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Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells

Vucic,V.; Isenovic,E.R.; Adzic,M.; Ruzdijic,S.; Radojcic,M.B.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2006 EN
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Gamma-irradiation (gamma-IR) is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of 60Co gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl)-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD), specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P < 0.001) antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control) to 49% (IR cells), with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner...

Histopathological characteristics of a novel knock-in mouse prostate cancer model

Wu,G.; Wang,D.; Wang,H.; Yuan,J.; Xuan,J.W.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2006 EN
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Prostate cancer is relatively unique to man. There is no naturally occurring prostate cancer in the mouse. Pre-clinical studies involve the establishment of a genetically engineered mouse prostate cancer model with features close to those of the human situation. A new knock-in mouse adenocarcinoma prostate (KIMAP) model was established, which showed close-to-human kinetics of tumor development. In order to determine if the similar kinetics is associated with heterogeneous tumor architecture similar to the human situation, we utilized a new mouse histological grading system (Gleason analogous grading system) similar to the Gleason human grading system and flow cytometry DNA analysis to measure and compare the adenocarcinoma of the KIMAP model with human prostate cancer. Sixty KIMAP prostate cancer samples from 60 mice were measured and compared with human prostate cancer. Flow cytometry DNA analysis was performed on malignant prostate tissues obtained from KIMAP models. Mice with prostate cancer from KIMAP models showed a 53.3% compound histological score rate, which was close to the human clinical average (50%) and showed a significant correlation with age (P = 0.001). Flow cytometry analyses demonstrated that most KIMAP tumor tissues were diploid...

Construction of a recombinant adenovirus co-expressing truncated human prostate-specific membrane antigen and mouse 4-1BBL genes and its effect on dendritic cells

Weng,Xiaodong; Kuang,Youlin; Liu,Xiuheng; Chen,Zhiyuan; Zhu,Hengcheng; Chen,Hui; Jiang,Botao; Shen,Hao
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2011 EN
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Our aim was to construct a recombinant adenovirus co-expressing truncated human prostate-specific membrane antigen (tPSMA) and mouse 4-1BBL genes and to determine its effect on dendritic cells (DCs) generated from bone marrow suspensions harvested from C57BL/6 mice for which the effect of 4-1BBL on DCs is not clear, especially during DCs processing tumor-associated antigen. Replication deficient adenovirus AdMaxTM Expression System was used to construct recombinant adenovirus Ad-tPSMA-internal ribosome entry site-mouse 4-1BBL (Ad-tPSMA-IRES-m4-1BBL) and Ad-enhanced green fluorescent protein. Day 7 proliferating DC aggregates generated from C57BL/6 mice were collected as immature DCs and further mature DCs were obtained by lipopolysaccharide activated immature DCs. After DCs were exposed to the recombinant adenovirus with 250 multiplicity of infection, the expression of tPSMA and m4-1BBL proteins were detected by Western blot, and the apoptosis and phenotype of DCs were analyzed by flow cytometry. Cytokines (IL-6 and IL-12) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Proliferation of T cells was detected by allogeneic mixed lymphocyte reactions. The tPSMA and m4-1BBL proteins were expressed correctly. The apoptosis rate of DCs transfected with Ad-tPSMA-IRES-m4-1BBL was 14.6%...

RNAi-mediated knockdown of pituitary tumor- transforming gene-1 (PTTG1) suppresses the proliferation and invasive potential of PC3 human prostate cancer cells

Huang,S.Q.; Liao,Q.J.; Wang,X.W.; Xin,D.Q.; Chen,S.X.; Wu,Q.J.; Ye,G.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/2012 EN
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Pituitary tumor-transforming gene-1 (PTTG1) is a proto-oncogene that promotes tumorigenesis and metastasis in numerous cell types and is overexpressed in a variety of human tumors. We have demonstrated that PTTG1 expression was up-regulated in both human prostate cancer specimens and prostate cancer cell lines. For a more direct assessment of the function of PTTG1 in prostate tumorigenesis, RNAi-mediated knockdown was used to selectively decrease PTTG1 expression in PC3 human prostate tumor cells. After three weeks of selection, colonies stably transfected with PTTG1-targeted RNAi (the knockdown PC3 cell line) or empty vector (the control PC3 cell line) were selected and expanded to investigate the role of PTTG1 expression in PC3 cell growth and invasion. Cell proliferation rate was significantly slower (28%) in the PTTG1 knockdown line after 6 days of growth as indicated by an MTT cell viability assay (P < 0.05). Similarly, a soft agar colony formation assay revealed significantly fewer (66.7%) PTTG1 knockdown PC3 cell colonies than control colonies after three weeks of growth. In addition, PTTG1 knockdown resulted in cell cycle arrest at G1 as indicated by fluorescence-activated cell sorting. The PTTG1 knockdown PC3 cell line also exhibited significantly reduced migration through Matrigel in a transwell assay of invasive potential...

