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https://www.readbyqxmd.com/read/28636979/exosomes-in-diagnosis-and-therapy-of-prostate-cancer
#1
REVIEW
Jun Pan, Meng Ding, Kai Xu, Chunhua Yang, Li-Jun Mao
Exosomes are small vesicular bodies released by a variety of cells. Exosomes contain miRNAs, mRNAs and proteins with the potential to regulate signaling pathways in recipient cells. Exosomes deliver nucleic acids and proteins to mediate the communication between cancer cells and stroma cells. In this review, we summarize recent progress in our understanding of the role of exosomes in prostate cancer. The tumorigenesis, metastasis and drug resistance of prostate cancer are associated with the cargos of exosomes such as miRNAs, lncRNAs and proteins...
June 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636389/tumor-microenvironment-responsive-multistaged-nanoplatform-for-systemic-rnai-and-cancer-therapy
#2
Xiaoding Xu, Phei Er Saw, Wei Tao, Yujing Li, Xiaoyuan Ji, Mikyung Yu, Morteza Mahmoudi, Jonathan Rasmussen, Dana Ayyash, Yuxiao Zhou, Omid C Farokhzad, Jinjun Shi
While RNA interference (RNAi) therapy has demonstrated significant potential for cancer treatment, effective and safe systemic delivery of RNAi agents such as small interfering RNA (siRNA) into tumor cells in vivo remains challenging. We herein reported a unique multistaged siRNA delivery nanoparticle (NP) platform, which is comprised of (i) a polyethylene glycol (PEG) surface shell, (ii) a sharp tumor microenvironment (TME) pH-responsive polymer that forms the NP core, and (iii) charge-mediated complexes of siRNA and tumor cell-targeting- and penetrating-peptide-amphiphile (TCPA) that are encapsulated in the NP core...
June 21, 2017: Nano Letters
https://www.readbyqxmd.com/read/28636052/chemically-induced-degradation-of-cdk9-by-a-proteolysis-targeting-chimera-protac
#3
Caroline M Robb, Jacob I Contreras, Smit Kour, Margaret A Taylor, Mohammad Abid, Yogesh A Sonawane, Muhammad Zahid, Daryl J Murry, Amarnath Natarajan, Sandeep Rana
Cyclin-dependent kinase 9 (CDK9), a member of the cyclin-dependent protein kinase (CDK) family, is involved in transcriptional elongation of several target genes. CDK9 is ubiquitously expressed and has been shown to contribute to a variety of malignancies such as pancreatic, prostate and breast cancers. Here we report the development of a heterobifunctional small molecule proteolysis targeting chimera (PROTAC) capable of cereblon (CRBN) mediated proteasomal degradation of CDK9. In HCT116 cells, it selectively degrades CDK9 while sparing other CDK family members...
June 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28635565/prostate-cancer-stem-cells-from-theory-to-practice
#4
Jan Adamowicz, Katayoon Pakravan, Babak Bakhshinejad, Tomasz Drewa, Sadegh Babashah
None of the generally accepted theories on prostate cancer development can fully explain many distinguishing features of the disease, such as intratumoral heterogeneity, metastatic growth, drug resistance and tumor relapse. Prostate stem cells are a heterogeneous and small subpopulation of self-renewing cells which can actively proliferate in response to changes in the androgen level and give rise to all the cell lineages that build the prostate epithelium. According to the cancer stem cell hypothesis, prostate cancer could be a stem cell disease...
February 7, 2017: Scandinavian Journal of Urology
https://www.readbyqxmd.com/read/28633436/membrane-androgen-receptor-zip9-induces-croaker-ovarian-cell-apoptosis-via-stimulatory-g-protein-alpha-subunit-and-mapkinase-signaling
#5
Aubrey Converse, Chenan Zhang, Peter Thomas
Recent studies show that androgen-induced apoptosis in Atlantic croaker primary granulosa/theca (G/T) cells and in human breast and prostate cancer cell lines is mediated by the novel membrane androgen receptor ZIP9 which belongs to the SLC39A zinc transporter family. However, the apoptotic signaling pathways remain unclear because ZIP9 activates an inhibitory G protein in human cancer cells, whereas recombinant croaker ZIP9 activates a stimulatory G protein (Gs) in transfected cancer cells. Here we investigated androgen-dependent apoptotic pathways in order to identify the signaling pathways regulated through wild-type croaker ZIP9 in ovarian follicle cells...
