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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
#1
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 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28182994/atm-deficient-colorectal-cancer-cells-are-sensitive-to-the-parp-inhibitor-olaparib
#2
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...
February 6, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28179481/apc-mutations-as-a-potential-biomarker-for-sensitivity-to-tankyrase-inhibitors-in-colorectal-cancer
#3
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
#4
Amanda Tivnan, Tatjana Heilinger, Joanne Ramsey, Gemma O'Connor, Jenny Pokorny, Jann Sarkaria, Brett Stringer, Bryan Day, Andrew Boyd, Ella Kim, Holger Lode, Sally-Ann Cryan, Jochen 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...
February 3, 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
#5
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
#6
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
https://www.readbyqxmd.com/read/28101239/naphthazarin-suppresses-cell-proliferation-and-induces-apoptosis-in-human-colorectal-cancer-cells-via-the-b-cell-lymphoma-2-b-cell-associated-x-protein-signaling-pathway
#7
Ai-Dong Chen, Hui Li, Yong-Chun Li, Hai Zeng
Colorectal cancer is the most common gastrointestinal cancer in the USA. Naphthazarin, one of the naturally available 1,4-naphthoquinone derivatives, is a natural bioactive molecule that exhibits an antitumor effect. To the best of our knowledge, this is the first study to investigate the anticancer effect of naphthazarin on cell proliferation and apoptosis in human SW480 colorectal cancer cells. In the present study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays were performed to assess the effect of napthazarin on cell proliferation and cytotoxicity of SW430 cells, respectively...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28089726/hne-and-cholesterol-oxidation-products-in-colorectal-inflammation-and-carcinogenesis
#8
Daniela Rossin, Simone Calfapietra, Barbara Sottero, Giuseppe Poli, Fiorella Biasi
Consistent experimental data suggest the importance of inflammation-associated oxidative stress in colorectal cancer (CRC) pathogenesis. Inflammatory bowel disease with chronic intestinal inflammation is now considered a precancerous condition. Oxidative stress is an essential feature of inflammation. Activation of redox-sensitive pro-inflammatory cell signals and inflammatory mediators concur to establish a pro-tumoral environment. In this frame, lipid oxidation products, namely 4-hydroxynonenal and oxysterols, can be produced in big quantity so as to be able to exert their function as inducers of cell signaling pathways of proliferation and survival...
January 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28076324/poly-c-binding-protein-1-mediates-drug-resistance-in-colorectal-cancer
#9
Jiani Guo, Changli Zhu, Kangqun Yang, Jin Li, Nan Du, Mingzhu Zong, Jianwei Zhou, Jingdong He
Oxaliplatin (L-OHP) is standard treatment for colorectal cancer. However, resistance to L-OHP often leads to treatment failure or cancer relapse. Understanding of the mechanism underlying L-OHP resistance is important to overcome the resistance and improve colorectal cancer treatment. This study aimed to identify new proteins that mediates L-OHP resistance in colorectal cancer and elucidate their mode of function. HT-29 cells were exposed to gradually increased concentration of L-OHP to select L-OHP resistant HT-29/L-OHP cell line...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28029617/di-block-plcl-and-tri-block-plclg-matrix-polymeric-nanoparticles-enhanced-the-anticancer-activity-of-loaded-5-fluorouracil
#10
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-co-caprolactone (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...
October 2016: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/27930363/upregulated-mir-16-expression-is-an-independent-indicator-of-relapse-and-poor-overall-survival-of-colorectal-adenocarcinoma-patients
#11
Marios A Diamantopoulos, Christos K Kontos, Dimitrios Kerimis, Iordanis N Papadopoulos, Andreas Scorilas
BACKGROUND: Colorectal adenocarcinoma is one of the most common malignant tumors of the gastrointestinal tract and the second leading cause of cancer-related deaths among adults in Western countries. miR-16 is heavily involved in cancer progression. In this study, we examined the potential diagnostic and prognostic utility of miR-16 expression in colorectal adenocarcinoma. METHODS: Total RNA was extracted from 182 colorectal adenocarcinoma specimens and 86 non-cancerous colorectal mucosae...
