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https://www.readbyqxmd.com/read/29048618/dual-action-of-nsc606985-on-cell-growth-and-apoptosis-mediated-through-pkc%C3%AE-in-prostatic-cancer-cells
#1
Xin Wang, Chen Tan, Guo Wang, Jing-Jing Cai, Li-Ping Wang, Julianne Imperato-McGinley, Yuan-Shan Zhu
Chemotherapy is a vital therapeutic strategy for castration-resistant prostate cancer (CRPC). We have previously shown that NSC606985 (NSC), a camptothecin (CPT) analog, induced cell apoptosis via interacting with topoisomerase I (Topo I) in prostate cancer cells. In the present study, the effect and mechanism of CPT analogs in LAPC4 cells were investigated. LAPC-4 cells were treated with NSC, CPT, and topotecan. Cell proliferation, apoptosis, and protein kinase Cδ (PKCδ) subcellular activation were measured at different doses and time-points, with or without PKCδ inhibition or knockdown of PKCδ expression...
September 27, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29031818/camptothecin-and-its-analog-sn-38-the-active-metabolite-of-irinotecan-inhibit-binding-of-the-transcriptional-regulator-and-oncoprotein-fubp1-to-its-dna-target-sequence-fuse
#2
Sabrina Khageh Hosseini, Stefanie Kolterer, Marlene Steiner, Victoria von Manstein, Katharina Gerlach, Jörg Trojan, Oliver Waidmann, Stefan Zeuzem, Jörg O Schulze, Steffen Hahn, Dieter Steinhilber, Volker Gatterdam, Robert Tampé, Ricardo M Biondi, Ewgenij Proschak, Martin Zörnig
The transcriptional regulator FUSE Binding Protein 1 (FUBP1) is overexpressed in more than 80% of all human hepatocellular carcinomas (HCCs) and other solid tumor entities including prostate and colorectal carcinoma. FUBP1 expression is required for HCC tumor cell expansion, and it functions as an important pro-proliferative and anti-apoptotic oncoprotein that binds to the single-stranded DNA sequence FUSE to regulate the transcription of a variety of target genes. In this study, we screened an FDA-approved drug library and discovered that the Topoisomerase I (TOP1) inhibitor camptothecin (CPT) and its derivative 7-ethyl-10-hydroxycamptothecin (SN-38), the active irinotecan metabolite that is used in the clinics in combination with other chemotherapeutics to treat carcinoma, inhibit FUBP1 activity...
October 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28840551/role-of-protein-linked-dna-breaks-in-cancer
#3
Walaa R Allam, Mohamed E Ashour, Amr A Waly, Sherif El-Khamisy
Topoisomerases are a group of specialized enzymes that function to maintain DNA topology by introducing transient DNA breaks during transcription and replication. As a result of abortive topoisomerases activity, topoisomerases catalytic intermediates may be trapped on the DNA forming topoisomerase cleavage complexes (Topcc). Topoisomerases trapping on the DNA is the mode of action of several anticancer drugs, it lead to formation of protein linked DAN breaks (PDBs). PDBs are now considered as one of the most dangerous forms of endogenous DNA damage and a major threat to genomic stability...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28753517/design-synthesis-and-antiproliferative-activity-of-decarbonyl-luotonin-analogues
#4
Abdulrahman I Almansour, Natarajan Arumugam, Raju Suresh Kumar, S M Mahalingam, Samaresh Sau, Giulia Bianchini, J Carlos Menéndez, Mohammad Altaf, Hazem A Ghabbour
A small library of benzimidazole-fused pyrrolo[3,4-b]quinoline has been synthesized from readily available benzimidazole 2-carbaldehyde and various substituted arylamines in good to excellent yields utilizing an intramolecular Povarov reaction catalyzed by boron trifluoride diethyl etharate as the key final step. The compounds thus synthesized can be considered as decarbonyl analogues of the anticancer alkaloid luotonin A and were evaluated in a DNA relaxation assay for their ability to inhibit human topoisomerase I...
