the first trimester, which decreased with gestational age. Expression of all the TGF-ß signaling proteins except Smad2/3, was significantly enhanced in various moles, relative to normal trophoblast. Moreover, TGF-ß signaling molecules were significantly downregulated in choriocarcinoma, compared to moles. In particular, TßRI and Smad2/3 levels were lower in choriocarcinoma than normal villous trophoblast (TßRI: p<0.025, Smad2/3: p<0.001). In conclusion, the TGF-ß signaling pathway plays an important role in the pathogenesis and progression of gestational trophoblastic disease, and may thus be employed as a potential therapeutic target and a diagnostic biomarker
Open Access
In vivo inhibition of human hepatocellular carcinoma related angiogenesis by vinblastine and rapamycin
(Murcia : F. Hernández, 2007) Ribatti, Doménico; Nico, Beatrice; Mangieri, Doménica; Longo, V.; Sansonno, D.; Vacca, A.; Dammacco, F.
This paper illustrates the use of the chick embryo chorioallantoic membrane (CAM) assay to determine the single and combined antiangiogenic effects of very low doses of vinblastine (VBL) and rapamycin (RAP) in human hepatocellular carcinoma (HCC). The angiogenic response induced by human HCC biopsy specimens was inhibited by each drug and sinergistically by their combination. Morever, immunohistochemical detection of microvessels with anti-CD31 mAB showed that their area was significantly lower in specimens treated with VBL and RAP in combination. Sinergy on the part of these well-known drugs when used in combination as antiangiogenics at very low doses may be of significance in the designing of new ways of treating HCC.
Open Access
Expression of the serine protease, matriptase, in breast ductal carcinoma of Chinese women: Correlation with clinicopathological parameters
(Murcia : F. Hernández, 2007) Jin, J.S.; Cheng, T.F.; Tsai, W.C.; Sheu, L.F.; Chiang, H.; Yu, C.P.
Matriptase is a serine protease expressed by cells of surface epithelial origin, including epithelial breast tumor cells. Matriptase cleaves and activates proteins implicated in the progression of cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine matriptase expression in breast tumors of Chinese women and to identify its clinicopathological correlations. Immunohistochemical analysis of matriptase was performed in tissue microarrays of 251 breast tumors including 30 fibroadenomas, 59 ductal carcinomas in situ (DCIS), 38 grade I invasive ductal carcinomas (IDC), 79 grade II IDC, and 45 grade III IDC. The matriptase scores were significantly higher in the tumors than their non-tumor counterparts (178±12 for fibroadenoma; 275±11 for DCIS; 299±10 for grade I IDC; 251±10 for grade II IDC; and 314±11 for grade III IDC). In cases of IDC, matriptase scores were significantly correlated with tumor staging and nodal staging. Our findings demonstrate that matriptase is over-expressed in breast ductal carcinoma of Chinese women. It therefore may be a good biomarker for diagnosis and treatment of malignant breast tumors
Open Access
Mutation, replicative infidelity of DNA and aneuploidy sequentially in the formation of malignant pleomorphic tumors
(Murcia : F. Hernández, 2007) Bignold, L.P.
Mutations are thought to be involved in tumor formation because (i) tumor cells transmit their abnormalities to their descendants; and (ii) many carcinogens are mutagens. Aneuploidy is thought to be involved in tumor formation because (i) it is a common phenomenon, especially among malignant neoplasms; (ii) certain particular types of tumors are associated with specific karyotypic changes; and (iii) many immortal tumor cell lines are hyperploid. In recent years, acquired somatic cell replicative infidelity of DNA (“mutator phenotype”) has been suggested as a mechanism of tumor formation, because more somatic genomic events occur in malignant tumor cells than could be caused by repeated exogenous mutagenic insults. Previously, theories of the genomic pathogenesis of tumors have involved these mechanisms individually. Here it is suggested that all three mechanisms may play roles in the formation of certain tumor types. For example, a sequence could occur such that first, a mutation affects genomic elements for control of growth, and for replicative fidelity of DNA, leading to “mutator phenotype”. Second, when replicative infidelity of DNA results in mutation of genomic elements for mitotic-andchromosomal stability, aneuploidy develops. Third, an asymmetric mitosis (in the course of the aneuploid stage) could produce occasional cells in which the “bad copy” is lost (or an extra “good copy” is gained) of the original genomic element which had supported replicative fidelity of DNA. These resulting cells would regain fidelity of replication of DNA, and hence could give rise to populations which are relatively genomically stable, hyperploid and immortal.
Open Access
Immunohistochemical characterization of Fas (CD95) and Fas Ligand (FasL-CD95L) expression in the injured brain: Relationship with neuronal cell death and inflammatory mediators
(Murcia : F. Hernández, 2007) Grosjean, M.B.; Lenzlinger, P.M.; Stahel, P.F.; Yatsiv, I.; Shohami, E.; Trentz, O.; Kossmann, T.; Morganti-Kossmann, M.C.
Traumatic brain injury causes progressive tissue atrophy and consequent neurological dysfunction, resulting from neuronal cell death in both animal models and patients. Fas (CD95) and Fas ligand (FasL/CD95L) are important mediators of apoptosis. However, little is known about the relationship between Fas and FasL and neuronal cell death in mice lacking the genes for inflammatory cytokines. In the present study, double tumor necrosis factor/lymphotoxin-a knockout (–/–) and interleukin-6–/– mice were subjected to closed head injury (CHI) and sacrificed at 24 hours or 7 days postinjury. Consecutive brain sections were evaluated for Fas and FasL expression, in situ DNA fragmentation (terminal deoxynucleotidyl transferase-mediated dUTPbiotin nick end-labeling; TUNEL), morphologic characteristics of apoptotic cell death and leukocyte infiltration. A peak incidence of TUNEL positive cells was found in the injured cortex at 24 hours which remained slightly elevated at 7 days and coincided with maximum Fas expression. FasL was only moderately increased at 24 hours and showed maximum expression at 7 days. A few TUNEL positive cells were also found in the ipsilateral hippocampus at 24 hours. Apoptotic, TUNEL positive cells mostly co-localized with neurons and Fas and FasL immunoreactivity. The amount of accumulated polymorphonuclear leukocytes and CD11b positive cells was maximal in the injured hemispheres at 24 hours. We show strong evidence that Fas and FasL might be involved in neuronal apoptosis after CHI. Furthermore, Fas and FasL upregulation seems to be independent of neuroinflammation since no differences were found between cytokine–/– and wild-type mice.

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