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The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in chromosome 22 of leukemia cancer cells. This chromosome is defective and unusually short because of reciprocal translocation,t(9;22)(q34;q11),of genetic material between chromosome 9 and chromosome 22,and contains a fusion gene called BCR-ABL1. This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22,coding for a hybrid protein:a tyrosine kinase signaling protein that is "always on",causing the cell to divide uncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle.
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Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer,others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine,targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth,rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals,the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However,the modalities can be combined;antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
K562 cells were the first human immortalised myelogenous leukemia cell line to be established. K562 cells are of the erythroleukemia type,and the cell line is derived from a 53-year-old female chronic myelogenous leukemia patient in blast crisis. The cells are non-adherent and rounded,are positive for the bcr:abl fusion gene,and bear some proteomic resemblance to both undifferentiated granulocytes and erythrocytes.
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Tyrosine-protein kinase receptor UFO is an enzyme that in humans is encoded by the AXL gene. The gene was initially designated as UFO,in allusion to the unidentified function of this protein. However,in the years since its discovery,research into AXL's expression profile and mechanism has made it an increasingly attractive target,especially for cancer therapeutics. In recent years,AXL has emerged as a key facilitator of immune escape and drug-resistance by cancer cells,leading to aggressive and metastatic cancers.
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Somatic evolution is the accumulation of mutations and epimutations in somatic cells during a lifetime,and the effects of those mutations and epimutations on the fitness of those cells. This evolutionary process has first been shown by the studies of Bert Vogelstein in colon cancer. Somatic evolution is important in the process of aging as well as the development of some diseases,including cancer.
Cancer cells are cells that divide continually,forming solid tumors or flooding the blood or lymph with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells,and these daughter cells are used to build new tissue or to replace cells that have died because of aging or damage. Healthy cells stop dividing when there is no longer a need for more daughter cells,but cancer cells continue to produce copies. They are also able to spread from one part of the body to another in a process known as metastasis.
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References
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- ↑ Levy, Doron; Tadmor, Eitan (January 11, 1998). "From Semidiscrete to Fully Discrete: Stability of Runge—Kutta Schemes by The Energy Method". SIAM Review. 40 (1): 40–73. Bibcode:1998SIAMR..40...40L. doi:10.1137/S0036144597316255. hdl: 1903/8644 – via CrossRef.
- ↑ "Wolfgang Pauli Institute (WPI)". www.wpi.ac.at.
- ↑ "Department of Mathematics – Levy, Doron". www-math.umd.edu.
- ↑ Levy, Doron; Puppo, Gabriella; Russo, Giovanni (May 1, 2000). "On the behavior of the total variation in CWENO methods for conservation laws". Applied Numerical Mathematics. 33 (1): 407–414. doi:10.1016/S0168-9274(99)00107-5 – via ScienceDirect.
- ↑ Levy, Doron; Puppo, Gabriella; Russo, Giovanni (January 11, 2000). "Compact Central WENO Schemes for Multidimensional Conservation Laws". SIAM Journal on Scientific Computing. 22 (2): 656–672. arXiv: math/9911089 . Bibcode:2000SJSC...22..656L. doi:10.1137/S1064827599359461. S2CID 12442855 – via CrossRef.
- ↑ Levy, Doron; Puppo, Gabriella; Russo, Giovanni (May 1, 2000). "A third order central WENO scheme for 2D conservation laws". Applied Numerical Mathematics. 33 (1): 415–421. doi:10.1016/S0168-9274(99)00108-7 – via ScienceDirect.
- ↑ Bryson, S.; Levy, D. (August 11, 2003). "High-order central WENO schemes for 1D Hamilton-Jacobi equations". In Brezzi, Franco; Buffa, Annalisa; Corsaro, Stefania; Murli, Almerico (eds.). Numerical Mathematics and Advanced Applications. Springer Milan. pp. 45–54. doi:10.1007/978-88-470-2089-4_4. hdl:2060/20020059594. ISBN 978-88-470-2167-9 – via Springer Link.
