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Sample records for human thyroid tumors

  1. Expression of somatostatin receptor subtypes in human thyroid tumors: the immunohistochemical and molecular biology (RT-PCR investigation

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    Pisarek Hanna

    2009-01-01

    Full Text Available Abstract Human endocrine tumors often express the somatostatin receptors SSTR 1–5 with different intensity. It has been widely investigated their distribution in pituitary adenomas, brain tumors, adrenal tumors and neuroendocrine tumors in gastrointestinal tract (NET. Some of studies also concern the expression of SSTRs in thyroid tumors but they are mainly limited to parafollicular C cells – derived medullary thyroid carcinomas (MTC. Results of SSTR 1–5 detection in other thyroid pathologies like follicular adenomas and papillary cancers are still scarce and often controversial, depending of investigation method used. The aim of this study was to report the presence of all the 5 subtypes of SSTR (including 2A and 2B SSTR isoforms in some surgically treated human thyroid tumors by means of immunohistochemistry and real-time PCR method and to correlate the results obtained with both techniques. SSTR 1 protein was expressed in 88.8% of investigated cases, SSTR 2A and 2B both in 44.4%, SSTR 3 in 55.5%, SSTR 4 in 11.2% and SSTR 5 in 33.3%. SSTR 1 is the dominant form in the thyroid gland tumor and hyperplasia. We found positive confirmation of both methods in 88.8% for SSTR 1, 2A, 3 subtypes, in 22.2% for SSTR 4 and in 100% for SSTR 5. It suggests that somatostatin multiligand analogs or selective SSTR 1 agonists may be used in thyroid tumors treatment.

  2. Global tyrosine kinome profiling of human thyroid tumors identifies Src as a promising target for invasive cancers

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    Cho, Nancy L., E-mail: nlcho@partners.org [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Lin, Chi-Iou [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Du, Jinyan [Broad Institute, Massachusetts Institute of Technology, Cambridge, MA 02142 (United States); Whang, Edward E. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Ito, Hiromichi [Department of Surgery, Michigan State University, Lansing, MI 48912 (United States); Moore, Francis D.; Ruan, Daniel T. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Kinome profiling is a novel technique for identifying activated kinases in human cancers. Black-Right-Pointing-Pointer Src activity is increased in invasive thyroid cancers. Black-Right-Pointing-Pointer Inhibition of Src activity decreased proliferation and invasion in vitro. Black-Right-Pointing-Pointer Further investigation of Src targeted therapies in thyroid cancer is warranted. -- Abstract: Background: Novel therapies are needed for the treatment of invasive thyroid cancers. Aberrant activation of tyrosine kinases plays an important role in thyroid oncogenesis. Because current targeted therapies are biased toward a small subset of tyrosine kinases, we conducted a study to reveal novel therapeutic targets for thyroid cancer using a bead-based, high-throughput system. Methods: Thyroid tumors and matched normal tissues were harvested from twenty-six patients in the operating room. Protein lysates were analyzed using the Luminex immunosandwich, a bead-based kinase phosphorylation assay. Data was analyzed using GenePattern 3.0 software and clustered according to histology, demographic factors, and tumor status regarding capsular invasion, size, lymphovascular invasion, and extrathyroidal extension. Survival and invasion assays were performed to determine the effect of Src inhibition in papillary thyroid cancer (PTC) cells. Results: Tyrosine kinome profiling demonstrated upregulation of nine tyrosine kinases in tumors relative to matched normal thyroid tissue: EGFR, PTK6, BTK, HCK, ABL1, TNK1, GRB2, ERK, and SRC. Supervised clustering of well-differentiated tumors by histology, gender, age, or size did not reveal significant differences in tyrosine kinase activity. However, supervised clustering by the presence of invasive disease showed increased Src activity in invasive tumors relative to non-invasive tumors (60% v. 0%, p < 0.05). In vitro, we found that Src inhibition in PTC cells decreased cell invasion and proliferation

  3. Nucleophosmin is overexpressed in thyroid tumors

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    Pianta, Annalisa; Puppin, Cinzia [Dipartimento di Scienze e Tecnologie Biomediche, Universita di Udine, Udine (Italy); Franzoni, Alessandra; Fabbro, Dora [Azienda Ospedaliero-Universitaria ' S. Maria della Misericordia' Udine, Udine (Italy); Di Loreto, Carla [Dipartimento di Ricerche Mediche e Morfologiche, Universita di Udine, Udine (Italy); Bulotta, Stefania [Department of Pharmacobiological Sciences, Universita di Catanzaro ' Magna Graecia' , Catanzaro (Italy); Deganuto, Marta; Paron, Igor; Tell, Gianluca [Dipartimento di Scienze e Tecnologie Biomediche, Universita di Udine, Udine (Italy); Puxeddu, Efisio [Department of Internal Medicine, Universita di Perugia, Perugia (Italy); Filetti, Sebastiano [Department of Clinical Sciences, Universita di Roma ' La Sapienza' , Roma (Italy); Russo, Diego [Department of Pharmacobiological Sciences, Universita di Catanzaro ' Magna Graecia' , Catanzaro (Italy); Damante, Giuseppe, E-mail: giuseppe.damante@uniud.it [Dipartimento di Scienze e Tecnologie Biomediche, Universita di Udine, Udine (Italy); Azienda Ospedaliero-Universitaria ' S. Maria della Misericordia' Udine, Udine (Italy)

    2010-07-02

    Nucleophosmin (NPM) is a protein that contributes to several cell functions. Depending on the context, it can act as an oncogene or tumor suppressor. No data are available on NPM expression in thyroid cells. In this work, we analyzed both NPM mRNA and protein levels in a series of human thyroid tumor tissues and cell lines. By using immunohistochemistry, NPM overexpression was detected in papillary, follicular, undifferentiated thyroid cancer, and also in follicular benign adenomas, indicating it as an early event during thyroid tumorigenesis. In contrast, various levels of NPM mRNA levels as detected by quantitative RT-PCR were observed in tumor tissues, suggesting a dissociation between protein and transcript expression. The same behavior was observed in the normal thyroid FRTL5 cell lines. In these cells, a positive correlation between NPM protein levels, but not mRNA, and proliferation state was detected. By using thyroid tumor cell lines, we demonstrated that such a post-mRNA regulation may depend on NPM binding to p-Akt, whose levels were found to be increased in the tumor cells, in parallel with reduction of PTEN. In conclusion, our present data demonstrate for the first time that nucleophosmin is overexpressed in thyroid tumors, as an early event of thyroid tumorigenesis. It seems as a result of a dysregulation occurring at protein and not transcriptional level related to an increase of p-Akt levels of transformed thyrocytes.

  4. [Malignant tumors of thyroid gland].

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    Uhliarová, B; Bugová, G; Hajtman, A

    2015-01-01

    The incidence of thyroid cancer has been increasing. The aim of this work was to determine risk factors, diagnostic methods and extent of surgical treatment of malignant goiter. The authors retrospectively analyzed patients who were surgically treated for thyroid disease at the Department of Otorhinolaryngology, Head and Neck Surgery, Comenius University, Jessenius Faculty of Medicine, Teaching Hospital in Martin, Slovakia, from the January 1st, 2006 to December 31st, 2013, for thyroid disease. The incidence, risk factors of malignant thyroid tumors, indication for surgery and its complications were evaluated. A total of 1,620 adult patients were surgically treated for thyroid disease at the Department of ENT, Head and Neck Surgery, CU JMF, UH in Martin, Slovakia, between 2006- 2013. Malignant tumors were identified in 238 patients (15%). Microcarcinoma (incidentally detected malignant tumor 1 cm) occurred in 78 cases (5%). Malignant thyroid tumor was more common in younger patients (p = 0.002). Newly created and larger nodules positively correlated with the occurrence of malignancy (p = 0.003, p = 0.041, resp.). Gender, family history of thyroid disorder, previous radiation therapy, and previous malignancy did not affect the incidence of malignant tumor of thyroid gland. High sensitivity and specificity in the dia-gnosis of malignant thyroid nodule was observed using aspiration cytology (75%, 97%, resp.) and intraoperative histopathological examination (88%, 100%, resp.). Malignant tumor of thyroid gland is more common in younger patients with newly developed nodule. The risk factors of malignancy increase with the size of the thyroid nodule. Aspiration cytology and peroperative histopathology have high sensitivity and specificity in the dia-gnosis of malignant thyroid tumor; therefore, they should be a standard method in the dia-gnosis of nodular goiter. The method of choice in the treatment of thyroid malignancy is total thyroidectomy.

  5. Calcitonin-negative primary neuroendocrine tumor of the thyroid ...

    African Journals Online (AJOL)

    nonmedullary" in humans is a rare tumor that arises primarily in the thyroid gland and may be mistaken for medullary thyroid carcinoma; it is characterized by the immunohistochemical (IHC) expression of neuroendocrine markers and the absence of ...

  6. Molecular diagnostics of thyroid tumors.

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    Nikiforov, Yuri E

    2011-05-01

    Thyroid cancer is the most common type of endocrine malignancy and its incidence is steadily increasing. Papillary carcinoma and follicular carcinoma are the most common types of thyroid cancer and represent those tumor types for which use of molecular markers for diagnosis and prognostication is of high clinical significance. To review the most common molecular alterations in thyroid cancer and their diagnostic and prognostic utility. PubMed (US National Library of Medicine)-available review articles, peer-reviewed original articles, and experience of the author. The most common molecular alterations in thyroid cancer include BRAF and RAS point mutations and RET/PTC and PAX8/PPAR γ rearrangements. These nonoverlapping genetic alterations are found in more than 70% of papillary and follicular thyroid carcinomas. These molecular alterations can be detected in surgically resected samples and fine-needle aspiration samples from thyroid nodules and can be of significant diagnostic use. The diagnostic role of BRAF mutations has been studied most extensively, and recent studies also demonstrated a significant diagnostic utility of RAS, RET/PTC, and PAX8/PPAR γ mutations, particularly in thyroid fine-needle aspiration samples with indeterminate cytology. In addition to the diagnostic use, BRAF V600E mutation can also be used for tumor prognostication, as this mutation is associated with higher rate of tumor recurrence and tumor-related mortality. The use of these and other emerging molecular markers is expected to improve significantly the accuracy of cancer diagnosis in thyroid nodules and allow more individualized surgical and postsurgical management of patients with thyroid cancer.

  7. Increased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation?

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    Schlumberger Martin

    2002-12-01

    Full Text Available Abstract Background Sodium/iodide symporter (NIS is a key protein in iodide transport by thyroid cells and this activity is a prerequisite for effective radioiodide treatment of thyroid cancer. In the majority of thyroid cancers, however, iodide uptake is reduced, probably as a result of decreased NIS protein expression. Methods To identify the mechanisms that negatively affect NIS expression in thyroid tumors, we performed electrophoresis mobility shift assays and immunoblot analysis of nuclear protein extracts from normal and tumoral thyroid tissues from 14 unrelated patients. Results Two proteins closely related to the transcription factors AP2 and Sp1 were identified in the nuclear extracts. Expression of both AP2 and Sp1 in nuclear extracts from thyroid tumors was significantly higher than that observed in corresponding normal tissues. Conclusion These observations raise the possibility that NIS expression, and subsequently iodide transport, are reduced in thyroid tumors at least in part owing to alterations in the binding activity of AP2 and Sp1 transcription factors to NIS promoter.

  8. Bisphenol A and estrogen induce proliferation of human thyroid tumor cells via an estrogen-receptor-dependent pathway.

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    Zhang, YongHong; Wei, Feng; Zhang, Jing; Hao, Lanxiang; Jiang, Jie; Dang, Liansheng; Mei, Dan; Fan, ShanShan; Yu, Yajin; Jiang, Ling

    2017-11-01

    To determine the relationship between papillary thyroid carcinoma and environmental exposure to bisphenol A (BPA) or 17-β estrogen (E2) by assessing the effects of these compounds on estrogen receptor expression and AKT/mTOR signaling. The effects of low levels of BPA (1mM-10nM) and 17β-estradiol (E2, 0.1mM-1nM) on ER expression and cellular proliferation were determined in human thyroid papillary cancer BHP10-3 cells. Protein and mRNA levels of estrogen nuclear receptors (ERα/ERβ) and membrane receptors (GPR30) were determined by immunofluorescence assay, Western blotting, and RT-PCR, respectively, and proliferation was assessed by CCK-8 assay. The proliferative effects of BPA and E2 were both concentration- and time-dependent. Expression of ERα/ERβ and GPR30 were enhanced by BPA and E2. BPA and E2 could quickly phosphorylate AKT/mTOR. Moreover, ICI suppressed ERα expression and activated GPR30 as did G-1. G-15 reversed the effects of E2 on GPR30 and AKT/mTOR, but did not alter the effect of BPA. BPA influences thyroid cancer proliferation by regulating expression of ERs and GPR30, a mechanism that differs from E2. In addition, ICI and G-15 may have the potential to be used as anti-thyroid cancer agents. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Thyroid Cancer and Tumor Collaborative Registry (TCCR).

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    Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B; Sherman, Simon

    2016-01-01

    A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC.

  10. Mitochondrial dynamics protein Drp1 is overexpressed in oncocytic thyroid tumors and regulates cancer cell migration.

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    Ferreira-da-Silva, André; Valacca, Cristina; Rios, Elisabete; Pópulo, Helena; Soares, Paula; Sobrinho-Simões, Manuel; Scorrano, Luca; Máximo, Valdemar; Campello, Silvia

    2015-01-01

    Oncocytic cell tumors are characterized by the accumulation of morphologically abnormal mitochondria in their cells, suggesting a role for abnormal mitochondrial biogenesis in oncocytic cell transformation. Little is known about the reason for the dysmorphology of accumulated mitochondria. The proteins regulating the morphology of mitochondria, the "mitochondria-shaping" proteins, can modulate their size and number; however, nothing is known hitherto about a possible involvement of mitochondrial dynamics in oncocytic cell transformation in tumors. Our aim was to assess the status of the mitochondria morphology and its role in oncocytic cell transformation. We therefore evaluated the expression pattern of the main mitochondrial fusion and fission proteins in a series of thyroid cell tumor samples, as well as in thyroid tumor cell lines, with and without oncocytic cell features. The expression of mitochondrial fusion (Opa1, Mfn1 and Mfn2) and fission (Drp1 and Fis1) proteins were evaluated by immunohistochemistry (IHC) in a series of 88 human thyroid tumors. In vitro studies, for comparative purposes and to deepen the study, were performed using TPC1--a papillary thyroid carcinoma derived cell line--and XTC.UC1, an oncocytic follicular thyroid carcinoma-derived cell line. Both IHC and in vitro protein analyses showed an overall increase in the levels of "mitochondrial-shaping" proteins in oncocytic thyroid tumors. Furthermore, overexpression of the pro-fission protein Drp1 was found to be associated with malignant oncocytic thyroid tumors. Interestingly, genetic and pharmacological blockage of Drp1 activity was able to influence thyroid cancer cells' migration/invasion ability, a feature of tumor malignancy. In this study we show that unbalanced mitochondrial dynamics characterize the malignant features of thyroid oncocytic cell tumors, and participate in the acquisition of the migrating phenotype.

  11. Total Thyroidectomy in the Mouse: the Feasibility Study in the Non thyroidal Tumor Model Expressing Human Sodium/Iodide Symporter Gene

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    Shim, Hye kyung; Kim, Seog Gyun; Kim, Tae Sung; Kim, Seok ki; Lee, Sang Jin [Hospital and Research Institute, National Cancer Center, Goyang (Korea, Republic of)

    2011-06-15

    This study sought to probe the feasibility of performing total thyroidectomy in the mouse using a non thyroidal hNIS expressing tumor model. Our thyroidectomy protocol included thorough excision of both lobes and the isthmus. For evaluating the completeness of thyroidectomy, we compared the {sup 99m}Tc pertechnetate scans taken before and after thyroidectomy. The prostate scans taken before and after thyroidectomy. The prostate cancer cell line was subcutaneously inoculated 2 weeks after the thyroidectomy. When the tumor reached 5-10mm in diameter, Ad5/35 E4PSESE1a hNIS was injected intratumorally, and {sup 131I} scans were performed. The radio iodine uptakes of the neck and the tumor were compared with those of the other regions. Total thyroidectomy was performed in 13 mice. Although 38.5% died during or just after thyroidectomy, the others survived in good health for 2 months. Thyroid tissue was completely eliminated using our protocol; the residual uptake of {sup 99m}Tc pertechnetate was minimal in the neck area. The neck/background uptake ratio after thyroidectomy (p<0.05). Non thyroidal tumor models were successfully established in all the surviving mice. Radioiodine accumulation in the tumors was visualized on {sup 131I} scans, and the neck uptakes were minimal. Using our total thyroidectomy protocol, we successfully established a hNIS transfected prostate cancer model with a minimal accumulation of radioiodine in the neck. The relatively high mortality after surgery can be a problem, and this might be reduced by minimizing the surgical stress.

  12. Estrogen-related receptor alpha modulates lactate dehydrogenase activity in thyroid tumors.

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    Mirebeau-Prunier, Delphine; Le Pennec, Soazig; Jacques, Caroline; Fontaine, Jean-Fred; Gueguen, Naig; Boutet-Bouzamondo, Nathalie; Donnart, Audrey; Malthièry, Yves; Savagner, Frédérique

    2013-01-01

    Metabolic modifications of tumor cells are hallmarks of cancer. They exhibit an altered metabolism that allows them to sustain higher proliferation rates in hostile environment outside the cell. In thyroid tumors, the expression of the estrogen-related receptor α (ERRα), a major factor of metabolic adaptation, is closely related to the oxidative metabolism and the proliferative status of the cells. To elucidate the role played by ERRα in the glycolytic adaptation of tumor cells, we focused on the regulation of lactate dehydrogenases A and B (LDHA, LDHB) and the LDHA/LDHB ratio. Our study included tissue samples from 10 classical and 10 oncocytic variants of follicular thyroid tumors and 10 normal thyroid tissues, as well as samples from three human thyroid tumor cell lines: FTC-133, XTC.UC1 and RO82W-1. We identified multiple cis-acting promoter elements for ERRα, in both the LDHA and LDHB genes. The interaction between ERRα and LDH promoters was confirmed by chromatin immunoprecipitation assays and in vitro analysis for LDHB. Using knock-in and knock-out cellular models, we found an inverse correlation between ERRα expression and LDH activity. This suggests that thyroid tumor cells may reprogram their metabolic pathways through the up-regulation of ERRα by a process distinct from that proposed by the recently revisited Warburg hypothesis.

  13. An in vivo mouse model of metastatic human thyroid cancer.

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    Zhang, Lisa; Gaskins, Kelli; Yu, Zhiya; Xiong, Yin; Merino, Maria J; Kebebew, Electron

    2014-04-01

    Mouse models of metastatic human cancers are important tools in preclinical studies for testing new systematic therapies and studying effectors of cancer metastasis. The major drawbacks of current mouse models for metastatic thyroid cancer are that they have low metastasis rates and do not allow in vivo tumor detection. Here, we report and characterize an in vivo detectable metastasis mouse model of human thyroid cancer using multiple thyroid cancer cell lines. Human anaplastic thyroid cancer cell lines 8505C, C-643, SW-1736, and THJ-16T; follicular thyroid cancer cell lines FTC-133, FTC-236, and FTC-238; and Hürthle cell carcinoma cell line XTC-1 were transfected with a linearized pGL4.51[luc2/CMV/Neo] vector or transduced with lentivirus containing Luc2-eGFP reporter genes. The stably transfected cells were injected intravenously into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. Tumors were detected with an in vivo imaging system-Xenogen IVIS. Vemurafenib, a BRAF inhibitor, was used to treat lung metastases generated from 8505C-Luc2 cells with a BRAF(V600E) mutation to test the accuracy of the model to evaluate response to therapy. Intravenous injection of as few as 30,000 8505C-Luc2 cells produced lung metastases in 100% of the injected mice, and many of these mice also developed bone metastases at a later stage of the disease. Similarly, metastatic tumors also developed in all mice injected with C-643-Luc2, THJ-16T-Luc2, FTC-133-Luc2, FTC-236-Luc2, FTC-238-Luc2, and XTC-1-Luc2 cells. The metastases were easily detectable in vivo, and tumor progression could be dynamically and accurately followed and correlated with the actual tumor burden. Furthermore, disease progression could be easily controlled by adjusting the number of injected cells. The in vivo treatment of 8505C xenograft lung metastases with vemurafenib dramatically reduced the growth and signal intensity with good correlation with actual tumor burden. Herein we report an in vivo detectable mouse model

  14. [Imprint cytology in the diagnosis of tumors of the thyroid].

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    Pluot, M; Faroux, M J; Rain, J; Patey, M; Mallaisy, T; Simatos, A

    1989-01-01

    We have correlated imprint cytology findings in thyroid tumors to the results of preoperative fine needle aspiration and operative specimen histology. Specificity of imprint cytology proved greater than that of fine needle aspiration cytology and topographic correlations were particularly helpful. Imprint cytology can improve the intraoperative histologic diagnosis. Because abundant cells are available, imprint thyroid cytology is ideal for teaching and training cytologists. Imprint cytology provides enough cells to perform special techniques, such as quantitative cytology, that are useful for the diagnosis of some tumor varieties (e.g. follicular tumors).

  15. Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer

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    Gao, Xuemei [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Wu, Xinchao [Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Zhang, Xiao; Hua, Wenjuan; Zhang, Yajing [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Maimaiti, Yusufu [Department of Thyroid and Breast Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Gao, Zairong, E-mail: gaobonn@163.com [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Zhang, Yongxue [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China)

    2016-01-15

    Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine {sup 131}I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from {sup 131}I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced {sup 131}I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.

  16. Autoantibody profiling of benign and malignant thyroid tumors and design of a prototype diagnostic array

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    K V Lanshchakov; P V Belousov; V E Vanushko; A Yu Abrosimov; D V Kuprash; N S Kuznetsov

    2012-01-01

    Currently the “gold standard” in diagnostics of thyroid tumors is a fine-needle aspiration cytology (FNAC). However, FNAC cannot discriminate between benign and malignant thyroid tumors in 15 to 30% of observations. In order to develop an additional tool for differential diagnostics of thyroid tumors we evaluated the diagnostic performance of 3-antigen serum autoantibody signature in groups of benign ( n = 22) and malignant ( n = 26) thyroid tumors using a dot-blot ELISA-based analysis The se...

  17. Defective ciliogenesis in thyroid hürthle cell tumors is associated with increased autophagy.

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    Lee, Junguee; Yi, Shinae; Kang, Yea Eun; Chang, Joon Young; Kim, Jung Tae; Sul, Hae Joung; Kim, Jong Ok; Kim, Jin Man; Kim, Joon; Porcelli, Anna Maria; Kim, Koon Soon; Shong, Minho

    2016-11-29

    Primary cilia are found in the apical membrane of thyrocytes, where they may play a role in the maintenance of follicular homeostasis. In this study, we examined the distribution of primary cilia in the human thyroid cancer to address the involvement of abnormal ciliogenesis in different thyroid cancers. We examined 92 human thyroid tissues, including nodular hyperplasia, Hashimoto's thyroiditis, follicular tumor, Hürthle cell tumor, and papillary carcinoma to observe the distribution of primary cilia. The distribution and length of primary cilia facing the follicular lumen were uniform across variable-sized follicles in the normal thyroid gland. However, most Hürthle cells found in benign and malignant thyroid diseases were devoid of primary cilia. Conventional variant of papillary carcinoma (PTC) displayed longer primary cilia than those of healthy tissue, whereas both the frequency and length of primary cilia were decreased in oncocytic variant of PTC. In addition, ciliogenesis was markedly defective in primary Hürthle cell tumors, including Hürthle cell adenomas and carcinomas, which showed higher level of autophagosome biogenesis. Remarkably, inhibition of autophagosome formation by Atg5 silencing or treatment with pharmacological inhibitors of autophagosome formation restored ciliogenesis in the Hürthle cell carcinoma cell line XTC.UC1 which exhibits a high basal autophagic flux. Moreover, the inhibition of autophagy promoted the accumulation of two factors critical for ciliogenesis, IFT88 and ARL13B. These results suggest that abnormal ciliogenesis, a common feature of Hürthle cells in diseased thyroid glands, is associated with increased basal autophagy.

  18. Autoantibody profiling of benign and malignant thyroid tumors and design of a prototype diagnostic array

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    K V Lanshchakov

    2012-06-01

    Full Text Available Currently the “gold standard” in diagnostics of thyroid tumors is a fine-needle aspiration cytology (FNAC. However, FNAC cannot discriminate between benign and malignant thyroid tumors in 15 to 30% of observations. In order to develop an additional tool for differential diagnostics of thyroid tumors we evaluated the diagnostic performance of 3-antigen serum autoantibody signature in groups of benign ( n = 22 and malignant ( n = 26 thyroid tumors using a dot-blot ELISA-based analysis The sensitivity and specificity of resultant array were estimated to be 55–60% and 95–100%, respectively ( p < 0.001 according to one-sided Fisher Exact Test. Thus, we created a prototype antigen array for differential diagnostics of thyroid tumors which can be regarded as a platform for design of more complicated panel, highly sensitive in thyroid cancer detection, which can significantly improve the accuracy of preoperative diagnosis of thyroid cancer.

  19. CASTLE Thyroid Tumor: A Case Report and Literature Review

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    Chris Lominska

    2017-09-01

    Full Text Available Carcinoma showing thymus-like differentiation is a rare tumor of the thyroid gland, which is structurally similar to thymic tissue. Overall, it has a favorable prognosis. Radiotherapy has been shown to be an effective local treatment, but there have been reports of distant recurrence. It has been suggested that adding chemotherapy may decrease the risk of recurrence. Here, we present a case report of a patient with a large tumor and extrathyroidal extension. The patient was treated with surgery, radiotherapy, and cisplatin with acceptable toxicity. The patient is free of locally recurrent or distant disease at 3 years.

  20. "Nodule in Nodule" on Thyroid Ultrasonography: Possibility of Follicular Carcinoma Transformed from Benign Thyroid Tumor.

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    Kobayashi, Kaoru; Ota, Hisashi; Hirokawa, Mitsuyoshi; Yabuta, Tomonori; Fukushima, Mitsuhiro; Masuoka, Hiroo; Higashiyama, Takuya; Kihara, Minoru; Ito, Yasuhiro; Miya, Akihiro; Miyauchi, Akira

    2017-04-01

    It is generally considered impossible to differentiate follicular carcinomas from follicular adenomas by means of ultrasonography or cytology before surgery. Therefore, follicular carcinoma is histopathologically diagnosed by verifying capsular and/or vascular invasion after surgery. However, ultrasonography may play an important role in diagnosing follicular carcinoma preoperatively in a small number of cases. Four cases of follicular carcinoma or follicular neoplasm that transformed from a benign thyroid tumor and demonstrated a "nodule in nodule" appearance on ultrasonography are presented in this report. Characteristic ultrasound features of such patients are: (1) a "nodule in nodule" appearance, (2) a well-defined boundary line between the nodules, and (3) separate distribution of blood signals within each nodule. A small number of patients with follicular carcinomas or follicular neoplasms may present with a "nodule in nodule" appearance on ultrasonography. It was suggested a long time ago that follicular carcinomas may develop from benign thyroid tumors. The fact that follicular carcinomas appear within benign tumors may be evidence of thyroid tumorigenesis.

  1. Survey of 548 oncogenic fusion transcripts in thyroid tumors supports the importance of the already established thyroid fusions genes.

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    Celestino, Ricardo; Sigstad, Eva; Løvf, Marthe; Thomassen, Gard O S; Grøholt, Krystyna K; Jørgensen, Lars H; Berner, Aasmund; Castro, Patrícia; Lothe, Ragnhild A; Bjøro, Trine; Sobrinho-Simões, Manuel; Soares, Paula; Skotheim, Rolf I

    2012-12-01

    Neoplasms frequently present structural chromosomal aberrations that can alter the level of expression of a protein or to the expression of an aberrant chimeric protein. In the thyroid, the PAX8-PPARG fusion is present in the neoplastic lesions that have a follicular architecture-follicular thyroid carcinoma (FTC) and follicular variant of papillary thyroid carcinoma (FVPTC), and less frequently in follicular thyroid adenoma (FTA), while the presence of RET/PTC fusions are largely restricted to papillary thyroid carcinoma (PTC). The ability to detect fusion genes is relevant for a correct diagnosis and for therapy. We have developed a new fusion gene microarray-based approach for simultaneous analysis of all known and predicted fusion gene variants. We did a comprehensive screen for 548 known and putative fusion genes in 27 samples of thyroid tumors and three positive controls-one thyroid cancer cell line (TPC-1) and two PTCs with known CCDC6-RET (alias RET/PTC1) fusion gene, using this microarray. Within the thyroid tumors tested, only well known, previously reported fusion genes in thyroid oncology were identified. Our results reinforce the pathogenic role played by RET/PTC1, RET/PTC3, and PAX8-PPARG fusion genes in thyroid tumorigenesis. Copyright © 2012 Wiley Periodicals, Inc.

  2. Target therapies for radioiodine refractory advanced thyroid tumors.

    Science.gov (United States)

    Schlumberger, M

    2012-01-01

    A small but not irrelevant percentage of differentiated thyroid cancers become refractory to radioiodine treatment either because they lose the ability of taking up iodine over the time or because, despite a persistent uptaking ability, the effect of the radioiodine is lost in terms of tumor burden reduction. These patients receive only few and transient benefits from other conventional therapies and particularly from chemotherapy. In the last decade, several new drugs have been discovered as potentially useful and tested in clinical trials. They are mainly represented by protein kinase inhibitor molecules that should be proposed to advanced and progressive 131I refractory thyroid cancer patients by enrolling them in clinical trials or by the "off label" use of the drug.

  3. Hurthle cell tumor of the thyroid gland: Report of a rare case and ...

    African Journals Online (AJOL)

    2013-07-09

    Jul 9, 2013 ... This article presents a case of Hurthle cell adenoma (HCA) of the thyroid gland with a review of literature on Hurthle cell tumors. This case presented is that of a 57‑year‑old woman with a recurrent thyroid swelling. She previously underwent a right hemithyroidectomy for thyroid mass 10 years prior.

  4. Hurthle cell tumor of the thyroid gland: Report of a rare case and ...

    African Journals Online (AJOL)

    This article presents a case of Hurthle cell adenoma (HCA) of the thyroid gland with a review of literature on Hurthle cell tumors. This case presented is that of a 57-year-old woman with a recurrent thyroid swelling. She previously underwent a right hemithyroidectomy for thyroid mass 10 years prior. A left lobectomy was ...

  5. SKI-606, a Src inhibitor, reduces tumor growth, invasion, and distant metastasis in a mouse model of thyroid cancer

    Science.gov (United States)

    Kim, Won Gu; Guigon, Celine J; Fozzatti, Laura; Park, Jeong Won; Lu, Changxue; Willingham, Mark C; Cheng, Sheue-yann

    2012-01-01

    Purpose Src is over-expressed or hyper-activated in a variety of human cancers including thyroid carcinoma. Src is a central mediator in multiple signaling pathways that are important in oncogenesis and cancer progression. In this study, we evaluated the effects of a Src inhibitor, SKI-606 (bosutinib), in a spontaneous metastatic thyroid cancer model with constitutively activated Src (ThrbPV/PVPten+/− mice). Experimental Design ThrbPV/PVPten+/− mice were treated with SKI-606 or vehicle controls, beginning at 6 weeks of age until the mice succumbed to thyroid cancer. We assessed the effects of SKI-606 on thyroid cancer progression and analyzed the impact of SKI-606 on aberrant Src-mediated signaling. Results SKI-606 effectively inhibited aberrant activation of Src and its downstream targets to markedly inhibit the growth of thyroid tumor, thereby prolonging the survival of treated mice. While Src inhibition did not induce cell apoptosis, it decreased cell proliferation by affecting the expression of key regulators of cell cycle progression. Importantly, SKI-606 dramatically prevented de-differentiation, vascular invasion, and lung metastasis of thyroid cancer cells. These responses were meditated by down-regulation of mitogen-activated protein kinase pathways and inhibition of the epithelial-mesenchymal transition. Conclusions Our findings suggest that Src is critical in the progression of thyroid cancer, making oral SKI-606 a promising treatment strategy for refractory thyroid cancer. PMID:22271876

  6. Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    O' Brien, Benjamin; Jossart, Gregg H.; Ito, Yuko; Greulich-Bode, Karin M.; Weier, Jingly F.; Munne, Santiago; Clark, Orlo H.; Weier, Heinz-Ulrich G.

    2010-08-19

    Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding

  7. ‘Chromosomal Rainbows’ Detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

    Science.gov (United States)

    O’Brien, Benjamin; Jossart, Gregg H.; Ito, Yuko; Greulich-Bode, Karin M.; Weier, Jingly F.; Munne, Santiago; Clark, Orlo H.; Weier, Heinz-Ulrich G.

    2011-01-01

    Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as ‘TRKA’), RET (‘Rearranged during Transfection protooncogene’, OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3′- end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabasepair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC’s). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding techniques for fine

  8. 'Chromosomal Rainbows' Detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors.

    Science.gov (United States)

    O'Brien, Benjamin; Jossart, Gregg H; Ito, Yuko; Greulich-Bode, Karin M; Weier, Jingly F; Munne, Santiago; Clark, Orlo H; Weier, Heinz-Ulrich G

    2010-01-01

    Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'- end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners.We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabasepair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding techniques for fine mapping of

  9. Metastatic thyroid carcinoma without identifiable primary tumor within the thyroid gland: a retrospective study of a rare phenomenon.

    Science.gov (United States)

    Xu, Bin; Scognamiglio, Theresa; Cohen, Perry R; Prasad, Manju L; Hasanovic, Adnan; Tuttle, Robert Michael; Katabi, Nora; Ghossein, Ronald A

    2017-07-01

    Metastatic papillary thyroid carcinoma (PTC) without an identifiable primary tumor despite extensive microscopic examination of the thyroid gland is a rare but true phenomenon.We retrieved 7 of such cases and described in detail the clinical and pathologic features of these tumors. BRAF V600E immunohistochemistry and Sequenom molecular profile were conducted in selected cases. All patients harbored metastatic disease in the central (n=3), lateral (n=3), or both neck compartments (n=1). The histotype of the metastatic disease was PTC (n=5), poorly differentiated thyroid carcinoma in association with a PTC columnar variant (n=1), and anaplastic thyroid carcinoma in association with a PTC tall cell variant (n=1). Fibrosis was present in the thyroid of 5 patients. All patients with PTC were alive without evidence of recurrence. The 76-year-old patient with poorly differentiated thyroid carcinoma did not recur and died of unknown causes. Finally, the patient with anaplastic thyroid carcinoma was alive with distant metastasis at last follow-up. The median follow-up for this cohort was 2.2years (range, 0.8-17). BRAF V600E was detected in 4 of 6 cases by immunohistochemistry. In conclusion, metastatic nodal disease without identifiable thyroid primary is a rare but real phenomenon of unknown mechanisms. Although most tumors are low grade and well differentiated, aggressive behavior due to poorly differentiated or anaplastic carcinoma can happen. Most cases are BRAFV600E-positive thyroid tumors. A papillary carcinoma phenotype is found in all reported cases. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Epidemiology of Goiter and Benign Tumors of the Thyroid Gland in Albania

    Science.gov (United States)

    Bruka, Ibrahim; Gjata, Arben; Roshi, Enver

    2014-01-01

    Aim: The aim of this study was to describe the demographic characteristics and disease patterns among patients with thyroid nodular abnormalities (goiter) and benign tumors of the thyroid gland in Albania, a transitional country in South Eastern Europe. Methods: Our study included all patients diagnosed with goiter and/or benign tumors of the thyroid gland who were hospitalized at the University Hospital Center (UHC) “Mother Teresa” in Tirana between 2004 and 2012 (N=2258). All patients underwent the same examination and interviewing procedures. Demographic characteristics included gender, age, and place of residence. Binary logistic regression was used to compare the demographic characteristics between patients with benign tumors of the thyroid gland and those with goiter. Results: Overall, there were 2204 patients with goiter and 54 patients with benign tumors of the thyroid gland hospitalized at UHC over the period 2004-2012. There was no evidence of statistically significant differences in demographic characteristics (age, gender, or place of residence) between patients with benign tumors of the thyroid gland and those with goiter. Conclusions: Our study provides useful evidence on the epidemiology of benign tumors of the thyroid gland and the thyroid nodular abnormalities (goiter) in the Albanian population. Future studies in Albania should assess the main determinants of thyroid gland disorders and compare them with findings pertinent to other similar populations. PMID:25395890

  11. Expression of FAS/APO 1/CD 95 in thyroid tumors.

    Directory of Open Access Journals (Sweden)

    Waldemar Balcerzak

    2007-06-01

    Full Text Available Using immunohistochemistry, Fas/Apo-1 protein expression was investigated in thyroid cancers of 67 patients. Thyroid biopsies from twenty eight patients with benign thyroid diseases were also examined. The patients with thyroid cancer manifested a variable histology of the cancer, including 14 patients with follicular carcinoma, 48 with papillary carcinoma, 5 patients with medullary carcinoma. The benign thyroid disease involved nodular goitre in 11 patients and follicular adenoma in other 17 patients. The study aimed at examining immunohistochemical expression of Fas protein in order to determine whether the level of its expression correlated with histological diagnosis. In individual patients Fas expression was more prevalent in thyroid carcinomas as compared to benign tumors (p=0.001. A marked increase in Fas expression was found in papillary carcinoma, as compared to follicular and medullary carcinomas (p=0.02. In conclusion, Fas was significantly more frequently overexpressed in thyroid cancer, indicating its role in thyroid tumorigenesis.

  12. Dysregulation of Parkin-mediated mitophagy in thyroid Hürthle cell tumors.

    Science.gov (United States)

    Lee, Junguee; Ham, Sujin; Lee, Min Hee; Kim, Soung Jung; Park, Ji Hoon; Lee, Seong Eun; Chang, Joon Young; Joung, Kyong Hye; Kim, Tae Yong; Kim, Jin Man; Sul, Hae Joung; Kweon, Gi Ryang; Jo, Young Suk; Kim, Koon Soon; Shong, Young Kee; Gasparre, Giuseppe; Chung, Jong Kyeong; Porcelli, Anna Maria; Shong, Minho

    2015-11-01

    Abnormal accumulation of defective mitochondria is the hallmark of oncocytes, which are frequently observed in thyroid Hürthle cell lesions. Autophagy is an essential cellular catabolic mechanism for the degradation of dysfunctional organelles and has been implicated in several human diseases. It is yet unknown how autophagic turnover of defective mitochondria in Hürthle cell tumors is regulated. We characterized the expression patterns of molecular markers including Beclin1, LC3, PINK1 and Parkin, which are required for autophagy or mitophagy, in human oncocytic lesions of the thyroid. To undertake mechanistic studies, we investigated autophagy and mitophagy using XTC.UC1 cells, the only in vitro model of Hürthle cell tumors. Beclin1 and LC3 were highly expressed in oncocytes of Hürthle cell tumors. XTC.UC1 showed autophagic responses to starvation and rapamycin treatment, whereas they displayed ineffective activation of mitophagy, which is triggered by the coordinated action of PINK1 and Parkin in response to CCCP. This resulted in a decreased turnover of abnormal mitochondria. The mechanisms underlying defective mitophagy and mitochondrial turnover were investigated by genetic analysis of the PARK2 gene in XTC.UC1 and Hürthle cell tumor tissues. XTC.UC1 and several tumors harbored the V380L mutation, resulting in dysfunctional autoubiquitination and decreased E3 ligase activity. Consistently, oncocytes in Hürthle cell tumors displayed comparable expression of PINK1 but decreased Parkin expression in comparison to normal thyrocytes. The introduction of wild-type Parkin sensitized XTC.UC1 to death induced by CCCP. This study provides a possible etiological basis for oncocytic formation in heterogeneous Hürthle cell tumors through insufficient mitophagy leading to ineffective turnover of aberrant mitochondria caused by dysfunctional Parkin-mediated pathways of mitochondria quality control. © The Author 2015. Published by Oxford University Press. All rights

  13. [PREOPERATIVE DIAGNOSTICS OF THYROID MEDULLARY CARCINOMA WITH EMPHASIS ON CYTOMORPHOLOGICAL FEATURES AND DIFFERENTIAL DIAGNOSIS OF PRIMARY AND SECONDARY THYROID TUMORS].

