Thyroid Cancer-1 Research Articles

Upregulated TC1 and downregulated Chibby were correlated with the aberrant β-catenin expression in laryngeal squamous cell carcinoma.

As an important member of Wnt/β-catenin signaling pathway, the aberrant expression of β-catenin has been implicated in many cancers. Chibby, a β-catenin binding partner, is an antagonist involved in this pathway. In contrast, thyroid cancer 1 (TC1) as an activator of this pathway can relieve the antagonistic activity of Chibby on the β-catenin-mediated transcription and is high expressed in human tumors. The objectives of this study were to examine the expression of TC1, Chibby, and β-catenin and investigate the association among them in laryngeal squamous cell carcinoma (LSCC). The expression of TC1, Chibby, β-catenin, c-Myc, Cyclin D1, and matrix metalloproteinase-7 (MMP-7) were examined by immunohistochemistry in samples from 53 LSCC patients. Compared with normal laryngeal squamous epithelium (NLSE), there were upregulated expression of TC1, downregulated expression of Chibby, and aberrant cytoplasmic expression of β-catenin in the LSCC tissues (P < .001). The high expression of TC1 was correlated with the tumor site, advanced TNM and T stage, lymphovascular invasion, and poor differentiation in LSCC tissues (P < .050). There were correlations between the aberrant expression of β-catenin and the tumor site, advanced TNM and T stage, lymphovascular invasion, perineurial invasion, and poor differentiation in LSCC tissues (P < .050). Upregulated TC1 and downregulated Chibby were correlated with aberrant expression of β-catenin (P < .001), but no correlation between them (P = .076). The percent of abnormal expression of β-catenin in LSCC was 96.00% in TC1+/Chibby-, 73.68% in TC1+/Chibby+, 0.00% in TC1-/Chibby-, and 0.00% in TC1-/Chibby + group (P < .001). High expression of c-Myc, Cyclin D1, and MMP-7 was observed in LSCC tissues (P < .001). There was statistically significant about the expression of Cyclin D1 and MMP-7 among the groups of TC1+/Chibby-, TC1+/Chibby+, TC1-/Chibby-, and TC1-/Chibby + (P < .001), but was not significance about the expression of c-Myc among them (P = .339). No association was found between overall survival and the expression of TC1, Chibby, and β-catenin (P > .05). The upregulated expression of TC1 and downregulated expression of Chibby were correlated with the aberrant expression of β-catenin and the high expression of Cyclin D1 and MMP-7 in LSCC tissues.

First report on molecular characterization and in silico analysis of caprine TCIM gene

Goats are used as animal models in physiological and biological studies since they can adapt to any harsh climate. The TCIM (transcriptional and immune response regulator) gene was highly expressed in thyroid cancer. The Wnt/-catenin, mitogen-activated ERK1/2, transforming growth factor, and NF-B signaling pathways were all regulated by TC1 protein. Heat shock response is upregulated by the TCIM gene. The caprine TC1 (Thyroid cancer 1) protein is a relatively new gene in livestock, and its different roles in carcinogenesis, cell stress, and heat shock warranted to be investigated. The present study was carried with the aim of molecular characterization of the caprine TCIM gene for the first time. In the present study, an allelic variant at the c.A300T that leads to an amino acid change in p.N100K was observed when compared with the reference sequence from the NCBI Genbank. The goat nucleotide sequence was 89.41% similar to the human TCIM gene. Intrinsically disordered regions of TC1 protein that are predicted in the current study may be important for transcriptional, translational regulation, and cell cycle control. The HSP (heat shock protein) inhibitor geldanamycin (anti-thyroid cancer drug) was used for docking study to find the interacting amino residues with the caprine TC1 protein. Further extensive studies on their association characters, as well as the experimental studies at the protein level, may be useful in the selection of the TCIM gene as a biomarker for carcinogenesis and heat stress in goats.

Targeting Integrins with Radiolabeled RGD Analogues for Radiotheranostics of Metastatic Radioactive Iodine Nonresponsive Thyroid Cancer: New Avenues in Personalized Medicine.

