Histology and histopathology Vol.22, nº11 (2007)

Ir a Estadísticas

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http://hdl.handle.net/10201/177595

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Open Access
Expression profile of tight junction protein claudin 3 and claudin 4 in ovarian serous adenocarcinoma with prognostic correlation
(Murcia : F. Hernández, 2007) Choi, Y.L.; Kim, J.B.; Kwon, M.J.; Choi, J.S.; Kim, T.J.; Bae, D.S.; Koh, S.S.; In, Y.H.; Park, Y.W.; Kim, S.H.; Ahn, G.H.; Shin, Y.K.
Tight junction proteins claudin 3 (CLDN3) and claudin 4 (CLDN4) are frequently altered in several human cancers, including ovarian carcinomas. Here, we examined the gene expression of CLDN3 and CLDN4 in various tumors, including 19 normal ovaries and 47 ovarian carcinomas by analyzing Affymetrix HG-U133 array data. Furthermore, a total of 114 ovarian serous tumors, including 10 adenomas, 20 borderline tumors and 84 carcinomas, were analyzed immunohistochemically to confirm the expression of two proteins and we assessed the association of their expression with the clinicopathological characteristics and survival of the patients. The microarray experiment revealed CLDN3 and CLDN4 transcripts were significantly up-regulated by 5-fold or more in most subtypes of ovarian epithelial carcinomas while the immunohistochemical analyses indicated that each protein was expressed in 68 (81.0%) and 72 (85.7%) of 84 serous adenocarcinomas, respectively. Borderline serous tumors and adenomas showed significantly lower expression of these proteins than the adenocarcinomas. Kaplan-Meier survival analysis showed that serous adenocarcinoma patients with high CLDN3 expression had substantially shorter survival (P=0.027). Multivariate analysis demonstrated that CLDN3 overexpression is an independent negative prognostic factor. Our findings suggest that CLDN3 overexpression can be used as a prognostic indicator in ovarian serous carcinomas. Moreover, CLDN3 may be a promising target for antibody-based therapy of ovarian carcinomas.
Open Access
Recent development of in vivo cryotechnique to cryobiopsy for living animals
(Murcia : F. Hernández, 2007) Ohno, N.; Terada, N.; Saitoh, S.; Zhou, H.; Fuji, Y.; Ohno, S.
Various microscopic methods have been used to analyze the morphology and molecular distribution of cells and tissues. Using conventional procedures, however, ischemic or anoxic artifacts are inevitably caused by tissue-resection or perfusion-fixation. The in vivo cryotechnique (IVCT) was developed to overcome these problems, and was found to be useful with light microscopy for analyses of the distribution of watersoluble molecules without anoxic effects at high time resolution. But there are limitations to the application of IVCT, such as exposure of target organs of living small animals and immunoreactivity of lipid-soluble molecules owing to freeze-substitution with acetone. Recently, a new cryotechnique called “cryobiopsy” has been developed, which enables one to obtain tissue specimens of large animals including humans without ischemia or anoxia, and has almost the same technical advantages as IVCT. Both IVCT and cryobiopsy complement other live-imaging techniques, and are useful for not only the morphological observation of cells and tissues under normal conditions, but also the preservation of all components in frozen tissue specimens. Therefore, morphofunctional information in vivo would be obtained by freeze-substituion for light or electron microscopy, and also by other analytical methods, such as freezefracture replication, X-ray microanalyses, or Raman microscopy. Considering the merits of both IVCT and cryobiopsy, their application should be expanded into other microscopic fields and also from experimental animal studies to clinical medicine.
Open Access
The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury
(Murcia : F. Hernández, 2007) Chong, Z.Z.; Maiese, K.
