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Platinum resistance

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https://www.readbyqxmd.com/read/28221868/somatic-brca1-2-recovery-as-a-resistance-mechanism-after-exceptional-response-to-poly-adp-ribose-polymerase-inhibition
#1
Stephanie Lheureux, Jeff P Bruce, Julia V Burnier, Katherine Karakasis, Patricia A Shaw, Blaise A Clarke, S Y Cindy Yang, Rene Quevedo, Tiantian Li, Mark Dowar, Valerie Bowering, Trevor J Pugh, Amit M Oza
Purpose Durable and long-term responses to the poly (ADP-ribose) polymerase inhibitor olaparib are observed in patients without BRCA1/2 mutations. However, beyond BRCA1/2 mutations, there are no approved biomarkers for olaparib in high-grade serous ovarian cancer (HGSOC). To determine mechanisms of durable response and resistance to olaparib therapy, we performed an analysis of HGSOC tumors from three patients without germline BRCA1/2 mutations who experienced exceptional responses to olaparib. Patients and Methods We performed integrated exome, low-pass genome, and RNA sequence analysis of tumors at diagnosis and upon relapse from patients with platinum-sensitive HGSOC recurrence who were treated > 5 years with olaparib therapy as a single agent...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28219202/-precision-treatment-after-resistance-to-first-generation-egfr-tki-in-patients-with-non-small-cell-lung-cancer
#2
C Pi, Y C Zhang, C R Xu, Q Zhou
Recently, with the research progress in molecular classification, the treatment of advanced non-small cell lung cancer (NSCLC) has been established as a model of anti-tumor treatment of precision medicine. The discovery of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) has transformed the treatment of NSCLC from platinum based doublet chemotherapy into era of target therapy. EGFR-TKI, such as erlotinib and gefitinib, have been recommended as standard first-line treatment of patients with EGFR mutation...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28215839/unraveling-the-etiology-of-ovarian-cancer-racial-disparity-in-the-deep-south-is-it-nature-or-nurture
#3
Jerlinda Ross, Katelyn V Braswell, Luciana Madeira da Silva, Frances Mujica, Sam Stutsman, Michael A Finan, William Nicolson, Mary Danner Harmon, Megan Missanelli, Alex Cohen, Ajay Singh, Jennifer M Scalici, Rodney P Rocconi
BACKGROUND: Our objective was to evaluate racial treatment and survival disparities in black women with ovarian cancer in the Deep South and to determine how environmental factors / socioeconomic status (SES) influence survival. METHODS: A retrospective study of ovarian cancer patients from 2007 to 2014 was performed. Socioeconomic status (SES) was obtained though U.S. Census block data and compared using Yost scores. Comparisons were performed using standard statistical approaches...
February 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28215024/pharmacogenomics-of-platinum-based-chemotherapy-in-non-small-cell-lung-cancer-focusing-on-dna-repair-systems
#4
REVIEW
Yi Xiong, Bi-Yun Huang, Ji-Ye Yin
Drug therapy for non-small cell lung cancer consists mainly of platinum-based chemotherapy regimens. However, toxicity, drug resistance, and high risk of death have been seen in the clinic, which means there is a need for optimizing the use of medications. Platinum resistance could be mediated by a series of DNA repair pathways, and therefore, these pathways should be taken into account for optimizing drug using. The goal of pharmacogenomics is to elucidate genetic factors, such as DNA repair genes, which might underlie drug efficacy and effectiveness, and to improve therapeutic effects or guide personalized therapy as well...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28214754/new-pt-nnso-core-anticancer-agents-structural-optimization-and-investigation-of-their-anticancer-activity
#5
Shu Xian Chong, Yinxue Jin, Steve Chik Fun Au-Yeung, Kenneth Kin Wah To
A series of new platinum Pt(II) compounds possessing a bidentate leaving ligand modified from oxaliplatin has been synthesized, with one of the oxygen ligating atom substituted for a sulphur atom (resulting in a Pt-NNSO coordination core structure). The general structures are R,R-diaminocyclohexane (DACH)-Pt-(methylthio)acetic acid (K4) and DACH-Pt-(thiophenylacetic acid) (K4 derivatives). Substitution of an electron donating or withdrawing group at the ortho or para position on the phenyl ring of K4 derivatives was found to affect the complexes' stability, reactivity with the biological molecules (5'-guanosine monophosphate (5'-GMP) and L-methionine (L-Met)) and anticancer activity...