ThyroidVol. 30, No. 4 Editorial and CommentariesTargeting Integrins with Radiolabeled RGD Analogues for Radiotheranostics of Metastatic Radioactive Iodine Nonresponsive Thyroid Cancer: New Avenues in Personalized MedicineJoanna Klubo-Gwiezdzinska and Xiaoyuan ChenJoanna Klubo-GwiezdzinskaAddress correspondence to: Joanna Klubo-Gwiezdzinska, MD, PhD, MHSc, Thyroid Tumors and Functional Thyroid Disorders Section, Metabolic Disease Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Building 10m room 9c103, Bethesda, MD 20892 E-mail Address: joanna.klubo-gwiezdzinska@nih.govThyroid Tumors and Functional Thyroid Disorders Section, Metabolic Disease Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.Search for more papers by this author and Xiaoyuan ChenMolecular Imaging and Nanomedicine Laboratory, National Institutes of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland.Search for more papers by this authorPublished Online:15 Apr 2020https://doi.org/10.1089/thy.2020.0169AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited byEvaluation of integrin αvβ3-targeted imaging for predicting disease progression in patients with high-risk differentiated thyroid cancer (using 99mTc-3PRGD2)19 December 2022 | Cancer Imaging, Vol. 22, No. 1Radiometal-theranostics: the first 20 years*24 November 2022 | Journal of Radioanalytical and Nuclear Chemistry, Vol. 132Theranostic Options for Radioiodine-Refractory Differentiated Thyroid Carcinoma: Recent Advances, Challenges, and Road Ahead12 July 2022 | Frontiers in Endocrinology, Vol. 13Investigation of the Presence of Integrin Alpha-3 and Beta-1 Receptors on Tumor Tissue, Metastatic Lymph Node and Normal Tissue in Thyroid Cancer1 June 2022 | Molecular Imaging and Radionuclide Therapy, Vol. 31, No. 2Translating Molecules into Imaging—The Development of New PET Tracers for Patients with Melanoma29 April 2022 | Diagnostics, Vol. 12, No. 5Multimodal Imaging of Target Detection Algorithm under Artificial Intelligence in the Diagnosis of Early Breast CancerJournal of Healthcare Engineering, Vol. 2022Bioinspired peptide adhesion on Ti implants alleviates wear particle-induced inflammation and improves interfacial osteogenesisJournal of Colloid and Interface Science, Vol. 605Non-Cationic RGD-Containing Protein Nanocarrier for Tumor-Targeted siRNA Delivery17 December 2021 | Pharmaceutics, Vol. 13, No. 12IVUS\IVPA hybrid intravascular molecular imaging of angiogenesis in atherosclerotic plaques via RGDfk peptide-targeted nanoprobesPhotoacoustics, Vol. 22 Volume 30Issue 4Apr 2020 InformationCopyright 2020, Mary Ann Liebert, Inc., publishersTo cite this article:Joanna Klubo-Gwiezdzinska and Xiaoyuan Chen.Targeting Integrins with Radiolabeled RGD Analogues for Radiotheranostics of Metastatic Radioactive Iodine Nonresponsive Thyroid Cancer: New Avenues in Personalized Medicine.Thyroid.Apr 2020.476-478.http://doi.org/10.1089/thy.2020.0169Published in Volume: 30 Issue 4: April 15, 2020Online Ahead of Editing: March 2, 2020PDF download

Correlations of ultrasound and pathological features of thyroid carcinoma with TC-1 mRNA and protein expression.

To investigate the correlations of ultrasound and pathological characteristics of thyroid carcinoma through evaluating the messenger ribonucleic acid (mRNA) level and protein expression of thyroid cancer-1 (TC-1). The patients with papillary thyroid carcinoma (PTC) hospitalized in our hospital were enrolled. Then, real-time fluorescence quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) streptavidin-peroxidase (SP) technique were applied to measure the mRNA and protein expression levels of TC-1 in PTC and corresponding adjacent tissues (NCE) of 50 patients. The relations with clinicopathological and ultrasound characteristics were analyzed. The expression of TC-1 mRNA in PTC tissues was statistically higher than that in corresponding adjacent tissues and significantly correlated with tumor-node-metastasis (TNM) stage, pathological grade, and lymph node metastasis of PTC (p<0.05). According to IHC, TC-1 positive expression was mainly found in the cytoplasm in PTC samples, which was statistically increased compared to adjacent tissues (p<0.05). Western blotting results revealed that the relative protein expression of TC-1 in PTC tissues was 2.646±195, which was significantly higher than that in corresponding adjacent tissues (892±76) (p<0.05). The TC-1 protein expression also showed significant associations with TNM stage, pathological grade, and lymph node metastasis of patients (p<0.05). The level of TC-1 mRNA in PTC tissues with micro-calcification detected by ultrasound (87.46±49.55) was higher than that in those without micro-calcification (38.46±29.15) (p<0.05). The expression of TC-1 plays an important role in the occurrence and development of PTC. Ultrasound characteristics reflect the expression of TC-1 in PTC tissues to some extent, providing a certain value in evaluating the prognosis of PTC.

