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Cancer cells AND Lactic acid

Arvin Eskandari, Janine N Boodram, Paul B Cressey, Chunxin Lu, Peter M Bruno, Michael T Hemann, Kogularamanan Suntharalingam
We report the cancer stem cell (CSC) potency of a novel series of copper(ii)-phenanthroline complexes bearing nonsteriodial anti-inflammatory drugs: naproxen, tolfenamic acid, and indomethacin (2a-3c). Two of the complexes, 2a and 3c, kill breast CSC-enriched HMLER-shEcad cells (grown in both monolayer and three-dimensional cell cultures) to a significantly better extent than salinomycin, a well-established CSC toxin. The most potent complex in the series, 3c induces its cytotoxic effect by generating intracellular reactive oxygen species (ROS) and inhibiting cyclooxgenase-2 (COX-2) activity...
October 24, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Xiao-Bin Fang, Ying-Qi Xu, Hon-Fai Chan, Chun-Ming Wang, Qing Zheng, Fei Xiao, Mei-Wan Chen
Hepatocellular carcinoma (HCC) is an aggressive malignancy and the second leading cause of cancer death worldwide. Most current therapeutic agents lack the tumor-targeting efficiency and result in a nonselective biodistribution in the body. In our previous study, we identified a peptide Ala-Pro-Asp-Thr-Lys-Thr-Gln (APDTKTQ) that can selectively bind to the receptor of advanced glycation end-products (RAGE), an immunoglobulin superfamily cell surface molecule overexpressed during HCC malignant progression. Here, we report the design of a mixed micelles system modified with this peptide to target HCC cells...
October 21, 2016: Molecular Pharmaceutics
Qian Chen, Ligeng Xu, Chao Liang, Chao Wang, Rui Peng, Zhuang Liu
A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions...
October 21, 2016: Nature Communications
Alice Gutjahr, Capucine Phelip, Anne-Line Coolen, Claire Monge, Anne-Sophie Boisgard, Stéphane Paul, Bernard Verrier
Vaccines have successfully eradicated a large number of diseases. However, some infectious diseases (such as HIV, Chlamydia trachomatis or Bacillus anthracis) keep spreading since there is no vaccine to prevent them. One way to overcome this issue is the development of new adjuvant formulations which are able to induce the appropriate immune response without sacrificing safety. Lymph nodes are the site of lymphocyte priming by antigen-presenting cells and subsequent adaptive immune response, and are a promising target for vaccine formulations...
October 12, 2016: Vaccines
Hui Liu, Mei Zhao, Jin Wang, Mingpei Pang, Zhenzhou Wu, Liqing Zhao, Zhinan Yin, Zhangyong Hong
Photodynamic therapy (PDT) has many advantages in treating cancers, but the lack of ideal photosensitizers continues to be a major limitation restricting the clinical utility of PDT. This study aimed to overcome this obstacle by generating pyropheophorbide-a-loaded polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles (NPs) for efficient tumor-targeted PDT. The fabricated NPs were efficiently internalized in the mitochondrion by cancer cells, and they efficiently killed cancer cells in a dose-dependent manner when activated with light...
2016: International Journal of Nanomedicine
Yan Wang, Ling Zhou, Meng Xiao, Zhong-Liang Sun, Chang-Yuan Zhang
In the present study, we have synthesized an amphiphilic pH-sensitive structure of poly(ethylene glycol) methyl ether-b-(poly lactic acid-co-poly(b-amino esters)) (MPEG-b-(PLA-co-PAE)) to load paclitaxel to increase the therapeutic efficacy in leukemia. The micelles exhibit excellent drug-loading capacities for paclitaxel (PTX) and exhibited a typical pH-responsive drug release pattern. The release of PTX from the micelles was significantly accelerated by decreasing pH from 7.4 to 5.0 which just fitted the pathological process...
September 13, 2016: Colloids and Surfaces. B, Biointerfaces
Samira Eynali, Samideh Khoei, Sepideh Khoei, Elaheh Esmaelbeygi
The purpose of this study was to evaluate the combined effects of heat and poly lactic-co-glycolic acid (PLGA) nanoparticles, as 5-fluorouracil carriers with/without iron oxide core, on the viability and proliferation capacity of human colon cancer cell line HT-29 in the spheroid model. HT-29 spheroid cells were treated with different concentrations of 5-FU or 5-FU loaded into both nanoparticles for 74 h. Hyperthermia was then performed at 43°C for 60 min. Finally, the effects of the mentioned treatments on cell viability and proliferation capacity were evaluated using the trypan blue dye exclusion test and colony formation assay, respectively...