June 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28623637/pure-small-cell-recurrent-prostate-cancer-developing-syndrome-of-inappropriate-antidiuretic-hormone-secretion
#6
Giorgia Peverelli, Paolo Grassi
PURPOSE: Pure small cell neuroendocrine carcinoma of the prostate is a rare entity characterized by a poor prognosis due to early metastatic spread as well as resistance to treatment. Considering its increasing occurrence, clinicians should be aware of its aggressive behavior, the relevance of an early diagnosis, and proper management. METHODS: A 71-year-old man treated with brachytherapy for localized low-risk prostate cancer developed widespread disease 7 years later with a prostate-specific antigen-negative neuroendocrine small cell phenotype...
June 14, 2017: Tumori
https://www.readbyqxmd.com/read/28621319/foxa2-is-a-sensitive-and-specific-marker-for-small-cell-neuroendocrine-carcinoma-of-the-prostate
#7
Jung Wook Park, John K Lee, Owen N Witte, Jiaoti Huang
The median survival of patients with small cell neuroendocrine carcinoma is significantly shorter than that of patients with classic acinar-type adenocarcinoma. Small cell neuroendocrine carcinoma is traditionally diagnosed based on histologic features because expression of current immunohistochemical markers is inconsistent. This is a challenging diagnosis even for expert pathologists and particularly so for pathologists who do not specialize in prostate cancer. New biomarkers to aid in the diagnosis of small cell neuroendocrine carcinoma are therefore urgently needed...
June 16, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28618396/vitamin-d-receptor-binding-site-variants-affect-prostate-cancer-progression
#8
Victor C Lin, Shu-Pin Huang, Huei-Ju Ting, Wen-Lung Ma, Chia-Cheng Yu, Chao-Yuan Huang, Hsin-Ling Yin, Tsung-Yi Huang, Cheng-Hsueh Lee, Ta-Yuan Chang, Te-Ling Lu, Bo-Ying Bao
Vitamin D is an important modulator of cellular proliferation through the vitamin D receptor (VDR) that binds to DNA in the regulatory sequences of target genes. We hypothesized that single nucleotide polymorphisms (SNPs) in VDR-binding sites might affect target gene expression and influence the progression of prostate cancer. Using a genome-wide prediction database, 62 SNPs in VDR-binding sites were selected for genotyping in 515 prostate cancer patients and the findings were replicated in an independent cohort of 411 patients...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28607007/synergistic-activity-with-notch-inhibition-and-androgen-ablation-in-erg-positive-prostate-cancer-cells
#9
Ahmed A Mohamed, Shyh-Han Tan, Charles P Xavier, Shilpa Katta, Wei Huang, Lakshmi Ravindranath, Muhammad Jamal, Hua Li, Meera Srivastava, Eri S Srivatsan, Taduru L Sreenath, David G McLeod, Alagarsamy Srinivasan, Gyorgy Petrovics, Albert Dobi, Shiv Srivastava
The oncogenic activation of the ETS related gene (ERG) due to gene fusions is present in over half of prostate cancer (CaP) in Western countries. Due to its high incidence and oncogenic role, ERG and components of ERG network have emerged as potential drug targets for CaP. Utilizing gene expression datasets, from matched normal and prostate tumor epithelial cells, an association of NOTCH transcription factors with ERG expression status was identified; confirming that NOTCH factors are direct transcriptional targets of ERG...
June 12, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28606732/constitutive-and-acquired-mechanisms-of-resistance-to-immune-checkpoint-blockade-in-human-cancer
#10
Matteo Bellone, Angela Rita Elia
Cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes has been revolutionizing medical oncology, and the clinical success of monoclonal antibodies targeting either cytotoxic T lymphocyte antigen-4 (CTLA-4) or program death-1 (PD-1) in patients affected by melanoma, Hodgkin's lymphoma, Merkel cell carcinoma, and head and neck, bladder, renal cell or non-small cell lung cancer is way beyond the most optimistic expectation. However, immune checkpoint blockade (ICB) has failed to arrest progression in a consistent amount of patients affected by those tumors, and various histological types, including breast, colon and prostate cancer, are less sensitive to this therapeutic approach...