Interest in the diverse biology of protein tyrosine phosphatases that are encoded by more than 100 genes in the human genome continues to grow at an accelerated pace. In particular, two cytoplasmic protein tyrosine phosphatases composed of two Src homology 2 (SH2) NH2-terminal domains and a C-terminal proteintyrosine phosphatase domain referred to as SHP-1 and SHP-2 are known to govern a host of cellular functions. SHP-1 and SHP-2 modulate progenitor cell development, cellular growth, tissue inflammation, and cellular chemotaxis, but more recently the role of SHP-1 and SHP-2 to directly control cell survival involving oxidative stress pathways has come to light. SHP-1 and SHP-2 are fundamental for the function of several growth factor and metabolic pathways yielding far reaching implications for disease pathways and disorders such as diabetes, neurodegeneration, and cancer. Although SHP-1 and SHP-2 can employ similar or parallel cellular pathways, these proteins also clearly exert opposing effects upon downstream cellular cascades that affect early and late apoptotic programs. SHP-1 and SHP-2 modulate cellular signals that involve phosphatidylinositol 3-kinase, Akt, Janus kinase 2, signal transducer and activator of transcription proteins, mitogen-activating protein kinases, extracellular signalrelated kinases, c-Jun-amino terminal kinases, and nuclear factor-kB. Our progressive understanding of the impact of SHP-1 and SHP-2 upon multiple cellular environments and organ systems should continue to facilitate the targeted development of treatments for a variety of disease entities.
Open Access
Histological evaluation of colonic anastomotic healing, during perioperative Capecitabine administration. Experimental study in rats
(Murcia : F. Hernández, 2007) Konstantinidis, H.D.; Sioga, A.C.; Economou, L.; Mpallas, K.D.; Demertzidis, C.I.; Pissanidou, T.T.
Background: Neoadjuvant chemotherapy is a highly promising treatment modality for colorectal cancer. One of the basic side effects of this method is the possible impact on anastomotic healing. Capecitabine is a tumor selective pro-drug of 5-fluorouracil, indicated for the therapy of colorectal cancer. The aim of this study is to estimate the effect of perioperative Capecitabine administration on the colonic anastomotic healing process, by evaluating histopathological findings. Methods: We studied the effect of Capecitabine on hand sutured colonic anastomosis in rats. Sixty Wistar rats were randomized in two groups. In the study group (n=30) Capecitabine was given p.o. in therapeutic dose of 359 mg/kg, (2/3 of the mean toxic dose), 1 week prior the anastomosis and throughout the study. In the control group (n=30) placebo medication was administrated. Both groups were further subdivided into 3 groups, each consisting of 10 animals. Rats of each group were sacrificed on the 3rd, 7th and 14th postoperative day, in both study and control groups. Results: No negative impact on the healing process of colonic anastomosis was found. Histological findings indicated a more effective healing during the early postoperative days, with lesser necrosis effects on the anastomotic line for the study group, in comparison with the control group. The median bursting pressure was found to be significantly higher in the subdivision of the study group sacrificed on the 3rd day, in comparison to respective control subdivision. Conclusion: Perioperative administration of Capecitabine, as neoadjuvant chemotherapy, does not impair the healing of colonic anastomosis in rats.
Open Access
Soluble CD30 serum level - an adequate marker for allograft rejection of solid organs?
(Murcia : F. Hernández, 2007) Schlaf, G.; Altermann, W.W.; Rothhoff, A.; Seliger, B.
The CD30 molecule, a 120 kDa cell surface glycoprotein, is a member of the tumor necrosis factor receptor (TNF-R) superfamily and was originally identified on the surface of Reed-Sternberg cells and anaplastic large cell lymphomas in Hodgkin’s disease patients. In addition to lymphoproliferative disorders the expression of CD30 was found in both activated CD8+ and CD4+ Th2 cells which lead to the activation of Bcells and consequently to the inhibition of the Th1-type cellular immunity. The membrane-bound CD30 molecule can be proteolytically cleaved, thereby generating a soluble form (sCD30) of about 85 kDa. Low serum levels of soluble CD30 were found in healthy humans, whereas increased sCD30 serum concentrations were detected under pathophysiological situations such as systemic lupus erythematosus, rheumatoid arthritis, certain viral infections and adult T cell leukaemia/lymphoma. In addition, it has recently been suggested that pre- or post-transplant levels of sCD30 represent a biomarker for graft rejection associated with an impaired outcome for transplanted patients. We here review (i) the current knowledge of the clinical significance of sCD30 serum levels for solid organ transplantations and (ii) our own novel data regarding inter- and intra-individual variations as well as time-dependent alterations of sCD30 levels in patients. (iii) Based on this information the implementation of sCD30 as predictive pre-transplant or post-transplant parameter for solid organ transplantation is critically discussed.

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