Molecular and cellular therapies最新文献

{"title":"Retinoids Induced Cancer Stem Cell Differentiation and Apoptosis for Cancer Therapies","authors":"Xin Cao","doi":"10.13052/MCT2052-8426.711","DOIUrl":"https://doi.org/10.13052/MCT2052-8426.711","url":null,"abstract":"Retinoids show great potential in various kinds of cancer chemotherapy due to its ability to induce signals for cell differentiation or death, as well as inhibit cancer stem cell proliferation. This paper summarized the recent progress of retinoids induced cancer stem cell differentiation and apoptosis in cancer therapy field, with the highlighted novel retinoid named WYC-209 in our lab, which could inhibit the tumor stem cell and malignant melanoma tumors with high efficacy and little toxicity.","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46891233","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":"Understanding Hydrogen Sulfide in Inflammation: Opportunities and Challenges","authors":"M. Bhatia","doi":"10.13052/MCT2052-8426.712","DOIUrl":"https://doi.org/10.13052/MCT2052-8426.712","url":null,"abstract":"Inflammation is an adaptive response to injury, but uncontrolled inflammation can lead to tissue damage and disease. Research in our laboratory (since confirmed in different laboratories worldwide) has shown that hydrogen sulfide (H2S) acts as a mediator of inflammation in different disease conditions. Learning about a novel mediator of inflammation results in unique opportunities with which to approach inflammatory diseases. At the same time, the complexity of biological systems and translation of research from the bed to the bedside also presents challenges. This Editorial aims to discuss the opportunities and challenges in relation to the role of H2S in inflammation, and the future prospects for this research.","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49455595","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":"M. Larsen, M. Kuhlmann, M. L. Hvam, K. Howard","doi":"10.13052/S40591-016-0049-7","DOIUrl":"https://doi.org/10.13052/S40591-016-0049-7","url":null,"abstract":"Background: Medulloblastoma (MB) is the most common malignant childhood brain tumor with the propensity todisseminate at an early stage, and is associated with high morbidity. New treatment strategies are needed toimprove 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 clearerunderstanding of cell-to-cell communication in tumors can be achieved by studying EV secretion inmedullospheres. This can reveal subtle modifications induced by the passage from adherent to non-adherentgrowth, as spheres may account for the adaptation of tumor cells to the mutated environment.Methods: Formation of medullospheres from MB cell lines stabilized in adherent conditions was obtained throughculture 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 andproteomics.Results: Interestingly, iron carrier proteins were only found in EVs shed by CSC-enriched tumor cell population ofspheres. We used iron chelators when culturing MB cell lines as spheres. Iron chelators induced a decrease innumber/size of spheres and in stem cell populations able to initiate in vitro spheres formation.Conclusions: This work suggests a not yet identified role of iron metabolism in MB progression and invasion andopens the possibility to use chelators as adjuvants in anti-tumoral chemotherapy.","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42694278","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":"The role of mitochondria-targeted antioxidant MitoQ in neurodegenerative disease","authors":"Linlin Zhang, A. Reyes, Xiangdong Wang","doi":"10.26781/2052-8426-2018-01","DOIUrl":"https://doi.org/10.26781/2052-8426-2018-01","url":null,"abstract":"\u0000 \u0000Abstract: The discovery of charged molecules being able to cross the mitochondrial membrane has prompted many scholars to exploit this idea to find a way of preventing or slowing down aging. In this paper, we will focus on mitochondriatargeted antioxidants, which are cationic derivatives of plastoquinone, and in particular on the mitochondria-targeted antioxidant therapy of neurodegenerative diseases. It is well known that the accumulation of amyloid-β peptide (Aβ) in mitochondria and its related mitochondrial dysfunction are critical signatures of Alzheimer’ s disease (AD). In another neurodegenerative disease, Parkinson’s disease (PD), the loss of dopaminergic neurons in the substantia nigra and the production of Lewy bodies are among their pathological features. Pathogenesis of Parkinson’s disease and Alzheimer’s disease has been frequently linked to mitochondrial dysfunction and oxidative stress. Recent studies show that MitoQ, a mitochondria-targeted antioxidant, may possess therapeutic potential for Aβ-related and oxidative stress-associated neurodegenerative diseases, especially AD. Although MitoQ has been developed to the stage of clinical trials in PD, its true clinical effect still need further verification. This review aims to discuss the role of mitochondrial pathology in neurodegenerative diseases, as well as the recent development of mitochondrial targeted antioxidants as a potential treatment for these diseases by removing excess oxygen