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https://www.readbyqxmd.com/read/28738408/cgas-surveillance-of-micronuclei-links-genome-instability-to-innate-immunity
#1
Karen J Mackenzie, Paula Carroll, Carol-Anne Martin, Olga Murina, Adeline Fluteau, Daniel J Simpson, Nelly Olova, Hannah Sutcliffe, Jacqueline K Rainger, Andrea Leitch, Ruby T Osborn, Ann P Wheeler, Marcin Nowotny, Nick Gilbert, Tamir Chandra, Martin A M Reijns, Andrew P Jackson
DNA is strictly compartmentalized within the nucleus to prevent autoimmunity; despite this, cyclic GMP-AMP synthase (cGAS), a cytosolic sensor of double-stranded DNA, is activated in autoinflammatory disorders and by DNA damage. Precisely how cellular DNA gains access to the cytoplasm remains to be determined. Here, we report that cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells. Such micronuclei occur after mis-segregation of DNA during cell division and consist of chromatin surrounded by its own nuclear membrane...
July 24, 2017: Nature
https://www.readbyqxmd.com/read/28737827/cytotoxic-and-chemosensitization-effects-of-scutellarin-from-traditional-chinese-herb-scutellaria%C3%A2-altissima%C3%A2-l-in-human-prostate-cancer-cells
#2
Chen Gao, Yinglu Zhou, Zhongling Jiang, Yuan Zhao, Dongjun Zhang, Xia Cong, Rongfeng Cao, Huatao Li, Wenru Tian
Scutellaria altissima L. is a common traditional Chinese medicine used to treat inflammation in some countries. Scutellarin, an active major flavone glycoside isolated from the traditional Chinese medicine Scutellaria altissima L., has been shown to offer various beneficial biochemical effects on cerebrovascular diseases and inflammation. However, the antiproliferative effects of Scutellarin in prostate cancer and the underlying mechanism are not fully elucidated. In the present study, we aimed to ascertain whether Scutellarin inhibits cancer cell growth and to further explore the molecular mechanism...
July 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28736869/photon-induced-near-field-electron-microscopy-pinem-of-eukaryotic-cells
#3
Mohammed Kaplan, Byung-Kuk Yoo, Jau Tang, Tony Karam, Bolin Liao, Devdoot Majumdar, David Baltimore, Grant Jensen, Ahmed Zewail
Photon-induced near-field electron microscopy (PINEM) is a technique to produce and then image evanescent electromagnetic fields on the surfaces of nanostructures. Most previous applications of PINEM have imaged surface plasmon-polariton waves on conducting nanomaterials. Here, the application of PINEM on whole human cancer cells and membrane vesicles isolated from them is reported. We show that photons induce time-, orientation-, and polarization-dependent evanescent fields on the surfaces of A431 cancer cells and isolated membrane vesicles...
July 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28736788/characterisation-of-anticancer-peptides-at-the-single-cell-level
#4
L Armbrecht, G Gabernet, F Kurth, J A Hiss, G Schneider, P S Dittrich
The development of efficacious anticancer therapeutics is difficult due to the heterogeneity of the cellular response to chemotherapy. Anticancer peptides (ACPs) are promising drug candidates that have been shown to be active against a range of cancer cells. However, few ACP studies focus on tumour single-cell heterogeneities. In order to address this need, we developed a microfluidic device and an imaging procedure that enable the capture, monitoring, and analysis of several hundred single cells for the study of drug response...
July 24, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28736504/pleomorphism-and-drug-resistant-cancer-stem-cells-are-characteristic-of-aggressive-primary-meningioma-cell-lines
#5
Ishaq Khan, Saleh Baeesa, Mohammed Bangash, Hans-Juergen Schulten, Fahad Alghamdi, Hanadi Qashqari, Nawal Madkhali, Angel Carracedo, Mohamad Saka, Awatif Jamal, Jaudah Al-Maghrabi, Mohammed AlQahtani, Saleh Al-Karim, Ghazi Damanhouri, Kulvinder Saini, Adeel Chaudhary, Adel Abuzenadah, Deema Hussein
BACKGROUND: Meningioma tumors arise in arachnoid membranes, and are the most reported central nervous system (CNS) tumors worldwide. Up to 20% of grade I meningioma tumors reoccur and currently predictive cancer stem cells (CSCs) markers for aggressive and drug resistant meningiomas are scarce. METHODS: Meningioma tissues and primary cell lines were investigated using whole transcriptome microarray analysis, immunofluorescence staining of CSCs markers (including CD133, Sox2, Nestin, and Frizzled 9), and drug treatment with cisplatin or etoposide...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28736304/advances-in-cancer-stem-cell-targeting-how-to-strike-the-evil-at-its-root
#6
Brigitte M Pützer, Manish Solanki, Ottmar Herchenröder
Cancer progression to metastatic stages is still unmanageable and the promise of effective anti-metastatic therapy remains largely unmet, emphasizing the need to develop novel therapeutics. The special focus here is on cancer stem cells (CSC) as the seed of tumor initiation, epithelial-mesenchymal transition, chemoresistance and, as a consequence, drivers of metastatic dissemination. We report on targeted therapies gearing towards the CSC's internal and membrane-anchored markers using agents such as antibody derivatives, nucleic therapeutics, small molecules and genetic payloads...