The expression of thyroid cancer-1 in breast cancer and its effect on proliferation and apoptosis of breast cancer cells

Objective To investigate the expression of thyroid cancer-1 (TC-1) in breast cancer and its influence on the proliferation and apoptosis of breast cancer cells. Methods Reverse transcriptase-polymerase chain reaction (RT-qPCR) and Western blotting were used to detect the expression of TC-1 in breast cancer tissues and corresponding paracancerous tissues. The breast cancer cell MCF-7 were transfected with TC-1 siRNA and siRNA control, it was named as interference group and negative group, the cells without treatment were used as control group. Cell proliferation was detected by methyl thiazol tetrazolium (MTT), apoptosis was detected by flow cytometry, the expressions of β-catenin, c-Myc, Cleaved Caspase-3 were detected by Western blotting. Results The level of TC-1 in breast cancer tissues was higher than that in paracancerous tissues (t=17.746, P=0.000; t=12.705, P=0.000). The apoptosis rate, survival rate, TC-1, β-catenin, c-Myc, Cleaved Caspase-3 in the control group and the negative group did not change significantly. The rate of apoptosis in the interference group was higher than that in the control group, the cell survival rate was lower than that of the control group, and the levels of β-catenin and c-Myc were lower than those of the control group, the levels of Cleaved Caspase-3 was higher than those of the control group (t=13.986, P=0.000; t=7.015, P=0.002; t=10.457, P=0.001; t=27.886, P=0.000; t=7.426, P=0.002). Conclusion The expression of TC-1 was up-regulated in breast cancer tissues, interference with TC-1 can inhibit proliferation of breast cancer cells, promoting apoptosis of breast cancer cells, the Wnt signaling pathway may be one of its mechanisms. Key words: Breast cancer; Proliferation; Apoptosis; Thyroid cancer-1

The 30‐year mental health legacy of the Chernobyl disaster

The 30‐year mental health legacy of the <scp>C</scp>hernobyl disaster

Abstract 3581: Rapid conversion to resistance, of a colon PDX with ret-fusion, by ponatinib treatment could potentially be attributed to the introduction of the gate keeper mutation V804M

Abstract RET encodes a receptor tyrosine kinase (RTK) involved in cellular mechanisms of proliferation, migration and differentiation. RET fusions with different genes at 10q11.2 result in constitutively activation and drive tumor development in various cancers: 10-20% of sporadic papillary thyroid cancer1, spitzoid neoplasms, CMML and 1% of lung adenocarcinomas2,3. RET fusions have been suggested to be important therapeutic targets. Ponatinib, a multi-kinase inhibitor, was approved for the treatment of Ph+ chronic myeloid leukemia (CML) and acute lymphoblast leukemia (ALL), including CML with T315I/imatinib-resistance. Ponatinib has recently been found to potently inhibit the common NSCLC fusion variant, KIF5B-RET at clinically-achievable concentrations. We have established large collection of colorectal patient derived xenografts (PDXs)4,5. Two of the poorly differentiated adenocarcinoma, CR1520 and CR2518, contain two different chromosome 10 in-frame RET-fusions, CCDC6-RET (CR2518) and NCOA4-RET (CR1520), as revealed by RNAseq and Sanger Sequencing6. Both models have also demonstrated over-expressing ret gene at mRNA levels. More importantly, they both responded Ponatinib significantly along with dephosphorylation of RET and downstream AKT, confirming these two types of Ret fusions as oncogenic drivers in these two models6. In addition, we also observed that Ponatinib treatment also rapidly drives CR2518 into its resistance (The resistant derivative is called CR2545). To investigate the underlying mechanism of the resistance, we performed RNAseq analysis of CR2545, which revealed retaining of the ret-fusion, but also the introduction of a previously described gate-keeper mutation, V804M, at ret kinase domain. V804M, a mutation frequently found in familial medullary thyroid carcinoma (FMTC), introduces bulky amino acid at position 804 and found to resistant to vandetanib. This may contribute to the resistance. However, this notion apparently contradicts to the previous observation/claim that V804M is sensitive to Ponatinib7, and ponatinib should be used to treat RET-V804M/L cancers. It is possible that the described V804M containing vandetanib resistant cells are sensitive to ponatinib, but via a non-RET mechanism for the multi-kinase inhibition nature of ponatinib; or in our case, there are other non-RET Ponatinib resistant mechanisms been introduced in CR2545 where RET is no longer the key oncogenic driver. We are currently testing other RET inhibitors and also assessing pharmacodanamic (PD) parameters to further investigate RET resistant mechanism. The further findings from the ongoing studies will be presented at the meeting. Citation Format: Mengmeng Yang, Jie Cai, Sheng Guo, Jean-Pierre Wery, Henry Qixiang Li. Rapid conversion to resistance, of a colon PDX with ret-fusion, by ponatinib treatment could potentially be attributed to the introduction of the gate keeper mutation V804M. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3581. doi:10.1158/1538-7445.AM2015-3581

Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast.

