Ki-67 and CD100 immunohistochemical expression is associated with local recurrence and poor prognosis in soft tissue sarcomas, respectively

Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors of >50 subtypes. However, STSs represent <1% of types of cancer. Despite this low frequency, the disease is aggressive and treatment, when possible, is based on traditional chemotherapies. A number of cases of resistance to adjuvant therapies have been reported. Metastases are commonly identified in STS patients during diagnosis and the development of effective clinical parameters is crucial for correct management of the disease. The use of biological markers in cancer is a useful tool to determine patient prognosis. Ki-67 is a protein marker for proliferation of somatic cells and is widely used in prognostic studies of various types of tumor, including STSs. Cluster of differentiation 100 (CD100) is a member of the semaphorin family. The family was initially described as axon guidance molecules important for angiogenesis, organogenesis, apoptosis and neoplasia. CD100 was previously utilized as a prognostic factor in tumors and also in STSs. In the present study, protein expression of Ki-67 and CD100 was analyzed by immunohistochemistry in samples of STS patients of the Barretos Cancer Hospital (Barretos, Brazil) to establish prognostic criteria of the disease. Results demonstrate a correlation between CD100 expression and poor prognosis, consistent with a previous study. Moreover, the expression of Ki-67 was identified to correlate with presence of local or locoregional recurrence. To the best of our knowledge, no large casuistic study has revealed this correlation between Ki-67 and local recurrence in STSs. The use of Ki-67 and CD100 as markers in clinical pathological analysis may be suitable as a prognostic criterion in disease progression

Postnatal development of gerbil ventral prostate (meriones unguiculatus) and histopathologic lesions associated to the aging

Orientador: Sebastiao Roberto TabogaTese (doutorado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: Há um grande interesse em melhor compreender a biologia da próstata devido à sua alta propensão em desenvolver lesões proliferativas, estando entre as mais comuns neoplasias que acometem o homem na atualidade. Entre os fatores de risco que contribuem para o aumento destas doenças destaca-se o envelhecimento, período em que ocorrem acentuados desequilíbrios hormonais. Vários grupos de pesquisa vêm tentando desenvolver, caracterizar e validar modelos roedores para análise do câncer de próstata sob diferentes aspectos e, modelos autóctones, têm desempenhado papel relevante nesse campo. Neste trabalho foi realizada a avaliação do comportamento biológico da próstata ventral do roedor gerbilo (Meriones unguiculatus) em fases distintas de seu desenvolvimento pós-natal. Em uma primeira etapa caracterizou-se através de análises morfológicas (estruturais e ultra-estruturais) e quantitativas os componentes celulares dos compartimentos epitelial e estromal, bem como o papel funcional de suas populações celulares na glândula. Para tanto foram utilizados gerbilos jovens, adultos e velhos. Considerando a próstata de animais jovens, constatou-se que nestes a glândula encontra-se estrutural e funcionalmente imatura. Já em animais adultos e velhos a atividade sintética está bem estabelecida e permanece estável nestas duas idades. Entretanto, a morfologia prostática em animais velhos apresentou-se diferenciada. Em uma mesma glândula puderam ser constatadas regiões funcionais com epitélio secretor semelhante aos adultos e, em outras, áreas completamente alteradas, dispondo de lesões histopatológicas. O comportamento prostático nas três fases do desenvolvimento analisadas foi diretamente influenciado pelos níveis de testosterona no soro, comprovando a importância desse andrógeno para homeostase e funcionalidade glandular. E, em animais velhos, o declínio de testosterona esteve associado a alterações proliferativas na glândula. Devido a essas constatações em uma segunda etapa, avaliou-se, exclusivamente, a próstata de animais velhos com o intuito de se caracterizar os principais tipos de lesões que podem acometê-la. As alterações mais freqüentes foram de origem epitelial, como as neoplasias intra-epiteliais (PIN), carcinomas microinvasivos e adenocarcinomas. O potencial invasivo das células anômalas pôde ser comprovado ultra-estruturalmente através da ruptura da membrana basal em alguns ácinos. No estroma, hiperplasia celular, quando constatada, esteve sempre associada a sítios de epitélio anômalo. Adicionalmente, uma maior deposição de fibrilas de colágeno (gerando fibrose estromal) foi encontrada em todos gerbilos velhos analisados. Parâmetros nucleares e nucleolares somente não foram efetivos para diagnosticar o potencial de severidade das alterações. Os índices de proliferação e morte celular, porém indicaram maior turnover celular à medida que alterações histopatológicas tornaram-se invasivas. A partir destes dados constatou-se que o gerbilo é um bom modelo para análise do comportamento prostático em diferentes fases do desenvolvimento pós-natal. Adicionalmente, o animal velho tem alta propensão em desenvolver alterações prostáticas espontâneas e estas podem auxiliar na melhor compreensão da evolução biológica do câncer prostático humano propriamenteAbstract: There is a great interest in understanding the prostate biology due to its high propensity in developing proliferative lesions. At the present time, this kind of illnes is one of the most common neoplasias which may damage men. Among the risk factors that contribute to the prostate cancer increase stands out aging, period when an accentuated hormonal unbalances happens. Several research groups are trying to develop, characterize and validate rodent models for analysis of the prostate cancer and, autochthonous models have been playing a relevant role in these aspects. In the present work, the biological behavior evaluation of the ventral prostate of gerbil rodent (Meriones unguiculatus) was accomplished in three different phases of postnatal development. Initially, the cellular components of epithelial and stromal compartments, as well as, the functional activity of those cellular populations in the gland were characterized through morphologic (structural and ultrastructural) and quantitative analyses. For this, young, adult and old gerbils were employed. Considering the prostate of young animals, it was verified that the prostate gland is structural and functionally immature. In adult and old animals the synthetic activity is well established and remained stable. However, in old animals, the prostatic morphology presented alterations. In a same gland it could be observed functional areas with a secretor epithelium similar to adults and regions completely modified, exhibiting histopathologic lesions. The prostatic behavior in the three phases of development was influenced directly by the serum testosterone levels, proving the importance of this androgen for glandular homeostasis and its functionality. In the old animals the testosterone decline was associated to the proliferative alterations presented in the gland. Because of these results, in a second stage of experiments, it was evaluated only the prostate of old animals with the purpose of characterizing the main types of lesions which may be develop in these gerbils. The most frequent changes noted were those originated in the epithelium, as the prostatic intraepithelial neoplasia (PIN), microinvasive carcinomas and adenocarcinomas. Ultrastructurally, the invasive potential of anomalous cells could be confirmed by the basement membrane disrupted noted in some acini. In the stroma, the cellular hiperplasia, when verified, it was always associated to the anomalous epithelium sites. Additionally, a larger deposition of collagen fibrils, which generates stromal fibrosis, it was found in all old gerbils analyzed. Nuclear and nucleolar parameters were not effective in diagnosing the severity potential of those alterations. The cellular proliferation and death indexes, however, indicated a larger cellular turnover according as the histhopatologic lesions become invasives. Concluding, these analyses allow confirming that the rodent gerbil is a good model for prostate behavior analysis in different phases of postnatal development. The old animal revealed a high propensity in developing spontaneous prostatic alterations and these changes may help to comprehend the natural course of the neoplasia's multistep and its biological behavior, contributing to a better understanding of the human prostate cancerDoutoradoBiologia CelularDoutor em Biologia Celular e Estrutura