Comparative antiproliferation of human prostate cancer cells by ethanolic extracts of two groups of Brazilian propolis

Moraes,Cleber Silveira; Daugsch,Andreas; Li,Hongzhen; Rhim,Johng Suk; Park,Yong Kun
Fonte: Sociedade Brasileira de Ciência e Tecnologia de Alimentos Publicador: Sociedade Brasileira de Ciência e Tecnologia de Alimentos
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2010 EN
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Two groups of propolis, group 12, which was collected in the southeastern Brazil and group 13, which was collected in the northeastern Brazil, were examined for antiproliferation of primary malignant tumor (RC-58T/h/SA#4)-derived human prostate cancer cells and human prostate epithelial cells. The strongest inhibition of RC-58T/h/SA#4 cells was observed in propolis group 13 extracts, whereas moderate growth inhibition was observed in human prostate epithelial cells in comparison with group 12. It can be said that the Brazilian propolis of group 13 contains important chemical ingredients.

Inorganic arsenic and human prostate cancer

Benbrahim-Tallaa,Lamia; Waalkes,Michael
Fonte: ABRASCO - Associação Brasileira de Saúde Coletiva Publicador: ABRASCO - Associação Brasileira de Saúde Coletiva
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2009 EN
Relevância na Pesquisa
57.44507%
We critically evaluated the etiologic role of inorganic arsenic in human prostate cancer. We assessed data from relevant epidemiologic studies concerning environmental inorganic arsenic exposure. Whole animal studies were evaluated as were in vitro model systems of inorganic arsenic carcinogenesis in the prostate. Multiple studies in humans reveal an association between environmental inorganic arsenic exposure and prostate cancer mortality or incidence. Many of these human studies provide clear evidence of a dose-response relationship. Relevant whole animal models showing a relationship between inorganic arsenic and prostate cancer are not available. However, cellular model systems indicate arsenic can induce malignant transformation of human prostate epithelial cells in vitro. Arsenic also appears to impact prostate cancer cell progression by precipitating events leading to androgen independence in vitro. Available evidence in human populations and human cells in vitro indicates that the prostate is a target for inorganic arsenic carcinogenesis. A role for this common environmental contaminant in human prostate cancer initiation and/or progression would be very important.

Establishment of Short-Term Primary Human Prostate Xenografts for the Study of Prostate Biology and Cancer

Presnell, Sharon C.; Werdin, Eric S.; Maygarden, Susan; Mohler, James L.; Smith, Gary J.
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /09/2001 EN
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Human tissue xenograft models are currently the only tool for conducting in vivo analyses of intact human tissue. The goal of the present study was to develop reliable methods for successful generation of short-term primary tissue xenografts from benign and tumor-derived human prostate tissue. Primary human prostate xenografts were established in athymic nu/nu mice from eight of eight benign and five of five prostate cancer tissues, collected from a total of 10 patients who underwent radical prostatectomy for the treatment of prostate cancer. An average of 13 xenografts was established per specimen. Two tissue specimens were cryopreserved for >1 month before successful generation of prostate xenografts. After 1 month in vivo, xenograft tissues were harvested and examined regarding: gross evidence of vascularization; tissue morphology; proliferation; apoptosis; and expression of androgen receptor, prostate-specific antigen, and high molecular weight cytokeratins specific for basal cells in the prostate. Direct comparison of the original tissue specimen and the 1-month xenografts revealed similar histology; similar apoptotic and proliferative fractions in most cases; and comparable expression levels and expression patterns of androgen receptor...