The human Thyroid Cancer-1 (hTC-1) protein, also known as C8orf4 was initially identified as a gene that was up-regulated in human thyroid cancer. Here we show that hTC-1 is a peptide that prevents the effects of over-expressing Bax in yeast. Analysis of the 106 residues of hTC-1 in available protein databases revealed direct orthologues in jawed-vertebrates, including mammals, frogs, fish and sharks. No TC-1 orthologue was detected in lower organisms, including yeast. Here we show that TC-1 is a general pro-survival peptide since it prevents the growth- and cell death-inducing effects of copper in yeast. Human TC-1 also prevented the deleterious effects that occur due to the over-expression of a number of key pro-apoptotic peptides, including YCA1, YBH3, NUC1, and AIF1. Even though the protective effects were more pronounced with the over-expression of YBH3 and YCA1, hTC-1 could still protect yeast mutants lacking YBH3 and YCA1 from the effects of copper sulfate. This suggests that the protective effects of TC-1 are not limited to specific pathways or processes. Taken together, our results indicate that hTC-1 is a pro-survival protein that retains its function when heterologously expressed in yeast. Thus yeast is a useful model to characterize the potential roles in cell death and survival of cancer related genes.

TC-1 overexpression promotes cell proliferation in human non-small cell lung cancer that can be inhibited by PD173074.

Thyroid cancer-1 (TC-1), a natively disordered protein, is widely expressed in vertebrates and overexpressed in many kinds of tumors. However, its exact role and regulation mechanism in human non-small cell lung cancer (NSCLC) are still unclear. In the present study, we found that TC-1 is highly expressed in NSCLC and that its aberrant expression is strongly associated with NSCLC cell proliferation. Exogenous TC-1 overexpression promotes cell proliferation, accelerates the cell G1-to-S-phase transition, and reduces apoptosis in NSCLC. The knockdown of TC-1, however, inhibits NSCLC cell proliferation, cycle transition, and apoptosis resistance. Furthermore, we also demonstrated that PD173074, which functions as an inhibitor of the TC-1 in NSCLC, decreases the expression of TC-1 and inhibits TC-1 overexpression mediated cell proliferation in vitro and in vivo. Nevertheless, the inhibition function of PD173074 on NSCLC cell proliferation was eliminated in cells with TC-1 knockdown. These results suggest that PD173074 plays a significant role in TC-1 overexpression mediated NSCLC cell proliferation and may be a potential intervention target for the prevention of cell proliferation in NSCLC.

TC-1 (c8orf4) enhances aggressive biologic behavior in lung cancer through the Wnt/β-catenin pathway

BackgroundThe thyroid cancer-1 (TC-1) or c8orf4 gene encodes a 106-residue naturally disordered protein that has been found to be associated with thyroid, gastric, and breast cancer. A recent study has indicated that the protein functions as a positive regulator in the Wnt/β-catenin signaling pathway in human breast cancer. However, no research has been done in the area of lung cancer. Therefore, the goal of the present study was to confirm the relationship among TC-1, lung cancer, and the Wnt/β-catenin signaling pathway. Materials and methodsThe expression of TC-1 was immunohistochemically examined in 147 patients with non–small-cell lung cancer. TC-1–overexpressed and silenced A549 cells were infected using lentivirus and MTT cell proliferation analysis, and Matrigel invasion assays and scratch-wound assays were performed to confirm the biologic behavioral changes in different A549 cell subsets. The Wnt/β-catenin signaling pathway, key gene β-catenin, target genes of vascular endothelial growth factor, cyclin D1, matrix metalloproteinase-7, c-myc, and survivin were tested at the mRNA and protein level. ResultsTC-1 was detected in 97 of the 147 non–small-cell lung cancer primary tumor specimens, and its expression correlated with the TNM stage and regional lymph node metastasis (P < 0.01). In vitro experiments demonstrated that TC-1 expression affected both proliferation and invasion in the A549 cell line. Furthermore, expression of TC-1 protein affected the Wnt/β-catenin signaling pathway’s downstream genes, such as vascular endothelial growth factor and matrix metalloproteinase-7, at the mRNA and protein level. ConclusionsTC-1 expression is associated with aggressive biologic behavior in lung cancer and might coordinate with the Wnt/β-catenin pathway as a positive upstream regulator that induces these behaviors.

