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Pten and prostate

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https://www.readbyqxmd.com/read/28915722/correction-a-novel-highly-potent-trivalent-tgf-%C3%AE-receptor-trap-inhibits-early-stage-tumorigenesis-and-tumor-cell-invasion-in-murine-pten-deficient-prostate-glands
#1
Tai Qin, Lindsey Barron, Lu Xia, Haojie Huang, Maria M Villarreal, John Zwaagstra, Cathy Collins, Junhua Yang, Christian Zwieb, Ravindra Kodali, Cynthia S Hinck, Sun Kyung Kim, Robert L Reddick, Chang Shu, Maureen D O'Connor-McCourt, Andrew P Hinck, Lu-Zhe Sun
[This corrects the article DOI: 10.18632/oncotarget.13343.].
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915623/inhibition-of-the-pi3k-akt-mtor-pathway-activates-autophagy-and-compensatory-ras-raf-mek-erk-signalling-in-prostate-cancer
#2
Dominika E Butler, Christopher Marlein, Hannah F Walker, Fiona M Frame, Vincent M Mann, Matthew S Simms, Barry R Davies, Anne T Collins, Norman J Maitland
The PI3K/AKT/mTOR pathway is frequently activated in advanced prostate cancer, due to loss of the tumour suppressor PTEN, and is an important axis for drug development. We have assessed the molecular and functional consequences of pathway blockade by inhibiting AKT and mTOR kinases either in combination or as individual drug treatments. In established prostate cancer cell lines, a decrease in cell viability and in phospho-biomarker expression was observed. Although apoptosis was not induced, a G1 growth arrest was observed in PTEN null LNCaP cells, but not in BPH1 or PC3 cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915599/copy-number-variations-of-circulating-cell-free-dna-in-urothelial-carcinoma-of-the-bladder-patients-treated-with-radical-cystectomy-a-prospective-study
#3
Armin Soave, Felix K-H Chun, Timo Hillebrand, Michael Rink, Lars Weisbach, Bettina Steinbach, Margit Fisch, Klaus Pantel, Heidi Schwarzenbach
The aim of the present study was to establish a rapid profiling method using multiplex ligation-dependent probe amplification (MLPA) and characterize copy number variations (CNV) in circulating, cell-free DNA (cfDNA) in 85 urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). MLPA was tested for the use of cfDNA extracted from serum and plasma by various commercial extraction kits. Eighteen probes served as reference to control denaturation, ligation and amplification efficiency...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903364/kif7-attenuates-prostate-tumor-growth-through-lkb1-mediated-akt-inhibition
#4
Kai Yau Wong, Jing Liu, Kwok Wah Chan
This study investigated kinesin family member 7 (KIF7) expression and function in prostate cancer (PCa). Our results showed that KIF7 was significantly downregulated in PCa, compared with normal, benign prostatic hyperplasia and prostate intraepithelial neoplasia tissues, partially through promoter hypermethylation. We further investigated the effects of KIF7 coiled coil (CC) domain and motor domain (MD) on PCa development in vitro and in vivo. Our results showed that KIF7-CC but not KIF7-MD significantly attenuated proliferation and colony formation, impeded migration and invasion, induced apoptosis and sensitized PCa cells to paclitaxel...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900498/correlation-between-erg-fusion-protein-and-androgen-receptor-expression-by-immunohistochemistry-in-prostate-possible-role-in-diagnosis-and-therapy
#5
Amir Hassan Navaei, Beatriz A Walter, Vanessa Moreno, Svetlana D Pack, Peter Pinto, Maria J Merino
Background: Recent discovery of gene rearrangements have brought a new look to the molecular pathogenesis of cancer. Gene fusions occur in nearly 60% of prostate adenocarcinoma, being the TMPRSS2-ERG one of the most common. Evidence supports the role of ERG fusion in tumorigenesis, progression and invasion via effecting pathways such as WNT, MYC, uPA, PI3K/AKT/PTEN, RAS/RAF/MAPF, NKX3.1, GST-pi and androgen receptor (AR) mediated signaling. Most of the ERG fusions involve 5'-partners androgen responsive. Therefore, we aimed to evaluate AR and ERG fusion protein expression on prostate tissue to find clinicopathological applications and possible role in therapy...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28889725/oncogene-mir-106a-promotes-proliferation-and-metastasis-of-prostate-cancer-cells-by-directly-targeting-pten-in-vivo-and-in-vitro
#6
Bo Luo, Na Kang, Yan Chen, Lihong Liu, Yongmei Zhang
BACKGROUD: Prostate cancer (PCa) is the second leading contributor to male malignancy-associated death in developed countries. The study aimed to evaluate the effects of miR-106a on prostate cancer cells and the underlying molecular mechanism. METHODS: The cell proliferation was detected using the MTT and colony formation, and cells migration and invasion were also analyzed. Luciferase reporter assay was carried out to explore the correlation between miR-106a and PTEN...
