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https://www.readbyqxmd.com/read/29781035/knockdown-of-kpna2-inhibits-autophagy-in-oral-squamous-cell-carcinoma-cell-lines-by-blocking-p53-nuclear-translocation
#1
Feng Lin, Li Gao, Zhenyu Su, Xiaofang Cao, Yuanbo Zhan, Ying Li, Bin Zhang
Oral squamous cell carcinoma (OSCC), one of the 10 most common types of neoplasms in the US, constitutes ~90% of all cases of oral malignancies. Chemoresistance and metastasis are difficult to avoid during the course of treatment, leading to a poor prognosis and a high mortality rate for patients with OSCC. Autophagy, a critical conserved cellular process, has been reported to be highly associated with the regulation of chemoresistance and metastasis of cancer cells. The present study investigated the role of karyopherin α2 (KPNA2), a member of the importin α family, which may serve an important role in p53 nucleocytoplasmic transport in the process of OSCC autophagy...
May 17, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29780561/triple-action-pt-iv-derivatives-of-cisplatin-a-new-class-of-potent-anticancer-agents-that-overcome-resistance
#2
Emanuele Petruzzella, Roman Sirota, Irene Solazzo, Valentina Gandin, Dan Gibson
A series of triple action Pt(iv) prodrugs was designed to test the hypothesis that multi-action compounds, where each bioactive moiety intervenes in several cellular processes, might be more effective than a single agent at killing cancer cells. In particular, "triple action" Pt(iv) derivatives of cisplatin, where the axial ligands are inhibitors of cyclooxygenase (COXi), histone deacetylase (HDACi) or pyruvate dehydrogenase kinase (PDKi) were developed. All compounds, ctc-[Pt(NH3 )2 (COXi)(PDKi)Cl2 ], ctc-[Pt(NH3 )2 (COXi)(HDACi)Cl2 ] and ctc-[Pt(NH3 )2 (HDACi)(PDKi)Cl2 ], where COXi = aspirin or ibuprofen, PDKi = dichloroacetate and HDACi = valproate or phenylbutyrate, were significantly more cytotoxic than cisplatin against all cell lines of an in-house panel of human cancer cells...
May 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29774110/high-throughput-3-dimensional-culture-of-epithelial-ovarian-cancer-cells-as-preclinical-model-of-disease
#3
Victoria Heredia-Soto, Andrés Redondo, Alberto Berjón, María Miguel-Martín, Esther Díaz, Roberto Crespo, Alicia Hernández, Laura Yébenes, Alejandro Gallego, Jaime Feliu, David Hardisson, Marta Mendiola
Background: Recent reports have identified distinct genomic patterns in ovarian carcinoma, including proliferative and mesenchymal-like groups, with worse outcome. The exact mechanisms driving the onset and progression of these tumors are still poorly understood. Additionally, researchers are concerned about the correct subtype stratification of the available cell line models, and the exploration of alternatives to monolayer culture. Identification of biomarkers to stratify cell lines, characterization of important processes as epithelial-mesenchymal transition (EMT), and the use of three-dimensional (3D) cultures as alternative models could be useful for cell line classification...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29772714/modulating-chemosensitivity-of-tumors-to-platinum-based-antitumor-drugs-by-transcriptional-regulation-of-copper-homeostasis
#4
REVIEW
Yu-Hsuan Lai, Chin Kuo, Macus Tien Kuo, Helen H W Chen
Platinum (Pt)-based antitumor agents have been effective in treating many human malignancies. Drug importing, intracellular shuffling, and exporting-carried out by the high-affinity copper (Cu) transporter ( hCtr1 ), Cu chaperone (Ato x1), and Cu exporters (ATP7A and ATP7B), respectively-cumulatively contribute to the chemosensitivity of Pt drugs including cisplatin and carboplatin, but not oxaliplatin. This entire system can also handle Pt drugs via interactions between Pt and the thiol-containing amino acid residues in these proteins; the interactions are strongly influenced by cellular redox regulators such as glutathione...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772519/p53-and-p-glycoprotein-influence-chemoresistance-in-hepatocellular-carcinoma
#5
ShengLei Li, Ming Gao, ZongMing Li, LiJie Song, XianZheng Gao, Jing Han, Feng Wang, YongFang Chen, WenCai Li, JianPing Yang
Chemoresistance is a critical obstacle to the treatment of hepatocellular carcinoma (HCC). The mechanisms underlying resistance to doxorubicin, cisplatin, and 5-fluorouracil involve p53 and P-glycoprotein (P-gp). p53 plays a role in cell growth; therefore, resistance mechanisms involve chemotherapy-induced apoptosis and p53 mutation and inactivation. P-gp is an energy-dependent drug efflux pump regulated by p53. Its role in drug resistance has provided new insights into the mechanisms underlying the involvement of p53 and P-gp in chemoresistance and may alter our traditional understanding of p53 and P-gp function...