Tolerancia a choque frio em Triatoma infestans klug

Orientador : Maria Luiza Silveira MelloDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de BiologiaMestrad

Biological Behavior Of The Gerbil Ventral Prostate In Three Phases Of Postnatal Development.

In this study, we characterized the gerbil's ventral prostate histology ultrastructurally and quantitatively throughout three phases of postnatal development (young, adult, and old) in order to comprehend its biological behavior and propensity to developing spontaneous lesions with aging. The gerbil prostate is composed of alveoli and ducts immersed in a stroma composed of smooth muscle, fibroblasts, collagen and elastic fibers and vessels. The prostate tissue components present morphological and quantitative aspects that vary according to age. Young animals have an immature gland with modest secretory activity. Synthetic activity remained stable in adult and old gerbil. However, prostatic morphology was altered in the aging, showing an increased epithelium and stromal fibrosis. The nuclei of the secretory cells increased with aging, whereas nucleoli presented few alterations during postnatal development. The epithelial proliferation and stromal remodeling noted in this study indicate that the gerbil prostate may respond to the androgen declines typical of senescence through epithelial proliferation and stromal remodeling.288723-3

Do mineral and corn oil serve as potential endocrine disruptors in the gerbil prostate?

Vegetable oils are frequently used as a vehicle in the administration of lipophilic drugs in animal tests. However, the composition of these oils may interfere with the results. One alternative to reduce this potential bias is the use of mineral oil, which is not supposed to interfere in the physiology of experimental models, since this oil is considered to be innocous. The present study shows for the first time the effects of the oral administration of corn and mineral on the prostate, demonstrating their interference in homeostasis and revealing their potential to act as endocrine disruptors. Mineral oil treatment increased the expression of AR and ERa and serum estradiol concentrations, while corn oil increased the expression of positive cells for both types of estrogen receptors. The variation in the expression of these hormone receptors resulted in morphological changes in the prostate90141149COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESnão te

Key participants of the tumor microenvironment of the prostate: An approach of the structural dynamic of cellular elements and extracellular matrix components during epithelial-stromal transition

Cancer is a multistep process that begins with the transformation of normal epithelial cells and continues with tumor growth, stromal invasion and metastasis. The remodeling of the peritumoral environment is decisive for the onset of tumor invasiveness. This event is dependent on epithelial–stromal interactions, degradation of extracellular matrix components and reorganization of fibrillar components. Our research group has studied in a new proposed rodent model the participation of cellular and molecular components in the prostate microenvironment that contributes to cancer progression. Our group adopted the gerbil Meriones unguiculatus as an alternative experimental model for prostate cancer study. This model has presented significant responses to hormonal treatments and to development of spontaneous and induced neoplasias. The data obtained indicate reorganization of type I collagen fibers and reticular fibers, synthesis of new components such as tenascin and proteoglycans, degradation of basement membrane components and elastic fibers and increased expression of metalloproteinases. Fibroblasts that border the region, apparently participate in the stromal reaction. The roles of each of these events, as well as some signaling molecules, participants of neoplastic progression and factors that promote genetic reprogramming during epithelial–stromal transition are also discussed