September 8, 2017: Minerva Medica
https://www.readbyqxmd.com/read/28881646/modeling-african-american-prostate-adenocarcinoma-by-inducing-defined-genetic-alterations-in-organoids
#7
Kenji Unno, Meejeon Roh, Young A Yoo, Yousef Al-Shraideh, Lu Wang, Larisa Nonn, Sarki A Abdulkadir
Genomic studies are rapidly identifying genetic alterations in human cancer, but functional validation of such alterations has been slow. Here, using human prostate cancer as a model, we have assessed the feasibility of engineering defined genetic alterations in well-known cancer driver genes to transform benign prostate epithelial organoids derived from African American men. Benign human prostate organoids were transduced with lentiviruses expressing MYC, shPTEN, shTP53 and AR, alone and in various combinations, to recapitulate prostate cancer development...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28875501/the-protein-kinase-c-super-family-member-pkn-is-regulated-by-mtor-and-influences-differentiation-during-prostate-cancer-progression
#8
Chun-Song Yang, Tiffany A Melhuish, Adam Spencer, Li Ni, Yi Hao, Kasey Jividen, Thurl E Harris, Chelsi Snow, Henry F Frierson, David Wotton, Bryce M Paschal
BACKGROUND: Phosphoinositide-3 (PI-3) kinase signaling has a pervasive role in cancer. One of the key effectors of PI-3 kinase signaling is AKT, a kinase that promotes growth and survival in a variety of cancers. Genetically engineered mouse models of prostate cancer have shown that AKT signaling is sufficient to induce prostatic epithelial neoplasia (PIN), but insufficient for progression to adenocarcinoma. This contrasts with the phenotype of mice with prostate-specific deletion of Pten, where excessive PI-3 kinase signaling induces both PIN and locally invasive carcinoma...
September 6, 2017: Prostate
https://www.readbyqxmd.com/read/28874658/liver-x-receptors-constrain-tumor-development-and-metastasis-dissemination-in-pten-deficient-prostate-cancer
#9
Anthony Alioui, Julie Dufour, Valerio Leoni, Anke Loregger, Martina Moeton, Luigi Iuliano, Chiara Zerbinati, Amandine Septier, Pierre Val, Allan Fouache, Vincenzo Russo, David H Volle, Jean-Marc A Lobaccaro, Noam Zelcer, Silvère Baron
Advanced prostate cancer (PCa) is a clinical challenge as no curative therapeutic is available. In this context, a better understanding of metastasis and resistance mechanisms in PCa is an important issue. As phosphatase and tensin homolog (PTEN) loss is the most common genetic lesion in such cancer, we investigate human data sets for mechanisms that can constrain cancer evolution in this setting. Here we report a liver X receptor (LXR) signature, which tightly correlates with PTEN loss, in PCa. Accordingly, the LXR pathway is deregulated in prostate carcinomas in Pten-null mice...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28868343/disentangling-pten-cooperating-tumor-suppressor-gene-networks-in-cancer
#10
Jorge de la Rosa, Julia Weber, Roland Rad, Allan Bradley, Juan Cadiñanos
We have recently performed a whole-body, genome-wide screen in mice using a single-copy inactivating transposon for the identification of Pten (phosphatase and tensin homolog)-cooperating tumor suppressor genes (TSGs). We identified known and putative TSGs in multiple cancer types and validated the functional and clinical relevance of several promising candidates for human prostate cancer.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28856634/the-anti-tumor-effect-of-pachymic-acid-on-osteosarcoma-cells-by-inducing-pten-and-caspase-3-7-dependent-apoptosis
#11
Huilong Wen, Zhong Wu, Huidong Hu, Yixiong Wu, Gang Yang, Jiajun Lu, Guang Yang, Gang Guo, Qirong Dong
Pachymic acid (PA) is a lanostane type triterpenoid isolated from Poria cocos, which possesses an anti-tumor effect in breast cancer, prostate cancer, lung cancer, and bladder cancer cells. In this study, we investigated the effect of PA on the growth and apoptosis of human immortalized cell line (HOS) and primary osteosarcoma cells by a Cell Counting Kit-8 (CCK-8) and Annexin V and propidium iodide (PI) staining, respectively. Western blot was used to measure the expression of cleaved Caspase 3, PTEN, and AKT, as well as the AKT phosphorylation...
