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https://www.readbyqxmd.com/read/28810651/kanglaite-inhibits-the-expression-of-drug-resistance-genes-through-suppressing-pvt1-in-cisplatin-resistant-gastric-cancer-cells
#1
Xian-Wen Zhang, Liang Liu, Xi-Zhi Zhang, Ping Bo
Kanglaite (KLT) was shown to alleviate the development of multidrug resistance (MDR) clinically. The purpose of this study is to examine the mechanism of KLT for chemotherapy resistance in gastric cancer cells involving the regulation of MDR-related proteins. The cisplatin-resistant BGC823/DPP and SGC7901/DDP cells were treated with 1, 2.5 and 5 µl/ml of KLT for 24, 36 and 48 h. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were performed to detect the cell viability and cell apoptosis, respectively...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808038/the-phosphatidylinositol-3-kinase-pathway-as-a-potential-therapeutic-target-in-bladder-cancer
#2
Shuxiong Zeng, Yanjun Zhu, Ai-Hong Ma, Weimin Yu, Hongyong Zhang, Tzu-Yin Lin, Wei Shi, Clifford G Tepper, Paul T Henderson, Susan Airhart, Jianming Guo, Chuanliang Xu, Ralph de Vere White, Chong-Xian Pan
PURPOSE: Activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action and resistant mechanisms of drugs targeting the PI3K pathway. EXPERIMENTAL DESIGN: Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine...
August 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28801607/enhancing-nk-cell-mediated-cytotoxicity-to-cisplatin-resistant-lung-cancer-cells-via-mek-erk-signaling-inhibition
#3
Li Yang, MingJing Shen, Li Jun Xu, Xiaodong Yang, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
Major progress has been made clinically in inhibiting the programmed death receptor 1 (PD-1)/PD-L1 interaction to enhance T cell-mediated immune function, yet the effectiveness of anti-PD-L1/PD-1 agents in enhancing natural killer (NK) cell's function remains largely unknown. Susceptibilities of cisplatin-resistant A549CisR and H157CisR cells vs. parental cells to the cytotoxic action of NK cells were examined. We found cisplatin-resistant cells more resistant to NK cell cytotoxicity than parental cells. There were constitutively higher expressions of PD-L1 in A549CisR and H157CisR cells than in parental cells in vitro, as well as in H157CisR cell-derived tumors than H157P cell-derived tumors...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801080/reprint-of-anticancer-activity-of-hydroxy-and-sulfonamide-azobenzene-platinum-ii-complexes-in-cisplatin-resistant-ovarian-cancer-cells
#4
Katia G Samper, Sierra C Marker, Pau Bayón, Samantha N MacMillan, Ivan Keresztes, Òscar Palacios, Justin J Wilson
The syntheses of three platinum(II) complexes bearing sulfonamide-((E)-2-(4-methylphenylsulfonamido)-2',6'-difluoroazobenzene, HL1) and hydroxy-azo-2,6-difluorobenzene ((E)-2-((2,6-difluorophenyl)diazenyl)phenol, HL2) bidentate ligands is described. These complexes, [Pt(L1)(DMSO)Cl] (1), [Pt(L2)(DMSO)Cl] (2), and [Pt(L2)2] (3), were characterized by multinuclear NMR spectroscopy, mass spectrometry, and X-ray crystallography. Despite bearing azobenzene functional groups, none of the three complexes undergo photoisomerization...
August 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28800871/malignant-pleural-mesothelioma-state-of-the-art-and-advanced-cell-therapy
#5
Giorgio Facchetti, Francesco Petrella, Lorenzo Spaggiari, Isabella Rimoldi
Malignant Pleural Mesothelioma (MPM) is an aggressive malignancy highly resistant to chemotherapy, with a response rate of 20% of patients and for this reason an efficient treatment is still a challenge. Platinum-based chemotherapy in association with a third-generation antifolate is the front-line standard of care whereas any second-line treatment was approved for MPM thus making it a pathology that evokes the need for new therapeutic agents. Different platinum-drugs were synthesised and tested as an option for patients who are not candidates to cisplatin-based therapy...