    Science.gov (United States)

    Katović, Sandra Kojić; Vasilj, Ankica

    2014-12-01

    Medullary thyroid cancer is a rare neuroendocrine neoplasm that arises from the parafollicular C cells that produce calcitonin, a hormone essential for the regulation of calcium metabolism. It accounts for 4%-10% of all thyroid cancers. In most cases (75%-80%), it is sporadic, while in other cases it is part of the multiple endocrine neoplasia (MEN) syndrome. Most often, medullary thyroid carcinoma is presenting as a solitary nodule. At the time of diagnosis, about half of the patients have enlarged cervical lymph nodes, while a small number of patients have distant metastases in the liver, lungs, bones and brain. If the tumor is hormone active, the patient may have systemic symptoms such as diarrhea or flushing. Ultrasonically, medullary carcinoma usually appears as a hypoechogenic node with marked vascularity and uneven contours that can sometimes contain microcalcifications, and in most cases is located in the upper poles of the thyroid. The sample obtained by fine needle aspiration is usually cellular, tumor cells are disseminated or arranged in poorly cohesive groups. They are most often plasmacytoid, but sometimes can also be spindled. The nuclei are eccentric and chromatin shows features of neuroendocrine tumors. Cytoplasms of tumor cells are abundant, triangular or polygonal, amphophilic, finely granulated and unsharply limited. Background is clean and sometimes amyloid can be found. Depending on the cytologic picture, differential diagnostic problems can be well differentiated thyroid tumors, primarily follicular neoplasm, lymphomas, poorly differentiated insular carcinoma, metastatic small cell carcinoma, mesenchymal tumors or melanoma. In case of differential diagnostic difficulties, of great help is to determine calcitonin immunocytochemically or in aspirate or serum. Medullary carcinoma may show low progression and long-time survival, but can also be a rapidly progressive tumor where survival is measured in months. Good prognostic indicators are

  14. Circadian clock characteristics are altered in human thyroid malignant nodules.

    Science.gov (United States)

    Mannic, Tiphaine; Meyer, Patrick; Triponez, Frederic; Pusztaszeri, Marc; Le Martelot, Gwendal; Mariani, Olivia; Schmitter, Daniel; Sage, Daniel; Philippe, Jacques; Dibner, Charna

    2013-11-01

    The circadian clock represents the body's molecular time-keeping system. Recent findings revealed strong changes of clock gene expression in various types of human cancers. Due to emerging evidence on the connection between the circadian oscillator, cell cycle, and oncogenic transformation, we aimed to characterize the circadian clockwork in human benign and malignant thyroid nodules. Clock transcript levels were assessed by quantitative RT-PCR in thyroid tissues. To provide molecular characteristics of human thyroid clockwork, primary thyrocytes established from normal or nodular thyroid tissue biopsies were subjected to in vitro synchronization with subsequent clock gene expression analysis by circadian bioluminescence reporter assay and by quantitative RT-PCR. The expression levels of the Bmal1 were up-regulated in tissue samples of follicular thyroid carcinoma (FTC), and in papillary thyroid carcinoma (PTC), as compared with normal thyroid and benign nodules, whereas Cry2 was down-regulated in FTC and PTC. Human thyrocytes derived from normal thyroid tissue exhibited high-amplitude circadian oscillations of Bmal1-luciferase reporter expression and endogenous clock transcripts. Thyrocytes established from FTC and PTC exhibited clock transcript oscillations similar to those of normal thyroid tissue and benign nodules (except for Per2 altered in PTC), whereas cells derived from poorly differentiated thyroid carcinoma exhibited altered circadian oscillations. This is the first study demonstrating a molecular makeup of the human thyroid circadian clock. Characterization of the thyroid clock machinery alterations upon thyroid nodule malignant transformation contributes to understanding the connections between circadian clocks and oncogenic transformation. Moreover, it might help in improving the thyroid nodule preoperative diagnostics.

  15. A study of FoxA1 expression in thyroid tumors.

    Science.gov (United States)

    Nonaka, Daisuke

    2017-07-01

    FoxA1 regulates a variety of tissues during embryogenesis and early life. In thyroid, FoxA1 expression has recently been shown in C cells and medullary thyroid carcinomas but not in follicular cells. FoxA1 has also been proposed as a potential oncogene in anaplastic thyroid carcinomas. However, FoxA1 expression has not been extensively investigated in a spectrum of thyroid nonneoplastic lesions and tumors. A variety of thyroid tumors and lesions and their morphologic mimics were stained with monoclonal anti-FoxA1 antibody. For the medullary carcinomas, its expression pattern was compared with those of other conventional markers. All 67 medullary thyroid carcinomas (100%), including 1 calcitonin-negative medullary carcinoma, showed diffuse and strong FoxA1 nuclear expression. The expression pattern was homogeneous throughout the tumor. Expressions of other markers in medullary thyroid carcinomas were as follows: calcitonin, 94.7%; CEA, 91.2%; and chromogranin, 100%, generally in variable intensity. FoxA1 was completely negative in follicular neoplasms, papillary thyroid carcinomas, and poorly differentiated carcinomas, whereas it was expressed in 55% of anaplastic thyroid carcinomas (33/60) in variable intensity. FoxA1 was also strongly expressed in C-cell hyperplasia as well as solid cell nests. No FoxA1 expression was seen in thyroid gland affected by nodular hyperplasia, Hashimoto thyroiditis, and Graves disease, or in paragangliomas or parathyroid lesions. FoxA1 discriminates between medullary thyroid carcinoma and tumors of follicular derivation with sensitivity and specificity greater than calcitonin and CEA; therefore, it may serve as a reliable ancillary marker for the diagnosis of medullary thyroid carcinoma because of its reliably uniform quality of staining. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  16. Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity.

    Science.gov (United States)

    Imam, Shahnawaz; Paparodis, Rodis; Sharma, Deepak; Jaume, Juan Carlos

    2014-06-01

    Thyroid cancers are usually surrounded by a significant number of immune-reactive cells. Tumor-associated lymphocytes as well as background lymphocytic thyroiditis are frequently mentioned in pathology reports of patients who have undergone surgery for thyroid cancer. The nature of this lymphocytic reaction is not well understood. The fact that cancer can survive in this adverse microenvironment is indicative of immune regulation. We characterized the lymphocytic infiltration that accompanies thyroid cancer and compared it with that present in thyroid autoimmunity. We found that double-negative (DN) T cells were significantly more abundant in thyroid cancer than in thyroid autoimmunity. Although FOXP3(+) regulatory T cells were also present, DN T cells were the dominant cell type, associated with thyroid cancer. Furthermore, upon stimulation, the DN T cells associated with cancer remained unchanged, while the few (thyroid autoimmunity increased in numbers (>20%). CD25 expression on DN T cells remained unchanged after stimulation, which indicates that the increase in the absolute number of DN T cells in thyroid autoimmunity was at the expense of inactivation of single-positive T cells. We concluded that in the setting of thyroid cancer, DN T cells appear to suppress tumor immunity. In contrast, in thyroid autoimmunity, DN T cells were barely present and only increased at the expense of inactivated, single-positive T cells upon induction. Together, these findings indicate that thyroid cancer-associated DN T cells might regulate proliferation and effector function of T cells and thereby contribute to tumor tolerance and active avoidance of tumor immunity. © 2014 Society for Endocrinology.

  17. Thyroiditis

    Science.gov (United States)

    ... inflammation but presenting in different ways. For example, Hashimoto’s thyroiditis is the most common cause of hypothyroidism ... This would be the case in patients with Hashimoto’s thyroiditis. If the thyroiditis causes rapid thyroid cell ...

  18. Number of tumor foci predicts prognosis in papillary thyroid cancer.

    Science.gov (United States)

    Qu, Ning; Zhang, Ling; Ji, Qing-hai; Zhu, Yong-xue; Wang, Zhuo-ying; Shen, Qiang; Wang, Yu; Li, Duan-shu

    2014-12-04

    Papillary thyroid cancer (PTC) often presents as multifocal. However, the association of multifocality with poor prognosis remains controversial. The aim of this retrospective study was to identify the characteristics of PTC with multiple foci and to evaluate the association between multifocality and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as G1 (1 tumor focus), G2 (2 foci), and G3 (3 or more foci). We analyzed the clinicopathological features and clinical outcomes in each classification. A Cox regression model was used to assess the relationship between multifocality and recurrence or cancer mortality. The G1, G2 and G3 groups included 287, 141 and 68 patients, respectively. The mean age was 47.1±16.1 yr in G1, 41.1±18.4 yr in G2, and 35.5±15.9 yr in G3 and differed significantly among the 3 groups (p=0.001). The proportion of extrathyroidal extension, central lymph node metastasis (CLNM), and lateral lymph node metastasis (LLNM) in the G1 to G3 groups increased with increasing number of tumor foci. The Kaplan-Meier curves revealed that G3 had the shortest recurrence-free survival, and differences were significant among the 3 groups (p=0.001, Log Rank test). Furthermore, cancer-specific survival rates decreased significantly with increasing number of tumor foci (p=0.041). Independent predictors of recurrence by multivariate Cox analysis included >3 tumor foci [HR 2.60, 95% confidence interval (CI) 1.53-4.39, p=0.001] and extrathyroidal extension (HR 1.95, CI 1.12-3.38, p=0.018). An increase in the number of tumors is associated with a tendency toward more aggressive features and predicts poor prognosis in PTC.

  19. Tumor angiogenic factor and human skin tumors.

    Science.gov (United States)

    Wolf, J E; Hubler, W R

    1975-03-01

    A transparent acrylic hamster cheek-pouch chamber was used to investigate the elaboration of a tumor angiogenic factor (TAF) by human cutaneous neoplasms; direct tumor implantations, transfilter diffusion, and soluble tumor extracts were used in the study. A diffusible and filterable TAF was extracted from cutaneous tumors and produced distinctive patterns of sequential vasodilatation, tortuosity, and neovascular proliferation in the cheek-pouch membrane. Malignant human neoplasms (eg, melanoma, basal cell epithelioma, squamous cell carcinoma, lymphoma) produced striking neovascularization; vascular tumors (eg, Kaposi sarcoma, pyogenic granuloma, vascular histiocytoma) stimulated dramatic hyperemia and ectasia. Angiogenesis was conspicuously absent after implantation of control materials and nevoid or normal cutaneous components (with the exception of epidermis). Tumor angiogenic factor appears to induce direct stimulation of endothelial cell mitosis and may be essential for survival of nutritionally ravenous neoplastic tissues. The interference with TAF has therapeutic implications.

  20. Epigenetic modifications in human thyroid cancer

    Science.gov (United States)

    FAAM, BITA; GHAFFARI, MOHAMMAD ALI; GHADIRI, ATA; AZIZI, FEREIDOUN

    2015-01-01

    Thyroid carcinoma is the most common endocrine malignancy of the endocrine organs, and its incidence rate has steadily increased over the last decade. Over 95% of thyroid carcinoma is derived from follicular cells that have a spectrum of differentiation to the most invasive malignancy. The molecular pathogenesis of thyroid cancer remains to be clarified, although activating the RET, RAS and BRAF oncogenes have been well characterized. Increasing evidence from previous studies demonstrates that acquired epigenetic abnormalities participating with genetic alteration results in altered patterns of gene expression/function. Aberrant DNA methylation has been established in the CpG regions and microRNAs (miRNAs) expression profile recognized in cancer development. In the present review, a literature review was performed using MEDLINE and PubMed with the terms ‘epigenetic patterns in thyroid cancer [or papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid cancer (MTC), anaplastic thyroid cancer (ATC)]’, ‘DNA methylation in thyroid cancer (or PTC, FTC, MTC, ATC)’, ‘miRNA expression in thyroid cancer (or PTC, FTC, MTC, ATC)’, ‘epigenetic patterns in cancer’ and the current understanding of epigenetic patterns in thyroid cancer was discussed. PMID:25469237

  1. Carcinome anaplasique de la thyroide | Lachkhem | Journal ...

    African Journals Online (AJOL)

    Objectives: Thyroid anaplasic carcinoma is a rare variety of thyroid cancer and one of the most aggressive tumors known to affect humans. It accounts for less than 2%of thyroid cancers and it is often extremelymalignant and rapidly fatal. Material and methods: It is a retrospective study of 12 cases of thyroid anaplasic ...

  2. Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer

    Directory of Open Access Journals (Sweden)

    Ma Jianjun

    2008-10-01

    Full Text Available Abstract Background NDRG2 (N-Myc downstream-regulated gene 2 was initially cloned in our laboratory. Previous results have shown that NDRG2 expressed differentially in normal and cancer tissues. Specifically, NDRG2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of NDRG2 inhibited the proliferation of cancer cells. NDRG2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether NDRG2 participates in carcinogenesis of the thyroid. Methods In this study, we investigated the expression profile of human NDRG2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40 and carcinomas (n = 35, along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc. Results The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of NDRG2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of NDRG2 expression with gender, age, different histotypes of thyroid cancers or distant metastases. Conclusion Our data indicates that NDRG2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of NDRG2 in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of NDRG2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma.

  3. Thyroid

    Science.gov (United States)

    ... thyroid hormone). Symptoms of hypothyroidism include lack of energy, depression, constipation, weight gain, hair loss, dry skin, ... you are allergic to thyroid, any other medications, pork, or any of the ingredients in thyroid tablets. ...

  4. Correlation of thyroid cancer Doppler hemodynamic indexes with tumor proliferation and angiogenesis indexes

    Directory of Open Access Journals (Sweden)

    Li Wei

    2016-07-01

    Full Text Available Objective: To explore the correlation of thyroid cancer Doppler hemodynamic indexes with tumor proliferation and angiogenesis indexes. Methods: A total of 108 cases of thyroid cancer were diagnosed by B-ultrasound and pathology and then included in the observation group of the research, 107 cases of non-cancer patients who received excision of thyroid adenoma in our hospital during the same period were selected as healthy control group, thyroid hemodynamic indexes, tumor proliferation-related indexes and serum angiogenesis-related indexes of two groups were detected, and the correlation of thyroid cancer hemodynamic indexes with tumor proliferation and angiogenesis indexes was further analyzed. Results: S and D values of observation group were higher than those of control group (P0.05; p53, PCNA and Ki-67 expression levels in thyroid tumor of observation group were higher than those of control group while TIPE2 protein expression level was lower than that of control group (P<0.05; serum VEGF, Ang-2, HIF-1毩, IGF-栻 and endostatin values of observation group were higher than those of control group while MBP value was lower than that of control group (P<0.05; thyroid artery peak systolic velocity (S and end diastolic velocity (D were directly proportional to p53, PCNA, Ki-67, VEGF, Ang-2, HIF-1毩, IGF-栻 and endostatin values, and inversely proportional to TIPE2 and MBP values (P<0.05. Conclusions: Artery blood flow velocity in patients with thyroid cancer is directly correlated with tumor proliferation and angiogenesis, and can be used as the reliable index to judge tumor condition and curative effect.

  5. Comparison of transcriptomic signature of post-Chernobyl and postradiotherapy thyroid tumors.

    Science.gov (United States)

    Ory, Catherine; Ugolin, Nicolas; Hofman, Paul; Schlumberger, Martin; Likhtarev, Illya A; Chevillard, Sylvie

    2013-11-01

    We previously identified two highly discriminating and predictive radiation-induced transcriptomic signatures by comparing series of sporadic and postradiotherapy thyroid tumors (322-gene signature), and by reanalyzing a previously published data set of sporadic and post-Chernobyl thyroid tumors (106-gene signature). The aim of the present work was (i) to compare the two signatures in terms of gene expression deregulations and molecular features/pathways, and (ii) to test the capacity of the postradiotherapy signature in classifying the post-Chernobyl series of tumors and reciprocally of the post-Chernobyl signature in classifying the postradiotherapy-induced tumors. We now explored if postradiotherapy and post-Chernobyl papillary thyroid carcinomas (PTC) display common molecular features by comparing molecular pathways deregulated in the two tumor series, and tested the potential of gene subsets of the postradiotherapy signature to classify the post-Chernobyl series (14 sporadic and 12 post-Chernobyl PTC), and reciprocally of gene subsets of the post-Chernobyl signature to classify the postradiotherapy series (15 sporadic and 12 postradiotherapy PTC), by using conventional principal component analysis. We found that the five genes common to the two signatures classified the learning/training tumors (used to search these signatures) of both the postradiotherapy (seven PTC) and the post-Chernobyl (six PTC) thyroid tumor series as compared with the sporadic tumors (seven sporadic PTC in each series). Importantly, these five genes were also effective for classifying independent series of postradiotherapy (five PTC) and post-Chernobyl (six PTC) tumors compared to independent series of sporadic tumors (eight PTC and six PTC respectively; testing tumors). Moreover, part of each postradiotherapy (32 genes) and post-Chernobyl signature (16 genes) cross-classified the respective series of thyroid tumors. Finally, several molecular pathways deregulated in post

  6. Effect of cell phone-like electromagnetic radiation on primary human thyroid cells.

    Science.gov (United States)

    Silva, Veronica; Hilly, Ohad; Strenov, Yulia; Tzabari, Cochava; Hauptman, Yirmi; Feinmesser, Raphael

    2016-01-01

    To evaluate the potential carcinogenic effects of radiofrequency energy (RFE) emitted by cell phones on human thyroid primary cells. Primary thyroid cell culture was prepared from normal thyroid tissue obtained from patients who underwent surgery at our department. Subconfluent thyroid cells were irradiated under different conditions inside a cell incubator using a device that simulates cell phone-RFE. Proliferation of control and irradiated cells was assessed by the immunohistochemical staining of antigen Kiel clone-67 (Ki-67) and tumor suppressor p53 (p53) expression. DNA ploidy and the stress biomarkers heat shock protein 70 (HSP70) and reactive oxygen species (ROS) was evaluated by fluorescence-activated cell sorting (FACS). Our cells highly expressed thyroglobulin (Tg) and sodium-iodide symporter (NIS) confirming the origin of the tissue. None of the irradiation conditions evaluated here had an effect neither on the proliferation marker Ki-67 nor on p53 expression. DNA ploidy was also not affected by RFE, as well as the expression of the biomarkers HSP70 and ROS. Our conditions of RFE exposure seem to have no potential carcinogenic effect on human thyroid cells. Moreover, common biomarkers usually associated to environmental stress also remained unchanged. We failed to find an association between cell phone-RFE and thyroid cancer. Additional studies are recommended.

  7. Thyroglobulin and other tumor markers in the follow-up of differentiated thyroid carcinoma

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    Reiners, C.; Becker, W.; Berger, P.; Eilles, C.; Gerhards, W.; Rendl, J.; Schaede, B.; Scheler, S.; Schneider, P.; Spiegel, W.

    1986-04-01

    The diagnostic value of thyroglobulin (hTg) serum measurements for the follow-up of papillary, follicular and oncocytic thyroid carcinoma has been re-evaluated after more than 6 years of clinical experience with this tumor marker in 370 cancer patients. The sensitivity of hTg RIA for the detection of metastases or recurrence amounts to 94%, provided that residual thyroid tissue has been totally ablated and that serum samples are drawn after withdrawal of thyroid hormone replacement. The I-131 scan may be replaced under certain conditions by hTg RIA which has proven a valid, reasonable and convenient diagnostic method for long time follow-up of differentiated thyroid cancer. The somewhat reduced sensitivity of hTg determinations under continued thyroid hormone medication can be tolerated, provided that a standardised follow-up protocol is used including clinical, sonographic and radiological investigations. (orig./TRV).

  8. Expression of the human sodium/iodide symporter (hNIS) in xenotransplanted human thyroid carcinoma

    NARCIS (Netherlands)

    Smit, J.W.A.; Schröder - van der Elst, J.P.; Karperien, M.; Que, I.; Romijn, J.A.; Heide, van der D.

    2001-01-01

    The uptake of iodide in thyroid epithelial cells is mediated by the sodium/iodide symporter (NIS). The uptake of iodide is of vital importance for thyroid physiology and is a prerequisite for radioiodine therapy in thyroid cancer. Loss of iodide uptake due to diminished expression of the human NIS

  9. Aberrant expression of tumor-associated carbohydrate antigen Globo H in thyroid carcinoma.

    Science.gov (United States)

    Cheng, Shih-Ping; Yang, Po-Sheng; Chien, Ming-Nan; Chen, Ming-Jen; Lee, Jie-Jen; Liu, Chien-Liang

    2016-12-01

    The induction of tumor-associated carbohydrate antigen results from altered glycosylation in transformed cells. Globo H is a hexasaccharide glycosphingolipid overexpressed on malignancies of epithelial origin and has become an attractive vaccine target. We aimed to investigate the expression patterns and prognostic value of Globo H in thyroid neoplasms. Globo H expression was examined by immunohistochemical analysis using commercial and in-house tissue microarrays. The expression was correlated with clinicopathologic characteristics in papillary thyroid cancer. Normal or benign thyroid lesions were negative for Globo H expression. Globo H was positive in 33% medullary, 24% papillary, 11% undifferentiated, and 8% follicular thyroid cancer. Globo H expression in papillary thyroid cancer was associated with extrathyroidal invasion (P = 0.017), BRAF mutation (P = 0.010), AMES high risk (P = 0.045), and increased ATA risk of recurrence (P = 0.022). Globo H is specifically expressed in a subset of thyroid malignancies. In papillary thyroid cancer, Globo H expression is associated with invasiveness and BRAF mutation. Immunotherapy targeting Globo H may have potential applications in thyroid cancer. J. Surg. Oncol. 2016;114:853-858. © 2016 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Iodide kinetics and experimental (131)I therapy in a xenotransplanted human sodium-iodide symporter-transfected human follicular thyroid carcinoma cell line.

    Science.gov (United States)

    Smit, Jan W A; Schröder-van der Elst, Janny P; Karperien, Marcel; Que, Ivo; Stokkel, Marcel; van der Heide, Daan; Romijn, Johannes A

    2002-03-01

    Uptake of iodide is a prerequisite for radioiodide therapy in thyroid cancer. However, loss of iodide uptake is frequently observed in metastasized thyroid cancer, which may be explained by diminished expression of the human sodium-iodide symporter (hNIS). We studied whether transfection of hNIS into the hNIS-deficient follicular thyroid carcinoma cell line FTC133 restores the in vivo iodide accumulation in xenografted tumors and their susceptibility to radioiodide therapy. In addition, the effects of low-iodide diets and thyroid ablation on iodide kinetics were investigated. Tumors were established in nude mice injected with the hNIS-transfected cell line FTC133-NIS30 and the empty vector transfected cell line FTC133-V4 as a control. Tumors derived from FTC133-NIS30 in mice on a normal diet revealed a high peak iodide accumulation (17.4% of administered activity, measured with an external probe) as compared with FTC133-V4 (4.6%). Half-life in FTC133-NIS30 tumors was 3.8 h. In mice kept on a low-iodide diet, peak activity in FTC133-NIS30 tumors was diminished (8.1%), whereas thyroid iodide accumulation was increased. In thyroid-ablated mice kept on a low-iodide diet, half-life of radioiodide was increased considerably (26.3 h), leading to a much higher area under the time-radioactivity curve than in FTC133-NIS30 tumors in mice on a normal diet without thyroid ablation. Experimental radioiodide therapy with 2 mCi (74 MBq) in thyroid-ablated nude mice, kept on a low-iodide diet, postponed tumor development (4 wk after therapy, one of seven animals revealed tumor vs. five of six animals without therapy). However, 9 wk after therapy, tumors had developed in four of the seven animals. The calculated tumor dose was 32.2 Gy. We conclude that hNIS transfection into a hNIS-defective thyroid carcinoma cell line restores the in vivo iodide accumulation. The unfavorable iodide kinetic characteristics (short half-life) can be partially improved by conventional conditioning with

  11. Characterization of human follicular thyroid cancer cell lines in preclinical mouse models

    Directory of Open Access Journals (Sweden)

    Ashley N Reeb

    2016-04-01

    Full Text Available Follicular thyroid cancer (FTC is the second most common type of thyroid cancers. In order to develop more effective personalized therapies, it is necessary to thoroughly evaluate patient-derived cell lines in in vivo preclinical models before using them to test new, targeted therapies. This study evaluates the tumorigenic and metastatic potential of a panel of three human FTC cell lines (WRO, FTC-238, and TT1609-CO2 with defined genetic mutations in two in vivo murine models: an orthotopic thyroid cancer model to study tumor progression and a tail vein injection model to study metastasis. All cell lines developed tumors in the orthotopic model, with take rates of 100%. Notably, WRO-derived tumors grew two to four times faster than tumors arising from the FTC-238 and TT2609-CO2 cell lines. These results mirrored those of a tail vein injection model for lung metastasis: one hundred percent of mice injected with WRO cells in the tail vein exhibited aggressive growth of bilateral lung metastases within 35 days. In contrast, tail vein injection of FTC-238 or TT2609-CO2 cells did not result in lung metastasis. Together, our work demonstrates that these human FTC cell lines display highly varied tumorigenic and metastatic potential in vivo with WRO being the most aggressive cell line in both orthotopic and lung metastasis models. This information will be valuable when selecting cell lines for preclinical drug testing.

  12. [Molecular Aspects of Thyroid Tumors with Emphasis on MicroRNA and Their Clinical Implications].

    Science.gov (United States)

    Ludvíková, M; Kholová, I; Kalfeřt, D

    Central to neoplastic transformation and tumor progression is alteration of the signaling pathways that control cell proliferation and apoptosis. The key mechanisms for this neoplastic process are genetic changes (mutations of cancer-related genes) and recently identified epigenetic changes that involve DNA methylation, chromatin remodeling (which has a profound effect on the control of gene expression), and noncoding, regulatory RNA (notably, microRNA - miRNA). MiRNAs control expression of their target gene post-transcriptionally. These molecular factors have potential as diagnostic, prognostic, and predictive molecular markers. Epithelial tumors of the thyroid gland are a histogenetically, morphologically, and pathobiologically heterogeneous group of neoplasms and require new, molecular approaches in clinical practice. This review aims to present contemporary scientific knowledge of this molecular (genetic and epigenetic) field of sporadic thyroid tumors of follicular cell origin and their potential clinical implications. The fundamental mutations (BRAFV600E, RET/PTC, RAS, and PAX8-PPARG) in selected tumor types are described comprehensively. Special attention is paid to miRNAs, including their biogenesis, function, and expression profiles in the most common thyroid tumors - follicular adenoma, follicular carcinoma, and papillary carcinoma. Thyroid cancer medicine has recently entered a new, molecular era. Comprehensive knowledge of all molecular aspects may improve diagnostics and management of thyroid neoplasms through the introduction of novel, progressive treatment strategies for this cancer. Further research on signaling pathway-related targets, standardization of methods, and evaluation of results are required.Key words: thyroid tumors - cancerogenesis - genetics - epigenetics - microRNA The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript

  13. Medullary and papillary carcinoma of the thyroid gland occurring as a collision tumor with lymph node metastasis: A case report

    Directory of Open Access Journals (Sweden)

    Sadat Alavi Mehr

    2011-12-01

    Full Text Available Abstract Introduction Papillary thyroid carcinoma and medullary thyroid carcinoma are two different thyroid neoplasia. The simultaneous occurrence of medullary thyroid carcinoma and papillary thyroid carcinoma as a collison tumor with metastases from both lesions in the regional lymph nodes is a rare phenomenon. Case presentation A 32-year-old Iranian man presented with a fixed anterior neck mass. Ultrasonography revealed two separate thyroid nodules as well as a suspicious neck mass that appeared to be a metastatic lesion. The results of thyroid function tests were normal, but the preoperative calcitonin serum value was elevated. Our patient underwent a total thyroidectomy with neck exploration. Two separate and ill-defined solid lesions grossly in the right lobe were noticed. Histological and immunohistochemical studies of these lesions suggested the presence of medullary thyroid carcinoma and papillary thyroid carcinoma. The lymph nodes isolated from a neck dissection specimen showed metastases from both lesions. Conclusions The concomitant occurrence of papillary thyroid carcinoma and medullary thyroid carcinoma and the exact diagnosis of this uncommon event are important. The treatment strategy should be reconsidered in such cases, and genetic screening to exclude multiple endocrine neoplasia 2 syndromes should be performed. For papillary thyroid carcinoma, radioiodine therapy and thyroid-stimulating hormone suppressive therapy are performed. However, the treatment of medullary thyroid carcinoma is mostly radical surgery with no effective adjuvant therapy.

  14. [Incidence of anaplastic tumor in structure of other histologic forms of the thyroid gland cancer].

    Science.gov (United States)

    Vinnik, Iu A; Gorbenko, V N; Vas'ko, A R; Kikhtenko, E V; Gargin, V V

    2014-01-01

    The degrees of invasiveness, proliferative activity, morphofunctional activity of nuclei in the thyroidal gland tumors were studied, while analyzing material, obtained in 1343 patients, suffering thyroidal gland cancer (THGC) and operated on in 2000-2013 yrs. Morphological point quantity of malignancy (as a criterion of the tumor progression grade) and mitotic activity in cellular population were determined in various kinds of THGC. Undifferentiated (anaplastic carcinoma) type of THGC is the most malignant one. There were determined a spindle-like, giant-cell and squamous-cell forms of undifferentiated THGC. The presence of sites of differentiated cancer in 33% of histological preparations witnesses the interrelationship with the earlier existed pathological process.

  15. Selenium glutathione peroxidase activities and thyroid functions in human individuals

    Science.gov (United States)

    Bellisola, G.; Calza Contin, M.; Ceccato, D.; Cinque, G.; Francia, G.; Galassini, S.; Liu, N. Q.; Lo Cascio, C.; Moschini, G.; Sussi, P. L.

    1996-04-01

    At least two enzymes are involved in metabolism of thyroid hormones. GSHPx protects thyrocyte from high H 2O 2 levels that are required for iodination of prohormones to form T4 in thyroid cell. Type I iodothyronine 5'-deiodinase (5'-D) catalyzes the deiodination of L-thyroxin (T4) to the biologically active thyroid hormone 3,3'-5-triiodothyronine (T 3) in liver, in kidney and in thyroid tissues. Circulating thyroid hormones, plasma Se levels, GSHPx activities in platelets and in plasma were investigated in 29 human individuals with increased thyroid mass. PIXE was applied to measure Se in 1 ml of plasma because we supposed patients were in a marginal carential status for Se. Plasma Se concentrations were compared with those of normal individuals. Correlation studies between plasma Se level and both GSHPx activities were carried out as well as between platelets and plasma GSHPx activities to verify the hypothesis of a marginal Se deficiency in patients. Significance of circulating thyroid hormones levels will be discussed.

  16. Multifocality of thyroid carcinomas: a "privilege" of papillary tumors or not?

    Science.gov (United States)

    Papageorgiou, M S; Liratzopoulos, N; Efremidou, E I; Karanikas, M; Minipoulos, G; Manolas, K J

    2010-01-01

    To study the frequency of multifocality in well-differentiated non-medullary thyroid carcinomas and correlate it with various epidemiological factors, as well as with patients' survival. A retrospective study was conducted on 80 patients who underwent total thyroidectomy from January 1985 to December 2004 in the First Department of Surgery of University General Hospital of Alexandroupolis, Democritus University of Thrace, Greece, for well-differentiated non-medullary thyroid cancer (papillary and follicular). Patients' medical records and demographics, including age, gender, histological type (papillary, follicular), multiple foci of tumors, overall and specific survival were analyzed. Multifocality was established in 17/80 patients (21,25%). Multifocal tumors were found in 4/20 male patients (20%) and 13/60 female ones (21,67%), percentages which are almost identical. Increased rates of multifocal tumors were found in the age groups of 20-29, 30-39 and 70-79 years old, while low rates were documented in the age groups of 0-9, 10-19 and 60-69 years old. Follicular tumors had a 20% rate, similar to papillary tumors (22,2%), and an impressive multifocal rate of mixed papillary-follicular neoplasms (75%) was found. Finally, survival was not found to be influenced by the multifocality of the tumor, under the prerequisition that total thyroidectomy is applied. Multifocality should not be considered as a "privilege" of papillary thyroid tumors, but as a privilege of thyroid carcinomas in general. If total thyroidectomy is applied in all benign and malignant thyroid diseases, the presence of multiple foci does not affect the prognosis and the survival of the patients.

  17. Multiple endocrine neoplasia similar to human subtype 2A in a dog: Medullary thyroid carcinoma, bilateral pheochromocytoma and parathyroid adenoma

    Directory of Open Access Journals (Sweden)

    E.A. Soler Arias

    2016-10-01

    Full Text Available Human multiple endocrine neoplasia subtype 2A (MEN 2A is characterized by medullary thyroid carcinoma, pheochromocytoma and parathyroid hyperplasia or adenoma in the same individual. In this report, a case of a female Rottweiler with medullary thyroid carcinoma, bilateral pheochromocytoma and parathyroid adenoma was described. Clinical manifestations of muscle weakness, polydipsia, polyuria, diarrhea and weight loss were observed. Two adrenal neoplasms were identified incidentally by ultrasonography, and tumor in the left thyroid lobe was identified by palpation. Primary hyperparathyroidism was diagnosed by biochemical testing. Histopathology report was consistent with diagnosis of bilateral pheochromocytoma and parathyroid adenoma. Immunohistochemical staining was positive for calcitonin and synaptophysin, and negative for thyroglobulin, which confirmed medullary thyroid carcinoma. This case in a dog is presenting neoplastic characteristics similar to human MEN 2A and emphasizing the importance of using immunohistochemistry for confirmation.

  18. Peculiarities of synchronic and metachronous malignant tumors of reproductive system in thyroid gland cancer.

    Science.gov (United States)

    Makaridze, T; Mardaleishvili, K

    2009-12-01

    The aim of our study was to establish a reliable method for the evaluation of mechanisms of tumor development and early diagnostics of tumors of the breast and female genital organs in patients with thyroid gland cancer. For this purpose 29 female patients with thyroid gland cancer and different accompanied diseases of reproductive tract system have been studied for six months. During this period patients' clinical, hormonal and ultrasonographyc indicators were analyzed. The study showed that, suppressive therapy is preventive method in development of pre-cancer diseases of reproductive system. Thyrotrophic hormone hypersecretion (long current latent hypothyroidism) conditions thyroid gland proliferative activity; high level of gonadoliberin provides proliferative activity of organs of reproductive system.

  19. Napsin A and Thyroid Transcription Factor-1-Positive Cerebellar Tumor with Epidermal Growth Factor Receptor Mutation

    Directory of Open Access Journals (Sweden)

    Taiji Kuwata

    2011-12-01

    Full Text Available We present a very rare case of cerebellar metastasis of unknown origin, in which a primary lung adenocarcinoma was diagnosed by pathological examination of a cerebellar metastatic tumor, using immunohistochemical markers and epidermal growth factor receptor (EGFR mutation of primary lung cancer. A 69-year-old woman was admitted to our hospital because of a hemorrhagic cerebellar tumor and multiple small brain tumors. She underwent cerebellar tumor resection. On pathological examination, the tumor was diagnosed as adenocarcinoma. However, the primary tumor site was unidentifiable even with several imaging inspections. On immunohistochemical analysis, the resected tumor was positive for napsin A and thyroid transcription factor-1. In addition, an EGFR mutation was detected in the tumor. Therefore, primary lung cancer was diagnosed and the patient was started on gefitinib (250 mg/day therapy.

  20. Late bone metastasis from an apparently benign oncocytic follicular thyroid tumor

    Science.gov (United States)

    Boronat, Mauro; Cabrera, Juan J; Perera, Carmen; Isla, Concepción; Nóvoa, Francisco J

    2013-01-01

    A man underwent total thyroidectomy for goiter when he was 62 years old. The pathology report informed on a 5.5 cm oncocytic follicular adenoma and a 3.5 mm papillary microcarcinoma. Due to the papillary tumor, he was treated with ablative radioiodine therapy and suppressive doses of levothyroxine. After uneventful follow-up for 9 years, increased levels of serum thyroglobulin were detected. Further imaging studies including a whole body scan (WBS) after an empirical dose of 200 mCi 131I were negative. Two years later, a 99mTc SestaMIBI WBS and a 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography showed a well-delimited focal uptake in the right femur. A bone biopsy of the lesion demonstrated metastasis of follicular thyroid carcinoma. Retrospective histological reexamination of available material from the primary oncocytic thyroid tumor failed to reveal definitive traits of malignancy. Learning points Oncocytic follicular thyroid tumors are a relatively uncommon variant of follicular thyroid neoplasms mostly composed of distinctive large oxyphilic cells (Hürthle cells).Criteria for the distinction between benign and malignant oncocytic neoplasms are not different from those used in the diagnosis of ordinary follicular tumors.Some cases of apparently benign oncocytic neoplasms have been found to develop malignant behavior.Search to rule out vascular and capsular invasion should be particularly exhaustive in histological assessment of oncocytic thyroid tumors.Even so, long-term surveillance remains appropriate for patients with large apparently benign oncocytic tumors. PMID:24616777

  1. Immunoproteasome overexpression underlies the pathogenesis of thyroid oncocytes and primary hypothyroidism: studies in humans and mice.

    Directory of Open Access Journals (Sweden)

    Hiroaki J Kimura

    2009-11-01

    Full Text Available Oncocytes of the thyroid gland (Hürthle cells are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular eosinophilic cytoplasm and hyperchromatic nucleus. Their pathogenesis has remained, thus far, unknown.Using transgenic mice chronically expressing IFNgamma in thyroid gland, we showed changes in the thyroid follicular epithelium reminiscent of the human oncocyte. Transcriptome analysis comparing transgenic to wild type thyrocytes revealed increased levels of immunoproteasome subunits like LMP2 in transgenics, suggesting an important role of the immunoproteasome in oncocyte pathogenesis. Pharmacologic blockade of the proteasome, in fact, ameliorated the oncocytic phenotype. Genetic deletion of LMP2 subunit prevented the development of the oncocytic phenotype and primary hypothyroidism. LMP2 was also found expressed in oncocytes from patients with Hashimoto thyroiditis and Hürthle cell tumors.In summary, we report that oncocytes are the result of an increased immunoproteasome expression secondary to a chronic inflammatory milieu, and suggest LMP2 as a novel therapeutic target for the treatment of oncocytic lesions and autoimmune hypothyroidism.

  2. THYROID HORMONE: A “PRIME SUSPECT” IN HUMAN IMMUNO ...

    African Journals Online (AJOL)

    Daniel Owu

    .nips; www.cas.org. THYROID HORMONE: A “PRIME SUSPECT” IN HUMAN IMMUNO. DEFICIENCY VIRUS (HIV/AIDS) PATIENTS? K. AMADI, A. M. SABO, O. O. OGUNKEYE and F. S. OLUWOLE. 1. Department of Human Physiology, College ...

  3. Attenuation Coefficient Estimation of the Healthy Human Thyroid In Vivo

    Science.gov (United States)

    Rouyer, J.; Cueva, T.; Portal, A.; Yamamoto, T.; Lavarello, R.

    Previous studies have demonstrated that attenuation coefficients can be useful towards characterizing thyroid tissues. In this work, ultrasonic attenuation coefficients were estimated from healthy human thyroids in vivo using a clinical scanner. The selected subjects were five young, healthy volunteers (age: 26 ± 6 years old, gender: three females, two males) with no reported history of thyroid diseases, no palpable thyroid nodules, no smoking habits, and body mass index less than 30 kg/m2. Echographic examinations were conducted by a trained sonographer using a SonixTouch system (Ultrasonix Medical Corporation, Richmond, BC) equipped with an L14-5 linear transducer array (nominal center frequency of 10 MHz, transducer footprint of 3.8 cm). Radiofrequency data corresponding to the collected echographic images in both transverse and longitudinal views were digitized at a sampling rate of 40 MHz and processed with Matlab codes (MathWorks, Natick, MA) to estimate attenuation coefficients using the spectral log difference method. The estimation was performed using an analysis bandwidth spanning from 4.0 to 9.0 MHz. The average value of the estimated ultrasonic attenuation coefficients was equal to 1.34 ± 0.15 dB/(cm.MHz). The standard deviation of the estimated average attenuation coefficient across different volunteers suggests a non-negligible inter-subject variability in the ultrasonic attenuation coefficient of the human thyroid.

  4. [Tumors of the thyroid gland in dogs--a local characteristic in the area of Leipzig].