July 20, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28735865/rps27a-enhances-ebv-encoded-lmp1-mediated-proliferation-and-invasion-by-stabilizing-of-lmp1
#7
Seung-Woo Hong, Seung-Mi Kim, Dong-Hoon Jin, Yeong Seok Kim, Dae Young Hur
Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is an oncoviral protein that plays a pivotal role in EBV-induced oncogenic transformation. The function of LMP1 in EBV-induced oncogenesis has been well studied. However, the molecular mechanisms underlying LMP1 protein stability remain poorly understood. In this study, we found that ribosomal protein s27a (RPS27a) regulates LMP1 stability by a tandem affinity purification analysis. RPS27a interacts directly with LMP1 in vitro and in vivo. Furthermore, overexpression of RPS27a increases the half-life of LMP1 in 293T cells, whereas downregulation of RPS27a using lentiviral shRNA technology accelerates the decrease in LMP1 protein level in EBV-transformed B cells...
July 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28735186/development-of-a-robust-reporter-gene-assay-to-measure-the-bioactivity-of-anti-pd-1-anti-pd-l1-therapeutic-antibodies
#8
Lan Wang, Chuanfei Yu, Yalan Yang, Kai Gao, Junzhi Wang
Being regarded as the 'cancer panacea', the anti-PD-1/anti-PD-L1 monoclonal antibodies (mAbs) have become the R&D focus of biopharmaceutical industries. Several marketed such mAbs have been proved particularly effective in treating various cancers. However, the cell-based bioassay to measure the biological activities of the anti-PD-1/anti-PD-L1 mAbs as the lot release or stability test has been a great challenge to quality control laboratories due to the immunomodulating nature of the mAbs. Here, we describe the development and validation of a reporter gene assay consisting of two-cell systems to measure the bioactivity of the anti-PD-1/anti-PD-L1 mAbs...
May 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28735175/cancer-cell-membrane-coated-biomimetic-platform-for-tumor-targeted-photodynamic-therapy-and-hypoxia-amplified-bioreductive-therapy
#9
Shi-Ying Li, Hong Cheng, Wen-Xiu Qiu, Lu Zhang, Shuang-Shuang Wan, Jing-Yue Zeng, Xian-Zheng Zhang
Modulating tumor microenvironment to amplify the therapeutic efficiency would be a novel strategy for effective cancer treatment. In this work, based on the TPZ-loaded porphyrinic metal organic framework PCN-224 (PCN stands for porous coordination network), a cancer cell membrane-coated nanoplatform (TPZ@PCN@Mem) was fabricated for tumor targeted PDT and the successively resulting hypoxia-amplified bioreductive therapy. After administration, TPZ@PCN@Mem exhibited the selective accumulation and long-term retention at tumor tissue due to the immune escape and homologous targeting endowed by the cancer membrane coating...
July 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28734180/bottom-up-assembly-of-salivary-gland-microtissues-for-assessing-myoepithelial-cell-function
#10
Tugba Ozdemir, Padma Pradeepa Srinivasan, Daniel R Zakheim, Daniel A Harrington, Robert L Witt, Mary C Farach-Carson, Xinqiao Jia, Swati Pradhan-Bhatt
Myoepithelial cells are flat, stellate cells present in exocrine tissues including the salivary glands. While myoepithelial cells have been studied extensively in mammary and lacrimal gland tissues, less is known of the function of myoepithelial cells derived from human salivary glands. Several groups have isolated tumorigenic myoepithelial cells from cancer specimens, however, only one report has demonstrated isolation of normal human salivary myoepithelial cells needed for use in salivary gland tissue engineering applications...
