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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.
Testicular stem cells, spermatogenesis and infertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Deepa Bhartiya, Sandhya Anand, Hiren Patel, Ankita Kaushik, Sreepoorna Pramodh
To conclude, rather than Pax7, which is currently considered the ideal marker for SSCs, nuclear OCT-4 positive, small-sized VSELs are the bona fide and most primitive stem cells in the testis. They largely remain quiescent, undergo rare ACD to give rise to slightly bigger SSCs (that express Id4, Pax7, Ngn3 and other markers), which in turn undergo SCD and clonal expansion (rapid proliferation with incomplete cytokinesis) prior to meiosis, followed by further differentiation into sperm. Pax7 and Id4 are also expressed by the spermatogonial cells undergoing rapid proliferation, SCD and also clonal expansion. Compared to about 3,856 + 1,968.78 VSELs in normal testis, the number of ID4+ cells are 5,000–6,000 and PAX7+ cells are about 500. In comparison to the quiescent VSELs, ID4+ and PAX7+ stem cells are actively dividing and undergo symmetric cell divisions. ID4 and PAX7 are expressed on Asingle spermatogonia, but all Asingle cells are not SSCs. VSELs are located in the basal lamina of the tubules unlike the Pax7+ and Id4+ cells that are located outside the conventional niche (37). It is possible that Pax7+ cells appear to be resistant to oncotherapy, possibly because the quiescent VSELs increase in number after busulphan treatment and undergo ACD to give rise to Pax7+ SSCs in an attempt to restore homeostasis. Thus, Pax7 cells do not survive but rather increase in number by ACD of VSELs in response to chemotherapy-induced stress.
FOXO1 and PAX5 Rearrangement in Alveolar Rhabdomyosarcoma in Saudi Pediatric Patients
Published in Fetal and Pediatric Pathology, 2023
ARMS is an aggressive pediatric malignancy of striated muscle characterized in 60% of cases by FOXO1::PAX3 fusion transcript [1,25]. Human Forkhead-box (FOX) gene family consists of at least 43 members [25]. Several pathogenesis and tumorigenesis were attributed to the deregulation of FOX family genes. FOXA1 gene is amplified and overexpressed in esophageal and lung cancer [25]. The upregulation of FOXM1 gene in pancreatic carcinoma was reported to the transcriptional regulation by Sonic Hedgehog pathway [26,27]. FOXO1 gene is fused to PAX3 or PAX7 genes in rhabdomyosarcoma. ARMS cases show whole-chromosome copy number changes, notably gain of chromosome 8 with associated high levels of expression of genes from this chromosome [16,28].
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).
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.