    Science.gov (United States)

    Aupperle, H; Gliesche, K; Schoon, H A

    2003-04-01

    During 17 years (1985-2002) 4.072 necropsies in dogs were performed at the Institut für Veterinär-Pathologie of the University of Leipzig. 154 of them showed tumors of the thyroid. Retrospective classification of the neoplasia between 1992-2002 revealed 6 adenomas, 18 follicular, 33 solid-follicular and 21 solid carcinomas as well as one squamous cell carcinoma, one medullary (C-cell) carcinoma and one fibrosarcoma. During the time investigated, the number of thyroidal neoplasia out of all tumorous diseases in dogs decreased from 48% in 1986 to 3.8% in 2002. This phenomenon may be the result of an increased use of commercially produced animal food with supplementation of iodine. This may have led to the disappearance of the "typical" disease--thyroidal cancer--in dogs in this endemic area of iodine deficiency. The use of immunohistochemical markers shows that the expression pattern in neoplastic follicular areas mostly corresponds to the intact thyroidea. But in solid tumor regions the expression of thyroglobulin, cytokeratin 19 and neuron specific enolase (NSE) has diminished in most areas. Thyroid transcription factor 1 (TTF-1) is expressed in all carcinomas in variable intensity. Medullary carcinoma typically express calcitonin.

  5. Lenvatinib induces early tumor shrinkage in patients with advanced thyroid carcinoma.

    Science.gov (United States)

    Masaki, Chie; Sugino, Kiminori; Saito, Naoko; Saito, Yoshiyuki; Tanaka, Tomoaki; Ogimi, Yuna; Maeda, Tetsuyo; Osaku, Tadatoshi; Akaishi, Junko; Hames, Kiyomi Y; Tomoda, Chisato; Suzuki, Akifumi; Matsuzu, Kenichi; Uruno, Takashi; Ohkuwa, Keiko; Kitagawa, Wataru; Nagahama, Mitsuji; Takami, Hiroshi; Ito, Koichi

    2017-08-30

    Although advanced thyroid carcinoma patients who cannot be cured by conventional therapy have lacked effective treatment, multitargeted tyrosine kinase inhibitors have recently become available. Phase 3 trials of lenvatinib showed a median time to objective response of 2 (95 % confidence interval (CI) 1.9-3.5) months, demonstrating that shrinks tumors rapidly. The phenomenon of immediate tumor shrink is known as early tumor shrinkage (ETS) which is related to clinical outcome in other malignancies. However, precisely when within 8 weeks lenvatinib starts to affect tumors remains unclear. In tumors near the carotid arteries, trachea, or esophagus, a rapid therapeutic effect can induce fistula formation or arterial bleeding. To prevent such treatment-emergent serious adverse events (SAE), early imaging evaluation seems to be very important. In this study, the point in time when lenvatinib started to shrink tumors was retrospectively investigated. The subjects were 16 patients who started lenvatinib administration between May and August 2015. Tumor size was evaluated by computed tomography (CT) scans frequently within the first 8 weeks according to the Response Evaluation Criteria In Solid Tumors (RECIST) guideline. Initial tumor response was defined as ≥ 10% tumor reduction. Serum thyroglobulin (Tg) level was monitored in 8 differentiated thyroid carcinoma (DTC) without TgAb patients. At the first evaluation, 13 patients (83.3 %) showed tumor reduction and that decreased with time. Thirteen patients (83.3 %) showed >10 % tumor reduction within 8 weeks. In all DTC patients, serum Tg level was markedly decreased. In conclusion, lenvatinib immediately shrinks tumors, the so-called ETS phenomenon. Therefore, careful attention should be paid to fistula formation from the early phase.

  6. Parvovirus B19 infection in Hashimoto's thyroiditis, papillary thyroid carcinoma, and anaplastic thyroid carcinoma.

    Science.gov (United States)

    Adamson, Laura A; Fowler, Larry J; Clare-Salzler, Michael J; Hobbs, Jacqueline A

    2011-04-01

    The human pathogenic parvovirus B19 (B19) has recently been detected in papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) tissues at a high frequency in two studies of a Chinese cohort. We wanted to extend these data to include another cohort and expand the thyroid tumor tissue types assessed. In particular, we were interested to find whether B19 also infects anaplastic thyroid carcinoma (ATC), one of the most aggressive human cancers. Commercially available thyroid tumor tissue arrays were used to detect B19 capsid protein by immunohistochemistry in various types of thyroid tumors and disorders. The arrays were representative of the four main types of thyroid tumors, as well as other thyroid autoimmune disorders such as HT and Graves' disease, and adenomas, goiters, lymphomas, and normal thyroid tissue. In total, at least 12 different types of thyroid conditions as well as normal tissue were represented, many with multiple subjects. Twenty-one of the 24 (88%) PTC tumors, 3 of the 3 ATC/undifferentiated tumors, and 3 of the 3 HT tissue samples were positive for B19 capsid protein by immunohistochemistry. The localization of the protein differed based on pathological disease type, with a nuclear to cytoplasmic shift seen from unaffected to tumor tissue. We extend the data available on B19 detection in the thyroid to show a high correlation of virus in another cohort of PTC and HT at the protein level. We also show, for the first time, B19 infection of much more highly aggressive ATC/undifferentiated tumors. Nuclear to cytoplasmic shift in B19 protein in cancer tissue suggests a possible link between B19 and thyroid cancer pathogenesis/progression.

  7. [Preliminary approach towards construction of peptide libraries as potential tools for diagnosis of malignant thyroid tumors].

    Science.gov (United States)

    Balcerzak, Waldemar; Bednarz, Wiktor; Domosławski, Paweł; Olewiński, Robert; Kolesińska, Justyna; Kaminski, Zbigniew; Dziarkowska, Katarzyna; Wieczorek, Piotr

    2006-01-01

    Cancer of thyroid gland is the most common malignancy of the endocrine system. The treatment improvement could be achieved by early diagnosis. The aim of the study was to identify cancer specific antigenes with use of peptide libraries. The material from 6 patients with thyroid cancer (4 with papillary cancer, 1 with follicular cancer and 1 with oxyphilic tumor) were analyzed. It was performed with use of lipophylic peptide libraries by direct comparison of staining of specimens prepared from normal and malignant tissue. Preliminary results confirm practical value of peptide libraries in early diagnostics of thyroid cancer. It is important to optimize construction of peptide libraries by using different staining agents hydrolyzed by proteases.

  8. A Histological Autopsy Study of the Thyroid gland in Human ...

    African Journals Online (AJOL)

    SITWALA COMPUTERS

    1Department of Pathology and Microbiology, University Teaching Hospital, Lusaka, Zambia. 2Department of Pathology and Microbiology, School of Medicine, University of Zambia, Lusaka, Zambia. Key Words: Thyroid histology, HIV infection, Autopsy, Adult. ABSTRACT. Background: Despite the high prevalence of Human.

  9. Depression, suicide ideation, and thyroid tumors among ukrainian adolescents exposed as children to chernobyl radiation.

    Science.gov (United States)

    Contis, George; Foley, Thomas P

    2015-05-01

    The Chernobyl Childhood Illness Program (CCIP) was a humanitarian assistance effort funded by the United States Congress. Its purpose was to assist the Ukrainian Government to identify and treat adolescents who developed mental and physical problems following their exposure as young children to Chernobyl radiation. Thirteen years after the Chernobyl nuclear plant accident in 1986, the CCIP examined 116,655 Ukrainian adolescents for thyroid diseases. Of these, 115,191 were also screened for depression, suicide ideation, and psychological problems. The adolescents lived in five of Ukraine's seven most Chernobyl radiation contaminated provinces. They were up to 6 years of age or in utero when exposed to nuclear fallout, or were born up to 45 months after Chernobyl. Ukrainian endocrinologist and ultrasonographers used physical examination and ultrasonography of the neck to evaluate the adolescents for thyroid tumors. The adolescents were then screened for depression by the Children's Depression Inventory (CDI). After this, Ukrainian psychologists conducted individual psychological interviews to corroborate the adolescents' CDI responses. Papillary thyroid carcinoma was diagnosed in eight adolescents, a high prevalence rate similar to that reported by other studies from the Soviet Union. Screening identified thyroid nodules in 1,967 adolescents (1.7%). Depression was diagnosed in 15,399 adolescents (13.2%), suicide ideation in 813 (5.3%), and attempted suicide in 354 (2.3%). Underlying components of the participants' depression were negative mood, interpersonal difficulties, negative self-esteem, ineffectiveness, and anhedonia. Depression was greater in females (77%). Those with thyroid and psychological problems were referred for treatment. The adolescents screened by CCIP represent the largest Ukrainian cohort exposed to Chernobyl radiation as children who were evaluated for both thyroid tumors and depression. The group had an increased prevalence of thyroid cancer

  10. Depression, Suicide Ideation, and Thyroid Tumors Among Ukrainian Adolescents Exposed as Children to Chernobyl Radiation

    Science.gov (United States)

    Contis, George; Foley, Thomas P.

    2015-01-01

    Background The Chernobyl Childhood Illness Program (CCIP) was a humanitarian assistance effort funded by the United States Congress. Its purpose was to assist the Ukrainian Government to identify and treat adolescents who developed mental and physical problems following their exposure as young children to Chernobyl radiation. Thirteen years after the Chernobyl nuclear plant accident in 1986, the CCIP examined 116,655 Ukrainian adolescents for thyroid diseases. Of these, 115,191 were also screened for depression, suicide ideation, and psychological problems. The adolescents lived in five of Ukraine’s seven most Chernobyl radiation contaminated provinces. They were up to 6 years of age or in utero when exposed to nuclear fallout, or were born up to 45 months after Chernobyl. Methods Ukrainian endocrinologist and ultrasonographers used physical examination and ultrasonography of the neck to evaluate the adolescents for thyroid tumors. The adolescents were then screened for depression by the Children’s Depression Inventory (CDI). After this, Ukrainian psychologists conducted individual psychological interviews to corroborate the adolescents’ CDI responses. Results Papillary thyroid carcinoma was diagnosed in eight adolescents, a high prevalence rate similar to that reported by other studies from the Soviet Union. Screening identified thyroid nodules in 1,967 adolescents (1.7%). Depression was diagnosed in 15,399 adolescents (13.2%), suicide ideation in 813 (5.3%), and attempted suicide in 354 (2.3%). Underlying components of the participants’ depression were negative mood, interpersonal difficulties, negative self-esteem, ineffectiveness, and anhedonia. Depression was greater in females (77%). Those with thyroid and psychological problems were referred for treatment. Conclusions The adolescents screened by CCIP represent the largest Ukrainian cohort exposed to Chernobyl radiation as children who were evaluated for both thyroid tumors and depression. The group

  11. Expression Patterns of Glucose Transporter-1 Gene and Thyroid Specific Genes in Human Papillary Thyroid Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sungeun; Chung, Junekey; Min Haesook and others

    2014-06-15

    The expression of glucose transporter-1 (Glut-1) gene and those of major thyroid-specific genes were examined in papillary carcinoma tissues, and the expressions of these genes were compared with cancer differentiation grades. Twenty-four human papillary carcinoma tissues were included in this study. The expressions of Glut-1- and thyroid-specific genes [sodium/iodide symporter (NIS), thyroid peroxidase, thyroglobulin, TSH receptor and pendrin] were analyzed by RT-PCR. Expression levels were expressed as ratios versus the expression of beta-actin. Pathologic differentiation of papillary carcinoma was classified into a relatively well-differentiated group (n=13) and relatively less differentiated group (n=11). Glut-1 gene expression was significantly higher in the less differentiated group (0.66±0.04) than in the well-differentiated group (0.59±0.07). The expression levels of the NIS, PD and TG genes were significantly higher in the well-differentiated group (NIS: 0.67±0.20, PD: 0.65±0.21, TG: 0.74±0.16) than in the less differentiated group (NIS: 0.36±0.05, PD: 0.49±0.08, TG: 0.60±0.11), respectively. A significant negative correlation was found between Glut-1 and NIS expression, and positive correlations were found between NIS and TG, and between NIS and PD. The NIS, PD and TG genes were highly expressed in well-differentiated thyroid carcinomas, whereas the Glut-1 gene was highly expressed in less differentiated thyroid carcinomas. These findings provide a molecular rationale for the management of papillary carcinoma, especially in the selection of FDG PET or radioiodine whole-body scan and I-131-based therapy.

  12. Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology.

    Science.gov (United States)

    Aghajanova, Lusine; Stavreus-Evers, Anneli; Lindeberg, Maria; Landgren, Britt-Marie; Sparre, Lottie Skjöldebrand; Hovatta, Outi

    2011-01-01

    To study the expression, distribution, and function of thyroid-stimulating hormone receptor (TSHR) and thyroid hormone receptors (TR) α1, α2, and β1 in human endometrium. Experimental clinical study. University hospital. 31 fertile women. Endometrial biopsy samples obtained throughout the menstrual cycle. Real-time reverse transcriptase polymerase chain reaction, immunohistochemistry and Western blot to study the expression of TSHR, TRα1, TRα2, and TRβ1 messenger RNA (mRNA) and proteins in human endometrium. We found TSHR, TRα1, TRα2 and TRβ1 mRNA and proteins expressed in human endometrium. Immunostaining for TSHR in the luminal epithelium and TRα1 and β1 in the glandular and luminal epithelium increased statistically significantly on luteinizing hormone (LH) days 6 to 9, coinciding with appearance of pinopodes. Endometrial stromal and Ishikawa cells expressed mRNA for TSHR, TR, and iodothyronine deiodinases 1-3. After 48 hours, TSH significantly increased leukemia inhibitory factor (LIF) and LIF receptor (LIFR) messenger RNA (mRNA) in endometrial stromal cells, but decreased their expression in Ishikawa cells. Glucose transporter 1 mRNA was up-regulated by TSH in Ishikawa cells. We found that TSH statistically significantly increased secretion of free triiodothyronine (T3) and total thyroxin (T4) by Ishikawa cells compared with nonstimulated cells. Thyroid hormones are directly involved in endometrial physiology. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Isolated carcinoid tumor metastatic to the thyroid gland: report of a case initially diagnosed by fine needle aspiration cytology.

    Science.gov (United States)

    Maly, Alexander; Meir, Karen; Maly, Bella

    2006-01-01

    Neuroendocrine tumor metastatic to the thyroid gland is rare and may be difficult to differentiate from primary thyroid neuroendocrine tumors, such as medullary thyroid carcinoma (M/ITC). This report describes an unusual case of bronchial carcinoid metastatic to the thyroid diagnosed by fine needle aspiration cytology (FNAC). A 42-year-old woman with an undiagnosed bronchial carcinoid tumor presented to our clinic with a solitary nodule in the thyroid gland. FNAC of the nodule showed loosely cohesive groups of cuboidal tumor cells with scant, slightly granular cytoplasm; centrally located nuclei with a coarsely granular, salt-and-pepper chromatin pattern and inconspicuous nucleoli. Immunocytochemically the tumor cells were positive for neuron-specific enolase, chromogranin and synaptophysin and negative for thyroglobulin, calcitonin and carcinoembryonic antigen. The cytologic diagnosis of a metastatic neuroendocrine carcinoma was confirmed histologically. Metastasis to the thyroid gland may pose a diagnostic problem, particularly with tumors of neuroendocrine origin, as these have similar cytologic features in various organs. The correct preoperative cytologic diagnosis of metastatic carcinoid tumor in patients without a prior history of cancer and differential diagnosis with MTC are crucial because prognosis, workup and treatment are different in each.

  14. 21 CFR 201.316 - Drugs with thyroid hormone activity for human use; required warning.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs with thyroid hormone activity for human use... Drug Products § 201.316 Drugs with thyroid hormone activity for human use; required warning. (a) Drugs with thyroid hormone activity have been promoted for, and continue to be dispensed and prescribed for...

  15. Genetic and pharmacological targeting of CSF-1/CSF-1R inhibits tumor-associated macrophages and impairs BRAF-induced thyroid cancer progression.

    Science.gov (United States)

    Ryder, Mabel; Gild, Matti; Hohl, Tobias M; Pamer, Eric; Knauf, Jeff; Ghossein, Ronald; Joyce, Johanna A; Fagin, James A

    2013-01-01

    Advanced human thyroid cancers are densely infiltrated with tumor-associated macrophages (TAMs) and this correlates with a poor prognosis. We used BRAF-induced papillary thyroid cancer (PTC) mouse models to examine the role of TAMs in PTC progression. Following conditional activation of BRAF(V600E) in murine thyroids there is an increased expression of the TAM chemoattractants Csf-1 and Ccl-2. This is followed by the development of PTCs that are densely infiltrated with TAMs that express Csf-1r and Ccr2. Targeting CCR2-expressing cells during BRAF-induction reduced TAM density and impaired PTC development. This strategy also induced smaller tumors, decreased proliferation and restored a thyroid follicular architecture in established PTCs. In PTCs from mice that lacked CSF-1 or that received a c-FMS/CSF-1R kinase inhibitor, TAM recruitment and PTC progression was impaired, recapitulating the effects of targeting CCR2-expressing cells. Our data demonstrate that TAMs are pro-tumorigenic in advanced PTCs and that they can be targeted pharmacologically, which may be potentially useful for patients with advanced thyroid cancers.

  16. Genetic and pharmacological targeting of CSF-1/CSF-1R inhibits tumor-associated macrophages and impairs BRAF-induced thyroid cancer progression.

    Directory of Open Access Journals (Sweden)

    Mabel Ryder

    Full Text Available Advanced human thyroid cancers are densely infiltrated with tumor-associated macrophages (TAMs and this correlates with a poor prognosis. We used BRAF-induced papillary thyroid cancer (PTC mouse models to examine the role of TAMs in PTC progression. Following conditional activation of BRAF(V600E in murine thyroids there is an increased expression of the TAM chemoattractants Csf-1 and Ccl-2. This is followed by the development of PTCs that are densely infiltrated with TAMs that express Csf-1r and Ccr2. Targeting CCR2-expressing cells during BRAF-induction reduced TAM density and impaired PTC development. This strategy also induced smaller tumors, decreased proliferation and restored a thyroid follicular architecture in established PTCs. In PTCs from mice that lacked CSF-1 or that received a c-FMS/CSF-1R kinase inhibitor, TAM recruitment and PTC progression was impaired, recapitulating the effects of targeting CCR2-expressing cells. Our data demonstrate that TAMs are pro-tumorigenic in advanced PTCs and that they can be targeted pharmacologically, which may be potentially useful for patients with advanced thyroid cancers.

  17. Molecular cytogenetic characterization of a human thyroid cancercell line

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich G.; Tuton, Tiffany B.; Ito, Yuko; Chu, LisaW.; Lu, Chung-Mei; Baumgartner, Adolf; Zitzelsberger, Horst F.; Weier,Jingly F.

    2006-01-04

    The incidence of papillary thyroid carcinoma (PTC) increases significantly after exposure of the head and neck region to ionizing radiation, yet we know neither the steps involved in malignant transformation of thyroid epithelium nor the specific carcinogenic mode of action of radiation. Such increased tumor frequency became most evident in children after the 1986 nuclear accident in Chernobyl, Ukraine. In the twelve years following the accident, the average incidence of childhood PTCs (chPTC) increased over one hundred-fold compared to the rate of about 1 tumor incidence per 10{sup 6} children per year prior to 1986. To study the etiology of radiation-induced thyroid cancer, we formed an international consortium to investigate chromosomal changes and altered gene expression in cases of post-Chernobyl chPTC. Our approach is based on karyotyping of primary cultures established from chPTC specimens, establishment of cell lines and studies of genotype-phenotype relationships through high resolution chromosome analysis, DNA/cDNA micro-array studies, and mouse xenografts that test for tumorigenicity. Here, we report the application of fluorescence in situ hybridization (FISH)-based techniques for the molecular cytogenetic characterization of a highly tumorigenic chPTC cell line, S48TK, and its subclones. Using chromosome 9 rearrangements as an example, we describe a new approach termed ''BAC-FISH'' to rapidly delineate chromosomal breakpoints, an important step towards a better understanding of the formation of translocations and their functional consequences.

  18. Conservative multimodal management of a primitive neuroectodermal tumor of the thyroid

    Directory of Open Access Journals (Sweden)

    Juliette Haudebourg

    2013-04-01

    Full Text Available Primitive neuroectodermal tumors (PNET represent 1% of sarcomas. Head and neck peripheral PNETs have an intermediate prognosis between abdominopelvic disease and extremities. We here report the case of a 40-year old male who presented with primitive neuroectodermal tumor of the thyroid and was treated by multimodal treatment, including surgery, chemotherapy and intermediate dose radiotherapy. The patient is alive and fit with a functional larynx at 27 months. Multimodal treatments yield five-year survival rates of about 60%. Major drug regimens use vincristine, doxorubicin, ifosfamide or cyclophosphamide, dactinomycin and/or etoposide. Complete surgical excision is undertaken whenever possible to improve long-term survival. However, the relative radiosensitivity of tumors of the Ewing family, suggest multimodal treatment including adjuvant conformal radiotherapy in case of positive margins or poor response to chemotherapy rather than resection with 2-3 cm margins, which would imply laryngeal sacrifice for thyroid tumors. The role of expert rare tumor networks is crucial for optimal decision-making and management of such rare tumors on a case by case basis.

  19. The Thyro-Gastric syndrome: from thyroid autoimmunity to neuroendocrine gastric tumors

    OpenAIRE

    VALDES SOCIN, Hernan Gonzalo; Beckers, Albert

    2011-01-01

    THE THYRO-GASTRIC SYNDROME: FROM THYROID AUTOIMMUNITY TO NEUROENDOCRINE GASTRIC TUMORS. In 1849, Prof Addison described a fatal case of anemia, or anemia perniciosa. Dr Biermer expanded this original description in 1872. Nowadays, this pathological condition associating a megaloglastic anemia associated with a metabolic polyneuropathy is recognized as Biermer disease. Biermer anemia or anemia perniciosa and its associated polyneuropathy are the consequence of vitamine B12 malabsorpti...

  20. Hepatitis C Virus E2 Protein Induces Upregulation of IL-8 Pathways and Production of Heat Shock Proteins in Human Thyroid Cells.

    Science.gov (United States)

    Hammerstad, Sara Salehi; Stefan, Mihaela; Blackard, Jason; Owen, Randall P; Lee, Hanna J; Concepcion, Erlinda; Yi, Zhengzi; Zhang, Weijia; Tomer, Yaron

    2017-02-01

    Thyroiditis is one of the most common extrahepatic manifestations of hepatitis C virus (HCV) infection. By binding to surface cell receptor CD81, HCV envelope glycoprotein E2 mediates entry of HCV into cells. Studies have shown that different viral proteins may individually induce host responses to infection. We hypothesized that HCV E2 protein binding to CD81 expressed on thyroid cells activates a cascade of inflammatory responses that can trigger autoimmune thyroiditis in susceptible individuals. Human thyroid cell lines ML-1 and human thyrocytes in primary cell culture were treated with HCV recombinant E2 protein. The expression of major proinflammatory cytokines was measured at the messenger RNA and protein levels. Next-generation transcriptome analysis was used to identify early changes in gene expression in thyroid cells induced by E2. HCV envelope protein E2 induced strong inflammatory responses in human thyrocytes, resulting in production of interleukin (IL)-8, IL-6, and tumor necrosis factor-α. Furthermore, the E2 protein induced production of several heat shock proteins including HSP60, HSP70p12A, and HSP10, in human primary thyrocytes. In thyroid cell line ML-1, RNA sequencing identified upregulation of molecules involved in innate immune pathways with high levels of proinflammatory cytokines and chemokines and increased expression of costimulatory molecules, specifically CD40, known to be a major thyroid autoimmunity gene. Our data support a key role for HCV envelope protein E2 in triggering thyroid autoimmunity through activation of cytokine pathways by bystander mechanisms.

  1. Characteristic Dynamic Enhancement Pattern of Magnetic Resonance Imaging for Malignant Thyroid Tumor: A Preliminary Report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Young Nam; Hwang, Hee Young; Shim, Young Sup; Byun, Sung Su; Choi, Hye Young; Kim, Hyung Sik [Dept. of Radiology, Gil Hospital, Gachon University College of Medicine and Science, Incheon (Korea, Republic of)

    2011-11-15

    The purpose of this study is to determine the characteristic dynamic enhancement pattern of magnetic resonance (MR) imaging for malignant thyroid tumor. Eight patients who were pathology proven to have a malignant thyroid tumor, preoperatively. There are 5 papillary carcinomas, 1 medullary carcinoma, 1 follicular carcinoma, and 1 fine needle aspiration biopsy proven atypical cell. Based on preoperative MR imaging, we compared the dynamic MR enhancement pattern relating to the pathologic type. On contrast agent-enhanced dynamic T1-weighted image (T1WI), 5 papillary carcinoma and one medullary carcinoma showed delayed enhancement compared to normal parenchyma. In addition, one follicular carcinoma shows stronger enhancement than normal parenchyma, with one papillary carcinoma showing a persistent decrease in enhancement compared to normal parenchyma. Although this study is limited by a small patients population, the data suggests that delayed enhancement on enhanced dynamic T1WI is a possible characteristic MR finding of a malignant thyroid tumor. I think that the comparison of MR imaging between benign and malignant nodules is required for a correct characterization.

  2. MicroRNA-146b: A Novel Biomarker and Therapeutic Target for Human Papillary Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Chen-Kai Chou

    2017-03-01

    Full Text Available Papillary thyroid cancer (PTC is the most common tumor subtype of thyroid cancer. However, not all PTCs are responsive to current surgical and radioiodine treatment. The well-established clinical prognostic factors include tumor size, lymph node/distal metastasis, and extrathyroidal invasion. The RET/PTC-RAS-BRAF linear molecular signaling cascade is known to mediate PTC pathogenesis. However, whether presence of BRAF mutation, the most common genetic alteration in PTC, can affect PTC behavior and prognosis is controversial. MicroRNAs (miRNAs have been labeled as promising molecular prognostic markers in several tumor types. Our recent studies demonstrated that microRNA-146b (miR-146b deregulation is associated with PTC aggressiveness and prognosis. Here we summarize the current knowledge related to the functional roles, regulated target genes, and clinical applications of miR-146b in PTC and discuss how these studies provide insights into the key role of miR-146b as an oncogenic regulator promoting cellular transformation as well as a prognosis marker for tumor recurrence in PTC. In conjunction with the current perspectives on miRNAs in a wide variety of human cancers, this review will hopefully translate these updated findings on miR-146b into more comprehensive diagnostic or prognostic information regarding treatment in PTC patients before surgical intervention and follow up strategies.

  3. Metallothioneins in human tumors and potential roles in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cherian, M. George; Jayasurya, A.; Bay, Boon-Huat

    2003-12-10

    Metallothioneins (MT) are a group of low-molecular weight, cysteine rich intracellular proteins, which are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins have been associated with protection against DNA damage, oxidative stress and apoptosis. Moreover, MT may potentially activate certain transcriptional factors by donating zinc. Although MT is a cytosolic protein in resting cells, it can be translocated transiently to the cell nucleus during cell proliferation and differentiation. A number of studies have shown an increased expression of MT in various human tumors of the breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, salivary gland, testes, thyroid and urinary bladder. However, MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors, but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. In certain tumors such as germ cell carcinoma, the expression of MT is closely related to the tumor grade and proliferative activity. Increased expression of MT has also been observed in less differentiated tumors. Thus, expression of MT may be a potential prognostic marker for certain tumors. There are few reports on the expression of the different isoforms of MT which have been analyzed by specific gene probes. They reveal that certain isoforms are expressed in specific cell types. The factors which can influence MT induction in human tumors are not yet understood. Down-regulation of MT synthesis in hepatic tumors may be related to hypermethylation of the MT-promoter or mutation of other genes such as the p53 tumor suppressor gene. In vitro studies using human cancer cells suggest a possible role for p53 and the estrogen-receptor on the expression and induction of MT in epithelial neoplastic cells

  4. Role of maternal thyroid hormones in the developing neocortex and during human evolution

    Science.gov (United States)

    Stenzel, Denise; Huttner, Wieland B.

    2013-01-01

    The importance of thyroid hormones during brain development has been appreciated for many decades. In humans, low levels of circulating maternal thyroid hormones, e.g., caused by maternal hypothyroidism or lack of iodine in diet, results in a wide spectrum of severe neurological defects, including neurological cretinism characterized by profound neurologic impairment and mental retardation, underlining the importance of the maternal thyroid hormone contribution. In fact, iodine intake, which is essential for thyroid hormone production in the thyroid gland, has been related to the expansion of the brain, associated with the increased cognitive capacities during human evolution. Because thyroid hormones regulate transcriptional activity of target genes via their nuclear thyroid hormone receptors (THRs), even mild and transient changes in maternal thyroid hormone levels can directly affect and alter the gene expression profile, and thus disturb fetal brain development. Here we summarize how thyroid hormones may have influenced human brain evolution through the adaptation to new habitats, concomitant with changes in diet and, therefore, iodine intake. Further, we review the current picture we gained from experimental studies in rodents on the function of maternal thyroid hormones during developmental neurogenesis. We aim to evaluate the effects of maternal thyroid hormone deficiency as well as lack of THRs and transporters on brain development and function, shedding light on the cellular behavior conducted by thyroid hormones. PMID:23882187

  5. Expression of Notch 1 receptor associated with tumor aggressiveness in papillary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Fu H

    2016-03-01

    Full Text Available Hongliang Fu,1 Chao Ma,1 Wenbin Guan,2 Weiwei Cheng,1 Fang Feng,1 Hui Wang1 1Department of Nuclear Medicine, 2Department of Pathology, Xin Hua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China Aim: The aim of this study was to assess if the expression of Notch 1 receptor is associated with tumor aggressiveness in papillary thyroid carcinomas (PTCs.Patients and methods: By searching the electronic medical record system of Xin Hua Hospital, all cases of PTC patients who underwent thyroidectomy in the hospital between 2013 and 2014 were retrieved. Then, the cases of patients who had a history of any other malignancy or whose thyroid tumor specimen was not available for assay were rejected. Finally, 68 cases of PTC patients were obtained. Formalin-fixed paraffin-embedded tissue blocks of these patients were studied by immunohistochemistry to learn the expression of Notch 1 receptor. Meanwhile, the clinical data of these patients including sex, age, size of the tumor, presence of node metastasis or distant metastasis, and presence of capsule invasion and tumor multicentricity were collected. Pearson’s chi-square test or Fisher’s exact test was used for measuring statistical differences in categorical variables. All the statistical tests were two-sided. A P-value <0.05 was considered to be statistically significant.Results: A total of 19 male and 49 female PTC patients with a mean age of 44.8±13.6 years (range 18–78 years were studied. Notch 1 receptor expression was found in 15/68 (22% samples of PTC. The expression of Notch 1 receptor was significantly associated with tumor size (P=0.021, distant metastasis (P=0.008, capsule invasion (P=0.001, tumor multicentricity (P=0.018, and age (P=0.033. However, the expression of Notch 1 receptor was not significantly correlated with node metastasis (P=0.096 and sex (P=0.901.Conclusion: The expression of Notch 1 receptor is associated with tumor

  6. Regional localization of the gene for thyroid peroxidase to human chromosome 2pter----p12

    NARCIS (Netherlands)

    de Vijlder, J. J.; Dinsart, C.; Libert, F.; Geurts van Kessel, A.; Bikker, H.; Bolhuis, P. A.; Vassart, G.

    1988-01-01

    A 2.0-kb thyroid peroxidase cDNA of human origin was used as probe for Southern blot hybridization of genomic DNA from human somatic cells and human-rodent somatic cell hybrids. The results showed that the gene coding for human thyroid peroxidase is located on chromosome. 2. Further analysis of

  7. Smoldering medullary thyroid carcinoma liver metastasis 37 years after resection of an organ-confined tumor.

    Science.gov (United States)

    Waters, Kevin M; Ali, Syed Z; Erozan, Yener S; Olson, Matthew T

    2015-01-01

    Medullary thyroid carcinoma (MTC) is an uncommon thyroid tumor that usually behaves aggressively. After resection, serological surveillance for calcitonin and carcinoembryonic antigen (CEA) is used to prompt a radiographic search for metastatic disease. We report a case of a 65-year-old woman who presented with a large liver metastasis 37 years after she underwent thyroidectomy for organ-confined MTC. Her clinical course over that time showed a smoldering pattern in which she was symptom free until presentation even though her serum calcitonin and CEA concentrations were elevated for 17 years, and a small equivocal radiographic lesion in the liver was detected 10 years prior to presentation. Cytopathology from an ultrasound guided fine needle aspiration of the hepatic lesion was diagnostic for metastatic MTC. This case highlights the ability for smoldering residual MTC to suddenly transform to aggressive biological behavior after a long period of clinical remission. © 2014 Wiley Periodicals, Inc.

  8. Iodine-129 in human thyroids and seaweed in China

    DEFF Research Database (Denmark)

    Hou, Xiaolin; Dahlgaard, H.; Nielsen, S.P.

    2000-01-01

    The concentrations of I-129 and the ratios of I-129/I-127 in normal human thyroids collected in Tianjin, China, and some seaweed samples from the Chinese coast were determined by neutron activation analysis. The mean I-129/I-127 ratio in these thyroids was found to be 1.13 x 10(-9), which is two...... are considered not to have been directly exposed to 129I emission from a nuclear source, such as Chile, Taiwan and Tokyo. The mean I-129/I-127 ratio in seaweed from the Chinese coast is 2.35 x 10(-10), approximately two orders of magnitude higher than in seaweed collected in the pre-nuclear age, and similar...

  9. Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer

    Science.gov (United States)

    2017-11-20

    BRAF Gene Mutation; Poorly Differentiated Thyroid Gland Carcinoma; RAS Family Gene Mutation; Recurrent Thyroid Gland Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7

  10. Diet-induced obesity increases tumor growth and promotes anaplastic change in thyroid cancer in a mouse model.

    Science.gov (United States)

    Kim, Won Gu; Park, Jeong Won; Willingham, Mark C; Cheng, Sheue-yann

    2013-08-01

    Recent epidemiological studies provide strong evidence suggesting obesity is a risk factor in several cancers, including thyroid cancer. However, the molecular mechanisms by which obesity increases the risk of thyroid cancer are poorly understood. In this study, we evaluated the effect of diet-induced obesity on thyroid carcinogenesis in a mouse model that spontaneously develops thyroid cancer (Thrb(PV/PV)Pten(+/-) mice). These mice harbor a mutated thyroid hormone receptor-β (denoted as PV) and haplodeficiency of the Pten gene. A high-fat diet (HFD) efficiently induced the obese phenotype in Thrb(PV/PV)Pten(+/-) mice after 15 weeks. Thyroid tumor growth was markedly greater and survival was significantly lower in Thrb(PV/PV)Pten(+/-) mice fed an HFD than in controls fed a low-fat diet (LFD). The HFD increased thyroid tumor cell proliferation by increasing the protein levels of cyclin D1 and phosphorylated retinoblastoma protein to propel cell cycle progression. Histopathological analysis showed that the frequency of anaplasia of thyroid cancer was significantly greater (2.6-fold) in the HFD group than the LFD group. The HFD treatment led to an increase in parametrial/epididymal fat pad and elevated serum leptin levels in Thrb(PV/PV)Pten(+/-) mice. Further molecular analyses indicated that the HFD induced more aggressive pathological changes that were mediated by increased activation of the Janus kinase 2-signaling transducer and activator of transcription 3 (STAT3) signaling pathway and induction of STAT3 target gene expression. Our findings demonstrate that diet-induced obesity exacerbates thyroid cancer progression in Thrb(PV/PV)Pten(+/-) mice and suggest that the STAT3 signaling pathway could be tested as a potential target for the treatment of thyroid cancer.

  11. Promotion of thyroid tumors in rats by pregnenolone-16alpha-carbonitrile (PCN) and polychlorinated biphenyl (PCB).

    Science.gov (United States)

    Vansell, Nichole R; Muppidi, Jagan R; Habeebu, Sultan M; Klaassen, Curtis D

    2004-09-01

    Pregnenolone-16alpha-carbonitrile (PCN) and Aroclor 1254 (PCB) both reduce serum thyroid hormone levels in rats, but only PCN consistently produces an increase in serum thyrotropin (TSH). PCN-mediated increases in TSH result in increased thyroid follicular cell proliferation and hyperplasia, which may represent early events on a morphological continuum leading to neoplasia. The purpose of this study was to assess whether PCN, a compound that increases serum TSH, and PCB, which does not increase TSH, promote thyroid tumors in a two-stage carcinogenesis model. Male SD rats were administered the thyroid tumor initiator diisopropanolnitrosamine (2.5 g/kg, sc), and after seven days were fed control diet, diet containing 1000 ppm PCN, or diet containing 100 ppm PCB for 19 weeks. Body weights were unaffected by PCN treatment, but were reduced 21% after 19 weeks of PCB treatment compared to control. PCN treatment significantly reduced serum T4 through week 3 before returning to control concentrations, whereas T4 levels following PCB treatment fell below detection limits by week 3 and remained drastically reduced through week 19. TSH concentrations in PCN-treated rats increased three-fold at week 2, then declined to near control values at week 19. After one week of PCB treatment, TSH concentrations reached nearly twice that of controls, and were sustained until week 6. The incidence of thyroid follicular cell proliferative lesions, including cystic and follicular hyperplasia, cystic and follicular adenoma, and follicular carcinoma, was significantly increased following PCN treatment, but not following PCB treatment. PCB treatment caused an increase in thyroid carcinomas (4 of 22 rats) not associated with the proliferative-type lesions produced by PCN, despite an increase in TSH serum concentrations. In conclusion, PCN appears to promote thyroid tumors in a manner consistent with known effects of excessive TSH stimulation. However, thyroid carcinomas stemming from PCB

  12. Hyalinizing trabecular tumor of the thyroid: Diagnosed of a rare tumor using ultrasonography, cytology, and intraoperative frozen sections

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Hyun Sik; Kim, Eun Kyung; Kwak, Jin Young; Moon, Hee Jung; Yoon, Jung Hyun [Dept. of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul (Korea, Republic of); Park, Cheol Keun; Son, Eun Ju [Gangnam Severance Hospital, Yonsei University, College of Medicine, Seoul (Korea, Republic of)

    2016-03-15

    The goal of this study was to evaluate the clinicopathological and imaging features of thyroid nodules surgically diagnosed as hyaline trabecular tumor (HTT), and to assess the role of cytology and frozen sections (FS) in the diagnosis of HTT. This study included 21 thyroid nodules in 21 patients treated from August 2005 to March 2015 (mean age, 53.3 years) who were either diagnosed as HTT or had HTT suggested as a possible diagnosis based on cytology, FS, or the final pathology report. Patients' medical records were retrospectively reviewed for cytopathologic results and outcomes during the course of follow-up. Sonograms were reviewed and categorized. Twelve nodules from 12 patients were surgically confirmed as HTT. Ultrasonography (US)-guided fine needle aspiration (FNA) was performed on 11 nodules, of which six (54.5%) were papillary thyroid carcinoma (PTC) or suspicious for PTC and three (27.3%) were HTT or suspicious for HTT. Intraoperative FS suggested the possibility of HTT in seven nodules, of which four (57.1%) were confirmed as HTT. US-FNA suggested the diagnosis of HTT in 10 nodules, of which three (30.0%) were confirmed as HTT. Common US features of the 12 pathologically confirmed cases of HTT were hypoechogenicity or marked hypoechogenicity (83.4%), absence of calcifications (91.7%), parallel shape (100.0%), presence of vascularity (75.0%), and probable benignity (58.3%). HTT should be included in the differential diagnosis of solid tumors with hypoechogenicity or marked hypoechogenicity and otherwise benign US features that have been diagnosed as PTC through cytology.

  13. [The role of urgent intraoperative morphological investigation in differential diagnostics of pretumor lesions and tumors of the thyroid].

    Science.gov (United States)

    Bondarenko, V O; Depiui, T I; Magomedov, R B; Shapiro, N A

    2010-01-01

    Results of examination and treatment of 3794 patients with nodular formations of the thyroid gland were analyzed. All the operations were followed by cytological investigation of the intraoperation scrape whose results determined the indications to urgent histological investigation. It was shown that the data of intraoperative cytological and histological diagnostics were comparable, the cytological diagnosis of atypical adenoma being an indication to urgent histological investigation. Urgent cytological investigations make the detection of thyroid cancer 2 times higher and risk of reoperations 10 times less at this nozology. The data obtained demonstrate effectiveness of the intraoperative cytological investigation in the present-day diagnostics of pretumor diseases and tumors of the thyroid gland.