June 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/29769618/inhibitor-of-apoptosis-proteins-iaps-mediate-collagen-type-xi-alpha-1-driven-cisplatin-resistance-in-ovarian-cancer
#6
Miran Rada, Sameera Nallanthighal, Jennifer Cha, Kerry Ryan, Jessica Sage, Catherine Eldred, Maria Ullo, Sandra Orsulic, Dong-Joo Cheon
Although, cisplatin resistance is a major challenge in the treatment of ovarian cancer, the precise mechanisms underlying cisplatin resistance are not fully understood. Collagen type XI alpha 1 (COL11A1), a gene encoding a minor fibrillar collagen of the extracellular matrix, is identified as one of the most upregulated genes in cisplatin-resistant ovarian cancer and recurrent ovarian cancer. However, the exact functions of COL11A1 in cisplatin resistance are unknown. Here we demonstrate that COL11A1 binds to integrin α1β1 and discoidin domain receptor 2 (DDR2) and activates downstream signaling pathways to inhibit cisplatin-induced apoptosis in ovarian cancer cells...
May 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29768255/asiatic-acid-aa-sensitizes-multidrug-resistant-human-lung-adenocarcinoma-a549-ddp-cells-to-cisplatin-ddp-via-downregulation-of-p-glycoprotein-mdr1-and-its-targets
#7
Qilai Cheng, Meixiang Liao, Haibo Hu, Hongliang Li, Longhuo Wu
BACKGROUND/AIMS: P-glycoprotein (P-gp, i.e., MDR1) is associated with the phenotype of multidrug resistance (MDR) and causes chemotherapy failure in the management of cancers. Searching for effective MDR modulators and combining them with anticancer drugs is a promising strategy against MDR. Asiatic acid (AA), a natural triterpene isolated from the plant Centella asiatica, may have an antitumor activity. The present study assessed the reversing effect of AA on MDR and possible molecular mechanisms of AA action in MDR1-overexpressing cisplatin (DDP)-resistant lung cancer cells, A549/DDP...
May 11, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29768183/ndrg1-disruption-alleviates-cisplatin-sodium-glycididazole-induced-dna-damage-response-and-apoptosis-in-ercc1-defective-lung-cancer-cells
#8
Lang He, Kang Liu, Xiaoshan Wang, Hong Chen, Jin Zhou, Xun Wu, Tao Liu, Yongxue Yang, Xuemei Yang, Dandan Cui, Guiqin Song, Jianguo Lei, Jun Wang
BACKGROUND: Resistance to platinum-based chemotherapy becomes a major obstacle in lung cancer treatment. Compensatory activation of nucleotide excision repair (NER) pathway is the major mechanism accounting for cisplatin-resistance. We aimed at identifying additional regulators in NER-mediated chemoresistance in a hypoxic setting induced by sodium glycididazole (CMNa)-sensitized cisplatin chemotherapy of non-small cell lung cancer (NSCLC). METHODS: We performed an RNA-sequencing (RNA-Seq) analysis to identify the genes whose expression had been differentially regulated in NER-deficient cells that had been treated by cisplatin/CMNa...
May 13, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29766327/characterization-of-carfilzomib-resistant-non-small-cell-lung-cancer-cell-lines
#9
Neale T Hanke, Elliot Imler, Marilyn T Marron, Bruce E Seligmann, Linda L Garland, Amanda F Baker
PURPOSE: We previously showed that carfilzomib (CFZ) has potent anti-proliferative and cytotoxic activity in a broad range of lung cancer cell lines. Here we investigate possible mechanisms of CFZ acquired resistance in lung cancer cell lines. METHODS: CFZ-resistant non-small cell lung cancer (NSCLC) cell lines were developed by exposing A549 and H520 cells to stepwise increasing concentrations of CFZ. Resistance to CFZ and cross-resistance to bortezomib and other chemotherapy drugs was measured using the MTT assay...
May 15, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29763634/novel-long-noncoding-rna-nmr-promotes-tumor-progression-via-nsun2-and-bptf-in-esophageal-squamous-cell-carcinoma
#10
Yuan Li, Jiagen Li, Mei Luo, Chengcheng Zhou, Xuejiao Shi, Wenhui Yang, Zhiliang Lu, Zhaoli Chen, Nan Sun, Jie He
Long noncoding RNAs (lncRNA) have been implicated in cancer but most of them remain largely unstudied. Here, we identified a novel NSUN2 methylated lncRNA (NMR), which was significantly upregulated in esophageal squamous cell carcinoma (ESCC), functioned as a key regulator of ESCC tumor metastasis and drug resistance. Upregulation of NMR correlated with tumor metastasis and indicated poor overall survival in ESCC patients. Functionally, NMR could promote tumor cell migration and invasion, inhibit cisplatin-induced apoptosis and increase drug resistance in ESCC cells...
