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https://www.readbyqxmd.com/read/29050279/ssecks-akap12-scaffolding-functions-suppress-b16f10-induced-peritoneal-metastasis-by-attenuating-cxcl9-10-secretion-by-resident-fibroblasts
#1
Masashi Muramatsu, Lingqiu Gao, Jennifer Peresie, Benjamin Balderman, Shin Akakura, Irwin H Gelman
SSeCKS/Gravin/AKAP12 (SSeCKS) is a kinase scaffolding protein known to suppress metastasis by attenuating tumor-intrinsic PKC- and Src-mediated signaling pathways [1]. In addition to downregulation in metastatic cells, in silico analyses identified SSeCKS downregulation in prostate or breast cancer-derived stroma, suggesting a microenvironmental cell role in controlling malignancy. Although orthotopic B16F10 and SM1WT1[Braf(V600E)] mouse melanoma tumors grew similarly in syngeneic WT or SSeCKS-null (KO) mice, KO hosts exhibited 5- to 10-fold higher levels of peritoneal metastasis, and this enhancement could be adoptively transferred by pre-injecting naïve WT mice with peritoneal fluid (PF), but not non-adherent peritoneal cells (PC), from naïve KO mice...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#2
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29038344/blocking-myristoylation-of-src-inhibits-its-kinase-activity-and-suppresses-prostate-cancer-progression
#3
Sungjin Kim, Omar Awad Alsaidan, Octavia Goodwin, Qianjin Li, Essilvo Sulejmani, Zhen Han, Aiping Bai, Thomas Albers, Zanna Beharry, Y George G Zheng, James S Norris, Zdzislaw M Szulc, Alicja Bielawska, Iryna Lebedyeva, Scott D Pegan, Houjian Cai
Protein N-myristoylation enables localization to membranes and helps maintain protein conformation and function. N-myristoyltransferases (NMT) catalyze co- or post-translational myristoylation of Src family kinases and other oncogenic proteins, thereby regulating their function. In this study, we provide genetic and pharmacological evidence that inhibiting the N-myristoyltransferase NMT1 suppresses cell cycle progression, proliferation and malignant growth of prostate cancer cells. Loss of myristoylation abolished the tumorigenic potential of Src and its synergy with androgen receptor in mediating tumor invasion...
October 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/29025989/low-level-endogenous-prostate-specific-membrane-antigen-psma-expression-in-non-prostatic-tumor-xenografts-is-sufficient-for-in-vivo-tumor-targeting-and-imaging
#4
Sridhar Nimmagadda, Mrudula Pullambhatla, Ying Chen, Princy Parsana, Ala Lisok, Samit Chatterjee, Ronnie Mease, Steven P Rowe, Shawn E Lupold, Kenneth J Pienta, Martin G Pomper
Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and within the neovasculature of other solid tumors. The non-prostatic expression of PSMA has been reported exclusively within the neovasculature endothelial cells of non-prostate cancers, however, there are few reports on PSMA expression on epithelial cells. Herein we describe PSMA expression in non-prostatic epithelial cells and characterize the potential of PSMA-binding agents to non-invasively detect that expression. METHODS: PSMA expression data was extracted from publicly available genomic databases...