Role of thyroid cancer-1 in tumorigenesis and progression

thyroid cancer(TC-1 ),a nuclear protein coded by TC-1,regulates the cell cycle,participates transcription and translation,and is correlated with the proliferation of normal and cancer cells.TC-1 participates in the Wnt/beta-catenin signaling pathway which can promote the up-regulation of proto-oncogene.Hence it plays an important role in the malignant transformation and development of the tumors,such as thyroid cancer,gastric cancer and breast cancer.Therefore,as a potential tumor-associated protein,it's likely to be used for fundamental research and gene targeting therapy. Key words: Neoplasms; Genes; Signal transduction; TC-1

The American Thyroid Association and American Association of Clinical Endocrinologists Hyperthyroidism and Other Causes of Thyrotoxicosis Guidelines: Viewpoints from Japan and Korea

ThyroidVol. 21, No. 6 EditorialsThe American Thyroid Association and American Association of Clinical Endocrinologists Hyperthyroidism and Other Causes of Thyrotoxicosis Guidelines: Viewpoints from Japan and KoreaShunichi Yamashita, Nobuyuki Amino, and Young Kee ShongShunichi YamashitaMember of the council of the Asia & Oceania Thyroid Association (AOTA).Director, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.Search for more papers by this author, Nobuyuki AminoAOTA advisory member to the World Thyroid Foundation.Kuma Hospital, Kobe, Japan.Search for more papers by this author, and Young Kee ShongMember of the council of the Asia & Oceania Thyroid Association (AOTA).Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.Search for more papers by this authorPublished Online:10 Jun 2011https://doi.org/10.1089/thy.2011.2106.ed1AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited ByEvaluation of analytic and clinical performance of two immunoassays for detecting thyroid‐stimulating receptor antibody in the diagnosis of Graves’ disease9 November 2021 | Journal of Clinical Laboratory Analysis, Vol. 35, No. 12Aeromedical Decision Making for Military Aircrew with Graves’ DiseaseAerospace Medicine and Human Performance, Vol. 92, No. 12Graves’ Disease4 May 2021Hyperthyreose8 December 2021Safety of long-term antithyroid drug treatment? A systematic review27 May 2019 | Journal of Endocrinological Investigation, Vol. 42, No. 11Is Hyperthyroidism Diagnosed and Treated Appropriately in the United States?Advances in Surgery, Vol. 53When should antithyroid drug therapy to reduce the relapse rate of hyperthyroidism in Graves’ disease be discontinued?24 June 2019 | Endocrine, Vol. 65, No. 2Change of surgical strategy for Graves’ disease from subtotal thyroidectomy to total thyroidectomy: a single institutional experienceEndocrine Journal, Vol. 66, No. 2Determining patient selection tool and response predictor for outpatient 30 mCi radioiodine ablation dose in non-metastatic differentiated thyroid carcinoma: a Japanese perspectiveEndocrine Journal, Vol. 65, No. 3Long-Term Antithyroid Drug Treatment: A Systematic Review and Meta-Analysis Fereidoun Azizi and Ramin Malboosbaf1 October 2017 | Thyroid, Vol. 27, No. 10Emphasis on the early diagnosis of antithyroid drug-induced agranulocytosis: retrospective analysis over 16 years at one Chinese center24 February 2017 | Journal of Endocrinological Investigation, Vol. 40, No. 7Comparative Effectiveness of Treatment Choices for Graves' Hyperthyroidism: A Historical Cohort Study Vishnu Sundaresh, Juan P. Brito, Prabin Thapa, Rebecca S. Bahn, and Marius N. Stan1 April 2017 | Thyroid, Vol. 27, No. 4A SURVEY OF CLINICAL PRACTICE PATTERNS IN MANAGEMENT OF GRAVES DISEASE IN THE MIDDLE EAST AND NORTH AFRICAEndocrine Practice, Vol. 23, No. 3HyperthyroidismThe Lancet, Vol. 388, No. 10047Punica granatum (pomegranate) peel extract exerts potent antitumor and anti-metastasis activity in thyroid cancer1 January 2016 | RSC Advances, Vol. 6, No. 87A 2013 European survey of clinical practice patterns in the management of Graves' disease9 January 2015 | Clinical Endocrinology, Vol. 84, No. 1Antithyroid Arthritis Syndrome: A Case Report and Review of the LiteratureInternal Medicine, Vol. 55, No. 24Thyroidectomy in Patients with Graves’ DiseaseEstablishment of Trimester-Specific Reference Intervals for Thyroid Hormones in Korean Pregnant WomenAnnals of Laboratory Medicine, Vol. 35, No. 2A Case of Marine-Lenhart Syndrome with a Negative TSH Receptor Antibody Titer Successfully Treated with a Fixed, Low Dose of I 131Case Reports in Endocrinology, Vol. 2014Diagnosis and management of Graves disease: a global overview15 October 2013 | Nature Reviews Endocrinology, Vol. 9, No. 12Dual Thyroid Ectopia with Graves’ Disease: a Case Report and a Review of the Literature9 August 2012 | Nuclear Medicine and Molecular Imaging, Vol. 46, No. 4Subclinical Thyroid Disease: Time to Enter the Age of Evidence-Based Medicine Bernard Goichot and Simon H. Pearce1 August 2012 | Thyroid, Vol. 22, No. 8Changes in the thyroid function of Graves^|^rsquo; disease patients treated by subtotal thyroidectomyEndocrine Journal, Vol. 59, No. 12 Volume 21Issue 6Jun 2011 InformationCopyright 2011, Mary Ann Liebert, Inc.To cite this article:Shunichi Yamashita, Nobuyuki Amino, and Young Kee Shong.The American Thyroid Association and American Association of Clinical Endocrinologists Hyperthyroidism and Other Causes of Thyrotoxicosis Guidelines: Viewpoints from Japan and Korea.Thyroid.Jun 2011.577-580.http://doi.org/10.1089/thy.2011.2106.ed1Published in Volume: 21 Issue 6: June 10, 2011PDF download

