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https://www.readbyqxmd.com/read/28323527/design-synthesis-and-anticancer-evaluation-of-novel-pyrazole-pyrazolo-3-4-d-pyrimidine-and-their-glycoside-derivatives
#1
Ibrahim F Nassar, Ahmed F El Farargy, Fathy M Abdelrazek, Nasser S M Ismail
The chalcone derivatives 3a,b were cyclized upon reaction with thiourea to give the pyrazolo[3,4-d]pyrimidine derivatives 5a,b. Condensation of 5a,b and their hydrazide derivatives 8a,b with cyclic and acyclic glucose gave the condensed S- and N-glycosides 7a,b and 9a,b, respectively. Reaction of 3b with ethyl cyanoacetate followed by reaction with cyclic glucose afforded a mixture of the O- and/or N-glycoside isomers 12 and 13, respectively. The pyrazolo[3,4-c]pyrazole derivative 14 was also obtained from the reaction of 3b with hydrazine hydrate...
March 21, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28318508/effects-of-novel-brominated-flame-retardant-tbph-and-its-metabolite-tbmehp-on-human-vascular-endothelial-cells-implication-for-human-health-risks
#2
Ping Xiang, Rong-Yan Liu, Hong-Jie Sun, Yun-Wen Yang, Xin-Yi Cui, Lena Q Ma
As a replacement for polybrominated diphenyl ethers, bis-(2-ethylhexyl) tetrabromophthalate (TBPH) is widely used as a novel flame retardant and has been detected in many environmental matrix including human blood. TBPH can be metabolized into mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP) by carboxylesterase. However, their adverse effects on human vascular endothelium and their potential impacts on human cardiovascular disease are unknown. In this study, their adverse effects and associated molecular mechanisms on human vascular endothelial cells (HUVECs) were investigated...
March 16, 2017: Environmental Research
https://www.readbyqxmd.com/read/28314474/sulforaphane-as-an-adjunctive-to-everolimus-counteracts-everolimus-resistance-in-renal-cancer-cell-lines
#3
Eva Juengel, Stephanie Euler, Sebastian Maxeiner, Jochen Rutz, Saira Justin, Frederik Roos, Wael Khoder, Karen Nelson, Wolf O Bechstein, Roman A Blaheta
BACKGROUND: The mechanistic target of rapamycin (mTOR) inhibitors, everolimus and temsirolimus, have widened therapeutic options to treat renal cell carcinoma (RCC). However, chronic treatment with these inhibitors often induces resistance, leading to therapeutic failure. PURPOSE: The natural compound, sulforaphane (SFN), was added to an everolimus based regime in vitro in the hopes of preventing resistance development. METHODS: A panel of RCC cell lines (A498, Caki-1, KTCTL-26) was treated with everolimus or SFN or with an everolimus-SFN-combination, either short- (24h) or long-term (8 weeks), and cell growth, proliferation, apoptosis, and cell cycle phases were measured...
April 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28300289/dehydrocostus-lactone-suppresses-proliferation-of-human-chronic-myeloid-leukemia-cells-through-bcr-abl-jak-stat-signaling-pathways
#4
Hong Cai, Xiaosong Qin, Chunhui Yang
This study evaluates the anticancer effects of dehydrocostus lactone, a plant-derived sesquiterpene lactone, on human chronic myeloid leukemia cells. Dehydrocostus lactone significantly inhibits cell proliferation by inducing cells to undergo cell cycle arrest, apoptosis and differentiation. Dehydrocostus lactone suppresses the expression of cyclin B1, cyclin A, cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin-dependent kinase 1 (CDK2) and increases p21 expression, resulting in S-G2/M phase arrest in K562 cells...
March 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28297760/-promoting-effect-of-cyclin-d1-overexpression-on-proliferation-and-epithelial-mesenchymal-transition-of-cervical-squamous-cell-carcinoma-siha-cells
#5
P Wang, S Liu, B Cheng, X Z Wu, S S Ding, L Xu, Y Liu, L Duan, S Z Sun
Objective: To study effects of cyclin D1 overexpression on the proliferation and differentiation of cervical squamous cell carcinoma SiHa cells and to investigate related signaling molecules. Methods: Primers were designed to amplify the full length of cyclin D1 gene and cyclin D1 gene was amplified by PCR for constructing pcDNA3.1 plasmid vector. The construct was then transfected into SiHa cells, and the cells with stable overexpression of cyclin D1 were established, cyclin D1 gene and protein expression were detected by RT-PCR and Western blot, respectively...