October 12, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28977599/inhibition-of-androgen-receptor-function-and-level-in-castration-resistant-prostate-cancer-cells-by-2-isoxazol-4-ylmethyl-thio-1-4-phenylpiperazin-1-yl-ethanone
#5
Khalid Z Masoodi, Kurtis Eisermann, Zhenyu Yang, Javid A Dar, Laura E Pascal, Minh Nguyen, Katherine O'Malley, Erica Parrinello, Firuz G Feturi, Alex N Kenefake, Joel B Nelson, Paul A Johnston, Peter Wipf, Zhou Wang
The androgen receptor (AR) plays a critical role in the development of castration-resistant prostate cancer (CRPC) as well as in the resistance to the second-generation AR antagonist enzalutamide and the selective inhibitor of cytochrome P450 17A1 (CYP17A1) abiraterone. Novel agents targeting AR may inhibit the growth of prostate cancer cells resistant to enzalutamide and/or abiraterone. Through a high-throughput/high-content screening of a 220,000-member small molecule library, we have previously identified 2-[(isoxazol-4-ylmethyl)thio]-1-(4-phenylpiperazin-1-yl)ethanone (IMTPPE) (SID 3712502) as a novel small molecule capable of inhibiting AR transcriptional activity and protein level in C4-2 prostate cancer cells...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28975495/evaluation-of-tumor-morphologies-and-association-with-biochemical-recurrence-after-radical-prostatectomy-in-grade-group-5-prostate-cancer
#6
Trevor A Flood, Nicola Schieda, Jordan Sim, Rodney H Breau, Chris Morash, Eric C Belanger, Susan J Robertson
We assessed Gleason pattern 5 (GP5) and other prostatic adenocarcinoma (PCa) morphologies to determine their association with biochemical recurrence (BCR). A search for grade group 5 PCa with radical prostatectomy (RP) yielded 49 patients. RPs were reviewed for %GP5 and morphologies (sheets, single cells, cords, small solid cylinders, solid medium to large nests with rosette-like spaces [SMLNRS], comedonecrosis, cribriform glands, glomerulations, intraductal carcinoma of the prostate [IDC-P], and prostatic ductal adenocarcinoma [PDCa])...
October 3, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28971310/recombinant-production-and-characterization-of-sac-the-core-domain-of-par-4-by-sumo-fusion-system
#7
Jian Zhang, Aiyou Sun, Yuguo Dong, Dongzhi Wei
Prostate apoptosis response-4 (Par-4), an anticancer protein that interacts with cell surface receptor GRP78, can selectively suppress proliferation and induce apoptosis of cancer cells. The core domain of Par-4 (aa 137-195), designated as SAC, is sufficient to inhibit tumor growth and metastasis without harming normal tissues and organs. Nevertheless, the anticancer effects of SAC have not been determined in ovarian cancer cells. Here, we developed a novel method for producing native SAC in Escherichia coli using a small ubiquitin-related modifier (SUMO) fusion system...
October 2, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28969082/positive-expression-of-nr6a1-ct150-as-a-predictor-of-biochemical-recurrence-free-survival-in-prostate-cancer-patients
#8
Gong Cheng, Shangqian Wang, Xiao Li, Shuang Li, Yang Zheng, Lei Zhang, Meiling Bao, Chao Liang, Zhengkai Huang, Yiyang Liu, Chao Qin, Pengfei Shao, Jie Li, Lixin Hua, Changjun Yin, Zengjun Wang
NR6A1/CT150, as an orphan receptor, is a novel member of the cancer-testis (CT) antigen family. Here, we investigated the expression and function of NR6A1 and its underlying mechanisms in prostate cancer (PCa) patients who underwent radical prostatectomy. A total of 303 cases of prostate cancer after radical prostatectomy were analysed in a tissue microarray (TMA) for NR6A1 immunohistochemistry-based protein expression. Kaplan-Meier/log-rank analysis and Cox regression analysis were used to investigate the relationship between NR6A1 expression and clinicopathological factors in PCa...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968984/a-novel-deubiquitinase-inhibitor-b-ap15-triggers-apoptosis-in-both-androgen-receptor-dependent-and-independent-prostate-cancers
#9
Jianyu Cai, Xiaohong Xia, Yuning Liao, Ningning Liu, Zhiqiang Guo, Jinghong Chen, Li Yang, Huidan Long, Qianqian Yang, Xiaolan Zhang, Lu Xiao, Xuejun Wang, Hongbiao Huang, Jinbao Liu
Prostate cancer (PCa) remains a leading cause of cancer-related death in men. Especially, a subset of patients will eventually progress to the metastatic castrate-resistant prostate cancer (CRPC) which is currently incurable. Deubiquitinases (DUBs) associated with the 19S proteasome regulatory particle are increasingly emerging as significant therapeutic targets in numerous cancers. Recently, a novel small molecule b-AP15 is identified as an inhibitor of the USP14/UCHL5 (DUBs) of the 19S proteasome, resulting in cell growth inhibition and apoptosis in several human cancer cell lines...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968981/structure-based-design-synthesis-and-activity-studies-of-small-hybrid-molecules-as-hdac-and-g9a-dual-inhibitors