December 8, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/27929457/advanced-animal-model-of-colorectal-metastasis-in-liver-imaging-techniques-and-properties-of-metastatic-clones
#12
Go Oshima, Melinda E Stack, Sean C Wightman, Darren Bryan, Elizabeth Poli, Lai Xue, Kinga B Skowron, Abhineet Uppal, Sean P Pitroda, Xiaona Huang, Mitchell C Posner, Samuel Hellman, Ralph R Weichselbaum, Nikolai N Khodarev
Patients with a limited number of hepatic metastases and slow rates of progression can be successfully treated with local treatment approaches(1,2). However, little is known about the heterogeneity of liver metastases, and animal models capable of evaluating the development of individual metastatic colonies are needed. Here, we present an advanced model of hepatic metastases that provides the ability to quantitatively visualize the development of individual tumor clones in the liver and estimate their growth kinetics and colonization efficiency...
November 30, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27923905/%C3%AE-lapachone-inhibits-lung-metastasis-of-colorectal-cancer-by-inducing-apoptosis-of-ct26-cells
#13
Ji-Ye Kee, Yo-Han Han, Jinbong Park, Dae-Seung Kim, Jeong-Geon Mun, Kwang Seok Ahn, Hyun-Jung Kim, Jae-Young Um, Seung-Heon Hong
BACKGROUND: β-Lapachone is a quinone-containing compound found in red lapacho (Tabebuia impetiginosa, syn. T avellanedae) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of β-lapachone and the underlying mechanisms using colon cancer cells. METHODS: This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38)...
December 5, 2016: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/27818240/gen-27-a-newly-synthesized-flavonoid-inhibits-glycolysis-and-induces-cell-apoptosis-via-suppression-of-hexokinase-ii-in-human-breast-cancer-cells
#14
Lei Tao, Libing Wei, Yishi Liu, Yang Ding, Xiuting Liu, Xin Zhang, Xiaoping Wang, Yuyuan Yao, Jinrong Lu, Qing Wang, Rong Hu
We have previously reported that Gen-27, a newly synthesized flavonoid, exhibits anticancer effects against human colorectal cancer cells. In this study, we investigated the anticancer effects in human breast cancer cell lines and its underlying mechanisms. We demonstrated that Gen-27 inhibited the growth and proliferation of human breast cancer cells in concentration and time-dependent manners. It was found that Gen-27 induced mitochondrial-mediated apoptosis, characterized by the dissipation of mitochondrial membrane potential (ΔΨm), cytochrome c (Cyt c) release from mitochondria to cytosol, activation of caspases and induction of poly (ADP-ribose) polymerase (PARP)...
November 3, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27756887/anti-firs-puf60-auto-antibodies-are-detected-in-the-sera-of-early-stage-colon-cancer-patients
#15
Sohei Kobayashi, Tyuji Hoshino, Takaki Hiwasa, Mamoru Satoh, Bahityar Rahmutulla, Sachio Tsuchida, Yuji Komukai, Tomoaki Tanaka, Hisahiro Matsubara, Hideaki Shimada, Fumio Nomura, Kazuyuki Matsushita
Anti-PUF60, poly(U)-binding-splicing factor, autoantibodies are reported to be detected in the sera of dermatomyositis and Sjogren's syndrome that occasionally associated with malignancies. PUF60 is identical with far-upstream element-binding protein-interacting repressor (FIR) that is a transcriptional repressor of c-myc gene. In colorectal cancers, a splicing variant of FIR that lacks exon2 (FIRΔexon2) is overexpressed as a dominant negative form of FIR. In this study, to reveal the presence and the significance of anti-FIRs (FIR/FIRΔexon2) antibodies in cancers were explored in the sera of colorectal and other cancer patients...
October 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27746584/the-effect-of-poly-adp-ribose-polymerase-1-gene-3-untranslated-region-polymorphism-in-colorectal-cancer-risk-among-saudi-cohort
#16
COMPARATIVE STUDY
Abdullah M Alhadheq, Jilani Purusottapatnam Shaik, Abdullah Alamri, Abdulrahman M Aljebreen, Othman Alharbi, Majid A Almadi, Faten Alhadeq, Nahla A Azzam, Abdelhabib Semlali, Mohammad Alanazi, Mohammad D Bazzi, Narasimha Reddy Parine
Background. DNA repair systems are essential for each cell to repair and maintain the genome integrity. Base excision repair pathway is one of the crucial pathways to maintain genome integrity and PARP-1 plays a key role in BER pathway. The purpose of this study is to evaluate the association between polymorphisms in PARP-1 3'untranslated region (3'UTR) SNP rs8679 and its expression in colorectal cancer. Methods. Genotyping and gene expression were performed using TaqMan assays. The effects of age, gender, and tumor location were evaluated in cases and controls regarding the genotyping results...
