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cisplatin resistance

Midori Tanaka, Hidenobu Ishii, Hayato Moribuchi, Yoshiko Naito, Norikazu Matsuo, Masayuki Nakamura, Takaaki Tokito, Koichi Azuma, Kazuhiko Yamada, Tomoaki Hoshino
Small-cell lung cancer (SCLC) combined with epidermal growth factor receptor (EGFR) mutations is extremely rare, and standard chemotherapeutic strategies have not yet been established. In the present study, we report a case of a 67-year-old man who presented with combined SCLC with EGFR mutation (exon 19 deletion). Systemic chemotherapy with cisplatin and irinotecan was initiated as first-line chemotherapy, and computed tomography findings revealed tumor shrinkage after two cycles of chemotherapy. However, after the third cycle of the treatment, disease progression was observed including the appearance of pleural and pericardial effusion...
March 15, 2018: Investigational New Drugs
Yangfeng Xiang, Jianqiang Zhao, Ming Zhao, Kejing Wang
Allicin has been reported to inhibit cancer cell proliferation, induce cell apoptosis and enhance the accumulation of reactive oxygen species. However, it has remained elusive whether allicin improves multidrug resistance in thyroid cancer cells through modulating autophagy. The present study demonstrated that combined use of allicin and cisplatin or carboplatin resulted in an enhanced growth inhibitory effect on SW1736 and HTh-7 cells. Furthermore, treatment with allicin significantly increased SW1736 and HTh-7 cell autophagy...
April 2018: Experimental and Therapeutic Medicine
S Wang, Z Zou, X Luo, Y Mi, H Chang, D Xing
Liver receptor homolog-1 (LRH1) has been shown to promote tumor proliferation and development. However, the functions of LRH1 in mediating cancer cells chemoresistance are still not clear. Here, we found LRH1 levels were significantly elevated in primary breast cancer tissues in patients who developed early recurrence. Similarly, adriamycin (ADR)-resistant breast cancer cell lines also exerted high LRH1 expression. Indeed, overexpression of LRH1 attenuated cytotoxicity of chemotherapeutic drugs ADR and cisplatin (DDP) in breast cancer cells in vitro and in nude mice tumor model...
March 16, 2018: Oncogene
Jiao Zou, Linlin Zhu, Xiaomei Jiang, Yang Wang, Yue Wang, Xiangwei Wang, Bin Chen
Flap endonuclease 1 (FEN1) overexpression promotes breast cancer. We investigated the role of FEN1 in cisplatin resistance and the chemosensitizing effects of curcumin in breast cancer cells. We demonstrated that FEN1 overexpression promotes cisplatin resistance in breast cancer cells, and that FEN1 knockdown enhances cisplatin sensitivity. Curcumin down-regulated FEN1 expression in a dose-dependent manner. A combination of cisplatin and curcumin enhanced breast cancer cell sensitivity to cisplatin by down-regulating FEN1 expression in vitro and in vivo ...
February 16, 2018: Oncotarget
Ziwei Wang, Feng Ji
MicroRNAs (miRNAs/miRs) are endogenous small non-coding RNAs that post-transcriptionally regulate the expression of genes and serve crucial roles in diverse biological processes. The present study aimed to examine the miRNA expression profile and drug resistance in the SGC7901 cell line and its isogenic drug-resistant counterpart, SGC7901/cisplatin (DDP) cell line. The potential role of miR-17-5p in modulating drug resistance in gastric cancer cells was investigated. Different levels of miRNA expression between SGC7901/DDP and SGC7901 cells were analyzed by miRNA microarray and validated by quantitative polymerase chain reaction...
April 2018: Oncology Letters
Chao Liu, Quan Gong, Ting Chen, Juan Lv, Zhiping Feng, Pengjie Liu, Zhiyong Deng
Multidrug resistance (MDR) is an obstacle for cancer chemotherapy. It was reported that 20(S)-ginsenoside Rg3 (hereafter Rg3) was able to regulate MDR in mouse leukemia cells. The present study investigated the effect of Rg3 on the MDR of A549 lung cancer cells. A cell viability assay revealed that Rg3 treatment increased cisplatin (DDP) cytotoxicity in DDP resistant A549 cells (A549/DDP). Furthermore, Rg3 increases the antitumor effect of DDP on A549/DDP xenograft mice. The expression of MDR-mediated proteins, including P-glycoprotein (P-gp), multidrug resistance-associated protein (MPR1) and lung resistance protein 1 (LPR1), was detected in tumor tissue of A549/DDP xenograft mice...
