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Molecular adaptation to resistance exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
MRFs help satellite cells proliferate and then differentiate into a muscle fibre. In inactive, or quiescent, satellite cells, the MRFs are generally expressed at low levels. During the quiescent stage, the paired box transcription factor Pax7 is essential to maintain satellite cells (Figure 8.10). In fact, mice where Pax7 has been knocked out, satellite cell numbers are very low indicating that Pax7 is key for the development of satellite cells. In the absence of Pax7+ satellite cells, muscle does not grow as big and is not able to regenerate after injury, demonstrating the importance of satellite cells in developmental muscle growth and regeneration after injury (93). Today, Pax7 is used as a marker to identify satellite cells immunohistochemically. However, Pax7 is only important for generating satellite cells and is not required for their function in adult muscle. This was demonstrated in an experiment where Pax7 was only knocked out in adult muscle, after satellite cells had formed, and muscle regeneration occurred normally (94).
Soft Tissue Sarcomas
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Thomas F. DeLaney, David C. Harmon, Karol Sikora, Francis J. Hornicek
Alveolar rhabdomyosarcomas show a translocation at t(2;13)(q35;q14) or less often t(1;13)(p36;q14); the chimeric genes have been cloned and have been termed PAX3–FKHR and PAX7–FKHR, respectively. These translocations are associated with over-expression of the fusion product. PAX7–FKHR tumors more often present with extremity lesions, are more likely to be localized, and are less likely to metastasize widely than PAX3–FKHR tumors. A downstream target of PAX3–FKHR may be MET, which encodes a receptor involved in growth and motility signaling. Molecular determination of minimal residual disease in alveolar rhabdomyosarcoma is possible, and patients with positive peripheral blood after treatment show poorer survival than patients without micro-circulating disease.
Soft tissue sarcomas
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
Thomas F. Delaney, David C. Harmon, Sam S. Yoon, David G. Kirsch, Andrew E. Rosenberg, Henry J. Mankin, Daniel I. Rosenthal, Francis J. Hornicek
Alveolar rhabdomyosarcomas show a translocation at t(2;13)(q35;q14) or less often t(1; 13)(p36;q14); the chimeric genes have been cloned and have been termed PAX3–FKHR and PAX7–FKHR, respectively.48,49 These translocations are associated with over-expression of the fusion product.49PAX7-FKHR tumours more often present with extremity lesions, are more likely to be localized, and are less likely to metastasize widely than PAX3–FKHR tumours.50 A downstream target of PAX3–FKHR may be MET, which encodes a receptor involved in growth and motility signalling.51 Molecular determination of minimal residual disease in alveolar rhabdomyosarcoma is possible52 and patients with positive peripheral blood after treatment show poorer survival than patients without microcirculating disease.53
A Review of the Role of Cytogenetics in the Diagnosis of Orbital Rhabdomyosarcoma
Published in Seminars in Ophthalmology, 2019
Paula Cortes Barrantes, Frederick A. Jakobiec, Thaddeus P. Dryja
FOX01 (previously known as FKHR) is a member of the Forkhead box transcription family of genes. Members of this gene family code for transcription factors that affect embryonic development and tissue-specific gene expression in mature adult tissues.15 PAX3 and PAX7 belong to the Paired box family of proteins, and they govern the expression of the transcription factors MyoD and myogenin. PAX3 and PAX7 are expressed during early striated muscle differentiation. Studies on muscle development have shown that although required in early stages, down-regulation of PAX3 and PAX7 is necessary for the terminal differentiation of skeletal muscle cells. In vivo experimental studies have demonstrated that continuous expression of these genes prevents muscle differentiation.16 (Figure 3).
Muscle-derived stem cells: important players in peripheral nerve repair
Published in Expert Opinion on Therapeutic Targets, 2018
Leila Musavi, Gerald Brandacher, Ahmet Hoke, Halley Darrach, W.P. Andrew Lee, Anand Kumar, Joseph Lopez
Tamaki et al. sought to further characterize the role of MDSCs in the promotion of nerve regrowth in vivo [22]. They enzymatically isolated and sorted two populations of human muscle-derived cells based on cell surface markers: CD34−/CD45−/CD29+ cells (Sk-DN/29+) and CD34+/CD45− cells (Sk-34). They found that the Sk-DN/29+ population, which contained a large number of Pax7+ putative satellite cells, promoted muscle regeneration in vivo, as demonstrated by human nuclear antigen-positive (HNA+) myofiber nuclei seen in Sk-DN/29+ cell-transplanted mouse muscles. Meanwhile, the Sk-34 population, which did not contain Pax7+ cells, demonstrated vigorous engraftment in the interstitium associated with differentiation into SCs (p75+/HNA+), vascular endothelial cells (CD31+/HNA+), and pericytes (NG2+/HNA+). Interestingly, the authors also found that the cell engraftment ratio and differentiation capacities of the SK-DN/29+ and Sk-34 cells in vivo were significantly reduced when the two populations were cultured together prior to transplantation compared to when they were cultured separately. Thus, they recommended separately culturing the two populations, followed by combined transplantation for optimal nerve repair. Still, further characterization of SK-DN/29+ and Sk-34 cells, their distinct roles, and their synergistic effects in functional recovery are needed.
Systematic identification of cancer-specific MHC-binding peptides with RAVEN
Published in OncoImmunology, 2018
Michaela C. Baldauf, Julia S. Gerke, Andreas Kirschner, Franziska Blaeschke, Manuel Effenberger, Kilian Schober, Rebeca Alba Rubio, Takayuki Kanaseki, Merve M. Kiran, Marlene Dallmayer, Julian Musa, Nurset Akpolat, Ayse N. Akatli, Fernando C. Rosman, Özlem Özen, Shintaro Sugita, Tadashi Hasegawa, Haruhiko Sugimura, Daniel Baumhoer, Maximilian M. L. Knott, Giuseppina Sannino, Aruna Marchetto, Jing Li, Dirk H. Busch, Tobias Feuchtinger, Shunya Ohmura, Martin F. Orth, Uwe Thiel, Thomas Kirchner, Thomas G. P. Grünewald
In both the pediatric and carcinoma datasets, we observed significant enrichments (P < 0.0001, two-tailed Chi2-test with Yates’ correction) of established cancer-testis antigens (Supplementary Figure 1, CTDatabase, www.cta.lncc.br38), but also identified many novel candidates including the pioneer transcription factor PAX7.39PAX7 encodes a paired box transcription factor required for embryonal neural development40 and renewal of skeletal muscle stem cells.41 Translocations involving PAX7 and FKHR are found in the majority of alveolar rhabdomyosarcomas (ARMS), indicating a role of PAX7 in the pathogenesis of myogenic tumors.42 Using RAVEN, we identified PAX7 as a strong CSG in multiple oligo-mutated cancer entities such as Ewing sarcoma, Ewing-like sarcomas with a BCOR-CCNB3-translocation and embryonal as well as alveolar fusion-negative rhabdomyosarcoma. Its exclusive expression in these cancer entities was confirmed on protein level by IHC. Strikingly, PAX7 encodes a 9-mer peptide (GLVSSISRV) with very high affinity for the most frequent MHC-I subtype in Caucasians (HLA-A02:01),34 rendering PAX7 as an attractive target for immunotherapy for multiple oligo-mutated cancers. As we focused here on the validation of peptide affinities for HLA-A02:01, future experimental validation for predicted peptides for other HLAs is required.