Evaluation of Tissue Metabolites with High Resolution Magic Angle Spinning MR Spectroscopy Human Prostate Samples After Three-Year Storage at −80 °C

Jordan, Kate W.; He, Wenlei; Halpern, Elkan F.; Wu, Chin-Lee; Cheng, Leo
Fonte: Libertas Academica Publicador: Libertas Academica
Tipo: Artigo de Revista Científica
EN_US
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Accurate interpretation and correlation of tissue spectroscopy with pathological conditions requires disease-specific tissue metabolite databases; however, specimens for research are often kept in frozen storage for various lengths of time. Whether such frozen storage results in alterations to the measured metabolites is a critical but largely unknown issue. In this study, human prostate tissues from specimens that had been stored at −80 °C for 32 months were analyzed with high resolution magic angle spinning (HRMAS) magnetic resonance (MR) spectroscopy, and compared with the initial measurements of the adjacent specimens from the same cases when snap frozen in the operation room and kept frozen for less than 24 hours. Results of the current study indicate that that the storage-induced metabolite alterations are below the limits that tissue MR spectroscopy can discriminate. Furthermore, quantitative pathology evaluations suggest the observed alterations in metabolite profiles measured from the adjacent specimens of the same prostates may be accounted for by tissue pathological heterogeneities and are not a result of storage conditions. Hence, these results indicate that long-term frozen storage of prostate specimens can be quantitatively analyzed by HRMAS MR spectroscopy without concerns regarding significant metabolic degradation or alteration.

SOXs in Human Prostate Cancer: Implication as Progression and Prognosis Factors

Zhong, Wei-de; Qin, Guo-qiang; Dai, Qi-shan; Han, Zhao-dong; Chen, Shan-ming; Ling, Xiao-hui; Fu, Xin; Chen, Jia-hong; Chen, Xi-bin; Lin, Zhuo-yuan; Deng, Ye-han; He, Hui-chan; Wu, Chin-Lee; Wu, Shulin; Cai, Chao
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
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Background: SOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa). Methods: The gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa. Results: The microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover...

Evidence for efficacy of new Hsp90 inhibitors revealed by ex vivo culture of human prostate tumors

Centenera, M.; Gillis, J.; Hanson, A.; Jindal, S.; Taylor, R.; Risbridger, G.; Sutherland, P.; Scher, H.; Raj, G.; Knudsen, K.; Yeadon, T.; Tilley, W.; Butler, L.
Fonte: Amer Assoc Cancer Research Publicador: Amer Assoc Cancer Research
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
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PURPOSE: Targeting Hsp90 has significant potential as a treatment for prostate cancer, but prototypical agents such as 17-allylamino-17 demethoxygeldanamycin (17-AAG) have been ineffective in clinical trials. Recently, a phase I study aimed at defining a biologically active dose reported the first response to an Hsp90 inhibitor in a patient with prostate cancer, which supports the development of new generation compounds for this disease. EXPERIMENTAL DESIGN: The biological actions of two new synthetic Hsp90 inhibitors, NVP-AUY922 and NVP-HSP990, were evaluated in the prostate cancer cell lines PC-3, LNCaP, and VCaP and in an ex vivo culture model of human prostate cancer. RESULTS: In cell lines, both NVP-AUY922 and NVP-HSP990 showed greater potency than 17-AAG with regard to modulation of Hsp90 client proteins, inhibition of proliferation, and induction of apoptotic cell death. In prostate tumors obtained from radical prostatectomy that were cultured ex vivo, treatment with 500 nmol/L of NVP-AUY922, NVP-HSP990, or 17-AAG caused equivalent target modulation, determined by the pharmacodynamic marker Hsp70, but only NVP-AUY922 and NVP-HSP990 showed antiproliferative and proapoptotic activity. CONCLUSIONS: This study provides some of the first evidence that new generation Hsp90 inhibitors are capable of achieving biologic responses in human prostate tumors...

Hedgehog signaling is active in human prostate cancer stroma and regulates proliferation and differentiation of adjacent epithelium