Oestrogen supplementation following castration promotes stromal remodelling and histopathological alterations in the Mongolian gerbil ventral prostate

The effect of oestradiol on the intact and castrated adult gerbil prostate was evaluated by focussing on stromal and epithelial disorders, and hormonal receptor immunoreactivity. The experimental animals were studied by histological, histochemical and immunohistochemical techniques, morphometric-stereological analysis and transmission electron microscopy. Epithelial alterations in the oestradiol-treated animals were frequent, with an increase in epithelial cell height, areas of intense dysplasia and hyperplasia and formation of prostatic intraepithelial neoplasia (PIN). Another aspect that did not depend on the presence of testosterone was the arrangement of the fibrillar and non-fibrillar elements of the extracellular matrix among smooth muscle cells (SMC), suggesting a possible role of these cells in rearrangement and synthesis of these components, after oestrogenic treatment. In the castrated animals, an accumulation of extracellular matrix elements under the epithelium was evident, while in the intact animals the same compounds were dispersed and scarce. In the groups of intact and castrated animals, SMC and fibroblasts exhibited a secretory phenotype, which was accentuated after oestradiol administration. There was an increase of the immunoreactivity to alpha-oestrogen and androgen receptors in hyperplastic areas compared to normal epithelium, revealing the involvement of these steroid receptors in the hyperplasia and PIN development

Oestrogen Supplementation Following Castration Promotes Stromal Remodelling And Histopathological Alterations In The Mongolian Gerbil Ventral Prostate.

The effect of oestradiol on the intact and castrated adult gerbil prostate was evaluated by focussing on stromal and epithelial disorders, and hormonal receptor immunoreactivity. The experimental animals were studied by histological, histochemical and immunohistochemical techniques, morphometric-stereological analysis and transmission electron microscopy. Epithelial alterations in the oestradiol-treated animals were frequent, with an increase in epithelial cell height, areas of intense dysplasia and hyperplasia and formation of prostatic intraepithelial neoplasia (PIN). Another aspect that did not depend on the presence of testosterone was the arrangement of the fibrillar and non-fibrillar elements of the extracellular matrix among smooth muscle cells (SMC), suggesting a possible role of these cells in rearrangement and synthesis of these components, after oestrogenic treatment. In the castrated animals, an accumulation of extracellular matrix elements under the epithelium was evident, while in the intact animals the same compounds were dispersed and scarce. In the groups of intact and castrated animals, SMC and fibroblasts exhibited a secretory phenotype, which was accentuated after oestradiol administration. There was an increase of the immunoreactivity to alpha-oestrogen and androgen receptors in hyperplastic areas compared to normal epithelium, revealing the involvement of these steroid receptors in the hyperplasia and PIN development.8925-3

Long-term effects of developmental exposure to di-n-butyl-phthalate (DBP) on rat prostate: Proliferative and inflammatory disorders and a possible role of androgens

In the present study we evaluated the toxic effects on the male adult rat prostate of DBP exposure during fetal and lactational periods, because although many studies have addressed the influence of phthalates on the male reproductive system, only a few have discussed their possible effects on prostate development. Pregnant females were distributed into two experimental groups: Control (C) and Treated (T). The females of the T group received DBP (100 mg/kg, by gavage) from gestation day 12 to postnatal day 21, while C rats received the vehicle (corn oil). In adulthood (90 days old), the animals were euthanized. The serum and testicular testosterone levels were measured. Ventral prostate was removed and weighed. Distal segment fragments of the ventral prostate were fixed and processed for histochemistry and immunohistochemistry to detect androgen receptor (AR) and Ki67 antigens. Protein extraction from ventral prostate fragments was performed for AR immunoblotting and Gelatin zymography for MMP-2 and MMP-9 (MMP, metalloproteinase). Stereological and histopathological analyses were also performed. Serum and testicular testosterone levels and prostate weight were comparable between groups. In the T group the relative proportions (%) of epithelial (C=32.86; T=42.04*) and stromal (C=21.61; T=27.88*) compartments were increased, while the luminal compartment was decreased (C=45.54; T=30.08*), *p < 0.05. In T, disseminated inflammatory infiltrate in the stroma, associated or not with epithelial dysplasia and PIN (Prostatic Intraepithelial Neoplasia), was observed. Increases in AR expression, proliferation index and metalloproteinase 9 (MMP-9) activity were noted in T animals. In some T animals, collagen fibrils accumulated adjacent to the epithelium. As far as we are aware, this is the first report in the literature showing that phthalates could play a role in proliferative and inflammatory disorders of the rat prostate. (C) 2009 Elsevier Ireland Ltd. All rights reserved.State of Sao Paulo Research Foundation (FAPESP)[2006/59783-0