Browsing by Subject "Prostate"
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- PublicationOpen AccessA role of junction-mediated interactions in cells of the male reproductive tract: Impact of prenatal, neonatal, and prepubertal exposure to anti-androgens on adult reproduction(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Hejmej, Anna; Bilinska, BarbaraMale sexual development and male reproductive functions are dependent on the normal action of androgens, and an unbalanced ratio of the active androgens can lead to varying degrees of structural and functional abnormalities within the reproductive organs. Endocrine balance can be disturbed by environmental and pharmaceutical anti-androgens (i.e. vinclozolin, phthalates, procymidone, and flutamide) that antagonize normal androgen action. Such chemical compounds enter the cell, bind to the receptor and inactivate transcription leading to disruption of androgen-mediated signaling. Assembling and functioning of cell junctions in hormone-dependent tissues, such as testis, epididymis and prostate appeared to be controlled by steroid hormones, predominantly by androgens. This review presents recent findings on the tight junction proteins mainly responsible for normal functioning of the barrier within the testis, epididymis and prostate, anchoring junction proteins that play a crucial role in normal cell-cell adhesion, and gap junction proteins through which intercellular communication takes place in the male reproductive tract. The review gives examples of animal models that are used in endocrine disruption studies with a focus on the author’s own data from studies in the pig.
- PublicationOpen AccessHistochemical study of apoptotic epithelial cells depending on testosterone in primary cultured rat prostatic tissues(Murcia : F. Hernández, 2000) Furuya, T.; Kubo, M.; Ueno, A.; Fuji, Y.; Baba, T.; Ohno, S.To clarify whether apoptosis can be induced in cultured rat prostatic epithelial cells, they were investigated at various time points, depending on different concentrations of testosterone. Ventral lobes of rat prostates were cultured as small pieces of tissues up to 14 days. They were examined by anti-Fas antibody immunostaining and also compared to findings revealed by in situ end-labelling (ISEL) technique. To clarify apoptotic nuclei at high resolution, the quick-freezing and deep-etching (QF-DE) method was also used, as reported before. The localization and appearance of Faspositive cells were detected more widely and earlier than those of ISEL-positive cells, but both label-positive localizations were closely related to each other. In addition, they were detected more often in epithelial cells cultured with low testosterone concentrations. By the QF-DE method, chromatin fibers were found to be broken in spotty parts of apoptotic nuclei. We could control the concentration of testosterone in culture medium and detect the appearance of Fas antigen in cultured prostatic epithelial cells, followed by apoptotic changes. So, Fas and Fas-ligand system is one candidate for apoptosis in the prostate glands, depending on removal of hormonal testosterone.
- PublicationOpen AccessHistopathological changes induced by therapies in the benign prostate and prostate adenocarcinoma(Murcia : F. Hernández, 2007) Petraki, C.; Sfikas, C.P.The effect of androgen deprivation and other hormonal therapies, radiation therapy, thermal ablation therapies, chemotherapy, and other systemic treatments is evident in the histology of non-neoplastic and neoplastic human prostate gland. Androgen deprivation may be achieved with: a. orchidectomy, b. exogenous oestrogen administration, c. drugs with the capacity to deplete the hypothalamus of luteinizing hormonereleasing hormone, d. antiandrogens administration: drugs, which block the conversion of testosterone to its active form of 5-alpha dihydrotestosterone (i.e. finasteride, dutasteride), and drugs which block the androgen receptor on individual cells (i.e. flutamide). Androgen deprivation therapies cause atrophy of nonneoplastic and neoplastic prostatic epithelium, as the result of apoptosis, and are mainly used as a palliative measure in metastatic prostate cancer or as neoadjuvant or adjuvant treatment, in clinically localized prostate cancer. Morphological tumour regression may complicate the recognition and grading of treated carcinomas in radical prostatectomy specimens. Radiation therapy may be applied in the form of external beam, interstitial implantation (brachytherapy), or a combination, as a mainstay or adjuvant (external beam) treatment in localized prostate cancer. The primary effect is the damage of endothelial cells, which cause ischemia that leads to atrophy. The difficulty of post-radiation prostate needle biopsy interpretation includes the distinction of treatment effect in normal prostatic tissue from recurrent or residual tumour. Histological changes after thermal ablation mainly include lesions observed in prostatic infarcts due to periurethral coagulative type necrosis of variable volume. The correlation between the histopathological effects of the above therapies and their clinical significance is not absolutely clear.
