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Small cell prostate cancer

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https://www.readbyqxmd.com/read/28716080/pretreatment-antigen-specific-immunity-and-regulation-association-with-subsequent-immune-response-to-anti-tumor-dna-vaccination
#1
Laura E Johnson, Brian M Olson, Douglas G McNeel
BACKGROUND: Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28715227/balancing-passive-and-active-targeting-to-different-tumor-compartments-using-riboflavin-functionalized-polymeric-nanocarriers
#2
Yoanna Tsvetkova, Nataliia Beztsinna, Maike Baues, Dionne Klein, Anne Rix, Susanne Katherina Golombek, Wa'el Al Rawashdeh, Felix Gremse, Matthias Barz, Kaloian Koynov, Srinivas Banala, Wiltrud Lederle, Twan Lammers, Fabian Kiessling
Riboflavin Transporters (RFTs) and the Riboflavin Carrier Protein (RCP) are highly upregulated in many tumor cells, tumor stem cells and tumor neovasculature, which makes them attractive targets for nanomedicines. Addressing cells in different tumor compartments requires drug carriers, which are not only able to accumulate via the EPR effect, but also to extravasate, target specific cell populations, and get internalized by cells. Reasoning that antibodies are among the most efficient targeting systems developed by nature, we consider their size (~10-15 nm) to be ideal for balancing passive and active tumor targeting...
July 17, 2017: Nano Letters
https://www.readbyqxmd.com/read/28714370/phosphatase-and-tensin-homolog-deleted-on-chromosome-10-degradation-induced-by-nedd4-promotes-acquired-erlotinib-resistance-in-non-small-cell-lung-cancer
#3
Huake Sun, Huiwen Ma, Jianmin Wang, Liqin Xia, Guangkuo Zhu, Zhoufei Wang, Jianguo Sun, Zhengtang Chen
Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors, such as gefitinib and erlotinib, is a critical issue in the treatment of patients with epidermal growth factor receptor mutant-positive non-small-cell lung cancer. Recent evidence suggests that downregulation of gene of phosphatase and tensin homolog deleted on chromosome 10 plays an important role in acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in various types of cancers, including lung cancer...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28710641/a-ligand-binding-assay-to-measure-the-affinity-and-specificity-of-sterol-binding-proteins-in-vitro
#4
Rabih Darwiche, Roger Schneiter
Sterols are major constituents of the plasma membrane of eukaryotic cells and serve as a precursor for several classes of signaling molecules, including steroids and hydroxy sterols. They maintain the functionality and permeability barrier of the plasma membrane through lipid-lipid and lipid-protein interactions. The S. cerevisiae pathogen-related yeast proteins 1, 2, and 3 (Pry) belong to a large protein superfamily known as CAP/SCP/TAPS. Members of this superfamily have been implicated in a wide variety of processes, including immune defense in mammals and plants, pathogen virulence, sperm maturation and fertilization, venom toxicity, and prostate and brain cancer...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28706131/structure-based-design-synthesis-and-activity-studies-of-small-hybrid-molecules-as-hdac-and-g9a-dual-inhibitors
#5
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...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28705714/aristeromycin-and-dznep-cause-growth-inhibition-of-prostate-cancer-via-induction-of-mir-26a
#6
Noriko Uchiyama, Yukiya Tanaka, Tomohiro Kawamoto
Most prostate cancers initially respond to androgen deprivation therapy, but then progress from androgen-dependent to androgen-independent prostate cancers. In the present study, a differential cytotoxicity screen of hormone-resistant prostate cancer LNCaP-hr cells and the parental LNCaP-FGC cells against normal MRC5 fibroblast cells, identified a small molecule compound, Aristeromycin (a derivative of 3-deazaneplanocin A (DZNeP)). The molecular target was shown to be S-adenosylhomocysteine hydrolase (AHCY), which catalyzes reversible hydrolysis of S-adenosylhomocysteine (SAH) to adenosine and L-homocysteine...
