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https://www.readbyqxmd.com/read/27922057/antiproliferative-activities-of-amaryllidaceae-alkaloids-from-lycoris-radiata-targeting-dna-topoisomerase-i
#1
Gui-Lin Chen, Yong-Qiang Tian, Jian-Lin Wu, Na Li, Ming-Quan Guo
Crude Amaryllidaceae alkaloids (AAs) extracted from Lycoris radiata are reported to exhibit significant anti-cancer activity. However, the specific alkaloids responsible for the pharmacodynamic activity and their targets still remain elusive. In this context, we strived to combine affinity ultrafiltration with topoisomerase I (Top I) as a target enzyme aiming to fish out specific bioactive AAs from Lycoris radiata. 11 AAs from Lycoris radiata were thus screened out, among which hippeastrine (peak 5) with the highest Enrichment factor (EF) against Top I exhibited good dose-dependent inhibition with IC50 at 7...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922047/new-arylated-benzo-h-quinolines-induce-anti-cancer-activity-by-oxidative-stress-mediated-dna-damage
#2
Dharmendra K Yadav, Reeta Rai, Naresh Kumar, Surjeet Singh, Sanjeev Misra, Praveen Sharma, Priyanka Shaw, Horacio Pérez-Sánchez, Ricardo L Mancera, Eun Ha Choi, Mi-Hyun Kim, Ramendra Pratap
The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921393/the-role-of-the-microvascular-network-structure-on-diffusion-and-consumption-of-anti-cancer-drugs
#3
P Mascheroni, R Penta
We investigate the impact of microvascular geometry on the transport of drugs in solid tumors, focusing on the diffusion and consumption phenomena. We embrace recent advances in the asymptotic homogenization literature starting from a double Darcy, double advection-diffusion-reaction system of partial differential equations that is obtained exploiting the sharp length separation between the intercapillary distance and the average tumor size. The geometric information on the microvascular network is encoded into effective hydraulic conductivities and diffusivities, which are numerically computed by solving periodic cell problems on appropriate microscale representative cells...
December 6, 2016: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/27919950/development-of-a-novel-experimental-in-vitro-model-of-isothiocyanate-induced-apoptosis-in-human-malignant-melanoma-cells
#4
Theodora Mantso, Aristeidis P Sfakianos, Aithne Atkinson, Ioannis Anestopoulos, Melina Mitsiogianni, Sotirios Botaitis, Sebachedin Perente, Constantinos Simopoulos, Stavros Vasileiadis, Rodrigo Franco, Aglaia Pappa, Mihalis I Panayiotidis
BACKGROUND: Isothiocyanates are constituents of cruciferous vegetables which have been associated with reduced cancer risk partially through their ability to induce apoptosis in malignant cells including melanoma. MATERIALS AND METHODS: We have utilized human malignant melanoma (A375), epidermoid carcinoma (A431) and immortalized keratinocyte (HaCaT) cells exposed to various isothiocyanates, under different experimental conditions. RESULTS: An experimental in vitro model utilizing low isothiocyanate concentrations (0...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919797/maximising-the-potential-of-akt-inhibitors-as-anti-cancer-treatments
#5
REVIEW
Jessica S Brown, Udai Banerji
PI3K/AKT signalling is commonly disrupted in human cancers, with AKT being a central component of the pathway, influencing multiple processes that are directly involved in tumourigenesis. Targeting AKT is therefore a highly attractive anti-cancer strategy with multiple AKT inhibitors now in various stages of clinical development. In this review, we summarise the role and regulation of AKT signalling in normal cellular physiology. We highlight the mechanisms by which AKT signalling can be hyperactivated in cancers and discuss the past, present and future clinical strategies for AKT inhibition in oncology...
