Histology and histopathology Vol.24, nº8 (2009)
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- PublicationOpen AccessIn situ detection of APRIL-rich niches for plasma-cell survival and their contribution to B-cell lymphoma development(Murcia : F. Hernández, 2009) Burjanadze, M.; Matthes, T.A proliferation inducing ligand (APRIL) is one of the most recently cloned members of the tumor necrosis factor (TNF) family. Early experiments implicated a pathophysiological role for APRIL in the promotion of solid tumors. Later, identification of APRIL receptors on B lymphocytes indicated a physiological role for APRIL in humoral responses. We have been able to generate antibodies that detect APRIL protein in human tissues. The study of in situ APRIL expression showed that APRIL mainly regulates late stages of B-cell humoral responses. It also provided evidence that APRIL may modulate tumor development in patients, but only for specific B-cell malignancies. Here, we will review to what extent fine characterization of in situ expression adds valuable information on APRIL (patho) physiological functions.
- PublicationOpen AccessBreast carcinoma vascularity, A comparison of manual microvessel count and Chalkley count(Murcia : F. Hernández, 2009) Dhakal, Hari Prasad; Bassarova, A.V.; Naume, Bjørn; Synnestvedt, Marit; Borgen, Elin; Kaaresen, Rolf; Schlichting, Ellen; Wiedswang, Gro; Giercksky, Karl- Erik; Nesland, Jahn M.. Manual counting of microvessels as intratumoral microvessel density (MVD) and Chalkley counting have been used in several studies to assess the prognostic impact of vascularity in invasive breast carcinomas. In our present study, the aim was to evaluate the prognostic value of angiogenesis in invasive breast carcinoma assessed by MVD and Chalkley techniques in the same series of patients. A total of 498 breast carcinoma patients with median follow up time 85 months were evaluated. The tumour vascularity was quantified by both manual microvessel count (MVD) and Chalkley count in CD34 stained breast carcinoma slides by a single investigator blinded to clinical information. Other relevant clinicopathological parameters were noted, including breast cancer related death and both loco-regional and systemic relapse. The patients were stratified by converting MVD and Chalkley counts to categorical variables to assess prognostic impact, and results were compared. High vascular grades using MVD count did not demonstrate any prognostic significance for breast cancer specific survival (BCSS) or distant disease free survival (DDFS) either in whole patient group (BCSS, p=0.517, DDFS, p=0.301) or in non-treated node negative patients (p>0.05). Chalkley count showed prognostic significance for both DDFS and BCSS in whole patient group (p<0.001) and also in untreated node negative patient group (p<0.05). In multivariate analysis, Chalkley count, but not MVD, retained the prognostic value for BCSS (p=0.007) and DDFS (p=0.014). The Chalkley count for assessing angiogenesis in invasive breast carcinomas demonstrated prognostic value. The Chalkley method appears to be the better method in estimating the prognostic impact of vascularity in invasive breast carcinomas.
- PublicationOpen AccessExpression and distribution of GABAergic system in rat knee joint synovial membrane(Murcia : F. Hernández, 2009) Tamura, Shigenori; Watanabe, M.; Kanbara, Kiyoto; Yanagawa, Tetsuji; Watanabe, K.; Otsuki, Yoshinori; Kinoshita, MitsuoThe GABAergic system, found in the adult mammalian brain and composed of γ-aminobutyric acid (GABA), GABA synthesizing enzyme glutamate decarboxylase (GAD) and GABA receptors, is also located in many peripheral nonneuronal tissues. Studies suggest that synovial membranes possess GABA, and that GABA participates in the control of the inflammatory response in rheumatoid arthritis (RA). However, no studies on the GABAergic system in synovial membranes have been done so far. Therefore, expression and distribution of the GABAergic system in the synovial membrane of the normal rat knee joint were investigated by reverse transcription-polymerase chain reaction (RT-PCR) analyses and immunohistochemistry. Results of RT-PCR analysis showed that mRNA encoding the GAD65 and GABAB receptor subunits necessary for the assembly of functional receptors, R1 and R2, are expressed in the synovial membrane. GAD and GABAB receptor subunits were localized in macrophage-like A cells of the synovial membrane. Macrophage-like A cells of the synovial membrane have a GABA production system and GABAB receptors, and GABA seems to play functional roles in the synovial membrane.
