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https://www.readbyqxmd.com/read/29352235/systems-modeling-accurately-predicts-responses-to-genotoxic-agents-and-their-synergism-with-bcl-2-inhibitors-in-triple-negative-breast-cancer-cells
#1
Federico Lucantoni, Andreas U Lindner, Norma O'Donovan, Heiko Düssmann, Jochen H M Prehn
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29344837/evaluation-of-the-profile-and-mechanism-of-neurotoxicity-of-water-soluble-cu-p-4-pf6-and-au-p-4-pf6-p-thp-or-pta-anticancer-complexes
#2
C Ceresa, G Nicolini, S Semperboni, V Gandin, M Monfrini, F Avezza, P Alberti, A Bravin, M Pellei, C Santini, Guido Cavaletti
[Cu(thp)4]PF6, [Cu(PTA)4]PF6, [Au(thp)4]PF6 and [Au(PTA)4]PF6 are phosphane (thp = tris(hydroxymethyl)phosphane; PTA = 1,3,5-triaza-7-phosphaadamantane) copper(I) and gold(I) water-soluble complexes characterized by high anticancer activity in a wide range of solid tumors, often able to overcome drug resistance of platinum-based compounds. For these reasons, they have been proposed as a valid alternative to platinum-based chemotherapeutic drugs (e.g., cisplatin and oxaliplatin). In vitro experiments performed on organotypic cultures of dorsal root ganglia (DRG) from 15-day-old rat embryos revealed that copper-based compounds were not neurotoxic even at concentrations higher than the IC50 obtained in human cancer cells while [Au(PTA)4]PF6 was neurotoxic at lower concentration than IC50 in cancer cell lines...
January 17, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29344283/antigen-presentation-of-the-oct4-and-sox2-peptides-by-cd154-activated-b-lymphocytes-enhances-the-killing-effect-of-cytotoxic-t-lymphocytes-on-tumor-stem-like-cells-derived-from-cisplatin-resistant-lung-cancer-cells
#3
Xueyan Zhang, Yanwei Zhang, Jianlin Xu, Huimin Wang, Xiaoxuan Zheng, Yuqing Lou, Baohui Han
The present study investigated whether antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B lymphocytes can enhance the killing effect of CD8+ cytotoxic T lymphocytes (CTLs) on lung stem-like cancer cells (SLCCs). The CTLs were generated using an accelerated co-cultured dendritic cells (DC) (acDC) assay by incubating human peripheral blood mononuclear cells (PBMCs) from non-small-cell lung cancer patients with antigen peptides of Oct4 and Sox2 in the presence of several DC-activating agents...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344219/upregulation-of-mir-146a-increases-cisplatin-sensitivity-of-the-non-small-cell-lung-cancer-a549-cell-line-by-targeting-jnk-2
#4
Linrong Pang, Jinger Lu, Jia Huang, Caihong Xu, Hui Li, Guangbo Yuan, Xiaochun Cheng, Jun Chen
The aim of the present study was to investigate the effects of microRNA (miR-)146a on the cisplatin sensitivity of the non-small cell lung cancer (NSCLC) A549 cell line and study the underlying molecular mechanism. The differences in expression of miRNAs between A549 and A549/cisplatin (A549/DDP) cells were determined, and miR-146a was selected to study its effect on cisplatin sensitivity of A549/DDP cells. miR-146a mimic and inhibitor transient transfection systems were constructed using vectors, and A549/DDP cells were infected with miR-146a mimic and inhibitor to investigate growth, apoptosis and migration...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344202/metformin-in-combination-with-cisplatin-inhibits-cell-viability-and-induces-apoptosis-of-human-ovarian-cancer-cells-by-inactivating-erk-1-2
#5
Jian-Hong Dang, Zhi-Jun Jin, Xiao-Jun Liu, Dian Hu, Jing Wang, Yan Luo, Ling-Ling Li
Metformin protects against insulin resistance by restoring insulin sensitivity and may also possess anticancer activity. The aim of the present study was to investigate the effects of metformin alone or combined with cisplatin (DDP) on the cell viability and apoptosis of HO-8910 human ovarian cancer cells, and to investigate metformin as a potential novel therapeutic for treating ovarian cancer. The viability of HO-8910 cells was assessed using a cell proliferation and cytotoxicity assay following treatment with different concentrations of metformin (0...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344124/molecular-biological-characterization-and-drug-sensitivity-of-chidamide-resistant-non-small-cell-lung-cancer-cells
#6
Song'e Luo, Kai Ma, Hongxia Zhu, Shuren Wang, Mei Liu, Weina Zhang, Shufang Liang, Ningzhi Xu