August 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28800781/knowledge-guided-gene-prioritization-reveals-new-insights-into-the-mechanisms-of-chemoresistance
#6
Amin Emad, Junmei Cairns, Krishna R Kalari, Liewei Wang, Saurabh Sinha
BACKGROUND: Identification of genes whose basal mRNA expression predicts the sensitivity of tumor cells to cytotoxic treatments can play an important role in individualized cancer medicine. It enables detailed characterization of the mechanism of action of drugs. Furthermore, screening the expression of these genes in the tumor tissue may suggest the best course of chemotherapy or a combination of drugs to overcome drug resistance. RESULTS: We developed a computational method called ProGENI to identify genes most associated with the variation of drug response across different individuals, based on gene expression data...
August 11, 2017: Genome Biology
https://www.readbyqxmd.com/read/28797843/blockade-of-stearoyl-coa-desaturase-1-activity-reverts-resistance-to-cisplatin-in-lung-cancer-stem-cells
#7
Maria Elena Pisanu, Alessia Noto, Claudia De Vitis, Stefania Morrone, Giosuè Scognamiglio, Gerardo Botti, Federico Venuta, Daniele Diso, Ziga Jakopin, Fabrizio Padula, Alberto Ricci, Salvatore Mariotta, Maria Rosaria Giovagnoli, Enrico Giarnieri, Ivano Amelio, Massimiliano Agostini, Gerry Melino, Gennaro Ciliberto, Rita Mancini
Poor prognosis in lung cancer has been attributed to the presence of lung cancer stem cells (CSCs) which resist chemotherapy and cause disease recurrence. Hence, the strong need to identify mechanisms of chemoresistance and to develop new combination therapies. We have previously shown that Stearoyl-CoA-desaturase 1 (SCD1), the enzyme responsible for the conversion of saturated to monounsaturated fatty acids is upregulated in 3D lung cancer spheroids and is an upstream activator of key proliferation pathways β-catenin and YAP/TAZ...
August 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28796401/combination-cisplatin-and-sulforaphane-treatment-reduces-proliferation-invasion-and-tumor-formation-in-epidermal-squamous-cell-carcinoma
#8
Candace Kerr, Gautam Adhikary, Daniel Grun, Nicholas George, Richard L Eckert
Epidermal squamous cell carcinoma is an extremely common type of cancer. Early tumors can be successfully treated by surgery, but recurrent disease is aggressive and resistant to therapy. Cisplatin is often used as a treatment, but the outcome is rarely satisfactory. For this reason new strategies are required. Sulforaphane is a diet-derived cancer prevention agent that is effective in suppressing tumor growth in animal models of skin cancer. We monitored the efficacy of sulforaphane and cisplatin as a combined therapy for squamous cell carcinoma...
August 10, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28791708/exosomal-dnmt1-mediates-cisplatin-resistance-in-ovarian-cancer
#9
Ya-Lei Cao, Ting Zhuang, Bao-Heng Xing, Na Li, Qin Li
Ovarian cancer is the most common malignancy in women. Owing to late syndromic presentation and lack of efficient early detection, most cases are diagnosed at advanced stages. Surgery and platinum-based chemotherapy are still the standard care currently. However, resistance invoked often compromises the clinical value of the latter. Expression of DNA methyltransferase 1 (DNMT1) was analysed by gene array. Protein was determined by immunoblotting. Exosome was isolated with commercial kit. Cell proliferation was measured by CCK8 method...
August 8, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28790395/knockdown-of-hif-1%C3%AE-by-sirna-expressing-plasmid-delivered-by-attenuated-salmonella-enhances-the-antitumor-effects-of-cisplatin-on-prostate-cancer
#10
Junlian Gu, Yang Li, Jun Zeng, Bo Wang, Kun Ji, Yufeng Tang, Qing Sun
Resistance to cisplatin (DDP) and dose-related toxicity remain two important obstacles in the treatment of prostate cancer (PCa) patients with DDP-based chemotherapy. We have investigated whether the knockdown of hypoxia-inducible factor-1 alpha (HIF-1α) by siRNA could enhance the antitumor activity of DDP, and aimed to determine the underlying mechanisms. Intravenous injection of attenuated Salmonella carrying a HIF-1α siRNA-expressing plasmid was used to knockdown HIF-1α in a PC-3 xenograft model. The in vitro and in vivo effects of HIF-1α siRNA treatment and/or DPP on PCa cell proliferation, apoptosis, glycolysis, and production of reactive oxygen species (ROS) were assessed by examining molecular markers specific to each process...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28780469/role-of-pannexin1-channels-in-the-resistance-of-i-10-testicular-cancer-cells-to-cisplatin-mediated-by-atp-ip3-pathway
#11
Dandan Wu, Jianfeng Wu, Haofeng Liu, Meiling Yu, Liang Tao, Shuying Dong, Xuhui Tong
Cisplatin (DDP) is the most commonly used drug in testicular cancer. However, drug resistance severely limits its clinical use and the underlying mechanisms need to be further clarified. The aim of present study was to investigate the role of ATP/IP3 pathway mediated by pannexin1 (Panx-1) channels on DDP-induced apoptosis and to reveal the potential mechanisms of DDP-resistance in testicular cancer. We found that the expression of Panx-1 in I-10/DDP cells (DDP-resistance) was decreased compared with parental I-10 cells determined by western blotting and immunofluorescence assay...
