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https://www.readbyqxmd.com/read/28433505/chemotherapy-induces-alternative-transcription-and-splicing-facts-and-hopes-for-cancer-treatment
#1
Charles A Lambert, Nancy Garbacki, Alain C Colige
Alternative promoter usage, alternative splicing and alternative cleavage/polyadenylation (referred here as to alternative transcription and splicing) are main instruments to diversify the transcriptome from a limited set of genes. There is a good deal of evidence that chemotherapeutic drugs affect these processes, but the therapeutic incidence of these effects is poorly documented. The scope of this study is to review the impact of chemotherapy on alternative transcription and splicing and to discuss potential implications in cancer therapy...
April 19, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28433067/chloroquine-and-hydroxychloroquine-inhibit-bladder-cancer-cell-growth-by-targeting-basal-autophagy-and-enhancing-apoptosis
#2
Yi-Chia Lin, Ji-Fan Lin, Sheng-I Wen, Shan-Che Yang, Te-Fu Tsai, Hung-En Chen, Kuang-Yu Chou, Thomas I-Sheng Hwang
Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7)...
May 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28423575/activated-notch-signaling-augments-cell-growth-in-hepatocellular-carcinoma-via-up-regulating-the-nuclear-receptor-nr4a2
#3
Bo Zhu, Lichun Sun, Wei Luo, Min Li, David H Coy, Long Yu, Wenbo Yu
Hepatocellular carcinoma (HCC) is one of the most malignant cancers. Conventional therapies are limited due to the human liver being such a unique organ and easily showing side-effects. The unclear molecular mechanisms are tough challenges for scientists searching for new and effective anti-HCC targeting drugs. We identified that the nuclear receptor NR4A2 is a novel oncogene in HCC progression. In this study, we show that NR4A2 and the notch recceptor Notch1 were expressed highly in primary HCC tissues and immortal HCC cells by using qPCR, western blot and immuno-histochemistry assays...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401035/development-and-application-of-human-renal-proximal-tubule-epithelial-cells-for-assessment-of-compound-toxicity
#4
Shuaizhang Li, Jinghua Zhao, Ruili Huang, Toni Steiner, Maureen Bourner, Michael Mitchell, David C Thompson, Bin Zhao, Menghang Xia
Kidney toxicity is a major problem both in drug development and clinical settings. It is difficult to predict nephrotoxicity in part because of the lack of appropriate in vitro cell models, limited endpoints, and the observation that the activity of membrane transporters which plays important roles in nephrotoxicity by affecting the pharmacokinetic profile of drugs is often not taken into account. We developed a new cell model using pseudo-immortalized human primary renal proximal tubule epithelial cells. This cell line (SA7K) was characterized by the presence of proximal tubule cell markers as well as several functional properties, including transporter activity and response to a few well-characterized nephrotoxicants...
2017: Current Chemical Genomics and Translational Medicine
https://www.readbyqxmd.com/read/28379424/combination-therapy-with-potent-pi3k-and-mapk-inhibitors-overcomes-adaptive-kinome-resistance-to-single-agents-in-preclinical-models-of-glioblastoma
#5
Robert S McNeill, Demitra A Canoutas, Timothy J Stuhlmiller, Harshil D Dhruv, David M Irvin, Ryan E Bash, Steven P Angus, Laura E Herring, Jeremy M Simon, Kasey R Skinner, Juanita C Limas, Xin Chen, Ralf S Schmid, Marni B Siegel, Amanda E D Van Swearingen, Michael J Hadler, Erik P Sulman, Jann N Sarkaria, Carey K Anders, Lee M Graves, Michael E Berens, Gary L Johnson, C Ryan Miller
Background.: Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Prognosis remains poor despite multimodal therapy. Developing alternative treatments is essential. Drugs targeting kinases within the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) effectors of receptor tyrosine kinase (RTK) signaling represent promising candidates. Methods.: We previously developed a non-germline genetically engineered mouse model of GBM in which PI3K and MAPK are activated via Pten deletion and KrasG12D in immortalized astrocytes...
