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https://www.readbyqxmd.com/read/29156833/targeting-aggressive-prostate-cancer-associated-cd44v6-using-phage-display-selected-peptides
#1
Ying Peng, Austin R Prater, Susan L Deutscher
There is a crucial need to identify new biomarkers associated with aggressive prostate cancer (PCa) including those associated with cancer stem cells (CSCs). CD44v6, generated by alternative splicing of CD44, has been proposed as a CSC biomarker due to its correlation with aggressive PCa disease. We hypothesized that phage display selected peptides that target CD44v6 may serve as theranostic agents for aggressive PCa. Here, a 15 amino acid peptide ("PFT") was identified by affinity selection against a peptide derived from the v6 region of CD44v6...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156807/halofuginone-inhibits-tgf-%C3%AE-bmp-signaling-and-in-combination-with-zoledronic-acid-enhances-inhibition-of-breast-cancer-bone-metastasis
#2
Patricia Juárez, Pierrick G J Fournier, Khalid S Mohammad, Ryan C McKenna, Holly W Davis, Xiang H Peng, Maria Niewolna, Alain Mauviel, John M Chirgwin, Theresa A Guise
More efficient therapies that target multiple molecular mechanisms are needed for the treatment of incurable bone metastases. Halofuginone is a plant alkaloid-derivative with antiangiogenic and antiproliferative effects. Here we demonstrate that halofuginone is an effective therapy for the treatment of bone metastases, through multiple actions that include inhibition of TGFβ and BMP-signaling. Halofuginone blocked TGF-β-signaling in MDA-MB-231 and PC3 cells showed by inhibition of TGF-β-induced Smad-reporter, phosphorylation of Smad-proteins, and expression of TGF-β-regulated metastatic genes...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156794/salen-mn-compounds-induces-cell-apoptosis-in-human-prostate-cancer-cells-through-promoting-ampk-activity-and-cell-autophagy
#3
Xiaoshuang Tang, Jing Jia, Feng Li, Wei Liu, Chao Yang, Bin Jin, Qi Shi, Xinyang Wang, Dalin He, Peng Guo
Currently only docetaxel has been approved to be used in the chemotherapy of prostate cancer and new drugs are urgent need. Salen-Mn is a novel type of synthetic reagent bionic and exerts remarkable anticancer activities. However, the effect of Salen-Mn on human prostate cancer has not been elucidated yet. In this study, we found that treatment of PC-3 and DU145 human prostate cancer cells with Salen-Mn inhibited cell growth in dose and time dependent manner. Moreover, Salen-Mn induced cell apoptosis, and increased the expression of apoptotic proteins, such as cleaved caspase-3, cleaved PARP, and Bax, in PC-3 and DU145 prostate cancer cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156772/stat3-and-stat5a-are-potential-therapeutic-targets-in-castration-resistant-prostate-cancer
#4
Sambit K Mohanty, Kader Yagiz, Dinesh Pradhan, Daniel J Luthringer, Mahul B Amin, Serhan Alkan, Bekir Cinar
Mechanisms of castration-resistant prostate cancer (CRPC) are not well understood, thus hindering rational-based drug design. Activation of STAT3/5A, key components of the JAK/STAT pathway, is implicated in aggressive PC, yet their clinical relevance in CRPC remains elusive. Here, we evaluated the possible role of STAT3/5A in CRPC using immunological, quantitative mRNA expression profiling, and pharmacological methods. We observed a strong nuclear immunoreactivity for STAT3 and STAT5A in 93% (n=14/15) and 80% (n=12/15) of CRPC cases, respectively, compared with benign prostatic hyperplasia (BPH)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156765/network-directed-cis-mediator-analysis-of-normal-prostate-tissue-expression-profiles-reveals-downstream-regulatory-associations-of-prostate-cancer-susceptibility-loci
#5
