Molecular and cellular therapies最新文献

{"title":"Albumin-based drug delivery: harnessing nature to cure disease","authors":"M. Larsen, M. Kuhlmann, M. L. Hvam, K. Howard","doi":"10.1186/s40591-016-0048-8","DOIUrl":"https://doi.org/10.1186/s40591-016-0048-8","url":null,"abstract":"","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40591-016-0048-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65709364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Albumin-based drug delivery: harnessing nature to cure disease.","authors":"Maja Thim Larsen, Matthias Kuhlmann, Michael Lykke Hvam, Kenneth A Howard","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>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. This review will give an overview of albumin-based products with focus on the natural biological properties and molecular interactions that can be harnessed for the design of a next-generation drug delivery platform. </p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"4 ","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2016-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138048981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PI3K signaling pathway as a pharmacological target in Autism related disorders and Schizophrenia.","authors":"Lilian Enriquez-Barreto, Miguel Morales","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>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. In the brain, components of the PI3K pathway regulate synaptic formation and plasticity; thus, disruption of this pathway leads to synapse dysfunction and pathological behaviors. Here, we recapitulate recent evidences that demonstrate the imbalance of several PI3K elements as leading causes of Autism and Schizophrenia, together with the plausible new pharmacological paths targeting this signaling pathway. </p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"4 ","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2016-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138048983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PI3K signaling pathway as a pharmacological target in Autism related disorders and Schizophrenia","authors":"Lilian Enriquez-Barreto, M. Morales","doi":"10.1186/s40591-016-0047-9","DOIUrl":"https://doi.org/10.1186/s40591-016-0047-9","url":null,"abstract":"","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40591-016-0047-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65709349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin 20 regulates dendritic cell migration and expression of co-stimulatory molecules.","authors":"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","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Here, we investigated the influence of IL-20 in monocyte-derived dendritic cell (MDDCs) in vitro. This work addressed IL-20 effects on DC maturation, receptor expression and signaling. By use of extra cellular matrix components mimicking the skin environment, we also studied the functional effects of IL-20 on the chemotactic migration of DCs. Based on the recent finding that CD18 integrin are shed during migration of myeloid leukocytes, the concentration of these adhesion molecules was measured in MDDCs culture supernatants post migration.</p><p><strong>Results: </strong>Following stimulation with IL-20, immature human MDDCs enhanced the expression of the co-stimulatory molecule CD86, further enabling activation of the p38 MAPK, but not the STAT3, pathway. IL-20 increased the migration of MDDCs in a biphasic response narrowly controlled by the interleukin concentration. A concomitant change in the shedding of CD18 integrins suggested that these adhesion molecules play a role in the migration of the MDDCs through the extracellular matrix layer.</p><p><strong>Conclusion: </strong>Taken together, our findings points to a possible, yet subtle, role of IL-20 in DCs migration. The biphasic response suggests that the aberrant IL-20 expression in psoriasis impedes DC migration, which could be a part of the processes that precipitates the dysregulated inflammatory response associated with this disease.</p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"4 ","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2016-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138048982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin 20 regulates dendritic cell migration and expression of co-stimulatory molecules","authors":"R. Bech, B. Jalilian, R. Agger, L. Iversen, M. Erlandsen, K. Otkjaer, C. Johansen, S. Paludan, C. Rosenberg, K. Kragballe, T. Vorup-Jensen","doi":"10.1186/s40591-016-0046-x","DOIUrl":"https://doi.org/10.1186/s40591-016-0046-x","url":null,"abstract":"","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40591-016-0046-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65709311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic analysis of extracellular vesicles from medullospheres reveals a role for iron in the cancer progression of medulloblastoma.","authors":"Brigitte Bisaro, Giorgia Mandili, Alice Poli, Andrea Piolatto, Valentina Papa, Francesco Novelli, Giovanna Cenacchi, Marco Forni, Cristina Zanini","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>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. This can reveal subtle modifications induced by the passage from adherent to non-adherent growth, as spheres may account for the adaptation of tumor cells to the mutated environment.</p><p><strong>Methods: </strong>Formation of medullospheres from MB cell lines stabilized in adherent conditions was obtained through culture conditioning based on low attachment flasks and specialized medium. EVs collected by ultracentrifugation, in adherent conditions and as spheres, were subjected to electron microscopy, NanoSight measurements and proteomics.</p><p><strong>Results: </strong>Interestingly, iron carrier proteins were only found in EVs shed by CSC-enriched tumor cell population of spheres. We used iron chelators when culturing MB cell lines as spheres. Iron chelators induced a decrease in number/size of spheres and in stem cell populations able to initiate in vitro spheres formation.</p><p><strong>Conclusions: </strong>This work suggests a not yet identified role of iron metabolism in MB progression and invasion and opens the possibility to use chelators as adjuvants in anti-tumoral chemotherapy.</p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"3 ","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2015-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34255022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategic internal covalent cross-linking of TNF produces a stable TNF trimer with improved TNFR2 signaling.","authors":"Liqin Ban, Willem Kuhtreiber, John Butterworth, Yoshiaki Okubo, Éva S Vanamee, Denise L Faustman","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Findings: </strong>Covalent internal cross-linking of TNF monomers by double mutations, S95C/G148C, results in stable trimers with improved TNFR2 function. The resulting mutein induced the selective death of autoreactive CD8 T cells in type-1 diabetic patients and demonstrates targeted proliferation and expansion of human CD4 Tregs.</p><p><strong>Conclusions: </strong>Stable TNF trimers, created by internal covalent cross-linking, show improved signaling. The high structural homology within the TNF superfamily provides an opportunity to extend internal cross-linking to other TNF superfamily proteins to produce active trimers with improved stability and receptor signaling, and with potential applications for cancer, autoimmunity, infections, and transplantation.</p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"3 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2015-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34086229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prospective, randomized, three arm, open label study comparing the safety and efficacy of PP110, a novel treatment for hemorrhoids to preparation-H® maximum strength cream in the treatment of grade 2-3 hemorrhoids.","authors":"Ehud Klein, Ron Shapiro, Jose Ben-Dahan, Moshe Simcha, Yosef Azuri, Ada Rosen","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>PP110 Gel, PP110 Wipes and the comparator Preparation-H® were used on three patient cohorts. Treatment was administered once daily for PP110, and three-four times daily for Preparation-H®, for 14 days. Six different clinical parameters relating to common symptoms of hemorrhoids were monitored.</p><p><strong>Results: </strong>PP110 Gel was significantly better than Preparation-H® in reducing bleeding (Δ = 6 %), providing pain relief (Δ = 10 %) and controlling itching (Δ = 11 %). These three parameters are considered as the most common distressing symptoms for hemorrhoids patients, demonstrating that PP110 is superior to conventional treatment.</p><p><strong>Conclusion: </strong>This study demonstrated the efficacy of the PP110 Gel in treating hemorrhoids and its superiority to conventional treatments. The PP110 film-based formulation provides a slow-release mechanism and as a consequence, a prolonged therapeutic window. PP110 was both more effective in reducing hemorrhoids symptoms and more convenient to use, in that it only required application once per day.</p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"3 ","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2015-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33919281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long noncoding RNAs in development and cancer: potential biomarkers and therapeutic targets.","authors":"Roshan Fatima, Vijay Suresh Akhade, Debosree Pal, Satyanarayana Mr Rao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>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. </p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"3 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2015-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33395657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}