December 2, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27919735/quercetin-attenuates-high-fructose-feeding-induced-atherosclerosis-by-suppressing-inflammation-and-apoptosis-via-ros-regulated-pi3k-akt-signaling-pathway
#6
Xue-Li Lu, Cui-Hua Zhao, Xin-Liang Yao, Han Zhang
Quercetin is a dietary flavonoid compound extracted from various plants, such as apple and onions. Previous studies have revealed its anti-inflammatory, anti-cancer, antioxidant and anti-apoptotic activities. This study investigated the ability of quercetin to inhibit high fructose feeding- or LPS-induced atherosclerosis through regulating oxidative stress, apoptosis and inflammation response in vivo and in vitro experiments. 50 and 100mg/kg quercetin were used in our study, showing significant inhibitory role in high fructose-induced atherosclerosis via reducing reactive oxygen species (ROS) levels, Caspase-3 activation, inflammatory cytokines releasing, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and collagen contents as well as modulating apoptosis- and inflammation-related proteins expression...
December 2, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27919267/targeted-drug-delivery-of-near-ir-fluorescent-doxorubicin-conjugated-poly-ethylene-glycol-bisphosphonate-nanoparticles-for-diagnosis-and-therapy-of-primary-and-metastatic-bone-cancer-in-a-mouse-model
#7
S Rudnick-Glick, E Corem-Salkmon, I Grinberg, S Margel
BACKGROUND: Most primary and metastatic bone tumors demonstrate increased osteoclast activity and bone resorption. Current treatment is based on a combination of surgery, radiotherapy and chemotherapy. Severe side effects are associated with chemotherapy due to use of high dosage and nonspecific uptake. Bisphosphonates have a strong affinity to Ca(2+) ions and are widely used in the treatment of bone disorders. RESULTS: We have engineered a unique biodegradable bisphosphonate nanoparticle (NPs) bearing two functional surface groups: (1) primary amine groups for covalent attachment of a dye/drug (e...
December 5, 2016: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/27919264/acidic-tumor-microenvironment-abrogates-the-efficacy-of-mtorc1-inhibitors
#8
Seraina Faes, Adrian P Duval, Anne Planche, Emilie Uldry, Tania Santoro, Catherine Pythoud, Jean-Christophe Stehle, Janine Horlbeck, Igor Letovanec, Nicolo Riggi, Nicolas Demartines, Olivier Dormond
BACKGROUND: Blocking the mechanistic target of rapamycin complex-1 (mTORC1) with chemical inhibitors such as rapamycin has shown limited clinical efficacy in cancer. The tumor microenvironment is characterized by an acidic pH which interferes with cancer therapies. The consequences of acidity on the anti-cancer efficacy of mTORC1 inhibitors have not been characterized and are thus the focus of our study. METHODS: Cancer cell lines were treated with rapamycin in acidic or physiological conditions and cell proliferation was investigated...
December 5, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27919216/topoisomerase-ii-inhibitors-and-poisons-and-the-influence-of-cell-cycle-checkpoints
#9
Nicholas D Arcy, Brian Gabrielli
Interactions between the decatenation checkpoint and Topoisomerase II (TopoII) are vital for maintaining integrity of the genome. Agents that target this enzyme have been in clinical use in cancer therapy for over 30 years with great success. The types of compounds that have been developed to target TopoII are broadly divided into poisons and catalytic inhibitors. The TopoII poisons are in clinical use as anti-cancer therapies, although in common to most chemotherapeutic agents, they display considerable normal tissue toxicity...
December 5, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27919208/is-metformin-a-therapeutic-paradigm-for-colorectal-cancer-insight-into-the-molecular-pathway
#10
Zar Chii Thent, Nurul Hannim Zaidun, Fairuz Azmi, Mu Izuddin Senin, Haszianaliza Haslan, Ahmad Ruzain Salehuddin
Colorectal cancer (CRC) remains one of the major leading causes of cancer related morbidity and mortality. Apart from the conventional anti-neoplastic agents, metformin, a biguanide anti-diabetic agent, has recently found to have anti-cancer property. Several studies observed the effect of metformin towards its anti-cancer effect on colon or colorectal cancer in diabetic patients. However, only a few studies showed its effect on colorectal cancer in relation to the non-diabetic status. The present review aimed to highlight the insight into the molecular pathway of metformin towards colorectal cancer in the absence of diabetes mellitus...