Nicholas B Larson, Shannon K McDonnell, Zach Fogarty, Melissa C Larson, John Cheville, Shaun Riska, Saurabh Baheti, Alexandra M Weber, Asha A Nair, Liang Wang, Daniel O'Brien, Jaime Davila, Daniel J Schaid, Stephen N Thibodeau
Large-scale genome-wide association studies have identified multiple single-nucleotide polymorphisms associated with risk of prostate cancer. Many of these genetic variants are presumed to be regulatory in nature; however, follow-up expression quantitative trait loci (eQTL) association studies have to-date been restricted largely to cis-acting associations due to study limitations. While trans-eQTL scans suffer from high testing dimensionality, recent evidence indicates most trans-eQTL associations are mediated by cis-regulated genes, such as transcription factors...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156763/elas1-induces-apoptotic-death-in-adenocarcinoma-du145-and-squamous-cell-carcinoma-sas-cancer-cells-but-not-in-normal-kd-cells
#6
Toshihiro Uchihashi, Kaori Ota, Yusuke Yabuno, Shouichi Ohno, Kohshiro Fukushima, Yoko Naito, Mikihiko Kogo, Norikazu Yabuta, Hiroshi Nojima
We previously reported that an ELAS1 peptide containing 29 amino acids induces apoptotic death in U2OS human osteosarcoma cells following DNA double-strand break insults. Here, we show that ELAS1 also caused apoptosis in prostate adenocarcinoma DU145 cells and tongue squamous-cell carcinoma SAS cells. ELAS1 appears to be safe because it induced apoptosis only in cancer cells, not in normal KD cells. Because the effect of ELAS1 is dependent on increased stability of p53 and enhanced phosphorylation of p53-S46, we exogenously expressed wild-type p53 protein to fully promote ELAS1-mediated induction of apoptosis in SAS cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156750/somatic-mutations-in-cdh1-and-ctnnb1-in-primary-carcinomas-at-13-anatomic-sites
#7
Evan L Busch, Jason L Hornick, Renato Umeton, Adem Albayrak, Neal I Lindeman, Laura E MacConaill, Elizabeth P Garcia, Matthew Ducar, Timothy R Rebbeck
Metastases are involved in most cancer deaths. Evidence has suggested that cancer cell detachment from primary tumors might occur largely via the mechanism of epithelial-mesenchymal transition (EMT) activated by epigenetic events, but data addressing other possible triggers of detachment, particularly genetic mutations, have been limited. Using the Profile study of cancer genomics at Dana-Farber Cancer Institute, we examined somatic mutations in the EMT genes CDH1 in 5,106 primary carcinomas and CTNNB1 in 7,578 primary carcinomas across 13 anatomic sites: urinary bladder, breast, colon/rectum, endometrium, esophagus, kidney, lung, ovary, pancreas, prostate, skin (non-melanoma), stomach, and thyroid...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156749/high-uric-acid-ua-downregulates-bone-alkaline-phosphatase-balp-expression-through-inhibition-of-its-promoter-activity
#8
Zhi-Qi Wu, Xiao-Ting Chen, Yan-Yan Xu, Ming-Jie Tian, Hai-Yan Chen, Guo-Ping Zhou, Hua-Guo Xu
Bone metastases often occur in prostate cancers, lung cancers and breast cancers. Bone alkaline phosphatase (BALP) is one of the most commonly used serological markers for clinical evaluation of bone metabolism. Here, we reported that high concentrations of uric acid (UA) caused decrease of BALP levels and revealed that the effect of high concentrations of UA on the BALP expression was through inhibition of its promoter activity. Our results suggested physicians to think about serum UA status of patients with advanced cancer to avoid misdiagnosis when BALP was used to diagnose or assess the extent of bone metastases...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156692/increased-transcriptional-and-metabolic-capacity-for-lipid-metabolism-in-the-peripheral-zone-of-the-prostate-may-underpin-its-increased-susceptibility-to-cancer
#9