October 4, 2016: International Journal of Hyperthermia
Hsin-I Hung, Oliver J Klein, Sam W Peterson, Sarah R Rokosh, Sam Osseiran, Nicholas H Nowell, Conor L Evans
Photodynamic therapy regimens, which use light-activated molecules known as photosensitizers, are highly selective against many malignancies and can bypass certain challenging therapeutic resistance mechanisms. Photosensitizers such as the small cationic molecule EtNBS (5-ethylamino-9-diethyl-aminobenzo[a]phenothiazinium chloride) have proven potent against cancer cells that reside within acidic and hypoxic tumour microenvironments. At higher doses, however, these photosensitizers induce "dark toxicity" through light-independent mechanisms...
September 30, 2016: Scientific Reports
Tao Jia, Shuo Huang, Cangjie Yang, Mingfeng Wang
Multifunctional stable and stimuli-responsive drug delivery systems are important for efficient cancer treatment due to their advantages such as enhanced cancer-targeting efficiency, improved pharmacokinetics, minimized drug leaching, and reduced undesirable side effects. Here we report a robust and pH-responsive anticancer drug delivery system based on unimolecular micelles of star-like amphiphilic copolymers. The polymers (denoted as CPOFs) were facilely synthesized via one-step atom transfer radical polymerization of functionalizable benzoaldehyde and hydrophilic poly[(oligo ethylene glycol) methyl ether methacrylate] as comonomers from the core of heptakis [2,3,6-tri-o-(2-bromo-2-methyl propionyl]-β-cyclodextrin as the initiator...
September 29, 2016: Molecular Pharmaceutics
Xun Jin, Bingwen Zou, Li Luo, Chuanhong Zhong, Peilan Zhang, Hao Cheng, Yanfang Guo, Maling Gou
Cancer chemotherapy can benefit from the combination of different anticancer drugs. Here, we prepared doxorubicin (Dox)- and thioridazine (Thio)-coloaded methoxy poly(ethylene glycol)-poly(l-lactic acid) (MPEG-PLA) nanoparticles (NPs) for breast cancer therapy. These NPs have an average particle size of 27 nm. The drug loading efficiencies of Thio and Dox are 4.71% and 1.98%, respectively. Compared to the treatment of Thio or Dox alone, the combination of Thio and Dox exhibited a synergistic effect in inhibiting the growth of 4T1 breast cancer cells in vitro...
2016: International Journal of Nanomedicine
Tie-Jun Liang, Zhong-Mei Zhou, Ying-Qing Cao, Ming-Ze Ma, Xiao-Jun Wang, Kai Jing
In this study, we have demonstrated gemcitabine (GEM)-conjugated amphiphilic biodegradable polymeric drug carriers. Our aim was to increase the chemotherapeutic potential of GEM in colon cancer by forming a unique polymer-drug conjugates. The polymer-drug conjugate micelles were nanosized with a typical spherical shape. The GEM-conjugated methoxy poly(ethylene glycol)-poly(lactic acid) (GEM-PL) exhibited a controlled release of drug in both the pH conditions. The developed GEM-PL efficiently killed the HT29 cancers cells in a typical time dependent manner...
September 6, 2016: International Journal of Pharmaceutics
Sitian Fang, Xiao Fang
Cancer cells uptake glucose at a higher rate and produce lactic acid rather than metabolizing pyruvate through the tricarboxylic acid cycle. This adaptive metabolic shift is termed the Warburg effect. Recently progress had been made regarding the mechanistic understanding of glucose metabolism and associated diagnostic and therapeutic methods, which have been investigated in colorectal cancer. The majority of novel mechanisms involve important glucose metabolism associated genes and miRNA regulation. The present review discusses the contribution of these research results to facilitate with the development of novel diagnosis and anticancer treatment options...
September 2016: Biomedical Reports
Lei Su, Hailin Zhang, Chen Yan, Aiping Chen, Gang Meng, Jiwu Wei, Decai Yu, Yitao Ding
Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, has anti-tumor properties in various carcinoma models. Diisopropylamine dichloroacetate (DADA), an over-the-counter drug for chronic liver disease, is a derivative of DCA. To date, few studies have evaluated the anticancer potential of DADA in breast cancer. In this study, MDA-MB-231 cells, a breast adenocarcinoma cell line, were used in in vitro and in vivo experiments to evaluate the anti-tumor efficacy of DADA and DCA. The half maximal inhibitory concentration (IC50) of DADA (7...
August 25, 2016: Oncotarget
Sonia Pandey, S M Vijayendra Swamy, Ubaid Ulla, Arti Gupta, Hetal Patel, Jitendra Singh Yadav
BACKGROUND: Capecitabine, an anti cancer drug, is having a very short drug elimination half-life (0.49 to 0.89 h). High dose and absence of targeting ability in colon region may lead to more side effects to the patients of colon cancer. PURPOSE: To develop sustained release nanoparticles for effective treatment of colon cancer. METHODS: Eudragit S100 - PLGA (poly (lactic-co-glycolic acid)) nanoparticles were prepared by double emulsification solvent evaporation method followed by high-pressure homogenisation and evaluated for surface morphology, particle size analysis, polydispersity index, drug content, % entrapment efficiency and in vitro drug release...