- PublicationOpen AccessImmunoexpression of gelatinase (MMP-2 and MMP-9) in the seminal vesicles and ventral prostate of Libyan jird (Meriones libycus) during the seasonal cycle of reproduction(Murcia : F. Hernández, 2010) Belhocine, M.; Gernigon-Spychalowicz, T.; Jacob, M.P.; Benazzoug, Y.; Exbrayat, Jean MarieAn immunohistochemical study of matrix metalloproteinases (MMP-2 and MMP-9) or gelatinase (gelatinase A and gelatinase B) was performed on the seminal vesicles and ventral prostate of the Libyan jird (Meriones libycus) collected in the Beni-Abbes area during breeding period (spring and early summer), during resting phase (late summer, autumn, winter) and from castrated animals in the spring. The work was done using the indirect immunohistochemistry protocol by amplification with streptavidin-biotin-peroxidase and AEC as chromogen. In the seminal vesicles, during the breeding period, an important immunohistochemical signal of MMP-2 and MMP-9 was observed in epithelial cells and smooth muscle cells (SMC) without any immunoexpression in the extracellular matrix (ECM) and secretion. During resting phase and in thirty days castrated Meriones libycus, the MMP-2 and MMP-9 immunoexpression was weak in the epithelial cells and persisted with the same intensity in the SMC. The ECM, with no immunostaining in active season, showed a pronounced immunoresponse of both the two gelatinase. Three days after castration, the MMP-9 immunohistochemical reaction in epithelial cells and SMC was as intense as during active season. A prolonged castration of 50 and 90 days resulted in the maintenance of the MMP-9 immunostaining in epithelial cells and SMC and its disappearance from the ECM, suggesting a slow process of regression. During the breeding period, in the ventral prostate, MMP-2 immunostaining was more important in the SMC than in epithelial cells. The MMP-9 immunoexpression pattern was the opposite, the epithelial cells showed a higher immunoreaction than SMC. ECM and secretion lacked MMP-2 and MMP-9 immunostaining. The ventral prostate lumen contained a granular secretion without any gelatinase immunolabelling and was hollowed by empty circular forms reflecting the disappearance of the product in these areas. Part of the secretion showed a positive MMP-2 and MMP-9 immunoreaction. The latter was subsequently filled and seemed involved in the progression of the secretion in the tubules, preventing their filling. In resting phase and in animals castrated since thirty days, the immunoreactivity of both the two gelatinases was maintained in the epithelial cells and in the SMC, and was absent in the ECM. The gelatinases are involved in the seasonal reproductive cycle of Meriones libycus
- PublicationOpen AccessIsoforms of Na+, K+-ATPase in human prostate; specificity of expression and apical membrane polarization(Murcia : F. Hernández, 2001) Mobasheri, A.; Oukrif, D.; Dawodu, S.P.; Sinha, M.; Greenwell, P.; Stewart, D.; Djamgoz, M.B.A.; Foster, C.S.; Martín-Vasallo, P.; Mobasheri, R.The cellular distribution of Na+, K+-ATPase subunit isoforms was mapped in the secretory epithelium of the human prostate gland by immunostaining with antibodies to the a and B subunit isoforms of the enzyme. Immunolabeling of the a l , B1 and B2 isoforms was observed in the apical and lateral plasma membrane domains of prostatic epithelial cells in contrast to human kidney where the al and B1 isoforms of Na+, K+- ATPase were localized in the basolateral membrane of both proximal and dista1 convoluted tubules. Using immunohistochemistry and PCR we found no evidence of Na+, K+-ATPase a 2 and a 3 isoform expression suggesting that prostatic Na+, K+-ATPase consists of allí31 and allí32 isozymes. Our immunohistochemical findings are consistent with previously proposed models placing prostatic Na+, K+-ATPase in the apical plasma membrane domain. Abundant expression of Na+, K+- ATPase in epithelial cells lining tubulo-alveoli in the human prostate gland confirms previous conclusions drawn from biochemical, pharmacological and physiological data and provides further evidence for the critica1 role of this enzyme in prostatic cell physiology and ion homeostasis. Na+, K+-ATPase most likely maintains an inwardly directed Na+ gradient essential for nutrient uptake and active citrate secretion by prostatic epithelial cells. Na+, K+-ATPase may also regulate lumenal Na+ and K+, major counter-ions for citrate
- PublicationOpen Accesslntravesicular Fas localization in epithelial cells of castrated rat prostate glands(Murcia : F. Hernández, 2001) Serizawa, Y.; Ueda, H.; Baba, T.; Ueno, A.; Takeda, M.; Ohno, S.Androgenic steroids regulate the development and size of mammalian prostate epithelial cells. To evaluate the relationship between Fas-Fas ligand system and apoptosis in prostate epithelial cells of the castrated rats, we have examined immunocytochemical localization of Fas antigen in the castrated rat prostate glands at a series of different times. We used a rabbit polyclonal anti-Fas antibody with a streptavidinbiotin method and confocal laser scanning method or an immunogold method. Fas immunolocalization was exarnined in ventral lobes of prostate glands taken from intact or castrated adult male Wistar rats on day 1,2,3,4 and 5 by light or electron microscopy. At a light microscopic level, the castrated prostate epithelial cells showed mostly Fas immunolocalization in their apical parts of cytoplasm on day 2 after the castration. In addition, their extent of the Fas expression was expanded throughout the cytoplasm in proportion to the androgen ablation periods, and later the Fas expression was detected at luminar or basolateral sides of the epithelial cells. Both immunogold labeling with ultrathin sections and immunoperoxidase technique with cryostat sections demonstrated that Fas was localized mainly in secretory granules of the castrated prostate epithelial cells and some parts of their cell membranes at later stages. Our immunocytochemical findings showed that Fas expression was time-dependently induced in most of the prostatic epithelial cells after castration of rats. The rate of Fas-expressing epithelial cells was too high and inconsistent with the previously reported rate of TUNEL-positive ones. The membrane-associated Fas may have little effect on the apoptosis in the present case, bacause a lot of soluble Fas was secreted from the prostatic epithelial cells. A further study is needed to clarify some significance of the secretory Fas in the prostatic epithelium after the rat castration.
