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https://www.readbyqxmd.com/read/28917518/genome-stability-of-programmed-stem-cell-products
#1
REVIEW
Ulrich Martin
Inherited and acquired genomic abnormalities are known to cause genetic diseases and contribute to cancer formation. Recent studies demonstrated a substantial mutational load in mouse and human embryonic and induced pluripotent stem cells (ESCs and iPSCs). Single nucleotide variants, copy number variations, and larger chromosomal abnormalities may influence the differentiation capacity of pluripotent stem cells and the functionality of their derivatives in disease modelling and drug screening, and are considered a serious risk for cellular therapies based on ESC or iPSC derivatives...
September 13, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#2
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916148/chemokine-receptor-directed-imaging-and-therapy
#3
REVIEW
Andreas K Buck, Antje Stolzenburg, Heribert Hänscheid, Andreas Schirbel, Katharina Lückerath, Margret Schottelius, Hans-Jürgen Wester, Constantin Lapa
The C - X - C chemokine receptor 4 (CXCR4) and its natural ligand CXCL12 are key factors in the process of cell migration, homing of hematopoietic stem cells to the bone marrow, and represent important mediators of angiogenesis and cell proliferation. The CXCR4/CXCL12 interplay can be disrupted by CXCR4 antagonists such as Plerixafor which are already in daily clinical use, i.e. for mobilization and subsequent harvesting of hematopoietic progenitor cells and stem cell transplantation. In a pathological condition, involvement in the process of metastasis and homing of cancer cells to a protective niche has been described, making CXCR4 an attractive target for imaging and treatment of malignant diseases...
September 12, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28915611/metformin-increases-chemo-sensitivity-via-gene-downregulation-encoding-dna-replication-proteins-in-5-fu-resistant-colorectal-cancer-cells
#4
Sung-Hee Kim, Soon-Chan Kim, Ja-Lok Ku
Metformin is most widely prescribed for type 2 diabetes. Recently, evidences have shown that metformin has anticancer effects on pancreatic-, colorectal-, ovarian-, and other cancers. Because metformin has less adverse effects and is inexpensive, it could be a useful chemo-therapeutic agent with anticancer effects. In this study, we demonstrated metformin inhibited by cell proliferation, cell migration ability, clonogenic ability, and cancer stem cell population. Metformin also induced cell cycle arrest in parental-(SNU-C5), and 5-Fu resistant-colorectal cancer cell line (SNU-C5_5FuR)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915578/targeting-hypoxic-cancer-stem-cells-cscs-with-doxycycline-implications-for-optimizing-anti-angiogenic-therapy
#5
Ernestina Marianna De Francesco, Marcello Maggiolini, Herbert B Tanowitz, Federica Sotgia, Michael P Lisanti
Here, we report new mechanistic insight into how chronic hypoxia increases 'stemness' in cancer cells. Using chemical inhibitors, we provide direct experimental evidence that ROS production and mitochondrial biogenesis are both required for the hypoxia-induced propagation of CSCs. More specifically, we show that hypoxic CSCs can be effectively targeted with i) simple mitochondrial anti-oxidants (Mito-TEMPO) and/or ii) inhibitors of mitochondrial biogenesis (Doxycycline). In this context, we discuss the idea that mitochondrial biogenesis itself may be a primary driver of "stemness" in hypoxic cancer cells, with metabolic links to fatty acid oxidation (FAO)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914637/signal-transducer-and-activator-of-transcription-gain-of-function-primary-immunodeficiency-immunodysregulation-disorders
#6
Filippo Consonni, Laura Dotta, Francesca Todaro, Donatella Vairo, Raffaele Badolato
PURPOSE OF REVIEW: To describe primary immunodeficiencies caused by gain-of-function (GOF) mutations of signal transducer and activator of transcription (STAT) genes, a group of genetically determined disorders characterized by susceptibility to infections and, in many cases, autoimmune manifestations. RECENT FINDINGS: GOF mutations affecting STAT1 result in increased STAT tyrosine phosphorylation and secondarily increased response to STAT1-signaling cytokines, such as interferons...
September 13, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28912136/tumor-resection-boosts-therapeutic-efficacy-of-encapsulated-stem-cells-expressing-a-highly-secretable-variant-of-interferon-%C3%AE-in-glioblastomas
#7
Sung Hugh Choi, Daniel W Stuckey, Sara Pignatta, Clemens Reinshagen, Jasneet K Khalsa, Nicolaas C Roozendaal, Jordi Martinez-Quintanilla, Kaoru Tamura, Erhan Keles, Khalid Shah
PURPOSE: Despite tumor resection being the frontline clinical care for glioblastoma (GBM) patients, nearly all preclinical immune therapy models intends to treat established GBM tumor. Characterizing cytoreductive surgery-induced immune-response combined with the administration of immune cytokines has the potential of offering a new treatment paradigm of immune therapy for GBMs.  Experimental design: We developed syngeneic orthotopic mouse GBM models of tumor-resection and characterized the immune response of intact and resected tumors...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28910490/regulation-of-wnt-%C3%AE-catenin-signalling-by-tankyrase-dependent-poly-adp-ribosyl-ation-and-scaffolding
#8
REVIEW
Laura Mariotti, Katie Pollock, Sebastian Guettler
The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled through the concerted interactions of concentration-limited pathway components and a wide range of posttranslational modifications, including phosphorylation, ubiquitylation, sumoylation, poly(ADP-ribosyl)ation (PARylation) and acetylation. Regulation of Wnt/β-catenin signalling by PARylation was discovered relatively recently...