Chidamide, a histone deacetylase (HDAC) inhibitor, has been applied in clinical trials for various types of hematological and solid tumors. Although acquired resistance is common in chemotherapy, the mechanism of resistance to chidamide is poorly characterized. The goal of the present study was to explore, in detail, the mechanism for the induced resistance to chidamide, and investigate a potential cross-resistance to other chemotherapeutic drugs. A549 cells were exposed to gradually increasing chidamide concentrations to establish a chidamide-resistant non-small cell lung cancer cell line (A549-CHI-R)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343747/computational-trans-omics-approach-characterised-methylomic-and-transcriptomic-involvements-and-identified-novel-therapeutic-targets-for-chemoresistance-in-gastrointestinal-cancer-stem-cells
#7
Masamitsu Konno, Hidetoshi Matsui, Jun Koseki, Ayumu Asai, Yoshihiro Kano, Koichi Kawamoto, Naohiro Nishida, Daisuke Sakai, Toshihiro Kudo, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii
We investigated the relationship between methylomic [5-methylation on deoxycytosine to form 5-methylcytosine (5mC)] and transcriptomic information in response to chemotherapeutic 5-fluorouracil (5-FU) exposure and cisplatin (CDDP) administration using the ornithine decarboxylase (ODC) degron-positive cancer stem cell model of gastrointestinal tumour. The quantification of 5mC methylation revealed various alterations in the size distribution and intensity of genomic loci for each patient. To summarise these alterations, we transformed all large volume data into a smooth function and treated the area as a representative value of 5mC methylation...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343567/parainfluenza-virus-infection-sensitizes-cancer-cells-to-dna-damaging-agents-implications-for-oncolytic-virus-therapy
#8
Candace R Fox, Griffith D Parks
We have previously shown that the Parainfluenza virus 5 (PIV5) mutant P/V-CPI- is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burden in mouse model systems. Here we show that P/V-CPI- infection of human laryngeal cancer HEp-2 cells results in the majority of the cells dying, but unexpectedly, over time there is an emergence of a population of cells which survive as P/V-CPI- persistently infected (PI) cells. P/V-CPI- PI cells had elevated levels of basal caspase activation, and viability was highly dependent on activity of cellular inhibitors of apoptosis (IAPs) such as Survivin and XIAP...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29342962/functional-analyses-of-runx3-and-camkiin%C3%AE-in-ovarian-cancer-cell-lines-reveal-tumor-suppressive-functions-for-camkiin%C3%AE-and-dichotomous-roles-for-runx3-transcript-variants
#9
Karolin Heinze, Daniel Kritsch, Alexander S Mosig, Matthias Dürst, Norman Häfner, Ingo B Runnebaum
(1) Background: Epithelial ovarian cancer (EOC) is the most lethal cancer of the female reproductive system. In an earlier study, we identified multiple genes as hypermethylated in tumors of patients with poor prognosis. The most promising combination of markers to predict a patient's outcome was CaMKIINα and RUNX3. Aim of this study was to functionally validate the importance of both genes. (2) Methods: IC50 measurements, cell cycle distribution-, proliferation, and migration experiments were conducted after transgene overexpression in two EOC cell lines...
January 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29340396/synthesis-and-antiproliferative-activity-of-a-series-of-new-platinum-and-palladium-diphosphane-complexes
#10
Carleen Cullinane, Glen B Deacon, Penny R Drago, Anja P Erven, Peter C Junk, Jenny Luu, Gerd Meyer, Simon Schmitz, Ingo Ott, Julia Schur, Lorraine K Webster, Axel Klein
New organometallic complexes [M(dppe)(R)2] {where M = Pt or Pd, dppe = 1,2-bis(diphenylphosphano)ethane, and R = C6F4H-x (x = 6,5,4), C6F3H2-3,5, C6F3H2-5,6, C6F3H2-3,6, C6F4(OMe)-4, and C6F4(cyclo-C5H10N)-4, the numbers x refer to the positions of the protons in the polyfluoroaryl ligands} were synthesised either through transmetalation from the dichlorido complexes [M(dppe)Cl2] or through ligand exchange using [M(diene)Cl2] precursor complexes with diene = 1,5-cyclooctadiene (cod) or 1,5-hexadiene (hex). Alternatively, [M(dppX)Cl(R)] complexes with dppX = dppm (1,1-bis(diphenylphosphano)methane), dppe, dppp (1,3-bis(diphenylphosphano)propane), and dppb (1,4-bis(diphenylphosphano)butane) were prepared in decarboxylation reactions from thallium(i) carboxylates Tl(O2CR)...