- PublicationOpen AccessModified gleason grading. An updated review(Murcia : F. Hernández, 2009) Helpap, Burkhard; Egevad, LarsAt an ISUP (International Society of Urological Pathology) consensus conference in 2005 in San Antonio, Texas, the old Gleason grading system for prostatic carcinoma from 1966 underwent its first major revision. With this modified Grading system a shift of the most frequent Gleason scores from 6 to 7a (3+4) in biopsy specimens and an increased degree of agreement between specimens of biopsies and radical prostatectomies with carcinoma of the prostate could be demonstrated. After modified grading of GS 3+4=7a tumours 95% were stage pT2, while 79% of GS 4+3=7b tumours were stage pT3-4. In cases with PSA <10ng/ml and tumour extent <20% the most frequent Gleason scores were 6 and 7a. Cases with serum PSA >10ng/ml or tumour extent >20% had higher scores (7b or higher). Cancers with tumour infiltration of <1mm in one of 12 cores and PSA <10ng/ml were mainly low grade (Gleason scores 6 and 7a) and may correspond to so called insignificant carcinoma of the prostate. Conclusion: With the modified Gleason At an ISUP (International Society of Urological Pathology) consensus conference in 2005 in San Antonio, Texas, the old Gleason grading system for prostatic carcinoma from 1966 underwent its first major revision. With this modified Grading system a shift of the most frequent Gleason scores from 6 to 7a (3+4) in biopsy specimens and an increased degree of agreement between specimens of biopsies and radical prostatectomies with carcinoma of the prostate could be demonstrated. After modified grading of GS 3+4=7a tumours 95% were stage pT2, while 79% of GS 4+3=7b tumours were stage pT3-4. In cases with PSA <10ng/ml and tumour extent <20% the most frequent Gleason scores were 6 and 7a. Cases with serum PSA >10ng/ml or tumour extent >20% had higher scores (7b or higher). Cancers with tumour infiltration of <1mm in one of 12 cores and PSA <10ng/ml were mainly low grade (Gleason scores 6 and 7a) and may correspond to so called insignificant carcinoma of the prostate. Conclusion: With the modified Gleason system, grade, stage, tumour extent and serum PSA show good correlations and characterize the difference between low and high grade malignancy of prostate carcinoma.
- PublicationOpen AccessPolyglucosan bodies in the prostatic stromal smooth muscles of aged dogs(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Kamiya, Shinji; Yoshimura, Hisashi; Okada, Keina; Yoshida, Ayaka; Fukuda, Yuki; Yamamoto, Masami; Soeta, Satoshi; Takahashi, KimimasaPolyglucosan bodies (PGB) in the prostate of aged dogs without neurological signs were examined by light microscopy, histochemistry and immunohistochemistry. Prostatic PGB were round or oval and slightly basophilic. Most of the bodies were situated within the stromal smooth muscle cells. PGB were intensely positive for PAS, Best’s carmine, Lugol’s iodine and Grocott’s methenamine silver method. Moreover, canine prostatic PGB were immunoreactive for monoclonal antibodies raised against human polyglucosan. The frequency of PGB in the smooth muscle cells was significantly correlated with the age of dogs. The occurrence of PGB in the canine prostate might be a non-specific finding related to ageing.