March 30, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28356007/fluorescent-immortalized-human-adipose-derived-stromal-cells-hascs-ts-gfp-for-studying-cell-drug-delivery-mediated-by-microvesicles
#6
Valentina Coccè, Luigi Balducci, Maria Laura Falchetti, Luisa Pascucci, Emilio Ciusani, Anna Teresa Brini, Francesca Sisto, Giovanna Piovani, Giulio Alessandri, Eugenio Parati, Laura Cabeza, Augusto Pessina
BACKGROUND: A new tool for the drug delivery is based on the use of Mesenchymal Stromal Cells (MSCs) loaded in vitro with anti-cancer drugs. Unfortunately, the restricted lifespan of MSCs represents a significant limitation to produce them in high amounts and for long time studies. Immortalized MSCs from adipose tissue (hASC) have been generated as good source of cells with stable features. These cells could improve the development of standardized procedures for both in vitro and preclinical studies...
March 27, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28346106/isolation-and-characterization-of-a-distinct-subpopulation-from-the-wm115-cell-line-that-resembles-in-vitro-properties-of-melanoma-cancer-stem-cells
#7
Sonia G Escobar, Mark H Chin, Mark L Sandberg, Han Xu
Despite key advances in cancer therapies, malignant tumors, such as melanoma, continue to be one of the leading causes of mortality. Recent debate on whether cancer can originate from a tumor-initiating subpopulation has permeated oncology and stem cell research. It has been well established that primary and immortalized tumor cells consist of heterogeneous cell populations. The profound effect of tumor heterogeneity on tumor growth and drug resistance remains elusive, but it is highly likely that subpopulations of cancer cells have different capabilities of self-renewal and drug resistance...
February 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28339479/mouse-newborn-cells-allow-highly-productive-mouse-cytomegalovirus-replication-constituting-a-novel-convenient-primary-cell-culture-system
#8
Vu Thuy Khanh Le-Trilling, Mirko Trilling
Mammalian cell culture is indispensable for most aspects of current biomedical research. Immortalized cell lines are very convenient, but transforming principles (e.g. oncogenic viruses or their oncogenes) can heavily influence the experimental outcome. Primary cells do not share this apparent disadvantage but are more laborious to generate. Certain viruses (e.g. mouse cytomegalovirus) do not replicate efficiently in most transformed cell lines. In the past, such viruses have been routinely propagated on primary mouse embryonic fibroblasts (MEF) established around day 17 (d17) of gestation...
2017: PloS One
https://www.readbyqxmd.com/read/28321651/effects-of-strontium-ranelate-treatment-on-osteoblasts-cultivated-onto-scaffolds-of-trabeculae-bovine-bone
#9
Gerluza Aparecida Borges Silva, Bruno Machado Bertassoli, Cristiane Aparecida Sousa, Juliano Douglas Albergaria, Rayan Silva de Paula, Erika Cristina Jorge
Blocks of Bovine bone have shown promising results as implantable scaffolds to promote bone regeneration. Strontium ranelate (SrR) is both an antiresorptive and an anabolic drug that has been indicated for oral administration to treat osteoporosis. Few studies, however, have investigated the local effects of SrR and its use in association with biomaterials thus far. In this work, we investigated SrR effects in cultures of primary osteoblasts (PO, from Wistar rats calvaria) and immortalized osteoblasts (IO, from MC3T3-E1 cell line) cultivated as a monolayer or in association with scaffolds of bovine bone in mineralized (MBB) and demineralized (DBB) forms...
March 20, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28315467/hce-t-cell-based-permeability-model-a-well-maintained-or-a-highly-variable-barrier-phenotype
#10
Marina Juretić, Bisera Jurišić Dukovski, Iva Krtalić, Stephan Reichl, Biserka Cetina-Čižmek, Jelena Filipović-Grčić, Jasmina Lovrić, Ivan Pepić
The most extensively characterized human-derived cell line used in transcorneal permeability studies, in terms of passive transcellular and paracellular transport, transporter expression and metabolic enzymes, is the immortalized human corneal epithelial cell line (HCE-T). The purpose of this study is to describe the changes in the HCE-T barrier phenotype in vitro when valid cultivation conditions, in accordance with the standardized HCE-T cell-based model protocol, were employed. Evaluation of the structural and functional barrier properties revealed two different HCE-T barrier phenotypes, depending on the polycarbonate membrane pore size...
