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https://www.readbyqxmd.com/read/28629980/polymer-nanoassemblies-with-hydrophobic-pendant-groups-in-the-core-induce-false-positive-sirna-transfection-in-luciferase-reporter-assays
#1
Steven Rheiner, Derek Reichel, Piotr Rychahou, Tadahide Izumi, Hsin-Sheng Yang, Younsoo Bae
Poly(ethylene glycol)-conjugated polyethylenimine (PEG-PEI) is a widely studied cationic polymer used to develop non-viral vectors for siRNA therapy of genetic disorders including cancer. Cell lines stably expressing luciferase reporter protein typically evaluate the transfection efficacy of siRNA/PEG-PEI complexes, however recent findings revealed that PEG-PEI can reduce luciferase expression independent of siRNA. This study elucidates a cause of the false positive effect in luciferase assays by using polymer nanoassemblies (PNAs) made from PEG, PEI, poly-(l-lysine) (PLL), palmitate (PAL), and deoxycholate (DOC): PEG-PEI (2P), PEG-PEI-PAL (3P), PEG-PLL (2P'), PEG-PLL-PAL (3P'), and PEG-PEI-DOC (2PD)...
June 16, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28628639/small-molecule-inhibitors-uncover-synthetic-genetic-interactions-of-human-flap-endonuclease-1-fen1-with-dna-damage-response-genes
#2
Thomas A Ward, Peter J McHugh, Stephen T Durant
Flap endonuclease 1 (FEN1) is a structure selective endonuclease required for proficient DNA replication and the repair of DNA damage. Cellularly active inhibitors of this enzyme have previously been shown to induce a DNA damage response and, ultimately, cell death. High-throughput screens of human cancer cell-lines identify colorectal and gastric cell-lines with microsatellite instability (MSI) as enriched for cellular sensitivity to N-hydroxyurea series inhibitors of FEN1, but not the PARP inhibitor olaparib or other inhibitors of the DNA damage response...
2017: PloS One
https://www.readbyqxmd.com/read/28625152/lipid-oxidation-products-in-the-pathogenesis-of-inflammation-related-gut-diseases
#3
Barbara Sottero, Daniela Rossin, Giuseppe Poli, Fiorella Biasi
A defective mucosal barrier function is the principal cause of the uncontrolled onset and progression of a number of human inflammatory gut diseases, most of which are characterized by chronic intermittent immune and inflammatory responses leading to structural intestinal damage, which can represent a potential risk for colorectal cancer development. During the active disease phase the production of pro-inflammatory cytokines and chemokines, and the induction of oxidative reactions by activated leukocytes and epithelial cells represent the main event in intestinal inflammation...
June 19, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28615517/mtor-signaling-mediates-resistance-to-tankyrase-inhibitors-in-wnt-driven-colorectal-cancer
#4
Tetsuo Mashima, Yoko Taneda, Myung-Kyu Jang, Anna Mizutani, Yukiko Muramatsu, Haruka Yoshida, Ayana Sato, Noritaka Tanaka, Yoshikazu Sugimoto, Hiroyuki Seimiya
Activation of Wnt/β-catenin signaling is essential for colorectal carcinogenesis. Tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, is a positive regulator of the Wnt/β-catenin signaling. Accordingly, tankyrase inhibitors are under preclinical development for colorectal cancer (CRC) therapy. However, Wnt-driven colorectal cancer cells are not equally sensitive to tankyrase inhibitors, and cellular factors that affect tankyrase inhibitor sensitivity remain elusive. Here, we established a tankyrase inhibitor-resistant cell line, 320-IWR, from Wnt/β-catenin-dependent CRC COLO-320DM cells...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28608760/plga-peg-ra-based-polymeric-micelles-for-tumor-targeted-delivery-of-irinotecan
#5
Jaber Emami, Parnian Maghzi, Farshid Hasanzadeh, Hojjat Sadeghi, Mina Mirian, Mahboubeh Rostami
To develop an effective therapeutic treatment, the potential of poly (lactic-co-glycolic acid)-polyethylene glycol-retinoic acid (PLGA-PEG-RA) polymeric micelles for targeted delivery of irinotecan to hepatocellular carcinoma (HepG2) and colorectal cancer cell lines (HT-29) was evaluated. PLGA-PEG-RA was synthesized by amide reaction of PLGA with NH2-PEG-NH2 and then PLGA-PEG-NH2 with RA and confirmed by FTIR and (1)H NMR spectroscopy. Irinotecan-loaded nanomicelles were prepared using thin-film hydration method and the impact of various formulation variables on their particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), and mean release time (MRT) were assessed using a Taguchi design...