- ↑ Bryson, Steve; Levy, Doron (January 11, 2003). "High-Order Central WENO Schemes for Multidimensional Hamilton-Jacobi Equations". SIAM Journal on Numerical Analysis. 41 (4): 1339–1369. doi:10.1137/S0036142902408404. hdl: 2060/20020066776 . S2CID 5842936 – via CrossRef.
- ↑ Levy, Doron; Nayak, Suhas; Shu, Chi-Wang; Zhang, Yong-Tao (January 11, 2006). "Central WENO Schemes for Hamilton–Jacobi Equations on Triangular Meshes". SIAM Journal on Scientific Computing. 28 (6): 2229–2247. Bibcode:2006SJSC...28.2229L. doi:10.1137/040612002 – via CrossRef.
- ↑ Peet, M. M.; Kim, P. S.; Niculescu, S.-I.; Levy, D. (January 11, 2009). "New Computational Tools for Modeling Chronic Myelogenous Leukemia". Mathematical Modelling of Natural Phenomena. 4 (2): 119–139. doi: 10.1051/mmnp/20094206 .
- ↑ Botesteanu, Dana-Adriana; Lipkowitz, Stanley; Lee, Jung-Min; Levy, Doron (July 11, 2016). "Mathematical models of breast and ovarian cancers". WIREs Systems Biology and Medicine. 8 (4): 337–362. doi:10.1002/wsbm.1343. PMC 4911289 . PMID 27259061.
- ↑ Botesteanu, Dana-Adriana; Lee, Jung-Min; Levy, Doron (June 3, 2016). "Modeling the Dynamics of High-Grade Serous Ovarian Cancer Progression for Transvaginal Ultrasound-Based Screening and Early Detection". PLOS ONE. 11 (6): e0156661. Bibcode:2016PLoSO..1156661B. doi: 10.1371/journal.pone.0156661 . PMC 4892570 . PMID 27257824.
- ↑ Wilson, Shelby; Levy, Doron (October 1, 2013). "Functional Switching and Stability of Regulatory T Cells". Bulletin of Mathematical Biology. 75 (10): 1891–1911. doi:10.1007/s11538-013-9875-9. PMID 23917986. S2CID 255314821 – via Springer Link.
- ↑ Greene, James M.; Levy, Doron; Fung, King Leung; Souza, Paloma S.; Gottesman, Michael M.; Lavi, Orit (February 21, 2015). "Modeling intrinsic heterogeneity and growth of cancer cells". Journal of Theoretical Biology. 367: 262–277. doi:10.1016/j.jtbi.2014.11.017. PMC 4308514 . PMID 25457229.
- ↑ Lorz, Alexander; Botesteanu, Dana-Adriana; Levy, Doron (August 11, 2017). "Modeling Cancer Cell Growth Dynamics In vitro in Response to Antimitotic Drug Treatment". Frontiers in Oncology. 7: 189. doi: 10.3389/fonc.2017.00189 . PMC 5582072 . PMID 28913178.
- ↑ Milzman, Jesse; Sheng, Wanqiang; Levy, Doron (January 12, 2021). "Modeling LSD1-Mediated Tumor Stagnation". Bulletin of Mathematical Biology. 83 (2): 15. doi:10.1007/s11538-020-00842-8. PMID 33433736. S2CID 231586558 – via Springer Link.
- ↑ Besse, Apollos; Clapp, Geoffrey D.; Bernard, Samuel; Nicolini, Franck E.; Levy, Doron; Lepoutre, Thomas (May 1, 2018). "Stability Analysis of a Model of Interaction Between the Immune System and Cancer Cells in Chronic Myelogenous Leukemia". Bulletin of Mathematical Biology. 80 (5): 1084–1110. doi:10.1007/s11538-017-0272-7. PMID 28536994. S2CID 4036621 – via Springer Link.
- ↑ "The role of the autologous immune response in chronic myelogenous leukemia".
- ↑ Clapp, Geoffrey D.; Lepoutre, Thomas; Nicolini, Franck E.; Levy, Doron (May 3, 2016). "BCR-ABL transcript variations in chronic phase chronic myelogenous leukemia patients on imatinib first-line: Possible role of the autologous immune system". OncoImmunology. 5 (5): e1122159. doi:10.1080/2162402X.2015.1122159. PMC 4910749 . PMID 27467931.