July 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28701587/prostate-cancer-diagnosis-using-epigenetic-biomarkers-3d-high-content-imaging-and-probabilistic-cell-by-cell-classifiers
#7
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...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698547/metabolic-reprogramming-is-associated-with-flavopiridol-resistance-in-prostate-cancer-du145-cells
#8
Xiaoran Li, Jie Lu, Quancheng Kan, Xiaoli Li, Qiong Fan, Yaqing Li, Ruixia Huang, Ana Slipicevic, Hiep Phuc Dong, Lars Eide, Junbai Wang, Hongquan Zhang, Viktor Berge, Mariusz Adam Goscinski, Gunnar Kvalheim, Jahn M Nesland, Zhenhe Suo
Flavopiridol (FP) is a pan-cyclin dependent kinase inhibitor, which shows strong efficacy in inducing cancer cell apoptosis. Although FP is potent against most cancer cells in vitro, unfortunately it proved less efficacious in clinical trials in various aggressive cancers. To date, the molecular mechanisms of the FP resistance are mostly unknown. Here, we report that a small fraction human prostate cancer DU145 cells can survive long-term FP treatment and emerge as FP-resistant cells (DU145(FP)). These DU145(FP) cells show accumulated mitochondrial lesions with stronger glycolytic features, and they proliferate in slow-cycling and behave highly migratory with strong anti-apoptotic potential...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698198/abcb1-mediates-cabazitaxel-docetaxel-cross-resistance-in-advanced-prostate-cancer
#9
Alan P Lombard, Chengfei Liu, Cameron M Armstrong, Vito Cucchiara, Xinwei Gu, Wei Lou, Christopher P Evans, Allen C Gao
in research have added several new therapies for castration-resistant prostate cancer (CRPC), greatly augmenting our ability to treat patients. However, CRPC remains an incurable disease due to the development of therapeutic resistance and the existence of cross-resistance between available therapies. Understanding the interplay between different treatments will lead to improved sequencing and the creation of combinations which overcome resistance and prolong survival. Whether there exists cross-resistance between docetaxel and the next-generation taxane cabazitaxel is poorly understood...
July 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28698102/neonatal-nav1-5-protein-expression-in-normal-adult-human-tissues-and-breast-cancer
#10
Rezan Fahrioglu Yamaci, Scott P Fraser, Esra Battaloglu, Handan Kaya, Kamil Erguler, Christopher S Foster, Mustafa B A Djamgoz
Expression of the neonatal splice variant of the voltage-gated sodium channel α-subunit (VGSC) subtype Nav1.5 (nNav1.5), encoded by the gene SCN5A, was shown earlier to be upregulated in human breast cancer (BCa), both in vitro and in vivo. Channel activity promoted BCa invasion of Matrigel(®)in vitro and metastasis in vivo. Consequently, expression of nNav1.5 has been proposed as a functional biomarker of BCa cells with metastatic potential. Here, we have determined immunohistochemically both nNav1.5 and total VGSC (tVGSC) protein expression in a range of adult human tissues...
June 6, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28695371/binding-of-%C3%AE-v%C3%AE-3-integrin-specific-radiotracers-is-modulated-by-both-integrin-expression-level-and-activation-status
#11
Alexandra Andriu, Julie Crockett, Sergio Dall'Angelo, Monica Piras, Matteo Zanda, Ian N Fleming
PURPOSE: Molecular imaging of αvβ3 integrin has exhibited real potential to guide the appropriate use of anti-angiogenic therapies. However, an incomplete understanding of the factors that influence binding of αvβ3 integrin-specific radiotracers currently limits their use for assessing response to therapy in cancer patients. This study identifies two fundamental factors that modulate uptake of these radiotracers. Procedures Experiments were performed in prostate cancer (PC3) and glioblastoma (U87MG) cells, which differentially express αvβ3 integrin...
