The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Norman J Maitland - One of the best experts on this subject based on the ideXlab platform.
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differential cytotoxic activity of a novel palladium based compound on Prostate Cell lines primary Prostate epithelial Cells and Prostate stem Cells
PLOS ONE, 2013Co-Authors: Engin Ulukaya, Michael J Stower, Fiona M Frame, Buse Cevatemre, Davide Pellacani, Hannah F Walker, Vincent M Mann, Matthew S Simms, Veysel T Yilmaz, Norman J MaitlandAbstract:The outcome for patients with advanced metastatic and recurrent Prostate cancer is still poor. Therefore, new chemotherapeutics are required, especially for killing cancer stem Cells that are thought to be responsible for disease recurrence. In this study, we screened the effect of a novel palladium-based anticancer agent (Pd complex) against six different Prostate cancer Cell lines, and primary cultures from seven Gleason 6/7 Prostate cancer, three Gleason 8/9 Prostate cancer and four benign Prostate hyperplasia patient samples, as well as cancer stem Cells selected from primary cultures. MTT and ATP viability assays were used to assess Cell growth and flow cytometry to assess Cell cycle status. In addition, immunofluorescence was used to detect γH2AX nuclear foci, indicative of DNA damage, and Western blotting to assess the induction of apoptosis and autophagy. The Pd complex showed a powerful growth-inhibitory effect against both Cell lines and primary cultures. More importantly, it successfully reduced the viability of cancer stem Cells as first reported in this study. The Pd complex induced DNA damage and differentially induced evidence of Cell death, as well as autophagy. In conclusion, this novel agent may be promising for use against the bulk of the tumour Cell population as well as the Prostate cancer stem Cells, which are thought to be responsible for the resistance of metastatic Prostate cancer to chemotherapy. This study also indicates that the combined use of the Pd complex with an autophagy modulator may be a more promising approach to treat Prostate cancer. In addition, the differential effects observed between Cell lines and primary Cells emphasise the importance of the model used to test novel drugs including its genetic background, and indeed the necessity of using Cells cultured from patient samples.
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human Prostate Cell lines from normal and tumourigenic epithelia differ in the pattern and control of choline lipid headgroups released into the medium on stimulation of protein kinase c
British Journal of Cancer, 2011Co-Authors: Martin G Rumsby, J Schmitt, Mike Sharrard, Greta Rodrigues, M Stower, Norman J MaitlandAbstract:Human Prostate Cell lines from normal and tumourigenic epithelia differ in the pattern and control of choline lipid headgroups released into the medium on stimulation of protein kinase C
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altered expression of neurotensin receptors is associated with the differentiation state of Prostate cancer
Cancer Research, 2010Co-Authors: Stephanie L Swift, Julie E Burns, Norman J MaitlandAbstract:In Prostate cancer, traditional treatments such as androgen response manipulation often provide only temporary resolution of disease, with emergence of a more aggressive, androgen-independent tumor following initial therapy. To treat recurrent disease, Cell surface proteins that are specifically overexpressed on malignant Cells may be useful for generating targeted therapeutics. Recent evidence suggests that neurotensin receptors (NTR) are recruited in advanced Prostate cancer as an alternative growth pathway in the absence of androgens. In this study, we assessed the potential use of these receptors as targets by analyzing NTR expression patterns in human Prostate Cell lines and primary Prostate tumor Cell cultures derived from patient samples. In primary tumor Cell cultures, NTR1 was upregulated in Cells with a basal phenotype (cytokeratin 1/5/10/14+), whereas NTR2 and NTR3 were upregulated in Cells with luminal phenotype (cytokeratin 18+). Similar patterns of NTR expression occurred in benign Prostate tissue sections, implicating differentiation state as a basis for the differences observed in tumor Cell lines. Our findings support the use of NTRs as tools for therapeutic targeting in Prostate cancers composed of both poorly differentiated and/or well-differentiated Cells. Cancer Res; 70(1); 347–56