September 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28368209/enhanced-cytotoxic-effect-of-camptothecin-nanosponges-in-anaplastic-thyroid-cancer-cells-in-vitro-and-in-vivo-on-orthotopic-xenograft-tumors
#5
Casimiro Luca Gigliotti, Benedetta Ferrara, Sergio Occhipinti, Elena Boggio, Giuseppina Barrera, Stefania Pizzimenti, Mirella Giovarelli, Roberto Fantozzi, Annalisa Chiocchetti, Monica Argenziano, Nausicaa Clemente, Francesco Trotta, Caterina Marchiò, Laura Annaratone, Renzo Boldorini, Umberto Dianzani, Roberta Cavalli, Chiara Dianzani
Anaplastic carcinoma of the thyroid (ATC) is a lethal human malignant cancer with median survival of 6 months. To date, no treatment has substantially changed its course, which makes urgent need for the development of novel drugs or novel formulations for drug delivery. Nanomedicine has enormous potential to improve the accuracy of cancer therapy by enhancing availability and stability, decreasing effective doses and reducing side effects of drugs. Camptothecin (CPT) is an inhibitor of DNA topoisomerase-I with several anticancer properties but has poor solubility and a high degradation rate...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/27771897/profiling-of-signaling-proteins-in-penumbra-after-focal-photothrombotic-infarct-in-the-rat-brain-cortex
#6
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27643560/novel-2-aryl-4-4-hydroxyphenyl-5h-indeno-1-2-b-pyridines-as-potent-dna-non-intercalative-topoisomerase-catalytic-inhibitors
#7
Seojeong Park, Tara Man Kadayat, Kyu-Yeon Jun, Til Bahadur Thapa Magar, Ganesh Bist, Aarajana Shrestha, Eung-Seok Lee, Youngjoo Kwon
On the basis of previous reports on the importance of thienyl, furyl or phenol group substitution on 5H-indeno[1,2-b]pyridine skeleton, a new series of rigid 2-aryl-4-(4'-hydroxyphenyl)-5H-indeno[1,2-b]pyridine derivatives were systematically designed and synthesized. Topoisomerase inhibitory activity and antiproliferative activity of all the synthesized compounds were determined using human colorectal (HCT15), breast (T47D), prostate (DU145) and cervix (HeLa) cancer cells. Compounds 9, 10, 12, 13, 15, 16, 18 and 19 with thienyl or furyl moiety at the 2-position and hydroxyl group at the meta or para positions of 4-phenyl ring displayed strong to moderate topoisomerase IIα (topo IIα) inhibitory activity and significant antiproliferative activity...
January 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27537875/the-role-of-%C3%AE-1-adrenoceptor-antagonists-in-the-treatment-of-prostate-and-other-cancers
#8
REVIEW
Mallory Batty, Rachel Pugh, Ilampirai Rathinam, Joshua Simmonds, Edwin Walker, Amanda Forbes, Shailendra Anoopkumar-Dukie, Catherine M McDermott, Briohny Spencer, David Christie, Russ Chess-Williams
This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects...
August 16, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27435006/new-spiro-acridines-dna-interaction-antiproliferative-activity-and-inhibition-of-human-dna-topoisomerases
#9
Sinara Mônica Vitalino de Almeida, Elizabeth Almeida Lafayette, Willams Leal Silva, Vanessa de Lima Serafim, Thais Meira Menezes, Jorge Luiz Neves, Ana Lucia Tasca Gois Ruiz, João Ernesto de Carvalho, Ricardo Olímpio de Moura, Eduardo Isidoro Carneiro Beltrão, Luiz Bezerra de Carvalho Júnior, Maria do Carmo Alves de Lima
Two new spiro-acridines were synthesized by introducing cyano-N-acylhydrazone between the acridine and phenyl rings followed by spontaneous cyclization. The final compounds (E)-1'-(benzylideneamino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-01) and (E)-1'-((4-methoxybenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-02) were evaluated for their interactions with calf thymus DNA, antiproliferative and human topoisomerase I and IIα inhibitory activities...
November 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27301177/in-vitro-and-in-vivo-therapeutic-evaluation-of-camptothecin-encapsulated-%C3%AE-cyclodextrin-nanosponges-in-prostate-cancer
#10
Casimiro Luca Gigliotti, Rosalba Minelli, Roberta Cavalli, Sergio Occhipinti, Giuseppina Barrera, Stefania Pizzimenti, Giuseppe Cappellano, Elena Boggio, Laura Conti, Roberto Fantozzi, Mirella Giovarelli, Francesco Trotta, Umberto Dianzani, Chiara Dianzani
Camptothecin (CPT), a pentacyclic alkaloid, is an inhibitor of DNA Topoisomerase-I and shows a wide spectrum of anti-cancer activities. The use of CPT has been hampered by poor aqueous solubility and a high degradation rate. Previously, it has been reported that CPT encapsulated in β-cyclodextrin-nanosponges (CN-CPT) overcomes these disadvantages and improves the CPT's inhibitory effect on DU145 prostate tumor cell lines, and PC-3 growth in vitro. This work extends these observations by showing that CN-CPT significantly inhibits the adhesion and migration of these tumor cells and their STAT3 phosphorylation...
