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https://www.readbyqxmd.com/read/28427184/kpnb1-mediated-nuclear-import-is-required-for-motility-and-inflammatory-transcription-factor-activity-in-cervical-cancer-cells
#1
Tamara Stelma, Virna D Leaner
Karyopherin β1 is a nuclear import protein involved in the transport of proteins containing a nuclear localisation sequence. Elevated Karyopherin β1 expression has been reported in cancer and transformed cells and is essential for cancer cell proliferation and survival. Transcription factors such as NFĸB and AP-1 contain a nuclear localisation sequence and initiate the expression of multiple factors associated with inflammation and cancer cell biology. Our study investigated the effect of inhibiting nuclear import via Karyopherin β1 on cancer cell motility and inflammatory signaling using siRNA and the novel small molecule, Inhibitor of Nuclear Import-43, INI-43...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426106/afatinib-versus-gefitinib-in-patients-with-egfr-mutation-positive-advanced-non-small-cell-lung-cancer-overall-survival-data-from-the-phase-iib-lux-lung-7-trial
#2
L Paz-Ares, E-H Tan, K O'Byrne, L Zhang, V Hirsh, M Boyer, J C-H Yang, T Mok, K H Lee, S Lu, Y Shi, D H Lee, J Laskin, D-W Kim, S A Laurie, K Kölbeck, J Fan, N Dodd, A Märten, K Park
Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data. Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R)...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425953/cancer-chemotherapy-specific-to-acidic-nests
#3
REVIEW
Hiroshi Kobayashi
The realization of cancer therapeutics specific to cancer cells with less of an effect on normal tissues is our goal. Many trials have been carried out for this purpose, but this goal is still far from being realized. It was found more than 80 years ago that solid cancer nests are acidified, but in vitro studies under acidic conditions have not been extensively studied. Recently, in vitro experiments under acidic conditions were started and anti-cancer drugs specific to acidic areas have been identified. Many genes have been reported to be expressed at a high level under acidic conditions, and such genes may be potent targets for anti-cancer drugs specific to acidic nests...
April 20, 2017: Cancers
https://www.readbyqxmd.com/read/28425525/exploiting-hydrogen-bonding-interactions-to-probe-smaller-linear-and-cyclic-diamines-binding-to-g-quadruplexes-a-dft-and-molecular-dynamics-study
#4
Mrinal Kanti Si, Anik Sen, Bishwajit Ganguly
G-quadruplexes are formed by the association of four guanine bases through Hoogsteen hydrogen bonding in guanine-rich sequences of DNA and exist in the telomere as well as in promoter regions of certain oncogenes. The sequences of G-quadruplex-DNA are targets for the design of molecules that can bind and can be developed as anti-cancer drugs. The linear and cyclic protonated diamines have been explored to bind to G-quadruplex-DNA through hydrogen bonding interactions. The quadruplex-DNA binders exploit π-stacking and hydrogen bonding interactions with the phosphate backbone of loops and grooves...
April 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28424988/overcoming-chemotherapy-drug-resistance-by-targeting-inhibitors-of-apoptosis-proteins-iaps
#5
REVIEW
Rama Rathore, Jennifer E McCallum, Elizabeth Varghese, Ana-Maria Florea, Dietrich Büsselberg
Inhibitors of apoptosis (IAPs) are a family of proteins that play a significant role in the control of programmed cell death (PCD). PCD is essential to maintain healthy cell turnover within tissue but also to fight disease or infection. Uninhibited, IAPs can suppress apoptosis and promote cell cycle progression. Therefore, it is unsurprising that cancer cells demonstrate significantly elevated expression levels of IAPs, resulting in improved cell survival, enhanced tumor growth and subsequent metastasis. Therapies to target IAPs in cancer has garnered substantial scientific interest and as resistance to anti-cancer agents becomes more prevalent, targeting IAPs has become an increasingly attractive strategy to re-sensitize cancer cells to chemotherapies, antibody based-therapies and TRAIL therapy...
