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Molecular and Cellular Therapies

Maja Thim Larsen, Matthias Kuhlmann, Michael Lykke Hvam, Kenneth A Howard
The effectiveness of a drug is dependent on accumulation at the site of action at therapeutic levels, however, challenges such as rapid renal clearance, degradation or non-specific accumulation requires drug delivery enabling technologies. Albumin is a natural transport protein with multiple ligand binding sites, cellular receptor engagement, and a long circulatory half-life due to interaction with the recycling neonatal Fc receptor. Exploitation of these properties promotes albumin as an attractive candidate for half-life extension and targeted intracellular delivery of drugs attached by covalent conjugation, genetic fusions, association or ligand-mediated association...
2016: Molecular and Cellular Therapies
Lilian Enriquez-Barreto, Miguel Morales
This review is focused in PI3K's involvement in two widespread mental disorders: Autism and Schizophrenia. A large body of evidence points to synaptic dysfunction as a cause of these diseases, either during the initial phases of brain synaptic circuit's development or later modulating synaptic function and plasticity. Autism related disorders and Schizophrenia are complex genetic conditions in which the identification of gene markers has proved difficult, although the existence of single-gene mutations with a high prevalence in both diseases offers insight into the role of the PI3K signaling pathway...
2016: Molecular and Cellular Therapies
Rikke Bech, Babak Jalilian, Ralf Agger, Lars Iversen, Mogens Erlandsen, Kristian Otkjaer, Claus Johansen, Søren R Paludan, Carina A Rosenberg, Knud Kragballe, Thomas Vorup-Jensen
BACKGROUND: Psoriasis is an inflammatory disease characterized by leukocyte skin infiltration. Interestingly, recent works suggest that the migration of dendritic cells (DCs) is abnormal in psoriatic skin. DCs have significant role in regulating the function of T lymphocytes, at least in part influenced by the local environment of cytokines. In psoriatic skin lesions the expression of IL-20 is highly up-regulated. It is unclear if this cytokine has any influence on DCs. METHODS: Here, we investigated the influence of IL-20 in monocyte-derived dendritic cell (MDDCs) in vitro...
2016: Molecular and Cellular Therapies
Brigitte Bisaro, Giorgia Mandili, Alice Poli, Andrea Piolatto, Valentina Papa, Francesco Novelli, Giovanna Cenacchi, Marco Forni, Cristina Zanini
BACKGROUND: Medulloblastoma (MB) is the most common malignant childhood brain tumor with the propensity to disseminate at an early stage, and is associated with high morbidity. New treatment strategies are needed to improve cure rates and to reduce life-long cognitive and functional deficits associated with current therapies. Extracellular Vesicles (EVs) are important players in cell-to-cell communication in health and diseases. A clearer understanding of cell-to-cell communication in tumors can be achieved by studying EV secretion in medullospheres...
2015: Molecular and Cellular Therapies
Liqin Ban, Willem Kuhtreiber, John Butterworth, Yoshiaki Okubo, Éva S Vanamee, Denise L Faustman
BACKGROUND: Soluble TNF superfamily (TNFSF) ligands are less stable and less active than their transmembrane (tm) analogues. This is a problem for the therapeutic use of recombinant TNFSF ligands in diverse diseases including cancer and autoimmunity. Creating TNFSF ligand analogues with improved targeting of their respective receptors is important for research and therapeutic purposes. FINDINGS: Covalent internal cross-linking of TNF monomers by double mutations, S95C/G148C, results in stable trimers with improved TNFR2 function...
2015: Molecular and Cellular Therapies
Ehud Klein, Ron Shapiro, Jose Ben-Dahan, Moshe Simcha, Yosef Azuri, Ada Rosen
BACKGROUND: Hemorrhoids are a common disorder that affects the quality of life of millions of people worldwide. The effectiveness of OTC medication is limited and they mainly provide symptomatic relief. In order to treat this ailment, we formulated PP110 Gel and Wipes, as a novel treatment for hemorrhoids. PP110 is based on known active ingredients with a topical film-forming agent designed to provide physical protection and prolonged tissue contact with the active ingredients. METHODS: PP110 Gel, PP110 Wipes and the comparator Preparation-H® were used on three patient cohorts...
2015: Molecular and Cellular Therapies
Roshan Fatima, Vijay Suresh Akhade, Debosree Pal, Satyanarayana Mr Rao
Long noncoding RNAs are emerging as key players in various fundamental biological processes. We highlight the varied molecular mechanisms by which lncRNAs modulate gene expression in diverse cellular contexts and their role in early mammalian development in this review. Furthermore, it is being increasingly recognized that altered expression of lncRNAs is specifically associated with tumorigenesis, tumor progression and metastasis. We discuss various lncRNAs implicated in different cancer types with a focus on their clinical applications as potential biomarkers and therapeutic targets in the pathology of diverse cancers...