#10
Lanlan Zang, Shukkoor M Kondengaden, Qing Zhang, Xiaobo Li, Dilep K Sigalapalli, Shameer M Kondengadan, Kenneth Huang, Keqin Kathy Li, Shanshan Li, Zhongying Xiao, Liuqing Wen, Hailiang Zhu, Bathini N Babu, Lijuan Wang, Fengyuan Che, Peng George Wang
Aberrant enzymatic activities or expression profiles of epigenetic regulations are therapeutic targets for cancers. Among these, histone 3 lysine 9 methylation (H3K9Me2) and global de-acetylation on histone proteins are associated with multiple cancer phenotypes including leukemia, prostatic carcinoma, hepatocellular carcinoma and pulmonary carcinoma. Here, we report the discovery of the first small molecule capable of acting as a dual inhibitor targeting both G9a and HDAC. Our structure based design, synthesis, and screening for the dual activity of the small molecules led to the discovery of compound 14 which displays promising inhibition of both G9a and HDAC in low micro-molar range in cell based assays...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28966917/advances-on-immunotherapy-in-genitourinary-and-renal-cell-carcinoma
#11
Gregory P Botta, Eric Granowicz, Carrie Costantini
Genitourinary (GU) cancers are a group of epithelial malignancies associated with the organs involved in the excretion of urine. Renal cell, urothelial, and prostatic carcinoma are the overwhelming subtypes diagnosed by oncologists. Each of these was traditionally treated surgically when local and non-invasive. When these carcinomas spread, invade, or metastasize, surgical control lacks in efficacy. Chemotherapeutic regimens have been implemented for decades and have increased overall survival but many patients progress...
February 2017: Translational Cancer Research
https://www.readbyqxmd.com/read/28949782/divergent-anticancer-activity-of-free-and-formulated-camel-milk-%C3%AE-lactalbumin
#12
Vladimir N Uversky, Esmail M El-Fakharany, Marwa M Abu-Serie, Hussein A Almehdar, Elrashdy M Redwan
Alpha-lactalbumin (α-LA), a small milk calcium-binding globular protein, is known to possess noticeable anticancer activity, which is determined by the ability of this protein to form complexes with oleic acid (OA). To date, in addition to human and bovine α-LA, the ability to form such anti-tumor complexes with OA was described for goat and camel α-LA. Although the mechanisms of the anticancer activity of human and bovine α-LA are already well-studied, little is currently known about the anticancer action of this camel protein...
September 26, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28938008/vca-nanobodies-target-n-wasp-to-reduce-invadopodium-formation-and-functioning
#13
Tim Hebbrecht, Isabel Van Audenhove, Olivier Zwaenepoel, Adriaan Verhelle, Jan Gettemans
Invasive cancer cells develop small actin-based protrusions called invadopodia, which perform a primordial role in metastasis and extracellular matrix remodelling. Neural Wiskott-Aldrich syndrome protein (N-WASp) is a scaffold protein which can directly bind to actin monomers and Arp2/3 and is a crucial player in the formation of an invadopodium precursor. Expression modulation has pointed to an important role for N-WASp in invadopodium formation but the role of its C-terminal VCA domain in this process remains unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28928839/analysis-of-resistance-associated-gene-expression-in-docetaxel-resistant-prostate-cancer-cells
#14
Sangchul Lee, Kwangtaek Kim, Jin-Nyoung Ho, Hyunjin Jin, Seok-Soo Byun, Eunsik Lee
Docetaxel-based chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (CRPC). However, a number of patients with metastatic CRPC are refractory to docetaxel or develop docetaxel resistance. The underlying molecular mechanisms of docetaxel resistance remain unclear, which is a significant burden to the management of metastatic prostate cancer. In the present study, the differential gene expression between docetaxel-sensitive (PC3) and docetaxel-resistant (PC3DR2) prostate cancer cells was identified using DNA microarrays, western blot analysis and reverse transcription-quantitative polymerase chain reaction...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927133/benefit-of-rebiopsy-for-deciding-treatment-strategy-in-rectal-cancer-a-case-report
#15
Kenta Kawasaki, Yasuo Hamamoto, Takeshi Suzuki, Kenro Hirata, Yasutaka Sukawa, Akiyoshi Kasuga, Yuichiro Hayashi, Hiromasa Takaishi, Kaori Kameyama, Takanori Kanai