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enhanced expression of vimentin in motile Prostate Cell lines and in poorly differentiated and metastatic Prostate carcinoma
The Prostate, 2002Co-Authors: Shona H Lang, Jeanmarie Villette, Catherine Hyde, Ian N Reid, Ian S Hitchcock, Claire A Hart, A Gordon A Bryden, Michael J Stower, Norman J MaitlandAbstract:BACKGROUND. The metastatic potential of a series of Prostate Cell lines was analysed bymeasuring motility and invasiveness, and further correlated to the expression of epithelialdifferentiation markers.METHODS. Invasion and motility were measured using in vitro assays. Immunohistochem-istry of Cell lines and tissues was used to identify expression of cytokeratins 8 and 1, 5, 10, 14,vimentin, Prostate specific antigen, Prostate specific membrane antigen, androgen receptor,desmoglein, E-cadherin, b1 integrin, CD44, hmet, vinculin and actin.RESULTS. Expressionofvimentinwastheonlymarkertocorrelatewithmotility, nomarkerscorrelated to invasion. Lower vimentin expression was observed in Cells with low motility(PNT2-C2) and high expression in Cells with high motility (P4E6, PNT1a, PC-3). Vimentinexpression was not detected in well differentiated tumours, moderately differentiated tumorscontained vimentin positive Cells (1/9 bone scan negative, 2/5 bone scan positive), but themajority of poorly differentiated cancers (4/11 bone scan negative, 9/14 bone scan positive)and bone metastases (7/8) had high vimentin expression in tumor Cells.CONCLUSIONS. Motile Prostate cancer Cell lines express vimentin. In tissue sections, thepresence of vimentin positive tumour Cells correlated positively to poorly differentiatedcancersandthepresenceofbonemetastases. Prostate52:253–263,2002.
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Prostate epithelial Cell lines form spheroids with evidence of glandular differentiation in three dimensional matrigel cultures
British Journal of Cancer, 2001Co-Authors: Shona H Lang, R M Sharrard, M Stark, Jeanmarie Villette, Norman J MaitlandAbstract:Normal (PNT2-C2) and metastatic (PC-3) Prostate Cell lines were grown in Matrigel to observe the effects on morphology and phenotype in comparison to monolayer culture. In monolayer cultures, PNT2-C2 showed typical round/cuboidal epithelial morphology, with tight Cell associations, whereas in Matrigel they formed smooth spheroids, tightly packed with Cells. In both monolayer and Matrigel, PNT2-C2 had a differentiated luminal epithelial phenotype with high expression of cytokeratin 8, Prostate specific antigen (PSA), Prostate specific membrane antigen (PSMA), E-cadherin and desmoglein. In contrast, PC-3 Cells possessed an epithelial/mesenchyme morphology in monolayer with loose Cell to Cell contact and pseudopodial extensions. Immunohistochemical phenotyping indicated the Cells were undifferentiated, expressing high levels of vimentin, β1 integrin, CD44 and low expression of cytokeratin 8. In Matrigel they formed smooth and irregular spheroids, which had a lumen surrounded by a single Cell layer. Matrigel also influenced the expression of PSA, PSMA and CD44. These results indicate that Matrigel culture can induce morphological differentiation of Prostate cancer Cells which initially had a basal phenotype. © 2001 CancerResearch Campaign http://www.bjcancer.com
Fioretta Palombi - One of the best experts on this subject based on the ideXlab platform.