Wilkinson, S.; Furic, L.; Buchanan, G.; Larsson, O.; Pedersen, J.; Frydenberg, M.; Risbridger, G.; Taylor, R.
Fonte: Wiley-Liss Publicador: Wiley-Liss
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
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BACKGROUND: Contribution of stromal Hedgehog (Hh) signaling is evident in the prostate gland in mice, but needs translation to human tissues if Hh therapeutics are to be used effectively. Our goal was to determine if primary human prostate fibroblasts contain cilia, and respond to prostate Hh signaling. METHODS: Primary human prostate cancer-associated (CAFs), and adjacent non-malignant (NPFs) fibroblasts isolated from human tissue specimens were analyzed using immunofluorescence, real-time PCR, and available array data. Cell culture and tissue recombination were used to determine responsiveness of human fibroblasts to Hh pathway manipulation and the paracrine effects of stromal Hh signaling, respectively. RESULTS: Prostatic fibroblasts were capable of forming primary cilia, with the capacity for active Hh signaling as seen by Smo co-localization to the tip of the primary cilium. Expression of genes known to represent a signature of active Hh signaling in the prostate (especially Fgf5 and Igfbp6) were increased in CAFs compared to NPFs. The level of canonical Hh genes and prostate Hh signature genes were rarely synchronous; with lower doses of Purmorphamine/BMS-833923 regulating canonical transcription factors, and higher doses effecting prostate Hh signature genes. Grafts consisting of NPFs with constitutively active Hh signaling induced increased proliferation and dedifferentiation of adjacent non-malignant BPH-1 epithelial cells. CONCLUSIONS: These data show that human prostatic fibroblasts have the capacity for Hh signaling and manipulation. Increased expression of a signature of prostatic Hh genes in the prostate tumor microenvironment suggests a role in the epithelial transformations driving prostate cancer (PCa).; Sarah E. Wilkinson...

Isoforms of Na+, K+-ATPase in human prostate; specificity of expression and apical membrane polarization

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.
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
ENG
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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+...

Effects of the antiandrogen flutamide on the expression of protein kinase C isoenzymes in LNCaP and PC3 human prostate cancer cells

Montalvo Zenarruzabeitia, Leire; Carmena Sierra, María José; Bolaños, Oscar; Rodríguez Henche, Nieves; Sánchez Chapado, Manuel; Prieto Villapún, Juan Carlos
Fonte: Portland Press Publicador: Portland Press
Tipo: Artigo de Revista Científica Formato: application/pdf
ENG
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Flutamide is a nonsteroidal antiandrogen that is frequently used for total androgen blockage in the treatment of advanced prostate cancer. We investigated the effect of this antiandrogen on the expression of protein kinase C (PKC) isoenzymes (a, b1, e, f) that are involved in cell growth, apoptosis and neoplastic transformation. Androgen-dependent (LNCaP) and independent (PC3) human prostate cancer cells were cultured in a medium that contained fetal bovine serum (FBS) or charcoal-stripped serum (CSS) and treated with 10 lM flutamide. The expression of PKC isoenzymes and the androgen receptor (AR) were analyzed by Western blot and RT-PCR, respectively. Serum steroids differentially regulate the expression of PKC isoenzymes in LNCaP and PC3 cells. Flutamide up-regulated the expression of a, b1 and f, but not e, PKC isoenzymes in CSS-LNCaP cells. These results were not homogeneously reproduced in the presence of androgens. We observed an opposite effect of flutamide, compared to CSS, on PKCb1 isoform expression in CSS-LNCaP suggesting that this antiandrogen exerts an agonistic effect. In PC3 cells flutamide potentiated the expression of the four PKC isoenzymes in almost all conditions tested (FBS- and CSScultured cells). Such effect of flutamide in PC3 cells is independent of AR since no expression of AR was detected. These results provide new evidence on antagonistic/agonistic responses of prostate cancer cells to antiandrogen drugs that are widely used in therapy and show that flutamide can elicit responses in prostate cancer cells that do not express AR.

Autocrine regulation of human prostate carcinoma cell proliferation by somatostatin through the modulation of the SH2 domain containing protein tyrosine phosphatase (SHP)-1

Zapata, Pedro Darío; Ropero, Rosa María; Valencia Torralba, Ana Montserrat; Buscail, Louis; Lopez, José Ignacio; Martín Orozco, Rosa María; Prieto Villapún, Juan Carlos; Angulo, Javier; Susini, Christiane; López Ruiz, María del Pilar; Colás Escud
Fonte: Endocrine Society Publicador: Endocrine Society
Tipo: Artigo de Revista Científica Formato: application/pdf
ENG
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The present study was intended to gain additional information on the growth regulation of prostate by somatostatin (SRIF) and the intracellular events involved. The humanprostate adenocarcinoma cell lines PC-3 and LNCaP produce SRIF and express subtypes 2 and 5 of SRIF receptors. The secretion of SRIF is related to the proliferative status of these cells; an inverse relationship exists between cell proliferation and the amount of secreted SRIF. Moreover, the growth of PC-3 cells is inhibited by SRIF overexpression and increased by blockage of endogenous SRIF. Coincident with the increase in SRIF secretion, the activity and levels of theSH2domain containing protein tyrosine phosphatase (SHP)-1, present in PC-3 cells are augmented, but the effect can be partially prevented by neutralization of secreted endogenously SRIF. The activity of SHP-1 is also stimulated by the SRIF analog RC160. Overexpression of SHP-1 induces inhibition of PC-3 cell growth. SHP-1 is also present in normal prostate, benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and well differentiated adenocarcinoma. In contrast, no signal is detected in poorly differentiated prostate cancer. These findings demonstrate that SRIF inhibits PC-3 and LNCaP cell proliferation through an autocrine/paracrine SRIF loop. This effect could be mediated by activation of the tyrosine phosphatase SHP-1 detected in these cells as well as in human prostate and prostate cancer.; Fundación para la Investigación en Urología; Ministerio de Asuntos Exteriores