2015: Molecular and Cellular Therapies
Fatemeh Pourrajab, Mohammad Baghi Yazdi, Mojtaba Babaei Zarch, Mohammadali Babaei Zarch, Seyedhossein Hekmatimoghaddam
Toll-like receptor family (TLRs), pattern recognition receptors, is expressed not only on immune cells but also on non-immune cells, including cardiomyocytes, fibroblasts, and vascular endothelial cells. One main function of TLRs in the non-immune system is to regulate apoptosis. TLRs are the central mediators in hepatic, pulmonary, brain, and renal ischemic/reperfusion (I/R) injury. Up-regulation of TLRs and their ligation by either exogenous or endogenous danger signals plays critical roles in ischemia/reperfusion-induced tissue damage...
2015: Molecular and Cellular Therapies
Jasmine L Hamilton, Jayachandran N Kizhakkedathu
Desferrioxamine (DFO), deferiprone (L1) and desferasirox (ICL-670) are clinically approved iron chelators used to treat secondary iron overload. Although iron chelators have been utilized since the 1960s and there has been much improvement in available therapy, there is still the need for new drug candidates due to limited long-term efficacy and drug toxicity. Moreover, all currently approved iron chelators are of low molecular weight (MW) (<600 Da) and the objectives reported for the "ideal" chelator of low MW, including possessing the ability to promote iron excretion without causing toxic side effects, has proven difficult to realize in practice...
2015: Molecular and Cellular Therapies
Lars Fransecky, Liliana H Mochmann, Claudia D Baldus
Technological advances allowing high throughput analyses across numerous cancer tissues have allowed much progress in understanding complex cellular signaling. In the future, the genetic landscape in cancer may have more clinical relevance than diagnosis based on tumor origin. This progress has emphasized PI3K/AKT/mTOR, among others, as a central signaling center of cancer development due to its governing control in cellular growth, survival, and metabolism. The discovery of high frequencies of mutations in the PI3K/AKT/mTOR pathway in different cancer entities has sparked interest to inhibit elements of this pathway...
2015: Molecular and Cellular Therapies
Maria Vittoria Enzo, Marco Rastrelli, Carlo Riccardo Rossi, Uros Hladnik, Daniela Segat
The canonical Wnt signaling pathway is involved in a variety of biological processes like cell proliferation, cell polarity, and cell fate determination. This pathway has been extensively investigated as its deregulation is linked to different diseases, including various types of cancer, skeletal defects, birth defect disorders (including neural tube defects), metabolic diseases, neurodegenerative disorders and several fibrotic diseases like desmoid tumors. In the "on state", beta-catenin, the key effector of Wnt signaling, enters the nucleus where it binds to the members of the TCF-LEF family of transcription factors and exerts its effect on gene transcription...
2015: Molecular and Cellular Therapies
Maged M Harraz, Jin-Chong Xu, Noah Guiberson, Ted M Dawson, Valina L Dawson
BACKGROUND: Small non-coding microRNA RNA molecules can regulate stem cell function. The role of microRNAs in neural stem/progenitor cells (NS/PCs) differentiation is not entirely clear. METHODS: MiRNA profiling, loss and gain of function studies coupled with dendritic tree development morphometric analysis and calcium influx imaging were utilized to investigate the role of micoRNA-223 in differentiating NS/PCs. RESULTS: MiRNA profiling in human NS/PCs before and after differentiation in vitro reveals modulation of miRNAs following differentiation of NS/PCs...
June 17, 2014: Molecular and Cellular Therapies
Marek Malecki, Emily Putzer, Chelsea Sabo, Afsoon Foorohar, Carol Quach, Chris Stampe, Michael Beauchaine, Raf Malecki, Xenia Tombokan, Mark Anderson
OBJECTIVE: Myocardial infarctions constitute a major factor contributing to non-natural mortality world-wide. Clinical trials of myocardial regenerative therapy, currently pursued by cardiac surgeons, involve administration of stem cells into the hearts of patients suffering from myocardial infarctions. Unfortunately, surgical acquisition of these cells from bone marrow or heart is traumatic, retention of these cells to sites of therapeutic interventions is low, and directed differentiation of these cells in situ into cardiomyocytes is difficult...