2016: Disease Markers
https://www.readbyqxmd.com/read/27694308/analyzing-structure-function-relationships-of-artificial-and-cancer-associated-parp1-variants-by-reconstituting-talen-generated-hela-parp1-knock-out-cells
#17
Lisa Rank, Sebastian Veith, Eva C Gwosch, Janine Demgenski, Magdalena Ganz, Marjolijn C Jongmans, Christopher Vogel, Arthur Fischbach, Stefanie Buerger, Jan M F Fischer, Tabea Zubel, Anna Stier, Christina Renner, Michael Schmalz, Sascha Beneke, Marcus Groettrup, Roland P Kuiper, Alexander Bürkle, Elisa Ferrando-May, Aswin Mangerich
Genotoxic stress activates PARP1, resulting in the post-translational modification of proteins with poly(ADP-ribose) (PAR). We genetically deleted PARP1 in one of the most widely used human cell systems, i.e. HeLa cells, via TALEN-mediated gene targeting. After comprehensive characterization of these cells during genotoxic stress, we analyzed structure-function relationships of PARP1 by reconstituting PARP1 KO cells with a series of PARP1 variants. Firstly, we verified that the PARP1\E988K mutant exhibits mono-ADP-ribosylation activity and we demonstrate that the PARP1\L713F mutant is constitutively active in cells...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27636556/dual-wavelength-stimulation-of-polymeric-nanoparticles-for-photothermal-therapy
#18
Sneha S Kelkar, Eleanor McCabe-Lankford, Richard Albright, Phil Harrington, Nicole H Levi-Polyachenko
BACKGROUND AND OBJECTIVE: Photothermal therapy (PTT) has several applications in the areas of wound healing, pain management, bacterial infection control, and cancer treatment dependent on the temperature that is generated. PTT is often used exclusively with near infrared (NIR) light and most nanoparticles (NP) used for PTT are designed to absorb within one narrow range of wavelengths. We have developed a dual-wavelength photothermal therapy by capitalizing on the dual absorption of nanoparticles in the blue and NIR range...
September 16, 2016: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/27616029/-3-r-hydroxytabernaelegantine-c-a-bisindole-alkaloid-with-potent-apoptosis-inducing-activity-in-colon-hct116-sw620-and-liver-hepg2-cancer-cells
#19
Angela Paterna, Sofia E Gomes, Pedro M Borralho, Silva Mulhovo, Cecília M P Rodrigues, Maria-José U Ferreira
ETHNOPHARMACOLOGICAL RELEVANCE: Tabernaemontana elegans Stapf. (Apocynaceae) is a medicinal plant traditionally used in African countries to treat cancer. AIMS OF THE STUDY: To discover new apoptosis inducing lead compounds from T. elegans and provide scientific validation of the ethnopharmacological use of this plant. MATERIALS AND METHODS: Through fractionation, (3'R)-hydroxytaberanelegantine C (1), a vobasinyl-iboga bisindole alkaloid, was isolated from a cytotoxic alkaloid fraction of the methanol extract of T...
December 24, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27539716/genome-wide-association-analysis-identifies-dcc-as-an-essential-factor-in-the-innervation-of-the-peripheral-vestibular-system-in-inbred-mice
#20
Pezhman Salehi, Anthony Myint, Young J Kim, Marshall X Ge, Joel Lavinsky, Maria K Ho, Amanda L Crow, Charlene Cruz, Maya Monges-Hernadez, Juemei Wang, Jaana Hartiala, Li I Zhang, Hooman Allayee, Aldons J Lusis, Takahiro Ohyama, Rick A Friedman
This study aimed to investigate the genetic causes of vestibular dysfunction. We used vestibular sensory-evoked potentials (VsEPs) to characterize the vestibular function of 35 inbred mouse strains selected from the Hybrid Mouse Diversity Panel and demonstrated strain-dependent phenotypic variation in vestibular function. Using these phenotypic data, we performed the first genome-wide association study controlling for population structure that has revealed two highly suggestive loci, one of which lies within a haplotype block containing five genes (Stard6, 4930503L19Rik, Poli, Mbd2, Dcc) on Chr...
October 2016: Journal of the Association for Research in Otolaryngology: JARO
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