Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD82 (KAI1) and CD63 (ME491) are highly glycosylated proteins which belong to the transmembrane 4 superfamily (TM4SF). CD82 has been implicated as a possible prostate cancer metastasis suppressor gene, whereas CD63 is involved in the progression of human melanoma cancer. Down-regulation of both CD82 and CD63 expression has been associated with the metastatic potential of several solid tumors. Currently, information is lacking on the role of CD82 and CD63 during thyroid carcinogenesis. The aim of this study was to determine whether the expression of CD82 and CD63 is a useful prognostic indicator in patients with thyroid carcinoma. The expression of CD82 and CD63 was analysed by reverse transcriptase-PCR (RT-PCR) and immunohistochemistry in benign goiter (n=12) and 75 primary thyroid carcinoma tissue specimens (PTC: 33, FTC: 24, UTC: 18) out of which 36 were non-metastasized primary tumors and 39 were metastasized tumors (regional lymph node and/or distant metastases). All of the benign goiter tissues showed CD82 expression. By contrast, a significant decrease in CD82 mRNA and protein levels was detected in carcinoma tissues as compared to benign goiter tissues (p<0.001). A similar down-regulation was observed in metastasized tumor tissues when compared with non-metastasized tumors (all p<0.05). CD82 expression was correlated with pTNM status of differentiated and undifferentiated thyroid tumor and the pathologic stage of differentiated thyroid tumor. In contrast to CD82, CD63 mRNA and protein expression was unchanged in all thyroid carcinomas. Benign goiter tissues showed weak expression of CD63. There were no significant correlation between CD63 mRNA/protein expression and any clinical/pathological parameters. Our results support the hypothesis that down-regulation of CD82 expression may reflect an increased in vivo metastatic potential of thyroid cancer cells. CD82 may serve as a prognostic marker of metastasis in thyroid cancer. Constitutive expression of CD63 may indicate that this factor does not play a direct role in thyroid carcinogenesis.
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PMID:CD82, and CD63 in thyroid cancer. 1537 77

Our recent findings have shown that the reverse transcriptase (RT) inhibitors, nevirapine and efavirenz, used for 10 years in human immunodeficiency virus (HIV) disease, act as cytostatic and differentiating agents by modulating gene expression in several human tumor cell models. In dedifferentiated thyroid cancer, they reestablish thyroid-stimulating hormone (TSH) signaling, Na/I symporter (NIS), thyroglobulin peroxidase (TPO) expression, and even radioiodine uptake (RIU). In this paper, we describe the case of a 76-year-old woman who was affected by thyroid papillary carcinoma and who underwent a total thyroidectomy and a debulking of the right laterocervical region for lymph-node metastases, vessel infiltration, and neoplastic thrombosis of the internal jugular vein, followed by 3 radioiodine treatments. At restaging, a computed tomography scan revealed that distant metastases were mostly not taking up the radioiodine at the 131I whole-body scan (WBS). An analysis of tumor cells obtained by fine-needle aspiration biopsy of a right laterocervical lymph-node revealed cell anisokaryosis, nuclear pleomorphism, and scanty colloid, as well as the undetectable expression of thyroglobulin and NIS proteins. After starting a nevirapine treatment (NT), higher thyroglobulin levels were observed and some metastases exhibited a significant increase in radioiodine uptake, which led us to again treat the patient with 131I. Five (5) months later, the 131I-WBS revealed the disappearance of RIU in some metastases and its significant reduction in other lesions, with a parallel drop in serum thyroglobulin. No new metastatic lesion was revealed by rh-TSH-stimulated 131IWBS and 18F-flourodeoxyglucose positron emission tomography scan. Cells obtained from the right laterocervical lymph-node 2 months after NT exhibited a reduced nuclear pleomorphism, an increase in colloid production, and a significant upregulation of thyroglobulin and NIS protein expression. This first in vivo molecular and morphologic evidence of cell differentiation in human cancer and low toxicity of nevirapine strongly encourage its use in dedifferentiated thyroid cancer treatment.
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PMID:Reinduction of cell differentiation and 131I uptake in a poorly differentiated thyroid tumor in response to the reverse transcriptase (RT) inhibitor nevirapine. 1760 Apr 78

Telomeres are specialized structures at the ends of chromosomes, consisting of hundreds of repeated hexanucleotides (TTAGGG)n. Genetic integrity is partly maintained by the architecture of telomeres and it is gradually lost as telomeres progressively shorten with each cell replication, due to incomplete lagging DNA strand synthesis and oxidative damage. Telomerase is a reverse transcriptase enzyme that counteracts telomere shortening by adding telomeric repeats to the G-rich strand. It is composed of a telomerase RNA component and a protein component, telomerase reverse transcriptase. In the absence of telomerase or when the activity of the enzyme is low compared to the replicative erosion, apoptosis is triggered. Patients who have inherited genetic defects in telomere maintenance seem to have an increased risk of developing familial benign diseases or malignant diseases. At the somatic level, telomerase is reactivated in the majority of human carcinomas, suggesting that telomerase reactivation is a critical step for cancerogenesis.In sporadic thyroid carcinoma telomerase activity is detectable in nearly 50% of thyroid cancer tissues and some authors proposed that the detection of telomerase activity may be used for differentiating between benign and malignant thyroid tumours. Recently a germline alteration of telomere-telomerase complex has been identified in patients with familial papillary thyroid cancer, characterized by short telomeres and increased expression and activity of telomerase compared to patients with sporadic papillary thyroid cancer.In this report, we will review the role of telomere-telomerase complex in sporadic and familial thyroid cancer.
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PMID:Telomeres and thyroid cancer. 2051 14

