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Cell AND Therapy

Franziska Hanisch, Linda Toresson, Thomas Spillmann
Cobalamin is a member of the B-group of vitamins and a cofactor for metabolic processes like nucleic acid synthesis, amino acid synthesis, and the citric acid cycle. Mammals are unable to synthesize cobalamin and therefore rely on adequate food intake. Cobalamin absorption is a complex process in the stomach, duodenum, and ileum, requiring a functional exocrine pancreas. Thus, a great number of gastrointestinal diseases like chronic enteropathies, intestinal lymphoma, or exocrine pancreatic insufficiency can lead to hypocobalaminemia...
October 2018: Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere
Michael R Rickels, R Paul Robertson
Pancreatic islet transplantation has become an established approach to β-cell replacement therapy for the treatment of insulin deficient diabetes. Recent progress in techniques for islet isolation, islet culture, and peri-transplant management of the islet transplant recipient have resulted in substantial improvements in metabolic and safety outcomes for patients. For patients requiring total or sub-total pancreatectomy for benign disease of the pancreas, isolation of islets from the diseased pancreas with intrahepatic transplantation of autologous islets can prevent or ameliorate post-surgical diabetes, and for patients previously experiencing painful recurrent acute or chronic pancreatitis, quality-of-life is substantially improved...
December 12, 2018: Endocrine Reviews
Norikatsu Miyoshi, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori
The classical cancer therapies, including chemotherapy and radiation therapy, can initially show good results and tumor shrinkage; however, for most cancer patients disease recurrence is a common event. This tumor regrowth following therapy is now thought to depend on a small population of cancer stem cells (CSCs), which, similar to other stem cells, have the capacity for self-renewal and multipotent differentiation. Cancer stem cells have been identified based on cell surface protein expression in many tumor types, and for all diseases studied, this specific cell population is required for serial transplantation in animal models...
December 12, 2018: Japanese Journal of Clinical Oncology
Yukie Morikawa, Naoki Takahashi, Kazuko Kamiyama, Kazuhisa Nishimori, Yudai Nishikawa, Sayu Morita, Mamiko Kobayashi, Sachiko Fukushima, Seiji Yokoi, Daisuke Mikami, Hideki Kimura, Kenji Kasuno, Tetsuya Yashiki, Hironobu Naiki, Masanori Hara, Masayuki Iwano
BACKGROUND/AIMS: Extracellular vesicles (EVs), including exosomes, are present in various bodily fluids, including urine. We and others previously reported that cells expressing fibroblast-specific protein 1 (FSP1) accumulate within damaged glomeruli, and that urinary FSP1, as well as urinary soluble CD163, could potentially serve as a biomarker of ongoing glomerular injury. METHODS: To test that idea, we collected urine samples from 37 patients with glomerular disease; purified the urinary EVs; characterized them using Nanosight, western blotting, and immunoelectron microscopy; and determined FSP1 and soluble CD163 levels using enzyme-linked immunosorbent assays...
December 12, 2018: Nephron
Jing Luo, Yang Cheng, Xiao-Yan He, Yi Liu, Na Peng, Zhi-Wei Gong, Kui Wu, Tao Zou
To realize efficiently cellular uptake and enhance the immunostimulation, thiolated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs) were self-assembled on hollow gold nanospheres (HGNs) to form CpG-HGNs. The cellular uptake of CpG-HGNs in immune cells was studied in RAW 264.7 cells. Due to the enhanced delivery efficiency, CpG-HGNs exhibited a higher immune stimulatory activity compared with CpG ODNs, resulting in a dramatically enhanced secretion of proinflammatory cytokines. In addition, CpG-HGNs showed low cytotoxicity in RAW 264...
