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https://www.readbyqxmd.com/read/28543772/parp-inhibitor-rucaparib-induces-changes-in-nad-levels-in-cells-and-liver-tissues-as-assessed-by-mrs
#1
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
#2
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
#3
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
#4
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...
April 22, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28246467/familial-pancreatic-cancer-concept-management-and-issues
#14
REVIEW
Hiroyuki Matsubayashi, Kyoichi Takaori, Chigusa Morizane, Hiroyuki Maguchi, Masamichi Mizuma, Hideaki Takahashi, Keita Wada, Hiroko Hosoi, Shinichi Yachida, Masami Suzuki, Risa Usui, Toru Furukawa, Junji Furuse, Takamitsu Sato, Makoto Ueno, Yoshimi Kiyozumi, Susumu Hijioka, Nobumasa Mizuno, Takeshi Terashima, Masaki Mizumoto, Yuzo Kodama, Masako Torishima, Takahisa Kawaguchi, Reiko Ashida, Masayuki Kitano, Keiji Hanada, Masayuki Furukawa, Ken Kawabe, Yoshiyuki Majima, Toru Shimosegawa
Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome (HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion (< 20%) and the familial aggregation is usually modest...
February 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28219770/silencing-of-the-mrna-binding-protein-hur-increases-the-sensitivity-of-colorectal-cancer-cells-to-ionizing-radiation-through-upregulation-of-caspase-2
#15
Amel Badawi, Stephanie Hehlgans, Josef Pfeilschifter, Franz Rödel, Wolfgang Eberhardt
Increased abundance of the mRNA-binding protein human antigen R (HuR) is a characteristic feature of many cancers and frequently associated with a high grade malignancy and therapy resistance. HuR elicits a broad cell survival program mainly by stabilizing or increasing the translation of mRNAs coding for anti-apoptotic effector proteins. Conversally, we previously identified the pro-apoptotic caspase-2 as a novel HuR target which is mainly regulated at the level of translation. In this study, we investigated whether siRNA-mediated HuR knockdown interferes with cell survival and radiation sensitivity by monitoring apoptosis, DNA repair and three-dimensional (3D) clonogenic survival...
February 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28182994/atm-deficient-colorectal-cancer-cells-are-sensitive-to-the-parp-inhibitor-olaparib
#16
Chen Wang, Nicholas Jette, Daniel Moussienko, D Gwyn Bebb, Susan P Lees-Miller
The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), and we previously showed that MCL cell lines with loss of ATM are sensitive to poly-ADP ribose polymerase (PARP) inhibitors...
April 2017: Translational Oncology
https://www.readbyqxmd.com/read/28179481/apc-mutations-as-a-potential-biomarker-for-sensitivity-to-tankyrase-inhibitors-in-colorectal-cancer
#17
Noritaka Tanaka, Tetsuo Mashima, Anna Mizutani, Ayana Sato, Aki Aoyama, Bo Gong, Haruka Yoshida, Yukiko Muramatsu, Kento Nakata, Masaaki Matsuura, Ryohei Katayama, Satoshi Nagayama, Naoya Fujita, Yoshikazu Sugimoto, Hiroyuki Seimiya
In most colorectal cancers (CRCs), Wnt/β-catenin signaling is activated by loss-of-function mutations in the adenomatous polyposis coli (APC) gene and plays a critical role in tumorigenesis. Tankyrases poly(ADP-ribosyl)ate and destabilize Axins, a negative regulator of β-catenin, and upregulate β-catenin signaling. Tankyrase inhibitors downregulate β-catenin and are expected to be promising therapeutics for CRC. However, CRC cells are not always sensitive to tankyrase inhibitors, and predictive biomarkers for the drug sensitivity remain elusive...
February 8, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28178667/anti-gd2-ch14-18-cho-coated-nanoparticles-mediate-glioblastoma-gbm-specific-delivery-of-the-aromatase-inhibitor-letrozole-reducing-proliferation-migration-and-chemoresistance-in-patient-derived-gbm-tumor-cells
#18
Amanda Tivnan, Tatjana Heilinger, Joanne M Ramsey, Gemma O'Connor, Jenny L Pokorny, Jann N Sarkaria, Brett W Stringer, Bryan W Day, Andrew W Boyd, Ella L Kim, Holger N Lode, Sally-Ann Cryan, Jochen H M Prehn
Aromatase is a critical enzyme in the irreversible conversion of androgens to oestrogens, with inhibition used clinically in hormone-dependent malignancies. We tested the hypothesis that targeted aromatase inhibition in an aggressive brain cancer called glioblastoma (GBM) may represent a new treatment strategy. In this study, aromatase inhibition was achieved using third generation inhibitor, Letrozole, encapsulated within the core of biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs). PLGA-NPs were conjugated to human/mouse chimeric anti-GD2 antibody ch14...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28117012/current-status-and-perspectives-regarding-the-therapeutic-potential-of-targeting-egfr-pathway-by-curcumin-in-lung-cancer
#19
Mojtaba Shafiee, Elham Mohamadzade, Soudabeh ShahidSales, Samaneh Khakpouri, Mina Maftouh, Seyed Alireza Parizadeh, Seyed Mahdi Hasanian, Amir Avan
Lung cancer is among the leading cause of cancer-related-deaths and non-small cell lung cancer (NSCLC) is the most common form of lung cancer. More than 70% of NSCLC patients have locally advanced or metastatic disease at diagnosis, which are then being treated with platinum-based chemotherapy or epidermal-growth-factor-receptor (EGFR) inhibitors in patients harboring activating EGFR-mutations. Several molecules which target multiple ErbB receptors and EGFR, have been developed, including gefitinib and erlotinib, although most of the patients become resistance...
January 23, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28114073/di-block-plcl-and-tri-block-plclg-matrix-polymeric-nanoparticles-enhanced-the-anticancer-activity-of-loaded-5-fluorouracil
#20
Abdelkader E Ashour, Mohammad M Badran, Ashok Kumar, Arun K Rishi, Alaa Eldeen Yassin
In the current study, 5-FU-loaded nanoparticles (NPs) were prepared using polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), di-block poly lactide-cocaprolactone (PLCL) and tri-block poly L-lactide-co-caprolactone-co-glycolide (PLCLG). The influence of these polymers on the particle sizes, morphology, drug loading, and in vitro drug release was investigated. The anticancer activity was assessed utilizing MTT assay in three human cancer cell lines of different tissue origin; brain (Daoy), liver (HepG2), and colorectal (HT29) using suitable negative and positive controls...
September 27, 2016: IEEE Transactions on Nanobioscience
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