free radicals and inhibiting lipid peroxidation in order to improve mitochondrial function. \u0000 \u0000 \u0000 ","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46382230","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":"Assessment of efficacy of trastuzumab (Herceptin) comprising adjuvant therapy of HER2+ breast cancer patients determined based upon statistical analysis of overall survival (OS) and disease-free survival (PFS)","authors":"B. Jagielska, A. Czubek, K. Tałasiewicz, Adam Twarowski, P. Rutkowski, M. Krzakowski, Bianka Saetre, M. Małecki","doi":"10.26781/2052-8426-2018-02","DOIUrl":"https://doi.org/10.26781/2052-8426-2018-02","url":null,"abstract":"\u0000 \u0000Abstract: In patients suffering from breast cancer, adjuvant radiation, chemotherapy, or immunotherapy, which immediately follow the surgery as the first line therapy, greatly improve overall (OS) and disease-free survival (DFS). Various regimens of adjuvant therapy for these patients have been tested contingent upon the clinical staging. Inclusion of adjuvant immunotherapy is particularly promising. \u0000 \u0000 \u0000 ","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41748191","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":"HIV Universal Vaccine.","authors":"Marek Malecki, Bianka Saetre","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>For many deadly viruses, there are no preventive and / or therapeutic vaccines approved by health authorities World-wide (e.g., HIV, Ebola, Dengue, and many others). Although, for some viruses, prophylactic vaccines are very effective (e.g., HBV, and many others).In this realm, we design, manufacture, test, and streamline into the clinics novel viral universal vaccines (VUV). VUV have such unique features, that medical vaccination or natural infection induced immunity against some viruses (e.g., HBV) upon the VUV's administration to the infected with other, different viruses patients, is redirected against these other, newly infecting viruses (e.g., HIV).</p><p><strong>Specific aim: </strong>The specific aim of this work was biomolecular engineering of the HIV universal vaccine comprising the two main functional domains: CD4 or anti-gp120 - as the HIV tagging domain and HBsAg - as the immune response eliciting domain, so that upon its administration the HBV medical immunization or natural infection induced immunity would be redirected, accelerated, and amplified to fight the HIV infection.</p><p><strong>Healthy donors and patients: </strong>Per the Institutional Review Board approval and in compliance with the Declaration of Helsinki, all healthy donors and patients were presented with the Patients' Bill of Rights and provided Patient Informed Consent. All the procedures were pursued by the licensed medical doctors.</p><p><strong>Methods & results: </strong>We have biomolecularly engineered HIV universal vaccine (HIVUV) comprising human CD4 or anti-gp120 and HBsAg of HBV. By immunoblotting and magnetic activated molecular sorting, we have demonstrated high specificity of this vaccine in binding HIV. By flow cytometry and nuclear magnetic resonance, we have demonstrated high efficacy of these vaccines to engage HBV immunized patients' immune system against HIV. Administration of HIVUV to blood or lymph of the HIV+ patients resulted in rapid reduction of the HIV viremia down to undetectable. It also resulted in protection of populations of CD4+ cells against HIV caused decline.</p><p><strong>Conclusions: </strong>We have demonstrated the proof of concept for high efficacy of VUV, specifically HIVUV, in annihilating HIV. Nevertheless, the same compositions, processes, and methods, for persons skilled in biotechnology, pharmacogenomics, and molecular medicine, are adaptable for other deadly viral infections, which we vigorously pursue.</p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388684/pdf/nihms-966594.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37168671","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":"RIPK1 and RIPK3 – emerging targets in cancer?","authors":"K. Gurol, Suraj Shah, A. Degterev","doi":"10.26781/2052-8426-2018-03","DOIUrl":"https://doi.org/10.26781/2052-8426-2018-03","url":null,"abstract":"\u0000 \u0000Abstract: RIPK1 and RIPK3 are homologous Ser/Thr kinases, which act in concert within the necrosome complexes to initiate a sub-type of regulated necrosis, termed necroptosis. Necroptosis has gradually emerged as a highly clinically relevant form of necrosis, which can be targeted therapeutically. Besides necroptosis, RIPK1 and RIPK3 have been implicated in other pathophysiologically-relevant responses, including regulation of apoptosis and inflammation. More recently, it became evident that RIPK1/RIPK3 pathways may be systematically altered in cancers. Status of these pathways may provide a prognostic value, and therapeutic modulation of RIPK1/RIPK3 signaling may represent a new strategy against various forms of human cancer. \u0000 \u0000 \u0000 ","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46404553","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":"Effects of phosphoinositide 3-kinase inhibitor SHBM1009 on cancer cells proliferation","authors":"Lingyan