January 2016: Journal of Biomedical Nanotechnology
https://www.readbyqxmd.com/read/27277821/dissociation-of-nsc606985-induces-atypical-er-stress-and-cell-death-in-prostate-cancer-cells
#11
Liping Wang, Pengcheng Fu, Yuan Zhao, Guo Wang, Richard Yu, Xin Wang, Zehai Tang, Julianne Imperato-McGinley, Yuan-Shan Zhu
Castration-resistant prostate cancer (CRPC) is a major cause of prostate cancer (Pca) death. Chemotherapy is able to improve the survival of CRPC patients. We previously found that NSC606985 (NSC), a highly water-soluble camptothecin analog, induced cell death in Pca cells via interaction with topoisomerase 1 and activation of the mitochondrial apoptotic pathway. To further elucidate the role of NSC, we studied the effect of NSC on ER-stress and its association with NSC-induced cell death in Pca cells. NSC produced a time- and dose-dependent induction of GRP78, CHOP and XBP1s mRNA, and CHOP protein expression in Pca cells including DU145, indicating an activation of ER-stress...
August 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27166396/testosterone-in-androgen-receptor-signaling-and-dna-repair-enemy-or-frenemy
#12
Melvin Lee Kiang Chua, Robert G Bristow
Androgen suppression mediates transcriptional downregulation of DNA repair genes. Stimulation with supraphysiologic levels of dihydrotestosterone induces formation of lethal DNA breaks through recruitment of topoisomerase II enzymes to fragile DNA sites. Bipolar castration and stimulation that contributes to increasing DNA damage represents a novel strategy of sensitizing prostate cancer to cytotoxic therapies, including radiotherapy. Clin Cancer Res; 22(13); 3124-6. ©2016 AACRSee related article by Hedayati et al...
July 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27139157/preliminary-evaluation-of-prostate-targeted-radiotherapy-using-131-i-mip-1095-in-combination-with-radiosensitising-chemotherapeutic-drugs
#13
Mathias Tesson, Colin Rae, Colin Nixon, John W Babich, Robert J Mairs
OBJECTIVES: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. (131) I-MIP-1095 is a recently developed prostate-specific membrane antigen (PSMA)-targeting, small molecular weight radiopharmaceutical which has anti-tumour activity as a single agent. Our purpose was to determine in vitro the potential benefit to be gained by combining (131) I-MIP-1095 with cytotoxic drug treatments...
July 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27128689/deazaflavin-inhibitors-of-tyrosyl-dna-phosphodiesterase-2-tdp2-specific-for-the-human-enzyme-and-active-against-cellular-tdp2
#14
Christophe Marchand, Monica Abdelmalak, Jayakanth Kankanala, Shar-Yin Huang, Evgeny Kiselev, Katherine Fesen, Kayo Kurahashi, Hiroyuki Sasanuma, Shunichi Takeda, Hideki Aihara, Zhengqiang Wang, Yves Pommier
Tyrosyl-DNA phosphodiesterase 2 repairs irreversible topoisomerase II-mediated cleavage complexes generated by anticancer topoisomerase-targeted drugs and processes replication intermediates for picornaviruses (VPg unlinkase) and hepatitis B virus. There is currently no TDP2 inhibitor in clinical development. Here, we report a series of deazaflavin derivatives that selectively inhibit the human TDP2 enzyme in a competitive manner both with recombinant and native TDP2. We show that mouse, fish, and C. elegans TDP2 enzymes are highly resistant to the drugs and that key protein residues are responsible for drug resistance...
July 15, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/26891441/-mitoxantrone-role-in-treatment-of-primary-progressive-multiple-sclerosis
#15
REVIEW
Żanna Pastuszak, Adam Stępień, Kazimierz Tomczykiewicz, Renata Piusińska-Macoch, Marta Durka-Kęsy
Multiple sclerosis is a chronic, autoimmunological disease of central nervous system in which axonal damage in brain and spinal cord is observed. It is second most common cause of disability in young adults in West Europe and North America after injuries. There is 2.5 million people suffered from multiple sclerosis worldwide. The worse prognosis is connected with primary progressive MS in which recovery after first symptoms of central nervous system damage isn't observed. That subtype of disease is seen in case of 10-20% people with MS...