  14. BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

    Directory of Open Access Journals (Sweden)

    Cohn AL

    2017-02-01

    Full Text Available Allen L Cohn,1 Bann-Mo Day,2 Sarang Abhyankar,3 Edward McKenna,2 Todd Riehl,4 Igor Puzanov5 1Medical Research, Rocky Mountain Cancer Centers, Denver, CO, 2US Medical Affairs, 3Global Safety and Risk Management, 4Product Development Oncology, Genentech, Inc., South San Francisco, CA, 5Melanoma Section, Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Background: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer or multiple myeloma harboring activating BRAFV600 mutations for enrollment in a vemurafenib clinical study.Methods: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAFV600 mutations by bidirectional direct Sanger sequencing.Results: Overall incidence of BRAFV600E mutation in evaluable patients (n=548 was 3% (95% confidence interval [CI], 1.7–4.7: 11% in colorectal tumors (n=75, 6% in biliary tract tumors (n=16, 3% in non-small cell lung cancers (n=71, 2% in other types of solid tumors (n=180, and 3% in multiple myeloma (n=31. There were no BRAFV600 mutations in this cohort of patients with ovarian tumors (n=68, breast cancer (n=86, or prostate cancer (n=21.Conclusion: This multicenter, national screening study confirms previously reported incidences of BRAFV600 mutations from single-center studies. Patients identified with BRAFV600 mutations were potentially eligible for enrollment in the VE-BASKET study. Keywords: genetic testing, proto-oncogene proteins B-raf, PLX4032

  15. A mutation screening of oncogenes, tumor suppressor gene TP53 and nuclear encoded mitochondrial complex I genes in oncocytic thyroid tumors.

    Science.gov (United States)

    Evangelisti, Cecilia; de Biase, Dario; Kurelac, Ivana; Ceccarelli, Claudio; Prokisch, Holger; Meitinger, Thomas; Caria, Paola; Vanni, Roberta; Romeo, Giovanni; Tallini, Giovanni; Gasparre, Giuseppe; Bonora, Elena

    2015-03-21

    Thyroid neoplasias with oncocytic features represent a specific phenotype in non-medullary thyroid cancer, reflecting the unique biological phenomenon of mitochondrial hyperplasia in the cytoplasm. Oncocytic thyroid cells are characterized by a prominent eosinophilia (or oxyphilia) caused by mitochondrial abundance. Although disruptive mutations in the mitochondrial DNA (mtDNA) are the most significant hallmark of such tumors, oncocytomas may be envisioned as heterogeneous neoplasms, characterized by multiple nuclear and mitochondrial gene lesions. We investigated the nuclear mutational profile of oncocytic tumors to pinpoint the mutations that may trigger the early oncogenic hit. Total DNA was extracted from paraffin-embedded tissues from 45 biopsies of oncocytic tumors. High-resolution melting was used for mutation screening of mitochondrial complex I subunits genes. Specific nuclear rearrangements were investigated by RT-PCR (RET/PTC) or on isolated nuclei by interphase FISH (PAX8/PPARγ). Recurrent point mutations were analyzed by direct sequencing. In our oncocytic tumor samples, we identified rare TP53 mutations. The series of analyzed cases did not include poorly- or undifferentiated thyroid carcinomas, and none of the TP53 mutated cases had significant mitotic activity or high-grade features. Thus, the presence of disruptive TP53 mutations was completely unexpected. In addition, novel mutations in nuclear-encoded complex I genes were identified. These findings suggest that nuclear genetic lesions altering the bioenergetics competence of thyroid cells may give rise to an aberrant mitochondria-centered compensatory mechanism and ultimately to the oncocytic phenotype.

  16. [Thyroid carcinomas: the present view on diagnostics and therapy].

    Science.gov (United States)

    Vlček, Petr; Nováková, Dana; Katra, Rami

    Thyroid carcinoma (TC) represents 1-2 % of all human tumors, and is the seventh most common tumor. Women are in large majority among new patients. For women, this is the fifth most common tumor. In the Czech Republic, 1 143 new cases of TC were diagnosed in 2015. It is the tumor with the highest increase in incidence. Among newly diagnosed tumors, most of those are differentiated thyroid gland carcinomas (DTCs) originating from follicular thyroid cells. These tumors are follicular and papillary carcinomas and Hurthle carcinoma, accounting for 95 % of new cases. Due to the great progress in treatment, the prognosis is most commonly good for these tumors. Treatment is more difficult for other types of tumors. Anaplastic thyroid cancer (representing less than 1 % of thyroid tumors) is a rare form of thyroid cancer that is very malignant. Also found in the thyroid gland is Euro-C-cell tumor, which originates in C cells. This is the so-called medullary thyroid carcinoma, which is less common (5 % of all thyroid carcinomas). It emerges from the parapolyclic neuroendocrine cells of the thyroid gland. This tumor often metastasizes to the cervical lymph nodes, and frequently occurs in distant bone, liver and lung metastases. In 2015, in this publication we published an article: Thyroid gland carcinomas, current therapeutic procedures. This article was devoted to the diagnosis of thyroid carcinoma and individual treatment procedures. In this article, we look at differentiated thyroid carcinomas (DTCs), especially current opinions on the treatment of low-risk carcinomas.Key words: differentiated thyroid cancer - radioidine - targeted therapy.

  17. Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas.

    Science.gov (United States)

    Mincione, Gabriella; Tarantelli, Chiara; Vianale, Giovina; Di Marcantonio, Maria Carmela; Cotellese, Roberto; Francomano, Franco; Di Nicola, Marta; Costantini, Erica; Cichella, Annadomenica; Muraro, Raffaella

    2014-09-10

    The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Mincione, Gabriella, E-mail: g.mincione@unich.it [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy); Tarantelli, Chiara [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Vianale, Giovina [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy); Di Marcantonio, Maria Carmela [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Cotellese, Roberto [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Francomano, Franco [Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Di Nicola, Marta; Costantini, Erica [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Cichella, Annadomenica [Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Muraro, Raffaella [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy)

    2014-09-10

    The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. - Highlights: • We reinforce the hypothesis of a cross talk between EGF and TGF-β1 in follicular thyroid carcinoma. • Increased migration MAPK-dependent is observed after EGF+TGF-β1 treatment in follicular thyroid carcinoma cells. • EGF and TGF-β1 caused opposite effect on the migratory ability in B-CPAP and in FTC-133 cells. • TGF-β1, TβRII and EGFR are overexpressed in follicular thyroid carcinoma.

  19. Expression of Hyaluronan in human tumor progression

    Directory of Open Access Journals (Sweden)

    Boregowda Rajeev K

    2006-01-01

    Full Text Available Abstract Background The development and progression of human tumors is accompanied by various cellular, biochemical and genetic alterations. These events include tumor cells interaction with extracellular matrix molecules including hyaluronan (HA. Hyaluronan is a large polysaccharide associated with pericellular matrix of proliferating, migrating cells. Its implication in malignant transformation, tumor progression and with the degree of differentiation in various invasive tumors has well accepted. It has been well known the role HA receptors in tumor growth and metastasis in various cancer tissues. Previously we have observed the unified over expression of Hyaluronic Acid Binding Protein (HABP, H11B2C2 antigen by the tumor cells in various types progressing tumor tissues with different grades. However, the poor understanding of relation between HA and HA-binding protein expression on tumor cells during tumor progression as well as the asymmetric observations of the role of HA expression in tumor progression prompted us to examine the degree of HA expression on tumor cells vs. stroma in various types of human tumors with different grades. Methods In the present study clinically diagnosed tumor tissue samples of different grades were used to screen the histopathological expression of hyaluronan by using b-PG (biotinylated proteoglycan as a probe and we compared the relative HA expression on tumor cells vs. stroma in well differentiated and poorly differentiated tumors. Specificity of the reaction was confirmed either by pre-digesting the tissue sections with hyaluronidase enzyme or by staining the sections with pre-absorbed complex of the probe and HA-oligomers. Results We show here the down regulation of HA expression in tumor cells is associated with progression of tumor from well differentiated through poorly differentiated stage, despite the constant HA expression in the tumor associated stroma. Conclusion The present finding enlighten the

  20. [Application value of fine needle aspiration and cell block in preoperative diagnosis of thyroid cancer and discrimination of follicular tumor].

    Science.gov (United States)

    Fang, Qingquan; Cai, Chengfu; Chen, Hong

    2015-08-01

    To study the application value of fine needle aspiration and cell block combined with molecular markers in early diagnosis of thyroid cancer and discriminate follicular tumor before operation. Fine needle biopsy of thyroid nodules was guided by color ultrasound, then the sample acquired was used to make smear and the rest to make cell block. The pathological diagnosis on smear, cell block or combination of both was made respectively. Then, the Envision immunohistochemical method was employed to detect the expressions of CK19, Galectin-3 in cell block samples, which had been used for the diagnosis of papillary thyroid carcinoma or thyroid nodules from benign lesions after operation and to detect the expressions of DDIT3, ki-67 of cell block that had been used for the diagnosis of follicular tumor nodules. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of cytopathology for the diagnosis of malignancy were 95.3%, 94.7%, 92.7%, 96.6% and 95.0% respectively; and the sensitivity, specificity and accuracy of the diagnosis used cell block alone or combined with smear were 88.1%, 95.3%, 92.3% and 95.3%, 94.7%, 95.0% respectively, which were higher than 53.8%, 83.7%, 71.3% from smear correspondingly. The positive expression rate of CK19 and Galectin-3 of papillary thyroid carcinoma cell block were 100% and 98.0% respectively, higher than the value 17.7% and 23.3% of thyroid benign lesions (P block was 84.6%, higher than the value 35.1% of follicular adenoma (P block (P > 0.05). It was conducive to early diagnose thyroid cancer with detection of CK19, Galection-3 of cell block made by ultrasound-guided fine needle biopsy of thyroid nodules. And it was also significant for DDIT3 detection to early discriminate follicular neoplasm before operation.

  1. Retinol oxidation to retinoic acid in human thyroid glandular cells.

    Science.gov (United States)

    Taibi, Gennaro; Gueli, Maria Concetta; Nicotra, Concetta M A; Cocciadiferro, Letizia; Carruba, Giuseppe

    2014-12-01

    Abstract Retinoic acid is regarded as the retinol metabolite that controls proliferation and differentiation of epithelial cells. In the present study, we investigated the potential role of xanthine dehydrogenase (XDH) in retinoic acid biosynthesis in human thyroid glandular cells (HTGC). In particular, we observed that cellular retinoids binding proteins (CRBPs) are also implicated in the biosynthetic pathway leading to retinoic acid formation in primary cultures of HTGC, as we have already reported for human mammary epithelial cells (HMEC). After partial protein purification, the enzyme responsible for retinoic acid biosynthesis was identified and quantified as XDH by immunoassay, by its ability to oxidize xanthine to uric acid and its sensitivity to the inhibitory effect of oxypurinol. The evidence of XDH-driven formation of retinoic acid in HTGC cultures further corroborates the potential role of XDH in retinoic acid biosynthesis in the epithelia.

  2. Genetic alterations in thyroid tumors from patients irradiated in childhood for tinea capitis treatment.

    Science.gov (United States)

    Boaventura, Paula; Pereira, Dina; Celestino, Ricardo; Mendes, Adélia; Nakasawa, Tadao; Teixeira-Gomes, José; Sobrinho-Simões, Manuel; Soares, Paula

    2013-11-01

    Exposure to ionizing radiation at young age is the strongest risk factor for the occurrence of papillary thyroid carcinoma (PTC). RET/PTC rearrangements are the most frequent genetic alterations associated with radiation-induced PTC, whereas BRAF and RAS mutations and PAX8-PPARG rearrangement have been associated with sporadic PTC. We decided to search for such genetic alterations in PTCs of patients subjected in childhood to scalp irradiation. We studied 67 thyroid tumors from 49 individuals irradiated in childhood for tinea capitis scalp epilation: 36 malignant (12 cases of conventional PTC (cPTC), two cPTC metastases, 20 cases of follicular variant PTC (FVPTC), one oncocytic variant of PTC and one follicular carcinoma) and 31 follicular thyroid adenomas. The lesions were screened for the BRAF(V600E) and NRAS mutations and for RET/PTC and PAX8-PPARG rearrangements. BRAF(V600E) mutation was detected in seven of 14 (50%) cPTC and two of 20 FVPTC (10%) (P=0.019). NRAS mutation was present in one case of FVPTC (5%). RET/PTC1 rearrangement was found, by RT-PCR, in one of 17 cases (5.9%) and by fluorescence in situ hybridization in two of six cases (33%). PAX8-PPARG rearrangement was not detected in any carcinoma. None of the follicular adenomas presented any of the aforementioned genetic alterations. The prevalence of BRAF(V600E) mutation in our series is the highest reported in series of PTCs arising in radiation-exposed individuals. The prevalence of RET/PTC1 rearrangement fits with the values recently described in a similar setting.

  3. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  4. Human neutrophils facilitate tumor cell transendothelial migration.

    Science.gov (United States)

    Wu, Q D; Wang, J H; Condron, C; Bouchier-Hayes, D; Redmond, H P

    2001-04-01

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  5. Glutathione Levels in Human Tumors

    Science.gov (United States)

    Gamcsik, Michael P.; Kasibhatla, Mohit S.; Teeter, Stephanie D.; Colvin, O. Michael

    2013-01-01

    This review summarizes clinical studies in which glutathione was measured in tumor tissue from patients with brain, breast, gastrointestinal, gynecological, head and neck and lung cancer. Glutathione tends to be elevated in breast, ovarian, head and neck and lung cancer and lower in brain and liver tumors compared to disease-free tissue. Cervical, colorectal, gastric and esophageal cancers show both higher and lower levels of tumor glutathione. Some studies show an inverse relationship between patient survival and tumor glutathione. Based on this survey, we recommend approaches that may improve the clinical value of glutathione as a biomarker. PMID:22900535

  6. Association of Cigarette Smoking with Aberrant Methylation of the Tumor Suppressor Gene RARβ2 in Papillary Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Katja eKiseljak-Vassiliades

    2011-12-01

    Full Text Available Aberrant gene methylation is often seen in thyroid cancer, a common endocrine malignancy. Tobacco smoking has been shown to be associated with aberrant gene methylation in several cancers, but its relationship with gene methylation in thyroid cancer has not been examined. In the present study, we investigated the relationship between smoking of patients and aberrant methylation of tumor suppressor genes for TIMP3, SLC5A8, death-associated protein kinase, and retinoic acid receptor β2 (RARβ2 in papillary thyroid cancer (PTC, the most common type of thyroid cancer. The promoter methylation status of these genes was analyzed using quantitative real-time methylation-specific PCR on bisulfite-treated genomic DNA isolated from tumor tissues and correlated with smoking history of the patients. Among the four genes, methylation of the RARβ2 gene was significantly associated with smoking and other three genes showed a trend of association. Specifically, among the 138 patients investigated, 13/42 (31.0% ever smokers vs. 10/96 (10.4% never smokers harbored methylation of the RARβ2 gene (P = 0.003. This association was highly significant also in the subset of conventional variant PTC (P = 0.005 and marginally significant in follicular variant PTC (p = 0.06. The results demonstrate that smoking-associated aberrant methylation of the RARβ2 gene is a specific molecular event that may represent an important mechanism in thyroid tumorigenesis in smokers.

  7. Cell Surface and Secreted Protein Profiles of Human Thyroid Cancer Cell Lines Reveal Distinct Glycoprotein Patterns

    Science.gov (United States)

    Arcinas, Arthur; Yen, Ten-Yang; Kebebew, Electron; Macher, Bruce A.

    2009-01-01

    Cell surface proteins have been shown to be effective therapeutic targets. In addition, shed forms of these proteins and secreted proteins can serve as biomarkers for diseases, including cancer. Thus, identification of cell surface and secreted proteins has been a prime area of interest in the proteomics field. Most cell surface and secreted proteins are known to be glycosylated and therefore, a proteomics strategy targeting these proteins was applied to obtain proteomic profiles from various thyroid cancer cell lines that represent the range of thyroid cancers of follicular cell origin. In this study, we oxidized the carbohydrates of secreted proteins and those on the cell surface with periodate and isolated them via covalent coupling to hydrazide resin. The glycoproteins obtained were identified from tryptic peptides and N-linked glycopeptides released from the hydrazide resin using 2-dimensional liquid chromatography-tandem mass spectrometry in combination with the gas phase fractionation. Thyroid cancer cell lines derived from papillary thyroid cancer (TPC-1), follicular thyroid cancer (FTC-133), Hürthle cell carcinoma (XTC-1), and anaplastic thyroid cancer (ARO and DRO-1) were evaluated. An average of 150 glycoproteins were identified per cell line, of which more than 57 percent are known cell surface or secreted glycoproteins. The usefulness of the approach for identifying thyroid cancer associated biomarkers was validated by the identification of glycoproteins (e.g. CD44, galectin 3 and metalloproteinase inhibitor 1) that have been found to be useful markers for thyroid cancer. In addition to glycoproteins that are commonly expressed by all of the cell lines, we identified others that are only expressed in the more well-differentiated thyroid cancer cell lines (follicular, Hürthle cell and papillary), or by cell lines derived from undifferentiated tumors that are uniformly fatal forms of thyroid cancer (i.e. anaplastic). Based on the results obtained, a

  8. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

    Science.gov (United States)

    Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

    2017-03-01

    Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

  9. Familial occurrence of subacute thyroiditis associated with human leukocyte antigen-B35

    NARCIS (Netherlands)

    Kramer, AB; Roozendaal, C; Dullaart, RPF

    Subacute thyroiditis (SAT) is a spontaneously remitting inflammatory disorder of the thyroid, associated with human leukocyte antigen (HLA)-B35, and may be virally induced in genetically predisposed individuals. A 57-year-old Caucasian man presented with symptoms of hyperthyroidism as well as

  10. Examining recombinant human TSH primed {sup 131}I therapy protocol in patients with metastatic differentiated thyroid carcinoma: comparison with the traditional thyroid hormone withdrawal protocol

    Energy Technology Data Exchange (ETDEWEB)

    Rani, Deepa; Kaisar, Sushma; Awasare, Sushma; Kamaldeep; Abhyankar, Amit; Basu, Sandip [Bhabha Atomic Research Centre (BARC), Radiation Medicine Centre, Mumbai (India)

    2014-09-15

    Recombinant human thyroid-stimulating hormone (rhTSH)-based protocol is a promising recent development in the management of differentiated thyroid carcinoma (DTC). The objectives of this prospective study were: (1) to assess the feasibility and efficacy of the rhTSH primed {sup 131}I therapy protocol in patients with DTC with distant metastatic disease, (2) to perform lesional dosimetry in this group of patients compared to the traditional protocol, (3) to document the practical advantages (patient symptoms and hospital stay) of the rhTSH protocol compared to the traditional thyroid hormone withdrawal protocol, (4) to document and record any adverse effect of this strategy, (5) to compare the renal function parameters, and (6) to compare the serum TSH values achieved in either of the protocols in this group of patients. The study included 37 patients with metastatic DTC having lung or skeletal metastases or both. A comparison of lesional radiation absorbed dose, hospital stay, renal function tests, and symptom profile was undertaken between the traditional thyroid hormone withdrawal protocol and rhTSH-based therapy protocol. Dosimetric calculations of metastatic lesions were performed using lesion uptake and survey meter readings for calculation of effective half-life. Non-contrast-enhanced CT was used for assessment of tumor volume. Quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL forms. A comparison of pretreatment withdrawal thyroglobulin (TG) was done with the withdrawal TG level 3 months after treatment. The mean effective half-life of {sup 131}I in metastatic lesions was less during the rhTSH protocol (29.49 h) compared to the thyroid hormone withdrawal protocol (35.48 h), but the difference was not statistically significant (p = 0.056). The mean 24-h % uptake of the lesions during the traditional protocol (4.84 %) was slightly higher than the 24-h % uptake during the rhTSH protocol (3.56 %), but

  11. Neoplastic transformation of human thyroid epithelial cells by ionizing radiation

    Science.gov (United States)

    Herceg, Zdenko

    Neoplastic transformation of human thyroid epithelial cells has been investigated following exposure to ionizing radiation in vitro. The effects of radiation type, irradiation regime, and postirradiation passaging were examined using a human thyroid epithelial cell line, designated HToriS, which was previously immortalized with SV40 genome. Exponentially growing HToriS cells were irradiated with graded doses of 137 Cs gamma- and 238pu alpha-irradiation. Cells were irradiated with either a single or multiple doses of 0.5, 1, 2, 3, or 4 Gy gamma-radiation, or single doses of 0.125, 0.25, 0.5, 1, or 1.5 Gy gamma-radiation. Following passaging, the cells were transplanted into the athymic nude mice, and the animals were screened for tumour formation. Statistically significant increases in tumour incidence were obtained with both gamma- and alpha-irradiation and with both single and multiple irradiation regimes as compared with the un-irradiated group. Regardless of radiation type and or radiation regime there appears to be a trend, with increasing doses of radiation, in which tumour incidence increases and reaches a maximum, after which the tumour incidence decreases. Tumours were characterized by histopathological examination as undifferentiated carcinomas. Investigation of expression time following irradiation demonstrated that post-irradiation passaging, generally regarded as a critical step for expression of radiation-induced DNA damage, was not a prerequisite for the neoplastic conversion of irradiated cells with this system. Cell lines were established from the tumours and their identification and characterization carried out. All cell lines established were determined to be derived from the parent HTori3 cells by DNA fingerprinting, karyotype analysis, cytokeratin staining, and SV40 large T-antigen staining. Tumorigenicity of the cell lines was confirmed by retransplantation. Comparison of the morphology in vitro showed that the tumour cell lines retained the

  12. Stimulated thyroglobulin level at ablation in differentiated thyroid cancer: the impact of treatment preparation modalities and tumor burden.

    Science.gov (United States)

    Ciappuccini, Renaud; Hardouin, Juliette; Heutte, Natacha; Vaur, Dominique; Quak, Elske; Rame, Jean-Pierre; Blanchard, David; de Raucourt, Dominique; Bardet, Stéphane

    2014-08-01

    In patients with differentiated thyroid cancer (DTC), the stimulated serum thyroglobulin (Tg) level at radioiodine ablation is a known predictive factor of persistent disease. This prognostic value is based on data obtained after thyroid hormone withdrawal (THW), but little is known about this prognostic value after recombinant human TSH (rhTSH) stimulation and about the relationship between the stimulated Tg level and the burden of persistent tumor. We aimed to assess the impact of both radioiodine preparation modalities and persistent tumor burden on stimulated Tg levels. The stimulated Tg level was measured at radioablation in 308 consecutive DTC patients without serum Tg antibodies. Of these, 123 (40%) were prepared with rhTSH and 185 with THW. Post-ablation scintigraphy included total-body scan and neck and thorax single photon emission computed tomography with computed tomography (SPECT-CT). During a mean follow-up of 43 months, persistent/recurrent disease (PRD) was found in 56 patients (18%). PRD was considered structural in the presence of lesions >1 cm and nonstructural otherwise. Nonstructural PRD was more frequent in the rhTSH group than in the THW group (64 vs 26%, P=0.01). Stimulated Tg levels were lower after rhTSH than after THW in patients with (13.5 vs 99.5 ng/ml, P<0.01) and without (1.2 vs 3.2 ng/ml, P<0.001) PRD. Also, Tg levels were lower in nonstructural disease than in structural disease in both rhTSH (3.8 vs 127.0 ng/ml, P<0.01) and THW (13.0 vs 143.5 ng/ml, P<0.0001) patients. The best Tg cutoff to predict PRD was 2.8 in rhTSH and 28 ng/ml in THW patients. Both radioiodine preparation modalities and the burden of persistent tumor affect the stimulated Tg level at ablation. © 2014 European Society of Endocrinology.

  13. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers.

    Science.gov (United States)

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-06-01

    A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers

  14. The ING tumor suppressor genes: status in human tumors.

    Science.gov (United States)

    Guérillon, Claire; Bigot, Nicolas; Pedeux, Rémy

    2014-04-01

    ING genes (ING1-5) were identified has tumor suppressor genes. ING proteins are characterized as Type II TSGs since they are involved in the control of cell proliferation, apoptosis and senescence. They may also function as Type I TSGs since they are also involved in DNA replication and repair. Most studies have reported that they are frequently lost in human tumors and epigenetic mechanisms or misregulation of their transcription may be involved. Recently, studies have described that this loss may be caused by microRNA inhibition. Here, we summarize the current knowledge on ING functions, their involvement in tumor suppression and, in order to give a full assessment of the current knowledge, we review all the studies that have examined ING status in human cancers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. miR-199a-3p displays tumor suppressor functions in papillary thyroid carcinoma

    National Research Council Canada - National Science Library

    Minna, Emanuela; Romeo, Paola; De Cecco, Loris; Dugo, Matteo; Cassinelli, Giuliana; Pilotti, Silvana; Degl'Innocenti, Debora; Lanzi, Cinzia; Casalini, Patrizia; Pierotti, Marco A; Greco, Angela; Borrello, Maria Grazia

    2014-01-01

    Thyroid cancer incidence is rapidly increasing. Papillary Thyroid Carcinoma (PTC), the most frequent hystotype, usually displays good prognosis, but no effective therapeutic options are available for the fraction of progressive PTC patients...

  16. EWSR1 rearrangement is a frequent event in papillary thyroid carcinoma and in carcinoma of the thyroid with Ewing family tumor elements (CEFTE).

    Science.gov (United States)

    Oliveira, G; Polónia, A; Cameselle-Teijeiro, J M; Leitão, D; Sapia, S; Sobrinho-Simões, M; Eloy, C

    2017-05-01

    Carcinomas of the thyroid with Ewing family tumor element (CEFTEs) are small-cell thyroid tumors with epithelial differentiation that disclose p63 expression and EWSR1-FLI1 rearrangement, carry a favorable prognosis and may co-exist with papillary thyroid carcinoma (PTC) foci. Two histogenetic hypotheses have been advanced regarding the origin of CEFTEs: arising in PTCs or in solid cell nests (SCN). A total of 3 CEFTEs, 54 PTCs, and 10 SCNs were reviewed, and fluorescence in situ hybridization (FISH) technique was performed in all cases to search for the presence of EWSR1 rearrangements. The three CEFTEs disclosed the EWSR1-FLI1 rearrangement both in the small cell and in the PTC component. Out of the 54 PTC cases, 28 (51.9%) were positive, 20 (37.0%) were negative, and 6 (11.1%) were inconclusive for EWSR1 rearrangement; in two of the positive PTC cases, the EWSR1-FLI1 rearrangement was detected. Classic PTC disclosed more often the EWSR1 rearrangement than other PTC variants (p = 0.031). PTCs with EWSR1 rearrangement disclosed a lower percentage of nuclei with EWSR1 polysomy than those without EWSR1 rearrangement (p = 0.001). Out of the 10 SCNs, 7 (70.0%) were negative and 3 (30.0%) were inconclusive for the EWSR1 rearrangement. Monosomic nuclei were more frequent (mean of 44.3%) in SCNs than in PTCs (p < 0.001). The presence of the EWSR1-FLI1 rearrangement in PTC component of all studied CEFTEs and the existence of the EWSR1 rearrangement in some PTCs favor the origin of CEFTE from PTC. The high frequency of EWSR1 rearrangements in PTC may represent a new diagnostic marker of these tumors.

  17. Perfluoroalkyl substances exposure and thyroid hormones in humans: epidemiological observations and implications

    Directory of Open Access Journals (Sweden)

    Jung Eun Lee

    2017-03-01

    Full Text Available Thyroid hormones play crucial roles in normal neurodevelopment of fetus and child. Many chemicals can affect control and homeostasis of thyroid hormones, and eventually lead to various adverse health effects including neurodevelopmental disorders. Perfluoroalkyl substances (PFASs are among the thyroid disrupting chemicals that can be encountered among general human population. Due to their unique physicochemical characteristics, PFASs have been used as surfactants and surface coating materials in many applications. Therefore, PFASs have been frequently detected in humans and environment worldwide. In cross-sectional studies using nationally representative general human populations of United States, several PFASs have shown significant associations with thyroid hormones. Moreover, among pregnant women and their infants, not only major PFASs such as perfluorooctane sulfonic acid and perfluorooctanoic acid, but also those with shorter or longer carbon chains showed significant associations with thyroid hormones. Often demographic characteristics such as sex, age, and disease status appear to influence the associations between PFASs exposure and thyroid hormones. In general, major PFASs showed hypothyroidism effects among pregnant women and infants. As 8 carbon based PFASs have been phased out, those with shorter or longer carbon chains have been used in growing amount as replacement. However, only limited information is available for their occurrences and toxicity among humans. Further investigations on these substituting PFASs are required. In addition, efforts are warranted to identify sources of and mitigate exposure to these thyroid disrupting chemicals especially during pregnancy and early stages of life.

  18. Crosstalk between integrin αvβ3 and estrogen receptor-α is involved in thyroid hormone-induced proliferation in human lung carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Ran Meng

    Full Text Available A cell surface receptor for thyroid hormone that activates extracellular regulated kinase (ERK 1/2 has been identified on integrin αvβ3. We have examined the actions of thyroid hormone initiated at the integrin on human NCI-H522 non-small cell lung carcinoma and NCI-H510A small cell lung cancer cells. At a physiologic total hormone concentration (10(-7 M, T(4 significantly increased proliferating cell nuclear antigen (PCNA abundance in these cell lines, as did 3, 5, 3'-triiodo-L-thyronine (T(3 at a supraphysiologic concentration. Neutralizing antibody to integrin αvβ3 and an integrin-binding Arg-Gly-Asp (RGD peptide blocked thyroid hormone-induced PCNA expression. Tetraiodothyroacetic acid (tetrac lacks thyroid hormone function but inhibits binding of T(4 and T(3 to the integrin receptor; tetrac eliminated thyroid hormone-induced lung cancer cell proliferation and ERK1/2 activation. In these estrogen receptor-α (ERα-positive lung cancer cells, thyroid hormone (T(4>T(3 caused phosphorylation of ERα; the specific ERα antagonist ICI 182,780 blocked T(4-induced, but not T(3-induced ERK1/2 activation, as well as ERα phosphorylation, proliferating-cell nuclear antigen (PCNA expression and hormone-dependent thymidine uptake by tumor cells. Thus, in ERα-positive human lung cancer cells, the proliferative action of thyroid hormone initiated at the plasma membrane is at least in part mediated by ERα. In summary, thyroid hormone may be one of several endogenous factors capable of supporting proliferation of lung cancer cells. Activity as an inhibitor of lung cancer cell proliferation induced at the integrin receptor makes tetrac a novel anti-proliferative agent.

  19. [High-definition real-time ultrasonic echography of tumors of the thyroid gland. Apropos of 379 surgically treated cases].

    Science.gov (United States)

    Bruneton, J N; Caramella, E; Fenart, D; Ettore, F; Manzino, J J; Demard, F; Vallicioni, J

    1985-01-01

    The authors present the results of a review of 379 cases of benign and malignant thyroid tumors examined by high frequency (7 MHz) ultrasound prior to surgery. Features of the 37 cases of cancer are described. Hyperechogenicity was almost always correlated with benign lesions (only 1 cancer out of 71 hyperechoic nodules). For 313 of the 342 cases of benign tumors a good correlation was found between sonograms and intraoperative examination of the two thyroid lobes. In the case of clinically evident polyadenomatous goiters, ultrasound is a highly accurate means of determining whether any zones of healthy tissue remain (sensitivity 104/110 cases, i. e. 93.7%). When a contralateral lobe is normal on sonograms, intraoperative examination only rarely reveals lesions (12/159 cases, including 2 false positives for surgical investigation). Due to the excellent concordance between ultrasound and intraoperative exploration, and the difficulties involved in anterior dissection, the results of sonograms can be used to decide on the surgical approach. Direct intraoperative surgical exploration of the lobe opposite a thyroid lesion appears unnecessary if the sonogram is normal (cases of non suspected occult thyroid cancer). Since intraoperative exploration can give false negatives, intraoperative ultrasound can be used in the rare cases where 1 or 2 deep micronodules have been detected by pre-surgery sonograms in the lobe contralateral to the main lesion.

  20. Thyroid Dysfunction Associated With Follicular Cell Steatosis in Obese Male Mice and Humans

    Science.gov (United States)

    Lee, Min Hee; Lee, Jung Uee; Joung, Kyong Hye; Kim, Yong Kyung; Ryu, Min Jeong; Lee, Seong Eun; Kim, Soung Jung; Chung, Hyo Kyun; Choi, Min Jeong; Chang, Joon Young; Lee, Sang-Hee; Kweon, Gi Ryang; Kim, Hyun Jin; Kim, Koon Soon; Kim, Seong-Min; Jo, Young Suk; Park, Jeongwon; Cheng, Sheue-Yann

    2015-01-01

    Adult thyroid dysfunction is a common endocrine disorder associated with an increased risk of cardiovascular disease and mortality. A recent epidemiologic study revealed a link between obesity and increased prevalence of hypothyroidism. It is conceivable that excessive adiposity in obesity might lead to expansion of the interfollicular adipose (IFA) depot or steatosis in thyroid follicular cells (thyroid steatosis, TS). In this study, we investigated the morphological and functional changes in thyroid glands of obese humans and animal models, diet-induced obese (DIO), ob/ob, and db/db mice. Expanded IFA depot and TS were observed in obese patients. Furthermore, DIO mice showed increased expression of lipogenesis-regulation genes, such as sterol regulatory element binding protein 1 (SREBP-1), peroxisome proliferator-activated receptor γ (PPARγ), acetyl coenzyme A carboxylase (ACC), and fatty acid synthetase (FASN) in the thyroid gland. Steatosis and ultrastructural changes, including distension of the endoplasmic reticulum (ER) and mitochondrial distortion in thyroid follicular cells, were uniformly observed in DIO mice and genetically obese mouse models, ob/ob and db/db mice. Obese mice displayed a variable degree of primary thyroid hypofunction, which was not corrected by PPARγ agonist administration. We propose that systemically increased adiposity is associated with characteristic IFA depots and TS and may cause or influence the development of primary thyroid failure. PMID:25555091

  1. Effect of excess iodine intake on thyroid on human health.

    Science.gov (United States)

    Koukkou, Eftychia G; Roupas, Nikolaos D; Markou, Kostas B

    2017-04-01

    The recommended daily intake of iodide, is 150 μg for adolescents and adults, 250 μg for pregnancy and lactation. Thyroid gland is an effective collector of iodine. The active iodine uptake along the basolateral membrane of thyroid cell is followed by its transport to the apical edge of the cell and then to the follicle lumen. TSH acts through cAMP and stimulates NIS gene expression and protein synthesis. The major proportion of iodine in the thyroid gland is bound to Thyroglobulin. The non-organic intrathyroidal iodine is usually low, but significantly greater compared to plasma. Large doses of iodine reduce both the uptake and the organification (Wolff-Chaikoff effect) and cause partial inhibition of Tg proteolysis. The thyroid gland has several protective mechanisms resulting on the maintenance of normal thyroid function despite wide fluctuations of the daily iodine intake. Ingestion of several commonly used drugs and food conservatives results in acute or chronic excessive iodine intake. Failure to escape from the iodine induced organification inhibition can cause hypothyroidism, which is temporary and subsides after iodine exposure ceases. Iodine excess may also establish a status of excessive thyroid hormone synthesis and release, thus inducing autonomic thyroid function in iodopenic areas or can contribute to the development of iodine-induced hyperthyroidism in iodine abundant areas. The anti-arrhythmic Amiodarone, is a benzofuranic product with a very high iodine content, is associated with either hypo- or hyperthyroidism development. In the presence of defective auto-protective mechanisms, excessive iodine ingestion can divert the normal thyroid function.

  2. Diffuse Optical Characterization of the Healthy Human Thyroid Tissue and Two Pathological Case Studies.

    Directory of Open Access Journals (Sweden)

    Claus Lindner

    Full Text Available The in vivo optical and hemodynamic properties of the healthy (n = 22 and pathological (n = 2 human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS and diffuse correlation spectroscopy (DCS system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (μa, μs' at three wavelengths (690, 785 and 830 nm to derive total hemoglobin concentration (THC and oxygen saturation (StO2. DCS measured the microvascular blood flow index (BFI. Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 μM to 144.8 μM, showing a 25-44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 × 10-9 cm2/s compared to the muscle (BFImuscle = 7.8 × 10-9 cm2/s, while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%, yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 μM and 62.8 × 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening.

  3. Comparison of radioiodine biokinetics following the administration of recombinant human thyroid stimulating hormone and after thyroid hormone withdrawal in thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Luster, Markus; Lassmann, Michael; Haenscheid, Heribert; Reiners, Christoph [Department of Nuclear Medicine, University of Wuerzburg, Josef-Schneider-Strasse 2, 97080, Wuerzburg (Germany); Sherman, Steven I. [Section of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, Houston, Texas (United States); Skarulis, Monica C. [Division of Intramural Research, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (United States); Reynolds, James R. [Department of Nuclear Medicine, Warren Grant Magnusen Clinical Center, NIH, Bethesda, Maryland (United States)

    2003-10-01

    Iodine kinetics were studied in patients with differentiated thyroid cancer while euthyroid under exogenous thyroid stimulating hormone (TSH) and while hypothyroid to detect differences in radioiodine uptake, distribution and elimination. Nine patients with total or near-total thyroidectomy on thyroid hormone suppressive therapy received two or three daily doses of 0.9 mg recombinant human TSH (rhTSH) followed by administration of a diagnostic activity of 2 mCi (74 MBq) iodine-131. After the biokinetics assessments had been performed, patients stopped taking thyroid hormones to become hypothyroid. A second 2 mCi (74 MBq) diagnostic activity of {sup 131}I was administered, followed by a second set of biokinetics assessments. One week later the patients underwent remnant ablation with a therapeutic activity of {sup 131}I. A comparison of the {sup 131}I kinetics in the patients while euthyroid and while hypothyroid showed major differences in the doses to the remnant as well as in residence times and radiation exposure to the blood. In the first diagnostic assessment the remnant dose was higher in eight of the nine patients and clearance of the activity from the blood was faster in all of them. The data from this study suggest that radioiodine administration is potent and safe when administered to euthyroid patients following rhTSH administration. Enhanced residence time in the remnant and decreased radiation exposure to the blood were noted when patients were euthyroid compared to when they were rendered hypothyroid. However, all patients received diagnostic activities in the same order: first while euthyroid, followed by hypothyroidism. It is quite possible that ''stunning'' from the radioiodine administered in the initial uptake study inhibited the subsequent uptake of radioiodine by the remnant lesions in the second uptake study. (orig.)

  4. Effects of fission neutrons on human thyroid tissues maintained in SCID mice.

    Science.gov (United States)

    Adachi, Shigeki; Ryo, Haruko; Hongyo, Tadashi; Nakajima, Hiroo; Tsuboi-Kikuya, Rie; Tokita, Yoriko; Matsuzuka, Fumio; Hiramatsu, Keizo; Fujikawa, Kazuo; Itoh, Tetsuo; Nomura, Taisei

    2010-02-01

    Morphology and function (secretion of thyroid hormone) of human thyroid tissues from Graves' disease patients are well maintained in C57BL/6J-scid mice. Serum level of thyroid hormone was reduced by fission neutrons from the nuclear reactor UTR-KINKI, and changes in thyroid hormone by fission neutrons were bigger than those by low LET radiations, X-rays and (137)Cs gamma-rays, suggesting high relative biological effectiveness (RBE; 6.5) of fission neutrons. Microarray analyses revealed that about 3% of genes showed more than 4-fold change in gene expression in the unexposed thyroid tissues against surgically resected thyroid tissues from the same patient, probably due to the difficult oxygen and nutrient supply shortly after transplantation. Dose-dependent changes in gene expression against unexposed concurrent controls were observed with increasing doses of fission neutrons (0.2-0.6Gy) and (137)Cs gamma-rays (1.0-3.0Gy) and showed high RBE (4.2). Furthermore, there were some specific genes which showed more than 4-fold change in gene expression in all the thyroid tissues exposed to higher doses of radiation, especially neutrons (0.4 and 0.6Gy), but none at lower doses (0.2Gy of neutrons and 1.0 and 2.0Gy of gamma-rays). These genes related to degeneration, regeneration, apoptosis, and transcription, respond specifically and very sensitively to neutron injury in human thyroid tissues. This is the first experimental report that fission neutrons can induce some morphological and functional disorders in human tissues, showing high RBE against gamma-ray exposure. These results are useful to evaluate the risks of fission neutrons and cosmic rays to humans. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Thyroid cancer and multiple primary tumors in the SEER cancer registries

    NARCIS (Netherlands)

    Ronckers, Cécile M.; McCarron, Peter; Ron, Elaine

    2005-01-01

    Thyroid cancer incidence rates have increased steadily in the United States and elsewhere. Radiation exposure at a young age is a strong risk factor, but otherwise the etiology is unclear. To explore etiologic clues, we studied the risk of thyroid cancer after an earlier primary cancer, as well as

  6. Surgeon-performed intraoperative tumor localization in recurrent papillary thyroid carcinoma by ultrasound-guided intratumoral indigo carmine injection.