March 14, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28287250/changes-in-the-expression-of-cyclin-dependent-kinase-inhibitors-during-differentiation-of-immortalized-fibroblasts-into-adipocytes
#11
Ibon Alonso, Antonio Baroja, Blanca Fernández, Raquel Vielba, Jon Elorriaga, Jairo Pérez-Sanz, Juan Aréchaga, Juan J Goiriena de Gandarias, Carmen de la Hoz
The mechanisms implicated in the differentiation of fibroblastic precursors into adipocytes can be analyzed in vitro using cell models, such as the 3T3-L1 cell line. Since cell differentiation involves an exit from the cell cycle, it is likely that molecules that inhibit proliferation participate in the control of adipogenesis. This study was aimed at determining the role, if any, of several cyclin-dependent kinase (CDK)-inhibitors and the transcription factor C/EBPα in the process of adipocyte differentitation...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28285358/fluoroquinolones-and-propionic-acid-derivatives-induce-inflammatory-responses-in-vitro
#12
Akira Nakajima, Hiroki Sato, Shingo Oda, Tsuyoshi Yokoi
Fluoroquinolones and propionic acid derivatives are widely used antibacterials and non-steroidal anti-inflammatory drugs, respectively, which have been reported to frequently trigger drug hypersensitivity reactions. Such reactions are induced by inflammatory mediators such as cytokines and chemokines. The present study investigated whether levofloxacin, a fluoroquinolone, and loxoprofen, a propionic acid derivative, have the potential to induce immune-related gene expression in dendritic cell-like cell lines such as HL-60, K562, and THP-1, and immortalized keratinocytes such as HaCaT...
March 11, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28280338/a-novel-ion-exchange-carrier-based-upon-liposome-encapsulated-montmorillonite-for-ophthalmic-delivery-of-betaxolol-hydrochloride
#13
Yi Huang, Qi Tao, Dongzhi Hou, Sheng Hu, Shuangyan Tian, Yanzhong Chen, Ruyi Gui, Lingling Yang, Yao Wang
As a novel ion-exchange carrier with high surface area and excellent exchangeability, montmorillonite (Mt) was intercalated with betaxolol hydrochloride (BH) to form a nanocomposite and then encapsulated by liposomes (Mt-BH-LPs) for an ophthalmic drug-delivery system. The Mt-BH and Mt-BH-LPs were prepared by an acidification process and ethanol injection combined with ammonium sulfate gradient methods. The successful formation of Mt-BH and Mt-BH-LPs was verified by thermogravimetric analysis, X-ray diffraction, Fourier-transform infrared spectra, and transmission electron microscopy...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28264565/dual-modulation-of-human-p-glycoprotein-and-abcg2-with-prodrug-dimers-of-the-atypical-antipsychotic-agent-paliperidone-in-a-model-of-the-blood-brain-barrier
#14
Kelsey Bohn, Allison Lange, Jean Chmielewski, Christine A Hrycyna
Many atypical antipsychotic drugs currently prescribed for the treatment of schizophrenia have limited brain penetration due to the efflux activity of ATP-binding cassette (ABC) transporters at the blood-brain barrier (BBB), including P-glycoprotein (P-gp) and ABCG2. Herein, we describe the design and synthesis of the first class of homodimeric prodrug dual inhibitors of P-gp and ABCG2. These inhibitors are based on the structure of the atypical antipsychotic drug paliperidone (Pal), a transport substrate for both transporters...
April 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28245768/therapeutic-targeting-of-nlrp3-inflammasomes-by-natural-products-and-pharmaceuticals-a-novel-mechanistic-approach-for-inflammatory-diseases
#15
Sadaf Jahan, Dipak Kumar, Swati Chaturvedi, Mamunur Rashid, Muhammad Wahajuddin, Yasir Akhtar Khan, Sameer N Goyal, C R Patil, Rajesh Mohanraj, Sandeep Subramanya, Shreesh Ojha
Inflammasomes are multiprotein complexes having nucleotide-binding domain and leucine-rich repeat consisting members along with pyrin and HIN domain family. An inflammasome mainly consists of cytoplasmic sensor molecule such as NLRP3, the adaptor apoptosis-associated speck-like protein containing caspase recruitment domain) protein along with effector procaspase-1. The inflammasome regulates caspase-1 activation, resulting in secretion of interleukin-1β and interleukin-18. The inflammasome activation is linked with infection, stress, or other immunological signals involved in inflammation...