August 30, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28842510/impact-of-therapy-on-genomics-and-transcriptomics-in-high-risk-prostate-cancer-treated-with-neoadjuvant-docetaxel-and-androgen-deprivation-therapy
#12
Himisha Beltran, Alexander W Wyatt, Edmund Chedgy, Adam Donoghue, Matti Annala, Evan Warner, Kevin Beja, Michael Sigouros, Fan Mo, Ladan Fazli, Colin C Collins, James A Eastham, Michael J Morris, Mary-Ellen Taplin, Andrea Sboner, Susan Halabi, Martin E Gleave
BACKGROUND: The combination of docetaxel chemotherapy and androgen deprivation therapy (ADT) has become a standard treatment for patients with metastatic prostate cancer. The recently accrued Phase III CALGB 90203 trial was designed to investigate the clinical effectiveness of this treatment approach earlier in the disease. Specimens from this trial offer a unique opportunity to interrogate the acute molecular response to docetaxel and ADT and identify predictive biomarkers. METHODS: We evaluated baseline clinical data, needle biopsies and radical prostatectomy (RP) specimens from 52 (of 788) patients enrolled on CALGB 90203 at one high volume center...
August 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28830008/up-regulation-of-biglycan-is-associated-with-poor-prognosis-and-pten-deletion-in-patients-with-prostate-cancer
#13
Frank Jacobsen, Juliane Kraft, Cornelia Schroeder, Claudia Hube-Magg, Martina Kluth, Dagmar S Lang, Ronald Simon, Guido Sauter, Jakob R Izbicki, Till S Clauditz, Andreas M Luebke, Andrea Hinsch, Waldemar Wilczak, Corinna Wittmer, Franziska Büscheck, Doris Höflmayer, Sarah Minner, Maria Christina Tsourlakis, Hartwig Huland, Markus Graefen, Lars Budäus, Imke Thederan, Georg Salomon, Thorsten Schlomm, Nathaniel Melling
Biglycan (BGN), a proteoglycan of the extracellular matrix, is included in mRNA signatures for prostate cancer aggressiveness. To understand the impact of BGN on prognosis and its relationship to molecularly defined subsets, we analyzed BGN expression by immunohistochemistry on a tissue microarray containing 12,427 prostate cancers. Seventy-eight percent of 11,050 interpretable cancers showed BGN expression, which was considered as low intensity in 47.7% and as high intensity in 31.1% of cancers. BGN protein expression rose with increasing pathological tumor stage, Gleason grade, lymph node metastasis and early PSA recurrence (P<...
August 19, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28827140/in-vivo-expression-of-mir-32-induces-proliferation-in-prostate-epithelium
#14
Leena Latonen, Mauro Scaravilli, Andrew Gillen, Samuli Hartikainen, Fu-Ping Zhang, Pekka Ruusuvuori, Paula Kujala, Matti Poutanen, Tapio Visakorpi
Micro RNAs (miRNAs) are important regulators of gene expression and often deregulated in cancer. We have previously shown that miR-32 is an androgen receptor-regulated miRNA overexpressed in castration resistant prostate cancer, and that miR-32 can improve prostate cancer cell growth in vitro. To assess effects of miR-32 in vivo, we developed transgenic mice overexpressing miR-32 in the prostate. The study indicated that transgenic miR-32 expression increases replicative activity in the prostate epithelium...