    Science.gov (United States)

    Ahn, Dongbin; Sohn, Jin Ho; Kim, Heejin

    2014-08-01

    Identification and removal of small, non-palpable tumors located within previous surgical scar tissue is challenging and time consuming and may be associated with increased risk in patients with recurrent papillary thyroid carcinoma (PTC). The purpose of the present study was to present our surgeon-performed technique and to evaluate the usefulness of ultrasound-guided intratumoral indigo carmine injection (US-III) for intraoperative tumor localization in patients with recurrent PTC. Sixteen patients with recurrent PTC in which tumors were indigo carmine was 0.56 mL (range 0.3-1.0 mL); this injection expanded the tumors by a mean of 0.2 cm (23.5% increase compared with the initial tumor size; range 0.0-0.4 cm), increasing the mean size of the target tumors to 1.05 cm (range 0.5-1.5 cm). In 15 (93.8%) of the 16 patients, the recurrent tumors were successfully removed with the aid of US-III. No complications occurred in any of the patients as a result of the US-III or subsequent surgeries. US-III is a safe and effective technique that can be performed by the surgeon for the intraoperative localization of small non-palpable tumors within previous scar tissue in patients with recurrent PTC.

  7. Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors

    DEFF Research Database (Denmark)

    Bisarro Dos Reis, Mariana; Barros-Filho, Mateus Camargo; Marchi, Fábio Albuquerque

    2017-01-01

    . Objective: To identify a prognostic epigenetic signature in thyroid cancer. Design: Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2......Context: Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis...... Hürthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database. Results: A specific epigenetic profile was detected according to each histological...

  8. Thyroid Hormone Deiodinases and Cancer

    Directory of Open Access Journals (Sweden)

    Antonio eBianco

    2012-06-01

    Full Text Available Deiodinases constitute a group of thioredoxin-containing selenoenzymes that play an important function in thyroid hormone homeostasis and control of thyroid hormone action. There are three known deiodinases: D1 and D2 activate the pro-hormone thyroxine (T4 to T3, the most active form of thyroid hormone, while D3 inactivates thyroid hormone and terminates T3 action. A number of studies indicate that deiodinase expression is altered in several types of cancers, suggesting that (i they may represent a useful cancer marker and/or (ii could play a role in modulating cell proliferation - in different settings thyroid hormone modulates cell proliferation. For example, although D2 is minimally expressed in human and rodent skeletal muscle, its expression level in rhabdomyosarcoma (RMS-13 cells is 3-4 fold higher. In basal cell carcinoma (BCC cells, sonic hedgehog (Shh-induced cell proliferation is accompanied by induction of D3 and inactivation of D2. Interestingly a 5-fold reduction in the growth of BCC in nude mice was observed if D3 expression was knocked down. A decrease in D1 activity has been described in renal clear cell carcinoma, primary liver cancer, lung cancer, and some pituitary tumors, while in breast cancer cells and tissue there is an increase in D1 activity. Furthermore D1 mRNA and activity were found to be decreased in papillary thyroid cancer while D1 and D2 activities were significantly higher in follicular thyroid cancer tissue, in follicular adenoma and in anaplastic thyroid cancer. It is conceivable that understanding how deiodinase dysregulation in tumor cells affect thyroid hormone signaling and possibly interfere with tumor progression could lead to new antineoplastic approaches.

  9. Molecular signature of the radioinduction in the thyroid tumors developed after radiotherapy; Signature moleculaire de la radio-induction dans des tumeurs de la thyroide developpees apres radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Mallard, Ch.

    2005-10-15

    Several epidemiological studies enlightens an increase of the number of thyroid cancers among children and adolescents exposed to ionizing radiation after an internal exposure ( Chernobylsk accident) or external one as a radiotherapy. No increase arose for adults.The analysis of the transcriptome was realised with micro arrays prepared on the genomic platform of the Cea at Evry that allow to study simultaneously the expression of 6000 genes. this study allows to enlighten a signature of radioinduction constituted by series of genes specifically expressed in one or other type of cancer in function of its etiology. This signature includes 59 genes expressed differentially between the sporadic carcinomas and 45 genes in the case of adenomas. with this signature an analysis in principal components allowed to determine correctly the etiology of 12 tumors among 13, the etiology of a sporadic adenoma was not determined. Besides, the study of the expression of genes specific to thyroid (TSHR, TG, TPO, TTF1, TTF2, PAX8) in relation with the presence of arrangements RET/PTC or mutations of BRAF was made. It allowed to enlighten the loss of TPO expression in the cancers changed for BRAF as well as a new mechanism of BRAF activation. (N.C.)

  10. Epigenetics modifications and therapeutic prospects in human thyroid cancer

    Directory of Open Access Journals (Sweden)

    Maria Graziella eCatalano

    2012-03-01

    Full Text Available At present no successful treatment is available for advanced thyroid cancer, which comprises poorly differentiated, anaplastic, and metastatic or recurrent differentiated thyroid cancer not responding to radioiodine. In the last few years, biologically targeted therapies for advanced thyroid carcinomas have been proposed on the basis of the recognition of key oncogenic mutations. Although the results of several phase II trials look promising, none of the patients treated had a complete response, and only a minority of them had a partial response, suggesting that the treatment is, at best, effective in stabilizing patients with progressive disease. Epigenetic refers to the study of heritable changes in gene expression that occur without any alteration in the primary DNA sequence. The epigenetic processes establish and maintain the global and local chroma¬tin states that determine gene expression. Epigenetic abnormalities are present in almost all cancers and, together with genetic changes, drive tumour progression. Various genes involved in the control of cell proliferation and invasion (p16INK4A, RASSF1A,PTEN, Rap1GAP, TIMP3, DAPK, RARβ2, E-cadherin, and CITED1 as well as genes specific of thyroid differentiation (Na+/I- symport, TSH receptor, pendrin, SL5A8, and TTF-1 present aberrant methylation in thyroid cancer.This review deals with the most frequent epigenetic alterations in thyroid cancer and focuses on epigenetic therapy, whose goal is to target the chromatin in rapidly dividing tumour cells and potentially restore normal cell functions. Experimental data and clinical trials, especially using deacetylase inhibitors and demethylating agents, are discussed.

  11. Comparison of therapeutic efficacy and clinical parameters between recombinant human thyroid stimulating hormone and thyroid hormone withdrawal in high-dose radioiodine treatment with differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Se Hun; Na, Chang Ju; Kim, Jeong Hun; Han, Yeon Hee; KIm, Hee Kwon; Jeong, Hwan Jeong; Sohn, Myung Hee; Lim, Seok Tae [Dept. of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2015-06-15

    High-dose radioiodine treatment (HD-RIT) after injection of recombinant human thyroid stimulating hormone (rh-TSH) has become widely used. This study compared the therapeutic efficacy of HD-RIT and clinical parameters between rh-TSH supplement and thyroid hormone withdrawal (THW) after total thyroidectomy in patients with differentiated thyroid cancer. We retrospectively reviewed 266 patients (47 male and 219 female; age, 49.0 ± 10.9 years) with differentiated thyroid cancer detected from September 2011 to September 2012. Patients comprised THW (217, 81.6 %) and rh-TSH (49, 18.4 %). Inclusion criteria were: first HD-RIT; any TN stage; absence of distant metastasis. To evaluate the complete ablation of the remnant thyroid tissue or metastasis, we reviewed stimulated serum thyroglobulin (sTg), I-123 whole-body scan (RxWBS) on T4 off-state, and thyroid ultrasonography (US) or [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) 6–8 months after HD-RIT. We defined a complete ablation state when all three of the follow-up conditions were satisfied; <2.0 ng/ml of the sTg, I-123 RxWBS (−), and thyroid US or F-18 FDG PET/CT (−). If one of the three was positive, ablation was considered incomplete. We also compared various clinical biomarkers (body weight, body mass index, liver and kidney function) between THW and rh-TSH groups. The rates of complete ablation were 73.7 % (160/217) for the THW group and 73.5 % (36/49) for the rh-TSH group. There was no significant difference between the two groups (p = 0.970). The follow-up aspartate transaminase (p = 0.001) and alanine transaminase (p = 0.001) were significantly higher in the THW group. The renal function parameters of blood urea nitrogen (p = 0.001) and creatinine (p = 0.005) tended to increase in the THW group. The change of body weight was + Δ0.96 (±1.9) kg for the THW group and was decreased by -Δ1.39 (±1.5) kg for the rh-TSH group. The change

  12. Thyroid Diseases

    Science.gov (United States)

    ... gland does not make enough thyroid hormones Thyroid cancer Thyroid nodules - lumps in the thyroid gland Thyroiditis - swelling of the thyroid To diagnose thyroid diseases, doctors use a medical history, physical exam, and thyroid tests. They sometimes also ...

  13. Practical Performance of the 2015 American Thyroid Association Guidelines for Predicting Tumor Recurrence in Patients with Papillary Thyroid Cancer in South Korea.

    Science.gov (United States)

    Lee, Seul Gi; Lee, Woo Kyung; Lee, Hye Sun; Moon, Jieun; Lee, Cho Rok; Kang, Sang Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Chung, Woong Youn; Jo, Young Suk; Lee, Jandee

    2017-02-01

    The 2015 American Thyroid Association (ATA) management guidelines for adult patients with differentiated thyroid cancer propose the use of the modified initial risk stratification and response to therapy re-stratification systems. This study was conducted to validate the practicality of the revised guidelines for predicting tumor recurrence in patients with differentiated thyroid cancer. Patients with papillary thyroid cancer (n = 2425) who underwent total thyroidectomy with central neck node dissection with or without modified radical neck node dissection at a single institution between October 1985 and July 2009 were retrospectively enrolled. The accuracy of three different risk-stratification strategies for predicting disease-free survival, set out in the 2009 and 2015 ATA management guidelines, was assessed: the initial risk stratification (ATA 2009-RSS), the modified initial risk stratification (ATA 2015-RSS), and the response to therapy re-stratification (ATA 2015-RTR). After applying the ATA 2015-RSS, 258/1913 (13.5%) of patients originally designated as intermediate risk by the ATA 2009-RSS were designated as low risk. This was mainly due to the small number of metastatic lymph nodes. Recurrence was detected in 136 (5.6%) patients during follow-up. Of the 2425 cases examined, 375 were designated as low risk by the ATA 2009-RSS, with a recurrence rate of 1.1%. However, the ATA 2015-RSS designated 633 (26.1%) cases as low risk, with a recurrence rate of 0.9%. Implementing the ATA 2015-RTR predicted an excellent response in 1597 (65.9%) cases, with a recurrence rate of 1.1%. According to the proportion of variance explained (PVE), the Akaike information criterion, Harrell's c index, and integrated area under the curve, comparing the predictive accuracy of the ATA 2009-RSS, ATA 2015-RSS, and ATA 2015-RTR revealed that the ATA 2015-RTR was a superior predictor of recurrence. A proportion of patients designated as intermediate risk by the ATA 2009-RSS were

  14. Thyroid hormone transporters and deiodinases in the developing human hypothalamus

    NARCIS (Netherlands)

    Friesema, E.C.; Visser, T.J.; Borgers, A.J.F.; Kalsbeek, A.; Swaab, D.F.; Fliers, E.; Alkemade, A.

    2012-01-01

    OBJECTIVE: Thyroid hormone (TH) signaling in brain cells is dependent on transport of TH across the plasma membrane followed by intracellular deiodination and binding to the nuclear TH receptors. The aim of this study is to investigate the expression of the specific TH transporters monocarboxylate

  15. Aberrantly methylated genes in human papillary thyroid cancer and their association with BRAF/RAS mutation.

    Directory of Open Access Journals (Sweden)

    Yasuko eKikuchi

    2013-12-01

    Full Text Available Cancer arises through accumulation of epigenetic and genetic alteration. Aberrant promoter methylation is a common epigenetic mechanism of gene silencing in cancer cells. We here performed genome-wide analysis of DNA methylation of promoter regions by Infinium HumanMethylation27 BeadChip, using 14 clinical papillary thyroid cancer samples and 10 normal thyroid samples. Among the 14 papillary cancer cases, 11 showed frequent aberrant methylation, but the other three cases showed no aberrant methylation at all. Distribution of the hypermethylation among cancer samples was non-random, which implied existence of a subset of preferentially methylated papillary thyroid cancer. Among 25 frequently methylated genes, methylation status of six genes (HIST1H3J, POU4F2, SHOX2, PHKG2, TLX3, HOXA7 was validated quantitatively by pyrosequencing. Epigenetic silencing of these genes in methylated papillary thyroid cancer cell lines was confirmed by gene re-expression following treatment with 5-aza-2'-deoxycytidine and trichostatin A, and detected by real-time RT-PCR. Methylation of these six genes was validated by analysis of additional 20 papillary thyroid cancer and 10 normal samples. Among the 34 cancer samples in total, 26 cancer samples with preferential methylation were significantly associated with mutation of BRAF/RAS oncogene (P=0.04, Fisher’s exact test. Thus we identified new genes with frequent epigenetic hypermethylation in papillary thyroid cancer, two subsets of either preferentially methylated or hardly methylated papillary thyroid cancer, with a concomitant occurrence of oncogene mutation and gene methylation. These hypermethylated genes may constitute potential biomarkers for papillary thyroid cancer.

  16. Identification of delta-iodolactone in iodide treated human goiter and its inhibitory effect on proliferation of human thyroid follicles.

    Science.gov (United States)

    Dugrillon, A; Uedelhoven, W M; Pisarev, M A; Bechtner, G; Gärtner, R

    1994-10-01

    There is evidence that iodoarachidonates are mediators of iodide in thyroid autoregulation, however, their occurrence in vivo has not yet been demonstrated. We therefore tried to identify delta-iodolactone (5-Hydroxy-6-iodo-8,11,14-eicosatrienoic delta-lactone, IL-delta) in thyroid tissue from a patient with Graves' disease treated with high doses of iodide. Lipids were extracted from thyroid tissue, purified by reversed phase chromatography and analyzed by gas chromatography--tandem mass spectrometry (GC-MSMS). The retention time in gas chromatography and fragmentation pattern in tandem mass spectrometry were determined with biochemically synthesized non-deuterated and deuterated IL-delta. According to retention time (13.44 min) and specific fragments (m/z 303, m/z 259) the occurrence of IL-delta could be demonstrated in the extract of iodide treated goiter. In vitro, potassium iodide (40 microM) as well as IL-delta (1.0 microM) significantly inhibited the proliferation of human thyroid follicular cells induced by phorbol ester TPA (12-O-tetradecanoylphorbol 13-acetate). These results demonstrate for the first time that Il-delta is present in iodide treated human thyroid. As cell proliferation is under negative control of IL-delta, a crucial role in thyroid involution following iodide treatment may be possible.

  17. (−) Arctigenin and (+) Pinoresinol Are Antagonists of the Human Thyroid Hormone Receptor β

    Science.gov (United States)

    2015-01-01

    Lignans are important biologically active dietary polyphenolic compounds. Consumption of foods that are rich in lignans is associated with positive health effects. Using modeling tools to probe the ligand-binding pockets of molecular receptors, we found that lignans have high docking affinity for the human thyroid hormone receptor β. Follow-up experimental results show that lignans (−) arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone receptor β. The modeled complexes show key plausible interactions between the two ligands and important amino acid residues of the receptor. PMID:25383984

  18. Fibroblast growth factor receptor-2 expression in thyroid tumor progression: potential diagnostic application.

    Directory of Open Access Journals (Sweden)

    Adriano Redler

    Full Text Available Fibroblast growth factor receptor-2 (FGFR-2 plays an important role in tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation, but the role of this receptor has not been yet clarified. Therefore, we decided to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in different histological thyroid variants such as hyperplasia, follicular adenoma and papillary carcinoma. Immunohistochemistry and quantitative Real-Time PCR analyses were performed on samples of hyperplasia, follicular adenoma and papillary carcinoma, compared with normal thyroid tissue. Thyroid hyperplasia did not show statistically significant reduction in FGFR-2 protein and mRNA levels. Interestingly, in both follicular adenoma and papillary carcinoma samples we observed a strongly reduced expression of both FGFR-2 isoforms. We speculate that FGFR-2 down-modulation might be an early event in thyroid carcinogenesis. Furthermore, we suggest the potential use of FGFR-2 as an early marker for thyroid cancer diagnosis.

  19. Human Tumor Antigens Yesterday, Today, and Tomorrow.

    Science.gov (United States)

    Finn, Olivera J

    2017-05-01

    The question of whether human tumors express antigens that can be recognized by the immune system has been answered with a resounding YES. Most were identified through spontaneous antitumor humoral and cellular immune responses found in cancer patients and include peptides, glycopeptides, phosphopeptides, viral peptides, and peptides resulting from common mutations in oncogenes and tumor-suppressor genes, or common gene fusion events. Many have been extensively tested as candidates for anticancer vaccines. More recently, attention has been focused on the potentially large number of unique tumor antigens, mutated neoantigens, that are the predicted products of the numerous mutations revealed by exome sequencing of primary tumors. Only a few have been confirmed as targets of spontaneous immunity and immunosurveillance, and even fewer have been tested in preclinical and clinical settings. The field has been divided for a long time on the relative importance of shared versus mutated antigens in tumor surveillance and as candidates for vaccines. This question will eventually need to be answered in a head to head comparison in well-designed clinical trials. One advantage that shared antigens have over mutated antigens is their potential to be used in vaccines for primary cancer prevention. Cancer Immunol Res; 5(5); 347-54. ©2017 AACR. ©2017 American Association for Cancer Research.

  20. Recombinant human TSH and ablation of post-surgical thyroid remnants in differentiated thyroid cancer: the effect of pre-treatment with furosemide and furosemide plus lithium

    Energy Technology Data Exchange (ETDEWEB)

    Barbaro, Daniele; Lapi, Paola; Pasquini, Cristina; Orsini, Paola; Turco, Anna [General Hospital of Livorno, Endocrinology Unit, Livorno (Italy); Grosso, Mariano; Boni, Giuseppe; Mariani, Giuliano [University of Pisa Medical School, Regional Center of Nuclear Medicine, Pisa (Italy); Meucci, Giuseppe [General Hospital of Livorno, Division of General Surgery, Livorno (Italy); Marzola, Maria Cristina; Rubello, Domenico [' Santa Maria della Misericordia' Hospital, Department of Nuclear Medicine, PET Centre, Rovigo (Italy); Berti, Piero; Miccoli, Paolo [University of Pisa Medical School, Department of Surgery, Pisa (Italy)

    2010-02-15

    Recombinant human TSH (rhTSH) can be used for post-surgical radioiodine (I-131) thyroid remnants ablation in differentiated thyroid cancer (DTC) patients after surgery. Debate exists in literature about the optimal amount of I-131 that should be given for obtaining an effective ablation and about the role of iodine pool during treatment. Therefore, the aim of the present study was to assess whether I-131 ablation during rhTSH stimulus can be improved by reducing the circulating iodine pool and by increasing thyroid cell uptake and retention of I-131 obtained by administering furosemide and lithium. A total of 201 consecutive DTC patients were entered in the study: they were treated by total thyroidectomy and I-131 therapy during rhTSH stimulus to ablate thyroid remnants. Patients were divided into two groups according to the TNM stage: group 1 included patients in stage I-II who were treated with a low 30-mCi I-131 dose, while group 2 included patients in stage III-IV who were treated by a high 100-mCi I-131 dose. Moreover, both groups were further subdivided into three subgroups. Subgroup (a) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-thyroxine (LT4). Subgroup (b) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-T4, and after furosemide administration (25 mg/day orally) during the 3 days before I-131. Subgroup (c) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day L-T4 withdrawal, and after administration of furosemide (25 mg/day orally) during the 3 days prior I-131 and lithium (450 mg/day orally) during the 3 days following I-131. Another group (group 3) of 20 patients characterized by a very low-risk cancer (unifocal tumor <1.0 cm in diameter, without extra-capsular extension, N0) was

  1. THE ASSOCIATION OF WELL-DIFFERENTIATED THYROID-CARCINOMA WITH INSULAR OR ANAPLASTIC THYROID-CARCINOMA - EVIDENCE FOR DEDIFFERENTIATION IN TUMOR PROGRESSION

    NARCIS (Netherlands)

    van der Laan, Bernard F.A.M.; FREEMAN, JL; TSANG, RW; ASA, SL

    1993-01-01

    The sequence of tumorigenesis in the thyroid is unclear. It has been proposed that anaplastic carcinomas of the thyroid develop by dedifferentiation in pre-existing differentiated carcinomas. We reviewed all anaplastic and insular (poorly differentiated) thyroid carcinomas in a consultation practice

  2. Galectin-3 expression in human papillary thyroid carcinoma.

    Science.gov (United States)

    Sawangareetrakul, Phannee; Srisomsap, Chantragan; Chokchaichamnankit, Daranee; Svasti, Jisnuson

    2008-01-01

    Previous studies have suggested that galectin-3 expression was markedly elevated in papillary thyroid carcinoma compared to other thyroid diseases. In order to better understand this protein, galectin-3 from papillary thyroid carcinoma was partially purified by affinity chromatography on lactose-agarose. Proteins eluted from the column were separated by SDS-PAGE, and galectin-3 was detected with antibodies against the N-terminus and C-terminus of galectin-3. Some protein bands from the lactose binding fraction were also selected for identification by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). Seven protein bands, with molecular weights ranging from 16 kDa to 31 kDa, were identified as galectin-3. The antibody raised against the C-terminus of galectin-3 gave a strong band for one of the bands detected by the N-terminal antibody and weak bands for the other three. One additional dark immunoreactive band with an approximate molecular weight of 20 kDa, was also detected by the C-terminal galectin-3 antibody. To determine the structural differences of each protein band, N-terminal amino acid sequencing of the seven protein bands was conducted. The three upper bands were N-terminally blocked, while the other bands had N-terminal amino acid sequences starting at positions Gly35, Gly65 (2 bands) and Ala100, respectively. Further studies are necessary to determine whether these are due to nonspecific proteolysis or post-translation modification.

  3. Conventional and molecular cytogenetics of human non-medullary thyroid carcinoma: characterization of eight cell line models and review of the literature on clinical samples

    Directory of Open Access Journals (Sweden)

    Rocha Ana

    2008-12-01

    Full Text Available Abstract Background Cell lines are often poorly characterized from a genetic point of view, reducing their usefulness as tumor models. Our purpose was to assess the genetic background of eight commonly used human thyroid carcinoma models and to compare the findings with those reported for primary tumors of the gland. Methods We used chromosome banding analysis and comparative genomic hybridization to profile eight non-medullary thyroid carcinoma cell lines of papillary (TPC-1, FB2, K1 and B-CPAP, follicular (XTC-1 or anaplastic origin (8505C, C643 and HTH74. To assess the representativeness of the findings, we additionally performed a thorough review of cytogenetic (n = 125 and DNA copy number information (n = 270 available in the literature on clinical samples of thyroid carcinoma. Results The detailed characterization of chromosomal markers specific for each cell line revealed two cases of mistaken identities: FB2 was shown to derive from TPC-1 cells, whereas K1 cells have their origin in cell line GLAG-66. All cellular models displayed genomic aberrations of varying complexity, and recurrent gains at 5p, 5q, 8q, and 20q (6/7 cell lines and losses at 8p, 13q, 18q, and Xp (4/7 cell lines were seen. Importantly, the genomic profiles were compatible with those of the respective primary tumors, as seen in the meta-analysis of the existing literature data. Conclusion We provide the genomic background of seven independent thyroid carcinoma models representative of the clinical tumors of the corresponding histotypes, and highlight regions of recurrent aberrations that may guide future studies aimed at identifying target genes. Our findings further support the importance of routinely performing cytogenetic studies on cell lines, to detect cross-contamination mishaps such as those identified here.

  4. Conventional and molecular cytogenetics of human non-medullary thyroid carcinoma: characterization of eight cell line models and review of the literature on clinical samples

    Science.gov (United States)

    Ribeiro, Franclim Ricardo; Meireles, Ana Margarida; Rocha, Ana Sofia; Teixeira, Manuel Rodrigues

    2008-01-01

    Background Cell lines are often poorly characterized from a genetic point of view, reducing their usefulness as tumor models. Our purpose was to assess the genetic background of eight commonly used human thyroid carcinoma models and to compare the findings with those reported for primary tumors of the gland. Methods We used chromosome banding analysis and comparative genomic hybridization to profile eight non-medullary thyroid carcinoma cell lines of papillary (TPC-1, FB2, K1 and B-CPAP), follicular (XTC-1) or anaplastic origin (8505C, C643 and HTH74). To assess the representativeness of the findings, we additionally performed a thorough review of cytogenetic (n = 125) and DNA copy number information (n = 270) available in the literature on clinical samples of thyroid carcinoma. Results The detailed characterization of chromosomal markers specific for each cell line revealed two cases of mistaken identities: FB2 was shown to derive from TPC-1 cells, whereas K1 cells have their origin in cell line GLAG-66. All cellular models displayed genomic aberrations of varying complexity, and recurrent gains at 5p, 5q, 8q, and 20q (6/7 cell lines) and losses at 8p, 13q, 18q, and Xp (4/7 cell lines) were seen. Importantly, the genomic profiles were compatible with those of the respective primary tumors, as seen in the meta-analysis of the existing literature data. Conclusion We provide the genomic background of seven independent thyroid carcinoma models representative of the clinical tumors of the corresponding histotypes, and highlight regions of recurrent aberrations that may guide future studies aimed at identifying target genes. Our findings further support the importance of routinely performing cytogenetic studies on cell lines, to detect cross-contamination mishaps such as those identified here. PMID:19087340

  5. Spindle epithelial tumor with thymus-like differentiation of the thyroid gland: A case report with ultrasonography and CT features, cytological findings and histopathological results

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Dong Joo; Lee, Yoo Jin; Kim, Dong Wook; Jung, Soo Jin [Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2016-11-15

    Spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid gland is a very rare tumor. It is believed to originate from ectopic thymus tissue within the thyroid gland or from branchial pouch remnants that differentiate along the thymic line. A few reports of SETTLE have been presented, but to the best of our knowledge, there is no case report in which detailed preoperative imaging features of SETTLE have been described. In addition, there are no case reports of SETTLE in Korean patients. Thus, we report a case of SETTLE with detailed preoperative ultrasonography and computed tomography features, cytological findings and histopathological results.

  6. Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells.

    Science.gov (United States)

    Hayase, Suguru; Sasaki, Yoshihito; Matsubara, Tsutomu; Seo, Daekwan; Miyakoshi, Masaaki; Murata, Tsubasa; Ozaki, Takashi; Kakudo, Kennichi; Kumamoto, Kensuke; Ylaya, Kris; Cheng, Sheue-yann; Thorgeirsson, Snorri S; Hewitt, Stephen M; Ward, Jerrold M; Kimura, Shioko

    2015-04-01

    Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer.

  7. Thyroid hormone: a “prime suspect” in human immuno deficiency ...

    African Journals Online (AJOL)

    Acquired Immunodeficiency Syndrome (AIDS) is the final and most serious stage of the disease caused by human immunodeficiency virus. The Immune system is the target of AIDS. We investigate presently any possible involvement of thyroid hormone, the deficiency of which gives rise to oedema and susceptibility to ...

  8. Thyroid hormone induced oxygen consumption and glucose-uptake in human mononuclear cells

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L E

    1989-01-01

    Cellular oxygen consumption and glucose metabolism were examined in human mononuclear blood cells. The cellular oxygen consumption and glucose uptake were dependent on the number of cells, the temperature and the duration of incubation. Stimulation of the cells by T4 and T3 led to a dose dependen...... thyroid hormones and insulin exerted an additive effect on glucose uptake. Our study indicates a direct intracellular effect of T4 independent of its conversion to T3 and a different mechanism for insulin dependent and thyroid hormone glucose uptake....

  9. Primary thyroid lymphoma: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo-Cheol; Han, Moon Hee E-mail: hanmh@radcom.snu.ac.kr; Kim, Keon Ha; Jae, Hwan Jun; Lee, Sang Hyun; Kim, Sam Soo; Kim, Kwang Hyun; Chang, Kee-Hyun

    2003-06-01

    Introduction: To evaluate the computed tomographic (CT) findings of primary thyroid lymphoma. Methods and material: The clinicopathological data and CT images of nine patients with primary thyroid lymphoma were retrospectively reviewed. The CT appearances were classified into three types: type 1, a solitary nodule surrounded by normal thyroid tissue; type 2, multiple nodules in the thyroid, and type 3, a homogeneously enlarged both thyroid glands with a reduced attenuation with or without peripheral thin hyperattenuating thyroid tissue. Results: All patients had a rapidly enlarging thyroid mass and coexistent Hashimoto's thyroiditis. One patient showed type 1 pattern, three type 2, and five type 3. Six patients had homogeneous tumor isoattenuating to surrounding muscles. The tumors had a strong tendency to compress normal remnant thyroid and the surrounding structure without invasion. Conclusion: Primary thyroid lymphoma should be included in the differential diagnosis when old female had a homogeneous thyroidal mass isoattenuating to muscles, which does not invade surrounding structures.

  10. Interaction of Proteins Identified in Human Thyroid Cells

    Science.gov (United States)

    Pietsch, Jessica; Riwaldt, Stefan; Bauer, Johann; Sickmann, Albert; Weber, Gerhard; Grosse, Jirka; Infanger, Manfred; Eilles, Christoph; Grimm, Daniela

    2013-01-01

    Influence of gravity forces on the regulation of protein expression by healthy and malignant thyroid cells was studied with the aim to identify protein interactions. Western blot analyses of a limited number of proteins suggested a time-dependent regulation of protein expression by simulated microgravity. After applying free flow isoelectric focusing and mass spectrometry to search for differently expressed proteins by thyroid cells exposed to simulated microgravity for three days, a considerable number of candidates for gravi-sensitive proteins were detected. In order to show how proteins sensitive to microgravity could directly influence other proteins, we investigated all polypeptide chains identified with Mascot scores above 100, looking for groups of interacting proteins. Hence, UniProtKB entry numbers of all detected proteins were entered into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and processed. The program indicated that we had detected various groups of interacting proteins in each of the three cell lines studied. The major groups of interacting proteins play a role in pathways of carbohydrate and protein metabolism, regulation of cell growth and cell membrane structuring. Analyzing these groups, networks of interaction could be established which show how a punctual influence of simulated microgravity may propagate via various members of interaction chains. PMID:23303277

  11. Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease.

    Science.gov (United States)

    Maia, Ana Luiza; Goemann, Iuri Martin; Meyer, Erika L Souza; Wajner, Simone Magagnin

    2011-06-01

    Thyroid hormone is essential for the normal function of virtually all tissues. The iodothyronine deiodinases catalyze the removal of an iodine residue from the pro-hormone thyroxine (T(4)) molecule, thus producing either the active form triiodothyronine (T(3); activation) or inactive metabolites (reverse T(3); inactivation). Type I deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on normal thyroid hormone metabolism and pathological processes. Although peripheral D1-generated T(3) production contributes to a portion of plasma T(3) in euthyroid state, pathologically increased thyroidal D1 activity seems to be the main cause of the elevated T(3) concentrations observed in hyperthyroid patients. On the other hand, D1-deficient mouse models show that, in the absence of D1, inactive and lesser iodothyronines are excreted in feces with the loss of associated iodine, demonstrating the scavenging function for D1 that might be particularly important in an iodine deficiency setting. Polymorphisms in the DIO1 gene have been associated with changes in serum thyroid hormone levels, whereas decreased D1 activity has been reported in the nonthyroid illness syndrome and in several human neoplasias. The current review aims at presenting an updated picture of the recent advances made in the biochemical and molecular properties of D1 as well as its role in human physiology.

  12. Diet-Induced Obesity Increases Tumor Growth and Promotes Anaplastic Change in Thyroid Cancer in a Mouse Model

    OpenAIRE

    Kim, Won Gu; Park, Jeong Won; Willingham, Mark C.; Cheng, Sheue-yann

    2013-01-01

    Recent epidemiological studies provide strong evidence suggesting obesity is a risk factor in several cancers, including thyroid cancer. However, the molecular mechanisms by which obesity increases the risk of thyroid cancer are poorly understood. In this study, we evaluated the effect of diet-induced obesity on thyroid carcinogenesis in a mouse model that spontaneously develops thyroid cancer (ThrbPV/PVPten+/− mice). These mice harbor a mutated thyroid hormone receptor-β (denoted as PV) and ...

  13. Associations between brominated flame retardants in human milk and thyroid-stimulating hormone (TSH) in neonates.

    Science.gov (United States)

    Eggesbø, Merete; Thomsen, Cathrine; Jørgensen, Jens V; Becher, Georg; Odland, Jon Øyvind; Longnecker, Matthew P

    2011-08-01

    Brominated flame retardants (BFRs) have been in widespread use in a vast array of consumer products since the 1970s. The metabolites of some BFRs show a structural similarity to thyroid hormones and experimental animal studies have confirmed that they may interfere with thyroid hormone homeostasis. A major concern has been whether intrauterine exposure to BFRs may disturb thyroid homeostasis since the fetal brain is particularly susceptible to alterations in thyroid hormones. However, few reports on newborns have been published to date. To evaluate the association between BFRs and neonatal thyroid-stimulating hormone (TSH). We studied six polybrominated diphenyl ethers (PBDEs) measured in milk samples from 239 women who were part of the "Norwegian Human Milk Study" (HUMIS), 2003-2006. Hexabromocyclododecane (HBCD) and BDE-209 were measured in a subset of the women (193 and 46 milk samples, respectively). The milk was sampled at a median of 33 days after delivery. TSH was measured in babies three days after delivery as part of the routine national screening program for early detection of congenital hypothyroidism. Additional information was obtained through the Medical Birth Registry and questionnaires to the mothers. The PBDE concentrations in human milk in Norway were comparable to concentrations reported from other European countries and Asia, but not the US and Canada where levels are approximately one order of higher magnitude. We observed no statistically significant associations between BDE-47, 99, 153, 154, 209 and HBCD in human milk and TSH in models adjusted for possible confounders and other environmental toxicants including polychlorinated biphenyls (PCBs). We did not observe an association between TSH and exposure to HBCD and PBDEs within the exposure levels observed. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Use of recombinant human thyrotropin (rh TSH) as a method of preparation for radioiodine therapy in thyroid disorders; Utilisation de la thyreostimuline humaine recombinante dans la preparation au traitement par iode-131 des pathologies thyroidiennes

    Energy Technology Data Exchange (ETDEWEB)

    Taieb, D.; Guillet, B.A.; Tessonnier, L.; Mundler, O. [Centre Hospitalo-Universitaire de la Timone, Service Central de Biophysique et de Medecine Nucleaire, 13 - Marseille (France)

    2008-02-15

    The introduction of recombinant human TSH (rh TSH) as a method of preparation for radioiodine therapy of follicular-derived thyroid tumors (benign and malignant) is a significant medical advance. Rh TSH has been approved for use in remnants ablation after total thyroidectomy for carcinoma. There are other potential uses for rh TSH that have not yet been licensed. The use of rh TSH allows to reduce administrated doses in goiters through an increase of iodine uptake and a more homogeneous distribution of radioiodine in the gland. Rh TSH also improves thyroid cancer patients quality of life by avoiding hypothyroidism. (authors)

  15. Effect of capsular dissection technique on the parathyroid function and recurrent laryngeal nerve in patients with thyroid tumor

    Directory of Open Access Journals (Sweden)

    Cheng-Ping He

    2017-04-01

    Full Text Available Objective: To explore the effect of capsular dissection technique on the parathyroid function and recurrent laryngeal nerve in patients with thyroid tumor. Methods: A total of 70 patients with differentiated thyroid carcinoma who were admitted in our hospital from May, 2011 to July, 2016 were included in the study and randomized into the observation group and the control group. The patients in the observation group were performed with total thyroidectomy by adoption of capsular dissection technique, while the patients in the control group were performed with the traditional thyroidectomy. The serum PTH, Ca2+ concentration, and adverse reactions before and after treatment in the two groups were compared. Results: The serum PTH and Ca2+ 1 d until 1 month after operation in the observation group were significantly higher than those in the control group (P0.05. The occurrence rate of temporary parathyroid damage in the observation group was significantly lower than that in the control group (P0.05. Conclusions: Capsular dissection technique in the total thyroidectomy can significantly reduce the parathyroid and recurrent laryngeal nerve damage, with a higher clinical application value.

  16. Biological characteristics and chemosensitivity profile of four human anaplastic thyroid carcinoma cell lines.

    Science.gov (United States)

    Sekiguchi, M; Shiroko, Y; Arai, T; Kishino, T; Sugawara, I; Kusakabe, T; Suzuki, T; Yamashita, T; Obara, T; Ito, K; Hasumi, K

    2001-10-01

    Anaplastic thyroid carcinoma is a rapidly growing, aggressive neoplasm affecting the elderly which does not respond to most of the therapies. We established cultured cell lines from four untreated tumors. The cultures grew in a monolayer of spindle-shaped cells in three cell lines and of small polygonal cells in one line, having relatively long doubling times and chromosomal abnormalities. The xenotransplantation of the lines in athymic nude mice produced tumors with a histology similar to the original tumors. The immunocytochemical staining showed the expression of PCNA, HLA-class 1, cytokeratin, vimentin and FAS (fatty acid synthase) but not CEA, desmin or P-glycoprotein. The lines secreted TPA, IL-6, IL-8 and few or no thyroid-related hormones in the culture supernatant. One cell line produced G-CSF. The chemosensitivity assay revealed intrinsic drug resistance to nine out of 11 antineoplastic agents. The reverse transcriptase-polymerase chain reaction (RT-PCR) detected MRP (multidrug resistance-associated protein) mRNA but not mdr (multidrug resistance protein)-1 and mdr-3 mRNAs. This finding indicates that the multidrug resistance of these lines is mediated by a P-glycoprotein-unrelated mechanism. The RT-PCR also presented FAS mRNA in all the lines, and IL-6 and IL-8 mRNAs in some of the lines.

  17. Thyroid tumor formation in the male mouse induced by fluopyram is mediated by activation of hepatic CAR/PXR nuclear receptors.