- PublicationOpen AccessProstate stem cells and cancer(Murcia : F. Hernández, 2007) Nikitin, Alexander Y.; Matoso, A.; Roy-Burman, P.Properties shared by neoplastic and stem cells indicate a possibility that somatic stem cells or transit-amplifying cells that have reacquired stem cell properties, particularly the ability for self-renewal, represent favorable targets for malignant transformation. In this review we discuss significance of the stem cell model for understanding prostate cancer pathogenesis and describe relevant studies in animals. It is proposed that dissemination of rare cancer stem cells may lead to metastatic disease and that resistance of such cells to multiple drugs and androgen ablation make them responsible for failure of current treatments. Thus further understanding of the cancer stem cell biology is needed for development of efficient rationally designed therapy permitting better targeting and better treatment outcomes for patients with prostate neoplasms
- PublicationOpen AccessProstatic sequestration of Cryptococcus neoformans in immunocompromised persons treated for cryptococcal meningoencephalitis(Murcia : F. Hernández, 1994) Ndimbie, O.K.; Dekker, A.; Martinez, A.J.; Dixon, B.We report a case of a patient with acquired immune deficiency syndrome who was successfully treated for cryptococcal meningoencephalitis with amphotericin B and 5-flucytosine. He died from other sequelae of acquired immune deficiency syndrome two years later. An autopsy revealed prominent cryptococcal prostatitis. Cryptococci were neither found in the central nervous system nor in other anatomic sites. The autopsy files yielded seven other cases of men with a history of cryptococcal meningoencephalitis. The possibility that the prostate sequesters Cryptococcus neoformans thereby contributing to systemic relapse is explored. To qualify as a sequestration, cyptococci must be cultured from the prostate, or from a midstream voided specimen after prostatic massage, and the prostate must be the only focus of infection.
- PublicationOpen AccessThe influence of water pH on the genesis of cadmium-induced cancer in a rat model(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Nai, Gisele Alborghetti; Golghetto, Gisele Maria Soria; Estrella, Mariani Paulino Soriano; Teixeira, Larissa Di Santi; Moura, Felipe do Carmo; Bremer Neto, Hermann; Pariz, José Luiz SantosCadmium is a heavy metal that is widely used in industry and can cause tumours in multiple organs. The purpose of our study was to investigate the effect of water pH in the genesis of cadmium-induced cancer. We divided 98 male Wistar rats into 7 groups: group A - 15 rats that received cadmium chloride (CdCl 2 – 400 mg/L) in their drinking water at a neutral pH of 7.0; group B - 15 rats that received CdCl 2 (400 mg/L) in their drinking water at an acidic pH of 5.0; group C - 15 rats that received CdCl 2 (400 mg/L) in their drinking water at a basic pH of 8.0; group D - 15 rats that received water at an acidic pH of 5.0; group E - 15 rats that received water at a basic pH of 8.0; group F - 15 rats that received water at a neutral pH of 7.0; and group G - 8 rats that were subcutaneously injected with a single dose of cyclophosphamide (50 mg/kg). Groups A through F were euthanised 6 months after the start of the experiment and group G was euthanised 24 hours after cyclophosphamide injection. We collected the liver, kidneys, pancreas, prostate, seminal vesicles and testes for histopathological analysis and the bone marrow for micronuclei testing. In all of the groups, neither neoplastic lesions nor an increase in micronuclei (p>0.05) were observed in the liver, kidney, pancreas, seminal vesicles and testes. We found that animals exposed to cadmium had grade one prostatic intraepithelial neoplasia, but this was found more frequently in animals from group B (p<0.05). The acidic pH increased the formation of pre-neoplastic lesions in the prostate glands of cadmium-exposed animals.
- PublicationOpen AccessTranscription regulators are transiently expressed during the prostate gland adaptation to the hypoandrogenic environment(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Nishan, Umar; Rosa Ribeiro, Rafaela; Lenz Cesar, Carlos; Carvalho, Hernandes F.The high incidence of prostatic diseases, including malignant tumors, makes the understanding of prostate biology very important. Androgen deprivation, blockade by orchiectomy, or chemical castration causes prostate and tumor shrinkage. The gene networks involved in a cell type-specific fashion are rather unknown. This work was undertaken to identify genes with annotated function in transcription regulation that might define transitions in gene expression. A total of 15 potential regulatory genes were identified. Validation by qRT-PCR showed that Zfp703 and Arid1a exhibit expression maxima at day 1; Ash2l, Nelf, Pbx3, Eya2 at day 4; Dmrt2 at day 5 and Lbh and Sox1 at day 7 after castration. Using immunohistochemistry, we further determined that PBX3 was found in both stromal and epithelial cells, whereas ARID1A and NELF were restricted to the epithelium, and DMRT2 and EYA2 were exclusively found in the stroma. Though the proteins ZFP703 and ASH2l were not found in any experimental condition, their mRNAs were located by in situ hybridization in both epithelium and stroma. In conclusion, androgen deprivation triggers the expression of temporally regulated gene sets in both epithelial and stromal cells. These gene subsets will help establish the regulatory gene expression programs orchestrating the castration-induced remodeling of the prostate gland, and represent putative targets to increase the efficacy of androgen-deprivation to induce epithelial (and cancer) cell death.