July 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/28734085/novel-menadione-hybrids-synthesis-anticancer-activity-and-cell-based-studies
#11
Chakka Vara Prasad, Vadithe Lakshma Nayak, Sistla Ramakrishna, Uppuluri Venkata Mallavadhani
A series of novel menadione based triazole hybrids were designed and synthesized by employing copper catalyzed azide-alkyne cycloaddition (CuAAC). All the synthesized hybrids were characterized by their spectral data ((1) H NMR, (13) C NMR, IR and HRMS). The synthesized compounds were evaluated for their anticancer activity against five selected cancer cell lines including lung (A549), prostate (DU-145), cervical (Hela), breast (MCF-7) and mouse melanoma (B-16) by using MTT assay. The screening results showed that majority of the synthesized compounds displayed significant anticancer activity...
July 22, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28733985/lalf32-51-e7-a-hpv-16-therapeutic-vaccine-candidate-forms-protein-body-like-structures-when-expressed-in-nicotiana-benthamiana-leaves
#12
Romana J R Yanez, Renate Lamprecht, Milaid Granadillo, Isis Torrens, Elsa Arcalís, Eva Stöger, Edward P Rybicki, Inga I Hitzeroth
High-risk Human papillomaviruses (HPVs) cause cervical cancer, and while there are good prophylactic vaccines on the market, these are ineffective against established infections, creating a clear need for therapeutic vaccines. The HPV E7 protein is one of the essential oncoproteins for the onset and maintenance of malignancy, and is therefore an ideal therapeutic vaccine target. We fused the HPV-16 E7 protein to the Limulus polyphemus anti-lipopolysaccharide factor (LALF32-51 ), a small hydrophobic peptide that can penetrate cell membranes and that has immunomodulatory properties...
July 22, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28733553/exosomal-tetraspanins-mediate-cancer-metastasis-by-altering-host-microenvironment
#13
Jun Lu, Jun Li, Shuo Liu, Teng Wang, Alessandro Ianni, Eva Bober, Thomas Braun, Rong Xiang, Shijing Yue
The metastases of malignant tumors develop through a cascade of events. The establishment of a pre-metastatic micro-environment is initiated by communication between tumors and host. Exosomes come into focus as the most potent intercellular communicators playing a pivotal role in this process. Cancer cells release exosomes into the extracellular environment prior to metastasis. Tetraspanin is a type of 4 times transmembrane proteins. It may be involved in cell motility, adhesion, morphogenesis, as well as cell and vesicular membrane fusion...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733164/the-role-of-oxysterol-binding-protein-and-its-related-proteins-in-cancer
#14
REVIEW
Ximing Du, Nigel Turner, Hongyuan Yang
Oxysterol-binding protein (OSBP) and its related proteins (ORPs) constitute a large, evolutionarily conserved family of lipid-binding proteins that are associated with a wide range of cellular activities. The core function of OSBP/ORPs appears to be moving lipids between cellular membranes in a non-vesicular manner. Recent studies have unveiled a novel, counter-transport mechanism of cellular lipid transfer mediated by OSBP/ORPs at the membrane contact sites that involves phosphatidylinositol 4-phosphate. Importantly, the OSBP/ORPs family has also been implicated in cell signalling pathways and cancer development...
July 18, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28733031/mkk4-activates-non-canonical-nf%C3%AE%C2%BAb-signaling-by-promoting-nf%C3%AE%C2%BAb2-p100-processing
#15
Jeong Seon Kim, Eun Ju Kim, Hee-Sun Kim, Jonathan M Kurie, Young-Ho Ahn
The NFκB family of transcription factors is crucial for innate or adaptive immunity, inflammation, and diseases including cancer. The two NFκB signaling pathways (canonical and non-canonical) differ from each other in extracellular signals, membrane receptors, signaling adaptors, and dimer subunits. The p52 (NFκB2) subunit, which participates in the non-canonical pathway, is generated by ubiquitin-mediated processing of the p100 precursor. Here, we found that NFκB2 processing and activation were mediated by mitogen-activated protein kinase kinase-4 (MKK4) and its substrate c-Jun N-terminal kinase (JNK)...