August 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28822038/translocator-protein-pet-imaging-in-a-preclinical-prostate-cancer-model
#15
Mohammed N Tantawy, H Charles Manning, Todd E Peterson, Daniel C Colvin, John C Gore, Wenfu Lu, Zhenbang Chen, C Chad Quarles
PURPOSE: The identification and targeting of biomarkers specific to prostate cancer (PCa) could improve its detection. Given the high expression of translocator protein (TSPO) in PCa, we investigated the use of [(18)F]VUIIS1008 (a novel TSPO-targeting radioligand) coupled with positron emission tomography (PET) to identify PCa in mice and to characterize their TSPO uptake. PROCEDURES: Pten(pc-/-), Trp53(pc-/-) prostate cancer-bearing mice (n = 9, 4-6 months old) were imaged in a 7T MRI scanner for lesion localization...
August 18, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28816549/implications-of-bcl-2-and-its-interplay-with-other-molecules-and-signaling-pathways-in-prostate-cancer-progression
#16
REVIEW
Ju-Ha Kim, Hyemin Lee, Eun Ah Shin, Dong Hee Kim, Jhin Baek Choi, Sung-Hoon Kim
Among several genetic alterations involved in the progression of prostate cancer, B cell lymphoma gene number 2 (BCL-2) is an important target molecule in the progression of androgen-independent prostate cancer (AIPC) after androgen ablation or castration. Nevertheless, the molecular mechanism of BCL-2 in prostate cancer progression remains elusive and controversial. In the current review, we discuss the critical role of BCL-2 in the carcinogenesis of prostate cancer with experimental evidences on the BCL-2 molecular networks in AIPC and androgen-dependent prostate cancer (ADPC) and subsequently suggest perspective research targeting BCL-2...
September 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28814964/milk-disrupts-p53-and-dnmt1-the-guardians-of-the-genome-implications-for-acne-vulgaris-and-prostate-cancer
#17
Bodo C Melnik
There is accumulating evidence that milk shapes the postnatal metabolic environment of the newborn infant. Based on translational research, this perspective article provides a novel mechanistic link between milk intake and milk miRNA-regulated gene expression of the transcription factor p53 and DNA methyltransferase 1 (DNMT1), two guardians of the human genome, that control transcriptional activity, cell survival, and apoptosis. Major miRNAs of milk, especially miRNA-125b, directly target TP53 and complex p53-dependent gene regulatory networks...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28807943/chromatin-associated-protein-sin3b-prevents-prostate-cancer-progression-by-inducing-senescence
#18
Anthony J Bainor, Fang-Ming Deng, Yu Wang, Peng Lee, David J Cantor, Susan K Logan, Gregory David
Distinguishing between indolent and aggressive prostate adenocarcinoma (PCa) remains a priority to accurately identify patients who need therapeutic intervention. SIN3B has been implicated in the initiation of senescence in vitro Here we show that in a mouse model of prostate cancer, SIN3B provides a barrier to malignant progression. SIN3B was required for PTEN-induced cellular senescence and prevented progression to invasive PCa. Furthermore, SIN3B was downregulated in human PCa correlating with upregulation of its target genes...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28801478/phosphatases-and-solid-tumors-focus-on-glioblastoma-initiation-progression-and-recurrences
#19
REVIEW
Matthias Dedobbeleer, Estelle Willems, Stephen Freeman, Arnaud Lombard, Nicolas Goffart, Bernard Rogister
Phosphatases and cancer have been related for many years now, as these enzymes regulate key cellular functions, including cell survival, migration, differentiation and proliferation. Dysfunctions or mutations affecting these enzymes have been demonstrated to be key factors for oncogenesis. The aim of this review is to shed light on the role of four different phosphatases (PTEN, PP2A, CDC25 and DUSP1) in five different solid tumors (breast cancer, lung cancer, pancreatic cancer, prostate cancer and ovarian cancer), in order to better understand the most frequent and aggressive primary cancer of the central nervous system, glioblastoma...
August 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28798471/identification-of-competing-endogenous-rnas-of-the-tumor-suppressor-gene-pten-a-probabilistic-approach
#20
Kourosh Zarringhalam, Yvonne Tay, Prajna Kulkarni, Assaf C Bester, Pier Paolo Pandolfi, Rahul V Kulkarni
Regulation by microRNAs (miRNAs) and modulation of miRNA activity are critical components of diverse cellular processes. Recent research has shown that miRNA-based regulation of the tumor suppressor gene PTEN can be modulated by the expression of other miRNA targets acting as competing endogenous RNAs (ceRNAs). However, the key sequence-based features enabling a transcript to act as an effective ceRNA are not well understood and a quantitative model associating statistical significance to such features is currently lacking...
August 10, 2017: Scientific Reports
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