December 3, 2018: Colloids and Surfaces. B, Biointerfaces
Xiaoxia Wu, Jing Liu, Lingyan Yang, Fu Wang
Chemotherapy is an important first-line strategy for tumor therapy in cancer treatment, but multidrug resistance (MDR) is a major problem that reduces the efficacy of chemotherapeutics. Herein, we report a novel photothermally controlled intelligent drug release system (AuNP@mSiO2 -DOX-FA) with a large amount of drugs loading for synergistic chemo-photothermal therapy of MDR in breast cancer. The nanoplatform utilized gold nanoparticles as a hyperthermia core, and large-mesoporous silica as a shell for doxorubicin (DOX) loading...
December 5, 2018: Colloids and Surfaces. B, Biointerfaces
Su Su, Anyonya R Guntur, Daniel C Nguyen, Shameem S Fakory, Chad C Doucette, Cassandra Leech, Humphrey Lotana, Matthew Kelley, Jaspreet Kohli, Julieta Martino, Sunder Sims-Lucas, Lucy Liaw, Calvin Vary, Clifford J Rosen, Aaron C Brown
Molecular- and cellular-based therapies have the potential to reduce obesity-associated disease. In response to cold, beige adipocytes form in subcutaneous white adipose tissue and convert energy stored in metabolic substrates to heat, making them an attractive therapeutic target. We developed a robust method to generate a renewable source of human beige adipocytes from induced pluripotent stem cells (iPSCs). Developmentally, these cells are derived from FOXF1+ mesoderm and progress through an expandable mural-like mesenchymal stem cell (MSC) to form mature beige adipocytes that display a thermogenically active profile...
December 11, 2018: Cell Reports
Don Benjamin, Dimitri Robay, Sravanth K Hindupur, Jens Pohlmann, Marco Colombi, Mahmoud Y El-Shemerly, Sauveur-Michel Maira, Christoph Moroni, Heidi A Lane, Michael N Hall
Highly glycolytic cancer cells prevent intracellular acidification by excreting the glycolytic end-products lactate and H+ via the monocarboxylate transporters 1 (MCT1) and 4 (MCT4). We report that syrosingopine, an anti-hypertensive drug, is a dual MCT1 and MCT4 inhibitor (with 60-fold higher potency on MCT4) that prevents lactate and H+ efflux. Syrosingopine elicits synthetic lethality with metformin, an inhibitor of mitochondrial NADH dehydrogenase. NAD+, required for the ATP-generating steps of glycolysis, is regenerated from NADH by mitochondrial NADH dehydrogenase or lactate dehydrogenase...
December 11, 2018: Cell Reports
István Szegedi, Imre Gáspár, Katalin Gyurina, Zsuzsa Zele, Csongor Kiss
Classification, staging and treatment response criteria of pediatric NHL have been revised. Long-term survival reaches ~90% at the expense of severe acute toxicities. The outcome of refractory and relapsed cases is poor. The small number of patients hinders introduction of targeted therapies. Here we summarize principles and perspectives of pediatric NHL supported by results of a retrospective clinical survey. Twenty-five patients (21 boys, 4 girls; mean age: 11.9 years) were registered between 2009 and 2018: 11 Burkitt lymphomas, 4 diffuse large B-cell lymphomas, 5 T-cell lymphoblastic lymphomas, and 1-1 grey-zone lymphoma, anaplastic large-cell lymphoma, cutaneous T-cell lymphoma, angioimmunoblastic lymphoma, and Castleman disease...
December 12, 2018: Magyar Onkologia
Jingling Li, Cyndhavi Narayanan, Jing Bian, Danielle Sambo, Thomas Brickler, Wancong Zhang, Sundari Chetty
The propensity for differentiation varies substantially across human pluripotent stem cell (hPSC) lines, greatly restricting the use of hPSCs for cell replacement therapy or disease modeling. Here, we investigate the underlying mechanisms and demonstrate that activation of the retinoblastoma (Rb) pathway in a transient manner is important for differentiation. In prior work, we demonstrated that pre-treating hPSCs with dimethylsulfoxide (DMSO) before directed differentiation enhanced differentiation potential across all three germ layers...