April 19, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28424418/the-aryl-hydrocarbon-receptor-is-required-for-induction-of-p21cip1-waf1-expression-and-growth-inhibition-by-su5416-in-hepatoma-cells
#6
Edmond F O'Donnell, Hyo Sang Jang, Martin Pearce, Nancy I Kerkvliet, Siva Kumar Kolluri
The aryl hydrocarbon receptor (AhR) is a potential clinical target for cancer and autoimmune dysfunction. Identifying selective AhR modulators that produce desirable clinical outcomes represents an opportunity for developing new anti-cancer agents. Repurposing clinically-used drugs with established safety profiles that activate the AhR represents a good starting place to pursue this goal. In this study, we characterized the AhR-dependent effects of SU5416 (Semaxanib) following its identification in a small-molecule library screen...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424409/clinical-genomic-profiling-to-identify-actionable-alterations-for-investigational-therapies-in-patients-with-diverse-sarcomas
#7
Roman Groisberg, David S Hong, Vijaykumar Holla, Filip Janku, Sarina Piha-Paul, Vinod Ravi, Robert Benjamin, Shreyas Kumar Patel, Neeta Somaiah, Anthony Conley, Siraj M Ali, Alexa B Schrock, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, Shiraj Sen, Cynthia Herzog, Funda Meric-Bernstam, Vivek Subbiah
BACKGROUND: There are currently no United States Food and Drug Administration approved molecularly matched therapies for sarcomas except gastrointestinal stromal tumors. Complicating this is the extreme diversity, heterogeneity, and rarity of these neoplasms. Few therapeutic options exist for relapsed and refractory sarcomas. In clinical practice many oncologists refer patients for genomic profiling hoping for guidance on treatment options after standard therapy. However, a systematic analysis of actionable mutations has yet to be completed...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424323/dosing-three-drug-combinations-that-include-targeted-anti-cancer-agents-analysis-of-37-763-patients
#8
Mina Nikanjam, Sariah Liu, Jincheng Yang, Razelle Kurzrock
BACKGROUND: Combining targeted and cytotoxic agents has the potential to improve efficacy and attenuate resistance for metastatic cancer. Information regarding safe starting doses for clinical trials of novel three-drug combinations is lacking. MATERIALS AND METHODS: Published phase I-III adult oncology clinical trials of three-drug combinations involving a targeted agent were identified by PubMed search (January 1, 2010 to December 31, 2013). A dose percentage was calculated to compare the dose used in combination to the single agent recommended dose: (U...
April 19, 2017: Oncologist
https://www.readbyqxmd.com/read/28423736/laminarin-promotes-anti-cancer-immunity-by-the-maturation-of-dendritic-cells
#9
Kyeongeun Song, Li Xu, Wei Zhang, Yun Cai, Bian Jang, Junghwan Oh, Jun-O Jin
This research evaluates the effects of laminarin on the maturation of dendritic cells and on the in vivo activation of anti-cancer immunity. In vivo treatment of C56BL/6 mice with laminarin increased the expression levels of co-stimulatory molecules and the production of pro-inflammatory cytokines in spleen dendritic cells. Laminarin enhanced ovalbumin antigen presentation in spleen dendritic cells and promoted the proliferation of OT-I and OT-II T cells. Laminarin also induced the maturation of dendritic cells in tumor-draining lymph nodes and protected interferon-γ and tumor necrosis factor-α and proliferation of OT-I and OT-II T cells in tumors...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423719/ampk%C3%AE-phosphatase-ppm1e-upregulation-in-human-gastric-cancer-is-required-for-cell-proliferation
#10
Min-Bin Chen, Yuan-Yuan Liu, Li-Bo Cheng, Jian-Wei Lu, Ping Zeng, Pei-Hua Lu
Activation of AMP-activated protein kinase (AMPK) is a valuable anti-cancer strategy. In the current study, we tested expression and potential function of Ca2+/calmodulin-dependent protein kinase phosphatase (Ppm1E), an AMPKα phosphatase, in human gastric cancers. Ppm1E expression was elevated in human gastric cancer tissues (vs. normal tissues), which was correlated with AMPK (p-AMPKα, Thr-172) dephosphorylation and mTOR complex 1 (mTORC1) activation. Ppm1E upregulation, AMPK inhibition and mTORC1 activation were also observed in human gastric cancer cell lines (AGS, HGC-27, and SNU601)...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423711/the-antitumor-activity-and-preliminary-modeling-on-the-potential-mechanism-of-action-of-human-peroxiredoxin-5
#11
Juanjuan Liu, Xiaozhou Feng, Yuanyuan Jin, Zhengyang Sun, Haoyi Meng, Zhifei Zhang, Laixing Hu, Zhaoyong Yang