- ↑ Lavi, Orit; Gottesman, Michael M.; Levy, Doron (February 1, 2012). "The dynamics of drug resistance: A mathematical perspective". Drug Resistance Updates. 15 (1): 90–97. doi:10.1016/j.drup.2012.01.003. PMC 3348255 . PMID 22387162.
- ↑ Tomasetti, C.; Levy, D. (2010). "An Elementary Approach to Modeling Drug Resistance in Cancer". Mathematical Biosciences and Engineering. 7 (4): 905–918. doi:10.3934/mbe.2010.7.905. PMC 3877932 . PMID 21077714.
- ↑ Tomasetti, C.; Levy, D. (August 11, 2010). "Drug Resistance always Depends on the Turnover Rate". In Herold, Keith E.; Vossoughi, Jafar; Bentley, William E. (eds.). 26th Southern Biomedical Engineering Conference SBEC 2010, April 30 - May 2, 2010, College Park, Maryland, USA. IFMBE Proceedings. Vol. 32. Springer. pp. 552–555. doi:10.1007/978-3-642-14998-6_141. ISBN 978-3-642-14997-9 – via Springer Link.
- ↑ Cho, Heyrim; Levy, Doron (December 1, 2017). "Modeling the Dynamics of Heterogeneity of Solid Tumors in Response to Chemotherapy". Bulletin of Mathematical Biology. 79 (12): 2986–3012. doi:10.1007/s11538-017-0359-1. PMID 29022203. S2CID 41563051 – via Springer Link.
- ↑ Becker, Matthew; Levy, Doron (October 1, 2017). "Modeling the Transfer of Drug Resistance in Solid Tumors". Bulletin of Mathematical Biology. 79 (10): 2394–2412. doi:10.1007/s11538-017-0334-x. hdl: 1903/20883 . PMID 28852953. S2CID 255318869 – via Springer Link.
- ↑ Cho, Heyrim; Wang, Zuping; Levy, Doron (November 21, 2020). "Study of dose-dependent combination immunotherapy using engineered T cells and IL-2 in cervical cancer". Journal of Theoretical Biology. 505: 110403. arXiv: 2001.10573 . Bibcode:2020JThBi.50510403C. doi:10.1016/j.jtbi.2020.110403. PMID 32693004. S2CID 210942624 – via ScienceDirect.
- ↑ "Mathematical Modeling Reveals That Changes to Local Cell Density Dynamically Modulate Baseline Variations in Cell Growth and Drug Response".
- ↑ "The Role of Cell Density and Intratumoral Heterogeneity in Multidrug Resistance".
- ↑ Greene, James; Lavi, Orit; Gottesman, Michael M.; Levy, Doron (March 1, 2014). "The Impact of Cell Density and Mutations in a Model of Multidrug Resistance in Solid Tumors". Bulletin of Mathematical Biology. 76 (3): 627–653. doi:10.1007/s11538-014-9936-8. PMC 4794109 . PMID 24553772 – via Springer Link.
- ↑ "Simplifying the complexity of resistance heterogeneity in metastasis: Trends in Molecular Medicine".
- ↑ Cho, Heyrim; Levy, Doron (December 1, 2018). "Modeling continuous levels of resistance to multidrug therapy in cancer". Applied Mathematical Modelling. 64: 733–751. arXiv: 1806.07557 . doi:10.1016/j.apm.2018.07.025. S2CID 49322143 – via ScienceDirect.
- ↑ Cho, Heyrim; Levy, Doron (August 11, 2020). "The impact of competition between cancer cells and healthy cells on optimal drug delivery". Mathematical Modelling of Natural Phenomena. 15: 42. arXiv: 1806.07477 . doi: 10.1051/mmnp/2019043 – via www.mmnp-journal.org.
- ↑ "Guggenheim Fellow - Doron Levy".
- ↑ Samuel Patrick Smith, ed. "The linking ring Vol 100 Issue 10", October 2020, p. 60
- ↑ "2024 Class of Fellows of the AMS". American Mathematical Society. Retrieved 2023-11-09.