June 13, 2017: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/28599477/novel-proapoptotic-agent-sm-1-enhances-the-inhibitory-effect-of-5-fluorouracil-on-colorectal-cancer-cells-in-vitro-and-in-vivo
#6
Ying Wang, Shoujun Yuan, Linna Li, Dexuan Yang, Chengwang Xu, Shanshan Wang, Danshen Zhang
5-Fluorouracil (5-FU) is one of the most important agents used to treat colorectal cancer. However, the therapeutic effect of 5-FU on colon cancer is limited. SM-1 is a novel type of proapoptotic agent that directly activates procaspase-3 to caspase-3, leading to apoptosis in human cancer cells. The aim of the present study was to evaluate the antitumor effects of 5-FU in combination with SM-1. The human colorectal cancer cell lines HCT116 and LoVo were cultured in the presence of SM-1 and 5-FU. The combination of SM-1 and 5-FU treatment exhibited increased proliferation inhibitory effects compared with 5-FU treatment alone in HCT116 and LoVo cells, as determined using an MTT assay...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28593843/under-representation-of-peritoneal-metastases-in-published-clinical-trials-of-metastatic-colorectal-cancer
#7
Jennifer Tseng, Darren S Bryan, Elizabeth Poli, Manish Sharma, Blase N Polite, Kiran K Turaga
No abstract text is available yet for this article.
June 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28543772/parp-inhibitor-rucaparib-induces-changes-in-nad-levels-in-cells-and-liver-tissues-as-assessed-by-mrs
#8
Gilberto S Almeida, Carlo M Bawn, Martin Galler, Ian Wilson, Huw D Thomas, Suzanne Kyle, Nicola J Curtin, David R Newell, Ross J Maxwell
Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy ((1) H-MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD(+) ) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response...
May 22, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28511044/bentonite-modified-with-zinc-enhances-aflatoxin-b1-adsorption-and-increase-survival-of-fibroblasts-3t3-and-epithelial-colorectal-adenocarcinoma-cells-caco-2
#9
Janaína Nones, Anita Solhaug, Gunnar Sundstøl Eriksen, Domingos Lusitâneo Pier Macuvele, Anicleto Poli, Cíntia Soares, Andrea Gonçalves Trentin, Humberto Gracher Riella, Jader Nones
Bentonites are commonly used as feed additives to reduce the bioavailability and thus the toxicity of aflatoxins by adsorbing the toxins in the gastrointestinal tract. Aflatoxins are particular harmful mycotoxins mainly found in areas with hot and humid climates. They occur in food and feedstuff as a result of fungal contamination before and after harvest. The aim of this study was to modify Brazilian bentonite clay by incorporation of zinc (Zn) ions in order to increase the adsorption capacity and consequently reduce the toxicity of aflatoxins...
May 6, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28468585/suppression-subtractive-hybridization-identified-differentially-expressed-genes-in-colorectal-cancer-microrna-451a-as-a-novel-colorectal-cancer-related-gene
#10
Ke Xu, Yuan-Yuan Zhang, Bin Han, Yang Bai, Yao Xiong, Yi Song, Li-Ming Zhou
To investigate differentially expressed genes regulated by microRNA-451a in colorectal cancer. We detected expression of microRNA-451a in colorectal cancer samples and normal pericarcinous tissues from 68 colorectal cancer patients and the correlation between microRNA-451a and clinical features of these patients. Then, the expression of microRNA-451a in HCT116, SW620, HT29, SW480, and DLD cells was also measured. The suppression subtractive hybridization method was used with two HCT116 cell lines with overexpressing or underexpressing microRNA-451a, respectively...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28442322/in-vitro-and-in-vivo-antitumor-activities-of-t-3764518-a-novel-and-orally-available-small-molecule-stearoyl-coa-desaturase-1-inhibitor
#11
Satoru Nishizawa, Hiroyuki Sumi, Yoshihiko Satoh, Yukiko Yamamoto, Satoshi Kitazawa, Kohei Honda, Hideo Araki, Kazuyo Kakoi, Keisuke Imamura, Masako Sasaki, Ikuo Miyahisa, Yoshinori Satomi, Ryuuichi Nishigaki, Megumi Hirayama, Kazunobu Aoyama, Hironobu Maezaki, Takahito Hara
Most cancer cells are characterized by elevated lipid biosynthesis. The rapid proliferation of cancer cells requires de novo synthesis of fatty acids. Stearoyl-CoA desaturase-1 (SCD1), a key enzyme for lipogenesis, is overexpressed in various types of cancer and plays an important role in cancer cell proliferation. Therefore, it has been studied as a candidate target for cancer therapy. In this study, we demonstrate the pharmacological properties of T-3764518, a novel and orally available small molecule inhibitor of SCD1...