- PublicationOpen AccessAberrant CCND1 copies and cyclin D1 mRNA expression do not result in the production of functional cyclin D1 protein in anaplastic large cell lymphoma(Murcia : F. Hernández, 2009) Bobos, Mattheos; Kotoula, Vassiliki; Kaloutsi, Vassiliki; Karayannopoulou, Georgia; Papadimitriou, Constantine S.; Kostopoulos, IoannisScattered reports in the literature have shown that Cyclin D1 mRNA and protein may be expressed in anaplastic large cell lymphoma (ALCL). ALCLs are characterized by the presence of ALK translocations. Aberrant Cyclin D1 expression seems to promote proliferation in other types of lymphoma, while a growth promoting CCND1/TACSD1(TROP2) fusion product has also been described in tumors. Herein, we investigated 44 ALCL cases for chromosome 11 and CCND1 status (by FISH), cyclin D1 mRNA expression (by in situ hybridization and RT-PCR) and Cyclin D1 protein (by immunohistochemistry with two different monoclonal antibodies), as well as for the expression of Trop-2/GA733-1 (by immunohistochemistry). Polysomy of CCND1 (11q13) and chromosome 11 was found in 15/38 evaluated cases (39.5%). This change was specific for CD30+ neoplastic cells, as shown by double fluorescent staining. Neoplastic cells in the majority of ALCL expressed cyclin D1 mRNA (29/41 [70.7%]), in association with the presence of ALK translocations (p=0.024) and systemic, rather than cutaneous disease (p=0.021). Remarkably, however, Cyclin D1 protein was not detected in neoplastic cells (0/44 cases), neither were these found positive for Trop-2. In conclusion, aberrant copies of CCND1 / chromosome 11 may be observed in ALCL, probably as a consequence of the reported ploidy changes in these tumors. ALCL may often express cyclin D1 mRNA, which, however, does not result in the production of functional Cyclin D1 protein or Trop-2, suggesting that these proteins do not play a role in the pathogenesis of ALCL.
- PublicationOpen AccessVaspin and amylin are expressed in human and rat placenta and regulated by nutritional status(Murcia : F. Hernández, 2009) Caminos, Jorge E.; Bravo, Susana B.; Garcés, Maria F.; González, C. Ruth; Cepeda, Libia A.; González, Adriana C.; Nogueiras, Rubén; Gallego, R.; Garcia-Caballero, Tomas; Cordido, Fernando; López, Miguel; Diéguez, C.Amylin (islet amyloid polypeptide) and vaspin (visceral adipose tissue specific serpin) are gut and adipocyte hormones involved in the regulation of body weight homeostasis. The aim of this study was to examine whether amylin and vaspin are expressed in human and rat placenta, as well as their regulation by nutritional status. Our results demonstrate that amylin and vaspin are localized in both human and rat placenta. In the rat term placenta vaspin was demonstrated in the trophoblast of the fetal villi, the labyrinth. Vaspin immunostaining in human placenta was localized in cytotrophoblast and syncytiotrophoblast in the first trimester placentas while in the third trimester vaspin was localized in the syncytiotrophoblast. Regarding amylin, rat placenta of 16 days of gestational age showed an intense immunostaining, mainly localized in the labyrinth. On the other hand, in the human third trimester placenta amylin immunoreactivity was intense in the syncytiotrophoblast of the chorionic villi and in decidual cells. Furthermore, placental amylin and vaspin showed an opposite pattern of expression during pregnancy, with vaspin showing the highest expression level at the end and amylin at the beginning of pregnancy. Finally, food restriction also has contrary effects on their expression, increasing vaspin but decreasing amylin placental mRNA and protein levels. Taken together, our results demonstrate that vaspin and amylin are modulated by energy status in the placenta, which suggests that these proteins may be involved in the regulation of placental metabolic functions.
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