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https://www.readbyqxmd.com/read/29352734/resistance-to-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer-the-role-of-cancer-stem-cells
#1
REVIEW
Marzia Del Re, Elena Arrigoni, Giuliana Restante, Antonio Passaro, Eleonora Rofi, Stefania Crucitta, Filippo De Marinis, Antonello Di Paolo, Romano Danesi
Among the potential mechanisms involved in resistance to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), the manifestation of stem-like properties in cancer cells seems to have a crucial role. Alterations involved in the development of TKI resistance may be acquired in a very early phase of tumorigenesis, supporting the hypothesis that these aberrations may be present in cancer stem cells (CSCs). In this regard, the characterization of tumor subclones in the initial phase and the identification of the CSCs may be helpful in planning a specific treatment to target selected biomarkers, suppress tumor growth, and prevent drug resistance...
January 20, 2018: Stem Cells
https://www.readbyqxmd.com/read/29352647/ifn-%C3%AE-and-tnf-%C3%AE-pre-licensing-protects-mesenchymal-stromal-cells-from-the-pro-inflammatory-effects-of-palmitate
#2
Lauren Boland, Anthony J Burand, Alex J Brown, Devlin Boyt, Vitor A Lira, James A Ankrum
The use of mesenchymal stromal cell (MSC) therapy for the treatment of type 2 diabetes (T2D) and T2D complications is promising; however, the investigation of MSC function in the setting of T2D has not been thoroughly explored. In our current study, we investigated the phenotype and function of MSCs in a simulated in vitro T2D environment. We show that palmitate, but not glucose, exposure impairs MSC metabolic activity with moderate increases in apoptosis, while drastically affecting proliferation and morphology...
December 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29352129/molecular-characterization-of-the-grape-seeds-extract-s-effect-against-chemically-induced-liver-cancer-in-vivo-and-in-vitro-analyses
#3
Alaaeldin Ahmed Hamza, Gehan Hussein Heeba, Hanan Mohamed Elwy, Chandraprabha Murali, Raafat El-Awady, Amr Amin
The purpose of this study was to investigate the anti-cancer property of grape seed extract (GSE) during early stages of developing liver cancer using a two-stage carcinogenic model combining diethylnitrosamine (DEN) and 2-Acetyl Aminofluorene (2-AAF). Administration of GSE at doses 25, 50 and 100 mg/kg per day started at the beginning of promotion periods and continued for 14 weeks. GSE dramatically inhibited pre-neoplastic foci formation as well as significantly decreased the number and the area of placental glutathione-S-transferase in livers of DEN-2AAF-treated rats by approximately 4 & 10 fold deductions, respectively...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352113/polo-like-kinase-4-mediates-epithelial-mesenchymal-transition-in-neuroblastoma-via-pi3k-akt-signaling-pathway
#4
Xiangdong Tian, Dejun Zhou, Lu Chen, Yao Tian, Benfu Zhong, Yanna Cao, Qiuping Dong, Meng Zhou, Jie Yan, Yalei Wang, Yanli Qiu, Lianmin Zhang, Zhongyuan Li, Huijuan Wang, Daowei Wang, Guoguang Ying, Qiang Zhao
Neuroblastoma (NB) is the most common malignant tumor in infancy and most common extracranial solid tumor in childhood. With the improvement of diagnosis and treatment, the survival rate of patients with low-risk and intermediate-risk NB can reach up to 90%. In contrast, for high-risk NBs, the long-term survival rate is still <40% because of heterogeneity of this tumor. The pathogenesis of NB is still not explicit, therefore it is of great significance to explore the mechanism of NB tumorigenesis and discover new therapeutic targets for NB...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29351902/targeting-the-sphk1-s1p-s1pr1-axis-that-links-obesity-chronic-inflammation-and-breast-cancer-metastasis
#5
Masayuki Nagahashi, Akimitsu Yamada, Eriko Katsuta, Tomoyoshi Aoyagi, Wei-Ching Huang, Krista P Terracina, Nitai C Hait, Jeremy C Allegood, Junko Tsuchida, Kizuki Yuza, Masato Nakajima, Manabu Abe, Kenji Sakimura, Sheldon Milstien, Toshifumi Wakai, Sarah Spiegel, Kazuaki Takabe
Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) which mediates cancer pathogenesis. A high fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29351887/synthesis-and-anti-tumor-activity-of-ef24-analogues-as-ikk%C3%AE-inhibitors
#6
Rong Jin, Qiuxiang Chen, Song Yao, Encheng Bai, Weitao Fu, Ledan Wang, Jiabing Wang, Xiaojing Du, Tao Wei, Haineng Xu, Chengxi Jiang, Peihong Qiu, Jianzhang Wu, Wulan Li, Guang Liang
EF24 is an IKKβ inhibitor (IC50: 72 μM) containing various anti-tumor activities. In this study, a series of EF24 analogs targeting IKKβ were designed and synthesized. Several IKKβ inhibitors with better activities than EF24 were screened out and B3 showed best IKKβ inhibitory (IC50: 6.6 μM). Molecular docking and dynamic simulation experiments further confirmed this inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC-7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF-κB signal pathway by inhibiting IKKβ phosphorylation, and followed arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34 expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up-regulating cleaved-caspase3...