Goat peroxiredoxin-5 (gPRDX5) was verified as a good anti-cancer bioactive peptide (ACBP) against different tumor cell lines. Considering the immunogenicity between species for further therapeutic application, it is necessary to similarly investigate the antitumor activity of human peroxiredoxin-5 (hPRDX5) with 89% similarity in sequence to gPRDX5. In order to evaluate its antitumor activity, the potential anti-neoplastic effect of hPRDX5 on a mouse model was observed directly. The results of its in vivo antitumor activity suggested that hPRDX5 could resist immunosuppression by promoting lymphocyte proliferation and up-regulating the levels of serum cytokines...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423677/identifying-the-structure-activity-relationship-of-leelamine-necessary-for-inhibiting-intracellular-cholesterol-transport
#12
Raghavendra Gowda, Gajanan S Inamdar, Omer Kuzu, Saketh S Dinavahi, Jacek Krzeminski, Madhu Babu Battu, Sreedhara R Voleti, Shantu Amin, Gavin P Robertson
Leelamine is an anticancer chemotherapeutic agent inhibiting intracellular cholesterol transport. Cell death mediated by leelamine occurs due to the lysosomotropic property of the compound, its accumulation in the lysosome, and inhibition of cholesterol transport leading to lack of availability for key processes required for functioning of cancer cells. The present study dissects the structure-activity-relationship of leelamine using synthesized derivatives of leelamine and abietic acid, a structurally similar compound, to identify the moiety responsible for anti-cancer activity...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423593/anti-cancer-effect-of-novel-pak1-inhibitor-via-induction-of-puma-mediated-cell-death-and-p21-mediated-cell-cycle-arrest
#13
Tae-Gyun Woo, Min-Ho Yoon, Shin-Deok Hong, Jiyun Choi, Nam-Chul Ha, Hokeun Sun, Bum-Joon Park
Hyper-activation of PAK1 (p21-activated kinase 1) is frequently observed in human cancer and speculated as a target of novel anti-tumor drug. In previous, we also showed that PAK1 is highly activated in the Smad4-deficient condition and suppresses PUMA (p53 upregulated modulator of apoptosis) through direct binding and phosphorylation. On the basis of this result, we have tried to find novel PAK1-PUMA binding inhibitors. Through ELISA-based blind chemical library screening, we isolated single compound, IPP-14 (IPP; Inhibitor of PAK1-PUMA), which selectively blocks the PAK1-PUMA binding and also suppresses cell proliferation via PUMA-dependent manner...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423521/therapeutic-sensitivity-to-rac-gtpase-inhibition-requires-consequential-suppression-of-mtorc1-akt-and-mek-signaling-in-breast-cancer
#14
Riley A Hampsch, Kevin Shee, Darcy Bates, Lionel D Lewis, Laurent Désiré, Bertrand Leblond, Eugene Demidenko, Kurtis Stefan, Yina H Huang, Todd W Miller
Rac GTPases have oncogenic roles in cell growth, survival, and migration. We tested response to the Rac inhibitor EHT1864 in a panel of breast cancer cell lines. EHT1864-induced growth inhibition was associated with dual inhibition of the PI3K/AKT/mTORC1 and MEK/ERK pathways. Breast cancer cells harboring PIK3CA mutations or HER2 overexpression were most sensitive to Rac inhibition, suggesting that such oncogenic alterations link Rac activation with PI3K/AKT/mTORC1 and MEK/ERK signaling. Interestingly, EHT1864 decreased activation of the mTORC1 substrate p70S6K earlier than AKT inhibition, suggesting that Rac may activate mTORC1/p70S6K independently of AKT...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423510/genistein-inhibits-the-growth-and-regulates-the-migration-and-invasion-abilities-of-melanoma-cells-via-the-fak-paxillin-and-mapk-pathways
#15
Shuna Cui, Juan Wang, Qingqing Wu, Jing Qian, Changshui Yang, Ping Bo
Genistein is one of the main components of soy-based foods, which are widely known for their many benefits, including anti-cancer, anti-inflammatory, and antioxidant effects. In this study, we investigated the anti-metastasis effects of genistein on B16F10 melanoma cells. Our results showed that genistein strongly inhibited B16F10 cell proliferation and induced apoptosis in time- and concentration-dependent manners. Genistein altered the morphology of B16F10 cells to an elongated shape with slim pseudopodia-like protrusions...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421296/metabolite-signatures-of-doxorubicin-induced-toxicity-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#16
Umesh Chaudhari, James K Ellis, Vilas Wagh, Harshal Nemade, Jürgen Hescheler, Hector C Keun, Agapios Sachinidis
Drug-induced off-target cardiotoxicity, particularly following anti-cancer therapy, is a major concern in new drug discovery and development. To ensure patient safety and efficient pharmaceutical drug development, there is an urgent need to develop more predictive cell model systems and distinct toxicity signatures. In this study, we applied our previously proposed repeated exposure toxicity methodology and performed (1)H NMR spectroscopy-based extracellular metabolic profiling in culture medium of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to doxorubicin (DOX), an anti-cancer agent...