August 17, 2016: Current Drug Delivery
Sijing Yan, Min Lu, Xiaoya Ding, Fei Chen, Xuemei He, Chunyan Xu, Hang Zhou, Qi Wang, Lan Hao, Jianzhong Zou
This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed...
2016: Scientific Reports
Noor Alam, Arem Qayum, Ashok Kumar, Vaibhav Khare, Parduman Raj Sharma, Samar Singh Andotra, Shashank K Singh, Surinder Koul, Prem N Gupta
Cisplatin is widely used for the treatment of various cancers including cervical, ovarian, lung and head and neck, however, its clinical success is limited owing to the dose-dependent adverse effects, mainly nephrotoxicity and neurotoxicity. In order to address this limitation, the present study was undertaken to investigate growth inhibitory effect of cisplatin in combination with a triterpenediol (3a, 24-dihydroxyurs-12-ene and 3a, 24-dihydroxyolean-12-ene, TPD) on human ovarian cancer cell line. Poly(dl-lactic-co-glycolic) acid nanoparticles loaded with TPD (TPD-PLGA-NPs) were successfully developed by emulsion solvent evaporation method...
November 1, 2016: Materials Science & Engineering. C, Materials for Biological Applications
Zhipeng Wang, Jiao Tan, Christopher McConville, Vinodh Kannappan, Patricia Erebi Tawari, James Brown, Jin Ding, Angel L Armesilla, Juan M Irache, Qi-Bing Mei, Yuhuan Tan, Ying Liu, Wenguo Jiang, Xiuwu Bian, Weiguang Wang
Disulfiram (DS), an anti-alcoholism drug, shows very strong cytotoxicity in many cancer types. However its clinical application in cancer treatment is limited by the very short half-life in the bloodstream. In this study, we developed a poly lactic-co-glycolic acid (PLGA)-encapsulated DS protecting DS from the degradation in the bloodstream. The newly developed DS-PLGA was characterized. The DS-PLGA has very satisfactory encapsulation efficiency, drug-loading content and controlled release rate in vitro. PLGA encapsulation extended the half-life of DS from shorter than 2minutes to 7hours in serum...
August 10, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Sayan Mullick Chowdhury, Tzu-Yin Wang, Sunitha Bachawal, Rammohan Devulapally, Jung Woo Choe, Lotfi Abou Elkacem, Butrus Khuri Yakub, David S Wang, Lu Tian, Ramasamy Paulmurugan, Jürgen K Willmann
Treatment options for patients with hepatocellular carcinoma (HCC) are limited, in particular in advanced and drug resistant HCC. MicroRNAs (miRNA) are non-coding small RNAs that are emerging as novel drugs for the treatment of cancer. The aim of this study was to assess treatment effects of two complementary miRNAs (sense miRNA-122, and antisense antimiR-21) encapsulated in biodegradable poly (lactic-co-glycolic acid) nanoparticles (PLGA-NP), administered by an ultrasound-guided and microbubble-enhanced delivery approach in doxorubicin-resistant and non-resistant human HCC xenografts...
September 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Zhi Li, Xuan Liu, Yi Li, Xiqian Lan, Polly Hangmei Leung, Jiashen Li, Gang Li, Maobin Xie, Yanxia Han, Xiaofen Lin
Antimicrobial peptides, produced by innate immune system of hosts in response to invading pathogens, are capable of fighting against a spectrum of bacteria, viruses, fungi, parasites and cancer cells. Here, a recombinant silkworm AMP Bmattacin2 from heterologous expression is studied, indicating a broad spectrum of antibacterial activity and showing selective killing ability towards skin and colon cancer cells over their normal cell counterparts. For the purpose of biomedical application, the electrospinning fabrication technique is employed to load Bmattacin2 into PLLA nanofibrous membrane...
2016: Scientific Reports
Kavindra Nath, Lili Guo, Bethany Nancolas, David S Nelson, Alexander A Shestov, Seung-Cheol Lee, Jeffrey Roman, Rong Zhou, Dennis B Leeper, Andrew P Halestrap, Ian A Blair, Jerry D Glickson
Lonidamine (LND) was initially introduced as an antispermatogenic agent. It was later found to have anticancer activity sensitizing tumors to chemo-, radio-, and photodynamic-therapy and hyperthermia. Although the mechanism of action remained unclear, LND treatment has been known to target metabolic pathways in cancer cells. It has been reported to alter the bioenergetics of tumor cells by inhibiting glycolysis and mitochondrial respiration, while indirect evidence suggested that it also inhibited l-lactic acid efflux from cells mediated by members of the proton-linked monocarboxylate transporter (MCT) family and also pyruvate uptake into the mitochondria by the mitochondrial pyruvate carrier (MPC)...
August 4, 2016: Biochimica et Biophysica Acta
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