January 17, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29340100/the-inhibition-of-cordycepin-on-cancer-stemness-in-tgf-beta-induced-chemo-resistant-ovarian-cancer-cell
#11
Chia-Woei Wang, Bao-Hong Lee, Chen-Jei Tai
Chemotherapy is one of the main approach for ovarian cancer. Cancer stem cells (CSCs) escape chemotherapy and lead to chemoresistance. We previously demonstrated that cordycepin (Cd) inhibited metastasis in human ovarian carcinoma cells, the aim of this study is to investigate the effects of Cd on ovarian cancer stemness. TGF-beta was used to induce chemoresistance of chemotherapeutic agent cisplatin in SKOV-3 ovarian cancer cells. After treating with 100 μM of Cd, cell viability, the percentage of cancer stem cells, and the levels of matrix metalloproteinases (MMPs) were decreased in TGF-beta-induced SKOV-3 cells...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340044/cepharanthine-hydrochloride-reverses-the-mdr1-p-glycoprotein-mediated-esophageal-squamous-cell-carcinoma-cell-cisplatin-resistance-through-jnk-and-p53-signals
#12
Pengjun Zhou, Rong Zhang, Ying Wang, Dandan Xu, Li Zhang, Jinhong Qin, Guifeng Su, Yue Feng, Hongce Chen, Siyuan You, Wen Rui, Huizhong Liu, Suhong Chen, Hongyuan Chen, Yifei Wang
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy that is often resistant to therapy. Nowadays, chemotherapy is still one of the main methods for the treatment of ESCC. However, the multidrug resistance (MDR)-mediated chemotherapy resistance is one of the leading causes of death. Exploring agents able to reverse MDR, which thereby increase the sensitivity with clinical first-line chemotherapy drugs, could significantly improve cancer treatment. Cepharanthine hydrochloride (CEH) has the ability to reverse the MDR in ESCC and the mechanism involved have not been reported...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339540/radio-resistant-cervical-cancers-are-sensitive-to-inhibition-of-glycolysis-and-redox-metabolism
#13
Ramachandran Rashmi, Xiaojing Huang, John M Floberg, Adnan Elhammali, Michael L McCormick, Gary J Patti, Douglas R Spitz, Julie K Schwarz
Highly glycolytic cervical cancers largely resist treatment by cisplatin and co-administered pelvic irradiation as the present standard of care. In this study, we investigated the effects of inhibiting glycolysis and thiol redox metabolism to evaluate them as alternate treatment strategies in these cancers. In a panel of multiple cervical cancer cell lines, we evaluated sensitivity to inhibition of glycolysis (2-DG) with or without simultaneous inhibition of glutathione and thioredoxin metabolism (BSO/AUR)...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29333543/in-vitro-evaluation-of-the-enantiomeric-r-and-s-1-1-binaphthyl-2-2-diaminodichlorido-pt-ii-complexes-in-human-burkitt-lymphoma-cells-emphasis-on-cellular-accumulation-cytotoxicity-dna-binding-and-ability-to-induce-apoptosis
#14
Belinda H Sørensen, Patrick Werth, Ian H Lambert, Patrick J Bednarski
The aim of this project is to gain insights into the uptake and cellular actions of the enantiomeric R- and S-1,1'-binaphthyl-2,2'-diaminodichlorido-Pt(ii) complexes (R- and S-[Pt(DABN)Cl2]) in the cisplatin-sensitive human Burkitt lymphoma cell line (Gumbus, IC50: 1.3 ± 0.2 μM) and its cisplatin-resistant sub-line (CDDPrGB, IC50: 6.6 ± 1.2 μM). The cellular uptakes of R- and S-[Pt(DABN)Cl2] are ca. 4-fold higher than cisplatin, and involve a transport mechanism independent of the volume-sensitive, organic anion-channel complex, which facilitates cisplatin accumulation...