February 12, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28210007/annealing-stability-study-of-co20fe60b20-mgo-co20fe60b20-perpendicular-magnetic-tunnel-junctions
#6
P J Chen, M Zhu, S Tibus, T Dyer, J Piccirillo, B Ocker, R D Shull
A full Co20Fe60B20\MgO\ Co20Fe60B20 perpendicular magnetic tunnel junction (pMTJ) with (Co\Pt) multilayers as pinning layers and different functional multilayers stacks were made and annealed at different temperatures. The tunneling magnetoresistance ratio (TMR) and MgO barrier resistance-area product (RA) were measured and analyzed as a function of annealing temperature. The TMR of pMTJs dramatically declines with increasing annealing temperatures from 320 °C to 400 °C while the RA increases with temperature from 375 °C to 450 °C...
January 18, 2017: Journal of Physics D: Applied Physics
https://www.readbyqxmd.com/read/28206967/calcium-regulatory-proteins-as-modulators-of-chemotherapy-in-human-neuroblastoma
#7
Ana-Maria Florea, Elizabeth Varghese, Jennifer E McCallum, Safa Mahgoub, Irfan Helmy, Sharon Varghese, Neha Gopinath, Steffen Sass, Fabian J Theis, Guido Reifenberger, Dietrich Büsselberg
Neuroblastoma (NB) is a pediatric cancer treated with poly-chemotherapy including platinum complexes (e.g. cisplatin (CDDP), carboplatin), DNA alkylating agents, and topoisomerase I inhibitors (e.g. topotecan (TOPO)). Despite aggressive treatment, NB may become resistant to chemotherapy. We investigated whether CDDP and TOPO treatment of NB cells interacts with the expression and function of proteins involved in regulating calcium signaling. Human neuroblastoma cell lines SH-SY5Y, IMR-32 and NLF were used to investigate the effects of CDDP and TOPO on cell viability, apoptosis, calcium homeostasis, and expression of selected proteins regulating intracellular calcium concentration ([Ca2+]i)...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205649/comparative-studies-of-oxaliplatin-based-platinum-iv-complexes-in-different-in-vitro-and-in-vivo-tumor-models
#8
Simone Göschl, Ekaterina Schreiber-Brynzak, Verena Pichler, Klaudia Cseh, Petra Heffeter, Ute Jungwirth, Michael A Jakupec, Walter Berger, Bernhard K Keppler
Using platinum(iv) prodrugs of clinically established platinum(ii) compounds is a strategy to overcome side effects and acquired resistances. We studied four oxaliplatin-derived platinum(iv) complexes with varying axial ligands in various in vitro and in vivo settings. The ability to interfere with DNA (pUC19) in the presence and absence of a reducing agent (ascorbic acid) was investigated in cell-free experiments. Cytotoxicity was compared under normoxic and hypoxic conditions in monolayer cultures and multicellular spheroids of colon carcinoma cell lines...
February 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28202521/ex-vivo-explant-cultures-of-non-small-cell-lung-carcinoma-enable-evaluation-of-primary-tumor-responses-to-anticancer-therapy
#9
Ellie Karekla, Wen-Jing Liao, Barry Sharp, John Pugh, Helen Reid, John Pc Le Quesne, David Moore, Catrin A Pritchard, Marion MacFarlane, J Howard Pringle
To improve treatment outcomes in non-small cell lung cancer (NSCLC), preclinical models that can better predict individual patient response to novel therapies are urgently needed. Using freshly resected tumor tissue, we describe an optimized ex vivo explant culture model that enables concurrent evaluation of NSCLC response to therapy while maintaining the tumor microenvironment. We found that ~70% of primary NSCLC specimens were amenable to explant culture with tissue integrity intact for up to 72 hours after explant...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28198375/haploinsufficiency-networks-identify-targetable-patterns-of-allelic-deficiency-in-low-mutation-ovarian-cancer
#10
Joe Ryan Delaney, Chandni B Patel, Katelyn McCabe Willis, Mina Haghighiabyaneh, Joshua Axelrod, Isabelle Tancioni, Dan Lu, Jaidev Bapat, Shanique Young, Octavia Cadassou, Alena Bartakova, Parthiv Sheth, Carley Haft, Sandra Hui, Cheryl Saenz, David D Schlaepfer, Olivier Harismendy, Dwayne G Stupack