August 3, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28775359/slc39a4-expression-is-associated-with-enhanced-cell-migration-cisplatin-resistance-and-poor-survival-in-non-small-cell-lung-cancer
#12
Dong-Ming Wu, Teng Liu, Shi-Hua Deng, Rong Han, Ying Xu
The zinc transporter SLC39A4 influences epithelial cell morphology and migration in various cancers; however, its role in regulating cell invasion and chemotherapeutic resistance in human lung cancer is not yet clear. Here, integrated analysis of gene expression in non-small cell lung cancer revealed that SLC39A4 expression is significantly correlated with increased tumour size and regional lymph node spread, as well as shorter overall survival (OS) and disease-free survival (DFS). SLC39A4 silencing by lentivirus-mediated shRNA blocked human lung cancer cell epithelial-mesenchymal transition and metastasis in vitro and in vivo, respectively...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28771580/glipr1-modulates-the-response-of-cisplatin-resistant-human-lung-cancer-cells-to-cisplatin
#13
Xin Gong, Jing Liu, Dan Zhang, Dawei Yang, Zhihui Min, Xiaoxing Wen, Guifang Wang, Huayin Li, Yuanlin Song, Chunxue Bai, Jing Li, Jian Zhou
BACKGROUND AND OBJECTIVE: Chemotherapy drugs, such as cisplatin (DDP), improve the survival of patients with lung cancer by inducing apoptosis in cancer cells, which quickly develop resistance to DDP through uncharacterized mechanisms. Glioma Pathogenesis-Related Protein 1 (GLIPR1) plays an important role in cell proliferation, migration and apoptosis. However, the expression and function of GLIPR1 in mediating DDP resistance in human lung adenocarcinoma A549/DDP and human large cell lung cancer H460/DDP cells has not yet been reported...
2017: PloS One
https://www.readbyqxmd.com/read/28768244/nrf2-induces-cisplatin-resistance-via-suppressing-the-iron-export-related-gene-slc40a1-in-ovarian-cancer-cells
#14
Jianfa Wu, Lingjie Bao, Zhenbo Zhang, Xiaofang Yi
Induction of Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) has been demonstrated to be involved in cisplatin resistance in ovarian cancer. Solute carrier family 40 member 1 (SLC40A1) is an iron exporter, which possesses many putative Nrf2 binding sites. Here we hypothesize that it may be a possible downstream gene of Nrf2. Elevated level of Nrf2 and reduced level of SLC40A1 were found in cisplatin-resistant ovarian cancer cells as compared with cisplatin-sensitive ovarian cancer cells. Exogenous knockdown of Nrf2 leaded to increased expression of SLC40A1...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28767691/crispr-cas9-mediated-knockout-of-c-rel-in-hela-cells-results-in-profound-defects-of-the-cell-cycle
#15
Carsten Slotta, Thomas Schlüter, Lucia M Ruiz-Perera, Hussamadin M Kadhim, Tobias Tertel, Elena Henkel, Wolfgang Hübner, Johannes F W Greiner, Thomas Huser, Barbara Kaltschmidt, Christian Kaltschmidt
Cervical cancer is the fourth common cancer in women resulting worldwide in 266,000 deaths per year. Belonging to the carcinomas, new insights into cervical cancer biology may also have great implications for finding new treatment strategies for other kinds of epithelial cancers. Although the transcription factor NF-κB is known as a key player in tumor formation, the relevance of its particular subunits is still underestimated. Here, we applied CRISPR/Cas9n-mediated genome editing to successfully knockout the NF-κB subunit c-REL in HeLa Kyoto cells as a model system for cervical cancers...