2018: PloS One
Karen E Wickersham, Theresa K Hodges, Martin J Edelman, Yang Song, Mintong Nan, Susan G Dorsey
BACKGROUND: Therapies targeting the epidermal growth factor receptor (EGFR) result in a painful rash, the most common and debilitating toxicity among patients with non-small cell lung cancer (NSCLC) who take EGFR tyrosine kinase inhibitor (TKI) therapy; however, predicting the development and the severity of the rash is difficult. OBJECTIVE: To examine how erlotinib-an EGFR TKI that NSCLC patients take to stop or slow tumor growth-altered the transcriptome of dermal fibroblasts...
December 12, 2018: Nursing Research
Arkadius Polasik, Marie Tzschaschel, Fabienne Schochter, Thomas W P Friedl, Brigitte Rack, Andreas Hartkopf, Peter A Fasching, Andreas Schneeweiss, Volkmar Müller, Jens Huober, Wolfgang Janni, Tanja Fehm
PURPOSE OF REVIEW: The possibility of tumor dissemination through the blood system has been known for years. Circulating tumor cells (CTCs) are detectable in the peripheral blood of patients with early as well as metastatic breast cancer. The prognostic relevance of this biomarker has already been described. By the use of repeated blood sampling along the course of disease, CTCs can be monitored in terms of a regular 'liquid biopsy'. This review aims to summarize recent research findings and actual ongoing clinical studies to demonstrate the actual and future relevance of CTCs in daily clinical routine...
December 11, 2018: Current Opinion in Obstetrics & Gynecology
Bruce Schaar, Venkatesh Krishnan, Supreeti Tallapragada, Anita Chanana, Oliver Dorigo
PURPOSE OF REVIEW: To provide an update on cell-based immunotherapies in solid tumors particularly in gynecological cancers. RECENT FINDINGS: Improvements have been made in engineering T cells to overcome the immunosuppressive environment in ovarian cancer. Significant efforts are underway to create 'off the shelf' cell therapies which leverage natural killer (NK) cells and would not rely on engineering a patient's T cells. SUMMARY: Efforts to target solid tumors using cell-based therapies are expanding into cell types other than T cells (NK cells and macrophages) which may have a lower risk of significant side effects and higher efficacy in solid tumors than chimeric antigen receptor T cells...
December 11, 2018: Current Opinion in Obstetrics & Gynecology
Kelly E McCann
PURPOSE OF REVIEW: Poly-ADP-ribosyl-polymerase (PARP) inhibitors are an increasingly-utilized therapy in women with high-grade serous ovarian carcinoma, but tumor resistance to PARP inhibitor monotherapy is inevitable. RECENT FINDINGS: PARP inhibitors have been most studied in patients with breast and ovarian cancers associated with deleterious germline BRCA1 or BRCA2 mutations, though their role has expanded to include use as maintenance therapy in women with platinum-sensitive high-grade serous ovarian cancer due to the high propensity of such cancers to have defects in DNA repair by homologous recombination...
December 11, 2018: Current Opinion in Obstetrics & Gynecology
Eva Schrezenmeier, Sarah Y Weißenberg, Ana-Luisa Stefanski, Franziska Szelinski, Annika Wiedemann, Andreia C Lino, Thomas Dörner
PURPOSE OF REVIEW: This review summarizes recent insights and current understanding of the role of postactivated B cells in SLE and related pathogenic and potential therapeutic implications. RECENT FINDING: B cells are considered key players in SLE and experience from various B-cell-targeted therapies underlines their clinical relevance. In the last years, new insights have been obtained on B-cell abnormality within the complex pathophysiology of SLE. These insights involve a revised understanding of BCR signaling, that has been reported to be hyperresponsive in the past, but newer studies suggest a postactivation functiotype in terms of reduced BCR and TLR signaling...