September 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28904834/methionine-mediated-synthesis-of-magnetic-nanoparticles-and-functionalization-with-gold-quantum-dots-for-theranostic-applications
#9
Arūnas Jagminas, Agnė Mikalauskaitė, Vitalijus Karabanovas, Jūrate Vaičiūnienė
Biocompatible superparamagnetic iron oxide nanoparticles (NPs) through smart chemical functionalization of their surface with fluorescent species, therapeutic proteins, antibiotics, and aptamers offer remarkable potential for diagnosis and therapy of disease sites at their initial stage of growth. Such NPs can be obtained by the creation of proper linkers between magnetic NP and fluorescent or drug probes. One of these linkers is gold, because it is chemically stable, nontoxic and capable to link various biomolecules...
2017: Beilstein Journal of Nanotechnology
https://www.readbyqxmd.com/read/28903376/improving-circulating-tumor-cells-enumeration-and-characterization-to-predict-outcome-in-first-line-chemotherapy-mcrpc-patients
#10
Luis León-Mateos, Helena Casas, Alicia Abalo, María Vieito, Manuel Abreu, Urbano Anido, Antonio Gómez-Tato, Rafael López, Miguel Abal, Laura Muinelo-Romay
INTRODUCTION: There is a critical need of new surrogate markers for improving the therapeutic selection and monitoring of metastatic prostate cancer patients. Nowadays clinical management of these patients is been driven by biochemical and clinical parameters without enough accuracy to allow a real personalized medicine. The present study was conducted to go insight the molecular profile of circulating tumor cells (CTCs) isolated from advanced metastatic castration-resistant prostate cancer (mCRPC) with the aim of identifying prognostic marker with potential utility for therapy selection and monitoring...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903367/exploratory-investigation-of-psca-protein-expression-in-primary-breast-cancer-patients-reveals-a-link-to-her2-neu-overexpression
#11
Theresa Link, Friederike Kuithan, Armin Ehninger, Jan Dominik Kuhlmann, Michael Kramer, Andreas Werner, Axel Gatzweiler, Barbara Richter, Gerhard Ehninger, Gustavo Baretton, Michael Bachmann, Pauline Wimberger, Katrin Friedrich
BACKGROUND: Prostate stem cell antigen (PSCA) has been suggested as biomarker and therapeutic target for prostate cancer. Recent advances showed that PSCA is up-regulated in other cancer entities, such as bladder or pancreatic cancer. However, the clinical relevance of PSCA-expression in breast cancer patients has not yet been established and is therefore addressed by the current study. METHODS: PSCA-protein expression was assessed in 405 breast cancer patients, using immunohistochemistry (PSCA antibody MB1) and tissue microarrays...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903350/zeb1-confers-stem-cell-like-properties-in-breast-cancer-by-targeting-neurogenin-3
#12
Chen Zhou, Huimin Jiang, Zhen Zhang, Guomin Zhang, Hang Wang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Shuang Yang
Cancer stem cells (CSCs) are a subpopulation of cancer cells believed to be implicated in cancer initiation, progression, and recurrence. Here, we report that ectopic expression of zinc finger E-box binding homeobox 1 protein (ZEB1) results in the acquisition of CSC properties by breast cancer cells, leading to tumor initiation and progression in vitro and in vivo. The neurogenin 3 gene (Ngn3) is a bona fide target of ZEB1, and its repression is a key factor contributing to ZEB1-induced cancer cell stemness...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903328/cd164-promotes-lung-tumor-initiating-cells-with-stem-cell-activity-and-determines-tumor-growth-and-drug-resistance-via-akt-mtor-signaling
#13
Wei-Liang Chen, Ai-Fang Huang, Shih-Ming Huang, Ching-Liang Ho, Yung-Lung Chang, James Yi-Hsin Chan
CD164 is a cell adhesion molecule that increases hematopoietic stem cell proliferation, adhesion, and migration via C-X-C chemokine receptor type 4 (CXCR4) signaling. Emerging evidence indicates that elevated CD164 expression is associated with aggressive metastasis, advanced stages, and shorter overall survival in lung cancer. However, no data are available regarding the clinical significance of CD164 expression in lung cancer. This study explores whether CD164 promotes tumor-initiation and drug resistance through the stem cell property...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902370/nano-let%C3%A2-7b-sensitization-of-eliminating-esophageal-cancer-stem%C3%A2-like-cells-is-dependent-on-blockade-of-wnt-activation-of-symmetric-division
#14
Yamei Pang, Jian Liu, Xiang Li, Yiwen Zhang, Boxiang Zhang, Jing Zhang, Ning Du, Chongwen Xu, Rui Liang, Hong Ren, Shou-Ching Tang, Xin Sun
The poor therapy response and poor prognosis of esophageal cancer has made it one of the most malignant carcinoma, and the complicated multidisciplinary treatment failed to achieve a long-term disease-free survival. To diagnose esophageal cancer at an earlier stage, and to improve the effect of anticancer therapy would improve the therapeutic efficacy. After retrospective analysis of the cancer samples of patients who received esophagectomy, we found the relevance between ratio of either ALDH1 or CD133-positive cancer stem cells and 2-year recurrence...
