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https://www.readbyqxmd.com/read/27933604/chemoresistant-lung-cancer-stem-cells-display-high-dna-repair-capability-to-remove-cisplatin-dna-damage
#1
Wai-Kin Yu, Zhigang Wang, Chi-Chun Fong, Dandan Liu, Tak-Chun Yip, Siu-Kie Au, Guangyu Zhu, Mengsu Yang
BACKGROUND AND PURPOSE: The persistence of lung cancer stem cells (LCSCs) has been proposed to be the main factor of lung cancer recurrence due to their high resistance to conventional chemotherapy. The underlying mechanisms, however, have not been fully addressed. EXPERIMENTAL APPROACH: In this study, we examined the cellular response of a human lung cancer stem cell line upon treatment with cisplatin, a DNA-damaging anticancer drug that is extensively applied in clinics...
December 9, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27932791/migration-and-invasion-of-drug-resistant-lung-adenocarcinoma-cells-are-dependent-on-mitochondrial-activity
#2
Ji Hoon Jeon, Dong Keon Kim, Youngmi Shin, Hee Yeon Kim, Bomin Song, Eun Young Lee, Jong Kwang Kim, Hye Jin You, Heesun Cheong, Dong Hoon Shin, Seong-Tae Kim, Jae-Ho Cheong, Soo Youl Kim, Hyonchol Jang
A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated...
December 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27927748/axl-receptor-signalling-suppresses-p53-in-melanoma-through-stabilization-of-the-mdmx-mdm2-complex
#3
Anna de Polo, Zhongling Luo, Casimiro Gerarduzzi, Xiang Chen, John B Little, Zhi-Min Yuan
Deregulation of the tyrosine kinase signalling is often associated with tumour progression and drug resistance, but its underlying mechanisms are only partly understood. In this study, we investigated the effects of the receptor tyrosine kinase AXL on the stability of the MDMX-MDM2 heterocomplex and the activity of p53 in melanoma cells. Our data demonstrated that AXL overexpression or activation through growth arrest-specific 6 (Gas6) ligand stimulation increases MDMX and MDM2 protein levels and decreases p53 activity...
November 9, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27925179/hepatoma-cell-functions-modulated-by-nek2-are-associated-with-liver-cancer-progression
#4
Sheng-Ming Wu, Syuan-Ling Lin, Kang-Yun Lee, Hsiao-Chi Chuang, Po-Hao Feng, Wan-Li Cheng, Chia-Jung Liao, Hsiang-Cheng Chi, Yang-Hsiang Lin, Chung-Ying Tsai, Wei-Jan Chen, Chau-Ting Yeh, Kwang-Huei Lin
NEK2 (NIMA-related expressed kinase 2) is a serine/threonine centrosomal kinase that acts as a critical regulator of centrosome structure and function. Aberrant NEK2 activities lead to failure in regulating centrosome duplication. NEK2 overexpression promotes tumorigenesis and is associated with poor prognosis in several cancers. Increased NEK2 expression during the late pathological stage has been detected in the Oncomine liver dataset and hepatocellular carcinoma (HCC) specimens. Elevated NEK2 protein is associated with poor overall survival in patients with HCC...
December 7, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27924308/ph-sensitive-pt-nanocluster-assembly-overcomes-cisplatin-resistance-and-heterogeneous-stemness-of-hepatocellular-carcinoma
#5
Hongping Xia, Fangyuan Li, Xi Hu, Wooram Park, Shuaifei Wang, Youngjin Jang, Yang Du, Seungmin Baik, Soojeong Cho, Taegyu Kang, Dong-Hyun Kim, Daishun Ling, Kam Man Hui, Taeghwan Hyeon
Response rates to conventional chemotherapeutics remain unsatisfactory for hepatocellular carcinoma (HCC) due to the high rates of chemoresistance and recurrence. Tumor-initiating cancer stem-like cells (CSLCs) are refractory to chemotherapy, and their enrichment leads to subsequent development of chemoresistance and recurrence. To overcome the chemoresistance and stemness in HCC, we synthesized a Pt nanocluster assembly (Pt-NA) composed of assembled Pt nanoclusters incorporating a pH-sensitive polymer and HCC-targeting peptide...
