Histology and histopathology Vol.24, nº1 (2009)
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- PublicationOpen AccessBone marrow stromal cells for spinal cord repair, A challenge for contemporary neurobiology(Murcia : F. Hernández, 2009) Vaquero, J.; Zurita, M.In the last years, it has been reported that bone marrow stromal cells (BMSC) are able to differentiate towards a neuronal phenotype, in vitro as well as in vivo, and consequently, the possible use of these cells for the treatment of neurological diseases has acquired enormous importance. The objective of this review is to discuss the experimental findings that suggested the utility of BMSC for the treatment of paraplegia, and the possibilities of its clinical application in patients. For this reason, we revise our previous experimental findings about neuronal transdifferentiation of BMSC, and the utility of local BMSC transplantation in an experimental model of chronic paraplegia. Our current experience supports that a neural transdifferentiation of BMSC is possible after these mesenchymal stem cells are transplanted into injured spinal cord tissue. Furthermore, this cell therapy achieves a clear functional improvement of paraplegic animals, together with morphological evidence of spinal cord regeneration. Although at present our efforts should be guided to obtain a better knowledge of the mechanisms of nervous regeneration induced by bonemarrow derived stem cells, it is obvious that cell therapy for nervous system repair is beginning, and BMSC transplantation offers new hope for the treatment of traumatic paraplegia in humans.
- PublicationOpen AccessGenetic and molecular alterations in rhabdomyosarcoma: mRNA overexpression of MCL1 and MAP2K4 genes(Murcia : F. Hernández, 2009) Pazzaglia, Laura; Chiechi, Antonella; Conti, Amalia; Gamberi, Gabriella; Magagnoli, Giovanna; Novello, Chiara; Morandi, Luca; Picci, Piero; Mercuri, Mario; Benassi, M.S.Rhabdomyosarcoma, the most common soft tissue sarcoma in childhood, belongs to the small round cell tumor family and is classified according to its histopathological features as embryonal, alveolar and pleomorphic. In this study we propose to explore genetic alterations involved in rhabdomyosarcoma tumorigenesis and assess the level of mRNA gene expression of controlling survival signalling pathways. For genetic and molecular analysis, array-based comparative genomic hybridization, combined with Real Time PCR using the comparative method, was performed on 14 primary well-characterized human primary rhabdomyosarcomas. Multiple changes affecting chromosome arms were detected in all cases, including gain or loss of specific regions harbouring cancer progression-associated genes. Evaluation of mRNA levels showed in the majority of cases overexpression of MCL1 and MAP2K4 genes, both involved in cell viability regulation. Our findings on rhabdomyosarcoma samples showed multiple copy number alterations in chromosome regions implicated in malignancy progression and indicated a strong expression of MAP2K4 and MCL1 genes, both involved in different biological functions of complicated signalling pathways.
- PublicationOpen AccessBRCA1 expression and molecular alterations in familial breast cancer(Murcia : F. Hernández, 2009) Mangia, Anita; Chiriatti, Annalisa; Tommasi, Stefania; Menolascina, Filippo; Petroni, Stella; Zito, Francesco A.; Simone, Giovanni; Schittulli, Francesco; Paradiso, AngeloThe aim of the study was to evaluate the performance of immunohistochemical MS110 expression in a series of familial and sporadic breast cancer patients. An immunohistochemical study was performed on TMA samples from 93 sporadic and 94 familial breast cancer patients with (7/94) and without BRCA1 germline mutations. BRCA1 protein expression level was evaluated using the monoclonal MS110 antibody. Immunohistochemistry, performed on TMA samples, showed positive nuclear staining for BRCA1 in 34 sporadic and 37 familial breast tumours, respectively. All the tumours from patients carrying BRCA1 mutations showed complete loss of both BRCA1 and ERa expression, regardless of the type of mutation. The percentage of MS110 positive cases was significantly lower in mutated versus wild type BRCA1 familial cases (p=0.02) while the percentage of patients with higher ERa expression was significantly lower in BRCA1- mutated versus BRCA1-wild type familial patients (p=0.05). Interestingly, the presence of the E1038G polymorphism in BRCA1 exon 11 was significantly associated with protein expression (p=0.029). The frequency of MS110 negative cases also detected in BRCA1-wild type tumours, points to the inability of the BRCA1 IHC expression in discriminating between familial and sporadic breast cancer.