December 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29351847/phosphorylation-of-ezh2-by-ampk-suppresses-prc2-methyltransferase-activity-and-oncogenic-function
#7
Lixin Wan, Kexin Xu, Yongkun Wei, Jinfang Zhang, Tao Han, Christopher Fry, Zhao Zhang, Yao Vickie Wang, Liyu Huang, Min Yuan, Weiya Xia, Wei-Chao Chang, Wen-Chien Huang, Chien-Liang Liu, Yuan-Ching Chang, Jinsong Liu, Yun Wu, Victor X Jin, Xiangpeng Dai, Jianfeng Guo, Jia Liu, Shulong Jiang, Jin Li, John M Asara, Myles Brown, Mien-Chie Hung, Wenyi Wei
Sustained energy starvation leads to activation of AMP-activated protein kinase (AMPK), which coordinates energy status with numerous cellular processes including metabolism, protein synthesis, and autophagy. Here, we report that AMPK phosphorylates the histone methyltransferase EZH2 at T311 to disrupt the interaction between EZH2 and SUZ12, another core component of the polycomb repressive complex 2 (PRC2), leading to attenuated PRC2-dependent methylation of histone H3 at Lys27. As such, PRC2 target genes, many of which are known tumor suppressors, were upregulated upon T311-EZH2 phosphorylation, which suppressed tumor cell growth both in cell culture and mouse xenografts...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29351801/high-expression-of-tmem40-is-associated-with-the-malignant-behavior-and-tumorigenesis-in-bladder-cancer
#8
Zhen-Fei Zhang, Han-Rong Zhang, Qing-Yan Zhang, Shu-Yu Lai, Yu-Zhen Feng, Yi Zhou, Si-Rong Zheng, Rong Shi, Jue-Yu Zhou
BACKGROUND: Bladder cancer (BCa) is one of the most common cancers in the urinary system among the world. Previous studies suggested that TMEM40 expression level was significantly associated with clinicopathological parameters including histological grade, clinical stage and pT status of bladder cancer. However, the molecular mechanism of TMEM40 in BCa remains poorly understood. METHODS: Real-time quantitative RT-PCR (qRT-PCR) and western blot (WB) were used to examine the expression levels of TMEM40 in BCa tissues, paired non-cancer tissues and cell lines...
January 19, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29351747/combination-of-pelargonium-sidoides-and-coptis-chinensis-root-inhibits-nuclear-factor-kappa-b-mediated-inflammatory-response-in-vitro-and-in-vivo
#9
Sang Mi Park, Byung-Gu Min, Ji Yun Jung, Kyung Hwan Jegal, Chul Won Lee, Kwang Youn Kim, Young Woo Kim, Youn-Woong Choi, Il Je Cho, Sae Kwang Ku, Sang Chan Kim
BACKGROUND: Pelargonium sidoides (PS) and Coptis chinensis root (CR) have traditionally been used to treat various diseases, including respiratory and gastrointestinal infections, dysmenorrhea, and hepatic disorders. The present study was conducted to evaluate the anti-inflammatory effects of a combination of PS and CR in vitro and in vivo. METHODS: The in vitro effects of PS + CR on the induction of inflammation-related proteins were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264...
January 19, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29350904/nanoplatform-assembled-from-a-cd44-targeted-prodrug-and-smart-liposomes-for-dual-targeting-of-tumor-microenvironment-and-cancer-cells
#10
Yaqi Lv, Chaoran Xu, Xiangmei Zhao, Chenshi Lin, Xin Yang, Xiaofei Xin, Li Zhang, Chao Qin, Xiaopeng Han, Lei Yang, Wei He, Lifang Yin
The tumor microenvironment (TME) plays a critical role in tumor initiation, progression, invasion and metastasis. Therefore, a therapy that combines chemotherapeutic drugs with a TME modulator could be a promising route for cancer treatment. This paper reports a nanoplatform self-assembled from a hyaluronic acid (HA)-paclitaxel (PTX) (HA-PTX) prodrug and marimastat (MATT)-loaded thermosensitive liposomes (LTSLs) (MATT-LTSLs) for the dual targeting of the TME and cancer cells. Interestingly, the prodrug HA-PTX can self-assemble on both positively and negatively charged liposomes, forming hybrid nanoparticles (HNPs, 100 nm)...