May 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29761938/lactoferricin-b-reverses-cisplatin-resistance-in-head-and-neck-squamous-cell-carcinoma-cells-through-targeting-pd-l1
#11
Pei Zhang, Jinzhong Liu, Wenlu Li, Shanshan Li, Xinguang Han
Head and neck squamous cell carcinoma (HNSCC) ranks among the top most common cancers with a poor prognosis. The mechanism of chemoresistance is still not well known. This study is to investigate the programmed death-ligand 1 (PD-L1) expression in HNSCC, and test the effect of lactoferricin B (LfcinB) on chemoresistance and its mechanism. We analyzed 510 HNSCC patients in TCGA database and investigated how CD274 expression was related to patient prognosis. PD-L1 was verified from HNSCC samples at local hospital with immunohistochemistry...
May 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29761796/study-on-the-mechanism-of-cell-cycle-checkpoint-kinase-2-chek2-gene-dysfunction-in-chemotherapeutic-drug-resistance-of-triple-negative-breast-cancer-cells
#12
Li Luo, Wei Gao, Jinghui Wang, Dingxue Wang, Xiaobo Peng, Zhaoyang Jia, Ye Jiang, Gongzhuo Li, Dongxin Tang, Yajie Wang
BACKGROUND This study aimed to investigate the mechanism of CHEK2 gene dysfunction in drug resistance of triple negative breast cancer (TNBC) cells. MATERIAL AND METHODS To perform our study, a stable CHEK2 wild type (CHEK2 WT) or CHEK2 Y390C mutation (CHEK2 Y390C) expressed MDA-MB-231 cell line was established. MTT assay, cell apoptosis assay and cell cycle assay were carried out to analyze the cell viability, apoptosis, and cell cycle respectively. Western blotting and qRT-PCR were applied for related protein and gene expression detection...
May 15, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29760419/plga-nanoparticles-co-delivering-mdr1-and-bcl2-sirna-for-overcoming-resistance-of-paclitaxel-and-cisplatin-in-recurrent-or-advanced-ovarian-cancer
#13
Chitra Risnayanti, Yeong-Su Jang, Jinju Lee, Hyung Jun Ahn
The inherent or acquired resistance to paclitaxel and cisplatin, which are commonly used chemotherapeutic agents for ovarian cancer treatment, remains an important issue in chemotherapy of multidrug resistant ovarian cancer. Currently, it is still challenging to deal with the recurrent or advanced stage ovarian cancer. When drug efflux and anti-apoptotic pathways are highly interdependent and also involved in developing the resistance of multidrug resistant ovarian cancer, simultaneous inhibition of both pathways represents the potential targets to enhance the efficacy of chemotherapy...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29757528/downregulation-of-hoxa13-sensitizes-human-esophageal-squamous-cell-carcinoma-to-chemotherapy
#14
Qi Shi, Luyan Shen, Bin Dong, Hao Fu, Xiaozheng Kang, Liang Dai, Yongbo Yang, Wanpu Yan, Ke-Neng Chen
BACKGROUND: Chemoresistance often develops in esophageal squamous cell carcinoma (ESCC), leading to poor prognosis. HOX genes play a crucial role in embryonic development and cell differentiation. Studies have recently linked HOX with chemoresistance, thus we explored whether HOXA13 is involved in ESCC chemoresistance. METHODS: One hundred thirty-one ESCC patients who received neoadjuvant chemotherapy were enrolled. HOXA13 expression was examined by immunohistochemistry...