November 23, 2016: ACS Central Science
https://www.readbyqxmd.com/read/27922681/cxcr4-promotes-cisplatin-resistance-of-non-small-cell-lung-cancer-in-a-cyp1b1-dependent-manner
#6
Songping Xie, Zhenbo Tu, Jie Xiong, Ganjun Kang, Lina Zhao, Weidong Hu, Haiyan Tan, Kingsley Miyanda Tembo, Qianshan Ding, Xinzhou Deng, Jie Huang, Qiuping Zhang
Chemoresistance is the main cause of treatment failure and high mortality in advanced lung cancer. Cisplatin, an important chemotherapeutic agent for lung cancer, has been observed to show enormously reduced chemotherapeutic efficacy owing to the development of chemoresistance. CXCR4, a stromal-derived-factor-1 specific chemokine receptor, is highly expressed in non-small cell lung cancer (NSCLC) tissues and participates in cancer progression by regulating cell growth, apoptosis or invasion. In this study, we therefore investigated whether CXCR4 plays a role in the cisplatin associated resistance in NSCLC...
December 2, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27919980/intraperitoneal-chemotherapy-in-patients-pretreated-for-ovarian-cancer-matched-with-patients-treated-with-parenteral-chemotherapy
#7
Maria Ornella Nicoletto, Alessandra Casarin, Alessandra Baldoni, Eliana Rulli, Giulia Tasca, Zora Baretta, Grazia Artioli, Giuseppe Lombardi, Alessandro Cappetta, Irene Floriani, Giovanni Randon, Sara Valpione, Piero Litta, Pierfranco Conte, Simone Mocellin, Camillo Aliberti
BACKGROUND: Our aim was to analyze the impact of intraperitoneal chemotherapy (IPC), administered with direct peritoneal puncture, on the survival of patients with pretreated ovarian cancer in a real-life setting. PATIENTS AND METHODS: This was a retrospective study comparing patients with advanced ovarian cancer treated with IPC (N=33) and patients treated with standard intravenous (i.v.) chemotherapy matching cases for known prognostic factors (age, platinum sensitivity, histological subgroup and grade)...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27918237/gpx3-promoter-methylation-predicts-platinum-sensitivity-in-colorectal-cancer
#8
Lorraine Pelosof, Sashidhar Yerram, Todd Armstrong, Nina Chu, Ludmila Danilova, Breann Yanagisawa, Manuel Hidalgo, Nilofer Azad, James G Herman
Epigenetic control of gene expression is a major determinant of tumor phenotype and has been found to influence sensitivity to individual chemotherapeutic agents. Glutathione peroxidase 3 (GPX3, plasma glutathione peroxidase) is a key component of cellular antioxidant regulation and its gene has been reported to be methylated in specific tumor types. GPX3 role in oxidative damage has been associated with sensitivity to platinums in other tumors but its importance in colorectal cancer (CRC) has not been determined...
December 5, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27918099/mir-193b-mediates-cebpd-induced-cisplatin-sensitization-through-targeting-ets1-and-cyclin-d1-in-human-urothelial-carcinoma-cells
#9
Siao-Ren Lin, Hsin-Chih Yeh, Wei-Jan Wang, Hung-Lung Ke, Hui-Hui Lin, Wei-Chi Hsu, Shi-Yi Chao, Tzyh-Chyuan Hour, Wen-Jeng Wu, Yeong-Shiau Pu, A-Mei Huang
Transcription factor CCAAT/enhancer-binding protein delta (CEBPD) plays multiple roles in tumor progression. Studies have demonstrated that cisplatin (CDDP) induced CEBPD expression and had led to chemotherapeutic drug resistance. However, the underlying molecular mechanisms of CDDP-regulated CEBPD expression and its relevant roles in CDDP responses remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Abnormal miRNAs expression is associated with tumor progression...
December 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27914365/developing-piperlongumine-directed-glutathione-s-transferase-inhibitors-by-an-electrophilicity-based-strategy
#10
Hai-Bo Wang, Xiao-Ling Jin, Jia-Fang Zheng, Fu Wang, Fang Dai, Bo Zhou
We report a case of successful design of glutathione S-transferase (GST) inhibitors via a natural product-inspired and electrophilicity-based strategy. Based on this strategy, a novel piperlongumine analog (PL-13) bearing a para-trifluoromethyl group and an α-chlorine on its aromatic and lactam rings, respectively, surfaced as a promising GST inhibitor, thereby overcoming cisplatin resistance in lung cancer A549 cells.