January 19, 2018: ACS Nano
https://www.readbyqxmd.com/read/29350902/hierarchically-self-assembled-supramolecular-host-guest-delivery-system-for-delivery-of-chemotherapeutics-to-drug-resistant-cancer-tumours
#11
Hongwei Cheng, Xiaoshan Fan, Xiaoyuan Wang, Enyi Ye, Xian Jun Loh, Zibiao Li, Yun-Long Wu
In this report, a new star-like copolymer -CD-g-(PNIPAAm-b-POEGA)x consisting of a -CD core, grafted with temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and biocompatible poly(oligo(ethylene glycol) acrylate) (POEGA) in a block copolymer of the arms, was used to deliver chemotherapeutics to drug resistant cancer tumours. The first step of the self-assembly process involves the encapsulation of chemotherapeutics through host-guest inclusion complexation between the -cyclodextrin cavity and the anti-cancer drug...
January 19, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29350750/the-hepatoprotective-effect-of-selenium-enriched-yeast-and-gum-arabic-combination-on-carbon-tetrachloride-induced-chronic-liver-injury-in-rats
#12
Mohammed Hamid, Yassin Abdulrahim, Dandan Liu, Gang Qian, Alamzeb Khan, Kehe Huang
The antioxidant and anti-inflammatory effects of selenium-enriched yeast (SY) and Gum Arabic (GA) have been reported. This study aimed to determine the hepatoprotective effect of SY and GA combination on carbon tetrachloride (CCl4 )-induced chronic liver injury in rats and to explore their synergistic mechanisms of action. Forty adult male Wistar rats randomly allotted to 5 groups: (A) worked as control, (B) was administered CCl4 , (C-E) were fed daily by GA, SY, and GA+SY respectively after mixing with basal diet, following CCl4 -intoxication...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29350052/protective-mechanisms-of-6-gingerol-in-dextran-sulfate-sodium-induced-chronic-ulcerative-colitis-in-mice
#13
B O Ajayi, I A Adedara, E O Farombi
Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon, with an increasing incidence worldwide. 6-Gingerol (6G) is a bioactive constituent of Zingiber officinale, which has been reported to possess various biological activities. This study was designed to evaluate the role of 6G in chronic UC. Chronic UC was induced in mice by three cycles of 2.5% dextran sulfate sodium (DSS) in drinking water. Each cycle consisted of 7 days of 2.5% DSS followed by 14 days of normal drinking water...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29349661/pkm2-is-involved-in-neuropathic-pain-by-regulating-erk-and-stat3-activation-in-rat-spinal-cord
#14
Binbin Wang, Siyuan Liu, Bingbing Fan, Xingguo Xu, Yonglin Chen, Rongxiang Lu, Zhongling Xu, Xiaojuan Liu
BACKGROUND: Pyruvate kinase isozymes M2 (PKM2), as a member of pyruvate kinase family, plays a role of glycolytic enzyme in glucose metabolism. It also functions as protein kinase in cell proliferation, signaling, immunity, and gene transcription. In this study, the role of PKM2 in neuropathic pain induced by chronic constriction injury (CCI) was investigated. METHODS: Rats were randomly grouped to establish CCI models. PKM2, extracellular regulated protein kinases (EKR), p-ERK, signal transducers and activators of transcription (STAT3), p-STAT3, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and p-PI3K/AKT proteins expression in spinal cord was examined by Western blot analysis...
January 18, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29349597/drug-repurposing-screening-identifies-bortezomib-and-panobinostat-as-drugs-targeting-cancer-associated-fibroblasts-cafs-by-synergistic-induction-of-apoptosis
#15
Hak-Min Lee, Eunmyong Lee, So-Young Yeo, Sang Shin, Hyun-Kyu Park, Do-Hyun Nam, Seok-Hyung Kim
Cancer associated fibroblasts (CAFs) are the most abundant components of cancer-microenvironment. They play important roles in cancer initiation, progression, and metastasis. In addition, CAFs can confer drug-resistance to cancer cells. Considering their pro-tumorigenic roles, it is recommended to remove CAFs to prevent cancer recurrence after chemotherapy. Despite their clinical significance, few anti-CAF drugs have been developed. The objective of this study was to find a drug that could suppress the viability of patient-derived CAFs through repurposed screening of 51 drugs that were in clinical trials or received FDA approval...