Ex vivo culture of human prostate tissue and drug development

Centenera, M.; Raj, G.; Knudsen, K.; Tilley, W.; Butler, L.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
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Although an array of new therapeutics exist for prostate cancer, the development of agents that can improve outcomes for men with prostate cancer remains inefficient, costly, and frustratingly slow. A major impediment to the clinical translation of research findings is the lack of preclinical models that can accurately predict the clinical efficacy of new drugs and, therefore, enable the selection of agents that are most suitable for clinical trials. An approach that is gaining popularity in the prostate cancer community is ex vivo culture of primary human tissues, which retains the native tissue architecture, hormone responsiveness, and cell-to-cell signalling of the tumour microenvironment in a dynamic and manipulable state. Ex vivo culture systems recapitulate the structural complexity and heterogeneity of human prostate cancers in a laboratory setting, making them an important adjunct to current cell-line-based and animal-based models. When incorporated into preclinical studies, ex vivo cultured tissues enable robust quantitative evaluation of clinically relevant end points representing drug efficacy, investigation of therapy resistance, and biomarker discovery. By providing new clinically relevant insights into prostate carcinogenesis...

Evaluating DNA damage response (DDR) activation in human prostate cancer

Delouya, Guila
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
EN
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57.511914%
Introduction: Au Canada, le cancer de la prostate est le cancer le plus fréquemment diagnostiqué chez les hommes et le plus mortel après les cancers du poumon et du côlon. Il y a place à optimiser le traitement du cancer de la prostate de manière à mettre en œuvre une médecine personnalisée qui s’adapte aux caractéristiques de la maladie de chaque patient de façon individuelle. Dans ce mémoire, nous avons évalué la réponse aux dommages de l’ADN (RDA) comme biomarqueur potentiel du cancer de la prostate. Les lésions potentiellement oncogènes de l'ADN déclenche une cascade de signalisation favorisant la réparation de l'ADN et l’activation des points de contrôle du cycle cellulaire pour préserver l’intégrité du génome. La RDA est un mécanisme central de suppression tumorale chez l’homme. La RDA joue un rôle important dans l’arrêt de la prolifération des cellules dont les génomes sont compromis, et donc, prévient la progression du cancer en agissant comme une barrière. Cette réponse cellulaire détermine également comment les cellules normales et cancéreuses réagissent aux agents utilisés pour endommager l'ADN lors du traitement du cancer comme la radiothérapie ou la chimiothérapie, en plus la présence d...

Secretion of prostatic specific antigen, proliferative activity and androgen response in epithelial–stromal co-cultures from human prostate carcinoma

Venegas, Karina; Contreras, Héctor; Huidobro, Christian; Sáenz, Leonardo; Castelló Vera, Enrique Alejandro
Fonte: Universidade do Chile Publicador: Universidade do Chile
Tipo: Artículo de revista
EN_US
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We investigate the proliferative activity, prostatic specific antigen (PSA) secretion, morphology and androgen response of human prostate tumour epithelial cells co-cultured with stromal cells in a bicameral system. Stromal and epithelial cells were isolated from prostate adenocarcinoma by enzyme digestion and cultured in defined media. Immunocytochemistry for prostate carcinoma tumour antigen (PCTA-1) was performed for culture purity evaluation. Also, the morphology of the epithelial cells in co-culture was evaluated by electron microscopy. PSA was determined by microparticle enzyme immunoassay (MEIA) automatized protocol and the proliferation was evaluated by a commercial spectrophotometric kit, based on formazan salt formation. Both cell cultures showed more than 90% of purity. The epithelial cell co-cultures showed marked membrane processes and cell interdigitations. The proliferative activity of the epithelial cells was increased in presence of stromal cells. Also, PSA secretion was significantly increased and maintained for at least 14 days, whereas the androgen response for PSA secretion was evidenced only in co-culture condition. Primary co-cultures of epithelial and stromal cells from human prostate carcinoma are able to maintain...