Structural Characterization of Partially Disordered Human Chibby: Insights into Its Function in the Wnt-Signaling Pathway

The Wnt/β-catenin signaling pathway is critical to embryonic development as well as adult tissue regeneration. Dysregulation of this pathway can lead to a variety of human diseases, in particular cancers. Chibby (Cby), a small and highly conserved protein, plays an antagonistic role in Wnt signaling by inhibiting the binding of β-catenin to Tcf/Lef family proteins, a protein interaction that is essential for the transcriptional activation of Wnt target genes. Cby is also involved in regulating intracellular distribution of β-catenin. Phosphorylated Cby forms a ternary complex with 14-3-3 protein and β-catenin, facilitating the export of β-catenin from the nucleus. On the other hand, the antagonistic function of Cby is inhibited upon binding to thyroid cancer-1 (TC-1). To dissect the structure−function relationship of Cby, we have used NMR spectroscopy, ESI-MS, CD, and DLS to extensively characterize the structure of human Cby. Our results show that the 126-residue Cby is partially disordered under nondenaturing conditions. While the N-terminal portion of the protein is predominantly unstructured in solution, the C-terminal half of Cby adopts a coiled-coil structure through self-association. Initial data for the binding studies of Cby to 14-3-3ζ (one of the isoforms in the 14-3-3 family) and TC-1 via these two distinct structural modules have also been obtained. It is noteworthy that in a recent large-scale analysis of the intrinsically disordered proteome of mouse, a substantial number of disordered proteins are predicted to have coiled-coil motif presence in their sequences. The combination of these two molecular recognition features could facilitate disordered Cby in assembling protein complexes via different modes of interaction.

Investigation of copy-number variations of C8orf4 in hematological malignancies

C8orf4, thyroid cancer-1 (TC1), was first identified in papillary thyroid carcinoma and encodes a nucleus-localized protein. A recent array-based study implicated the presence of copy-number variations (CNVs) of C8orf4 in the genomes of acute myelogenous leukemia. However, the functional impact of such regions needs to be extensively investigated in large amount of clinical samples. The purpose of this study is to confirm the relationship between C8orf4 CNVs and hematological malignancies. In our study, we collected bone marrow samples from 515 hematological malignancies and 102 healthy controls. And the CNVs of C8orf4 were detected by real-time PCR. We found significant association between the copy-number deletions of C8orf4 and the risk of these hematological malignancies including acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), multiple myeloma (MM), and myelodysplastic syndrome (MDS). We also found that the expression of C8orf4 mRNA was relatively lower in the samples with 1 copy of DNA than those with 2 copies of DNA. The CNVs of C8orf4 were associated with the risk of hematological malignancies.

Fractionated Radioiodine Therapy for Hyperthyroidism Caused by Widespread Metastatic Follicular Thyroid Carcinoma