November 15, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27912843/the-reduced-concentration-of-citrate-in-cancer-cells-an-indicator-of-cancer-aggressiveness-and-a-possible-therapeutic-target
#11
Icard Philippe, Lincet Hubert
Proliferating cells reduce their oxidative metabolism and rely more on glycolysis, even in the presence of O2 (Warburg effect). This shift in metabolism reduces citrate biosynthesis and diminishes intracellular acidity, both of which promote glycolysis sustaining tumor growth. Because citrate is the donor of acetyl-CoA, its reduced production favors a deacetylation state of proteins favoring resistance to apoptosis and epigenetic changes, both processes contributing to tumor aggressiveness. Citrate levels could be monitored as an indicator of cancer aggressiveness (as already shown in human prostate cancer) and/or could serve as a biomarker for response to therapy...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27911863/correlation-of-long-non-coding-rna-h19-expression-with-cisplatin-resistance-and-clinical-outcome-in-lung-adenocarcinoma
#12
Qi Wang, Ningning Cheng, Xuefei Li, Hui Pan, Chunyu Li, Shengxiang Ren, Chunxia Su, Weijing Cai, Chao Zhao, Limin Zhang, Caicun Zhou
The acquired drug resistance would influence the efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer. The present study aimed to investigate the correlation of long non-coding RNA (lncRNA) H19 with cisplatin-resistance and clinical outcome in lung adenocarcinoma. In our study, the expression of H19 in cisplatin-resistant A549/DDP cells was unregulated. Knockdown of H19 restored the response of A549/DDP cells to cisplatin. H19-mediated chemosensitivity enhancement was associated with metastasis, induction of G0/G1 cell-cycle arrest, cell proliferation, and increased apoptosis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910856/acquired-resistance-of-pancreatic-cancer-cells-to-cisplatin-is-multifactorial-with-cell-context-dependent-involvement-of-resistance-genes
#13
R Mezencev, L V Matyunina, G T Wagner, J F McDonald
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal of malignancies, in large measure, due to the propensity of PDAC cells to acquire resistance to chemotherapeutic agents. A better understanding of the molecular basis of acquired resistance is a major focus of contemporary PDAC research. We report here the results of a study to independently develop cisplatin resistance in two distinct parental PDAC cell lines, AsPC1 and BxPC3, and to subsequently examine the molecular mechanisms associated with the acquired resistance...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27909718/enzalutamide-inhibits-proliferation-of-gemcitabine-resistant-bladder-cancer-cells-with-increased-androgen-receptor-expression
#14
Koji Kameyama, Kengo Horie, Kosuke Mizutani, Taku Kato, Yasunori Fujita, Kyojiro Kawakami, Toshio Kojima, Tatsuhiko Miyazaki, Takashi Deguchi, Masafumi Ito
Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder cancer cells and also the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling...
November 24, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27907865/biophysical-characterization-and-antineoplastic-activity-of-new-bis-thiosemicarbazonato-cu-ii-complexes
#15
Elisa Palma, Filipa Mendes, Goreti Ribeiro Morais, Inês Rodrigues, Isabel Cordeiro Santos, Maria Paula C Campello, Paula Raposinho, Isabel Correia, Sofia Gama, Dulce Belo, Vítor Alves, Antero J Abrunhosa, Isabel Santos, António Paulo
Aiming to explore alternative mechanisms of cellular uptake and cytotoxicity, we have studied a new family of copper(II) complexes (CuL(1)-CuL(4)) with bis(thiosemicarbazone) (BTSC) ligands containing pendant protonable cyclic amines (morpholine and piperidine). Herein, we report on the synthesis and characterization of these new complexes, as well as on their biological performance (cytotoxic activity, cellular uptake, protein and DNA binding), in comparison with the parental Cu(II)ATSM (ATSM=diacetyl-bis(N4-methylthiosemicarbazonate) complex without pendant cyclic amines...