    Science.gov (United States)

    Rouquié, D; Tinwell, H; Blanck, O; Schorsch, F; Geter, D; Wason, S; Bars, R

    2014-12-01

    Fluopyram, a broad spectrum fungicide, caused an increased incidence of thyroid follicular cell (TFC) adenomas in males at the highest dose evaluated (750ppm equating to 105mg/kg/day) in the mouse oncogenicity study. A series of short-term mechanistic studies were conducted in the male mouse to characterize the mode of action (MOA) for the thyroid tumor formation and to determine if No Observed Effect Levels (NOELs) exist for each key event identified. The proposed MOA consists of an initial effect on the liver by activating the constitutive androstane (Car) and pregnane X (Pxr) nuclear receptors causing increased elimination of thyroid hormones followed by an increased secretion of thyroid stimulating hormone (TSH). This change in TSH secretion results in an increase of TFC proliferation which leads to hyperplasia and eventually adenomas after chronic exposure. Car/Pxr nuclear receptors were shown to be activated as indicated by increased activity of specific Phase I enzymes (PROD and BROD, respectively). Furthermore, evidence of increased T4 metabolism was provided by the induction of phase II enzymes known to preferentially use T4 as a substrate. Additional support for the proposed MOA was provided by demonstrating increased Tsh β transcripts in the pituitary gland. Finally, increased TFC proliferation was observed after 28days of treatment. In these dose-response studies, clear NOELs were established for phase 2 liver enzyme activities, TSH changes and TFC proliferation. Furthermore, compelling evidence for Car/Pxr activation being the molecular initiating event for these thyroid tumors was provided by the absence of the sequential key events responsible for the TCF tumors in Car/Pxr KO mice when exposed to fluopyram. In conclusion, fluopyram thyroid toxicity is mediated by activation of hepatic Car/Pxr receptors and shows a threshold dependent MOA. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Wnt/β-Catenin Signaling Pathway Is a Direct Enhancer of Thyroid Transcription Factor-1 in Human Papillary Thyroid Carcinoma Cells

    Science.gov (United States)

    Gilbert-Sirieix, Marie; Makoukji, Joelle; Kimura, Shioko; Talbot, Monique; Caillou, Bernard; Massaad, Charbel; Massaad-Massade, Liliane

    2011-01-01

    The Wnt/β-catenin signaling pathway is involved in the normal development of thyroid gland, but its disregulation provokes the appearance of several types of cancers, including papillary thyroid carcinomas (PTC) which are the most common thyroid tumours. The follow-up of PTC patients is based on the monitoring of serum thyroglobulin levels which is regulated by the thyroid transcription factor 1 (TTF-1): a tissue-specific transcription factor essential for the differentiation of the thyroid. We investigated whether the Wnt/β-catenin pathway might regulate TTF-1 expression in a human PTC model and examined the molecular mechanisms underlying this regulation. Immunofluorescence analysis, real time RT-PCR and Western blot studies revealed that TTF-1 as well as the major Wnt pathway components are co-expressed in TPC-1 cells and human PTC tumours. Knocking-down the Wnt/β-catenin components by siRNAs inhibited both TTF-1 transcript and protein expression, while mimicking the activation of Wnt signaling by lithium chloride induced TTF-1 gene and protein expression. Functional promoter studies and ChIP analysis showed that the Wnt/β-catenin pathway exerts its effect by means of the binding of β-catenin to TCF/LEF transcription factors on the level of an active TCF/LEF response element at [−798, −792 bp] in TTF-1 promoter. In conclusion, we demonstrated that the Wnt/β-catenin pathway is a direct and forward driver of the TTF-1 expression. The localization of TCF-4 and TTF-1 in the same area of PTC tissues might be of clinical relevance, and justifies further examination of these factors in the papillary thyroid cancers follow-up. PMID:21814573

  19. Expression of tpo mRNA in thyroid tumors: quantitative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes.

    Science.gov (United States)

    Di Cristofaro, J; Silvy, M; Lanteaume, A; Marcy, M; Carayon, P; De Micco, C

    2006-06-01

    Immunocytochemistry (ICC) of thyroid peroxidase (TPO) using the monoclonal antibody MoAb47 has been used as malignancy marker on thyroid fine needle aspiration. However, little is known about the fate of TPO in thyroid carcinoma. We performed a qualitative PCR (Q-PCR) analysis to measure the expression of variants of tpo mRNA in 13 normal tissue samples, 30 benign tumors (BT), 21 follicular carcinomas (FC), 20 classical papillary carcinomas (PCc), 12 follicular variants of papillary carcinomas (PCfv) and nine oncocytic carcinomas (OC). We also studied mutations involving the ras, Braf, ret or pax8 genes. Results of Q-PCR were closely correlated with those of ICC (P tpo expression was lower in all carcinomas than in normal and BT (P tpo2 or tpo3 to tpo1 was inversed in follicular tumors. Genetic mutations were observed in 90% of PCc, 61.9% of FC, 41.7% of PCfv, 0% of OC and 10% in BT. pax8-ppar gamma1 rearrangement was correlated with qualitative changes in tpo mRNA (P TPO expression in 97% of thyroid carcinomas regardless of histological type and the overexpression of shorter splice variants in follicular tumors. Both reduction in quantity of TPO and impairment of its maturation process could account for the atypical immunohistochemical reaction of MoAb47 with TPO.

  20. Iodide kinetics and experimental I-131 therapy in a xenotransplanted human sodium-iodide symporter-transfected human follicular thyroid carcinoma cell line

    NARCIS (Netherlands)

    Smit, J.W.A.; Elst, van der J.P.; Karperien, M.; Que, I.; Stokkel, M.; Heide, van der D.; Romijn, J.A.

    2002-01-01

    Uptake of iodide is a prerequisite for radioiodide therapy in thyroid cancer. However, loss of iodide uptake is frequently observed in metastasized thyroid cancer, which may be explained by diminished expression of the human sodium-iodide symporter (hNIS). We studied whether transfection of hNIS

  1. Iodide kinetics and experimental (131)I therapy in a xenotransplanted human sodium-iodide symporter-transfected human follicular thyroid carcinoma cell line

    NARCIS (Netherlands)

    Smit, Jan W. A.; Schröder-van der Elst, Janny P.; Karperien, Marcel; Que, Ivo; Stokkel, Marcel; van der Heide, Daan; Romijn, Johannes A.

    2002-01-01

    Uptake of iodide is a prerequisite for radioiodide therapy in thyroid cancer. However, loss of iodide uptake is frequently observed in metastasized thyroid cancer, which may be explained by diminished expression of the human sodium-iodide symporter (hNIS). We studied whether transfection of hNIS

  2. Case presentation – thyroid lymphoma

    Directory of Open Access Journals (Sweden)

    Belkisa Izić

    2011-11-01

    Full Text Available Malignant tumors of the thyroid gland account for about 1% of thenewly diagnosed malignant tumors each year, and their incidence inwomen is twice the incidence in men. According to the WHO classification (2004 thyroid tumors are divided into: carcinoma of the thyroid, adenoma and similar tumors, and other thyroid tumors which include: teratomas, angiosarcomas, paragangliomas and others, as well as primary lymphomas and plasmacytomas. Primary thyroid lymphomasare defined as lymphomas which originate in the thyroid gland. This study presents the case of a 68-year-old patient with a thyroid lymphoma, which caused compression of the airways. In the patientpresented there was reduced activity of the thyroid gland. The dominant symptoms were: breathing difficulties, hoarse voice and the enlargement of the thyroid. An ultrasound examination was performedbefore surgery on the neck, which showed a multinodular thyroid,with compromised and compressed trachea to the right and rear. Anemergency surgical procedure was performed to reduce the tumor.Pathohistological diagnosis confirmed diffuse large B cell lymphoma.The aim of the study was to present a patient with a thyroid lymphoma, who had previously not had any immunological changes to the gland,that is, she had not had any chronic lymphocyte thyroiditis, but due to the compressive syndrome it was necessary to perform an emergencysurgical procedure to reduce the tumor.

  3. Integrated Analysis of Thyroid Cancer Public Datasets Reveals Role of Post-Transcriptional Regulation on Tumor Progression by Targeting of Immune System Mediators.

    Directory of Open Access Journals (Sweden)

    Murilo V Geraldo

    Full Text Available Papillary thyroid carcinoma (PTC is a well-differentiated thyroid tumor that accounts for approximately 80% of thyroid cancer cases. On other hand, anaplastic thyroid carcinoma (ATC is a less frequent, but aggressive subtype, with poor prognosis. MicroRNAs (miRNAs, small non-coding RNAs, have emerged as potent post-transcriptional regulators of gene expression, which modulate the expression of cancer-related genes. Computational analyses estimate that a single miRNA may modulate hundreds of mRNA targets and, at the same time, cooperate with others to regulate one single mRNA transcript. Due to the large number of predicted targets and possible interactions, only a small number of miRNAs have characterized biological roles, and the panorama of miRNA-mediated regulation in thyroid cancer remains to be understood. Taking into consideration the large amount of gene expression data deposited in public databases we aligned miRNA target prediction and gene expression data from public PTC and ATC datasets to construct a network of post-transcriptional regulation in thyroid cancer. After a gene set enrichment analysis we identified signaling pathways and biological processes potentially modulated by the miRNAs deregulated in PTC and ATC. Our results show miRNA-mRNA interaction that could contribute with the de-regulation of key tumor-host mediators, such as extra-cellular matrix molecules, interleukins and interleukin receptors, which could drive a more aggressive behavior and tumor progression. Moreover, our analysis through The Cancer Genome Atlas (TCGA database revealed that aberrant expression of ECM and cytokines genes is frequent in PTC and is associated with aggressive behavior and decreased overall survival rate. In conclusion, we shed light on the post-transcriptional regulation of gene expression in differentiated and undifferentiated thyroid cancers, revealing a potential role of miRNAs in modulation of tumor-host interaction molecules

  4. In Vitro Efficient Expansion of Tumor Cells Deriving from Different Types of Human Tumor Samples

    Directory of Open Access Journals (Sweden)

    Ilaria Turin

    2014-03-01

    Full Text Available Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently establishing primary cultures starting from tumor samples of different types, while maintaining the immuno-histochemical characteristics of the original tumor. We compared two different strategies to disaggregate tumor specimens. After short or long term in vitro expansion, cells analyzed for the presence of malignant cells demonstrated their neoplastic origin. Considering that tumor cells may be isolated in a closed system with high efficiency, we propose this methodology for the ex vivo expansion of tumor cells to be used to evaluate suitable new drugs or to generate tumor-specific cytotoxic T lymphocytes or vaccines.

  5. Recombinant human TSH in differentiated thyroid cancer: a nuclear medicine perspective

    Energy Technology Data Exchange (ETDEWEB)

    Zanotti-Fregonara, P. [CEA, DSV, I2BM, SHFJ, LMNRB, Orsay (France); Rubello, D. [Osped S Maria Misericordia, IRCCS, IOV, Dept Nucl Med, PET Ctr, I-45100 Rovigo (Italy); Hindie, E. [Hop St Louis, Dept Nucl Med, Paris (France)

    2008-07-01

    The use of recombinant human thyroid-stimulating hormone (rhTSH) in differentiated thyroid cancer (DTC) is widely discussed in the literature with regard to the diagnostic and therapeutic aspects of the management of DTC patients. However, some controversy about the appropriate indications, advantages and potential disadvantages of the use of rhTSH may still exist within the community of nuclear medicine physicians. In our opinion, the clinical benefits of rhTSH in avoiding hypothyroidism outweigh its somewhat lesser diagnostic accuracy. However, we disagree on designating rhTSH as the 'golden standard' to obtain TSH stimulation, as suggested by some authors. Thus, the first follow-up examination after ablation, which is determinant for patients' prognostic classification, can be either done under rhTSH stimulation or after hormone withdrawal. In our practice, and for higher risk patients, we still favour performing the initial follow-up after thyroid hormone withdrawal. rhTSH also shows the ability to enhance radioiodine concentration into thyroid cells. This characteristic is obviously of great interest among the nuclear medicine community. In clinical practice, it seems preferable to perform {sup 131}I treatment for metastatic disease during hypothyroidism. rhTSH may find its utility for the treatment of specific populations of patients, i.e. those in whom hormone withdrawal is medically contraindicated or in whom adequate endogenous TSH levels cannot be obtained due to reduced pituitary reserve or continued thyroxine production by metastatic tissue. In conclusion, rhTSH has demonstrated to be a reliable alternative to hypothyroidism for the stimulation of Tg in the follow-up of thyroid cancer patients. However, its use must be more carefully chosen in the therapeutic setting. Our feeling is that rhTSH should no tbe used for remnant ablation in high-risk patients and for the treatment of metastatic disease, except for specific populations of

  6. A comparison of potency differences among thyroid peroxidase (TPO) inhibitors to induce developmental toxicity and other thyroid gland-linked toxicities in humans and rats.

    Science.gov (United States)

    Motonaga, Kozo; Ota, Mika; Odawara, Kyoko; Saito, Shoji; Welsch, Frank

    2016-10-01

    The potencies of resorcinol, 6-propylthiouracil (PTU) and methimazole (MMI) for inducing developmental toxicity and neurotoxicity were compared in pregnant rats, regarded as valid model for human thyroid toxicity. Profound differences on maternal thyroid hormone levels (THs), maternal toxicity as well as developmental and neurotoxicity sequelae occurred. Resorcinol affected none of those end points. PTU and MMI caused significant effects. Therapy with either PTU or MMI during the first trimester of human pregnancy can cause reductions of maternal THs, accompanied by disruptions of prenatal development. Clinical MMI studies show sporadic evidence of teratogenic effects, with equivocal relation to thyroid peroxidase (TPO) inhibition. In recent decades no MMI associated prenatal toxicity has been reported, an outcome possibly related to carefully managed therapy. Orally administered resorcinol was rapidly absorbed, metabolized and excreted and was undetectable in the thyroid. In contrast, PTU or MMI accumulated. Resorcinol's potency to inhibit TPO was profoundly lower than that of PTU or MMI. Quantum chemical calculations may explain low resorcinol reactivity with TPO. Thus, distinctions in the target organ and the TPO inhibitory potency between these chemicals are likely contributing to different reductions of maternal THs levels and affecting the potency to cause developmental toxicity and neurotoxicity. Copyright © 2016. Published by Elsevier Inc.

  7. Tumor

    Science.gov (United States)

    ... peanut plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by or linked with viruses are: Cervical cancer (human papillomavirus) Most anal cancers (human papillomavirus) Some ...

  8. Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation

    Science.gov (United States)

    Chakravarty, Debyani; Santos, Elmer; Ryder, Mabel; Knauf, Jeffrey A.; Liao, Xiao-Hui; West, Brian L.; Bollag, Gideon; Kolesnick, Richard; Thin, Tin Htwe; Rosen, Neal; Zanzonico, Pat; Larson, Steven M.; Refetoff, Samuel; Ghossein, Ronald; Fagin, James A.

    2011-01-01

    Advanced human thyroid cancers, particularly those that are refractory to treatment with radioiodine (RAI), have a high prevalence of BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations. However, the degree to which these cancers are dependent on BRAF expression is still unclear. To address this question, we generated mice expressing one of the most commonly detected BRAF mutations in human papillary thyroid carcinomas (BRAFV600E) in thyroid follicular cells in a doxycycline-inducible (dox-inducible) manner. Upon dox induction of BRAFV600E, the mice developed highly penetrant and poorly differentiated thyroid tumors. Discontinuation of dox extinguished BRAFV600E expression and reestablished thyroid follicular architecture and normal thyroid histology. Switching on BRAFV600E rapidly induced hypothyroidism and virtually abolished thyroid-specific gene expression and RAI incorporation, all of which were restored to near basal levels upon discontinuation of dox. Treatment of mice with these cancers with small molecule inhibitors of either MEK or mutant BRAF reduced their proliferative index and partially restored thyroid-specific gene expression. Strikingly, treatment with the MAPK pathway inhibitors rendered the tumor cells susceptible to a therapeutic dose of RAI. Our data show that thyroid tumors carrying BRAFV600E mutations are exquisitely dependent on the oncoprotein for viability and that genetic or pharmacological inhibition of its expression or activity is associated with tumor regression and restoration of RAI uptake in vivo in mice. These findings have potentially significant clinical ramifications. PMID:22105174

  9. Hashimoto's thyroiditis and papillary thyroid cancer: are they immunologically linked?

    Science.gov (United States)

    Ehlers, Margret; Schott, Matthias

    2014-12-01

    Hashimoto's thyroiditis (HT) is the most common autoimmune disease in humans frequently leading to hypothyroidism. HT is characterized by a cellular immune response with lymphatic infiltration of the thyroid gland by T and B cells, as well as by a humoral immune response leading to specific antibody production. The synchronous appearance of HT and papillary thyroid cancer (PTC) indicates an immunological link between the two entities. Three different pathomechanisms may be postulated, including preexisting autoimmunity leading to malignancy due to inflammation, immunity towards preexisiting tumor cells leading to specific autoimmunity, and immune tolerance leading to malignancy despite (auto)immunity. In this article we review data describing these potential mechanisms that might lead to the synchronous appearance of HT and PTC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Study on the induction of thyroid tumors in rats using x irradiation in conjunction with a goitrogen. [1 methyl--2 mercaptoimidazole (methimazole)

    Energy Technology Data Exchange (ETDEWEB)

    Mahler, P.

    1979-01-01

    The influence of acute localized thyroid x irradiation and chronic goitrogen administration, separately or combined, on thyroid tumor formation in mature female rats was studied. In the first experiment, the radiation doses were 0, 80, 160, 320, or 640 rads, and the dosages of goitrogen were 0, 4, or 40 parts per million (ppM) of 1 methyl - 2 mercaptoimidazole (MMI). The incidence of rats with thyroid tumors in any treated group receiving 0 or 4 ppM MMI was not significantly greater than the incidence in the nontreated control group. However, the incidence in any of the 40 ppM MMI groups was significantly greater than that in the nontreated control group. At all the radiation doses other than 80 rads, the incidence was significantly greater than that in the non-irradiated group. No significant difference was seen in the incidence of rats with thyroid tumors on the basis of radiation dose. The incidence was so high at 80 rads that there was little margin for further increase by increasing the radiation dose. The mean serum thyroxine levels at 40 ppM MMI, 4 ppM MMI, and 0 ppM MMI were 1.9, 3.5, and 3.7 ..mu..g/100 ml, respectively. No markedeffect of thyroid irradiation on mean serum thyroxine levels was seen. In the second experiment, rats receiving 200 ppM MMI and thyroid irradiation were sacrificed at 7-1/2 months after treatment. Nearly all rats in the 0 and 80 rad groups and all in the 160, the 320, and the 640 rad groups had thyroid tumors. In the third experiment, serum T/sub 4/ levels were measured in treated rats. Rats receiving 640 rads + 0 ppM MMI showed a slight decrease in serum T/sub 4/, while no change in serum T/sub 4/ levels was seen in rats receiving 0 rads + 4 ppM MMI or 640 rads + 4 ppM MMI. All rats receiving 40 ppM MMI, regardless of radiation dose, showed decreased serum T/sub 4/ levels.

  11. Loss of c-KIT expression in thyroid cancer cells.

    Science.gov (United States)

    Franceschi, Sara; Lessi, Francesca; Panebianco, Federica; Tantillo, Elena; La Ferla, Marco; Menicagli, Michele; Aretini, Paolo; Apollo, Alessandro; Naccarato, Antonio Giuseppe; Marchetti, Ivo; Mazzanti, Chiara Maria

    2017-01-01

    Papillary thyroid carcinoma is the most frequent histologic type of thyroid tumor. Few studies investigated the role of c-KIT expression in thyroid tumors, suggesting a role for this receptor and its ligand in differentiation and growth control of thyroid epithelium and a receptor loss following malignant transformation. We investigated and correlated c-KIT expression levels and two known markers of thyrocytes differentiation, PAX8 and TTF-1, in malignant and benign cytological thyroid samples. Moreover, we performed functional studies on human papillary thyroid carcinoma cell line to associated c-KIT expression to thyrocytes differentiation and tumor proliferation. c-KIT and PAX8 expression resulted higher in benign samples compared to the malignant ones, and the expression levels of these two genes were significantly correlated to each other. We also observed that c-KIT overexpression led to an increase of PAX8 expression level together with a decrease of proliferation. Furthermore, c-KIT overexpressing cells showed a regression of typical morphological features of malignancy. Taken together these results suggest that c-KIT could be involved in the differentiation of thyroid cells and in tumor progression.

  12. From reverse transcription to human brain tumors

    Directory of Open Access Journals (Sweden)

    Dmitrenko V. V.

    2013-05-01

    Full Text Available Reverse transcriptase from avian myeloblastosis virus (AMV was the subject of the study, from which the investi- gations of the Department of biosynthesis of nucleic acids were started. Production of AMV in grams quantities and isolation of AMV reverse transcriptase were established in the laboratory during the seventies of the past cen- tury and this initiated research on the cDNA synthesis, cloning and investigation of the structure and functions of the eukaryotic genes. Structures of salmon insulin and insulin-like growth factor (IGF family genes and their transcripts were determined during long-term investigations. Results of two modern techniques, microarray-ba- sed hybridization and SAGE, were used for the identification of the genes differentially expressed in astrocytic gliomas and human normal brain. Comparison of SAGE results on the genes overexpressed in glioblastoma with the results of microarray analysis revealed a limited number of common genes. 105 differentially expressed genes, common to both methods, can be included in the list of candidates for the molecular typing of glioblastoma. The first experiments on the classification of glioblastomas based on the data of the 20 genes expression were conducted by using of artificial neural network analysis. The results of these experiments showed that the expression profiles of these genes in 224 glioblastoma samples and 74 normal brain samples could be according to the Koho- nen’s maps. The CHI3L1 and CHI3L2 genes of chitinase-like cartilage protein were revealed among the most overexpressed genes in glioblastoma, which could have prognostic and diagnostic potential. Results of in vitro experiments demonstrated that both proteins, CHI3L1 and CHI3L2, may initiate the phosphorylation of ERK1/ ERK2 and AKT kinases leading to the activation of MAPK/ERK1/2 and PI3K/AKT signaling cascades in human embryonic kidney 293 cells, human glioblastoma U87MG, and U373 cells. The new human cell line

  13. Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

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    Yingjen Jeffrey Wu

    2009-02-01

    Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

  14. Identification and manipulation of tumor associated macrophages in human cancers

    Directory of Open Access Journals (Sweden)

    Heusinkveld Moniek

    2011-12-01

    Full Text Available Abstract Evading immune destruction and tumor promoting inflammation are important hallmarks in the development of cancer. Macrophages are present in most human tumors and are often associated with bad prognosis. Tumor associated macrophages come in many functional flavors ranging from what is known as classically activated macrophages (M1 associated with acute inflammation and T-cell immunity to immune suppressive macrophages (M2 associated with the promotion of tumor growth. The role of these functionally different myeloid cells is extensively studied in mice tumor models but dissimilarities in markers and receptors make the direct translation to human cancer difficult. This review focuses on recent reports discriminating the type of infiltrating macrophages in human tumors and the environmental cues present that steer their differentiation. Finally, immunotherapeutic approaches to interfere in this process are discussed.

  15. Effects of polybrominated diphenyl ethers on thyroid hormone, neurodevelopment and fertility in rodents and humans

    Directory of Open Access Journals (Sweden)

    Marta Czerska

    2013-08-01

    Full Text Available Polybrominated diphenyl ethers (PBDEs are used as flame retardants. Due to their widespread use in many consumer products, PBDEs can be found in food as well as in the environment. Their presence has also been found in the human serum, human adipose tissue and human breast milk. Results of experimental studies suggest that the presence of PBDE in the environment is not neutral to our health. In rats and mice exposed to PBDE disturbances in thyroid hormone homeostasis and reproductive system such as changes in reproductive organs weight and disorders in sperm motility and motion were found. In rodents, pre- and postnatal exposure to PBDE can cause neurobehavioral effects. Also in humans disturbances in thyroid hormone system, weight of reproductive organs and concentrations of sex hormones associated with PBDEs serum concentrations were found. Exposure to PBDEs during pregnancy may lead to slower mental and psychomotor development in infants. In this paper the results of previous animal a nd human studies are reviewed.

  16. Preparation with recombinant humanized thyroid-stimulating hormone before radioiodine ablation after thyroidectomy: a systematic review.

    Science.gov (United States)

    Yoo, J; Cosby, R; Driedger, A

    2009-09-01

    Standard treatment for differentiated thyroid cancer is thyroidectomy followed in selected cases by radioiodine ablation (RA). Recombinant humanized thyroid-stimulating hormone (rhTSH) is an exogenous source of tsh that can be administered to obviate the need for hormone withdrawal. In this systematic review, we analysed the evidence for the therapeutic use of (rhTSH for RA preparation. A systematic review of the MEDLINE and EMBASE databases from 1996 through January 2008 selected articles reporting randomized controlled trials, cohort studies, and retrospective studies published in English that compared ra using rhTSH with standard hormone withdrawal. Stimulation by rhTSH is equivalent to thyroid hormone withdrawal in achieving ablation while avoiding detrimental symptoms of hypothyroidism and significantly lowering the whole-body radiation dose. Furthermore, rhTSH may be the only option for patients who either cannot raise endogenous tsh or who would be at risk from the morbidity of hypothyroidism. Based on the results of validated instruments of physical and mental performance, there is agreement that rhTSH maintains a better quality of life. Studies of cost-effectiveness found that rhTSH-prepared patients lost less time from work and required fewer encounters with health care providers.

  17. Structure-activity relations in binding of perfluoroalkyl compounds to human thyroid hormone T3 receptor.

    Science.gov (United States)

    Ren, Xiao-Min; Zhang, Yin-Feng; Guo, Liang-Hong; Qin, Zhan-Fen; Lv, Qi-Yan; Zhang, Lian-Ying

    2015-02-01

    Perfluoroalkyl compounds (PFCs) have been shown to disrupt thyroid functions through thyroid hormone receptor (TR)-mediated pathways, but direct binding of PFCs with TR has not been demonstrated. We investigated the binding interactions of 16 structurally diverse PFCs with human TR, their activities on TR in cells, and the activity of perfluorooctane sulfonate (PFOS) in vivo. In fluorescence competitive binding assays, most of the 16 PFCs were found to bind to TR with relative binding potency in the range of 0.0003-0.05 compared with triiodothyronine (T3). A structure-binding relationship for PFCs was observed, where fluorinated alkyl chain length longer than ten, and an acid end group were optimal for TR binding. In thyroid hormone (TH)-responsive cell proliferation assays, PFOS, perfluorohexadecanoic acid, and perfluorooctadecanoic acid exhibited agonistic activity by promoting cell growth. Furthermore, similar to T3, PFOS exposure promoted expression of three TH upregulated genes and inhibited three TH downregulated genes in amphibians. Molecular docking analysis revealed that most of the tested PFCs efficiently fit into the T3-binding pocket in TR and formed a hydrogen bond with arginine 228 in a manner similar to T3. The combined in vitro, in vivo, and computational data strongly suggest that some PFCs disrupt the normal activity of TR pathways by directly binding to TR.

  18. Thyroid hormone effect on human mitochondria measured by flow cytometry

    DEFF Research Database (Denmark)

    Kvetny, Jan; Bomholt, Tobias; Pedersen, Palle

    2009-01-01

    BACKGROUND: Mitochondrial function may be impaired in a number of diseases including metabolic syndrome, cardiovascular disease and endocrine disorders. Therefore it is important to be able to measure mitochondrial function in human cells. PURPOSE: The aim of the present study was to evaluate a m...

  19. Bilateral Thyroid and Ultimobranchial Medullary Carcinoma.

    Science.gov (United States)

    Patey, Martine; Flament, Jean Bernard; Caron, Jean; Delisle, Marie Joelle; Delemer, Brigitte; Pluot, Michel

    1996-01-01

    The ultimobranchial bodies in human embryos develop from the fourth and fifth branchial pouch complexes along with thymic and parathyroid tissue. They become incorporated within the lateral thyroid lobes and are believed to be involved in the development of C-cells. We report a case of an unusual bilateral thyroid and neck prelaryngeal medullary carcinoma in a 23-year-old male patient who belongs to a multiple endocrine neoplasia type 2a (MEN type 2a) family with thyroid tumors and pheochromocytomas. The medullary carcinoma was located in an abnormal cystic structure that seems to be a remnant of the ultimobranchial body (UBB) in the neck. Within the contralateral thyroid lobe, the medullary carcinoma was associated with C-cell hyperplasia.

  20. Recombinant human erythropoietin alpha improves the efficacy of radiotherapy of a human tumor xenograft, affecting tumor cells and microvessels

    Energy Technology Data Exchange (ETDEWEB)

    Loevey, J. [Dept. of Radiotherapy, National Inst. of Oncology, Budapest (Hungary); Bereczky, B.; Gilly, R.; Kenessey, I.; Raso, E.; Simon, E.; Timar, J. [Dept. of Tumor Progression, National Inst. of Oncology, Budapest (Hungary); Dobos, J. [Dept. of Tumor Progression, National Inst. of Oncology, Budapest (Hungary); National Koranyi Inst. of TBC and Pulmonology, Budapest (Hungary); Vago, A. [Central Lab., National Inst. of Oncology, Budapest (Hungary); Kasler, M. [Head and Neck Surgery, National Inst. of Oncology, Budapest (Hungary); Doeme, B. [National Koranyi Inst. of TBC and Pulmonology, Budapest (Hungary); Tovari, J. [National Koranyi Inst. of TBC and Pulmonology, Budapest (Hungary); 1. Inst. of Pathology and Experimental Cancer Research, Semmelweis Univ., Budapest (Hungary)

    2008-01-15

    Background and purpose: tumor-induced anemia often occurs in cancer patients, and is corrected by recombinant human erythropoietins (rHuEPOs). Recent studies indicated that, besides erythroid progenitor cells, tumor and endothelial cells express erythropoietin receptor (EPOR) as well; therefore, rHuEPO may affect their functions. Here, the effect of rHuEPO{alpha} on irradiation in EPOR-positive human squamous cell carcinoma xenograft was tested. Material and methods: A431 tumor-bearing SCID mice were treated from the tumor implantation with rHuEPO{alpha} at human-equivalent dose. Xenografts were irradiated (5 Gy) on day 14, and the final tumor mass was measured on day 22. The systemic effects of rHuEPO{alpha} on the hemoglobin level, on tumor-associated blood vessels and on hypoxia-inducible factor-(HIF-)1{alpha} expression of the tumor xenografts were monitored. The proliferation, apoptosis and clonogenic capacity of A431 cancer cells treated with rHuEPO{alpha} and irradiation were also tested in vitro. Results: in vitro, rHuEPO{alpha} treatment alone did not modify the proliferation of EPOR-positive A431 tumor cells but enhanced the effect of irradiation on proliferation, apoptosis and clonogenic capacity. In vivo, rHuEPO{alpha} administration compensated the tumor-induced anemia in SCID mice and decreased tumoral HIF-1{alpha} expression but had no effect on tumor growth. At the same time rHuEPO{alpha} treatment significantly increased the efficacy of radiotherapy in vivo (tumor weight of 23.9 {+-} 4.7 mg and 34.9 {+-} 4.6 mg, respectively), mediated by increased tumoral blood vessel destruction. Conclusion: rHuEPO{alpha} treatment may modulate the efficacy of cancer radiotherapy not only by reducing systemic hypoxia and tumoral HIF-1{alpha} expression, but also by destroying tumoral vessels. (orig.)

  1. The intensity of 18FDG uptake does not predict tumor growth in patients with metastatic differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Terroir, Marie; Dercle, Laurent; Lumbroso, Jean; Baudin, Eric; Berdelou, Amandine; Deandreis, Desiree; Schlumberger, Martin; Leboulleux, Sophie [Gustave Roussy and Universite Paris Saclay, Department of Nuclear Medicine and Endocrine Oncology, Villejuif (France); Borget, Isabelle [University Paris Sud, Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif (France); Bidault, Francois [Gustave Roussy, Department of Radiology, Villejuif (France); Ricard, Marcel [Gustave Roussy, Department of Physic, Villejuif (France); Deschamps, Frederic; Tselikas, Lambros [Department of Interventional Radiology, Villejuif (France); Hartl, Dana [Gustave Roussy, Department of Surgery, Villejuif (France)

    2017-04-15

    In patients with metastatic differentiated thyroid carcinoma (DTC), fluorodeoxyglucose (FDG) uptake as well as age, tumor size and radioactive iodine (RAI) uptake are prognostic factors for survival. High FDG uptake is a poor prognostic factor and lesions with high FDG uptake are often considered aggressive, but the predictive value of FDG uptake for morphological progression is unknown. The principal aim of this retrospective single center study was to determine whether the intensity of FDG uptake was correlated on a per lesion analysis with tumor growth rate (TGR) expressed as the percentage of increase in tumor size during 1 year (1-year TGR). Fifty five patients with DTC were included between July 2012 and May 2014 with the following criteria: (i) at least one distant metastasis measuring ≥ 1 cm in diameter on CT scan (ii) evaluation by FDG-positron emission tomography/computed tomography (PET/CT) performed at our center (iii) at least one CT or another FDG-PET/CT performed 3 to 12 months after the reference FDG-PET/CT in the absence of systemic or local treatment between the two imaging procedures. One hundred and fifty-six metastatic lesions located in lungs (63), neck lymph nodes (28), chest lymph nodes (42), bone (11), liver (2) and other sites (12) were studied. The median size was 16 mm, median SUVmax/lesion: 8.7; median metabolic tumor volume/lesion (Metab.TV/lesion): 3.7 cm{sup 3}. The median 1-year TGR was 40.68 %. SUVmax and Metab.TV/lesion were not correlated to their 1-year TGR (p = 0.38 and p = 0.74 respectively). Among single patients with multiple lesions, the lesions with the highest SUVmax/lesion or the highest Metab.TV/lesion did not disclose the higher 1-year TGR. The intensity of FDG uptake on a per lesion analysis is not correlated to its 1-year TGR and cannot be used as a surrogate marker of tumour progression. (orig.)

  2. Diagnosis of Malignancy in Thyroid Tumors by Multi-Layer Perceptron Neural Networks With Different Batch Learning Algorithms.

    Science.gov (United States)

    Pourahmad, Saeedeh; Azad, Mohsen; Paydar, Shahram

    2015-03-30

    To diagnose the malignancy in thyroid tumor, neural network approach is applied and the performances of thirteen batch learning algorithms are investigated on accuracy of the prediction. Therefore, a back propagation feed forward neural networks (BP FNNs) is designed and three different numbers of neuron in hidden layer are compared (5, 10 and 20 neurons). The pathology result after the surgery and clinical findings before surgery of the patients are used as the target outputs and the inputs, respectively. The best algorithm(s) is/are chosen based on mean or maximum accuracy values in the prediction and also area under Receiver Operating Characteristic Curve (ROC curve). The results show superiority of the network with 5 neurons in the hidden layer. In addition, the better performances are occurred for Polak-Ribiere conjugate gradient, BFGS quasi-newton and one step secant algorithms according to their accuracy percentage in prediction (83%) and for Scaled Conjugate Gradient and BFGS quasi-Newton based on their area under the ROC curve (0.905).

  3. Stereology of the thyroid gland in Indo-Pacific bottlenose dolphin (Tursiops aduncus) in comparison with human (Homo sapiens): quantitative and functional implications.

    Science.gov (United States)

    Kot, Brian Chin Wing; Lau, Thomas Yue Huen; Cheng, Sammy Chi Him

    2013-01-01

    The mammalian thyroid gland maintains basal metabolism in tissues for optimal function. Determining thyroid volume is important in assessing growth and involution. Volume estimation is also important in stereological studies. Direct measurements of colloid volume and nuclear-to-cytoplasmic ratio of the follicular cells may provide important information about thyroid gland function such as hormone storage and secretion, which helps understand the changes at morphological and functional levels. The present study determined the colloid volume using simple stereological principle and the nuclear-to-cytoplasmic ratio of 4 Indo-Pacific bottlenose dolphins and 2 human thyroid glands. In both dolphin and human thyroid glands, the size of the follicles tended to be quite variable. The distribution of large and small follicles within the thyroid gland was also found to be random in both the dolphin and human thyroid gland; however, the size of follicles appeared to decrease as a function of increasing age in the dolphin thyroid gland. The mean colloid volume of the dolphin thyroid gland and human thyroid gland was 1.22×10(5) µm(3) and 7.02×10(5) µm(3) respectively. The dolphin and human subjects had a significant difference in the mean colloid volume. The mean N/C ratio of the dolphin thyroid follicular epithelia and human follicular epithelia was 0.50 and 0.64 respectively. The dolphin and human subjects had a significant difference in the mean N/C ratio. This information contributes to understanding dolphin thyroid physiology and its structural adaptations to meet the physical demands of the aquatic environment, and aids with ultrasonography and corrective therapy in live subjects.

  4. Stereology of the thyroid gland in Indo-Pacific bottlenose dolphin (Tursiops aduncus in comparison with human (Homo sapiens: quantitative and functional implications.

    Directory of Open Access Journals (Sweden)

    Brian Chin Wing Kot

    Full Text Available The mammalian thyroid gland maintains basal metabolism in tissues for optimal function. Determining thyroid volume is important in assessing growth and involution. Volume estimation is also important in stereological studies. Direct measurements of colloid volume and nuclear-to-cytoplasmic ratio of the follicular cells may provide important information about thyroid gland function such as hormone storage and secretion, which helps understand the changes at morphological and functional levels. The present study determined the colloid volume using simple stereological principle and the nuclear-to-cytoplasmic ratio of 4 Indo-Pacific bottlenose dolphins and 2 human thyroid glands. In both dolphin and human thyroid glands, the size of the follicles tended to be quite variable. The distribution of large and small follicles within the thyroid gland was also found to be random in both the dolphin and human thyroid gland; however, the size of follicles appeared to decrease as a function of increasing age in the dolphin thyroid gland. The mean colloid volume of the dolphin thyroid gland and human thyroid gland was 1.22×10(5 µm(3 and 7.02×10(5 µm(3 respectively. The dolphin and human subjects had a significant difference in the mean colloid volume. The mean N/C ratio of the dolphin thyroid follicular epithelia and human follicular epithelia was 0.50 and 0.64 respectively. The dolphin and human subjects had a significant difference in the mean N/C ratio. This information contributes to understanding dolphin thyroid physiology and its structural adaptations to meet the physical demands of the aquatic environment, and aids with ultrasonography and corrective therapy in live subjects.

  5. The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAFV600E-Positive Papillary and Anaplastic Thyroid Carcinoma

    Science.gov (United States)

    Vanden Borre, Pierre; McFadden, David G.; Gunda, Viswanath; Sadow, Peter M.; Varmeh, Shohreh; Bernasconi, Maria; Jacks, Tyler

    2014-01-01

    Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. Methods: We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous BrafV600E/WT and deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Results: Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. Conclusions: We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This

  6. Abnormal number cell division of human thyroid anaplastic carcinoma cell line, SW 1736

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2015-12-01

    Full Text Available Cell division, during which a mother cell usually divides into two daughter cells during one cell cycle, is the most important physiological event of cell biology. We observed one-to-four cell division during imaging of live SW1736 human thyroid anaplastic carcinoma cells transfected with a plasmid expressing the hybrid protein of green fluorescent protein and histone 2B (plasmid eGFP-H2B. Analysis of the images revealed a mother cell divided into four daughter cells. And one of the abnormally divided daughter cells subsequently formed a dinucleate cell.

  7. Preoperative calcitonin levels are predictive of tumor size and postoperative calcitonin normalization in medullary thyroid carcinoma. Groupe d'Etudes des Tumeurs a Calcitonine (GETC).

    Science.gov (United States)

    Cohen, R; Campos, J M; Salaün, C; Heshmati, H M; Kraimps, J L; Proye, C; Sarfati, E; Henry, J F; Niccoli-Sire, P; Modigliani, E

    2000-02-01

    Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-secreting endocrine tumor. Although plasma CT level is a specific and sensitive marker of MTC, its preoperative usefulness in predicting tumor size and postoperative CT normalization has not been documented. From a nationwide database set up by the French CT Tumor Study Group, 226 MTC patients were selected according to the following criteria: preoperative CT level determination by an immunoradiometric assay (normal value, normalization was ascertained by negative response of CT to pentagastrin stimulation (forms (15.0 vs. 7.0 mm, P forms. Furthermore, preoperative CT levels under 50 pg/mL appeared to be predictive of postoperative CT normalization (44 of 45 patients). However, higher CT levels did not mean absence of postoperative CT normalization (50 of 120 patients). We conclude that low preoperative CT levels are predictive of tumor size and postoperative CT normalization.

  8. Thyroid Lobectomy Is Associated with Excellent Clinical Outcomes in Properly Selected Differentiated Thyroid Cancer Patients with Primary Tumors Greater Than 1 cm

    Directory of Open Access Journals (Sweden)

    Fernanda Vaisman

    2013-01-01

    Full Text Available Background and Objective. An individualized risk-based approach to the treatment of thyroid cancer is being extensively discussed in the recent literature. However, controversies about the ideal surgical approach remain an important issue with regard to the impact on prognosis and follow-up strategies. This study was designed to describe clinical outcomes in a cohort of low and intermediate risk thyroid cancer patients treated with thyroid lobectomy. Methods. Retrospective review of 70 patients who underwent lobectomy. Results. After a median follow-up of 11 years, 5 patients (5/70, 7.1% recurred and 5 had a completion for benign lesions, while 60 patients (86% continued to be observed without evidence for disease recurrence. Suspicious ultrasound findings were significantly more common in patients that had structural disease recurrence (100% versus 4.3%, P<0.001. Furthermore, a rising suppressed Tg value over time was also associated with structural disease recurrence (80% versus 21.5%, P=0.01. After additional therapy, 99% of the patients had no evidence of disease. Conclusions. Properly selected thyroid cancer patients can be treated with lobectomy with excellent clinical outcomes.

  9. Developing a xenograft human tumor model in immunocompetent mice.

    Science.gov (United States)

    Basel, Matthew T; Narayanan, Sanjeev; Ganta, Chanran; Shreshta, Tej B; Marquez, Alejandro; Pyle, Marla; Hill, Jennifer; Bossmann, Stefan H; Troyer, Deryl L

    2018-01-01

    Animal models are essential to cancer research, but current xenograft models are limited in their utility especially due to the lack of an immune system. Here we demonstrate that a xenograft tumor model can be developed in immunocompetent mice by tolerizing murine fetuses to human tumor cells. A375 human melanoma cells were injected into day E14 fetuses and after birth mice were challenged with A375 cells to determine their ability to develop tumors. Intravenous injections of cells resulted in metastatic-like lung tumors, which were verified to be human in origin by immunohistochemistry and PCR. These results were replicated with several other human tumor types: BxPC3 (human pancreatic adenocarcinoma), MDA-MB-231 (human breast adenocarcinoma), M21 (human melanoma), and HeLa (human cervical adenocarcinoma). Development of an immunocompetent xenograft tumor model would allow the further elucidation of the interaction of the immune system with therapy in both preclinical research and patient derived xenografts. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Tumor endothelial inflammation predicts clinical outcome in diverse human cancers.