June 2, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28606127/augmentation-of-the-anticancer-activity-of-cyt997-in-human-prostate-cancer-by-inhibiting-src-activity
#11
Yong Teng, Yafei Cai, Wenhu Pi, Lixia Gao, Chloe Shay
BACKGROUND: Abnormalities of tubulin polymerization and microtubule assembly are often seen in cancer, which make them very suitable targets for the development of therapeutic approach against rapidly dividing and aggressive cancer cells. CYT997 is a novel microtubule-disrupting agent with anticancer activity in multiple cancer types including prostate cancer. However, the molecular mechanisms of action of CYT997 in prostate cancer have not been well characterized. METHODS: Src knockdown cells were achieved by lentiviral-mediated interference...
June 12, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28603843/characterization-of-vsig1-exerting-a-tumor-suppressor-function-in-gastric-lung-and-esophageal-cancer-cells
#12
Yusuke Inoue, Shun Matsuura, Katsuhiro Yoshimura, Yuji Iwashita, Tomoaki Kahyo, Akikazu Kawase, Masayuki Tanahashi, Matsuyoshi Maeda, Hiroshi Ogawa, Naoki Inui, Kazuhito Funai, Kazuya Shinmura, Hiroshi Niwa, Takafumi Suda, Haruhiko Sugimura
V-set and immunoglobulin domain containing 1 (VSIG1) is a newly discovered member of the immunoglobulin superfamily proteins, expressed in normal stomach and testis. In cancers, however, the clinical and biological roles of VSIG1 remain unknown. Here we investigated VSIG1 expression in 11 cancers and assessed the prognostic roles of VSIG1 in patients with gastric cancer (GC) (N = 362) and non-small-cell lung cancer (N = 650). VSIG1 was downregulated in 60.5% of GC specimens, and high VSIG1 expression was identified as an independent favorable prognostic factor for overall survival in GC patients (hazard ratio, 0...
June 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28602290/a-sensitive-and-disposable-electrochemical-immunosensor-for-detection-of-sox2-a-biomarker-of-cancer
#13
Elif Burcu Aydın, Mustafa Kemal Sezgintürk
A novel, sensitive, disposable indium tin oxide (ITO)-based electrochemical immunosensor was developed firstly for simple, rapid determination of Sex-determining region Y-box 2 (SOX2). SOX2 is a cancer biomarker and used for detecting small cell lung cancer, lung adenocarcinoma, squamous cell carcinoma, skin cancer, prostate cancer, and breast cancer. In this study, a disposable ITO thin film based electrode was used as working electrode for biosensing the interaction between SOX2 antigen and anti-SOX2 antibody...
September 1, 2017: Talanta
https://www.readbyqxmd.com/read/28599655/canine-reic-dkk-3-interacts-with-sgta-and-restores-androgen-receptor-signalling-in-androgen-independent-prostate-cancer-cell-lines
#14
Yuiko Kato, Kazuhiko Ochiai, Shota Kawakami, Nobuhiro Nakao, Daigo Azakami, Makoto Bonkobara, Masaki Michishita, Masami Morimatsu, Masami Watanabe, Toshinori Omi
BACKGROUND: The pathological condition of canine prostate cancer resembles that of human androgen-independent prostate cancer. Both canine and human androgen receptor (AR) signalling are inhibited by overexpression of the dimerized co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA), which is considered to cause the development of androgen-independency. Reduced expression in immortalised cells (REIC/Dkk-3) interferes with SGTA dimerization and rescues AR signalling...
June 9, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28598898/a-99mtc-labelled-scfv-antibody-fragment-that-binds-to-prostate-specific-membrane-antigen
#15
Saima Nawaz, Gregory E D Mullen, Philip J Blower, James R Ballinger
INTRODUCTION: Prostate-specific membrane antigen (PSMA) is an extensively studied antigen for imaging prostate cancer. We prepared a single-chain variable fragment (scFv) of J591, a monoclonal antibody that recognises an external epitope of PSMA, incorporating a His-tag for labelling with Tc tricarbonyl, and evaluated its binding using human PCa cell lines. METHODS: J591(scFv) was expressed in HEK-293T cells and purified by metal ion affinity chromatography, followed by size exclusion chromatography...