December 5, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27918469/dietary-compound-chrysin-inhibits-retinal-neovascularization-with-abnormal-capillaries-in-db-db-mice
#11
Min-Kyung Kang, Sin-Hye Park, Yun-Ho Kim, Eun-Jung Lee, Lucia Dwi Antika, Dong Yeon Kim, Yean-Jung Choi, Young-Hee Kang
Diabetic retinopathy (DR) develops in a significant proportion of patients with chronic diabetes, characterized by retinal macular edema and abnormal retinal vessel outgrowth leading to vision loss. Chrysin, a naturally-occurring flavonoid found in herb and honeycomb, has anti-inflammatory, antioxidant, and anti-cancer properties. This study sought to determine the protective effects of chrysin on retinal neovascularization with abnormal vessels and blood-retinal barrier (BRB) breakdown in 33 mM glucose-exposed human retinal endothelial cells and in db/db mouse eyes...
December 3, 2016: Nutrients
https://www.readbyqxmd.com/read/27918105/resveratrol-inhibits-proliferation-invasion-and-epithelial-mesenchymal-transition-by-increasing-mir-200c-expression-in-hct-116-colorectal-cancer-cells
#12
Fatemeh Karimi Dermani, Massoud Saidijam, Razieh Amini, Ali Mahdavinezhad, Korosh Heydari, Rezvan Najafi
OBJECTIVE: Colorectal cancer (CRC) is one of the most common malignancies, associated with high rates of relapse. A notable challenge in treatment is low response rate to current therapies for advanced CRC. The miR-200c plays an essential role in tumor suppression by inhibiting epithelial-mesenchymal transition (EMT). Resveratrol, a natural compound found in red wine, reveals anti-cancer properties in several types of cancers such as CRC. The aim of current study was to evaluate the effects of resveratrol on proliferation, apoptosis and invasion of HCT-116 cells and also expression of EMT-related genes in presences or absence of miR-200c...
December 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27917615/design-synthesis-and-evaluation-of-2-9-bis-substituted-aminomethyl-phenyl-1-10-phenanthroline-derivatives-as-g-quadruplex-ligands
#13
Nassima Meriem Gueddouda, Miyanou Rosales Hurtado, Stéphane Moreau, Luisa Ronga, Rabindra Nath Das, Solène Savrimoutou, Sandra Rubio, Adrien Marchand, Oscar Mendoza, Mathieu Marchivie, Lilian Elmi, Albain Chansavang, Vanessa Desplat, Valérie Gabelica, Anne Bourdoncle, Jean-Louis Mergny, Jean Guillon
Genomic sequences able to form guanine quadruplexes (G4) are found in oncogene promoters, in telomeres and in 5' and 3' untranslated regions as well as introns of messenger RNAs. These regions are potential targets for drugs designed to treat cancer. In the present work, we present the design and syntheses of ten new phenantroline derivatives and characterization of their interactions with G4-forming oligonucleotides. We evaluated ligand-induced stabilization and specificity and selectivity of ligands for various G4 conformations using FRET-melting experiments...
December 4, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27917404/the-emerging-role-of-cdk5-in-cancer
#14
Karine Pozo, James A Bibb
Cdk5 is an atypical cyclin-dependent kinase that is well characterized for its role in the central nervous system rather than in the cell cycle. However Cdk5 has been recently implicated in the development and progression of a variety of cancers including breast, lung, colon, pancreatic, melanoma, thyroid and brain tumors. This broad pro-tumorigenic role makes Cdk5 a promising drug target for the development of new cancer therapies. Here we review the contribution of Cdk5 to molecular mechanisms that confer upon tumors the ability to grow, proliferate and disseminate to secondary organs, as well as resistance to chemotherapies...
October 2016: Trends in Cancer
https://www.readbyqxmd.com/read/27916645/ppar%C3%AE-%C3%AE-in-human-cancer
#15
REVIEW
Rolf Müller
The nuclear receptor factor peroxisome proliferator-activated receptor (PPARβ/δ) can regulate its target genes by transcriptional activation or repression through both ligand-dependent and independent mechanism as well as by interactions with other transcription factors. PPARβ/δ exerts essential regulatory functions in intermediary metabolism that have been elucidated in detail, but clearly also plays a role in inflammation, differentiation, apoptosis and other cancer-associated processes, which is, however, mechanistically only partly understood...
