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Laboratory evaluation of thyroid function
Published in Pallavi Iyer, Herbert Chen, Thyroid and Parathyroid Disorders in Children, 2020
Although molecular testing is accepted for adult indeterminate nodules, these tests have not been thoroughly studied in pediatric populations. A positive mutation test is highly associated with malignancy. However, a negative test must be interpreted with caution due to the higher prevalence of malignancy for pediatric indeterminate nodules when compared to adults: Approximately 28% for Category III nodules and 35% for Category IV nodules (18). Currently the American Thyroid Association does not recommend molecular testing for routine pediatric clinical practice. Instead, the next recommended step for indeterminate nodules is surgery (18). However, molecular testing can be helpful if specific alternations identified in pediatric populations are found. Just as in adults, the BRAFV600E mutation is strongly associated with classical papillary thyroid carcinoma. RET/PTC1 has been associated with more aggressive variants of papillary thyroid carcinoma (19).
The thyroid gland
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
Short latency aggressive papillary cancer is associated with the ret/PTC3 oncogene and later developing, possibly less aggressive, cancers with ret/PTC1. The incidence of follicular carcinoma is high in endemic goitrous areas, possibly due to TSH stimulation. Malignant lymphomas sometimes develop in autoimmune thyroiditis, and the lymphocytic infiltration in the autoimmune process may be an aetiological factor.
Thyroid disease: Cytopathology and surgical pathology aspects
Published in Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner, Endocrine Surgery, 2017
Charvi A. Cassano, Arnold H. Szporn, G. Kenneth Haines
Hyalinizing trabecular tumor is an interesting tumor that initially was categorized as a form of PTC due to identical nuclear features. This tumor arises as a well-circumscribed solid nodule. Histologically, the tumor consists of elongated eosinophilic cells with PTC-like nuclei, arranged in trabeculi with hyalinized stroma (Figure 6.8a and b). RET/PTC1 rearrangements have been identified in some cases, but no RAS or BRAF mutations have been reported. The tumor has a unique membranous staining pattern with immunostains for the proliferation marker ki-67. The overwhelming majority of these tumors have followed a benign clinical course, although a few metastasized to regional lymph nodes [46, 47].
Discovery, preclinical development, and clinical application of pralsetinib in the treatment of thyroid cancer
Published in Expert Opinion on Drug Discovery, 2022
Pietro Locantore, Roberto Novizio, Andrea Corsello, Rosa Maria Paragliola, Alfredo Pontecorvi, Salvatore Maria Corsello
Starting from the necessity of having a drug capable of inhibiting WT RET and RET-altered gene products, possibly not influenced by peculiar RET variants (i.e. M918T, V804L, and V804M), a library of agnostic designed drugs has been screened. Agnostic drugs [29] use is not restricted to a specific tumor histotype but linked to the presence of a specific molecular alteration, regardless of the organ of origin. Their development is closely related to the mutational model. After chemistry optimization there was the generation of BLU-667. In bio-molecular assays, pralsetinib has shown the capability of inhibiting WT RET phosphotransferase action at subnanomolar potency (IC50 0.4 nmol/L), 8- to 28-fold more potent compared to MKIs cabozantinib and vandetanib. The same potent effect (IC50 0.4 nmol/L) has been demonstrated toward prevalent tumorigenic RET alterations, included RETM918T, the most frequent point mutation in MTC, along with CCDC6–RET (RET/PTC1) fusion notable in PTC and NSCLC [10].
Acupuncture combined with moxibustion promote the recovery of spinal cord injury in correlation with Shh/Gli-1 signaling pathway
Published in The Journal of Spinal Cord Medicine, 2022
Li-Li-Qiang Ding, Song-Feng Hu, Xing-Wei He, Peng Zhang, Fen-Fen Zhao, Ting-Ping Liu, Qin Zhang, Fan He, Ying Yu, Peng Xiong, Chang-Kang Wang
The Hedgehog (Hh) signaling pathway regulates an enormous variety of developmental events in embryo.4 The vertebrate Hh family is represented by at least three members: Desert Hedgehog (Dhh), Indian Hedgehog (Ihh) and Sonic Hedgehog (Shh). As one of three Hh signaling pathway members, Shh is the most extensively characterized homolog, and has been identified within a variety of species. Shh is expressed in the notochord, the floor plate of the neural tube in the human embryo.5 Shh ligand interacts with the transmembrane receptor Patched-1 (Ptc1) or Patched-2 (Ptc2) then relieves the signal transducer smoothened (Smo), which activating the zinc finger protein glioma-associated oncogene homolog-1 (Gli-1) and leads to Gli-1 protein entering the nucleus and acting as a transcriptional activator for downstream genes.6 Recent studies revealed that Shh signaling pathway could be abnormally activated in various tissues derived from endoderm, which lead to the continuous damage repair and regeneration of cells in tissue, in some cases inducing tumor formation ultimately.7,8 The Shh/Gli-1 signaling pathway has been recognized as key mediator of many fundamental processes in embryonic development, including the growth, patterning, and morphogenesis of CNS.9 Previous research has revealed that the Shh pathway could contribute to nerve regeneration and may ultimately promote SCI recovery.10
HER2 signaling regulates the tumor immune microenvironment and trastuzumab efficacy
Published in OncoImmunology, 2019
Tiziana Triulzi, Luca Forte, Viola Regondi, Martina Di Modica, Cristina Ghirelli, Maria Luisa Carcangiu, Lucia Sfondrini, Andrea Balsari, Elda Tagliabue
HER2-mediated production of CCL2 was found to be supported by the PI3K/AKT/NF-kB axis downstream of the oncogene, as demonstrated by the significant reduction in CCL2 expression at both the mRNA and protein level observed in BC cell lines upon treatment with PI3Ki and NF-kBi. Thus, an abnormal HER2 activation such as that occurring in tumors with HER2 amplification could generate an inflammatory environment, as has been described for other oncogenes such as RET/PTC1 in thyroid cancer,21 RAF in melanoma, and MYC in pancreatic tumors.22 Considering that the PI3K/AKT pathway is common to different membrane receptors, tumor cell signals other than HER2 may contribute to CCL2 expression albeit to a lesser extent in HER2-addicted BCs. In these tumors, signal derived from HER2 homodimerization and its heterodimerization with EGFR and HER3 would be the main driver of CCL2 production. Moreover, the low NF-kB activity in the presence of high expression of CCL2 as observed in MDAMB453 cells does not exclude that pathways other than PI3K/AKT may also be engaged in CCL2 regulation.