June 8, 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28594553/development-of-protein-degradation-inducers-of-androgen-receptor-by-conjugation-of-androgen-receptor-ligands-and-inhibitor-of-apoptosis-protein-iap-ligands
#16
Norihito Shibata, Katsunori Nagai, Yoko Morita, Osamu Ujikawa, Nobumichi Ohoka, Takayuki Hattori, Ryokichi Koyama, Osamu Sano, Yasuhiro Imaeda, Hiroshi Nara, Nobuo Cho, Mikihiko Naito
Targeted protein degradation using small molecules is a novel strategy for drug development. We have developed hybrid molecules named Specific and Non-genetic inhibitor of apoptosis protein [IAP]-dependent Protein Erasers (SNIPERs) that recruit IAP ubiquitin ligases to degrade target proteins. Here, we show novel SNIPERs capable of inducing proteasomal degradation of the androgen receptor (AR). Through derivatization of the SNIPER(AR) molecule at AR ligand, IAP ligand and linker, we developed 42a (SNIPER(AR)-51), which shows effective protein knockdown activity against AR...
June 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28593908/circulating-cell-free-micrornas-as-clinical-cancer-biomarkers
#17
REVIEW
Virginie Armand-Labit, Anne Pradines
MicroRNAs (miRNAs) are non-coding small RNAs that are master regulators of genic expression and consequently of many cellular processes. But their expression is often deregulated in human tumors leading to cancer development. Recently miRNAs were discovered in body fluids (serum, plasma and others) and their levels have often been reported to be altered in patients. Circulating miRNAs became one of the most promising biomarkers in oncology for early diagnosis, prognosis and therapeutic response prediction. Here we describe the origins and roles of miRNAs, and summarize the most recent studies focusing on their usefulness as cancer biomarkers in lung, breast, colon, prostate, ovary cancers and melanoma...
April 27, 2017: Biomolecular Concepts
https://www.readbyqxmd.com/read/28592703/real-time-transferrin-based-pet%C3%A2-detects-myc-positive-prostate-cancer
#18
Rahul Aggarwal, Spencer Behr, Pamela L Paris, Charles Truillet, Matthew F L Parker, Loc T Huynh, Junnian Wei, Byron Hann, Jack Youngren, Gayatri Premasekharan, Jiaoti Huang, Nimna Ranatunga, Emily Chang, Kenneth T Gao, Charles J Ryan, Eric J Small, Michael J Evans
Non-invasive biomarkers that detect the activity of important oncogenic drivers could significantly improve cancer diagnosis and management of treatment. The goal of this study was to determine if 68Ga-citrate (which avidly binds to circulating transferrin) labeled transferrin (Tf) can detect MYC-positive prostate cancer tumors, since the transferrin receptor is a direct MYC target gene. Positron emission tomography (PET) imaging paired with 68Ga-citrate and molecular analysis of preclinical models, human cell-free DNA (cfDNA) and clinical biopsies were conducted to determine whether 68Ga-citrate can detect MYC-positive prostate cancer...
June 7, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28592122/knockdown-of-cftr-enhances-sensitivity-of-prostate-cancer-cells-to-cisplatin-via-inhibition-of-autophagy
#19
Q Zhu, H Li, Y Liu, L Jiang
Prostate cancer is one of the most lethal diseases in men worldwide. Although the survival rate of men diagnosed with prostate cancer has increased with the improvement of treatments, drug resistance still remains a big challenge for improving overall survival. Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated anion channel, has been reported to have a pivotal role in the pathogenesis of various cancers, but its role in chemoresistance of prostate cancer cells is poorly understood...
June 8, 2017: Neoplasma
https://www.readbyqxmd.com/read/28591707/identification-of-novel-small-molecule-beclin-1-mimetics-activating-autophagy
#20
Jia Yu, Lan Lan, Seth J Lewin, Steven A Rogers, Anuradha Roy, Xiaoqing Wu, Philip Gao, John Karanicolas, Jeffrey Aubé, Baiwang Sun, Liang Xu
Anti-apoptotic proteins Bcl-2 and Bcl-xL could block autophagy by binding to Beclin 1 protein, an essential inducer of autophagy. Compounds mimicking Beclin 1 might be able to disrupt Bcl-xL/2-Beclin 1 interaction, free out Beclin 1, and thus trigger autophagy. In order to identify small molecule Beclin 1 mimetics, a fluorescence polarization-based high-throughput screening of 50,316 compounds was carried out with a Z' score of 0.82 ± 0.05, and an outcome of 58 hits. After the structure analysis, three acridine analogues were unveiled and confirmed using the fluorescence polarization assay and the surface plasmon resonance assay...
May 18, 2017: Oncotarget
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