March 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28291626/mus81-knockdown-sensitizes-colon-cancer-cells-to-chemotherapeutic-drugs-by-activating-chk1-pathway
#6
Fan Wu, Shu-Chao Su, Guo-Qian Tan, Lun Yan, Ting-Yue Li, Hao-Lu Zhang, Ji-Shang Yu, Bai-Lin Wang
PURPOSE: The inhibition of Mus81, a critical DNA repair gene, is recently related to the chemosensitivity of several human cancer cells such as hepatocellular carcinoma (HCC) cells. However, the role of Mus81 knockdown in chemotherapy response of colon cancer cells remains largely unknown. METHODS AND MATERIALS: The effects of Mus81 knockdown by lentivirus-mediated short hairpin RNA in sensitivity of HCT116 and LS180 colon cancer cell lines to four therapeutic drugs, including cisplatin (CDDP), were evaluated by MTT assay as well as a mouse model...
March 10, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28290601/ict1-knockdown-inhibits-breast-cancer-cell-growth-via-induction-of-cell-cycle-arrest-and-apoptosis
#7
Chen Wang, Chenlu Liang, Weiliang Feng, Xianghou Xia, Feng Chen, Enqi Qiao, Xiping Zhang, Daobao Chen, Zhiqiang Ling, Hongjian Yang
The protein encoded by immature colon carcinoma transcript 1 (ICT1) is a component of the human mitochondrial ribosome, and is reported to be implicated in cell proliferation, viability and apoptosis of HeLa cells. This study was conducted to investigate the role of ICT1 in human breast cancer. Oncomine database was used to investigate ICT1 expression in human breast cancer tissues compared to normal tissues. The results showed that ICT1 was highly overexpressed in various human breast cancer subtypes. Then short hairpin RNA (shRNA)-mediated knockdown of ICT1 was performed in human breast cancer ZR-75-30 and T-47D cells...
March 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28289384/theabrownin-inhibits-cell-cycle-progression-and-tumor-growth-of-lung-carcinoma-through-c-myc-related-mechanism
#8
Li Zhou, Feifei Wu, Wangdong Jin, Bo Yan, Xin Chen, Yingfei He, Weiji Yang, Wenlin Du, Qiang Zhang, Yonghua Guo, Qiang Yuan, Xiaoqiao Dong, Wenhua Yu, Jin Zhang, Luwei Xiao, Peijian Tong, Letian Shan, Thomas Efferth
Green tea, the fresh leaves of Camellia sinensis, is not only a health-promoting beverage but also a traditional Chinese medicine used for prevention or treatment of cancer, such as lung cancer. Theabrownin (TB) is the main fraction responsible for the medicinal effects of green tea, but whether it possesses anti-cancer effect is unknown yet. This study aimed to determine the in vitro and in vivo anti-lung cancer effect of TB and explore the underlying molecular mechanism, by using A549 cell line and Lewis lung carcinoma-bearing mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28288874/loss-of-exosomal-mir-320a-from-cancer-associated-fibroblasts-contributes-to-hcc-proliferation-and-metastasis
#9
Zhuochao Zhang, Xiao Li, Wei Sun, Shuqiang Yue, Jingyue Yang, Junjie Li, Ben Ma, Jianlin Wang, Xisheng Yang, Meng Pu, Bai Ruan, Ge Zhao, Qike Huang, Lin Wang, Kaishan Tao, Kefeng Dou
Cancer-associated fibroblasts (CAFs) play a pivotal role in regulating tumour progression. Therefore, understanding how CAFs communicate with hepatocellular carcinoma (HCC) is crucial for HCC therapy. Recently, exosomes have been considered an important "messenger" between cells. In this study, we performed microRNA (miRNA) sequencing of exosomes derived from CAFs and corresponding para-cancer fibroblasts (PAFs) of HCC patients. We found a significant reduction in the miR-320a level in CAF-derived exosomes...
March 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28269752/a-80-gene-set-potentially-predicts-the-relapse-in-laryngeal-carcinoma-optimized-by-support-vector-machine
#10
Bo Yang, Qing Guo, Fei Wang, Kemin Cai, Xueli Bao, Jiusheng Chu
OBJECTIVE: The present study was performed to identify a gene set for predicting the relapse in laryngeal carcinoma using large data analysis methods. METHODS: Two gene expression profile data of laryngeal carcinoma (GSE27020 and GSE25727) were downloaded from public database. Genes associated with tumor relapse, namely informative genes, were identified by Cox regression analysis. Then the protein-protein interaction (PPI) network consisting of informative genes was constructed...