July 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28431329/stealth-recombinant-human-serum-albumin-nanoparticles-conjugating-5-fluorouracil-augmented-drug-delivery-and-cytotoxicity-in-human-colon-cancer-ht-29-cells
#12
Ankita Sharma, Amanpreet Kaur, Upendra Kumar Jain, Ramesh Chandra, Jitender Madan
BACKGROUND AND OBJECTIVE: 5-Fluorouracil (5-FU) is a first-line chemotherapeutic drug in colorectal cancer. However, intravenous administration of 5-FU at the dose of 7-12mg/kg exhibits curbs like short half-life (20min) and toxic side-effects on bone marrow cells. Therefore, in present investigation, 5-FU was conjugated to poly (ethylene glycol) anchored recombinant human serum albumin nanoparticles (5-FU-rHSA-PEG-NPs) to improve the pharmacokinetic and therapeutic profiles. METHODS AND RESULTS: The mean particle size of 5-FU-rHSA-NPs was measured to be 44...
April 12, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28418861/brain-derived-neurotrophic-factor-involved-epigenetic-repression-of-ugt2b7-in-colorectal-carcinoma-a-mechanism-to-alter-morphine-glucuronidation-in-tumor
#13
Zi-Zhao Yang, Li Li, Ming-Cheng Xu, Hai-Xing Ju, Miao Hao, Jing-Kai Gu, Zai-Jie Jim Wang, Hui-Di Jiang, Lu-Shan Yu, Su Zeng
Uridine diphosphate-glucuronosyltransferase (UGT) 2B7, as one of significant drug enzymes, is responsible on the glucuronidation of abundant endobiotics or xenobiotics. We here report that it is markedly repressed in the tumor tissues of colorectal carcinoma (CRC) patients. Accordingly, morphine in CRC cells will stimulate the expression of its main metabolic enzyme, UGT2B7 during tolerance generation by activating the positive signals in histone 3, especially for trimethylated lysine 27 (H3K4Me3) and acetylated lysine 4 (H3K27Ac)...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414284/-antineoplastic-mechanisms-of-niclosamide-loaded-nanoparticles-in-human-colorectal-cancer-cells
#14
A S Zhirnik, Y P Semochkina, E Yu Moskaleva, N I Krylov, I A Tubasheva, S L Kuznetsov, E A Vorontsov
Using poly(lactic-co-glycolic) acid we developed a polymeric form of niclosamide (PFN) and investigated molecular mechanisms underlying its antitumor activity against human colorectal cancer cell lines (SW837, Caco-2, COLO 320 HSR). PFN was shown to be more cytotoxic against cancer cells and less cytotoxic against normal cells (human embryonic lung fibroblasts) as compared to niclosamide. Both niclosamide and its polymeric form caused mitochondrial damage (evaluated as a decrease in rhodamine 123 accumulation) and increased the levels of reactive oxygen species, particularly mitochondrial superoxide, resulting in the oxidative damage to biomolecules...
March 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28405803/mir-15a-5p-a-novel-prognostic-biomarker-predicting-recurrent-colorectal-adenocarcinoma
#15
Christos K Kontos, Panagiotis Tsiakanikas, Margaritis Avgeris, Iordanis N Papadopoulos, Andreas Scorilas
INTRODUCTION: Colorectal cancer is one of the most common gastrointestinal diseases and the second leading cause of cancer-associated deaths among adults. miR-15a-5p is a post-transcriptional regulator of the proto-oncogene MYB, a transcription factor essential for prolonged cancer cell proliferation and survival. In the current study, we assessed the potential diagnostic and prognostic utility of miR-15a-5p expression in colorectal adenocarcinoma. METHODS: To accomplish this goal, total RNA was extracted from 182 colorectal adenocarcinoma specimens and 86 non-cancerous colorectal mucosae...