    Directory of Open Access Journals (Sweden)

    Sean P Pitroda

    Full Text Available Vascular endothelial cells contribute to the pathogenesis of numerous human diseases by actively regulating the stromal inflammatory response; however, little is known regarding the role of endothelial inflammation in the growth of human tumors and its influence on the prognosis of human cancers.Using an experimental model of tumor necrosis factor-alpha (TNF-α-mediated inflammation, we characterized inflammatory gene expression in immunopurified tumor-associated endothelial cells. These genes formed the basis of a multivariate molecular predictor of overall survival that was trained and validated in four types of human cancer.We report that expression of experimentally derived tumor endothelial genes distinguished pathologic tissue specimens from normal controls in several human diseases associated with chronic inflammation. We trained these genes in human cancer datasets and defined a six-gene inflammatory signature that predicted significantly reduced overall survival in breast cancer, colon cancer, lung cancer, and glioma. This endothelial-derived signature predicted outcome independently of, but cooperatively with, standard clinical and pathological prognostic factors. Consistent with these findings, conditioned culture media from human endothelial cells stimulated by pro-inflammatory cytokines accelerated the growth of human colon and breast tumors in immunodeficient mice as compared with conditioned media from untreated endothelial cells.This study provides the first prognostic cancer gene signature derived from an experimental model of tumor-associated endothelial inflammation. These findings support the notion that activation of inflammatory pathways in non-malignant tumor-infiltrating endothelial cells contributes to tumor growth and progression in multiple human cancers. Importantly, these results identify endothelial-derived factors that could serve as potential targets for therapy in diverse human cancers.

  11. Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions

    Directory of Open Access Journals (Sweden)

    Eleftheria Lakiotaki

    2015-01-01

    Full Text Available The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2, their endogenous ligands (endocannabinoids, and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions. CB1 and CB2 proteins’ expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 87 patients with benign (n=43 and malignant (n=44 lesions and was statistically analyzed with clinicopathological parameters, follicular cells’ proliferative capacity, and risk of recurrence rate estimated according to the American Thyroid Association (ATA staging system. Enhanced CB1 and CB2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p=0.0010 and p=0.0005, resp.. Enhanced CB1 and CB2 expression was also significantly more frequently observed in papillary carcinomas compared to hyperplastic nodules (p=0.0097 and p=0.0110, resp.. In malignant thyroid lesions, elevated CB2 expression was significantly associated with the presence of lymph node metastases (p=0.0301. Enhanced CB2 expression was also more frequently observed in malignant thyroid cases with presence of capsular (p=0.1165, lymphatic (p=0.1989, and vascular invasion (p=0.0555, as well as in those with increased risk of recurrence rate (p=0.1165, at a nonsignificant level though, whereas CB1 expression was not associated with any of the clinicopathological parameters examined. Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia.

  12. Synergistic Signaling of KRAS and Thyroid Hormone Receptor β Mutants Promotes Undifferentiated Thyroid Cancer through MYC Up-Regulation

    Directory of Open Access Journals (Sweden)

    Xuguang Zhu

    2014-09-01

    Full Text Available Undifferentiated thyroid carcinoma is one of the most aggressive human cancers with frequent RAS mutations. How mutations of the RAS gene contribute to undifferentiated thyroid cancer remains largely unknown. Mice harboring a potent dominant negative mutant thyroid hormone receptor β, TRβPV (ThrbPV/PV, spontaneously develop well-differentiated follicular thyroid cancer similar to human cancer. We genetically targeted the KrasG12D mutation to thyroid epithelial cells of ThrbPV/PV mice to understand how KrasG12D mutation could induce undifferentiated thyroid cancer in ThrbPV/PVKrasG12D mice. ThrbPV/PVKrasG12D mice exhibited poorer survival due to more aggressive thyroid tumors with capsular invasion, vascular invasion, and distant metastases to the lung occurring at an earlier age and at a higher frequency than ThrbPV/PV mice did. Importantly, ThrbPV/PVKrasG12D mice developed frequent anaplastic foci with complete loss of normal thyroid follicular morphology. Within the anaplastic foci, the thyroid-specific transcription factor paired box gene 8 (PAX8 expression was virtually lost and the loss of PAX8 expression was inversely correlated with elevated MYC expression. Consistently, co-expression of KRASG12D with TRβPV upregulated MYC levels in rat thyroid pccl3 cells, and MYC acted to enhance the TRβPV-mediated repression of the Pax8 promoter activity of a distant upstream enhancer, critical for thyroid-specific Pax8 expression. Our findings indicated that synergistic signaling of KRASG12D and TRβPV led to increased MYC expression. Upregulated MYC contributes to the initiation of undifferentiated thyroid cancer, in part, through enhancing TRβPV-mediated repression of the Pax8 expression. Thus, MYC might serve as a potential target for therapeutic intervention.

  13. Human recombinant anti-thyroperoxidase autoantibodies: in vitro cytotoxic activity on papillary thyroid cancer expressing TPO.

    Science.gov (United States)

    Rebuffat, S A; Morin, M; Nguyen, B; Castex, F; Robert, B; Péraldi-Roux, S

    2010-03-02

    Thyroid cancers are difficult to treat due to their limited responsiveness to chemo- and radiotherapy. There is thus a great interest in and a need for alternative therapeutic approaches. We studied the cytotoxic activity of anti-thyroperoxidase autoantibodies (anti-TPO aAbs, expressed in baculovirus/insect cell (B4) and CHO cells (B4') or purified from patients' sera) against a papillary thyroid cancer (NPA) cell line. Anti-TPO aAbs from patients' sera led to a partial destruction of NPA cell line by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) and exhibited an anti-proliferative activity. Comparison of the cytotoxic activity of anti-TPO aAbs shows that B4' induced an anti-proliferative effect and a better ADCC than B4, but a lower one than anti-TPO aAbs from patients' sera. Antibody-dependent cell-mediated cytotoxicity was increased when human peripheral blood mononuclear cells were used as effector cells, suggesting that FcgammaRs, CD64, CD32 and CD16 are involved. Indeed, anti-TPO aAbs from patients' sera, but not B4 and B4', exhibited CDC activity. These data indicate that anti-TPO aAbs display moderate ADCC and anti-proliferative activities on NPA cells; IgG glycosylation appears to be important for cytotoxic activity and ADCC efficiency depends on FcgammaR-bearing cells. Finally, recombinant human anti-TPO aAbs cannot yet be considered as an optimal tool for the development of a novel therapeutic approach for thyroid cancer.

  14. Thyroid storm

    Science.gov (United States)

    Thyrotoxic storm; Hyperthyroid storm; Accelerated hyperthyroidism; Thyroid crisis; Thyrotoxicosis - thyroid storm ... Thyroid storm occurs due to a major stress such as trauma, heart attack , or infection. In rare ...

  15. Fetal microchimerism in human brain tumors.

    Science.gov (United States)

    Broestl, Lauren; Rubin, Joshua B; Dahiya, Sonika

    2017-09-18

    Sex differences in cancer incidence and survival, including central nervous system tumors, are well documented. Multiple mechanisms contribute to sex differences in health and disease. Recently, the presence of fetal-in-maternal microchimeric cells has been shown to have prognostic significance in breast and colorectal cancers. The frequency and potential role of these cells has not been investigated in brain tumors. We therefore selected two common primary adult brain tumors for this purpose: meningioma, which is sex hormone responsive and has a higher incidence in women, and glioblastoma, which is sex hormone independent and occurs more commonly in men. Quantitative PCR was used to detect the presence of male DNA in tumor samples from women with a positive history of male pregnancy and a diagnosis of either glioblastoma or meningioma. Fluorescence in situ hybridization for the X and Y chromosomes was used to verify the existence of intact male cells within tumor tissue. Fetal microchimerism was found in approximately 80% of glioblastoma cases and 50% of meningioma cases. No correlations were identified between the presence of microchimerism and commonly used clinical or molecular diagnostic features of disease. The impact of fetal microchimeric cells should be evaluated prospectively. © 2017 International Society of Neuropathology.

  16. A Redundant Role of Human Thyroid Peroxidase Propeptide for Cellular, Enzymatic, and Immunological Activity

    OpenAIRE

    Godlewska, Marlena; Góra, Monika; Buckle, Ashley M.; Porebski, Benjamin T.; Kemp, E. Helen; Sutton, Brian J.; Czarnocka, Barbara; Banga, J. Paul

    2014-01-01

    Background: Thyroid peroxidase (TPO) is a dimeric membrane-bound enzyme of thyroid follicular cells, responsible for thyroid hormone biosynthesis. TPO is also a common target antigen in autoimmune thyroid disease (AITD). With two active sites, TPO is an unusual enzyme, and thus there is much interest in understanding its structure and role in AITD. Homology modeling has shown TPO to be composed of different structural modules, as well as a propeptide sequence. During the course of studies to ...

  17. Tumor-derived exosomes elicit tumor suppression in murine hepatocellular carcinoma models and humans in vitro.

    Science.gov (United States)

    Rao, Quan; Zuo, Bingfeng; Lu, Zhen; Gao, Xianjun; You, Abin; Wu, Chenxuan; Du, Zhi; Yin, HaiFang

    2016-08-01

    Hepatocellular carcinoma (HCC) remains a global challenge due to high morbidity and mortality rates and poor response to treatment. Immunotherapy, based on introduction of dendritic cells (DCs) activated by tumor cell lysates as antigens ex vivo, shows limited response rates in HCC patients. Here, we demonstrate that tumor cell-derived exosomes (TEXs), displaying an array of HCC antigens, can elicit a stronger immune response than cell lysates in vitro and in vivo. Significant tumor growth inhibition was achieved in ectopic and orthotopic HCC mice treated with TEX-pulsed DCs. Importantly, the tumor immune microenvironment was significantly improved in orthotopic HCC mice treated by TEX-pulsed DCs, demonstrated by increased numbers of T lymphocytes, elevated levels of interferon-γ, and decreased levels of interleukin-10 and tumor growth factor-β in tumor sites. As expected, T cells played an essential role in the TEX-pulsed DC-mediated immune response. Notably, exosomes from HCC cells not only promoted HCC-specific cytolysis but also provided cross-protective effects against pancreatic cancer cells. Moreover, HCC-specific cytolysis, elicited by DCs pulsed with human HepG2 cell-derived exosomes, was observed across different human HCC cells irrespective of human leukocyte antigen types. HCC TEXs can potently carry HCC antigens, trigger a strong DC-mediated immune response, and improve the HCC tumor microenvironment. (Hepatology 2016;64:456-472). © 2016 by the American Association for the Study of Liver Diseases.

  18. Infrared Spectra of Human Breast Tumor Tissue and Experimental Animal Tumors

    Science.gov (United States)

    Tolstorozhev, G. B.; Belkov, M. V.; Skornyakov, I. V.; Pekhnyo, V. I.; Kozachkova, A. N.; Tsarik, H. V.; Kutsenko, I. P.; Sharykina, N. I.; Butra, V. A.

    2015-01-01

    We have used Fourier transform IR spectroscopy methods to conduct comparative studies of human breast tumors and sarcoma 180 tumor grafted into mice. The IR spectral parameters used to identify tumor tissue in mice with the sarcoma 180 strain proved to be identical to the parameters for human breast tissue in cancer. In the presence of a malignant tumor in humans, the most intense C=O vibrational bands in the protein molecules are observed in the interval 1710-1680 cm-1. For a benign tumor, in the IR spectra of breast tissue the intense bands are located in the interval 1670-1650 cm-1. We spectroscopically monitored the diagnosis and the chemotherapy process using the model of sarcoma 180 in mice. As the therapeutic drugs, we used synthesized coordination compounds based on palladium complexes with diphosphonic acid derivatives. We demonstrate the promising potential of palladium complexes with zoledronic acid as an effective cytostatic. In therapy using a palladium complex with zoledronic acid, the effect of tumor growth inhibition is accompanied by a change in its spectral characteristics. The parameters of the IR spectra for tumor tissue after treatment are close to those of the IR spectra for healthy tissue.

  19. Thyroid Nodules

    Science.gov (United States)

    ... Endocrinologist Search Featured Resource New Mobile App DOWNLOAD Thyroid Nodules September 2017 Download PDFs English Espanol Hindi ... Resources Mayo Clinic American Thyroid Association What are thyroid nodules and who is at risk? A thyroid ...

  20. Thyroid Antibodies

    Science.gov (United States)

    ... Fungal Infections Gout Graves Disease Guillain-Barré Syndrome Hashimoto Thyroiditis Heart Attack and Acute Coronary Syndrome Heart ... hypothyroidism or hyperthyroidism , such as Graves disease or Hashimoto thyroiditis . Thyroid antibody tests include: Thyroid peroxidase antibody ( ...

  1. Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases

    Science.gov (United States)

    Fröhlich, Eleonore; Wahl, Richard

    2017-01-01

    Autoimmune diseases have a high prevalence in the population, and autoimmune thyroid disease (AITD) is one of the most common representatives. Thyroid autoantibodies are not only frequently detected in patients with AITD but also in subjects without manifest thyroid dysfunction. The high prevalence raises questions regarding a potential role in extra-thyroidal diseases. This review summarizes the etiology and mechanism of AITD and addresses prevalence of antibodies against thyroid peroxidase, thyroid-stimulating hormone receptor (TSHR), and anti-thyroglobulin and their action outside the thyroid. The main issues limiting the reliability of the conclusions drawn here include problems with different specificities and sensitivities of the antibody detection assays employed, as well as potential confounding effects of altered thyroid hormone levels, and lack of prospective studies. In addition to the well-known effects of TSHR antibodies on fibroblasts in Graves’ disease (GD), studies speculate on a role of anti-thyroid antibodies in cancer. All antibodies may have a tumor-promoting role in breast cancer carcinogenesis despite anti-thyroid peroxidase antibodies having a positive prognostic effect in patients with overt disease. Cross-reactivity with lactoperoxidase leading to induction of chronic inflammation might promote breast cancer, while anti-thyroid antibodies in manifest breast cancer might be an indication for a more active immune system. A better general health condition in older women with anti-thyroid peroxidase antibodies might support this hypothesis. The different actions of the anti-thyroid antibodies correspond to differences in cellular location of the antigens, titers of the circulating antibodies, duration of antibody exposure, and immunological mechanisms in GD and Hashimoto’s thyroiditis. PMID:28536577

  2. Relation between Irofulven (MGI-114) systemic exposure and tumor response in human solid tumor xenografts.

    Science.gov (United States)

    Leggas, Markos; Stewart, Clinton F; Woo, Michael H; Fouladi, Maryam; Cheshire, Pamela J; Peterson, Jennifer K; Friedman, Henry S; Billups, Catherine; Houghton, Peter J

    2002-09-01

    Irofulven is a novel, small molecular weight semisynthetic compound, derived from a family of mushroom toxins known as illudins. This DNA alkylating agent has a chemical structure unlike any other chemotherapeutic agent in clinical use. The molecule is currently being studied in several Phase I, II, and III trials. The objectives of this study were to evaluate the antitumor activity of Irofulven in a panel of 20 pediatric solid tumor xenografts and to relate the Irofulven systemic exposure, defined as area under the concentration time curve, to the antitumor dose associated with tumor regression in the tumor models. Irofulven was administered i.v. daily for 5 days with courses repeated every 21 days for a total of three cycles. The minimum effective dose of Irofulven causing objective regression (> or =50% volume regression) of advanced tumors was determined for each of 19 of 20 independently derived tumor models (12 brain tumors, 4 neuroblastomas, and 4 rhabdomyosarcomas). At the maximum tolerated dose for three cycles of treatment (4.6 mg/kg/day) objective regressions were determined in 14 of 18 tumor lines (78%). However, the dose-response relationship was acute. At 2 mg/kg only 3 of 15 tumors tested demonstrated objective regressions, and in 3 additional tumors volume regressions were not achieved at a higher dose level (3 mg/kg), hence were not additionally tested. After administering the maximum tolerated dose (tolerated for one or two cycles of treatment) of Irofulven, 7 mg/kg, to mice bearing sensitive and resistant human tumors plasma concentration-time profiles were determined. Tumors were highly sensitive to Irofulven, but the systemic exposure required for a significant rate of objective response in this panel of tumors is in excess of that achievable in patients at tolerable doses, using this schedule of drug administration.

  3. Strategy to find molecular signatures in a small series of rare cancers: validation for radiation-induced breast and thyroid tumors.

    Science.gov (United States)

    Ugolin, Nicolas; Ory, Catherine; Lefevre, Emilie; Benhabiles, Nora; Hofman, Paul; Schlumberger, Martin; Chevillard, Sylvie

    2011-01-01

    Methods of classification using transcriptome analysis for case-by-case tumor diagnosis could be limited by tumor heterogeneity and masked information in the gene expression profiles, especially as the number of tumors is small. We propose a new strategy, EMts_2PCA, based on: 1) The identification of a gene expression signature with a great potential for discriminating subgroups of tumors (EMts stage), which includes: a) a learning step, based on an expectation-maximization (EM) algorithm, to select sets of candidate genes whose expressions discriminate two subgroups, b) a training step to select from the sets of candidate genes those with the highest potential to classify training tumors, c) the compilation of genes selected during the training step, and standardization of their levels of expression to finalize the signature. 2) The predictive classification of independent prospective tumors, according to the two subgroups of interest, by the definition of a validation space based on a two-step principal component analysis (2PCA). The present method was evaluated by classifying three series of tumors and its robustness, in terms of tumor clustering and prediction, was further compared with that of three classification methods (Gene expression bar code, Top-scoring pair(s) and a PCA-based method). Results showed that EMts_2PCA was very efficient in tumor classification and prediction, with scores always better that those obtained by the most common methods of tumor clustering. Specifically, EMts_2PCA permitted identification of highly discriminating molecular signatures to differentiate post-Chernobyl thyroid or post-radiotherapy breast tumors from their sporadic counterparts that were previously unsuccessfully classified or classified with errors.

  4. Strategy to find molecular signatures in a small series of rare cancers: validation for radiation-induced breast and thyroid tumors.

    Directory of Open Access Journals (Sweden)

    Nicolas Ugolin

    Full Text Available Methods of classification using transcriptome analysis for case-by-case tumor diagnosis could be limited by tumor heterogeneity and masked information in the gene expression profiles, especially as the number of tumors is small. We propose a new strategy, EMts_2PCA, based on: 1 The identification of a gene expression signature with a great potential for discriminating subgroups of tumors (EMts stage, which includes: a a learning step, based on an expectation-maximization (EM algorithm, to select sets of candidate genes whose expressions discriminate two subgroups, b a training step to select from the sets of candidate genes those with the highest potential to classify training tumors, c the compilation of genes selected during the training step, and standardization of their levels of expression to finalize the signature. 2 The predictive classification of independent prospective tumors, according to the two subgroups of interest, by the definition of a validation space based on a two-step principal component analysis (2PCA. The present method was evaluated by classifying three series of tumors and its robustness, in terms of tumor clustering and prediction, was further compared with that of three classification methods (Gene expression bar code, Top-scoring pair(s and a PCA-based method. Results showed that EMts_2PCA was very efficient in tumor classification and prediction, with scores always better that those obtained by the most common methods of tumor clustering. Specifically, EMts_2PCA permitted identification of highly discriminating molecular signatures to differentiate post-Chernobyl thyroid or post-radiotherapy breast tumors from their sporadic counterparts that were previously unsuccessfully classified or classified with errors.

  5. Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene.

    Science.gov (United States)

    Montero-Conde, Cristina; Leandro-Garcia, Luis J; Chen, Xu; Oler, Gisele; Ruiz-Llorente, Sergio; Ryder, Mabel; Landa, Iñigo; Sanchez-Vega, Francisco; La, Konnor; Ghossein, Ronald A; Bajorin, Dean F; Knauf, Jeffrey A; Riordan, Jesse D; Dupuy, Adam J; Fagin, James A

    2017-06-20

    Oncogenic RAS mutations are present in 15-30% of thyroid carcinomas. Endogenous expression of mutant Ras is insufficient to initiate thyroid tumorigenesis in murine models, indicating that additional genetic alterations are required. We used Sleeping Beauty (SB) transposon mutagenesis to identify events that cooperate with Hras(G12V) in thyroid tumor development. Random genomic integration of SB transposons primarily generated loss-of-function events that significantly increased thyroid tumor penetrance in Tpo-Cre/homozygous FR-Hras(G12V) mice. The thyroid tumors closely phenocopied the histological features of human RAS-driven, poorly differentiated thyroid cancers. Characterization of transposon insertion sites in the SB-induced tumors identified 45 recurrently mutated candidate cancer genes. These mutation profiles were remarkably concordant with mutated cancer genes identified in a large series of human poorly differentiated and anaplastic thyroid cancers screened by next-generation sequencing using the MSK-IMPACT panel of cancer genes, which we modified to include all SB candidates. The disrupted genes primarily clustered in chromatin remodeling functional nodes and in the PI3K pathway. ATXN7, a component of a multiprotein complex with histone acetylase activity, scored as a significant SB hit. It was recurrently mutated in advanced human cancers and significantly co-occurred with RAS or NF1 mutations. Expression of ATXN7 mutants cooperated with oncogenic RAS to induce thyroid cell proliferation, pointing to ATXN7 as a previously unrecognized cancer gene.

  6. Effective Cellular Uptake and Efflux of Thyroid Hormone by Human Monocarboxylate Transporter 10

    Science.gov (United States)

    Friesema, Edith C. H.; Jansen, Jurgen; Jachtenberg, Jan-willem; Visser, W. Edward; Kester, Monique H. A.; Visser, Theo J.

    2008-01-01

    Cellular entry of thyroid hormone is mediated by plasma membrane transporters, among others a T-type (aromatic) amino acid transporter. Monocarboxylate transporter 10 (MCT10) has been reported to transport aromatic amino acids but not iodothyronines. Within the MCT family, MCT10 is most homologous to MCT8, which is a very important iodothyronine transporter but does not transport amino acids. In view of this paradox, we decided to reinvestigate the possible transport of thyroid hormone by human (h) MCT10 in comparison with hMCT8. Transfection of COS1 cells with hMCT10 cDNA resulted in 1) the production of an approximately 55 kDa protein located to the plasma membrane as shown by immunoblotting and confocal microscopy, 2) a strong increase in the affinity labeling of intracellular type I deiodinase by N-bromoacetyl-[125I]T3, 3) a marked stimulation of cellular T4 and, particularly, T3 uptake, 4) a significant inhibition of T3 uptake by phenylalanine, tyrosine, and tryptophan of 12.5%, 22.2%, and 51.4%, respectively, and 5) a marked increase in the intracellular deiodination of T4 and T3 by different deiodinases. Cotransfection studies using the cytosolic thyroid hormone-binding protein μ-crystallin (CRYM) indicated that hMCT10 facilitates both cellular uptake and efflux of T4 and T3. In the absence of CRYM, hMCT10 and hMCT8 increased T3 uptake after 5 min incubation up to 4.0- and 1.9-fold, and in the presence of CRYM up to 6.9- and 5.8-fold, respectively. hMCT10 was less active toward T4 than hMCT8. These findings establish that hMCT10 is at least as active a thyroid hormone transporter as hMCT8, and that both transporters facilitate iodothyronine uptake as well as efflux. PMID:18337592

  7. Targeted Radionuclide Therapy of Human Tumors

    Directory of Open Access Journals (Sweden)

    Sergey V. Gudkov

    2015-12-01

    Full Text Available Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

  8. miR-182 targets CHL1 and controls tumor growth and invasion in papillary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Hongling [Department of Endocrine, Shanghai Pudong New Area Gongli Hospital, Shanghai (China); Fang, Jin [Department of Endocrine, The 118th Hospital of Chinese PLA, Wenzhou, Zhejiang (China); Zhang, Jichen; Zhao, Zefei; Liu, Lianyong; Wang, Jingnan; Xi, Qian [Department of Endocrine, Shanghai Pudong New Area Gongli Hospital, Shanghai (China); Gu, Mingjun, E-mail: mjgugonglihos@yeah.net [Department of Endocrine, Shanghai Pudong New Area Gongli Hospital, Shanghai (China)

    2014-07-18

    Highlights: • miR-182 and CHL1 expression patterns are negatively correlated. • CHL1 is a direct target of miR-182 in PTC cells. • miR-182 suppression inhibits PTC cell growth and invasion. • CHL1 is involved in miR-182-mediated cell behavior. - Abstract: In this study, we investigated the role and underlying mechanism of action of miR-182 in papillary thyroid carcinoma (PTC). Bioinformatics analysis revealed close homolog of LI (CHL1) as a potential target of miR-182. Upregulation of miR-182 was significantly correlated with CHL1 downregulation in human PTC tissues and cell lines. miR-182 suppressed the expression of CHL1 mRNA through direct targeting of the 3′-untranslated region (3′-UTR). Downregulation of miR-182 suppressed growth and invasion of PTC cells. Silencing of CHL1 counteracted the effects of miR-182 suppression, while its overexpression mimicked these effects. Our data collectively indicate that miR-182 in PTC promotes cell proliferation and invasion through direct suppression of CHL1, supporting the potential utility of miR-182 inhibition as a novel therapeutic strategy against PTC.

  9. 21 CFR 250.11 - Thyroid-containing drug preparations intended for treatment of obesity in humans.

    Science.gov (United States)

    2010-04-01

    ... laxatives, are being marketed for or as adjuncts to the treatment, control, or management of obesity in... connection with the treatment, control, or management of obesity in patients having normal thyroid function... treatment of obesity in humans. 250.11 Section 250.11 Food and Drugs FOOD AND DRUG ADMINISTRATION...

  10. A Big Bang model of human colorectal tumor growth.

    Science.gov (United States)

    Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng; Graham, Trevor A; Salomon, Matthew P; Zhao, Junsong; Marjoram, Paul; Siegmund, Kimberly; Press, Michael F; Shibata, Darryl; Curtis, Christina

    2015-03-01

    What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications.

  11. A novel pathway regulates thyroid hormone availability in rat and human hypothalamic neurosecretory neurons.

    Directory of Open Access Journals (Sweden)

    Imre Kalló

    Full Text Available Hypothalamic neurosecretory systems are fundamental regulatory circuits influenced by thyroid hormone. Monocarboxylate-transporter-8 (MCT8-mediated uptake of thyroid hormone followed by type 3 deiodinase (D3-catalyzed inactivation represent limiting regulatory factors of neuronal T3 availability. In the present study we addressed the localization and subcellular distribution of D3 and MCT8 in neurosecretory neurons and addressed D3 function in their axons. Intense D3-immunoreactivity was observed in axon varicosities in the external zone of the rat median eminence and the neurohaemal zone of the human infundibulum containing axon terminals of hypophysiotropic parvocellular neurons. Immuno-electronmicroscopy localized D3 to dense-core vesicles in hypophysiotropic axon varicosities. N-STORM-superresolution-microscopy detected the active center containing C-terminus of D3 at the outer surface of these organelles. Double-labeling immunofluorescent confocal microscopy revealed that D3 is present in the majority of GnRH, CRH and GHRH axons but only in a minority of TRH axons, while absent from somatostatin-containing neurons. Bimolecular-Fluorescence-Complementation identified D3 homodimers, a prerequisite for D3 activity, in processes of GT1-7 cells. Furthermore, T3-inducible D3 catalytic activity was detected in the rat median eminence. Triple-labeling immunofluorescence and immuno-electronmicroscopy revealed the presence of MCT8 on the surface of the vast majority of all types of hypophysiotropic terminals. The presence of MCT8 was also demonstrated on the axon terminals in the neurohaemal zone of the human infundibulum. The unexpected role of hypophysiotropic axons in fine-tuned regulation of T3 availability in these cells via MCT8-mediated transport and D3-catalyzed inactivation may represent a novel regulatory core mechanism for metabolism, growth, stress and reproduction in rodents and humans.

  12. Phosphorylethanolamine content of human brain tumors.

    Science.gov (United States)

    Kinoshita, Y; Yokota, A; Koga, Y

    1994-12-01

    Phosphorylethanolamine (PEA) is the major component of the phosphomonoester peak detected by phosphorus-31 magnetic resonance spectroscopy, but the absolute concentration has not been determined. This study measured the PEA concentration in biopsy specimens of brain tumors and lobectomized cerebral cortex using high-performance liquid chromatography. The concentration of PEA was 118.5 +/- 10.0 mumol/100 g wet wt in cortex, and was significantly higher in malignant gliomas, metastatic pulmonary adenocarcinoma, and neurinoma. The concentration of PEA was especially high in pituitary adenoma, malignant lymphoma, and medulloblastoma.

  13. SKI knockdown inhibits human melanoma tumor growth in vivo.

    Science.gov (United States)

    Chen, Dahu; Lin, Qiushi; Box, Neil; Roop, Dennis; Ishii, Shunsuke; Matsuzaki, Koichi; Fan, Tao; Hornyak, Thomas J; Reed, Jon A; Stavnezer, Ed; Timchenko, Nikolai A; Medrano, Estela E

    2009-12-01

    The SKI protein represses the TGF-beta tumor suppressor pathway by associating with the Smad transcription factors. SKI is upregulated in human malignant melanoma tumors in a disease-progression manner and its overexpression promotes proliferation and migration of melanoma cells in vitro. The mechanisms by which SKI antagonizes TGF-beta signaling in vivo have not been fully elucidated. Here we show that human melanoma cells in which endogenous SKI expression was knocked down by RNAi produced minimal orthotopic tumor xenograft nodules that displayed low mitotic rate and prominent apoptosis. These minute tumors exhibited critical signatures of active TGF-beta signaling including high levels of nuclear Smad3 and p21(Waf-1), which are not found in the parental melanomas. To understand how SKI promotes tumor growth we used gain- and loss-of-function approaches and found that simultaneously to blocking the TGF-beta-growth inhibitory pathway, SKI promotes the switch of Smad3 from tumor suppression to oncogenesis by favoring phosphorylations of the Smad3 linker region in melanoma cells but not in normal human melanocytes. In this context, SKI is required for preventing TGF-beta-mediated downregulation of the oncogenic protein c-MYC, and for inducing the plasminogen activator inhibitor-1, a mediator of tumor growth and angiogenesis. Together, the results indicate that SKI exploits multiple regulatory levels of the TGF-beta pathway and its deficiency restores TGF-beta tumor suppressor and apoptotic activities in spite of the likely presence of oncogenic mutations in melanoma tumors.

  14. Application of new therapies in Graves' disease and thyroid-associated ophthalmopathy: animal models and translation to human clinical trialsTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy, of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    Banga, J.P.; Gilbert, J.A.; El, Fassi D.

    2008-01-01

    Most current approaches for treating Graves' disease are based essentially upon regimes developed nearly 50 years ago. Moreover, therapeutic approaches for complications such as thyroid-associated ophthalmopathy (TAO) and dermopathy are singularly dependent on conventional approaches of nonspecific...... immunosuppression. The recent development of an induced model of experimental Graves' disease, although incomplete as it lacks the extrathyroidal manifestations, provided opportunities to investigate immune intervention strategies, including influence upon the autoreactive B and T cell players in the autoimmune...... process. These major advances are generating new possibilities for therapeutic interventions for patients with Graves' disease and TAO Udgivelsesdato: 2008/9...

  15. Tumour dosimetry and response in patients with metastatic differentiated thyroid cancer using recombinant human thyrotropin before radioiodine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Keizer, Bart de; Hoekstra, Anne; Rijk, Peter P. van; Klerk, John M.H. de [Department of Nuclear Medicine, Room E02.222, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht (Netherlands); Brans, Boudewijn; Dierckx, Rudi A. [Department of Nuclear Medicine, Ghent University Hospital, Ghent (Belgium); Zelissen, Pierre M.J.; Koppeschaar, Hans P.F.; Lips, Cees J.M. [Department of Endocrinology, University Medical Center Utrecht (Netherlands)

    2003-03-01

    The development of recombinant human thyrotropin (rhTSH) has given clinicians new options for diagnostic follow-up and treatment of patients with differentiated thyroid cancer (DTC). This paper evaluates the tumour dosimetry and response following -iodine-131 treatment of metastatic thyroid cancer patients after rhTSH stimulation instead of classical hormone withdrawal-induced hypothyroidism. Nineteen consecutive {sup 131}I treatments in 16 patients were performed after rhTSH stimulation. All patients had undergone a near-total thyroidectomy followed by an ablative dosage of {sup 131}I. They all suffered from metastatic or recurrent disease showing tumoral {sup 131}I uptake on previous post-treatment scintigraphy. Dosimetric calculations were performed using {sup 131}I tumour uptake measurements from post-treatment {sup 131}I scintigrams and tumour volume estimations from radiological images. Response was assessed by comparing pre-treatment serum thyroglobulin (Tg) level with the Tg level 3 months post treatment. In 18 out of 19 treatments, uptake of {sup 131}I in metastatic or recurrent lesions was seen. The median tumour radiation dose was 26.3 Gy (range 1.3-368 Gy), and the median effective half-life was 2.7 days (range 0.5-6.5 days). Eleven of 19 treatments (10/16 patients) were evaluable for response after 3 months. {sup 131}I therapy with rhTSH resulted in a biochemical partial response in 3/11 or 27% of treatments (two patients), biochemical stable disease in 2/11 or 18% of treatments and biochemical progressive disease in 6/11 or 55% of treatments. Our study showed that although tumour doses in DTC patients treated with {sup 131}I after rhTSH were highly variable, 45% of treatments led to disease stabilisation or partial remission when using rhTSH in conjunction with {sup 131}I therapy, without serious side-effects and with minimal impact on quality of life. RhTSH is therefore adequately satisfactory as an adjuvant tool in therapeutic settings and is

  16. Somatic mutations of the ret Protooncogene in sporadic medullary thyroid carcinoma are not restricted to exon 16 and are associated with tumor recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Romei, C.; Elisei, R.; Pinchera, A. [Univ. of Pisa (Italy)] [and others

    1996-04-01

    Germline point mutations in exons 10, 11, and 16 of the ret protooncogene have been identified as causative in multiple endocrine neoplasia type 2 and in familial medullary thyroid carcinoma (MTC). Somatic point mutations of the same gene, exclusively associated with codon 918 of exon 16, have also been reported in few cases of sporadic medullary thyroid carcinoma. We analyzed the blood and tumor DNA of 19 patients with sporadic MTC and 6 patients with primary parathyroid adenoma for point mutations at exons 10, 11, and 16 of the ret protooncogene by restriction analysis of the PCR-amplified product and by sequence analysis of exons 10 and 11. A Cys{sup 634}{r_arrow}Tyr mutation was found in both the tumoral and blood DNA of one patient, indicating that he was affected by an hereditary form of MTC, erroneously considered sporadic. In the other 18 patients with MTC, somatic point mutations of ret were found in 8 cases (44.4%). In 5 cases the mutation affected exon 16 (Met{sup 918}{r_arrow}Thr), and in 3 cases it affected exon 11 (Cys{sup 634}{r_arrow}Arg in 1 and Cys{sup 634}{r_arrow}Trp in 2); these 3 mutations were confirmed by sequence analysis. The remaining 10 patients had no mutation in exon 10 by either restriction analysis or sequence analysis. Clinical data showed that 75% of the patients whose tumor carried ret mutation had tumor recurrence and/or increased serum calcitonin concentrations during the postsurgical follow-up period as opposed to 10% of the patients without mutations (P < 0.02, by {chi}{sup 2} analysis). No ret mutation was found in the tumoral DNA from parathyroid adenomas. Our findings indicate that the somatic ret point mutation frequently found in sporadic MTC may affect not only exon 16 but also exon 11 and is associated with less favorable clinical outcome. 14 refs., 2 figs., 3 tabs.

  17. Comparison of the clinicopathologic features of solitary and multifocal papillary thyroid carcinoma and the utility of testing an additional tumor nodule for BRAFV600E in multifocal cases

    Directory of Open Access Journals (Sweden)

    Tan J

    2017-01-01

    Full Text Available A retrospective review of the tumor focality and BRAFV600E mutational status of all thyroidectomy cases diagnosed with papillary thyroid carcinoma (PTC between 1/2010 and 7/2013 was performed. A total of 122 cases were included in this study consisting of 65 solitary cases and 57 multifocal cases with a total of 209 tumor nodules. In the multifocal tumors with absent BRAFV600E mutation in the dominant nodule, an additional tumor focus was submitted for testing. The clinicopathologic characteristics of the cases were then compared and analyzed. Significant association with BRAFV600E mutation was driven by previously established unfavorable histologic features such as usual variant, capsular invasion, lymphovascular invasion, extrathyroidal extension, and lymph node metastasis. We did not establish this association with tumor multifocality in this study. Although more cases of mPTC (multifocal papillary thyroid carcinoma had BRAFV600E mutation in comparison with the solitary cases (56 vs 44%, we did not find a significant difference between the two groups (p = 0.0689. Furthermore, at least one of the unfavorable histologic features was also noted in three out of the five multifocal cases with discordant mutations in the two largest nodules. The heterogeneity of BRAFV600E mutational status in mPTC is evident in this study and although it seems prudent to further test additional foci, it appears that in most cases there are already histologic features that support a more aggressive behavior. Selective testing based on histomorphology may be a more practical approach in these cases.

  18. MUC-1 Tumor Antigen Agonist Epitopes for Enhancing T-cell Responses to Human Tumors | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    Scientists at NIH have identified 7 new agonist epitopes of the MUC-1 tumor associated antigen. Compared to their native epitope counterparts, peptides reflecting these agonist epitopes have been shown to enhance the generation of human tumor cells, which in turn have a greater ability to kill human tumor cells endogenously expressing the native MUC-1 epitope.

  19. Induction of tumor necrosis factor expression and resistance in a human breast tumor cell line.

    OpenAIRE

    Spriggs, D; Imamura, K; Rodriguez, C; Horiguchi, J; Kufe, D W

    1987-01-01

    Tumor necrosis factor (TNF) is a polypeptide cytokine that is cytotoxic to some but not all tumor cells. The basis for resistance to the cytotoxic effects of this agent remains unclear. We have studied the development of TNF resistance in human ZR-75-1 breast carcinoma cells. ZR-75-1 cells have undetectable levels of TNF RNA and protein. However, TNF transcripts are transiently induced in these cells by exposure to recombinant human TNF. This induction of TNF RNA is associated with production...

  20. Papillary thyroid microcarcinoma in a thyroid pyramidal lobe

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Tae Kwan; Kim, Dong Wook; Park, Ha Kyoung; Jung, Soo Jin [Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2014-12-15

    We report an extremely rare case of papillary thyroid microcarcinoma (PTMC) in the thyroid pyramidal lobe (TPL). A 48-year-old woman underwent ultrasound-guided fine-needle aspiration for a small thyroid nodule in the right lobe in local clinic, and it revealed a malignant cytology. On preoperative ultrasonography for tumor staging in our hospital, another small suspiciously malignant hypoechoic nodule was detected in the left TPL. Total thyroidectomy and central nodal dissection were performed. Histopathology confirmed PTMCs in the left TPL and both thyroid lobes. Ultrasonography for TPL should be required for complete evaluation of possible multifocality of thyroid malignancy.

  1. Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer treatment in Spanish hospitals.

    Science.gov (United States)

    Vallejo, J A; Muros, M A

    In thyroid cancer treatment, the thyroid-stimulating hormone (TSH) must be elevated before radioiodine ablation, either by exogenous (with recombinant human thyrotropin [rhTSH]) or endogenous stimulation by thyroid hormone withdrawal (THW). The use of rhTSH avoids hypothyroidism and favours the subsequent elimination of radioiodine, but involves the cost of the product. For this reason, a cost-effectiveness analysis was performed, taking into account all costs involved and the benefits associated with the use of this therapy. Using a Markov modelling with two analysis arms (rhTSH and THW), stratified into high (100mCi/3700 MBq) and low (30mCi/1110 MBq) radioiodine doses, and using 17 weekly cycles, the incremental cost per quality-adjusted life-year (QALY) related to the use of rhTSH was determined. The clinical inputs included in the model were based on published studies and in a treatment survey conducted in Spain. Radioablation preparation with rhTSH is superior to THW, showing additional benefits (0.048 AVAC), as well as cost savings (-€614.16), with an incremental cost-effectiveness rate (ICER) of -€12,795/QALY. The univariate and multivariate sensitivity analyses showed the result to be robust. The use of rhTSH previous to radioablation in Spain has cost savings, as well as a series of health benefits for the patient, making it highly cost-effective. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  2. Tim-3 expression defines regulatory T cells in human tumors.