May 14, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29755294/inhibition-of-the-pi3k-but-not-the-mek-erk-pathway-sensitizes-human-glioma-cells-to-alkylating-drugs
#15
Bodo Haas, Veronika Klinger, Christina Keksel, Verena Bonigut, Daniela Kiefer, Julia Caspers, Julia Walther, Maria Wos-Maganga, Sandra Weickhardt, Gabriele Röhn, Marco Timmer, Roland Frötschl, Niels Eckstein
Background: Intrinsic chemoresistance of glioblastoma (GBM) is frequently owed to activation of the PI3K and MEK/ERK pathways. These signaling cascades are tightly interconnected however the quantitative contribution of both to intrinsic resistance is still not clear. Here, we aimed at determining the activation status of these pathways in human GBM biopsies and cells and investigating the quantitative impact of both pathways to chemoresistance. Methods: Receptor tyrosine kinase (RTK) pathways in temozolomide (TMZ) treatment naive or TMZ resistant human GBM biopsies and GBM cells were investigated by proteome profiling and immunoblotting of a subset of proteins...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29754608/multiplex-polymerase-chain-reaction-in-combination-with-gel-electrophoresis-inductively-coupled-plasma-mass-spectrometry-a-powerful-tool-for-the-determination-of-gene-copy-number-variations-and-gene-expression-changes
#16
A Fernández Asensio, T Iglesias, A Cotarelo, M Espina, E Blanco-González, L M Sierra, M Montes-Bayón
During the last few years multiplex real-time or quantitative polymerase chain reaction PCR (qPCR) has become the method of choice for multiplex gene expression changes and gene copy number variations (CNVs) analysis. However, such determinations require the use of different fluorescent labels for the different amplified sequences, which increases significantly the costs of the analysis and limits the applicability of the technique for simultaneous amplification of many targets of interest in a single reaction...
September 6, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29752546/mir-514-attenuates-proliferation-and-increases-chemoresistance-by-targeting-atp-binding-cassette-subfamily-in-ovarian-cancer
#17
Sha Xiao, Ming Zhang, Chang Liu, Deling Wang
Cisplatin is one of the most popular chemotherapeutic drugs in treating ovarian cancer. Resistance to cisplatin is a common clinical challenge that needs to be solved to increase its anti-tumor effects. The relation of miR-514 expression with prognosis in ovarian cancer patients was analyzed based on GSE73584 datasets. The regulation of miR-514 on proliferation and cisplatin chemosensitivity of ovarian cells was examined by MTT assay, colony-formation assay and soft-agar colony-formation assay. Dual luciferase assay was performed to detect the direct interaction of miR-514 with its downstream targets...
May 11, 2018: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/29752286/genetic-and-cellular-sensitivity-of-caenorhabditis-elegans-to-the-chemotherapeutic-agent-cisplatin
#18
Francisco Javier García-Rodríguez, Carmen Martínez-Fernández, David Brena, Dmytro Kukhtar, Xènia Serrat, Ernest Nadal, Mike Boxem, Sebastian Honnen, Antonio Miranda-Vizuete, Alberto Villanueva, Julián Cerón
Cisplatin and derivatives are commonly used as chemotherapeutic agents. Although the cytotoxic action of cisplatin on cancer cells is very efficient, clinical oncologists need to deal with two major difficulties: (i) the onset of resistance to the drug, and (ii) the cytotoxic effect in patients. Here we use Caenorhabditis elegans to investigate factors influencing the response to cisplatin in multicellular organisms. In this hermaphroditic model organism, we observed that sperm failure is a major cause in cisplatin-induced infertility...
May 10, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29750170/electroporation-with-cisplatin-against-metastatic-pancreatic-cancer-in-vitro-study-on-human-primary-cell-culture
#19
Olga Michel, Julita Kulbacka, Jolanta Saczko, Justyna Mączyńska, Piotr Błasiak, Joanna Rossowska, Adam Rzechonek
Despite the rapid progression of cancer pharmacotherapy, the high drug resistance of pancreatic ductal adenocarcinoma (PDA) makes it one of the most lethal malignancies. Therefore, there are high expectations associated with experimental therapies, such as electrochemotherapy (ECT). This technique involves the application of short electric pulses to induce transitional permeabilization of the cellular membrane, thus enhancing drug molecules influx. The aim of the study was to investigate the influence of electroporation with cisplatin (CisEP) on the primary culture of human PDA cells from lung metastases-their survival and stress response...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29749526/human-hla%C3%A2-f-adjacent-transcript-10-promotes-the-formation-of-cancer-initiating-cells-and-cisplatin-resistance-in-bladder-cancer
#20
Chen Li, Zhenfan Wang, Ninghan Feng, Jian Dong, Xiaoyan Deng, Yin Yue, Yuehong Guo, Jianquan Hou
Epithelial to mesenchymal transition (EMT) serves important roles in tumor invasion, metastasis, formation of cancer initiating cells (CICs) and drug resistance. HLA‑F adjacent transcript 10 (FAT10) has been proposed as an oncogene in bladder cancer. However, the functional contribution of FAT10 to EMT and the formation of CICs remains unclear in bladder cancer. The present study reports that FAT10 protein expression is upregulated in bladder cancer cell lines, and the overexpression of FAT10 promotes EMT and the formation of CICs in bladder cancer UMUC‑3 cells...
May 9, 2018: Molecular Medicine Reports
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