April 12, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28392399/preparation-of-functional-human-lysophosphatidic-acid-receptor-2-using-a-p9-%C3%A2-expression-system-and-an-amphipathic-polymer-and-investigation-of-its-in%C3%A2-vitro-binding-preference-to-g%C3%AE-proteins
#16
Seong-Gu Han, Seung-Il Baek, Tae Jin Son, Hyeongjin Lee, Nam Hyuk Kim, Yeon Gyu Yu
Human lysophosphatidic acid receptor 2 (LPA2), a member of the G-protein coupled receptor family, mediates lysophosphatidic acid (LPA)-dependent signaling by recruiting various G proteins. Particularly, it is directly implicated in the progression of colorectal and ovarian cancer through G protein signaling cascades. To investigate the biochemical binding properties of LPA2 against various alpha subunits of G protein (Gα), a functional recombinant LPA2 was overexpressed in E. coli membrane with a P9(∗) expression system, and the purified protein was stabilized with an amphipathic polymer that had been synthesized by coupling octylamine, glucosamine, and diethyl aminoproylamine at the carboxylic groups of poly-γ-glutamic acid...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28302009/expression-and-single-nucleotide-polymorphism-of-poly-adp-ribose-polymerase-1-in-gastrointestinal-tumours-clinical-involvement
#17
Sandra María Martín-Guerreroa, Josefa Leóna, Rosa Quiles-Pereza, Laura Belmontee, David Martin-Olivaa, Ángeles Ruiz-Extremeraa, Javier Salmeróna, José Antonio Muñoz-Gámez
Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that plays a critical role in diverse cellular functions, such as DNA damage detection and repair, transcriptional regulation and cell death. Furthermore, PARP-1 has emerged as a key player in the pathogenesis of multiple inflammatory diseases and has become a promising target for the treatment of cardiovascular disorders, neurodegenerative diseases and cancer. An increasing body of evidence has linked alterations in the expression levels of PARP-1, enzymatic activity and presence of polymorphism to gastrointestinal malignancies, including oesophageal, gastric, pancreas, liver and colorectal cancers...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28280328/gambogic-acid-loaded-biomimetic-nanoparticles-in-colorectal-cancer-treatment
#18
Zhen Zhang, Hanqing Qian, Mi Yang, Rutian Li, Jing Hu, Li Li, Lixia Yu, Baorui Liu, Xiaoping Qian
Gambogic acid (GA) is expected to be a potential new antitumor drug, but its poor aqueous solubility and inevitable side effects limit its clinical application. Despite these inhe rent defects, various nanocarriers can be used to promote the solubility and tumor targeting of GA, improving antitumor efficiency. In addition, a cell membrane-coated nanoparticle platform that was reported recently, unites the customizability and flexibility of a synthetic copolymer, as well as the functionality and complexity of natural membrane, and is a new synthetic biomimetic nanocarrier with improved stability and biocompatibility...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28260087/knockdown-of-parp6-or-survivin-promotes-cell-apoptosis-and-inhibits-cell-invasion-of-colorectal-adenocarcinoma-cells
#19
Haipeng Wang, Shengguo Li, Xishun Luo, Zhike Song, Xiangkai Long, Xijia Zhu
Colorectal adenocarcinoma is the third most common cancer worldwide. PARP6, a novel member of the poly(ADP-ribose) polymerases (PARPs) and survivin, a member of the family of inhibitor of apoptosis (IAP) proteins are associated with a poor prognosis in various types of cancers. However, limited evidence exists regarding the interaction between PARP6 and survivin in colorectal adenocarcinoma. In the present study, we used the paired samples of 20 patients with colorectal adenocarcinoma to detect the expression of PARP6 and survivin in both tumor and adjacent normal colorectal mucosa...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28250648/the-influence-of-pluronic-f68-and-f127-nanocarrier-on-physicochemical-properties-in-vitro-release-and-antiproliferative-activity-of-thymoquinone-drug
#20
Salwa Shaarani, Shahrul Sahul Hamid, Noor Haida Mohd Kaus
BACKGROUND: This study reports on hydrophobic drug thymoquinone (TQ), an active compound found in the volatile oil of Nigella sativa that exhibits anticancer activities. Nanoformulation of this drug could potentially increase its bioavailability to specific target cells. OBJECTIVE: The aim of this study was to formulate TQ into polymer micelle, Pluronic F127 (5.0 wt %) and Pluronic F68 (0.1 wt %), as a drug carrier to enhance its solubility and instability in aqueous media...
January 2017: Pharmacognosy Research
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