2017: PloS One
https://www.readbyqxmd.com/read/28767070/various-mechanisms-involve-the-nuclear-factor-erythroid-derived-2-like-nrf2-to-achieve-cytoprotection-in-long-term-cisplatin-treated-urothelial-carcinoma-cell-lines
#16
Margaretha A Skowron, Günter Niegisch, Philipp Albrecht, Gommert van Koeveringe, Andrea Romano, Peter Albers, Wolfgang A Schulz, Michèle J Hoffmann
Therapeutic efficacy of cisplatin-based chemotherapy for advanced-stage urothelial carcinoma (UC) is limited by drug resistance. The nuclear factor (erythroid-derived 2)-like 2 (NRF2) pathway is a major regulator of cytoprotective responses. We investigated its involvement in cisplatin resistance in long-term cisplatin treated UC cell lines (LTTs). Expression of NRF2 pathway components and targets was evaluated by qRT-PCR and western blotting in LTT sublines from four different parental cells. NRF2 transcriptional activity was determined by reporter assays and total glutathione (GSH) was quantified enzymatically...
August 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28765565/telomerase-reverse-transcriptase-promotes-chemoresistance-by-suppressing-cisplatin-dependent-apoptosis-in-osteosarcoma-cells
#17
Zhengpei Zhang, Ling Yu, Guo Dai, Kezhou Xia, Gaiwei Liu, Qi Song, Chunjie Tao, Tian Gao, Weichun Guo
Cisplatin is one of the most efficacious antimitotic drugs used in the treatment of a range of malignant tumors. However, treatment failures are common due to the development of chemoresistance. In addition to its telomere maintenance function, telomerase plays a pro-survival role, inducing decreased apoptosis and increased resistance against DNA damage. Elucidation of the molecular mechanisms underlying this effect is critical to improve treatment outcomes. Previously, our group showed higher telomerase reverse transcriptase(TERT) expression in cisplatin resistant osteosarcoma cells...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28763458/synthesis-of-novel-coumarin-nucleus-based-dpa-drug-like-molecular-entity-in-vitro-dna-cu-ii-binding-dna-cleavage-and-pro-oxidant-mechanism-for-anticancer-action
#18
Saman Khan, Ali Mohammed Malla, Atif Zafar, Imrana Naseem
Despite substantial research on cancer therapeutics, systemic toxicity and drug-resistance limits the clinical application of many drugs like cisplatin. Therefore, new chemotherapeutic strategies against different malignancies are needed. Targeted cancer therapy is a new paradigm for cancer therapeutics which targets pathways or chemical entities specific to cancer cells than normal ones. Unlike normal cells, cancer cells contain elevated copper which plays an integral role in angiogenesis. Copper is an important metal ion associated with chromatin DNA, particularly with guanine...
2017: PloS One
https://www.readbyqxmd.com/read/28760320/the-microbiology-of-ruthenium-complexes
#19
Hannah M Southam, Jonathan A Butler, Jonathan A Chapman, Robert K Poole
Ruthenium is seldom mentioned in microbiology texts, due to the fact that this metal has no known, essential roles in biological systems, nor is it generally considered toxic. Since the fortuitous discovery of cisplatin, first as an antimicrobial agent and then later employed widely as an anticancer agent, complexes of other platinum group metals, such as ruthenium, have attracted interest for their medicinal properties. Here, we review at length how ruthenium complexes have been investigated as potential antimicrobial, antiparasitic and chemotherapeutic agents, in addition to their long and well-established roles as biological stains and inhibitors of calcium channels...
2017: Advances in Microbial Physiology
https://www.readbyqxmd.com/read/28759042/inhibition-of-the-spindle-assembly-checkpoint-kinase-mps-1-as-a-novel-therapeutic-strategy-in-malignant-mesothelioma
#20
A Szymiczek, M Carbone, S Pastorino, A Napolitano, M Tanji, M Minaai, I Pagano, J M Mason, H I Pass, M R Bray, T W Mak, H Yang
Malignant mesothelioma (MM) is an aggressive malignancy, highly resistant to current medical and surgical therapies, whose tumor cells characteristically show a high level of aneuploidy and genomic instability. We tested our hypothesis that targeting chromosomal instability in MM would improve response to therapy. Thr/Tyr kinase (TTK)/monopolar spindle 1 kinase (Mps-1) is a kinase of the spindle assembly checkpoint that controls cell division and cell fate. CFI-402257 is a novel, selective inhibitor of Mps-1 with antineoplastic activity...
July 31, 2017: Oncogene
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