Runx2/Cbfa1 is a member of the Runt-related transcription factor family and is an essential regulator of osteoblast/chondrocyte differentiation. Recently, aberrant expression of Runx2 and its oncogenic functions have been identified in the progression and metastasis of human cancers. In this study, we investigated the expression profile of Runx family genes in normal thyroid tissue, non-neoplastic but abnormal thyroid tissue, various types of thyroid tumors and representative human thyroid carcinoma cell lines. Using reverse transcriptase-PCR and western blotting, we found that Runx2 was consistently upregulated in papillary carcinomas (PCs) and thyroid carcinoma cell lines compared with normal thyroid tissue. With immunohistochemistry, we observed negative or focal immunoreactivity of Runx2 in the nuclei of normal thyroid follicular cells. None of the non-neoplastic thyroid tissues, including Graves' thyroid and adenomatous goiter, had diffuse positivity of Runx2. Expression of Runx2 in benign follicular adenomas varied from negative to diffusely positive. Meanwhile, all malignant thyroid tumors showed some Runx2 immunopositivity. It was diffuse and intense in 83% (19/23) of PCs, 71% (5/7) of follicular carcinomas (FCs) and 40% (4/10) of undifferentiated carcinomas (UCs). In thyroid carcinoma cell lines, the MEK inhibitor U0126 suppressed Runx2, suggesting an association of the MAPK/ERK pathway with Runx2 regulation. Effective silencing of Runx2 by short interfering RNA (siRNA) demonstrated downregulation of EMT-related molecules (SNAI2, SNAI3 and TWIST1), MMP2 and vasculogenic factors (VEGFA and VEGFC) in thyroid carcinoma cells. We also confirmed that Runx2 silencing suppresses thyroid carcinoma cell invasion in transwell assays. In conclusion, this study provides insight into the potential molecular mechanism of thyroid cancer invasion. Our data suggest that enhanced Runx2 is functionally linked to tumor invasion and metastasis of thyroid carcinoma by regulating EMT-related molecules, matrix metalloproteinases and angiogenic/lymphangiogenic factors.
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PMID:Transcription factor Runx2 is a regulator of epithelial-mesenchymal transition and invasion in thyroid carcinomas. 2264 Oct 97

The prospero homeobox 1 (PROX1) transcription factor is a product of one of the lymphangiogenesis master genes. It has also been suggested to play a role in carcinogenesis, although its precise role in tumour development and metastasis remains unclear. The aim of this study was to gain more knowledge on the PROX1 function in thyroid tumorigenesis. Follicular thyroid cancer-derived cells-CGTH-W-1-were transfected with PROX1-siRNA (small interfering RNA) and their proliferation, cell cycle, apoptosis and motility were then analysed. The transcriptional signature of PROX1 depletion was determined using RNA-Sequencing (RNA-Seq) and the expression of relevant genes was further validated using reverse transcriptase quantitative PCR (RT-qPCR), Western blot and immunocytochemistry. PROX1 depletion resulted in a decreased cell motility, with both migratory and invasive potential being significantly reduced. The cell morphology was also affected, while the other studied cancer-related cell characteristics were not significantly altered. RNA-seq analysis revealed significant changes in the expression of transcripts encoding genes involved in both motility and cytoskeleton organization. Our transcriptional analysis of PROX1-depleted follicular thyroid carcinoma cells followed by functional and phenotypical analyses provide, for the first time, evidence that PROX1 plays an important role in the metastasis of thyroid cancer cells by regulating genes involved in focal adhesion and cytoskeleton organization in tumour cells.
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PMID:Molecular Signature of Prospero Homeobox 1 (PROX1) in Follicular Thyroid Carcinoma Cells. 3106 Mar 42

Fine needle aspiration biopsy (FNAB) is a standard procedure for the detection of thyroid nodules malignancy, yet 10-25% of the sample diagnosed may go undetermined or suspicious. The utility of cancer stem cell markers (CSCM) as a differential diagnosis molecular marker in nodules of suspicious decision in FNAB was hypothesized. Papillary thyroid carcinoma (PTC) and thyroid fibroadenoma (TFA) samples were selected to test the hypothesis. The samples employed in this study were from patients who had thyroid hyperplasia and a suspicious or undetermined diagnosis by FNAB. The patient underwent a successful thyroidectomy at Al-Yarmouk Teaching Hospital in Baghdad between January 2015 and December 2017. All nodule samples underwent a systematic histopathological examination after resection. Tumors diagnosed as PTC and those diagnosed as fibroadenoma (TFA) were selected for this study. Collectively 39 PTC and 11 TFA nodules were included. Quantitative reverse transcriptase real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were used to determine levels of mRNA and proteins of CSCM ALDH1A1, CD44, ABCG2, and Oct3/4 in both types of tumors were used. This study revealed that the expression levels of CSCM were significantly increased in PTC tissues when compared to benign tissues and the positive correlation was found between the CSCM expression levels and tumor stage, size, and gender. In conclusion, for a more precise diagnosis, we suggest these markers be included in what is currently available to characterize malignancy from what is not in thyroid cancer, as well as for the staging process of PTC.
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PMID:Rationales for the Use of Cancer Stem Cells Markers in the Staging of Papillary Thyroid Carcinoma. 3134 76


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