November 23, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27906967/platinum-ii-iodido-complexes-of-7-azaindoles-with-significant-antiproliferative-effects-an-old-story-revisited-with-unexpected-outcomes
#16
Pavel Štarha, Ján Vančo, Zdeněk Trávníček, Jan Hošek, Jarmila Klusáková, Zdeněk Dvořák
A series of platinum(II) diiodido complexes containing 7-azaindole derivatives, having the general formula cis-[PtI2(naza)2] (1-8), has been prepared and thoroughly characterized, including X-ray structure analysis of cis-[PtI2(2Me4Claza)2]∙DMF (8∙DMF; 2Me4Claza = 2-methyl-4-chloro-7-azaindole). Complexes showed high in vitro cytotoxicity against nine human cancer cell lines (IC50 ranging from 0.4 to 12.8 μM), including the cisplatin-resistant ovarian cancer cell line (A2780R; IC50 = 1.0-3.5 μM). The results of in vivo testing, using the L1210 lymphocytic leukaemia model, at the equimolar doses of Pt with cisplatin (2 mg/kg) confirmed the activity of complex 8 comparable to cisplatin...
2016: PloS One
https://www.readbyqxmd.com/read/27906685/targeted-chimera-delivery-to-ovarian-cancer-cells-by-heterogeneous-gold-magnetic-nanoparticle
#17
Yao Chen, Mengjiao Xu, Yi Guo, Keyao Tu, Weimin Wu, Jianjun Wang, Xiaowen Tong, Wenjuan Wu, Lifeng Qi, Donglu Shi
Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer-siRNA chimera delivery system mediated by cationic Au-Fe3O4 nanoparticles (NPs). The chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with heterogeneous Au-Fe3O4 nanoparticles by electrostatic interaction. The obtained complex exhibited much higher silencing efficiency against Notch3 gene compared with chimera alone and lipofectamine-siRNA complex, and improved the antitumor effects of the loaded chimera...
December 1, 2016: Nanotechnology
https://www.readbyqxmd.com/read/27906433/microrna-185-5p-modulates-chemosensitivity-of-human-non-small-cell-lung-cancer-to-cisplatin-via-targeting-abcc1
#18
K Pei, J-J Zhu, C-E Wang, Q-L Xie, J-Y Guo
OBJECTIVE: MicroRNA-185-5p (miR-185-5p) dysregulation is found in various human cancers. Our purpose is to investigate the association of miR-185-5p expression with the sensitivity of non-small cell lung cancer (NSCLC) to cisplatin. MATERIALS AND METHODS: Real-time PCR or Western blot assay was performed to detect the expression of mature miR-185-5p and ATP-binding cassette, subfamily C, member 1 (ABCC1) protein. Cell lines with abnormal expression of miR-185-5p were generated using miR-185-5p inhibitor and mimics...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27904781/microrna-497-regulates-cisplatin-chemosensitivity-of-cervical-cancer-by-targeting-transketolase
#19
Hui Yang, Xiao-Li Wu, Kai-Hua Wu, Rong Zhang, Li-Li Ju, Ying Ji, Yan-Wei Zhang, Song-Lin Xue, Ye-Xin Zhang, Yong-Feng Yang, Min-Min Yu
Cervical cancer is one of the most lethal malignancies amongst women, partially because it is unresponsive to many chemotherapeutic drugs. The mechanism underlying cisplatin (DDP) resistance in cervical cancer remains largely elusive. In this study, by detecting the 12 most reported down-regulated miRNAs in chemotherapy-sensitive and -resistant cervical cancer cells, we found that miR-497 was significantly reduced in chemotherapy-resistant HeLa/DDP cells and contributed to DDP chemosensitivity. Transketolase (TKT), a thiamine-dependent enzyme that plays a role in the channeling of excess glucose phosphates to glycolysis in the pentose phosphate pathway, was identified as a direct target of miR-497...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27904686/fisetin-a-dietary-phytochemical-overcomes-erlotinib-resistance-of-lung-adenocarcinoma-cells-through-inhibition-of-mapk-and-akt-pathways
#20
Liang Zhang, Yi Huang, Wenlei Zhuo, Yi Zhu, Bo Zhu, Zhengtang Chen
Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells...
2016: American Journal of Translational Research
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