Identification of specific oncogenic gene changes has enabled the modern generation of targeted cancer therapeutics. In high-grade serous ovarian cancer (OV), the bulk of genetic changes is not somatic point mutations, but rather somatic copy-number alterations (SCNAs). The impact of SCNAs on tumour biology remains poorly understood. Here we build haploinsufficiency network analyses to identify which SCNA patterns are most disruptive in OV. Of all KEGG pathways (N=187), autophagy is the most significantly disrupted by coincident gene deletions...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28197632/pgrmc1-dependent-autophagy-by-hyperoside-induces-apoptosis-and-sensitizes-ovarian-cancer-cells-to-cisplatin-treatment
#11
Xiaofei Zhu, Mingde Ji, Yue Han, Yuanyuan Guo, Wenqiang Zhu, Feng Gao, Xuewen Yang, Chunbing Zhang
Cisplatin treatment some times leads to chemoresistance, which is now acknowledged partially due to the inductive expression of progesterone receptor membrane component (PGRMC)1 in ovarian cancer cells. PGRMC1 enhances autophagy, activates cytochrome p450, and inveigles signaling pathways to promote cell survival and reduce the effect of drug treatments. In this study, we give first line evidence that hyperoside inhibits cell viability, triggers autophagy and apoptosis in ovarian cancer cell lines. Mechanistically, PGRMC1-dependent autophagy was utilized by hyperoside to induce apoptotic cell death...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28192521/acquired-resistance-to-oxaliplatin-is-not-directly-associated-with-increased-resistance-to-dna-damage-in-sk-n-asroxali4000-a-newly-established-oxaliplatin-resistant-sub-line-of-the-neuroblastoma-cell-line-sk-n-as
#12
Emily Saintas, Liam Abrahams, Gulshan T Ahmad, Anu-Oluwa M Ajakaiye, Abdulaziz S H A M AlHumaidi, Candice Ashmore-Harris, Iain Clark, Usha K Dura, Carine N Fixmer, Chinedu Ike-Morris, Mireia Mato Prado, Danielle Mccullough, Shishir Mishra, Katia M U Schöler, Husne Timur, Maxwell D C Williamson, Markella Alatsatianos, Basma Bahsoun, Edith Blackburn, Catherine E Hogwood, Pamela E Lithgow, Michelle Rowe, Lyto Yiangou, Florian Rothweiler, Jindrich Cinatl, Richard Zehner, Anthony J Baines, Michelle D Garrett, Campbell W Gourlay, Darren K Griffin, William J Gullick, Emma Hargreaves, Mark J Howard, Daniel R Lloyd, Jeremy S Rossman, C Mark Smales, Anastasios D Tsaousis, Tobias von der Haar, Mark N Wass, Martin Michaelis
The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin...
2017: PloS One
https://www.readbyqxmd.com/read/28187748/characterization-of-ovarian-clear-cell-carcinoma-using-target-drug-based-molecular-biomarkers-implications-for-personalized-cancer-therapy
#13
Mengjiao Li, Haoran Li, Fei Liu, Rui Bi, Xiaoyu Tu, Lihua Chen, Shuang Ye, Xi Cheng
BACKGROUND: It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC)...
February 10, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28184025/metabolic-interrogation-as-a-tool-to-optimize-chemotherapeutic-regimens
#14
Vlad C Sandulache, Yunyun Chen, Lei Feng, William N William, Heath D Skinner, Jeffrey N Myers, Raymond E Meyn, Jinzhong Li, Ainiwaer Mijiti, James A Bankson, Clifton D Fuller, Marina Y Konopleva, Stephen Y Lai
Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC).We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28183801/fatty-acid-16-4-n-3-stimulates-a-gpr120-induced-signaling-cascade-in-splenic-macrophages-to-promote-chemotherapy-resistance
#15
Julia M Houthuijzen, Ilse Oosterom, Brian D Hudson, Akira Hirasawa, Laura G M Daenen, Chelsea M McLean, Steffen V F Hansen, Marijn T M van Jaarsveld, Daniel S Peeper, Sahar Jafari Sadatmand, Jeanine M L Roodhart, Chris H A van de Lest, Trond Ulven, Kenji Ishihara, Graeme Milligan, Emile E Voest
Although chemotherapy is designed to eradicate tumor cells, it also has significant effects on normal tissues. The platinum-induced fatty acid, 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid), induces systemic resistance to a broad range of DNA-damaging chemotherapeutics. We show that 16:4(n-3) exerts its effect by activating splenic F4/80(+)/CD11b(low) macrophages, which results in production of chemoprotective lysophosphatidylcholines (LPCs). Pharmacologic studies, together with analysis of expression patterns, identified GPR120 on F4/80(+)/CD11b(low) macrophages as the relevant receptor for 16:4(n-3)...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28179299/complex-of-platinum-ii-with-tris-2-carboxyethyl-phosphine-induces-apoptosis-in-canine-lymphoma-leukemia-cell-lines
#16
Marta Henklewska, Aleksandra Pawlak, Hanna Pruchnik, Bozena Obminska-Mrukowicz