July 10, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28694034/insertion-and-deletion-derived-tumour-specific-neoantigens-and-the-immunogenic-phenotype-a-pan-cancer-analysis
#12
Samra Turajlic, Kevin Litchfield, Hang Xu, Rachel Rosenthal, Nicholas McGranahan, James L Reading, Yien Ning S Wong, Andrew Rowan, Nnennaya Kanu, Maise Al Bakir, Tim Chambers, Roberto Salgado, Peter Savas, Sherene Loi, Nicolai J Birkbak, Laurent Sansregret, Martin Gore, James Larkin, Sergio A Quezada, Charles Swanton
BACKGROUND: The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution of small insertions and deletions (indels) less well characterised. We investigated whether the frameshift nature of indel mutations, which create novel open reading frames and a large quantity of mutagenic peptides highly distinct from self, might contribute to the immunogenic phenotype. METHODS: We analysed whole-exome sequencing data from 5777 solid tumours, spanning 19 cancer types from The Cancer Genome Atlas...
July 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28693582/oncogenic-mir-210-3p-promotes-prostate-cancer-cell-emt-and-bone-metastasis-via-nf-%C3%AE%C2%BAb-signaling-pathway
#13
Dong Ren, Qing Yang, Yuhu Dai, Wei Guo, Hong Du, Libing Song, Xinsheng Peng
BACKGROUND: The primary issue arising from prostate cancer (PCa) is its high prevalence to metastasize to bone, which severely affects the quality of life and survival time of PCa patients. miR-210-3p is a well-documented oncogenic miRNA implicated in various aspects of cancer development, progression and metastasis. However, the clinical significance and biological roles of miR-210-3p in PCa bone metastasis remain obscure. METHODS: miR-210-3p expression was evaluated by real-time PCR in 68 bone metastatic and 81 non-bone metastatic PCa tissues...
July 10, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28691803/development-of-an-activatable-fluorescent-probe-for-prostate-cancer-imaging
#14
Takao Yogo, Keitaro Umezawa, Mako Kamiya, Rumi Hino, Yasuteru Urano
Technology to visualize small prostate cancers is urgently needed because of the difficulty of discriminating prostate cancer from normal tissue with the naked eye, and a fluorescence imaging method would be advantageous. Here we describe the design and synthesis of a fluorogenic probe (Ac-KQLR-HMRG) that is activated by hepsin and matriptase (proteases overexpressed in prostate cancer). Ac-KQLR-HMRG exhibited significant turn-on fluorogenicity in the presence of hepsin (180-fold) and matriptase (80-fold), and allowed specific fluorescence imaging of various prostate cancer cell lines in vitro...
July 10, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28690874/sulforaphane-cysteine-induced-apoptosis-via-phosphorylated-erk1-2-mediated-maspin-pathway-in-human-non-small-cell-lung-cancer-cells
#15
Kai Lin, Ronghui Yang, Zhongnan Zheng, Yan Zhou, Yang Geng, Yabin Hu, Sai Wu, Wei Wu
Sulforaphane (SFN) was demonstrated to induce apoptosis in a variety of cancers via multiple mechanisms. However, owing to a short half-life in circulation, SFN was not used for clinical treatment yet. Interestingly, SFN analog, sulforaphane-cysteine (SFN-Cys) has a longer half-life in metabolism, and we previously demonstrated that SFN-Cys inhibited invasion in human prostate cancer cells. Here, we would investigate whether SFN-Cys induces apoptosis and find the underlying mechanisms in human non-small cell lung cancer (NSCLC) cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28689379/-influence-of-conjugated-linoleic-acids-on-metabolic-processes-in-cells-and-tissues
#16
Ewa Siwiec, Ewa Stachowska
Conjugated linoleic acids (CLA) are constitutional and geometric isomers of this acid. The most commonly consumed geometric isomers are cis-9,trans-11 (c9, t11) CLA and trans-10, cis-12 (t10,c12) CLA. These isomers together with trans-9,trans-11 CLA and trans-10,trans-12 CLA constitute about 90% of all CLA in natural products. Different structure of the isomers affects their functions in the body. Differences in the effects on organs and tissues are sometimes small and sometimes opposed, sometimes the isomers work synergistically...