Omar Al Kadhi, Maria H Traka, Antonietta Melchini, Perla Troncoso-Rey, Wiktor Jurkowski, Marianne Defernez, Purnima Pachori, Robert D Mills, Richard Y Ball, Richard F Mithen
The human prostate gland comprises three distinct anatomical glandular zones, namely the peripheral, central and transitional zones. Although prostate cancer can arise throughout the prostate, it is more frequent in the peripheral zone. In contrast, hyperplasia occurs most frequently in the transitional zone. In this paper, we test the hypothesis that peripheral and transitional zones have distinct metabolic adaptations that may underlie their different inherent predispositions to cancer and hyperplasia. In order to do this, we undertook RNA sequencing and high-throughput metabolic analyses of non-cancerous tissue from the peripheral and transitional zones of patients undergoing prostatectomy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156689/implications-of-pi3k-akt-inhibition-on-rest-protein-stability-and-neuroendocrine-phenotype-acquisition-in-prostate-cancer-cells
#10
Ruiqui Chen, Yinan Li, Ralph Buttyan, Xuesen Dong
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that arises as a consequence of rigorous androgen receptor (AR) pathway inhibition (ARPI) therapies. While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown. Here, we report that PI3K/AKT inhibition alone reduces RE-1 silencing transcription factor (REST) protein expression and induces multiple NE markers in PCa cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156665/new-ideas-in-preventing-castration-resistant-prostate-cancer
#11
EDITORIAL
Yuan-Chin Tsai, Yen-Nien Liu
No abstract text is available yet for this article.
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156657/moderate-hypofractionation-for-prostate-cancer
#12
EDITORIAL
Stefano Arcangeli, Giorgio Arcangeli
No abstract text is available yet for this article.
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156615/clinical-significance-of-measuring-global-hydroxymethylation-of-white-blood-cell-dna-in-prostate-cancer-comparison-to-psa-in-a-pilot-exploratory-study
#13
Alin Grelus, Dragos V Nica, Imola Miklos, Valerica Belengeanu, Ioan Ioiart, Cristina Popescu
This is the first study investigating the clinical relevance of 5-hydroxymethylcytosine (5hmC) in genomic DNA from white blood cells (WBC) in the context of prostate cancer (PCa) and other prostate pathologies. Using an enzyme-linked immunosorbent assay, we identified significantly different distributions of patients with low and elevated 5hmC content in WBC DNA across controls and patients with prostate cancer (PCa), atypical small acinar proliferation (ASAP), and benign prostatic hyperplasia (BPH). The measured values were within the normal range for most PCa patients, while the latter category was predominant for ASAP...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156544/endogenous-sphingolipid-signaling-pathway-implicated-in-the-action-of-croton-membranaceus-on-the-prostate-gland-in-bph-patients
#14
George Awuku Asare, Yvonne Anang, Daniel K Afriyie, Brodrick Yeboah Amoah, Bernice Asiedu, Derek Doku, Hannah Serwah Ocansey, Nana Yaw Odei Danso, Prince Tekpor, Sarah Osam
Background: Croton membranaceus extract has apoptotic effects on BPH-1 cells. This study determined if the apoptotic effects were created through the ceramide pathway. Methods: The study was a follow-up to a previous observational study of 30 histologically confirmed patients with benign prostatic hyperplasia (BPH) who were on C. membranaceus ethanolic extract at 20 mg t.i.d orally for 3 mo. Thereafter, total and free prostate-specific antigen (PSA), lipid profile plus Apo lipoprotein A and B, ceramide/Sphingophospho-kinase 1 (SphK1) and 2 (SphK2), sphingosine lyase (SPL), the cytotoxic adducts of oxidative stress 4-hydroxy-2-nonenal (4HNE) and malondialdehyde (MDA), were determined...