July 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28732311/solid-and-aqueous-magnetoliposomes-as-nanocarriers-for-a-new-potential-drug-active-against-breast-cancer
#16
Ana Rita O Rodrigues, Pedro M F Mendes, Pedro M L Silva, V A Machado, Bernardo G Almeida, J P Araújo, Maria-João R P Queiroz, Elisabete M S Castanheira, Paulo J G Coutinho
Iron oxide nanoparticles, with diameters around 12nm, were synthesized by coprecipitation method. The magnetic properties indicate a superparamagnetic behavior with a coercive field of 9.7Oe and a blocking temperature of 118K. Both aqueous and solid magnetoliposomes containing magnetite nanoparticles have sizes below 150nm, suitable for biomedical applications. Interaction between both types of magnetoliposomes and models of biological membranes was proven. A new antitumor compound, a diarylurea derivative of thienopyridine, active against breast cancer, was incorporated in both aqueous and solid magnetoliposomes, being mainly located in the lipid membrane...
July 8, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28732061/melatonin-pre-treatment-mitigates-shsy-5y-cells-against-oxaliplatin-induced-mitochondrial-stress-and-apoptotic-cell-death
#17
Mohammad Waseem, Upasana Sahu, Mohd Salman, Arnab Choudhury, Sudeshna Kar, Heena Tabassum, Suhel Parvez
Oxaliplatin (Oxa) treatment to SH-SY5Y human neuroblastoma cells has been shown by previous studies to induce oxidative stress, which in turn modulates intracellular signaling cascades resulting in cell death. While this phenomenon of Oxa-induced neurotoxicity is known, the underlying mechanisms involved in this cell death cascade must be clarified. Moreover, there is still little known regarding the roles of neuronal mitochondria and cytosolic compartments in mediating Oxa-induced neurotoxicity. With a better grasp of the mechanisms driving neurotoxicity in Oxa-treated SH-SY5Y cells, we can then identify certain pathways to target in protecting against neurotoxic cell damage...
2017: PloS One
https://www.readbyqxmd.com/read/28731046/pd-l1-expression-and-the-immune-microenvironment-in-primary-invasive-lobular-carcinomas-of-the-breast
#18
Elizabeth D Thompson, Janis M Taube, Rebecca J Asch-Kendrick, Aleksandra Ogurtsova, Haiying Xu, Rajni Sharma, Alan Meeker, Pedram Argani, Leisha A Emens, Ashley Cimino-Mathews
Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (<5%); 2+ (5-10%); 3+ (10-15%); or 4+ (>50%)...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28730962/phosphonium-salt-displays-cytotoxic-effects-against-human-cancer-cell-lines
#19
Dhanyalayam Dhanya, Giuseppe Palma, AnnaRita Cappello, Annaluisa Mariconda, Maria Stefania Sinicropi, Francesca Giordano, Vitale Del Vecchio, Anna Ramunno, Claudio Arra, Pasquale Longo, Carmela Saturnino
Aims/ Objective: Phosphonium salts are compounds whose structural characteristics enable them to cross the plasma and mitochondrial membrane with ease. Cancer cells have higher plasma membrane potentials than normal cells, phosphonium salts selectively accumulate in the mitochondria of neoplastic cells and inhibit mitochondrial function. METHOD: In the presente work, we investigate the cytotoxic activity of lipophilic phosphonium salt (11-methoxy11-oxo-undecyl) triphenylphosphonium bromide (MUTP) as well as of two new phosphine oxide salts, 3,3'-(methylphosphoryl) dibenzenaminium chloride (SBAMPO) and 3,3' (phenylphosphoryl) dibenzenaminium chloride (SBAPPO) on the proliferation of breast cancer cell line (MCF-7) and human uterin cervix adenocarcinoma cells (HeLa)...
July 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28730769/downregulation-and-subcellular-distribution-of-her2-involved-in-mda-mb-453-breast-cancer-cell-apoptosis-induced-by-lapatinib-celastrol-combination
#20
Yan-Yan Yan, Hong Bi, Wei Zhang, Qing Wen, Hong Liu, Jin-Xia Li, Hui-Zhi Zhang, Yan-Xia Zhang, Jia-Shan Li
PURPOSE: To investigate the effect and related molecular mechanisms of lapatinib/celastrol combination or single-agent treatment in HER2/neu-overexpressing MDA-MB-453 breast cancer cells. METHODS: The effects of treatment with lapatinib, celastrol or their combination on cell growth were determined using MTT assay. Drug synergy was determined using the combination index (CI) methods derived from Chou-Talalay equations using CalcuSyn software. Apoptotic morphology was observed by fluorescence microscope with Hoechst 33258 staining...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
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