October 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28901439/long-noncoding-rna%C3%A2-p21-modulates-cellular-senescence-via-the-wnt-%C3%AE-%C3%A2-catenin-signaling-pathway-in-mesenchymal-stem-cells
#15
Wenzheng Xia, Lei Zhuang, Xia Deng, Meng Hou
Mesenchymal stem cell (MSC)‑based therapies have demonstrated efficacy in animal models of cardiovascular diseases. However, MSCs decrease in quantity and quality with age, which reduces their capacity for damage repair. Long noncoding (lnc) RNAs regulate gene transcription and the fate of post‑transcriptional mRNA, affecting a broad range of age‑associated physiological and pathological conditions, including cardiovascular disease and cancer cell senescence. However, the functional role of lncRNAs in stem cell senescence remains largely unknown...
September 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28901390/microrna-132-induces-temozolomide-resistance-and-promotes-the-formation-of-cancer-stem-cell-phenotypes-by-targeting-tumor-suppressor-candidate%C3%A2-3-in-glioblastoma
#16
Zhen-Xiu Cheng, Wen-Bo Yin, Zhong-Yu Wang
The prognosis of patients suffering from glioblastoma [also referred to as glioblastoma multiforme (GBM)] is dismal despite multimodal therapy. Chemotherapy with temozolomide may suppress tumor growth for a certain period of time (a few months); however, invariable tumor recurrence suggests that glioblastoma initiating cells (GICs) render these tumors persistant. Thus, the understanding of the molecular mechanisms of action of GICs as regards their role in the progression of GBM is important as such knowledge will be helpful in the discovery of novel drug targets, as well as in the design of novel therapeutic strategies for more effective treatment of the disease...
September 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28895920/emt-and-treatment-resistance-in-pancreatic-cancer
#17
REVIEW
Nicola Gaianigo, Davide Melisi, Carmine Carbone
Pancreatic cancer (PC) is the third leading cause of adult cancer mortality in the United States. The poor prognosis for patients with PC is mainly due to its aggressive course, the limited efficacy of active systemic treatments, and a metastatic behavior, demonstrated throughout the evolution of the disease. On average, 80% of patients with PC are diagnosed with metastatic disease, and the half of those who undergo surgery and adjuvant therapy develop liver metastasis within two years. Metastatic dissemination is an early event in PC and is mainly attributed to an evolutionary biological process called epithelial-to-mesenchymal transition (EMT)...
September 12, 2017: Cancers
https://www.readbyqxmd.com/read/28895566/wnt-signalling-in-prostate-cancer
#18
REVIEW
Virginia Murillo-Garzón, Robert Kypta
Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours - particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion...
September 12, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28895435/intranasal-delivery-of-stem-cell-based-therapies-for-the-treatment-of-brain-malignancies
#19
Gina Li, Nicolas Bonamici, Mahua Dey, Maciej S Lesniak, Irina V Balyasnikova
Glioblastoma (GBM) is the most aggressive malignant brain cancer in adults, and its poor prognosis and resistance to the existing standard of care require the development of innovative therapeutic modalities. The local delivery of stem cells as therapeutic carriers against glioma has produced encouraging results, but encounters obstacles with regards to the repeatability and invasiveness of administration. Intranasal delivery of therapeutic stem cells could overcome these obstacles, among others, as a noninvasive and easily repeatable mode of administration...
September 12, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28895404/exosomes-of-human-mesenchymal-stem-stromal-medicinal-signaling-cells-a-review
#20
U Altanerova, J Jakubechova, V Repiska, C Altaner
In this review, we intend to explore the potential therapeutic effects of exosomes released from mesenchymal stem/stromal cells (MSCs). MSCs gained credibility as a therapeutic tool due to their potential to differentiate into many cell types like osteoblasts, chondrocytes, adipocytes, muscular, endothelial, cardiovascular, and neurogenic cells. They possess potent wound healing activity due to their immunosuppressive and anti-inflammatory properties. MSCs are tested in large number of clinical trials for treatment of diseases, which do not have adequate therapy at present...
September 12, 2017: Neoplasma
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