Exosomes for cancer therapy by Inês Baptista https://padlet.com/igbaptista1/3wzidxrg4amypjw7 Genome Biology | Inês Baptista (94403), Laura Gonçalves, Maurizia Difenza, Miguel Correia (94396), Moslem Malekshiri en-us 2022-04-09 10:12:18 UTC 2022-04-18 19:16:16 UTC hello@padlet.com https://padlet.net/icons/png/1f9ec.png (9) igbaptista1 https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2138247422
  • miRNA as therapeutic agents: EVs-mediated miRNA replacement therapy 

    • miRNA as therapeutic target: EV-mediated miRNA inhibition therapy 
    ]]>     2022-04-10 20:32:59 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2138247422     Introduction (1) igbaptista1 https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2138253536 1. COMPREHENSIVENESS: Build a comprehensive dataset on proteins and genomic sequences involved in exosome formation for cancer therapy.
    2. SCALE: The genomic scale is an aspect of functional genomics which in the case of cancer takes into account the multifactoriality of the disease state. To obtain large-scale data, use computational analyzes and databases. The programs responsible for these comparisons are based on sequence alignment algorithms and involve the comparison of the sequence of interest with those present in the databases, the function of which is known.
    3. TECHNOLOGY DEVELOPMENT: The study of exosomes in cancer therapy requires modern technologies to maintain high standards. State-of-the-art techniques are needed: extraction and identification of nucleic acids, gene manipulation, immunibiology, pathophysiology, etc.
    4. RAPID DATA RELEASE: Large-scale data must be a common resource that can be easily consulted, so there are also databases for exosomes. Example: http://www.exocarta.org/
    5. SOCIAL AND ETHICAL IMPLICATION: The study of therapies for human cancer necessarily requires previous steps of experimentation on animals, after also on humans. This creates ethical and social conflicts.]]>     2022-04-10 20:43:34 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2138253536     Exosomes as miRNA carrier for cancer therapy (8) igbaptista1 https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2138268983 microRNAs  
    • endogenous, small, non-coding RNAs
    • important roles in regulating gene expression
    • act as either tumor supressors or oncogenes
    • assist in the promotion or suppression of cancer growth
    ]]>     2022-04-10 21:12:03 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2138268983     Example (10) igbaptista1 https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2138288699 Exosomes enriched with the anti-glioma miRNA can suppress glioma growth in vitro and reduce remarkably glioma xenograft growth in rats.]]> 2022-04-10 21:48:56 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2138288699 Exosomes as a Drug Delivery System in Cancer Therapy (11) mmalekshiri https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2143758361 . exosomes potential in drug carriers

    . biogenesis of exosomes

    . key points in exosomes as drug delivery systems     ]]>     2022-04-14 11:32:06 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2143758361     Exosome-Based Drug Delivery Systems (12) mmalekshiri https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2143775035 . different loading strategies into exosomes 
    . direct loading
    . indirect parental cells     ]]>     2022-04-14 11:55:41 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2143775035     MSCs-Derived Exosomes as Drug Carriers (13) mmalekshiri https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2144265207  . Application of MSCs-Derived Exosomes as Drug Carrier ]]> 2022-04-14 19:08:35 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2144265207 Example (14) mmalekshiri https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2144378212 2022-04-14 21:50:31 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2144378212 Naturally derived exosomes for cancer therapy (2) miguelcorreia311 https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145154634 2022-04-15 20:19:22 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145154634 Dendritic cells and their exosomes (3) miguelcorreia311 https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145163479 - Dendritic cells (DC) act as the initial link between oncogenesis and the host's immune system.
    -The exosomes secreted by DC are called Dex and are nano-vesicles that have a size between 30-100 nm.
    -Dex contain many bioactive fillers, responsible for the presentation of antigens, being ideal for the treatment of cancer.
    -The clinical progress of cancer therapies involving DC and DEX is still in its infancy.]]>     2022-04-15 20:41:08 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145163479     Differences and Advantages of Dex therapy over CD therapy (4) miguelcorreia311 https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145173806 Advantages:
    -Exosomes have immunostimulatory characteristics identical to DC.
    -Due to the stable nature of their membranes, Dex are able to be stored at low temperatures for at least 6 months without losing their main characteristics.
    -Dex is also easier to produce and can be replicated in vivo without major problems.
    -Treatment using Dex is more resistant to immunomodulatory events that usually occur in tumors.]]>     2022-04-15 21:05:29 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145173806     Composition of Dex (5) miguelcorreia311 https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145183837 -MHC-I and MHC-II molecules
    -α and β integrin chains (αMβ2)
    -member of the ICAM-1 immunoglobulin family
    -EGF factor 8 milk fat globule (MFG-E8)
    -family of tetraspanin proteins, including CD9, CD63, and CD81
    - cytosolic proteins derived from the donor DC
    -mRNA and small RNA molecules (including miR)