February 27, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28266352/preparation-of-carotenoid-extracts-and-nanoemulsions-from-lycium-barbarum-l-and-their-effects-on-growth-of-ht-29-colon-cancer-cells
#11
H J Hsu, R F Huang, T H Kao, B S Inbaraj, B H Chen
Lycium barbarum L., a traditional Chinese herb widely used in Asian countries, has been demonstrated to be protective against chronic diseases such as age-related macular degeneration. The objectives of this study were to determine the carotenoid content in L. barbarum by high-performance liquid chromatography-mass spectrometry, followed by preparation of a carotenoid nanoemulsion to evaluate the mechanism of inhibition on HT-29 colon cancer cells. The highest extraction yield of carotenoids was attained by employing a solvent system of hexane-ethanol-acetone (1:1:1, v/v/v)...
March 7, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28263292/the-master-role-of-microphthalmia-associated-transcription-factor-in-melanocyte-and-melanoma-biology
#12
Akinori Kawakami, David E Fisher
Certain transcription factors have vital roles in lineage development, including specification of cell types and control of differentiation. Microphthalmia-associated transcription factor (MITF) is a key transcription factor for melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes to promote melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis, including genes encoding proteins involved in apoptosis (eg, BCL2) and the cell cycle (eg, CDK2)...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28260065/fignl1-is-overexpressed-in-small-cell-lung-cancer-patients-and-enhances-nci-h446-cell-resistance-to-cisplatin-and-etoposide
#13
Jian Ma, Jianlei Li, Xiaoling Yao, Shuangjun Lin, Ye Gu, Jianfang Xu, Zixin Deng, Wei Ma, Haiping Zhang
Abnormal DNA repair plays an important role in tumor occurrence, progression and resistance to therapy. Fidgetin-like 1 (FIGNL1) expression was assayed in 42 small cell lung cancer (SCLC) and 45 normal lung specimens from Chinese patients by qRT-PCR. Notably, FIGNL1 was upregulated by 1.5-fold in the SCLC specimens compared to that noted in the normal counterparts. The SCLC cell line NCI-H446 that overexpresses FIGNL1 was adopted to explore the biological significance of FIGNL1 in SCLC. Even when FIGNL1 expression was suppressed by up to 48...
March 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28259974/3-hydroxyterphenyllin-a-natural-fungal-metabolite-induces-apoptosis-and-s-phase-arrest-in-human-ovarian-carcinoma-cells
#14
Yaomin Wang, Casey Compton, Gary O Rankin, Stephen J Cutler, Yon Rojanasakul, Youying Tu, Yi Charlie Chen
In the present study, we evaluated 3-Hydroxyter-phenyllin (3-HT) as a potential anticancer agent using the human ovarian cancer cells A2780/CP70 and OVCAR-3, and normal human epithelial ovarian cells IOSE-364 as an in vitro model. 3-HT suppressed proliferation and caused cytotoxicity against A2780/CP70 and OVCAR-3 cells, while it exhibited lower cytotoxicity in IOSE-364 cells. Subsequently, we found that 3-HT induced S phase arrest and apoptosis in a dose-independent manner. Further investigation revealed that S phase arrest was related with DNA damage which mediated the ATM/p53/Chk2 pathway...
March 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28256105/cis-nerolidol-induces-endoplasmic-reticulum-stress-and-cell-death-in-human-hepatocellular-carcinoma-cells-through-extensive-cyp2c19-and-cyp1a2-oxidation
#15
Bruna Isabela Biazi, Thalita Alves Zanetti, Adrivanio Baranoski, Amanda Cristina Corveloni, Mário Sérgio Mantovani
Of late, many studies are attempting to find new molecules with anti-cancer properties, especially those with the capability to inhibit cell growth. The aim of this work was to evaluate nerolidol, a plant-based compound, as its cytotoxicity, genotoxicity, antiproliferative and apoptotic induction, cell cycle, mitochondrial membrane potential, and RT-qPCR of transcripts related to those pathways in the human hepatocellular carcinoma cell line (HepG2/C3A). Only cis-nerolidol (C-NER) demonstrated cytotoxicity (100 to 250 μM) activity and was selected to conduct the following experiments...
