Скачать с ютуб Epigenetic reprogramming: A new frontier of cancer therapy в хорошем качестве

Epigenetic reprogramming: A new frontier of cancer therapy

Reprogramming of a melanoma genome by nuclear transplantation. Hochedlinger K, Blelloch R, Brennan C, Yamada Y, Kim M, Chin L, Jaenisch R. Genes Dev. 2004 Aug 1;18(15):1875-85. doi: 10.1101/gad.1213504. OTHER VIDEOS YOU MIGHT LIKE: • The Ames Test: How Bruce Ames used bacteria to solve the mystery of the murderous mutagens -    • The Ames Test: How Bruce Ames used ba...   • The “scientific catastrophe” that made DNA boring - Chargaff versus the Tetranucleotide Hypothesis -    • The “scientific catastrophe” that mad...   • How scientists cracked the mystery of Mendel’s pea flower colour -    • How scientists cracked the mystery of...   Cancer are diseases characterised by the rapid proliferation of abnormal cells. As cancer cells spread throughout the body, they render the affected body parts dysfunctional. While the abnormal proliferation of cancer is usually attributed to genetic mutations, epigenetic modifications are also responsible. Epigenetic changes regulate gene expression without changing the DNA base pairs themselves. This can involve addition of acetyl or methyl groups to either DNA or the histone proteins they are wrapped around, which changes the accessibility of a gene to transcription factors, making it more or less likely to be expressed. In cancerous cells, epigenetic changes suppress tumour suppressor genes and increase oncogene expression. In 2002, Hochedlinger and colleagues discovered that nuclear transplantation of terminally differentiated cell nuclei into oocytes had the potential to reset epigenetic modifications, leaving the genome unaltered. In 2004, they investigated whether this process could be used on cancer cells to reprogram epigenetic changes responsible for cancer phenotypes and revert the cells back into pluripotent stem cells. In their study, Hochedlinger and colleagues transplanted melanoma nuclei into blastocysts and allowed them to develop into stem cells. They then injected these cells’ nucleus into Rag2 deficient blastocysts. Once the blastocysts had matured, their genotypes and phenotypes were analysed. Using FACS analysis with specific B/T-cell markers, it was found that the grown mice had B and T cells, unlike normal Rag2 deficient mice. It was concluded that the immune cells were created by the transformed cancer cells becoming pluripotent and differentiating into them. This, along with the mice lacking the cancerous phenotype, led to the conclusion that the nuclear transplantation had successfully reprogrammed the cancer cells’ epigenetics. These conclusions have since provided a strong foundation for the development of epigenetic cancer immunotherapies. However, a task for future researchers is to tackle the lack of efficiency and selectiveness of this method in order to develop a feasible treatment for cancer. Creator: Jay Ong References: Hochedlinger K, Blelloch R, Brennan C, Yamada Y, Kim M, Chin L, Jaenisch R. Reprogramming of a melanoma genome by nuclear transplantation. Genes Dev. 2004;18(15):1875-1885. Needham J. Embryonic development and induction. Nature 1939;143:44–45. Wakayama T, Yanagimachi R. Mouse cloning with nucleus donor cells of different age and type. Mol Reprod Dev. 2001;58(4):376-383. Hochedlinger K, Jaenisch R. Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. N Engl J Med. 2003;349(3):275-286. Carlson DL, Sauerbier W, Rollins-Smith LA, McKinnell RG. Fate of herpesvirus DNA in embryos and tadpoles cloned from Lucké renal carcinoma nuclei. J Comp Pathol. 1994;111(2):197-204. Corominas-Faja B, Cufí S, Oliveras-Ferraros C, Cuyàs E, López-Bonet E, Lupu R, Alarcón T, Vellon L, Iglesias JM, Leis O, Martín ÁG, Vazquez-Martin A, Menendez JA. Nuclear reprogramming of luminal-like breast cancer cells generates Sox2-overexpressing cancer stem-like cellular states harboring transcriptional activation of the mTOR pathway. Cell Cycle. 2013;12(18):3109-3124. Iskender B, Izgi K, Canatan H. Reprogramming bladder cancer cells for studying cancer initiation and progression. Tumour Biol. 2016;37(10):13237-13245. Zimmermannova O, Caiado I, Ferreira AG, Pereira CF. Cell Fate Reprogramming in the Era of Cancer Immunotherapy. Front Immunol. 2021;12:714822. Matoba S, Zhang Y. Somatic cell nuclear transfer reprogramming: Mechanisms and applications. Cell Stem Cell. 2018;23(4):471-485. Simmet K, Wolf E, Zakhartchenko V. Manipulating the epigenome in nuclear transfer cloning: Where, when and how. Int J Mol Sci. 2020;22(1):236.