February 27, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28216661/mir-194-5p-bclaf1-deregulation-in-aml-tumorigenesis
#16
C Dell'Aversana, C Giorgio, L D'Amato, G Lania, F Matarese, S Saeed, A Di Costanzo, V B Petrizzi, C Ingenito, J H A Martens, I Pallavicini, S Minucci, A Carissimo, H G Stunnenberg, L Altucci
Deregulation of epigenetic mechanisms, including miRNA, contributes to leukaemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal haematopoietic progenitors. In acute myeloid leukaemias (AMLs) this balance is perturbed, locking cells into an immature, potentially 'immortal' state. Enhanced expression of miR-194-5p by treatment with the HDAC inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol...
February 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28197378/identification-of-inhibitors-of-myeloid-derived-suppressor-cells-activity-through-phenotypic-chemical-screening
#17
Matthias Schröder, Simone Loos, Svenja Kerstin Naumann, Christopher Bachran, Marit Krötschel, Viktor Umansky, Laura Helming, Lee Kim Swee
Tumors are infiltrated by cells of the immune system that interact through complex regulatory networks. Although tumor-specific CD8(+) T cells can be found in peripheral blood and tumor samples from cancer patients, their function is inhibited by immunosuppressive cells such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). Recent clinical successes have demonstrated that alleviating immunosuppression and T cell exhaustion translates into long-term clinical benefits...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28191273/oxidative-stress-triggered-by-apigenin-induces-apoptosis-in-a-comprehensive-panel-of-human-cervical-cancer-derived-cell-lines
#18
Raquel P Souza, Patrícia de S Bonfim-Mendonça, Fabrícia Gimenes, Bianca A Ratti, Vanessa Kaplum, Marcos L Bruschi, Celso V Nakamura, Sueli O Silva, Silvya S Maria-Engler, Marcia E L Consolaro
Recently, the cytotoxic effects of apigenin (4',5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28178655/chl1-hypermethylation-as-a-potential-biomarker-of-poor-prognosis-in-breast-cancer
#19
Esperanza Martín-Sánchez, Saioa Mendaza, Ane Ulazia-Garmendia, Iñaki Monreal-Santesteban, Idoia Blanco-Luquin, Alicia Córdoba, Francisco Vicente-García, Noemí Pérez-Janices, David Escors, Diego Megías, Paula López-Serra, Manel Esteller, José Juan Illarramendi, David Guerrero-Setas
The CHL1 gene encodes a cell-adhesion molecule proposed as being a putative tumour-suppressor gene in breast cancer (BC). However, neither the underlying molecular mechanisms nor the clinical value of CHL1 downregulation in BC has been explored. The methylation status of three CpG sites in the CHL1 promoter was analysed by pyrosequencing in neoplastic biopsies from 142 patients with invasive BC and compared with that of non-neoplastic tissues. We found higher CHL1 methylation levels in breast tumours than in non-neoplastic tissues, either from mammoplasties or adjacent-to-tumour, which correlated with lower levels of protein expression in tumours measured by immunohistochemistry...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177527/effects-of-linagliptin-on-human-immortalized-podocytes-a-cellular-system-to-study-dipeptidyl-peptidase-4-inhibition
#20
Gianluca Miglio, Giovanna Vitarelli, Thomas Klein, Elisa Benetti
BACKGROUND AND PURPOSE: Dipeptidyl-peptidase 4 (DPP4) is expressed by resident renal cells, including glomerular cells. DPP4 inhibitors (gliptins) exert albuminuria lowering effects, but the role of renal DPP4 as a pharmacological target has not been elucidated. To better understand the actions of gliptins, the effects of linagliptin on the behaviour of immortalized human podocytes and mesangial cells were evaluated. EXPERIMENTAL APPROACH: The expression of DPP4 was measured at both the mRNA and protein levels...
May 2017: British Journal of Pharmacology
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