January 18, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29349577/combination-therapy-with-sulfasalazine-and-valproic-acid-promotes-human-glioblastoma-cell-death-through-imbalance-of-the-intracellular-oxidative-response
#16
Carlos Gustavo Garcia, Suzana Assad Kahn, Luiz Henrique Medeiros Geraldo, Igor Romano, Ivan Domith, Deborah Christinne Lima E Silva, Fernando Dos Santos Assunção, Marcos José Ferreira, Camila Cabral Portugal, Jorge Marcondes de Souza, Luciana Ferreira Romão, Annibal Duarte Pereira Netto, Flávia Regina Souza Lima, Marcelo Cossenza
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor and still lacks effective therapeutic strategies. It has already been shown that old drugs like sulfasalazine (SAS) and valproic acid (VPA) present antitumoral activities in glioma cell lines. SAS has also been associated with a decrease of intracellular glutathione (GSH) levels through a potent inhibition of xc- glutamate/cystine exchanger leading to an antioxidant deprotection. In the same way, VPA was recently identified as a histone deacetylase (HDAT) inhibitor capable of activating tumor suppression genes...
January 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29348886/frk-inhibits-breast-cancer-cell-migration-and-invasion-by-suppressing-epithelial-mesenchymal-transition
#17
Yetunde Ogunbolude, Chenlu Dai, Edward T Bagu, Raghuveera Kumar Goel, Sayem Miah, Joshua MacAusland-Berg, Chi Ying Ng, Rajni Chibbar, Scott Napper, Leda Raptis, Frederick Vizeacoumar, Franco Vizeacoumar, Keith Bonham, Kiven Erique Lukong
The human fyn-related kinase (FRK) is a non-receptor tyrosine kinase known to have tumor suppressor activity in breast cancer cells. However, its mechanism of action has not been fully characterized. We generated FRK-stable MDA-MB-231 breast cancer cell lines and analyzed the effect on cell proliferation, migration, and invasiveness. We also used kinome analysis to identify potential FRK-regulated signaling pathways. We employed both immunoblotting and RT-PCR to identify/validate FRK-regulated targets (proteins and genes) in these cells...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348882/microrna203a-suppresses-glioma-tumorigenesis-through-an-atm-dependent-interferon-response-pathway
#18
Chuan He Yang, Yinan Wang, Michelle Sims, Chun Cai, Ping He, Hans Häcker, Junming Yue, Jinjun Cheng, Frederick A Boop, Lawrence M Pfeffer
Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We previously showed that miR-203a is expressed at relatively low levels in GBM patients, and ectopic miR-203a expression in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon (IFN) or temozolomide in vitro, and inhibited GBM tumorigenesis in vivo...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348852/reduced-fbxw7-expression-in-pancreatic-cancer-correlates-with-poor-prognosis-and-chemotherapeutic-resistance-via-accumulation-of-mcl1
#19
Norihiro Ishii, Kenichiro Araki, Takehiko Yokobori, Dorgormaa Gantumur, Takahiro Yamanaka, Bolag Altan, Mariko Tsukagoshi, Takamichi Igarashi, Akira Watanabe, Norio Kubo, Yasuo Hosouchi, Hiroyuki Kuwano, Ken Shirabe
Pancreatic cancer is a highly malignant tumor type with poor outcomes, and elucidation of the mechanisms involved in cancer progression and therapeutic resistance is critical. FBXW7 is a key regulator of tumor malignant potential, and its substrate MCL1 regulates therapeutic resistance in human malignancies. Therefore, determination of the relevance of FBXW7 expression is critical for improving patient outcomes. In this study, we investigated the function and clinical significance of FBXW7 in pancreatic cancer...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348851/comprehensive-analysis-of-mrna-lncrna-co-expression-profile-revealing-crucial-role-of-imprinted-gene-cluster-dlk1-meg3-in-chordoma
#20
Hao Chen, Kai Zhang, Jian Lu, Guizhong Wu, Huilin Yang, Kangwu Chen
Chordoma is a rare bone tumor with high recurrence rate, but the mechanism of its development is unclear. Long non-coding RNAs(lncRNAs) are recently revealed to be regulators in a variety of biological processed by targeting on mRNA transcription. Their expression profile and function in chordoma have not been investigated yet. In this study, we firstly performed the comprehensive analysis of the lncRNA and coding genes expression analysis with three chordoma samples and three fetal nucleus pulposus tissues...
December 22, 2017: Oncotarget
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