- PublicationOpen AccessMacrophage populations and expressions of regulatory proinflammatory factors in the rat meninx under lipopolysaccharide treatment in vivo and in vitro(Murcia : F. Hernández, 2009) Yamate, J.; Ishimine, S.; Izawa, T.; Kumagai, D.; Kuwamura, M.Macrophages play important roles in host defense mechanisms. In the brain, besides microglial cells, meningeal macrophages are present. However, the pathobiological characteristics of meningeal macrophages in rats remain to be investigated. In normal meninx, immunohistochemically, macrophages reacting to CD163 (macrophage scavenger receptor) and major histocompatibility complex (MHC) class II-expressing cells (involving activated macrophages or dendritic cells) were sporadically seen without age-dependent changes. Injection of lipoplysaccharide (LPS) (5 μg; Escherichia coli) into the cerebrum increased the number of anti-CD68-positive macrophages (with greater phagocytic activity) in the meninx, with a peak at 12 h during observation period until 48 h; MHC class IIexpressing cells showed a gradual increase in number from 3 h after injection; however, anti-CD163-positive macrophages did not show significant change. In in vitro studies, LPS (0, 0.02, 0.05, 0.5, 5, 50 and 100 μg/ml) was added to KMY-1 or KMY-2 cells, both of which had been established from a rat malignant meningioma. KMY-1 originally reacted to CD163, but LPS addition at 0.5 μg/ml and greater concentrations decreased the anti- CD163-positive cell number and instead increased the anti-CD68-positive cell number. LPS-treated KMY-2 increased the anti-CD163-positive cell number at 0.05 and 0.5 μg/ml. By RT-PCR methods, LPS (0, 0.5, 5, 50, and 100 μg/ml)-treated KMY-1 and KMY-2 showed an increase in mRNA of monocyte chemoattractant protein- 1 (MCP-1, a chemokine), and LPS-treated KMY-2 increased mRNA of nerve growth factor (NGF, an immunological effecter). Collectively, under LPS treatment, macrophages with heterogeneous functions appear in rat meninx; rat meninx-forming cells may be involved in pathogenesis of meningeal inflammation by expressing different immunophenotypes and by producing regulatory proinflammatory factors such as MCP-1 and NGF.
- PublicationOpen AccessRUNX3 expression correlates with chief cell differentiation in human gastric cancers(Murcia : F. Hernández, 2009) Naotaka Ogasawara; Tetsuya Tsukamoto; Tsutomu Mizoshita; Ken-ichi Inada; Hisayo Ban; Shinya Kondo; Shinji Takasu; Toshikazu Ushijima; Kosei Ito; Yoshiaki Ito; Masao Ichinose; Takafumi Ogawa; Takashi Joh; Masae TatematsuRUNX3 is a novel tumor suppressor in gastric carcinogenesis and an important factor for differentiation of chief cells in the normal gastric fundic mucosa. In this study, we confirmed RUNX3 immunolocalization in the fundic gland (bottom part) but minimum in surface mucous cell epithelium (top part) in the isolated gland from fundic mucosa. We also analyzed RUNX3 expression by immunohistochemistry in 102 gastric cancers and made a histological assessment of the expression of differentiation markers to evaluate interrelations. Among them, 45 and 57 cases were judged to be RUNX3 positive and negative, respectively, and 33 and 69 cases were pepsinogen I positive and negative, with no link to histological types. RUNX3 expression was significantly associated with that of pepsinogen I (P<0.001), but not mucins, including MUC5AC and MUC6, or the parietal or intestinal phenotypes. In conclusion, the present study showed, for the first time to our knowledge, a relation between RUNX3 and pepsinogen I expression in human gastric cancers. RUNX3 is strongly associated with chief cell phenotypic expression in human gastric cancers, as well as in normal gastric mucosa, and could be considered to play an important role in maintaining the chief cell phenotype.
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