April 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28420185/melatonin-a-full-service-anti-cancer-agent-inhibition-of-initiation-progression-and-metastasis
#17
REVIEW
Russel J Reiter, Sergio A Rosales-Corral, Dun-Xian Tan, Dario Acuna-Castroviejo, Lilan Qin, Shun-Fa Yang, Kexin Xu
There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28420162/hepatocyte-growth-factor-a-key-tumor-promoting-factor-in-the-tumor-microenvironment
#18
REVIEW
Benjamin Yaw Owusu, Robert Galemmo, James Janetka, Lidija Klampfer
The tumor microenvironment plays a key role in tumor development and progression. Stromal cells secrete growth factors, cytokines and extracellular matrix proteins which promote growth, survival and metastatic spread of cancer cells. Fibroblasts are the predominant constituent of the tumor stroma and Hepatocyte Growth Factor (HGF), the specific ligand for the tyrosine kinase receptor c-MET, is a major component of their secretome. Indeed, cancer-associated fibroblasts have been shown to promote growth, survival and migration of cancer cells in an HGF-dependent manner...
April 17, 2017: Cancers
https://www.readbyqxmd.com/read/28419960/preferentially-enhancing-anti-cancer-isothiocyanates-over-glucosinolates-in-broccoli-sprouts-how-nacl-and-salicylic-acid-affect-their-formation
#19
Azadeh Esfandiari, Ali Saei, Marian J McKenzie, Adam J Matich, Mesbah Babalar, Donald A Hunter
Broccoli (Brassica oleracea L. var. italica) sprouts contain glucosinolates (GLs) that when hydrolysed yield health promoting isothiocyanates such as sulforaphane (SF). SF content can be increased by salt (NaCl) stress, although high salt concentrations negatively impact plant growth. Salicylic acid (SA) treatments can attenuate the negative effects of salt on growth. To test whether sprout isothiocyanate content could be elevated without sprout growth being compromised, broccoli seed were germinated and grown for seven days in salt (0, 80 and 160 mM) alone and in combination with 100 μM SA...
April 7, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28418885/development-of-11c-vemurafenib-employing-a-carbon-11-carbonylative-stille-coupling-and-preliminary-evaluation-in-mice-bearing-melanoma-tumor-xenografts
#20
Paul Slobbe, Albert D Windhorst, Kevin Adamzek, Marije Bolijn, Robert C Schuit, Daniëlle A M Heideman, Guus A M S van Dongen, Alex J Poot
Over the last decade kinase inhibitors have witnessed tremendous growth as anti-cancer drugs. Unfortunately, despite their promising clinical successes, a large portion of patients does not benefit from these targeted therapeutics. Vemurafenib is a serine/threonine kinase inhibitor approved for the treatment of melanomas specifically expressing the BRAFV600E mutation. The aim of this study was to develop vemurafenib as PET tracer to determine its potential for identification of tumors sensitive to vemurafenib treatment...
March 17, 2017: Oncotarget
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