Identification and characterization of a cytotoxic T-lymphocyte agonist epitope of brachyury, a transcription factor involved in epithelial to mesenchymal transition and metastasis

Abstract The transcription factor brachyury is a major driver of epithelial to mesenchymal transition in human carcinoma cells. It is overexpressed in several human tumor types versus normal adult tissues, except for testes and thyroid. Overexpression is associated with drug resistance and poor prognosis. Previous studies identified a brachyury HLA-A2 cytotoxic T-lymphocyte epitope. The studies reported here describe an enhancer epitope of brachyury. Compared to the native epitope, the agonist epitope: (a) has enhanced binding to MHC class I, (b) increased the IFN-γ production from brachyury-specific T cells, (c) generated brachyury-specific T cells with greater levels of perforin and increased proliferation, (d) generated T cells more proficient at lysing human carcinoma cells endogenously expressing the native epitope, and (e) achieved greater brachyury-specific T-cell responses in vivo in HLA-A2 transgenic mice. These studies also report the generation of a heat-killed recombinant Saccharomyces cerevisiae (yeast) vector expressing the full-length brachyury gene encoding the agonist epitope. Compared to yeast-brachyury (native) devoid of the agonist epitope, the yeast-brachyury (agonist) enhanced the activation of brachyury-specific T cells, which efficiently lysed human carcinoma cells. In addition to providing the rationale for the recombinant yeast-brachyury (agonist) as a potential vaccine in cancer therapy, these studies also provide the rationale f...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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CONCLUSION: There is a gradual temporal increase in the frequency of resected papillary cancer over a 16 year period while follicular has remained static. These changes may be attributable to better salt iodination. PMID: 31392867 [PubMed - in process]
Source: South African Journal of Surgery - Category: Surgery Tags: S Afr J Surg Source Type: research
AbstractThe Metastatic progression of solid tumors, such as thyroid cancer is a complex process which involves various factors. Current understanding on the role of epithelial –mesenchymal transition (EMT) in thyroid carcinomas suggests that EMT is implicated in the progression from follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC) to poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid cancer (ATC). According to the literature, the ini tiation of the EMT program in thyroid epithelial cells elevates the number of stem cells, which contribute to recurrent and metastatic diseases. The ...
Source: Endocrine - Category: Endocrinology Source Type: research
We describe a case of a 70-year-old women with a history of an indeterminate thyroid nodule on cytology. A painless, erythematous skin nodule of about 7 mm diameter was removed from the scalp and diagnosed as a metastasis from thyroid cancer. After total thyroidectomy, a histological diagnosis of follicular thyroid cancer was made. Two cycles of radioactive iodine were performed. Both the follicular thyroid carcinoma and the metastasis were investigated for the presence of BRAF/RAS and TERT promoter mutations. The results showed that the cutaneous metastasis was BRAF wild-type and TERT promoter-mutated (position g.1,295,22...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Authors: Zhang C, Li H, Wang J, Zhang J, Hou X Abstract Malignant melanoma (MM) is the most aggressive form of skin cancer originating from melanocytes with increased proliferative and metastatic ability. Previous studies have revealed that microRNA-338-3p (miR-338-3p) functions as a tumor suppressor in several types of cancer, including cervical cancer, renal cell carcinoma and thyroid cancer. However, the function and mechanism underlying the action of miR-383-3p in MM remain unclear. In the study, aberrant downregulation of miR-338-3p was observed in 60 pairs of MM and adjacent non-tumor tissue using quantitativ...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
CONCLUSION: VASN plays a crucial oncogene in thyroid cancer. Our results indicate that VASN could be a biomarker of thyroid cancer and may act in the YAP/TAZ pathway to regulate epithelial-mesenchymal transition (EMT). PMID: 31312369 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Papillary thyroid carcinoma (PTC) is the most commonly diagnosed endocrine cancer, and those with BRAFV600E mutation have high recurrence rate and less favorable clinical behavior. Genistein having anti-carcinoma effects in various types of carcinomas as an estrogen analog, but the mechanism of Genistein in the progression of PTC remains unknown. Genistein significantly inhibits the proliferation and the invasion (P
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
1262Objectives: To investigate the relationship between NIS protein expression of Papillary thyroid carcinoma (PTC) and GLUT1 and HK2, the proteins involved in the glycolysis process. Methods: 61 cases of thyroid papillary carcinoma resected from November 2017 to September 2018 in the first affiliated hospital of China medical university were selected.Among them, there were 61 cases of cancer tissue and 59 cases of paracancer tissue, aged from 12 to 69 years old, with an average age (43.84 12.28). There were 40 cases of lymph node metastasis and 21 cases without lymph node metastasis.All patients had no history of chemorad...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Head and Neck Posters Source Type: research
CONCLUSIONS: Our results suggest that exosomes expressing TSHR may be secreted from normal and cancerous thyroid cells. In thyroid gland of patients with GD, TSHR exosomes may exert a decoy effect by sequestering autoantibody, thereby ameliorating autoantibody-mediated activation of thyroid function. PMID: 31062662 [PubMed - as supplied by publisher]
Source: Thyroid : official journal of the American Thyroid Association - Category: Endocrinology Tags: Thyroid Source Type: research
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Santosh K. Ghosh1*, Thomas S. McCormick1,2 and Aaron Weinberg1* 1Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, OH, United States 2Dermatology, School of Medicine, Case Western Reserve University, Cleveland, OH, United States Human beta-defensins (hBDs, −1, 2, 3) are a family of epithelial cell derived antimicrobial peptides (AMPs) that protect mucosal membranes from microbial challenges. In addition to their antimicrobial activities, they possess other functions; e.g., cell activation, proliferation, regulation of cytokine/chemokine production, migration, diffe...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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