Label-free detection of human prostate-specific antigen (hPSA) using film bulk acoustic resonators (FBARs)

Zhao, Xiubo; Pan, Fang; Ashley, Gregory M.; Garc?a-Gancedo, Luis; Luo, Jikui; Flewitt, Andrew J.; Milne, William I.; Lu, Jian R.
Fonte: Elsevier Publicador: Elsevier
Tipo: Article; accepted version
EN
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This is the accepted manuscript version. The final published version of the article is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0925400513011052.; Label-free detection of cancer biomarkers using low cost biosensors has promising applications in clinical diagnostics. In this work, ZnO-based thin film bulk acoustic wave resonators (FBARs) with resonant frequency of ?1.5 GHz and mass sensitivity of 0.015 mg/m2 (1.5 ng/cm2) have been fabricated for their deployment as biosensors. Mouse monoclonal antibody, anti-human prostate-specific antigen (Anti-hPSA) has been used to bind human prostate-specific antigen (hPSA), a model cancer used in this study. Ellipsometry was used to characterize and optimise the antibody adsorption and antigen binding on gold surface. It was found that the best amount of antibody at the gold surface for effective antigen binding is around 1 mg/m2, above or below which resulted in the reduced antigen binding due to either the limited binding sites (below 1 mg/m2) or increased steric effect (above 1 mg/m2). The FBAR data were in good agreement with the data obtained from ellipsometry. Antigen binding experiments using FBAR sensors demonstrated that FBARs have the capability to precisely detect antigen binding...

Anticancer effects of daidzein, genistein and soy extracts on human prostate cancer cells

Dong, Xin
Fonte: University of Delaware Publicador: University of Delaware
Tipo: Tese de Doutorado
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Changqing Wu; Prostate cancer is one of the most common cancers in men. However, the incidence of clinical prostate cancer varies widely between ethnic populations and countries. Epidemiological studies have shown that higher intake of soy foods can lower risk of prostate cancer. Soy isoflavones, such as daidzein, genistein, and their sugar conjugates, daidzin and genistin, are considered to be major bioactive compounds in soy and provide chemoprotection of prostate cancer. The majority of studies to assess the anticancer efficacy of soy products for prostate cancer (PCa) have been performed using purified bioactive compounds such as daidzein and genistein at pharmacological concentrations for short periods using androgen independent PCa cells such as PC-3 or androgen sensitive PCa cells such as LNCaP. However, attention has been drawn to the safety of using high levels of soy isoflavones in humans and the limited effect of individual soy isoflavones and these studies cannot reflect the real effects that soy may induce through diets. Currently, little is known about the bioavailability of isoflavones from whole soy foods and their bioactivities after cooking and digestion. The objectives of this study include: 1) examine the antiproliferative and apoptotic effects of high-dose (25 to 200 μM) individual soy isoflavones...

Inorganic arsenic and human prostate cancer

Benbrahim-Tallaa,Lamia; Waalkes,Michael
Fonte: ABRASCO - Associação Brasileira de Saúde Coletiva Publicador: ABRASCO - Associação Brasileira de Saúde Coletiva
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2009 EN
Relevância na Pesquisa
57.44507%
We critically evaluated the etiologic role of inorganic arsenic in human prostate cancer. We assessed data from relevant epidemiologic studies concerning environmental inorganic arsenic exposure. Whole animal studies were evaluated as were in vitro model systems of inorganic arsenic carcinogenesis in the prostate. Multiple studies in humans reveal an association between environmental inorganic arsenic exposure and prostate cancer mortality or incidence. Many of these human studies provide clear evidence of a dose-response relationship. Relevant whole animal models showing a relationship between inorganic arsenic and prostate cancer are not available. However, cellular model systems indicate arsenic can induce malignant transformation of human prostate epithelial cells in vitro. Arsenic also appears to impact prostate cancer cell progression by precipitating events leading to androgen independence in vitro. Available evidence in human populations and human cells in vitro indicates that the prostate is a target for inorganic arsenic carcinogenesis. A role for this common environmental contaminant in human prostate cancer initiation and/or progression would be very important.