May 1, 2014: Molecular and Cellular Therapies
Nathan W Cummins, Amy M Sainski, Sekar Natesampillai, Gary D Bren, Andrew D Badley
BACKGROUND: HIV eradication strategies are now being evaluated in vitro and in vivo. A cornerstone of such approaches is maximal suppression of viral replication with combination antiretroviral therapy (ART). Since many antiretroviral agents have off target effects, and different classes target different components of the viral life cycle, we questioned whether different classes of ART might differentially affect the survival and persistence of productively HIV-infected CD4 T cells. METHODS: In vitro infections of primary CD4 T cells using clinical isolates of HIV-1 that were either protease inhibitor susceptible (HIV PI-S), or resistant (HIV PI-R) were treated with nothing, lopinavir, efavirenz or raltegravir...
2014: Molecular and Cellular Therapies
Noelle N Saillant, Carrie A Sims
A renewed understanding of Trauma Induced Coagulopathy (TIC) has implicated platelets as a crucial mediator and potential therapeutic target in hemostasis. While the importance of abnormal coagulation tests is well described in trauma, there is a paucity of data regarding the role of platelets in coagulopathy. New coagulation models, namely the cell-based-model of hemostasis, have refocused attention toward the platelet and endothelium as key regulators of clot formation. Although platelet dysfunction has been associated with worse outcomes in trauma, the mechanisms which platelet dysfunction contributes to coagulopathy are poorly understood...
2014: Molecular and Cellular Therapies
Sachiko Matsuzaki, Revaz Botchorishvili, Jean Luc Pouly, Michel Canis
Endometriosis is a chronic, estrogen-dependent disease associated with infertility and pelvic pain. Endometriosis is defined by the presence of extra-uterine endometrial tissue. It affects approximately 10% of reproductive-aged women. However, the underlying etiology, pathogenesis and pathophysiology remain to be fully elucidated. Knowledge of these factors is indispensable for the development of targeted therapies for prevention and treatment of endometriosis. Several studies, including those from our laboratory, have suggested that aberrant activation of the Wnt/β-catenin pathway may be involved in the pathophysiology of endometriosis...
2014: Molecular and Cellular Therapies
Christian Wiraja, David Yeo, Daniel Lio, Louai Labanieh, Mengrou Lu, Weian Zhao, Chenjie Xu
In fields such as cancer biology and regenerative medicine, obtaining information regarding cell bio-distribution, tropism, status, and other cellular functions are highly desired. Understanding cancer behaviors including metastasis is important for developing effective cancer treatments, while assessing the fate of therapeutic cells following implantation is critical to validate the efficacy and efficiency of the therapy. For visualization purposes with medical imaging modalities (e.g. magnetic resonance imaging), cells can be labeled with contrast agents (e...
2014: Molecular and Cellular Therapies
Mike-Andrew Westhoff, Georg Karpel-Massler, Oliver Brühl, Stefanie Enzenmüller, Katia La Ferla-Brühl, Markus D Siegelin, Lisa Nonnenmacher, Klaus-Michael Debatin
Members of the PI3K/Akt/mTor signaling cascade are among the most frequently altered proteins in cancer, yet the therapeutic application of pharmacological inhibitors of this signaling network, either as monotherapy or in combination therapy (CT) has so far not been particularly successful. In this review we will focus on the role of PI3K/Akt/mTOR in two distinct tumors, Glioblastoma multiforme (GBM), an adult brain tumor which frequently exhibits PTEN inactivation, and Neuroblastoma (NB), a childhood malignancy that affects the central nervous system and does not harbor any classic alterations in PI3K/Akt signaling...
2014: Molecular and Cellular Therapies
Simona Casarosa, Yuri Bozzi, Luciano Conti
Neural stem cells (NSCs) offer a unique and powerful tool for basic research and regenerative medicine. However, the challenges that scientists face in the comprehension of the biology and physiological function of these cells are still many. Deciphering NSCs fundamental biological aspects represents indeed a crucial step to control NSCs fate and functional integration following transplantation, and is essential for a safe and appropriate use of NSCs in injury/disease conditions. In this review, we focus on the biological properties of NSCs and discuss how these cells may be exploited to provide effective therapies for neurological disorders...
2014: Molecular and Cellular Therapies
Morten F Ebbesen, Konrad Bienk, Bent W Deleuran, Kenneth A Howard
BACKGROUND: We recently synthesized a hydrophilic polymer, poly(N-(2-hydroxypropyl)methacrylamide-co-N-(3-azidopropyl)methacrylamide), p(HPMA-co-AzMA), by RAFT polymerization using a novel azide-containing methacrylamide monomer that through a post modification strategy using click chemistry enabled facile preparation of a panel of versatile and well-defined bioconjugates. In this work we screen a panel of different molecular weight (Mw) fluorescently tagged p(HPMA-co-AzMA) in healthy mice, by live bioimaging, to select an extended circulatory half-life material for investigating joint accumulation in a murine collagen antibody-induced arthritis model...
2014: Molecular and Cellular Therapies
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