    ]]>     2022-04-15 21:31:47 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145183837     Ways of acting of Dex in cancer therapy (6) miguelcorreia311 https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145184755 2022-04-15 21:33:58 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145184755 Bibliography miguelcorreia311 https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145186822
  • Munich, Stephan, Andrea Sobo-Vujanovic, William J. Buchser, Donna Beer-Stolz, and Nikola L. Vujanovic. 2012. “Dendritic Cell Exosomes Directly Kill Tumor Cells and Activate Natural Killer Cells via TNF Superfamily Ligands.” OncoImmunology 1 (7): 1074–83. https://doi.org/10.4161/onci.20897.
  • Pitt, Jonathan M., Fabrice André, Sebastian Amigorena, Jean Charles Soria, Alexander Eggermont, Guido Kroemer, and Laurence Zitvogel. 2016. “Dendritic Cell-Derived Exosomes for Cancer Therapy.” Journal of Clinical Investigation 126 (4): 1224–32. https://doi.org/10.1172/JCI81137.
  • Schulze, Alex Von, and Fengyan Deng. 2020. “A Review on Exosome-Based Cancer Therapy.” Journal of Cancer Metastasis and Treatment 2020. https://doi.org/10.20517/2394-4722.2020.79.
  •  Nicolini, A.; Ferrari, P.; Biava, P.M. Exosomes and Cell Communication: From Tumour-Derived Exosomes and Their Role in Tumour Progression to the Use of Exosomal Cargo for Cancer Treatment. Cancers 2021, 13, 822. https://doi.org/10.3390/cancers13040822
  • Li J, Chen J, Wang S, Li P, Zheng C, Zhou X, Tao Y, Chen X, Sun L, Wang A, Cao K, Tang S, Zhou J. Blockage of transferred exosome-shuttled miR-494 inhibits melanoma growth and metastasis. J Cell Physiol. 2019 Feb 5. Epub ahead of print. PMID: 30723916. doi: 10.1002/jcp.28234. 
  • Christianson HC, Svensson KJ, van Kuppevelt TH, Li JP, Belting M. Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc Natl Acad Sci U S A. 2013;110(43):17380-17385. doi:10.1073/pnas.1304266110
  • Kibria, G.; Ramos, E.K.; Wan, Y.; Gius, D.R.; Liu, H. Exosomes as a Drug Delivery System in Cancer Therapy: Potential and Challenges. Mol. Pharm. 2018, 15, 3625–3633. https://doi.org/10.1021/acs.molpharmaceut.8b00277 
  • Gowda R, Robertson BM, Iyer S, et al. The role of exosomes in metastasis and progression of melanoma. Cancer Treat Rev. 2020;85: 101975.https://doi.org/10.1016/j.ctrv.2020.101975 
  • Ortega, A., Martinez-Arroyo, O., Forner, M. J., and Cortes, R. (2020). Exosomes as Drug Delivery Systems: Endogenous Nanovehicles for Treatment of Systemic Lupus                    Erythematosus. Pharmaceutics 13 (1), 3. https://doi.org/10.3390/pharmaceutics13010003
  • Ferreira, D.; Moreira, J.N.; Rodrigues, L.R. "New advances in exosome-based targeted drug delivery systems". Critical Reviews in Oncology/Hematology 172 (2022): 103628. http://dx.doi.org/10.1016/j.critrevonc.2022.103628
  • Chen L, Wang L, Zhu L, Xu Z, Liu Y, Li Z, Zhou J and Luo F (2022) Exosomes as Drug Carriers in Anti-Cancer Therapy. Front. Cell Dev. Biol. 10:728616. https://doi.org/10.3389/fcell.2022.728616
  • von Schulze, A., & Deng, F. (2020). A review on exosome-based cancer therapy. Journal of Cancer Metastasis and Treatment, 2020. https://doi.org/10.20517/2394-4722.2020.79
  • di Rocco, G., Baldari, S., & Toietta, G. (2017). Exosomes and other extracellular vesicles-mediated microRNA delivery for cancer therapy. In Translational Cancer Research (Vol. 6, pp. S1321–S1330). AME Publishing Company. https://doi.org/10.21037/tcr.2017.09.29
  • Hannafon, B. N., & Ding, W. Q. (2013). Intercellular communication by exosome-derived microRNAs in cancer. In International Journal of Molecular Sciences (Vol. 14, Issue 7, pp. 14240–14269). https://doi.org/10.3390/ijms140714240
    • ]]>     2022-04-15 21:39:32 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145186822     Interfering with cancer cell-derived exosomes for cancer therapy (7) mauriziadifenza https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145942277 There are a number of chemical messengers that help the progression of tumors. It can interfere in several ways:
    1- Inhibit the synthesis of cancer cell-derived exosomes (Rab27a)
    2- Inhibit the release of cancer cell-derived exosomes (miR-494)
    3- Inhibit the absorption of exosomes by tumor cells and destined for surrounding cells (Hemofiltration and HS)]]>     2022-04-17 10:42:45 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2145942277     Exosomes as protein carrier for cancer therapy (15) lauragoncalves4 https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2146258528 Exosomes