Rebiopsy is considered an option for specific types of cancer, such as breast, non-small cell lung, and prostate cancer, in clinical trials and in practice. The benefit of rebiopsy comes from the selection of a new treatment strategy based on the genetic profile of the cells, which may reflect the development of drug resistance or hormonal changes. For colorectal cancer, the presence of different genomic mutations between the primary tumor and its metastases is rare, and rebiopsy is therefore not generally performed...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927076/microrna-154-inhibits-the-growth-and-metastasis-of-gastric-cancer-cells-by-directly-targeting-mtdh
#16
Wenhui Qiao, Nong Cao, Lei Yang
MicroRNAs (miRNAs) are a group of non-protein-coding, highly conserved single-stranded RNA molecules. The abnormal expression of miRNAs has been demonstrated to have an important function in the carcinogenesis and progression of gastric cancer. microRNA-154 (miR-154) has been reported to be downregulated in non-small cell lung, colorectal and prostate cancer. However, the expression and roles of miR-154 in gastric cancer remain to be established. The present study measured the expression levels of miR-154 in gastric cancer tissues and cell lines...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28918838/inhibition-of-midkine-suppresses-prostate-cancer-cd133-stem-cell-growth-and-migration
#17
Suat Erdogan, Zeynep B Doganlar, Oguzhan Doganlar, Kader Turkekul, Riza Serttas
BACKGROUND: Midkine (MDK) is a tumor-promoting factor that is often overexpressed in various human carcinomas, and the role of MDK has not yet been fully investigated in prostate cancer stem cells. MATERIALS AND METHODS: Prostate cancer CD133(+) stem cells (PCSCs) were isolated from human castration-resistant PC3 cells. PCSCs were treated with different concentrations of MDK inhibitor, iMDK, for 24-72 hours. The IC50 values were determined by the MTT test. Endogenous MDK messenger RNA expression was knocked down by small interfering RNA...
September 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28915670/prostate-cancer-diagnosis-using-epigenetic-biomarkers-3d-high-content-imaging-and-probabilistic-cell-by-cell-classifiers
#18
Darko Stefanovski, George Tang, Kolja Wawrowsky, Raymond C Boston, Nils Lambrecht, Jian Tajbakhsh
BACKGROUND: Prostate cancer (PCa) management can benefit from novel concepts/biomarkers for reducing the current 20-30% chance of false-negative diagnosis with standard histopathology of biopsied tissue. METHOD: We explored the potential of selected epigenetic markers in combination with validated histopathological markers, 3D high-content imaging, cell-by-cell analysis, and probabilistic classification in generating novel detailed maps of biomarker heterogeneity in patient tissues, and PCa diagnosis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915537/mta1-expression-in-human-cancers-clinical-and-pharmacological-significance
#19
REVIEW
Vijaya Lakshmi Malisetty, Vasudevarao Penugurti, Prashanth Panta, Suresh Kumar Chitta, Bramanandam Manavathi
Remarkably, majority of the cancer deaths are due to metastasis, not because of primary tumors. Metastasis is one of the important hallmarks of cancer. During metastasis invasion of primary tumor cells from the site of origin to a new organ occurs. Metastasis associated proteins (MTAs) are a small family of transcriptional coregulators that are closely associated with tumor metastasis. These proteins are integral components of nuclear remodeling and deacetylation complex (NuRD). By virtue of being integral components of NuRD, these proteins regulate the gene expression by altering the epigenetic changes such as acetylation and methylation on the target gene chromatin...
September 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28913790/delivery-of-hsp90-inhibitor-using-water-soluble-polymeric-conjugates-with-high-drug-payload
#20
Jose A Suárez Del Pino, Rohit Kolhatkar
PURPOSE: HSP90 (Heat shock protein 90kD) has been validated as a therapeutic target in Castrate Resistant Prostate Cancer. Unfortunately, HSP90 inhibitors suffer from dose-limiting toxicities that hinder their clinical applications. Previously developed polymeric delivery systems for HSP90 inhibitors had either low drug content or low biological activity suggesting the need for better delivery system for HSP90 inhibitors. METHODS: We developed a simplified synthetic strategy to prepare polyethylene glycol based water-soluble polymeric system for model HSP90 inhibitor geldanamycin (GDM)...
September 14, 2017: Pharmaceutical Research
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