January 15, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29332411/%C3%AE-1-integrin-mediated-multicellular-resistance-in-hepatocellular-carcinoma-through-activation-of-the-fak-akt-pathway
#15
Tao Tian, Chun-Li Li, Xiao Fu, Shu-Hong Wang, Jun Lu, Hui Guo, Yu Yao, Ke-Jun Nan, Yu-Juan Yang
Objective To explore the role and mechanism of β1 integrin in the regulation of multicellular drug resistance in hepatocellular carcinoma (HCC). Methods This in vitro study used a liquid overlay technique to obtain multicellular spheroids of two human HCC cell lines, HepG2 and Bel-7402. The morphology of the spheroids was observed by optical and electron microscopy. The effects of exposure to 5-fluorouracil (5-FU) and cisplatin (CDDP) on cell proliferation and the induction of apoptosis were assessed in monolayer cells and multicellular spheroids...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29331417/down-regulation-of-rip3-potentiates-cisplatin-chemoresistance-by-triggering-hsp90-erk-pathway-mediated-dna-repair-in-esophageal-squamous-cell-carcinoma
#16
Yulin Sun, Linhui Zhai, Shouzhi Ma, Chengpu Zhang, Lina Zhao, Ning Li, Yang Xu, Tao Zhang, Zhimin Guo, Heng Zhang, Ping Xu, Xiaohang Zhao
Receptor interacting protein kinase 3 (RIP3) is a critical regulator of programmed necrotic cell death. Here, we observed that RIP3 was significantly down-regulated in esophageal cancer. And its remaining expression was associated with better response to chemotherapy and prolonged survival. Notably, re-expression of kinase-dead RIP3 also restored cisplatin sensitivity, suggesting that some roles of RIP3 beyond necroptosis may be involved in cisplatin-based chemosensitivity. To investigate the mechanisms, a large-scale quantitative proteomics study was performed after cisplatin treatment in RIP3-knockdown cells...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29330293/differential-regulation-of-let-7-by-lin28b-isoform-specific-functions
#17
Rei Mizuno, Priya Chatterji, Sarah F Andres, Kathryn E Hamilton, Lauren Simon, Shawn W Foley, Arjun N Jeganathan, Brian D Gregory, Blair B Madison, Anil K Rustgi
The RNA binding protein LIN28B plays an important role in development, stem cell biology and tumorigenesis. LIN28B has two isoforms: the LIN28B-long and -short isoforms. Although studies have revealed the functions of the LIN28B-long isoform in tumorigenesis, the role of the LIN28B-short isoform remains unclear and represents a major gap in the field. The LIN28B-long and -short isoforms are expressed in a subset of human colorectal cancers (CRCs) and adjacent normal colonic mucosa, respectively. To elucidate the functional and mechanistic aspects of these isoforms, CRC cells (Caco-2 and LoVo) were generated to either express no LIN28B or the -short or -long isoform...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29328459/%C3%AE-solanine-enhances-the-chemosensitivity-of-esophageal-cancer-cells-by-inducing-microrna%C3%A2-138-expression
#18
Jianbo Wu, Li Wang, Xinhui Du, Qianqian Sun, Yuanyuan Wang, Min Li, Wenqiao Zang, Kangdong Liu, Guoqiang Zhao
Esophageal cancer is a common malignant tumor worldwide. Inherent and acquired drug resistance are the major challenges faced in anticancer chemotherapy. This study aimed to explore the effects of α-solanine in regards to the chemosensitivity of esophageal cancer cells. We found that α-solanine enhanced the sensitivity of EC9706 and KYSE30 cells to 5-flurouracil (5-FU) and cisplatin (Cis) by promoting drug-induced apoptosis. qRT-PCR and western blotting results showed that α-solanine treatment promoted miR-138 expression and decreased survivin expression in EC9706 and KYSE30 cells...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328435/mir%C3%A2-214-reduces-cisplatin-resistance-by-targeting-netrin%C3%A2-1-in-bladder-cancer-cells
#19
Jiao Liu, Jianbin Bi, Zeliang Li, Zhenhua Li, Xiankui Liu, Chuize Kong
miR‑214 has been reported to be downregulated in several cancer types, such as bladder cancer. However, its involvement in apoptosis and chemoresistance has not been investigated. The present study aimed to clarify the biological function of miR‑214 and potential mechanisms in chemoresistance of bladder cancer cells. Reverse transcription‑quantitative polymerase chain reaction demonstrated that miR‑214 was downregulated in bladder cancer tissues compared with the level in normal tissues. miR‑214 was downregulated in bladder cancer cell lines compared with the level in the normal cell line SV‑HUC‑1...
January 10, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29328427/mir-133b-reverses-cisplatin-resistance-by-targeting-gstp1-in-cisplatin-resistant-lung-cancer-cells
#20
Chen Lin, Liyi Xie, Yan Lu, Zhihuang Hu, Jianhua Chang
MicroRNAs play a critical role in chemoresistance and are implicated in various biological and pathological processes of cells. The objective of the present study was to explore the role of miR‑133b and its mechanism in the regulation of cisplatin resistance and tumor progression in cisplatin‑resistant non‑small cell lung cancer (NSCLC) cells. Reverse transcription‑quantitative polymerase chain reaction and western blot assays of the cisplatin‑resistant cell lines A549/DPP and H1299/DDP displayed the reduced expression of miR‑133b and increased expression of glutathione-S-transferase P1 (GSTP1) in the resistant cells compared with the respective parental cell lines A549 and H1299...
January 11, 2018: International Journal of Molecular Medicine
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