March 2, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28253714/microarray-expression-analysis-of-mycn-amplified-neuroblastoma-cells-after-inhibition-of-cdk2
#16
H Song, F Wu, S Li, Z Wang, X Liu, Y Cui, C Lin
The study was aimed to explore the underlying molecular mechanisms of CDK2 inhibition in neuroblastoma by bioinformatics analysis. Gene expression profile GSE16480 was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) were identified from IMR32 between each time point and average expression of all time points. Gene significance was calculated using dSVDsig algorithm of dnet package. Protein-protein interaction (PPI) network was built. Then, integrated with gene significance, a core PPI network was detected by dNetPipeline algorithm in dnet package...
March 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28249908/kinome-wide-rna-interference-screen-reveals-a-role-for-pdk1-in-acquired-resistance-to-cdk4-6-inhibition-in-er-positive-breast-cancer
#17
Valerie M Jansen, Neil E Bhola, Joshua A Bauer, Luigi Formisano, Kyung-Min Lee, Katherine E Hutchinson, Agnieszka K Witkiewicz, Preston D Moore, Monica Valeria Estrada, Violeta Sanchez, Paula G Ericsson, Melinda Sanders, Paula R Pohlmann, Michael J Pishvaian, David A Riddle, Wenyi Wei, Teresa C Dugger, Erik Knudsen, Carlos L Arteaga
To discover mechanisms of resistance to CDK4/6 inhibitors, we used a kinome-wide siRNA screen to identify kinases that, when downregulated, promote sensitivity to ribociclib. We identified 3-phosphoinositide dependent protein kinase 1 (PDK1) as the top siRNA that sensitized ER+ MCF-7 cells to ribociclib. Pharmacological inhibition of PDK1 with GSK2334470 in combination with ribociclib or palbociclib, synergistically inhibited proliferation and increased apoptosis in a panel of ER+ breast cancer cell lines. Ribociclib-resistant MCF-7, T47D and HCC1428 cells, selected after chronic drug exposure, displayed increased levels of PDK1, P-RSK2, P-AKT and P-S6 compared to parental drug-sensitive cells...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28246384/a-c-myc-regulated-stem-cell-like-signature-in-high-risk-neuroblastoma-a-systematic-discovery-target-neuroblastoma-esc-like-signature
#18
Xinan Holly Yang, Fangming Tang, Jisu Shin, John M Cunningham
c-Myc dysregulation is hypothesized to account for the 'stemness' - self-renewal and pluripotency - shared between embryonic stem cells (ESCs) and adult aggressive tumours. High-risk neuroblastoma (HR-NB) is the most frequent, aggressive, extracranial solid tumour in childhood. Using HR-NB as a platform, we performed a network analysis of transcriptome data and presented a c-Myc subnetwork enriched for genes previously reported as ESC-like cancer signatures. A subsequent drug-gene interaction analysis identified a pharmacogenomic agent that preferentially interacted with this HR-NB-specific, ESC-like signature...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216226/nbs1-phosphorylation-status-dictates-repair-choice-of-dysfunctional-telomeres
#19
Rekha Rai, Chunyi Hu, Cayla Broton, Yong Chen, Ming Lei, Sandy Chang
Telomeres employ TRF2 to protect chromosome ends from activating the DNA damage sensor MRE11-RAD50-NBS1 (MRN), thereby repressing ATM-dependent DNA damage checkpoint responses. How TRF2 prevents MRN activation at dysfunctional telomeres is unclear. Here, we show that the phosphorylation status of NBS1 determines the repair pathway choice of dysfunctional telomeres. The crystal structure of the TRF2-NBS1 complex at 3.0 Å resolution shows that the NBS1 429YQLSP433 motif interacts specifically with the TRF2(TRFH) domain...
February 8, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28215542/hexachlorobenzene-alters-cell-cycle-by-regulating-p27-cyclin-e-cdk2-and-c-src-p27-protein-complexes
#20
C Ventura, M Núñez, V Gaido, C Pontillo, N Miret, A Randi, C Cocca
Hexachlorobenzene (HCB) is an organochlorine pollutant widely distributed in the environment around the entire world. Previous reports from our group and others have demonstrated that this compound is as an endocrine disruptor. We have also reported that HCB presents a co-carcinogenic effect in N-Nitroso-N-methyl-urea-induced mammary tumours in rats. In this work, we studied the effects of HCB on cell cycle progression and cell cycle regulating protein expression in the estrogen-sensitive breast cancer cell line, MCF-7...
March 15, 2017: Toxicology Letters
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