    TRAIL (TNF-alpha-related-apoptosis-inducing-ligand)-armed exosomes
    Effects:
    ·    promote apoptosis in cancer cells
    ·    control tumor progression in vivo

    IL-18 enriched exosomes
    Effects:
    ·  enhance Th1 cytokine release
    ·  proliferation of peripheral blood mononuclear cells

    What gives them the capability to induce more specific anti-tumor immunity as they trigger a bigger immune response

    IL-2 enriched exosomes
    Effects:
    ·  induce the antigen-specific Th1-polarized immune response
    ·  cytotoxic T lymphocyte response more efficiently

    This leads to a significant inhibition of tumor growth in mice.

    ]]>     2022-04-17 22:22:37 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2146258528     (16) lauragoncalves4 https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2147364133 Exosomes can also be used as carriers of protein antagonists
    Exemple:
    Exosomes carrying SIRPα ( signal regulatory protein that  can interact with CD47, a  signal that limits the ability of macrophages to engulf tumor cells α) antagonists could significantly increase tumor phagocytosis]]>     2022-04-18 18:27:52 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2147364133     Future perspectives and challenges of exosomes as drug carriers in cancer therapy mmalekshiri https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2147367696 . Correct selection of the cell of the origin for targeting

    . Transport drug to tumor tissue with high specificity and increasing the efficiency of the carried drugs

    . More preclinical studies in cancer models are required

    . Promising results in tumors expressing the MDR phenotype

    . Overcome challenges before scale-up development, translation into the clinic and their application in cancer therapy 
    ]]>     2022-04-18 18:30:32 UTC https://padlet.com/igbaptista1/3wzidxrg4amypjw7/wish/2147367696