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Central Nervous System
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Chordomas are malignant, embryonal tumors that arise from the notochordal remnant. They are found predominantly in the region of the clivus and at the sacrococcygeous, in the extradural space, but they grow slowly and may invade the dura as they do so (Figure 1.12). Histologically, the identifying features are “physaliferous” cells, which contain large mucus-filled vacuoles, show immunoreactivity for S-100 and epithelial markers such as the epithelial membrane antigen (MUC1) and cytokeratins, and are arranged in lobules, usually surrounded by extracellular mucus. These tumor cells typically express high levels of the notochord transcription factor brachyury, driven by gains of the TBXT gene.
Familial Chordoma
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Alexandra Suttman, Sydney T. Grob, Jean M. Mulcahy Levy
In contrast, heterozygous germline duplications in TBXT have been identified in approximately 40% families with multiple chordoma diagnoses. These duplications are thought to confer a significant susceptibility to the development of chordoma [2], although it is currently still unclear how this gene contributes to the pathogenesis of chordoma. In vitro, silencing brachyury halts chordoma tumor growth [8]. As noted previously, at least partial allelic gain of TBXT is a common somatic finding in sporadic chordomas, further implicating this gene in the pathogenesis of chordoma [12].
Integrin Function in Early Vertebrate Development: Perspectives from Studies of Amphibian Embryos
Published in Yoshikazu Takada, Integrins: The Biological Problems, 2017
Whittaker and DeSimone51 reported that the synthesis of α3, α4, and α6 mRNAs increases in animal cap cells in response to induction with activin. However, the expression of these α subunits is a relatively “late” event in comparison to early response genes such as the mesoderm gene marker, brachyury.66 Given the time course, increased synthesis of α subunits cannot account for the rapid acquisition of FN binding that is observed. Another possibility is that non-β1-containing integrins present in the egg are responsible for activin-induced adhesion to FN. This remains a formal possibility given that at least two other integrin subfamiles, β3 and β6, are expressed in eggs and early embryos.49 In the case of β3 mRNA, however, synthesis is also unaffected in animal cap cells exposed to activin.51 Further evaluation of these integrins awaits the availability of specific antibodies and the identification of α subunits that are known to form dimers with the β3 and β6 subunits and also function as FN receptors.1 It is possible that increased expression of one or more of these receptors at the cell surface might account for the increase in FN binding observed.
Chondroid chordoma of the parapharyngeal space: A case report and review of literature
Published in Acta Oto-Laryngologica Case Reports, 2020
Nasser Waleed Alobida, Aseel O. Doubi, Mohammed Alswayyed, Dima Z. Jamjoom, Khalid Al-Qahtani
Chordomas are rare primary tumor of the bone that arise from the remnants of the embryonic notochord, along the midline craniovertebral axis, most commonly in clivus and sacrococcygeal regions. They are slow-growing and locally aggressive malignant neoplasms [9]. The majority of head and neck chordomas arise in the skull base with a small minority arising along the cervical spine. Reports of extra-axial locations in the head and neck have found them arising in the nasopharynx, paranasal sinuses, lateral nasal wall, oropharynx, and the soft tissue of the neck [10]. Cranial chondroid chordoma (CC), a subtype of chordoma, was first described by Falconer et al. [11] in 1968 as a biphasic neoplasm consisting of cartilaginous and chordoid elements in variable proportions. In later years, Heffelfinger et al. [12] reported its clinical and morphological features. CCs were characterized by female predominance [13]. Other subtypes of chordomas include cellular, poorly differentiated and dedifferentiated. The chondroid subtype accounts for 7–63% of skull base chordomas. It consists of cords and nests of epitheloid cells with vacuolated clear cytoplasm (physaliphorous cells). The matrix, however, resembles neoplastic hyaline cartilage. Like all chordomas, they express cytokeratins and most are immunoreactive for epithelial membrane antigen (EMA) and S100 protein. Brachyury, a nuclear protein associated with notochord differentiation, is the most specific marker of chordoma. Occasionally though, chondroid chordoma may demonstrate only focal cytokeratin expression [10].
Effect of hyperthermia and proton beam radiation as a novel approach in chordoma cells death and its clinical implication to treat chordoma
Published in International Journal of Radiation Biology, 2021
Prerna Singh, John Eley, Ali Saeed, Binny Bhandary, Nayab Mahmood, Minjie Chen, Tijana Dukic, Sina Mossahebi, Dario B. Rodrigues, Javed Mahmood, Zeljko Vujaskovic, Hem D. Shukla
This study provides first-time in vitro evidence of enhancement of proton radiation cell kill by sensitization from hyperthermia in chordoma. We also found downregulation of the brachyury protein expression after the combination treatment and HT. Brachyury is known as a biomarker and a therapeutic target for chordoma and is currently a focus of clinical trials using a brachyury vaccine (Quilt 2019). The decrease in brachyury expression in chordoma after combination treatment in our study shows the potential of hyperthermia as a treatment modality in chordoma. The study also showed a decrease in cell survival in vitro and brachyury expression after hyperthermia treatment alone. In vivo study must be conducted to see whether hyperthermia alone has any effect on chordoma.
High-dose proton therapy and tomotherapy for the treatment of sacral chordoma: a retrospective monocentric study
Published in Acta Oncologica, 2021
Arnaud Beddok, Caroline Saint-Martin, Hamid Mammar, Loïc Feuvret, Sylvie Helfre, Stéphanie Bolle, Sebastien Froelich, Farid Goudjil, Sofia Zefkili, Malika Amessis, Dominique Peurien, Sophie Cornet, Rémi Dendale, Claire Alapetite, Valentin Calugaru
Forty-one consecutive patients, not included in clinical trials, were analysed in this study. Baseline characteristics are summarised in Table 2. The median age of the cohort was 64 years old, ranging from 37 to 86. Median tumour size at presentation was 255 cm3, interquartile range [IQR]: 136–525. Thirty patients (73%) were operated with a macroscopic residue for 15 of them (median residue size: 241 cm3, IQR: 46–643). Pre-surgical volume was significantly higher in the tomotherapy group than in the Proton - Tomo group (Supp Data 1). For all patients, the diagnosis was biopsy proved. The main histological subtype was myxoid, although it was mentioned in less than 50% of cases. The diagnosis of chordoma was most often confirmed by immunohistochemical analysis showing a positive EMA, cytokeratin, and S100. Brachyury was mentioned and positive in 12% of cases. Thirteen (32%) patients treated before 2013 received Tomotherapy alone; whereas after 2013, 28 patients (68%) received a combination of PT to CTV1 followed by Tomotherapy to CTV2 (Proton - Tomo). This combined protocol was developed in Institut Curie only from January 2013 in the context of a new gantry room. Among the 28 patients treated with the proton-photon combination, 24 (86%) were treated before March 2017 with the classical proton therapy technique (double scattering) while 4 (14%) were treated after March 2017 with the modern proton therapy technique (Pencil Beam Scanning). HR – CTV and HR – PTV were significantly higher in the tomotherapy group than in the Proton - Tomo group (Supp Data 1). None of the subjects had osteosynthetic material at the time of RT.