2017: Postepy Biochemii
https://www.readbyqxmd.com/read/28685435/hypoxia-related-tumor-acidosis-affects-microrna-expression-pattern-in-prostate-and-breast-tumor-cells
#17
A Riemann, S Reime, O Thews
MicroRNAs (miRNAs) are small non-coding RNA sequences which are able to modulate the expression of many functional proteins. The expression level of miRNAs can be modulated by parameters of the tumor microenvironment like hypoxia, nutrient deprivation or oxidative stress. Since miRNAs can act either as oncogenes or tumor suppressors, this may affect malignant progression or therapy resistance. In the present study it was analyzed whether extracellular acidosis can impact on miRNA expression. Therefore, tumor cells (R3327-AT-1 prostate and Walker-256 mammary carcinoma cells) were incubated at pH 6...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28676010/kca3-1-channel-modulators-as-potential-therapeutic-compounds-for-glioblastoma
#18
Brandon M Brown, Brandon Pressley, Heike Wulff
The intermediate-conductance Ca2+-activated K+ channel KCa3.1 is widely expressed in cells of the immune system such as T- and B-lymphocytes, mast cells, macrophages and microglia, but also found in dedifferentiated vascular smooth muscle cells, fibroblasts and many cancer cells including pancreatic, prostate, leukemia and glioblastoma. In all these cell types KCa3.1 plays an important role in cellular activation, migration and proliferation by regulating membrane potential and Ca2+ signaling. KCa3.1 therefore constitutes an attractive therapeutic target for diseases involving excessive proliferation or activation of one more of these cell types and researchers both in academia and in the pharmaceutical industry have developed several potent and selective small molecule inhibitors of KCa3...
June 30, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28673439/-neuroendocrine-prostate-cancer-natural-history-molecular-features-therapeutic-management-and-future-directions
#19
Luca Campedel, Myriam Kossaï, Paul Blanc-Durand, Morgan Rouprêt, Thomas Seisen, Eva Compérat, Jean-Philippe Spano, Gabriel Malouf
Neuroendocrine prostate cancer is a rare malignancy with a an adverse prognostic. Histologically, It can be pure (small cells or large cells neuroendocrine carcinoma) or mixed with a adenocarcinoma component. Rarely diagnosed de novo, neuroendocrine prostate cancer is generally associated with advanced stage disease resistant to castration. As such, this histological subtype could represent an aggressive evolution of prostatic adenocarcinoma, through the epithelio-neuroendocrine transdifferentiation mechanism (phenomenon of lineage plasticity)...
June 30, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28666623/geranylnaringenin-cg902-inhibits-constitutive-and-inducible-stat3-activation-through-the-activation-of-shp-2-tyrosine-phosphatase
#20
Yena Jin, Yae Jin Yoon, Yoon Jung Jeon, Jiyeon Choi, Yu-Jin Lee, Joonku Lee, Sangho Choi, Oyekanmi Nash, Dong Cho Han, Byoung-Mog Kwon
The roles and significance of signal transducer and activator of transcription 3 (STAT3) in human cancers have been extensively studied and STAT3 is a promising therapeutic target for cancer drug discovery. During the screening of natural products to identify STAT3 inhibitors, we identified geranylnaringenin (CG902), which decreased luciferase activity in a dose-dependent manner. CG902 specifically inhibited STAT3 phosphorylation at Tyr-705 in DU145 prostate cancer cells and decreased the expression levels of STAT3 target genes, such as cyclin D1, cyclin A, and survivin...
June 27, 2017: Biochemical Pharmacology
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