ThyroidVol. 20, No. 5 Letters to the EditorFractionated Radioiodine Therapy for Hyperthyroidism Caused by Widespread Metastatic Follicular Thyroid CarcinomaEijun Nishihara, Nobuyuki Amino, and Akira MiyauchiEijun NishiharaSearch for more papers by this author, Nobuyuki AminoSearch for more papers by this author, and Akira MiyauchiSearch for more papers by this authorPublished Online:7 May 2010https://doi.org/10.1089/thy.2009.0460AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Fractionated Radioiodine Therapy for Hyperthyroidism Caused by Widespread Metastatic Follicular Thyroid Carcinoma." , 20(5), pp. 569–570FiguresReferencesRelatedDetailsCited ByThyroid Papillary Carcinoma and Hyperthyroidism: A Case Study4 January 2022 | EMJ OncologyFollicular Thyroid Cancer1 January 2022Thyrotoxicosis with concomitant thyroid cancerEndocrine-Related Cancer, Vol. 26, No. 7Thyrotoxicosis: Diagnosis and ManagementMayo Clinic Proceedings, Vol. 94, No. 6Thyrotoxicosis Caused by Functioning Metastases of Differentiated Thyroid Cancer6 October 2018An upper cervical cord compression secondary to occult follicular thyroid carcinoma metastases successfully treated with multiple radioiodine therapiesMedicine, Vol. 96, No. 41Clinical Management and Outcomes in Patients with Hyperfunctioning Distant Metastases from Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Therapy Zhong-Ling Qiu, Chen-Tian Shen, and Quan-Yong Luo4 February 2015 | Thyroid, Vol. 25, No. 2Euthyroid Status After Total Thyroidectomy Due to Functioning Lung Metastases from a Clear Cell Variant of Papillary Thyroid Carcinoma Ji In Lee, Yun Jae Chung, Sung Jun Park, Han Suk Ryu, and Bo Youn Cho1 October 2012 | Thyroid, Vol. 22, No. 10 Volume 20Issue 5May 2010 InformationCopyright 2010, Mary Ann Liebert, Inc.To cite this article:Eijun Nishihara, Nobuyuki Amino, and Akira Miyauchi.Fractionated Radioiodine Therapy for Hyperthyroidism Caused by Widespread Metastatic Follicular Thyroid Carcinoma.Thyroid.May 2010.569-570.http://doi.org/10.1089/thy.2009.0460Published in Volume: 20 Issue 5: May 7, 2010Online Ahead of Print:April 12, 2010PDF download

Procalcitonin Can Be Used for Monitoring Sepsis in Patients with Medullary Thyroid Carcinoma

ThyroidVol. 19, No. 11 Letters to the EditorProcalcitonin Can Be Used for Monitoring Sepsis in Patients with Medullary Thyroid CarcinomaAlexander R. Novotny, Peter Luppa, Robert Rosenberg, H. Schneider, Matthias Maak, Holger Bartels, Bernhard Holzmann, and Helmut FriessAlexander R. NovotnyDepartment of Surgery, Technical University of Munich, Munich, Germany.Search for more papers by this author, Peter LuppaInstitute of Clinical Chemistry and Pathobiochemistry, Technical University of Munich, Munich, Germany.Search for more papers by this author, Robert RosenbergDepartment of Surgery, Technical University of Munich, Munich, Germany.Search for more papers by this author, H. SchneiderInstitute of Clinical Chemistry and Pathobiochemistry, Technical University of Munich, Munich, Germany.Search for more papers by this author, Matthias MaakDepartment of Surgery, Technical University of Munich, Munich, Germany.Search for more papers by this author, Holger BartelsDepartment of Surgery, Technical University of Munich, Munich, Germany.Search for more papers by this author, Bernhard HolzmannDepartment of Surgery, Technical University of Munich, Munich, Germany.Search for more papers by this author, and Helmut FriessDepartment of Surgery, Technical University of Munich, Munich, Germany.Search for more papers by this authorPublished Online:4 Nov 2009https://doi.org/10.1089/thy.2009.0093AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited ByProcalcitonin measured by three different assays is an excellent tumor marker for the follow-up of patients with medullary thyroid carcinoma14 July 2021 | Clinical Chemistry and Laboratory Medicine (CCLM), Vol. 59, No. 11Procalcitonin as an Alternative Tumor Marker of Medullary Thyroid Carcinoma12 August 2021 | The Journal of Clinical Endocrinology & Metabolism, Vol. 25Uso della procalcitonina come marker del carcinoma midollare tiroideo2 August 2018 | La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine, Vol. 14, No. 4Procalcitonin as a postoperative marker in the follow-up of patients affected by medullary thyroid carcinoma30 April 2018 | The International Journal of Biological Markers, Vol. 33, No. 2Procalcitonin as Marker of Recurrent Medullary Thyroid Carcinoma: A Systematic Review and Meta-AnalysisEndocrinology and Metabolism, Vol. 33, No. 2Procalcitonin for detecting medullary thyroid carcinoma: a systematic reviewEndocrine-Related Cancer, Vol. 22, No. 3Basal and Stimulated Calcitonin and Procalcitonin by Various Assays in Patients with and without Medullary Thyroid Cancer1 March 2011 | Clinical Chemistry, Vol. 57, No. 3 Volume 19Issue 11Nov 2009 InformationCopyright 2009, Mary Ann Liebert, Inc.To cite this article:Alexander R. Novotny, Peter Luppa, Robert Rosenberg, H. Schneider, Matthias Maak, Holger Bartels, Bernhard Holzmann, and Helmut Friess.Procalcitonin Can Be Used for Monitoring Sepsis in Patients with Medullary Thyroid Carcinoma.Thyroid.Nov 2009.1287-1289.http://doi.org/10.1089/thy.2009.0093Published in Volume: 19 Issue 11: November 4, 2009Online Ahead of Print:September 28, 2009PDF download