December 1, 2016: Biochimie
https://www.readbyqxmd.com/read/27916629/chitosan-nanoparticles-as-a-dual-drug-sirna-delivery-system-for-treatment-of-colorectal-cancer
#16
Sanam Sadreddini, Reza Safaralizadeh, Behzad Baradaran, Leili Aghebati-Maleki, Mohammad Ali Hosseinpour-Feizi, Dariush Shanehbandi, Farhad Jadidi-Niaragh, Sevil Sadreddini, Hossein Samadi Kafil, Vahid Younesi, Mehdi Yousefi
Nanoparticles are widely used to deliver anticancer drugs and inhibit tumor growth without systemic toxicity. Recently, chitosan has received much attention as a functional biopolymer for encapsulation of small interfering RNA (siRNA). Because of cationic nature, chitosan efficiently encapsulate siRNA and forming nanoparticles. Moreover, biocompatible and biodegradable properties represent chitosan as potential candidate for in vivo siRNA delivery. In the present study we designed carboxymethyl dextran (CMD) chitosan nanoparticles (ChNPs) to encapsulat snail siRNA and anticancer drug doxorubicin (DOX)...
December 1, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27915990/possible-molecular-mechanisms-by-which-vitamin-d-prevents-inflammatory-bowel-disease-and-colitis-associated-colorectal-cancer
#17
Zijian Luan, Yiming Ma, Yu Xin, Jiaming Qian, Hongying Wang
It is well accepted that inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is one of high risk factors for colorectal cancer (CRC). This supports the notion that inflammation plays a key role in cancer development. Epidemiologic studies have shown that vitamin D (Vit D) deficiency is associated with IBD and various types of cancer including colorectal cancer. Clinical trials and mouse models have shown that Vit D is beneficial in preventing or ameliorating inflammation and carcinogenesis...
December 2, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27914985/combination-therapy-with-doxorubicin-loaded-galactosylated-poly-ethyleneglycol-lithocholic-acid-to-suppress-the-tumor-growth-in-an-orthotopic-mouse-model-of-liver-cancer
#18
Bijay Singh, Yoonjeong Jang, Sushila Maharjan, Hyeon-Jeong Kim, Ah Young Lee, Sanghwa Kim, Nomundelger Gankhuyag, Myeon-Sik Yang, Yun-Jaie Choi, Myung-Haing Cho, Chong-Su Cho
Despite advances in technology, neither conventional anti-cancer drugs nor current nanoparticle (NP) drugs have gained substantial success in cancer treatment. While conventional chemotherapy drugs have several limitations such as low potency, poor in vivo stability and limited bioavailability, non-specific targeting of NP drugs diminishes their potency at actual target sites. In addition, the development of drug resistance to anti-cancer drugs is another challenging problem. To overcome these limitations, we aimed to develop a polymer-drug conjugate, which functions as an active NP drug and drug carrier both, to deliver a chemotherapeutic drug for combination therapy...
November 24, 2016: Biomaterials
https://www.readbyqxmd.com/read/27914946/design-synthesis-and-biological-evaluation-of-alkylamino-biphenylamides-as-hsp90-c-terminal-inhibitors
#19
Gaurav Garg, Huiping Zhao, Brian S J Blagg
Hsp90 is a promising therapeutic target for the development of anti-cancer agents due to its integral role in the stability and function of proteins associated with all ten hallmarks of cancer. Novobiocin, a coumarin antibiotic, was the first natural product identified that targeted the Hsp90 C-terminal domain and manifested anti-proliferative activity (SKBr3 IC50∼700μM). Subsequent structural investigations on novobiocin led to analogues with significantly improved anti-proliferative activity against multiple cancer cell lines...
November 19, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27914809/actein-enhances-trail-effects-on-suppressing-gastric-cancer-progression-by-activating-p53-caspase-3-signaling
#20
Zhi-Chao Yang, Ji Ma
Actein (ACT), isolated from the rthizomes of Cimicifuga foetida, is a triterpene glycoside, showing inhibitory role in breast cancer cells. However, the effects of ACT treatment on gastric cancer have little been known. Thus, the study is conducted to explore the in vitro and in vivo role of ACT in gastric cancer. And the interactions between ACT and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were investigated in gastric cancer cells. A synergistic effect of ACT and TRAIL combination on apoptosis induction in gastric cancer cells was observed...
November 30, 2016: Biochemical and Biophysical Research Communications
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