January 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/26831716/androgen-deprivation-followed-by-acute-androgen-stimulation-selectively-sensitizes-ar-positive-prostate-cancer-cells-to-ionizing-radiation
#16
Mohammad Hedayati, Michael C Haffner, Jonathan B Coulter, Raju R Raval, Yonggang Zhang, Haoming Zhou, Omar Mian, Emma J Knight, Nina Razavi, Susan Dalrymple, John T Isaacs, Aileen Santos, Russell Hales, William G Nelson, Srinivasan Yegnasubramanian, Theodore L DeWeese
PURPOSE: The current standard of care for patients with locally advanced prostate cancer is a combination of androgen deprivation and radiation therapy. Radiation is typically given with androgen suppression when testosterone levels are at their nadir. Recent reports have shown that androgen stimulation of androgen-deprived prostate cancer cells leads to formation of double-strand breaks (DSB). Here, we exploit this finding and investigate the extent and timing of androgen-induced DSBs and their effect on tumor growth following androgen stimulation in combination with ionizing radiation (IR)...
July 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26619196/in-vitro-anticancer-activities-of-schiff-base-and-its-lanthanum-complex
#17
Neelima, Kavita Poonia, Sahabjada Siddiqui, Md Arshad, Dinesh Kumar
Schiff base metal complexes are well-known to intercalate DNA. The La(III) complexes have been synthesized such that they hinder with the role of the topoisomerases, which control the topology of DNA during the cell-division cycle. Although several promising chemotherapeutics have been developed, on the basis of Schiff base metal complex DNA intercalating system they did not proceed past clinical trials due to their dose-limiting toxicity. Herein, we discuss an alternative compound, the La(III) complex, [La(L(1))2Cl3]·7H2O based on a Schiff base ligand 2,3-dihydro-1H-indolo-[2,3-b]-phenazin-4(5H)-ylidene)benzothiazole-2-amine (L(1)), and report in vitro cell studies...
February 15, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/26608463/osteoprotegerin-secreted-by-inflammatory-and-invasive-breast-cancer-cells-induces-aneuploidy-cell-proliferation-and-angiogenesis
#18
Sudeshna Goswami, Neelam Sharma-Walia
BACKGROUND: Osteoprotegerin (OPG) is a glycoprotein that has multifaceted role and is associated with several cancer malignancies like that of bladder carcinoma, gastric carcinoma, prostate cancer, multiple myeloma and breast cancer. Also OPG has been associated with several organ pathologies. The widespread expression of OPG suggests that OPG may have multiple biological activities that are yet to be explored. METHODS: The anchorage-independent sphere cultures of the adherent cells were instrumental in our study as it provided a deeper insight into the complexity of a 3D tumor...
2015: BMC Cancer
https://www.readbyqxmd.com/read/26571387/tumor-repression-of-vcap-xenografts-by-a-pyrrole-imidazole-polyamide
#19
Amanda E Hargrove, Thomas F Martinez, Alissa A Hare, Alexis A Kurmis, John W Phillips, Sudha Sud, Kenneth J Pienta, Peter B Dervan
Pyrrole-imidazole (Py-Im) polyamides are high affinity DNA-binding small molecules that can inhibit protein-DNA interactions. In VCaP cells, a human prostate cancer cell line overexpressing both AR and the TMPRSS2-ERG gene fusion, an androgen response element (ARE)-targeted Py-Im polyamide significantly downregulates AR driven gene expression. Polyamide exposure to VCaP cells reduced proliferation without causing DNA damage. Py-Im polyamide treatment also reduced tumor growth in a VCaP mouse xenograft model...
2015: PloS One
https://www.readbyqxmd.com/read/26560244/topoisomerase-2-alpha-cooperates-with-androgen-receptor-to-contribute-to-prostate-cancer-progression
#20
J L Schaefer-Klein, Stephen J Murphy, Sarah H Johnson, George Vasmatzis, Irina V Kovtun
Overexpression of TOP2A is associated with risk of systemic progression in prostate cancer patients, and higher levels of TOP2A were found in hormone-resistant cases. To elucidate the mechanism by which high levels of TOP2A contribute to tumor progression we generated TOP2A overexpressing prostate cancer cell lines. We show that TOP2A promotes tumor aggressiveness by inducing chromosomal rearrangements of genes that contribute to a more invasive phenotype. Anti-androgen treatment alone was ineffective in killing TOP2A overexpressing cells due to activation of an androgen receptor network...
2015: PloS One
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