December 11, 2018: Current Opinion in Rheumatology
Feng Liu, Jin Zhang, Long Qin, Ziyao Yang, Jianxia Xiong, Yanyan Zhang, Ruihuan Li, Shujing Li, Huifang Wang, Bo Yu, Wenjun Zhao, Weiran Wang, Zhensu Li, Jing Liu
Anaplastic thyroid carcinoma (ATC) responds for the majority of death of thyroid carcinoma and often causes chemotherapy resistance. We investigated the influence of circEIF6 (Hsa_circ_0060060) on the cisplatin-sensitivity in papillary thyroid carcinoma (PTC) and ATC cells, and explored its regulation to downstream molecules miR-144-3p and Transforming Growth Factor α (TGF-α). Differentially expressed circRNAs in PTC were analyzed using the GSE93522 data downloaded. Expressions of circEIF6, miR-144-3p, TGF-α, autophagy-related proteins and apoptosis-related proteins were determined using qRT-PCR or western blot...
December 12, 2018: Aging
Clelia Baccari, Elena Antonova, Steven Lindow
Effective preventive measures and therapies are lacking for control of Pierce's disease of grape caused by the xylem-colonizing bacterium Xylella fastidiosa responsible for serious losses in grape production. In this study we explored the potential for endophytic bacteria to alter the disease process. While most endophytic bacteria found within grape did not grow or multiply when inoculated into mature grape vines, Paraburkholderia phytofirmans strain PsJN achieved population sizes as large as 106 cells/g and moved 1 m or more within 4 weeks after inoculation into vines...
December 12, 2018: Phytopathology
Ji Won Choi, Siwon Kim, Jong-Hyun Park, Hyeon Jeong Kim, Su Jeong Shin, Jin Woo Kim, Seo Yeon Woo, Changho Lee, Sang Moon Han, Jaeick Lee, Ae Nim Pae, Gyoonhee Han, Ki Duk Park
We previously developed a novel series of vinyl sulfones as nuclear factor E2-related factor 2 (Nrf2) activators with therapeutic potential for Parkinson's disease (PD). However, the previously developed lead compound (1) exhibited undesirable drug-like properties. Here we optimized vinyl sulfones by introducing nitrogen heterocycles to improve drug-like properties. Among the synthesized compounds, 17e was the most promising drug candidate with good drug-like properties. 17e showed superior effects on Nrf2 activation in cell-based assays compared to compound 1 (17e: EC50 = 346 nM; 1: EC50 = 530 nM)...
December 12, 2018: Journal of Medicinal Chemistry
Fernanda Antunes, Adolfo Garcia Erustes, Angélica Jardim Costa, Ana Carolina Nascimento, Claudia Bincoletto, Rodrigo Portes Ureshino, Gustavo José Silva Pereira, Soraya Soubhi Smaili
Cancer is a leading cause of death worldwide, and its incidence is continually increasing. Although anticancer therapy has improved significantly, it still has limited efficacy for tumor eradication and is highly toxic to healthy cells. Thus, novel therapeutic strategies to improve chemotherapy, radiotherapy and targeted therapy are an important goal in cancer research. Macroautophagy (herein referred to as autophagy) is a conserved lysosomal degradation pathway for the intracellular recycling of macromolecules and clearance of damaged organelles and misfolded proteins to ensure cellular homeostasis...
December 10, 2018: Clinics
Carlos Roberto Koscky Paier, Sarah Sant'Anna Maranhão, Teiliane Rodrigues Carneiro, Lídia Moreira Lima, Danilo Damasceno Rocha, Renan da Silva Santos, Kaio Moraes de Farias, Manoel Odorico de Moraes-Filho, Claudia Pessoa
Cell cycle control genes are frequently mutated in cancer cells, which usually display higher rates of proliferation than normal cells. Dysregulated mitosis leads to genomic instability, which contributes to tumor progression and aggressiveness. Many drugs that disrupt mitosis have been studied because they induce cell cycle arrest and tumor cell death. These antitumor compounds are referred to as antimitotics. Vinca alkaloids and taxanes are natural products that target microtubules and inhibit mitosis, and their derivatives are among the most commonly used drugs in cancer therapy worldwide...
December 10, 2018: Clinics
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