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the adherent invasive escherichia coli strain lf82 invades and persists in human Prostate Cell line rwpe 1 activating a strong inflammatory response
Infection and Immunity, 2016Co-Authors: Maria Pia Conte, Marta Aleandri, Massimiliano Marazzato, Antonietta Lucia Conte, Cecilia Ambrosi, Mauro Nicoletti, Carlo Zagaglia, Guido Gambara, Fioretta PalombiAbstract:Adherent/invasive Escherichia coli (AIEC) strains have recently been receiving increased attention because they are more prevalent and persistent in the intestine of Crohn's disease (CD) patients than in healthy subjects. Since AIEC strains show a high percentage of similarity to extraintestinal pathogenic E. coli (ExPEC), neonatal meningitis-associated E. coli (NMEC), and uropathogenic E. coli (UPEC) strains, here we compared AIEC strain LF82 with a UPEC isolate (strain EC73) to assess whether LF82 would be able to infect Prostate Cells as an extraintestinal target. The virulence phenotypes of both strains were determined by using the RWPE-1 Prostate Cell line. The results obtained indicated that LF82 and EC73 are able to adhere to, invade, and survive within Prostate epithelial Cells. Invasion was confirmed by immunofluorescence and electron microscopy. Moreover, cytochalasin D and colchicine strongly inhibited bacterial uptake of both strains, indicating the involvement of actin microfilaments and microtubules in host Cell invasion. Moreover, both strains belong to phylogenetic group B2 and are strong biofilm producers. In silico analysis reveals that LF82 shares with UPEC strains several virulence factors: namely, type 1 pili, the group II capsule, the vacuolating autotransporter toxin, four iron uptake systems, and the pathogenic island (PAI). Furthermore, compared to EC73, LF82 induces in RWPE-1 Cells a marked increase of phosphorylation of mitogen-activated protein kinases (MAPKs) and of NF-κB already by 5 min postinfection, thus inducing a strong inflammatory response. Our in vitro data support the hypothesis that AIEC strains might play a role in prostatitis, and, by exploiting host-Cell signaling pathways controlling the innate immune response, likely facilitate bacterial multiplication and dissemination within the male genitourinary tract.
Guido Gambara - One of the best experts on this subject based on the ideXlab platform.
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the adherent invasive escherichia coli strain lf82 invades and persists in human Prostate Cell line rwpe 1 activating a strong inflammatory response
Infection and Immunity, 2016Co-Authors: Maria Pia Conte, Marta Aleandri, Massimiliano Marazzato, Antonietta Lucia Conte, Cecilia Ambrosi, Mauro Nicoletti, Carlo Zagaglia, Guido Gambara, Fioretta PalombiAbstract:Adherent/invasive Escherichia coli (AIEC) strains have recently been receiving increased attention because they are more prevalent and persistent in the intestine of Crohn's disease (CD) patients than in healthy subjects. Since AIEC strains show a high percentage of similarity to extraintestinal pathogenic E. coli (ExPEC), neonatal meningitis-associated E. coli (NMEC), and uropathogenic E. coli (UPEC) strains, here we compared AIEC strain LF82 with a UPEC isolate (strain EC73) to assess whether LF82 would be able to infect Prostate Cells as an extraintestinal target. The virulence phenotypes of both strains were determined by using the RWPE-1 Prostate Cell line. The results obtained indicated that LF82 and EC73 are able to adhere to, invade, and survive within Prostate epithelial Cells. Invasion was confirmed by immunofluorescence and electron microscopy. Moreover, cytochalasin D and colchicine strongly inhibited bacterial uptake of both strains, indicating the involvement of actin microfilaments and microtubules in host Cell invasion. Moreover, both strains belong to phylogenetic group B2 and are strong biofilm producers. In silico analysis reveals that LF82 shares with UPEC strains several virulence factors: namely, type 1 pili, the group II capsule, the vacuolating autotransporter toxin, four iron uptake systems, and the pathogenic island (PAI). Furthermore, compared to EC73, LF82 induces in RWPE-1 Cells a marked increase of phosphorylation of mitogen-activated protein kinases (MAPKs) and of NF-κB already by 5 min postinfection, thus inducing a strong inflammatory response. Our in vitro data support the hypothesis that AIEC strains might play a role in prostatitis, and, by exploiting host-Cell signaling pathways controlling the innate immune response, likely facilitate bacterial multiplication and dissemination within the male genitourinary tract.
Chawnshang Chang - One of the best experts on this subject based on the ideXlab platform.