The intrinsically disordered TC‐1 interacts with Chibby via regions with high helical propensity

Thyroid cancer 1 (TC-1) is a 106-residue naturally disordered protein that has been found to associate with thyroid, gastric, and breast cancers. Recent studies showed that the protein functions as a positive regulator in the Wnt/beta-catenin signaling pathway, a pathway that is known to play essential roles in developmental processes and causes tumor formation when misregulated. By competing with beta-catenin for binding to Chibby (Cby), a conserved nuclear protein that antagonizes the beta-catenin-mediated transcriptions, TC-1 up-regulates a number of beta-catenin target genes that are known to be involved in the aggressive behavior of cancers. In order to gain a molecular understanding of the role TC-1 plays in regulating the Wnt/beta-catenin signaling pathway, detailed structural studies of the protein and its interaction with Cby are essential. In this work, we used nuclear magnetic resonance (NMR) spectroscopy to elucidate the structure of TC-1 and its interaction with Cby. Our results indicate that even though TC-1 is naturally disordered, the protein adopts fairly compact conformations under nondenaturing conditions. Chemical shift analysis and relaxation measurements show that three regions (D44-R53, K58-A64, and D73-T88) with high-helical propensity are present in the C-terminal portion of TC-1. Upon addition of Cby, significant broadening of resonance signals derived from these helical regions of TC-1 was observed. The result indicates that the intrinsically disordered TC-1 interacts with Cby via its transient helical structure.

C8orf4/TC-1(Thyroid Cancer-1) Gene Expression in Thyroid Cancer and Goiter

Background: The expression of the thyroid cancer-1(TC-1) gene seems to be related with malignant transformation in the thyroid tissue. Objective: We evaluated the potential use of TC-1 gene expression as a marker of malignancy in thyroid nodules. Methods: A total of 92 frozen thyroid samples were studied, including 46 samples from thyroid nodules (19 papillary carcinomas, 1 follicular carcinoma, 24 adenomatous goiters, and 2 follicular adenomas) and 46 samples from normal surrounding thyroid tissue. Total RNA was extracted and TC-1 expression was assessed by semiquantitative Multiplex PCR. Results were verified using real-time RT-PCR in some of the samples. Results: Overall mean TC-1 gene expression (normalized by the ABL gene) was 1.73 ± 1.67 (0.33–9.33). There was a significant difference (p < 0.001) between TC-1 gene expression in benign thyroid lesions (1.07 ± 0.10) and carcinomas (2.73 ± 0.51). Conclusion: Our results suggest that TC-1 gene expression may be useful in the differential diagnosis of goiters and thyroid papillary carcinomas.

TC-1 is a novel tumorigenic and natively disordered protein associated with thyroid cancer.

A novel gene, thyroid cancer 1 (TC-1), was found recently to be overexpressed in thyroid cancer. TC-1 shows no homology to any of the known thyroid cancer-associated genes. We have produced stable transformants of normal thyroid cells that express the TC-1 gene, and these cells show increased proliferation rates and anchorage-independent growth in soft agar. Apoptosis rates also are decreased in the transformed cells. We also have expressed recombinant TC-1 protein and have undertaken a structural and functional characterization of the protein. The protein is monomeric and predominantly unstructured under conditions of physiologic salt and pH. This places it in the category of natively disordered proteins, a rapidly expanding group of proteins, many members of which play critical roles in cell regulation processes. We show that the protein can be phosphorylated by cyclic AMP-dependent protein kinase and protein kinase C, and the activity of both of these kinases is up-regulated when cells are stably transfected with TC-1. These results suggest that overexpression of TC-1 may be important in thyroid carcinogenesis.

Cloning of TC-1 (C8orf4), a Novel Gene Found to Be Overexpressed in Thyroid Cancer

A novel gene highly expressed in thyroid cancer, designated TC-1 (thyroid cancer-1), was cloned from suppression subtractive hybridization between papillary thyroid carcinoma and its surrounding normal thyroid tissue. Overexpression of TC-1 in thyroid cancer was confirmed in 15/16 paired samples by RT-PCR and Northern analysis. Ubiquitously expressed in human tissues, the TC-1 sequence showed no homology to any known gene, but matched a cluster of ESTs. After alignment of our sequence with the ESTs, the missing transcription start site was obtained by 5′-RACE and verified by primer extension analysis. The full-length mRNA sequence of 1327 bp has an open reading frame of 321 bp, which encodes a highly conserved protein. Three regulatory motifs were identified at the expected positions within 1 kb of the 5′ flanking sequence obtained by genome walking. Using fluorescence in situ hybridization, TC-1 was localized to chromosome 8p11.2. The overexpression of TC-1 in papillary carcinoma suggests that it may have an important role in thyroid carcinogenesis.