April 2018: Oncology Letters
Peng Yin, Guizhen Song, Zhenhua Jiang
PURPOSE: Nasopharyngeal carcinoma (NPC) is one of the most commonly diagnosed cancers worldwide with significantly high prevalence in Southern China. Chemoprevention of cancer with alkylating agent compounds could potentially reverse, suppress, or prevent cancer progression. Cisplatin (CIS) is an antineoplastic or cytotoxic platinum-based drug used for chemotherapy of different types of human cancers such as NPC. Nevertheless, the effects of CIS on the migration and invasion of human NPC cells and the underlying molecular mechanisms have not yet been fully scrutinized...
March 14, 2018: Cancer Chemotherapy and Pharmacology
R Mezencev, R M Wartell
Cisplatin is an important anticancer drug with a complex mode of action, a variety of possible targets, and numerous resistance mechanisms. While genomic DNA has traditionally been considered to be its most critical anticancer target, several lines of evidence suggest that various RNAs and other biomolecules may play a role in its anticancer mode of action. In this report we demonstrate that cisplatin modifies pre-miR-200b, impairs its processing to mature miRNA, and decreases miR-200b expression in ovarian cancer cells...
2018: Neoplasma
M Fiorentzis, H Kalirai, P Katopodis, B Seitz, A Viestenz, S E Coupland
Electrochemotherapy (ECT) enhances responsiveness to cytotoxic drugs in numerous cell lines in vitro. Clinically ECT is widely applied for skin tumor ablation and has shown efficacy in treating non-resectable colorectal liver metastases. There is limited experience of ECT for ocular tumor therapy. We investigated the cytotoxic effect of bleomycin and cisplatin in combination with electroporation on chemoresistant human uveal melanoma (UM) cell lines in vitro. Four UM cell lines (Mel 270, 92-1, OMM-1, OMM-2...
2018: Neoplasma
Kathrin Oehl, Jelena Kresoja-Rakic, Isabelle Opitz, Bart Vrugt, Walter Weder, Rolf Stahel, Peter Wild, Emanuela Felley-Bosco
Experimental models closely representing in vivo conditions allow investigating mechanisms of resistance. Our aims were to establish a live-cell biobank of malignant pleural mesothelioma (MPM) samples and to obtain proof of principle that primary culture chemoresistant models, mimicking tumor progression observed in patients, can be obtained in vitro , providing a useful tool to investigate underlying mechanisms. Primary mesothelioma cultures were established from 235 samples between 2007 and 2014. Of two MPM patients, primary cultures obtained at different time points: at initial diagnosis, after neoadjuvant treatment at surgery and/or after tumor recurrence, were deeply investigated...
2018: Frontiers in Oncology
Hong-Ying Chu, Xue Chen, Yu-E Jiang, Wei Wang, Xiao Qi, Zhao-Ming Zhong, Mu-Sheng Zeng, Xiao-Feng Zhu, Chuan-Zheng Sun
The role of autophagy in tongue squamous cell carcinoma (TSCC) cisplatin resistance is unclear. We aimed to identify a possible synergistic effect of autophagy inhibitors and cisplatin in TSCC cells and explore the underlying mechanism. Our results indicate that autophagic flux was high in TSCC cells; Autophagy inhibitor bafilomycin A1 increased cisplatin cytotoxicity in TSCC cells by inhibiting lysosomal uptake of platinum and enhancing intracellular platinum ion binding to DNA; Autophagy gene (Atg5) knockout in TSCC cells did not duplicate the above-mentioned sensitization of bafilomycin A1...
March 7, 2018: Cancer Letters
Risa Akizuki, Ryohei Maruhashi, Hiroaki Eguchi, Kazuki Kitabatake, Mitsutoshi Tsukimoto, Takumi Furuta, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari
Chemotherapy resistance is a major problem in the treatment of cancer, but the underlying mechanisms are not fully understood. We found that the expression levels of claudin-1 (CLDN1) and 3, tight junctional proteins, are upregulated in cisplatin (CDDP)-resistant human lung adenocarcinoma A549 (A549R) cells. A549R cells showed cross-resistance to doxorubicin (DXR). Here, the expression mechanism and function of CLDN1 and 3 were examined. CLDN1 and 3 were mainly localized at tight junctions concomitant with zonula occludens (ZO)-1, a scaffolding protein, in A549 and A549R cells...
March 7, 2018: Biochimica et Biophysica Acta
Wangie Yu, Yunyun Chen, Julien Dubrulle, Fabio Stossi, Vasanta Putluri, Arun Sreekumar, Nagireddy Putluri, Dodge Baluya, Stephen Y Lai, Vlad C Sandulache
Cisplatin is commonly utilized in the treatment of solid tumors. Its mechanism of action is complex and multiple mechanisms of resistance have been described. We sought to determine the impact of cisplatin-generated oxidative stress on head and neck squamous cell carcinoma (HNSCC) proliferation, survival and metabolic activity in order to identify a potential metabolic signature associated with cisplatin response. DNA-bound cisplatin represents a small fraction of total intra-cellular cisplatin but generates a robust oxidative stress response...