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phosphorylation dependent ubiquitylation and degradation of androgen receptor by akt require mdm2 e3 ligase
The EMBO Journal, 2002Co-Authors: Hui Kuan Lin, Liang Wang, Saleh Altuwaijri, Chawnshang ChangAbstract:The androgen receptor (AR) controls several biological functions including Prostate Cell growth and apoptosis. However, the mechanism by which AR maintains its stability to function properly remains largely unknown. Here we show that Akt and Mdm2 form a complex with AR and promote phosphorylation-dependent AR ubiquitylation, resulting in AR degradation by the proteasome. The effect of Akt on AR ubiquitylation and degradation is markedly impaired in a Mdm2-null Cell line compared with the wild-type Cell line, suggesting that Mdm2 is involved in Akt-mediated AR ubiquitylation and degradation. Furthermore, we demonstrate that the E3 ligase activity of Mdm2 and phosphorylation of Mdm2 by Akt are essential for Mdm2 to affect AR ubiquitylation and degradation. These results suggest that phosphorylation-dependent AR ubiquitylation and degradation by Akt require the involvement of Mdm2 E3 ligase activity, a novel mechanism that provides insight into how AR is targeted for degradation.
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cloning and characterization of a specific coactivator ara70 for the androgen receptor in human Prostate Cells
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Shuyuan Yeh, Chawnshang ChangAbstract:The androgen receptor (AR) is a member of the steroid receptor superfamily that plays an important role in male sexual differentiation and Prostate Cell proliferation. Mutations or abnormal expression of AR in Prostate cancer can play a key role in the process that changes Prostate cancer from androgen-dependent to an androgen-independent stage. Using a yeast two-hybrid system, we were able to isolate a ligand-dependent AR-associated protein (ARA70), which functions as an activator to enhance AR transcriptional activity 10-fold in the presence of 10(-10) M dihydrotestosterone or 10(-9) M testosterone, but not 10(-6) M hydroxyflutamide in human Prostate cancer DU145 Cells. Our data further indicated that ARA70 Will only slightly induce the transcriptional activity of other steroid receptors such as estrogen receptor, glucocorticoid receptor, and progesterone receptor in DU145 Cells. Together, these data suggest that AR may need a specific coactivator(s) such as ARA70 for optimal androgen activity.
Anne Margrete Oyan - One of the best experts on this subject based on the ideXlab platform.
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epithelial to mesenchymal transition of a primary Prostate Cell line with switches of Cell adhesion modules but without malignant transformation
PLOS ONE, 2008Co-Authors: Xisong Ke, Yi Qu, Naomi Goldfinger, Kari Rostad, Randi Hovland, Lars A Akslen, Varda Rotter, Anne Margrete OyanAbstract:Background Epithelial to mesenchymal transition (EMT) has been connected with cancer progression in vivo and the generation of more aggressive cancer Cell lines in vitro. EMT has been induced in Prostate cancer Cell lines, but has previously not been shown in primary Prostate Cells. The role of EMT in malignant transformation has not been clarified. Methodology/Principal Findings In a transformation experiment when selecting for Cells with loss of contact inhibition, the immortalized Prostate primary epithelial Cell line, EP156T, was observed to undergo EMT accompanied by loss of contact inhibition after about 12 weeks in continuous culture. The changed new Cells were named EPT1. EMT of EPT1 was characterized by striking morphological changes and increased invasion and migration compared with the original EP156T Cells. Gene expression profiling showed extensively decreased epithelial markers and increased mesenchymal markers in EPT1 Cells, as well as pronounced switches of gene expression modules involved in Cell adhesion and attachment. Transformation assays showed that EPT1 Cells were sensitive to serum or growth factor withdrawal. Most importantly, EPT1 Cells were not able to grow in an anchorage-independent way in soft agar, which is considered a critical feature of malignant transformation. Conclusions/Significance This work for the first time established an EMT model from primary Prostate Cells. The results show that EMT can be activated as a coordinated gene expression program in association with early steps of transformation. The model allows a clearer identification of the molecular mechanisms of EMT and its potential role in malignant transformation.