Wang, Li‐Hao Huang, Q. Shen, Fangming Liu, Bijun Zhu, Duojiao Wu","doi":"10.26781/2052-8426-2018-04","DOIUrl":"https://doi.org/10.26781/2052-8426-2018-04","url":null,"abstract":"\u0000 \u0000Abstract: Phosphoinositide 3-kinase (PI3K) plays an important role in cellular proliferation and tumor progression. The objective of this study is to evaluate the potential mechanism and therapeutic effects of new PI3K inhibitor SHBM1009 on various cancer cells of digestive system on proliferation. \u0000 \u0000 \u0000 ","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46278419","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":"HIV Apheresis Tags (HIVAT) Aided Elimination of Viremia.","authors":"Marek Malecki, Bianka Saetre","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>HIV viremia is the essential element for progression of an initial HIV infection into AIDS and death. The currently approved management relies primarily on chemotherapy repressing the HIV replication in the infected CD4+ cells, although with severe systemic adverse effects. The problem is that it does not physically eliminate viruses, which then not only keep infecting healthy cells of these patients, but also promote infections of other people.</p><p><strong>Specific aim: </strong>An overall objective of our work is biomolecular engineering of virus apheresis tags (VAT) that eliminate viremias without adverse effects. The specific aim of this project was biomolecular engineering of Human Immunodeficiency Virus Apheresis Tags (HIVAT): CD4-Au-Fe₃O₄, CD4-SiO₂-Fe₃O₄, anti-gp120-Au-Fe₃O₄, and anti-gp120-SiO₂-Fe₃O₄.</p><p><strong>Healthy donors and patients: </strong>Per the Institutional Review Board's approval and in compliance with Declaration of Helsinki, healthy donors and patients were presented with Patient Bill of Rights and provided Patient Informed Consent, while all the procedures were pursued by the licensed physicians.</p><p><strong>Materials and methods: </strong>CD4, gp120, gp41, gp160, anti-gp120, p24 were transgenomically expressed. Superparamagnetic core-shell particles (SPM-CSP) were synthesized. SPM-CSP were used as the nucleation centers for assembling the expressed molecules upon them to create virus apheresis tags (VAT). VAT were injected into the blood or lymph acquired from the HIV+ and HBV+ patients followed by apheresis at 0.47 - 9.4 T. VAT efficacy in eliminating viremia was determined through immunoblots, NMR and q-RT-PCR.</p><p><strong>Results: </strong>Treatment of blood or lymph of the HIV+ patients' with VAT followed by virus apheresis resulted in rapid elimination of the HIV viremia. Efficacy of apheresis was contingent upon the gravity of viremia versus doses and regimens of VAT. Importantly, administration of VAT also effectively improved levels of non-infected CD4+ lymphocytes.</p><p><strong>Discussion / conclusions: </strong>Herein, we present the proof of concept for a new, effective treatment with virus apheresis tags (VAT), specifically Human Immunodeficiency Virus Apheresis Tags (HIVAT), of the HIV+ patients' blood and lymph, which is eliminating the HIV viremia.It can be easily adapted as treatments of viremias perpetrated by other deadly viruses, which we vigorously pursue.</p>","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438618/pdf/nihms-997766.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37107469","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":"Inhibitory effects of Actinidia Chinensis planch root extracts (acRoots) on human lung cancer cells through retinoic acid receptor beta","authors":"Lingyan Wang, Jiayun Hou, Lin Shi","doi":"10.26781/2052-8426-2017-02","DOIUrl":"https://doi.org/10.26781/2052-8426-2017-02","url":null,"abstract":"\u0000 \u0000Abstract: Actinidia Chinensis Planch roots (acRoots) are used to treat many cancers, although the antitumor mechanism by which acRoots inhibit cancer cell growth remains unclear. The present study aims at investigating inhibitory effects of acRoots on human lung cancer cells and potential mechanisms. Our data demonstrate that the inhibitory effects of acRoots on lung cancer cells depend on genetic backgrounds and phenotypes of cells. We furthermore found the expression of metabolism-associated gene profiles varied between acRoots-hypersensitive (H460) or hyposensitive lung cancer cells (H1299) after screening lung cancer cells with different genetic backgrounds. We selected retinoic acid receptor beta (RARB) as the core target within metabolism-associated core gene networks and evaluated RARB changes and roles in cells treated with acRoots at different concentrations and timeframes. Hypersensitive cancer cells with the deletion of RARB expression did not response to the treatment with acRoots, while RARB deletion did not change effects of acRoots on hyposensitive cells. Thus, it seems that RARB as the core target within metabolism-associated networks plays important roles in the regulation of lung cancer cell sensitivity to acRoots. \u0000 \u0000 \u0000 ","PeriodicalId":90271,"journal":{"name":"Molecular and cellular therapies","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41507646","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}