BACKGROUND/AIM: Platinum-based drugs are a very potent class of anticancer drugs commonly used in anticancer therapy. However, resistance development and severe adverse effects make further research on new platinum derivatives necessary. In this study, cytotoxic activity of a new platinum(II) compound containing tris(2-carboxyethyl)phosphine (TCEP) ligand cis-[PtCl2(TCEP)2] was tested against canine lymphoma and leukemia cell lines and its activity was compared to that of cisplatin. MATERIALS AND METHODS: Cells were exposed for 24 h to increasing concentrations of the studied compounds and cell viability was assessed by propidium iodide staining...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28178839/substrate-selectivity-in-the-low-temperature-atomic-layer-deposition-of-cobalt-metal-films-from-bis-1-4-di-tert-butyl-1-3-diazadienyl-cobalt-and-formic-acid
#17
Marissa M Kerrigan, Joseph P Klesko, Sara M Rupich, Charles L Dezelah, Ravindra K Kanjolia, Yves J Chabal, Charles H Winter
The initial stages of cobalt metal growth by atomic layer deposition are described using the precursors bis(1,4-di-tert-butyl-1,3-diazadienyl)cobalt and formic acid. Ruthenium, platinum, copper, Si(100), Si-H, SiO2, and carbon-doped oxide substrates were used with a growth temperature of 180 °C. On platinum and copper, plots of thickness versus number of growth cycles were linear between 25 and 250 cycles, with growth rates of 0.98 Å/cycle. By contrast, growth on ruthenium showed a delay of up to 250 cycles before a normal growth rate was obtained...
February 7, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28178720/erbb4-expression-in-ovarian-serous-carcinoma-resistant-to-platinum-based-therapy
#18
COMPARATIVE STUDY
Ozlen Saglam, Yin Xiong, Douglas C Marchion, Carolina Strosberg, Robert M Wenham, Joseph J Johnson, Daryoush Saeed-Vafa, Christopher Cubitt, Ardeshir Hakam, Anthony M Magliocco
Few data exist on the prognostic and predictive impact of erb-b2 receptor tyrosine kinase 4 (ERBB4) in ovarian cancer. Thus, we evaluated ERBB4 expression by immunohistochemistry in a tumor microarray consisting of 100 ovarian serous carcinoma specimens (50 complete responses [CRs] and 50 incomplete responses [IRs] to platinum-based therapy), 51 normal tissue controls, and 16 ovarian cancer cell lines. H scores were used to evaluate expression and were semiquantitatively classified into low, intermediate, and high categories...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28166401/maximizing-synergistic-activity-when-combining-rnai-and-platinum-based-anticancer-agents
#19
Haihua Xiao, Ruogu Qi, Ting Li, Samuel G Awuah, Yaorong Zheng, Wei Wei, Xiang Kang, Haiqin Song, Yongheng Wang, Yingjie Yu, Molly A Bird, Xiabin Jing, Michael B Yaffe, Michael J Birrer, P Peter Ghoroghchian
RNAi approaches have been widely combined with platinum-based anticancer agents to elucidate cellular responses and to target gene products that mediate acquired resistance. Recent work has demonstrated that platination of siRNA prior to transfection may negatively influence RNAi efficiency based on the position and sequence of its guanosine nucleosides. Here, we used detailed spectroscopic characterization to demonstrate rapid formation of Pt-guanosine adducts within 30 min after coincubation of oxaliplatin [OxaPt(II)] or cisplatin [CisPt(II)] with either guanosine monophosphate or B-cell lymphoma 2 (BCL-2) siRNA...
February 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28155621/recent-approaches-to-platinum-iv-prodrugs-a-variety-of-strategies-for-enhanced-delivery-and-efficacy
#20
Anas Najjar, Naeema Rajabi, Rafik Karaman
BACKGROUND: Intensive efforts have been implemented to improve the efficacy of platinum complexes especially with emerging cisplatin resistance and elevated cancer deaths. Platinum(IV) agents show better pharmacokinetics and decreased side effects compared to Platinum(II) agents. METHODS: This review aims to summarize and categorize the strategies being employed to improve the efficacy of Platinum-based anticancer agents in recent years. RESULTS: Nanoparticles and nanoplatforms offer a vast variety of strategies in targeting specific tumor types and delivering one or two lethal drugs simultaneously...
February 1, 2017: Current Pharmaceutical Design
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