November 18, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/29156407/ultrasensitive-detection-of-prostate-specific-antigen-by-electrochemical-aptasensor-using-enzyme-free-recycling-amplification-via-target-induced-catalytic-hairpin-assembly
#15
Juncai Zhao, Zhanfang Ma
Based on the target-induced catalytic hairpin assembly and bimetallic catalyst, the enzyme-free recycling amplification strategy for sensitive detection of prostate specific antigen (PSA) has been designed. The aptamer and its complementary DNA (C-apt) are modified on the magnetic particles. The aptamer-PSA binding event can release the C-apt that triggers the catalytic assembly between hairpin capture DNA and hairpin help DNA. Then the catalytic hairpin assembly leads to cyclic reuse the C-apt and the generation of many opened hairpin capture DNA, which can associate with the prepared Au/Pt-polymethylene blue (PMB) probes to yield electrochemical signal...
November 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29156299/outcomes-from-ovarian-cancer-screening-in-the-plco-trial-histologic-heterogeneity-impacts-detection-overdiagnosis-and-survival
#16
Sarah M Temkin, Eric A Miller, Goli Samimi, Christine D Berg, Paul Pinsky, Lori Minasian
AIM: A mortality benefit from screening for ovarian cancer has never been demonstrated. The aim of this study was to evaluate the screening outcomes for different histologic subtypes of ovarian cancers. METHODS: Women in the screening arm of the Prostate, Lung, Colorectal and Ovarian Screening Trial underwent CA-125 and transvaginal ultrasound annually for 3-5 years. We compared screening test characteristics (including overdiagnosis) and outcomes by tumour type (type II versus other) and study arm (screening versus usual care)...
November 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29156009/discovering-cancer-vulnerabilities-using-high-throughput-micro-rna-screening
#17
Iva Nikolic, Benjamin Elsworth, Eoin Dodson, Sunny Z Wu, Cathryn M Gould, Pieter Mestdagh, Glenn M Marshall, Lisa G Horvath, Kaylene J Simpson, Alexander Swarbrick
Micro-RNAs (miRNAs) are potent regulators of gene expression and cellular phenotype. Each miRNA has the potential to target hundreds of transcripts within the cell thus controlling fundamental cellular processes such as survival and proliferation. Here, we exploit this important feature of miRNA networks to discover vulnerabilities in cancer phenotype, and map miRNA-target relationships across different cancer types. More specifically, we report the results of a functional genomics screen of 1280 miRNA mimics and inhibitors in eight cancer cell lines, and its presentation in a sophisticated interactive data portal...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29155628/mr-imaging-guided-strategies-for-detection-of-prostate-cancer-in-biopsy-naive-men
#18
Mustafa Zafer Temiz
No abstract text is available yet for this article.
December 2017: Radiology
https://www.readbyqxmd.com/read/29155624/functional-and-targeted-lymph-node-imaging-in-prostate-cancer-current-status-and-future-challenges
#19
Harriet C Thoeny, Sebastiano Barbieri, Johannes M Froehlich, Baris Turkbey, Peter L Choyke
Patients with prostate cancer who have regional lymph node (LN) metastases face an increased risk of death from disease and are therefore treated aggressively. Surgical LN dissection is the established method of staging regional nodes; however, this invasive technique carries substantial morbidities and a noninvasive imaging method is needed to reduce or eliminate the need for extended pelvic LN dissections (ePLND). Conventional computed tomography and magnetic resonance (MR) imaging have proven insensitive and nonspecific because both use nodal size criteria, which is notoriously inaccurate...
December 2017: Radiology
https://www.readbyqxmd.com/read/29155498/global-impact-of-nephropathies
#20
REVIEW
Philip Kam-Tao Li, Terry King-Wing Ma
The global burden of chronic kidney disease (CKD) has increased substantially in recent years, partly attributed to the global epidemic of diabetes mellitus. In many countries including China, glomerulonephritis was the most common cause of end stage renal disease (ESRD). The mortality rate of dialysis patients can be as high as patients with colon, breast and prostate cancers. CKD has important socio-economic impact on the healthcare system and society. Increasing awareness and early detection of CKD cannot be overemphasized...
December 2017: Nephrology
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