March 9, 2018: Scientific Reports
Xiaohui Shen, Xia Gao, Hui Li, Yajun Gu, Junguo Wang
Laryngeal carcinoma is a kind of head and neck carcinoma with high incidence and mortality. Chemotherapy treatments ofhuman laryngeal carcinoma may fail due to the development of chemo-resistance. Tissue inhibitor of metalloproteinases 3 (TIMP3) has been shown to be implicated in a number of pathological processes typical for cancer. The present study aims to investigate the involvement of TIMP-3 in chemo-resistance of laryngeal carcinoma. We showed that TIMP3 expression was significantly decreased in chemo-resistant laryngeal carcinoma tissues compared with chemo-sensitivity tissues...
March 9, 2018: Oncology Research
Danyang Zhou, Wenjing Liu, Songhe Liang, Banghao Sun, Anqi Liu, Zhongqi Cui, Xue Han, Lijie Yuan
The prognosis of gastric cancer (GC) remains poor due to clinical drug resistance, and novel drugs are urgently needed. Apoptin-derived peptide (AdP) is an antitumor polypeptide constructed in our laboratory that has been used to combat cisplatin (CDDP) resistance in GC cells. MTT and colony-formation assays and Hoechst 33342 staining were used to measure the cytotoxicity of CDDP and AdP in GC cells. Cell apoptosis was measured using an Annexin-V-FITC/PI dual staining assay. Western blot analysis was conducted to detect the expression of proteins in the PI3K/AKT signaling pathway and resistance-related markers...
March 9, 2018: Cancer Medicine
Andrea Erxleben
Since the serendipitous discovery of the antitumor activity of cisplatin, there has been a continuous surge in studies aimed at the development of new cytotoxic metal complexes. While the majority of these complexes have been designed to interact with nuclear DNA, other targets for anticancer metallodrugs attract increasing interest. In cancer cells the mitochondrial metabolism is deregulated. Impaired apoptosis, insensitivity to anti-growth signals and unlimited proliferation have been linked to mitochondrial dysfunction...
March 6, 2018: Current Medicinal Chemistry
Navin Sarin, Florian Engel, Florian Rothweiler, Jindrich Cinatl, Martin Michaelis, Roland Frötschl, Holger Fröhlich, Ganna V Kalayda
The major obstacle in the clinical use of the antitumor drug cisplatin is inherent and acquired resistance. Typically, cisplatin resistance is not restricted to a single mechanism demanding for a systems pharmacology approach to understand a whole cell's reaction to the drug. In this study, the cellular transcriptome of untreated and cisplatin-treated A549 non-small cell lung cancer cells and their cisplatin-resistant sub-line A549r CDDP2000 was screened with a whole genome array for relevant gene candidates...
March 7, 2018: International Journal of Molecular Sciences
Vachirapong Sompakdee, Auemduan Prawan, Laddawan Senggunprai, Upa Kukongviriyapan, Papavee Samathiwat, Jaroon Wandee, Veerapol Kukongviriyapan
AIMS: Transcription factor Nrf2, which regulates the expression of cytoprotective and antioxidant enzymes, contributes to proliferation and resistance to chemotherapy in cancer. The inhibition of Nrf2 can sensitize cholangiocarcinoma (CCA) cells to the cytotoxicity of several chemotherapeutic agents. In this study, we investigated the mechanism of this chemosensitizing effect. MAIN METHODS: KKU-100 cells were used in the study. Nrf2 expression was knocked down by siRNA and expression was validated by reverse transcription and polymerase chain reaction...
March 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Christoph Oing, Christoph Seidel, Carsten Bokemeyer
Most germ cell cancer patients with metastatic disease are cured by cisplatin-based combination chemotherapy. 30% of metastatic patients will develop relapse or progress despite adequate first-line treatment and will require salvage therapy, with about 10% of metastasized patients ultimately developing platinum-resistant and fatal disease. Areas covered: Based on a comprehensive literature search of MEDLINE, EMBASE and conference proceedings of ESMO, ASCO and EAU meetings, this review provides an overview on current and potential future treatment options for platinum-refractory germ cell cancer patients including cytostatics and molecularly targeted therapies...
March 8, 2018: Expert Review of Anticancer Therapy
Hiroaki Miyazaki, Ryou-U Takahashi, Marta Prieto-Vila, Yumi Kawamura, Seiji Kondo, Tatsuo Shirota, Takahiro Ochiya
A number of studies report that epithelial to mesenchymal transition (EMT) supports the generation and maintenance of cancer stem cells (CSCs), which show tumor seeding ability and drug resistance; however, the molecular mechanisms underlying induction of EMT-associated tumor malignancy remain unclear. The present study reports that oral cancer cells switch from expressing the CD44 variant form (CD44v) to expressing the standard form (CD44s) during acquisition of cisplatin-resistance, which resulted in EMT induction...
February 9, 2018: Oncotarget
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