    Directory of Open Access Journals (Sweden)

    Jing Yan

    Full Text Available Tim-3, a member of the novel Tim (T cell immunoglobulin and mucin domain family, has been reported to negatively regulate the immune responses against viral infection and had implications for autoimmune disease. However, the nature and role of Tim-3(+ CD4 T cells in human tumors remain largely unknown. In the present study, we characterized Tim-3(+ CD4 T cells in 100 specimens from human hepatocellular, cervical, colorectal and ovarian carcinoma patients. Compared with peripheral blood and nontumor-infiltrating lymphocytes, the lymphocytes isolated from the corresponding tumor tissues of hepatocellular, cervical, colorectal and ovarian carcinoma patients contained significantly greater proportion of Tim-3(+ CD4 T cells. The majority of tumor-derived Tim-3(+ CD4 T cells exhibited an impaired capacity to produce IFN-γ and IL-2, but expressed higher levels of CD25, Foxp3, CTLA-4 and GITR than their Tim-3(- CD4 T cell counterparts. In contrast, most Tim-3(+ CD4 T cells isolated from the paired nontumor tissues and peripheral blood did not express these molecules. Moreover, tumor-derived Tim-3(+ CD4 T cells, but not tumor-derived Tim-3(- CD4 T cells, significantly suppressed the proliferation of autologous CD8(+ T cells in vitro. Notably, multi-color immunofluorescence and confocal microscopy demonstrated that Tim-3(+Foxp3(+CD4(+ cells were preferentially distributed in the tumor nest rather than the peritumoral stroma of hepatocellular carcinoma. Together, our data indicate that Tim-3-expressing CD4 T cells in human tumors could represent the functional regulatory T cells which contribute to the formation of the immune-suppressive tumor micromilieu.

  3. Environmental chemicals and thyroid function

    DEFF Research Database (Denmark)

    Boas, Malene; Feldt-Rasmussen, Ulla; Skakkebaek, Niels E

    2006-01-01

    There is growing evidence that environmental chemicals can disrupt endocrine systems. Most evidence originates from studies on reproductive organs. However, there is also suspicion that thyroid homeostasis may be disrupted. Several groups of chemicals have potential for thyroid disruption....... There is substantial evidence that polychlorinated biphenyls, dioxins and furans cause hypothyroidism in exposed animals and that environmentally occurring doses affect human thyroid homeostasis. Similarly, flame retardants reduce peripheral thyroid hormone (TH) levels in rodents, but human studies are scarce. Studies...

  4. Tc-99m-Labeled-rhTSH Analogue (TR1401) for Imaging Poorly Differentiated Metastatic Thyroid Cancer

    NARCIS (Netherlands)

    Galli, Filippo; Manni, Isabella; Piaggio, Giulia; Balogh, Lajos; Weintraub, Bruce D.; Szkudlinski, Mariusz W.; Fremont, Valerie; Dierckx, Rudi A. J. O.; Signore, Alberto

    2014-01-01

    Background: Differentiated thyroid carcinomas originating from thyroid follicular cells are frequent tumors of the thyroid with relatively good prognosis due to improved surgical techniques and follow-up procedures. Poorly differentiated thyroid cancers, which lose iodine uptake ability, in most

  5. Sensitive detection of viral transcripts in human tumor transcriptomes.

    Directory of Open Access Journals (Sweden)

    Sven-Eric Schelhorn

    Full Text Available In excess of 12% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped 14 transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates

  6. PRDM1 expression via human parvovirus B19 infection plays a role in the pathogenesis of Hashimoto thyroiditis.

    Science.gov (United States)

    Wang, Lu; Zhang, Wei-Ping; Yao, Li; Zhang, Wei; Zhu, Jin; Zhang, Wei-Chen; Zhang, Yue-Hua; Wang, Zhe; Yan, Qing-Guo; Guo, Ying; Fan, Lin-Ni; Liu, Yi-Xiong; Huang, Gao-Sheng

    2015-12-01

    Ectopic lymphoid follicle infiltration is a key event in Hashimoto thyroiditis (HT). Positive regulatory domain zinc finger protein 1 (PRDM1), which is induced by antigen stimulation, can regulate all lymphocyte lineages. Several groups independently demonstrated that human parvovirus B19 (PVB19) is closely associated with HT. Hence, we determined whether PRDM1 is expressed in HT thyroid tissue and whether there is any correlation between PRDM1 expression and PVB19 in the pathogenesis of HT. We detected PRDM1 expression in HT (n = 86), normal thyroid tissue (n = 30), and nontoxic nodular goiter (n = 20) samples using immunohistochemistry. We also detected PVB19 protein in HT samples in a double-blind manner and analyzed the correlation between the 2 proteins using immunofluorescence confocal detection and coimmunoprecipitation. Furthermore, we detected changes of the expression levels of PRDM1 and PVB19 in transfected primary thyroid follicular epithelial cells using real-time quantitative polymerase chain reaction. We found that PRDM1 protein is significantly highly expressed in the injured follicular epithelial cells in HT (83/86 cases) than in normal thyroid cells (0/30 cases) or in nontoxic nodular goiter cells (0/20 cases) (P < .001). In HT, the PRDM1 expression pattern was the same as that of PVB19, whereas PRDM1 and PVB19 were coexistent in the involved epithelial cells. Statistical analysis showed a significant correlation between PRDM1 and PVB19 (P < .001). In addition, primary thyroid epithelial cells also showed PRDM1 up-regulation after PVB19 NS1 transfection. Our findings suggest a previously unrecognized role of PRDM1 and PVB19 in the pathogenesis of HT. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer.

    Science.gov (United States)

    Khatami, Fatemeh; Larijani, Bagher; Heshmat, Ramin; Keshtkar, Abbasali; Mohammadamoli, Mahsa; Teimoori-Toolabi, Ladan; Nasiri, Shirzad; Tavangar, Seyed Mohammad

    2017-01-01

    Promoter methylation in a number of tumor-suppressor genes (TSGs) can play crucial roles in the development of thyroid carcinogenesis. The focus of the current meta-analysis was to determine the impact of promoter methylation of eight selected candidate TSGs on thyroid cancer and to identify the most important molecules in this carcinogenesis pathway. A comprehensive search was performed using Pub Med, Scopus, and ISI Web of Knowledge databases, and eligible studies were included. The methodological quality of the included studies was evaluated according to the Newcastle Ottawa scale table and pooled odds ratios (ORs); 95% confidence intervals (CIs) were used to estimate the strength of the associations with Stata 12.0 software. Egger's and Begg's tests were applied to detect publication bias, in addition to the "Metatrim" method. A total of 55 articles were selected, and 135 genes with altered promoter methylation were found. Finally, we included eight TSGs that were found in more than four studies (RASSF1, TSHR, PTEN, SLC5A, DAPK, P16, RARβ2, and CDH1). The order of the pooled ORs for these eight TSGs from more to less significant was CDH1 (OR = 6.73), SLC5 (OR = 6.15), RASSF1 (OR = 4.16), PTEN (OR = 3.61), DAPK (OR = 3.51), P16 (OR = 3.31), TSHR (OR = 2.93), and RARβ2 (OR = 1.50). Analyses of publication bias and sensitivity confirmed that there was very little bias. Thus, our findings showed that CDH1 and SCL5A8 genes were associated with the risk of thyroid tumor genesis.

  8. Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer.

    Directory of Open Access Journals (Sweden)

    Fatemeh Khatami

    Full Text Available Promoter methylation in a number of tumor-suppressor genes (TSGs can play crucial roles in the development of thyroid carcinogenesis. The focus of the current meta-analysis was to determine the impact of promoter methylation of eight selected candidate TSGs on thyroid cancer and to identify the most important molecules in this carcinogenesis pathway. A comprehensive search was performed using Pub Med, Scopus, and ISI Web of Knowledge databases, and eligible studies were included. The methodological quality of the included studies was evaluated according to the Newcastle Ottawa scale table and pooled odds ratios (ORs; 95% confidence intervals (CIs were used to estimate the strength of the associations with Stata 12.0 software. Egger's and Begg's tests were applied to detect publication bias, in addition to the "Metatrim" method. A total of 55 articles were selected, and 135 genes with altered promoter methylation were found. Finally, we included eight TSGs that were found in more than four studies (RASSF1, TSHR, PTEN, SLC5A, DAPK, P16, RARβ2, and CDH1. The order of the pooled ORs for these eight TSGs from more to less significant was CDH1 (OR = 6.73, SLC5 (OR = 6.15, RASSF1 (OR = 4.16, PTEN (OR = 3.61, DAPK (OR = 3.51, P16 (OR = 3.31, TSHR (OR = 2.93, and RARβ2 (OR = 1.50. Analyses of publication bias and sensitivity confirmed that there was very little bias. Thus, our findings showed that CDH1 and SCL5A8 genes were associated with the risk of thyroid tumor genesis.

  9. [Diagnostics of thyroid cancer: limitations of the existing methods and perspectives for future developments].

    Science.gov (United States)

    Sharova, N P; Sumedi, I R; Astakhova, T M; Plekhanova, A S; Liupina, Iu V; Shashova, E E; Kondakova, I V; Rodoman, G V

    2014-01-01

    A novel approach to the development of a precise method of intraoperative diagnostics of thyroid cancer has been proposed on the basis of fundamental study of proteasomes in malignant tumors of mammals and human. The method is based on estimation of proteasome activity in small fragments of the tumor and adjacent tissues.

  10. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  11. Isolevuglandins as a gauge of lipid peroxidation in human tumors.

    Science.gov (United States)

    Yan, H P; Roberts, L J; Davies, S S; Pohlmann, P; Parl, F F; Estes, S; Maeng, J; Parker, B; Mernaugh, R

    2017-05-01

    The cellular production of free radicals or reactive oxygen species (ROS) can lead to protein, lipid or DNA modifications and tumor formation. The cellular lipids undergo structural changes through the actions of enzymes (e.g. cyclooxygenases) or free radicals to form a class of compounds called Isolevuglandins (IsoLGs). The recruitment and continued exposure of tissue to ROS and IsoLGs causes increased cell proliferation, mutagenesis, loss of normal cell function and angiogenesis. The elevated concentration of ROS in cancerous tissues suggests that these mediators play an important role in cancer development. We hypothesized that tumors with elevated ROS levels would similarly possess an increased concentration of IsoLGs when compared with normal tissue. Using D11, an ScFv recombinant antibody specific for IsoLGs, we utilized immunohistochemistry to visualize the presence of IsoLG in human tumors compared to normal adjacent tissue (NAT) to the same tumor. We found that IsoLG concentrations were elevated in human breast, colon, kidney, liver, lung, pancreatic and tongue tumor cells when compared to NAT and believe that IsoLGs can be used as a gauge indicative of lipid peroxidation in tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Tumor Associated Neutrophils in Human Lung Cancer

    Science.gov (United States)

    2016-10-01

    isolated from the samepatientwithNSCLC.Tcellproliferation in responsetoCD3/CD28wasperformedasdescribed inMaterials andMethods. Cell proliferationwas...PMNswere isolated as described inMaterials andMethods and then added to allogeneic MLR in the presence of neutralizing mouse anti-human LOX-1 antibody (10 mg

  13. Prospective clinical trial of a human tumor cloning system.

    Science.gov (United States)

    Von Hoff, D D; Clark, G M; Stogdill, B J; Sarosdy, M F; O'Brien, M T; Casper, J T; Mattox, D E; Page, C P; Cruz, A B; Sandbach, J F

    1983-04-01

    A prospective clinical trial was performed to evaluate the usefulness of a human tumor cloning system for selecting single-agent chemotherapy for patients with advanced cancers. Six hundred four single-agent trials were performed in the 470 patients whose tumors were submitted for drug sensitivity testing. Only 246 of these 604 trials (41%) could be directed by the cloning system results because of inadequate tumor growth and other difficulties. In these 246 prospective trials, there was a 60% true positive and an 85% true negative rate for predicting for response or lack of response of an individual patient's tumor to the single agent. There was also a relationship between the percentage of decrease in survival of tumor colony-forming units and the probability of a clinical response of the patient's tumor to the same drug used in vivo. Despite these encouraging findings, work to improve tumor growth and additional prospective clinical trials of the system are needed before the system can be recommended for routine clinical use.

  14. Comparative expression pathway analysis of human and canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Marconato Laura

    2009-03-01

    Full Text Available Abstract Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.

  15. Thyroid Metastasis from Breast Carcinoma Accompanied by Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Song-I Yang

    2014-07-01

    Full Text Available Metastasis to the thyroid gland is very rare. Recently, we experienced a case of thyroid metastasis from breast cancer accompanying a papillary thyroid. A 51-year-old female patient presented with a palpated lymph node on her left lateral neck. The patient had undergone a left modified radical mastectomy followed by chemotherapy and hormonal therapy 12 years prior. Ultrasonography of the neck revealed a malignant looking nodule at the left thyroid lobe, measuring 0.9 × 0.9 cm, and several cystic nodules at the right thyroid lobe. Ultrasonography of the neck additionally revealed a malignant looking lymph node at the right level VI. Fine-needle aspiration of the left thyroid lobe resulted in a diagnosis of papillary thyroid carcinoma and that of the right level VI in Hurthle cell lesion. The patient had a total thyroidectomy with selective dissection of the left neck node. Pathologic assessment of the specimen revealed metastatic carcinoma from the breast carcinoma and papillary thyroid carcinoma. Although the thyroid gland is highly vascularized, metastasis of malignant tumors to the thyroid is relatively rare and detection of metastasis shows a low frequency. So a careful evaluation of thyroid tumor should be considered in a patient with a history of other malignancy.

  16. Development of the thyroid gland.

    Science.gov (United States)

    Nilsson, Mikael; Fagman, Henrik

    2017-06-15

    Thyroid hormones are crucial for organismal development and homeostasis. In humans, untreated congenital hypothyroidism due to thyroid agenesis inevitably leads to cretinism, which comprises irreversible brain dysfunction and dwarfism. Elucidating how the thyroid gland - the only source of thyroid hormones in the body - develops is thus key for understanding and treating thyroid dysgenesis, and for generating thyroid cells in vitro that might be used for cell-based therapies. Here, we review the principal mechanisms involved in thyroid organogenesis and functional differentiation, highlighting how the thyroid forerunner evolved from the endostyle in protochordates to the endocrine gland found in vertebrates. New findings on the specification and fate decisions of thyroid progenitors, and the morphogenesis of precursor cells into hormone-producing follicular units, are also discussed. © 2017. Published by The Company of Biologists Ltd.

  17. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

    Science.gov (United States)

    Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

    2003-01-01

    Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

  18. Neuro-endocrine correlations of hypothalamic-pituitary-thyroid axis in healthy humans.

    Science.gov (United States)

    Mazzoccoli, G; Carughi, S; Sperandeo, M; Pazienza, V; Giuliani, F; Tarquini, R

    2011-01-01

    Neuro-endocrine hormone secretion is characterized by circadian rhythmicity. Melatonin, GRH and GH are secreted during the night, CRH and ACTH secretion peak in the morning, determining the circadian rhythm of cortisol secretion, TRH and TSH show circadian variations with higher levels at night. Thyroxine levels do not change with clear circadian rhythmicity. In this paper we have considered a possible influence of cortisol and melatonin on hypothalamic-pituitary-thyroid axis function in humans. Melatonin, cortisol, TRH, TSH and FT4 serum levels were determined in blood samples obtained every four hours for 24 hours from ten healthy males, aged 36-51 years. We correlated hormone serum levels at each sampling time and evaluated the presence of circadian rhythmicity of hormone secretion. In the activity phase (06:00 h-10:00 h-14:00 h) cortisol correlated negatively with FT4, TSH correlated positively with TRH, TRH correlated positively with FT4 and melatonin correlated positively with TSH. In the resting phase (18:00 h-22:00 h-02:00 h) TRH correlated positively with FT4, melatonin correlated negatively with FT4, TSH correlated negatively with FT4, cortisol correlated positively with FT4 and TSH correlated positively with TRH. A clear circadian rhythm was validated for the time-qualified changes of melatonin and TSH secretion (with acrophase during the night), for cortisol serum levels (with acrophase in the morning), but not for TRH and FT4 serum level changes. In conclusion, the hypothalamic-pituitary-thyroid axis function may be modulated by cortisol and melatonin serum levels and by their circadian rhythmicity of variation.

  19. Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models.

    Directory of Open Access Journals (Sweden)

    Fang Peng

    Full Text Available BACKGROUND: Hypoxic tumor cells can reduce the efficacy of radiation. Antiangiogenic therapy may transiently "normalize" the tumor vasculature to make it more efficient for oxygen delivery. The aim of this study is to investigate whether the recombinant human endostatin (endostar can create a "vascular normalization window" to alleviate hypoxia and enhance the inhibitory effects of radiation therapy in human nasopharyngeal carcinoma (NPC in mice. METHODOLOGY/PRINCIPAL FINDINGS: Transient changes in morphology of tumor vasculature and hypoxic tumor cell fraction in response to endostar were detected in mice bearing CNE-2 and 5-8F human NPC xenografts. Various treatment schedules were tested to assess the influence of endostar on the effect of radiation therapy. Several important factors relevant to the angiogenesis were identified through immunohistochemical staining. During endostar treatment, tumor vascularity decreased, while the basement membrane and pericyte coverage associated with endothelial cells increased, which supported the idea of vessel normalization. Hypoxic tumor cell fraction also decreased after the treatment. The transient modulation of tumor physiology caused by endostar improved the effect of radiation treatment compared with other treatment schedules. The expressions of vascular endothelial growth factor (VEGF, matrix metalloproteinase-2 (MMP-2, MMP-9, and MMP-14 decreased, while the level of pigment epithelium-derived factor (PEDF increased. CONCLUSIONS: Endostar normalized tumor vasculature, which alleviated hypoxia and significantly sensitized the function of radiation in anti-tumor in human NPC. The results provide an important experimental basis for combining endostar with radiation therapy in human NPC.

  20. Cytostatic and apoptotic effects of paclitaxel in human ovarian tumors.

    Science.gov (United States)

    Millenbaugh, N J; Gan, Y; Au, J L

    1998-01-01

    The present study evaluated the cytostatic and apoptotic effects of a 24-hr paclitaxel treatment in ovarian tumors. Three-dimensional histocultures of surgical specimens from patients (n = 17) were used. The cytostatic effect was measured by inhibition of 96-hr cumulative DNA precursor incorporation and induction of apoptosis was determined by morphological changes. Paclitaxel produced partial inhibition of DNA precursor incorporation in about 40% of tumors (maximum inhibition of approximately 30%) and induced apoptosis in about 90% of tumors (maximum apoptotic index of approximately 15%). In responsive tumors, maximum cytostatic and apoptotic effects were achieved at < or = 1 microM with no further enhancement by increasing the drug concentration to 10 microM. In individual tumors, the apoptotic effect inversely correlated with cytostatic effect (r2 = 0.27, p = 0.031), and the maximal apoptotic index correlated with the LI for the untreated controls (r2 = 0.38, p < 0.01). More than 95% of apoptotic cells after paclitaxel treatment were labeled with DNA precursor. The incomplete cytostatic and apoptotic effects of paclitaxel and the link between DNA synthesis and apoptosis in ovarian tumors are similar to our previous findings in other human solid tumors. These findings suggest that (a) apoptosis is the major paclitaxel effect in advanced ovarian tumors, (b) tumor sensitivity to drug-induced cytostatic effect is opposite to sensitivity to apoptotic effect, (c) paclitaxel-induced apoptosis increases with increased cell proliferation and is completed after DNA synthesis, and (d) further increasing the dose to elevate plasma concentration beyond 1 microM may not improve treatment outcome.

  1. Herpes and polyoma family viruses in thyroid cancer.

    Science.gov (United States)

    Stamatiou, Dimitris P; Derdas, Stavros P; Zoras, Odysseas L; Spandidos, Demetrios A

    2016-03-01

    Thyroid cancer is considered the most common malignancy that affects the endocrine system. Generally, thyroid cancer derives from follicular epithelial cells, and thyroid cancer is divided into well-differentiated papillary (80% of cases) and follicular (15% of cases) carcinoma. Follicular thyroid cancer is further divided into the conventional and oncocytic (Hürthle cell) type, poorly differentiated carcinoma and anaplastic carcinoma. Both poorly differentiated and anaplastic carcinoma can arise either de novo , or secondarily from papillary and follicular thyroid cancer. The incidence of thyroid cancer has significantly increased for both males and females of all ages, particularly for females between 55-64 years of age, from 1999 through 2008. The increased rates refer to tumors of all stages, though they were mostly noted in localized disease. Recently, viruses have been implicated in the direct regulation of epithelial-mesenchymal transition (EMT) and the development of metastases. More specifically, Epstein-Barr virus (EBV) proteins may potentially lead to the development of metastasis through the regulation of the metastasis suppressor, Nm23, and the control of Twist expression. The significant enhancement of the metastatic potential, through the induction of angiogenesis and changes to the tumor microenvironment, subsequent to viral infection, has been documented, while EMT also contributes to cancer cell permissiveness to viruses. A number of viruses have been identified to be associated with carcinogenesis, and these include lymphotropic herpesviruses, namely EBV and Kaposi's sarcoma-associated herpesvirus [KSHV, also known as human herpesvirus type 8 (HHV8)]; two hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV); human papillomaviruses (HPVs); human T cell lymphoma virus (HTLV); and a new polyomavirus, Merkel cell polyomavirus identified in 2008. In this review, we examined the association between thyroid cancer and two oncogenic

  2. Humanized mouse xenograft models: narrowing the tumor-microenvironment gap

    OpenAIRE

    Morton, J. Jason; Bird, Gregory; Refaeli, Yosef; Jimeno, Antonio

    2016-01-01

    Cancer research has long been hampered by the limitations of the current model systems. Both cultured cells and mouse xenografts grow in an environment highly dissimilar to that of their originating tumor, frequently resulting in promising treatments that are ultimately clinically ineffective. The development of highly immunodeficient mouse strains into which human immune systems can be engrafted can help bridge this gap. Humanized mice (HM) allow researchers to examine xenograft growth in th...

  3. Postpartum Thyroiditis

    Science.gov (United States)

    ... to be an autoimmune disease very similar to Hashimoto’s thyroiditis. In fact, these two disorders cannot be ... from one another on pathology specimens. As in Hashimoto’s thyroiditis, postpartum thyroiditis is associated with the development ...

  4. Special pattern of endochondral ossification in human laryngeal cartilages: X-ray and light-microscopic studies on thyroid cartilage.

    Science.gov (United States)

    Claassen, Horst; Schicht, Martin; Sel, Saadettin; Paulsen, Friedrich

    2014-04-01

    Endochondral ossification is a process that also occurs in the skeleton of the larynx. Differences in the ossification mechanism in comparison to growth plates are not understood until now. To get deeper insights into this process, human thyroid cartilage was investigated by the use of X-rays and a series of light-microscopic stainings. A statistical analysis of mineralization was done by scanning areas of mineralized cartilage and of ossification. We detected a special mode of endochondral ossification which differs from the processes in growth plates. Thyroid cartilage ossifies very slowly and in a gender-specific manner. Compared with age-matched women, bone formation in thyroid cartilage of men is significantly higher in the age group 41-60 years. Endochondral ossification is prepared by internal changes of extracellular matrix leading to areas of asbestoid fibers with ingrowing cartilage canals. In contrast to growth plates, bone is deposited on large areas of mineralized cartilage, which appear at the rims of cartilage canals. Furthermore, primary parallel fibered bone was observed which was deposited on woven bone. The predominant bone type is cancellous bone with trabeculae, whereas compact bone with Haversian systems was seldom found. Trabeculae contain a great number of reversal and arresting lines meaning that the former were often reconstructed and that bone formation was arrested and resumed again with advancing age. It is hypothesized that throughout life trabeculae of ossified thyroid cartilage undergo adaptation to different loads due to the use of voice. Copyright © 2014 Wiley Periodicals, Inc.

  5. Papillary thyroid carcinoma

    DEFF Research Database (Denmark)

    Godballe, C; Asschenfeldt, P; Sørensen, J A

    1994-01-01

    The age influence on the prognosis of papillary thyroid carcinoma was analyzed in a group of 67 patients. A marked decline in cause-specific survival was found for patients older than 60 years of age at the time of diagnosis. In order to find a tumor-biological explanation of the prognostic...... invasion and distant metastases. The results indicate that 60 years of age the time of diagnosis may be the "prognostic break-point" for papillary thyroid carcinoma....

  6. Identification of novel tumor-associated cell surface sialoglycoproteins in human glioblastoma tumors using quantitative proteomics.

    Directory of Open Access Journals (Sweden)

    François Autelitano

    Full Text Available Glioblastoma multiform (GBM remains clinical indication with significant "unmet medical need". Innovative new therapy to eliminate residual tumor cells and prevent tumor recurrences is critically needed for this deadly disease. A major challenge of GBM research has been the identification of novel molecular therapeutic targets and accurate diagnostic/prognostic biomarkers. Many of the current clinical therapeutic targets of immunotoxins and ligand-directed toxins for high-grade glioma (HGG cells are surface sialylated glycoproteins. Therefore, methods that systematically and quantitatively analyze cell surface sialoglycoproteins in human clinical tumor samples would be useful for the identification of potential diagnostic markers and therapeutic targets for malignant gliomas. In this study, we used the bioorthogonal chemical reporter strategy (BOCR in combination with label-free quantitative mass spectrometry (LFQ-MS to characterize and accurately quantify the individual cell surface sialoproteome in human GBM tissues, in fetal, adult human astrocytes, and in human neural progenitor cells (NPCs. We identified and quantified a total of 843 proteins, including 801 glycoproteins. Among the 843 proteins, 606 (72% are known cell surface or secreted glycoproteins, including 156 CD-antigens, all major classes of cell surface receptor proteins, transporters, and adhesion proteins. Our findings identified several known as well as new cell surface antigens whose expression is predominantly restricted to human GBM tumors as confirmed by microarray transcription profiling, quantitative RT-PCR and immunohistochemical staining. This report presents the comprehensive identification of new biomarkers and therapeutic targets for the treatment of malignant gliomas using quantitative sialoglycoproteomics with clinically relevant, patient derived primary glioma cells.

  7. Humanized Mouse Xenograft Models: Narrowing the Tumor-Microenvironment Gap.

    Science.gov (United States)

    Morton, J Jason; Bird, Gregory; Refaeli, Yosef; Jimeno, Antonio

    2016-11-01

    Cancer research has long been hampered by the limitations of the current model systems. Both cultured cells and mouse xenografts grow in an environment highly dissimilar to that of their originating tumor, frequently resulting in promising treatments that are ultimately clinically ineffective. The development of highly immunodeficient mouse strains into which human immune systems can be engrafted can help bridge this gap. Humanized mice (HM) allow researchers to examine xenograft growth in the context of a human immune system and resultant tumor microenvironment, and recent studies have highlighted the increased similarities in attendant tumor structure, metastasis, and signaling to those features in cancer patients. This setting also facilitates the examination of investigational cancer therapies, including new immunotherapies. This review discusses recent advancements in the generation and application of HM models, their promise in cancer research, and their potential in generating clinically relevant treatments. This review also focuses on current efforts to improve HM models by engineering mouse strains expressing human cytokines or HLA proteins and implanting human bone, liver, and thymus tissue to facilitate immune cell maturation and trafficking. Finally, we discuss how these improvements may help direct future HM model cancer studies. Cancer Res; 76(21); 6153-8. ©2016 AACR. ©2016 American Association for Cancer Research.

  8. Decoding NADPH oxidase 4 expression in human tumors

    Directory of Open Access Journals (Sweden)

    Jennifer L. Meitzler

    2017-10-01

    Full Text Available NADPH oxidase 4 (NOX4 is a redox active, membrane-associated protein that contributes to genomic instability, redox signaling, and radiation sensitivity in human cancers based on its capacity to generate H2O2 constitutively. Most studies of NOX4 in malignancy have focused on the evaluation of a small number of tumor cell lines and not on human tumor specimens themselves; furthermore, these studies have often employed immunological tools that have not been well characterized. To determine the prevalence of NOX4 expression across a broad range of solid tumors, we developed a novel monoclonal antibody that recognizes a specific extracellular region of the human NOX4 protein, and that does not cross-react with any of the other six members of the NOX gene family. Evaluation of 20 sets of epithelial tumors revealed, for the first time, high levels of NOX4 expression in carcinomas of the head and neck (15/19 patients, esophagus (12/18 patients, bladder (10/19 patients, ovary (6/17 patients, and prostate (7/19 patients, as well as malignant melanoma (7/15 patients when these tumors were compared to histologically-uninvolved specimens from the same organs. Detection of NOX4 protein upregulation by low levels of TGF-β1 demonstrated the sensitivity of this new probe; and immunofluorescence experiments found that high levels of endogenous NOX4 expression in ovarian cancer cells were only demonstrable associated with perinuclear membranes. These studies suggest that NOX4 expression is upregulated, compared to normal tissues, in a well-defined, and specific group of human carcinomas, and that its expression is localized on intracellular membranes in a fashion that could modulate oxidative DNA damage.

  9. Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

    Energy Technology Data Exchange (ETDEWEB)

    Paz-Filho, G.J.; Mesa-Junior, C.O.; Boguszewski, C.L.; Carvalho, G.A.; Graf, H. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Endocrinologia e Metabologia; Olandoski, M. [Pontificia Univ. Catolica do Parana, Curitiba, PR (Brazil). Nucleo de Bioestatistica; Woellner, L.C. [Centro de Medicina Nuclear, Curitiba, PR (Brazil); Goedert, C.A. [Centro de Tomografia Computadorizada, Curitiba, PR (Brazil)

    2007-12-15

    Recombinant human thyroid-stimulating hormone (rhTSH) enhances {sup 131}I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi {sup 131}I, in patients with MNG. Seventeen patients (15 females, 59.0 {+-} 13.1 years), who had never been submitted to {sup 131}I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi {sup 131}I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 {+-} 64.4 mL. {sup 131}I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean {sup 131}I 24-h uptake increased from 18.1 {+-} 9.7 to 49.6 {+-} 13.4% (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 {+-} 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 {+-} 0.48 ng/dL for free-T4, 204.61 {+-} 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%), painful thyroiditis (29.4%) and hypothyroidism (52.9%). Thyroid volume was reduced by 34.3 {+-} 14.3% after 6 months (P < 0.001) and by 46.0 {+-} 14.6% after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of {sup 131}I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects. (author)

  10. Significance of rat mammary tumors for human risk assessment.

    Science.gov (United States)

    Russo, Jose

    2015-02-01

    We have previously indicated that the ideal animal tumor model should mimic the human disease. This means that the investigator should be able to ascertain the influence of host factors on the initiation of tumorigenesis, mimic the susceptibility of tumor response based on age and reproductive history, and determine the response of the tumors induced to chemotherapy. The utilization of experimental models of mammary carcinogenesis in risk assessment requires that the influence of ovarian, pituitary, and placental hormones, among others, as well as overall reproductive events are taken into consideration, since they are important modifiers of the susceptibility of the organ to neoplastic development. Several species, such as rodents, dogs, cats, and monkeys, have been evaluated for these purposes; however, none of them fulfills all the criteria specified previously. Rodents, however, are the most widely used models; therefore, this work will concentrate on discussing the rat rodent model of mammary carcinogenesis. © 2014 by The Author(s).

  11. Cowden Syndrome and Concomitant Pulmonary Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Langer, Seppo W; Ringholm, Lene; Dali, Christine I

    2015-01-01

    Cowden Syndrome is a rare autosomal dominantly inherited disorder. Patients with Cowden Syndrome are at increased risk of various benign and malignant neoplasms in breast, endometrium, thyroid, gastrointestinal tract, and genitourinary system. Neuroendocrine tumors are ubiquitous neoplasms that may...... occur anywhere in the human body. Bronchopulmonary neuroendocrine tumors include four different histological subtypes, among these, typical and atypical pulmonary carcinoids. No association between Cowden Syndrome and neuroendocrine tumors has previously been described. We present two cases of Cowden...

  12. [A patient with thyroid cancer evaluated according to Response Evaluation Criteria in Solid Tumors during treatment for breast cancer recurrence in hepatic and cervical lymph nodes].

    Science.gov (United States)

    Hayashi, Keiko; Enomoto, Takumo; Oshida, Sayuri; Habiro, Takeyoshi; Hatate, Kazuhiko; Sengoku, Norihiko; Watanabe, Masahiko

    2013-11-01

    We describe a case of a 69-year-old woman who underwent left breast-preserving surgery and axillary dissection for left-sided breast cancer at 60 years of age. The histopathological diagnosis was papillotubular carcinoma, luminal A (pathological T1N0M0).In the eighth year after surgery, computed tomography (CT) revealed recurrence in the liver and cervical lymph node metastasis. The patient did not respond to 3 months of treatment with letrozole (progressive disease [PD]). Six courses of chemotherapy with epirubicin and cyclophosphamide (EC) were administered. Subsequently, the attending physician was replaced while the patient was receiving paclitaxel( PTX).After 4 courses of treatment with PTX, the liver metastasis disappeared (complete response [CR]).However, the cervical lymph nodes did not shrink (PD).The cytological diagnosis was papillary thyroid cancer with associated cervical lymph node metastasis. Total thyroidectomy and D3b cervical lymph node dissection were performed. The pathological diagnosis was pEx0T1bN1Mx, pStage IVA disease. Replacement of the attending physician is a critical turning point for patients. During chemotherapy or hormone therapy for breast cancer, each organ should be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST).In the case of our patient, thyroid cancer was diagnosed according to RECIST. Cancer specialists should bear in mind that the treatment policy may change dramatically depending on the results of RECIST assessment.

  13. Absence of human cytomegalovirus infection in childhood brain tumors.

    Science.gov (United States)

    Sardi, Iacopo; Lucchesi, Maurizio; Becciani, Sabrina; Facchini, Ludovica; Guidi, Milena; Buccoliero, Anna Maria; Moriondo, Maria; Baroni, Gianna; Stival, Alessia; Farina, Silvia; Genitori, Lorenzo; de Martino, Maurizio

    2015-01-01

    Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients' neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors.

  14. Ex Vivo Behaviour of Human Bone Tumor Endothelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Infante, Teresa [SDN-Foundation, Institute of Diagnostic and Nuclear Development, IRCCS, 80143 Naples (Italy); Cesario, Elena [Department of Biochemistry and Biophysics, Second University of Naples, 80138 Naples (Italy); Gallo, Michele; Fazioli, Flavio [Division of Skeletal Muscles Oncology Surgery, National Cancer Institute, Pascale Foundation, 80131 Naples (Italy); De Chiara, Annarosaria [Anatomic Pathology Unit, National Cancer Institute, Pascale Foundation, 80131 Naples (Italy); Tutucci, Cristina; Apice, Gaetano [Medical Oncology of Bone and Soft Sarcoma tissues Unit, National Cancer Institute, Pascale Foundation, 80131 Naples (Italy); Nigris, Filomena de, E-mail: filomena.denigris@unina2.it [Department of Biochemistry and Biophysics, Second University of Naples, 80138 Naples (Italy)

    2013-04-11

    Cooperation between endothelial cells and bone in bone remodelling is well established. In contrast, bone microvasculature supporting the growth of primary tumors and metastasis is poorly understood. Several antiangiogenic agents have recently been undergoing trials, although an extensive body of clinical data and experimental research have proved that angiogenic pathways differ in each tumor type and stage. Here, for the first time, we characterize at the molecular and functional level tumor endothelial cells from human bone sarcomas at different stages of disease and with different histotypes. We selected a CD31{sup +} subpopulation from biopsies that displayed the capability to grow as adherent cell lines without vascular endothelial growth factor (VEGF). Our findings show the existence in human primary bone sarcomas of highly proliferative endothelial cells expressing CD31, CD44, CD105, CD146 and CD90 markers. These cells are committed to develop capillary-like structures and colony formation units, and to produce nitric oxide. We believe that a better understanding of tumor vasculature could be a valid tool for the design of an efficacious antiangiogenic therapy as adjuvant treatment of sarcomas.

  15. Interphase ribosomal RNA cistron staining in thyroid epithelial cells in Grave's disease, Hashimoto's thyroiditis and benign and malignant tumours of the thyroid gland

    OpenAIRE

    Mamaev, N N; Grynyeva, E N; Blagosklonnaya, Y V

    1996-01-01

    Aim—To evaluate the expression of ribosomal cistrons in human thyroid epithelial cells (TECs) of patients with Grave's disease, Hashimoto's thyroiditis and benign and malignant tumours of the thyroid gland.

  16. Metastatic Follicular Thyroid Carcinoma Secreting Thyroid Hormone and Radioiodine Avid without Stimulation: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Syed A. Abid

    2014-01-01

    Full Text Available Introduction. This is an extremely rare case of a patient with metastatic follicular thyroid cancer who continued to produce thyroid hormone and was iodine scan positive without stimulation after thyroidectomy and radioiodine (I-131 therapy. Patient Findings. A 76-year-old Caucasian male was diagnosed with metastatic follicular thyroid carcinoma on lung nodule biopsy. Total thyroidectomy was performed and he was ablated with 160 mCi of I-131 after recombinant human thyrotropin (rhTSH stimulation. Whole body scan (WBS after treatment showed uptake in bilateral lungs, right sacrum, and pelvis. The thyroglobulin decreased from 2,063 to 965 four months after treatment but rapidly increased to 2,506 eleven months after I-131. Thyroid stimulating hormone (TSH remained suppressed and free T4 remained elevated after I-131 therapy without thyroid hormone supplementation. He was treated with an additional 209 mCi with WBS findings positive in lung and pelvis. Despite I-131, new metastatic lesions were noted in the left thyroid bed and large destructive lesion to the first cervical vertebrae four months after the second I-131 dose. Conclusions. This case is exceptional because of its rarity and also due to the dissociation between tumor differentiation and aggressiveness. The metastatic lesions continued to secrete thyroid hormone and remained radioiodine avid with rapid progression after I-131 therapy.

  17. A Placebo-Controlled, Blinded and Randomised Study on the Effects of Recombinant Human Thyrotropin on Quality of Life in the Treatment of Thyroid Cancer

    DEFF Research Database (Denmark)

    Nygaard, Birte; Bastholt, Lars; Bennedbæk, Finn Noe

    2013-01-01

    BACKGROUND: It is well known that thyroid hormone withdrawal (THW) in thyroid cancer patients can induce a decrease in quality of life (QOL). Recombinant human thyrotropin (rh-TSH) has been used to avoid this; however, no blinded studies have ever documented the effect. OBJECTIVE: To compare QOL...... in patients with differentiated thyroid cancer (DTC) treated with either rh-TSH or liothyronine (L-T3) THW for 10 days. STUDY DESIGN: Double-blind, randomised cross-over. PATIENTS: Fifty-six patients with DTC treated by total thyroidectomy and indication for postsurgery radioiodine (RI) ablation therapy...

  18. Thyroglobulin may affect telomerase activity in thyroid follicular cells.

    Science.gov (United States)

    Nagasaka, Akio; Oda, Naohisa; Nakai, Akira; Hotta, Keiko; Nagata, Mutsuko; Kato, Taiya; Suzuki, Atsushi; Itoh, Mitsuyasu; Miura, Hitoshi; Hakuta, Motoo; Yoshida, Shonen; Hibi, Yatsuka; Iwase, Katsumi

    2009-04-01

    Telomerase (TA) activity is known to be present in malignant tumor cells, but not in most somatic differentiated cells. TA shows relatively high activity in thyroid cancer cells, but reports vary. This fact prompted us to elucidate whether cell component inhibitors of TA in the thyroid follicles can modulate its activity. The activity of TA extracted from Hela cells was inhibited by mixing with the supernatant fraction of human thyroid tissue extract. To examine the effect of iodine, thyroid hormones (l-T3 and l-T4) and human thyroglobulin (hTg) contained in the thyroid follicles, l-T3, l-T4 and hTg were added to the TRAP assay system in vitro, using TA from Hela cells. Iodine, l-T3 and l-T4 did not affect TA activity, but hTg inhibited the TA activity in a dose-dependent manner (IC(50) of hTg: ca 0.45 microM: inhibiting concentration of hTg was from 0.15 microM to 3.0 microM). The hTg inhibition was not evident in the RT-PCR system, suggesting no effect of hTg on Taq DNA polymerase activity. The hTg inhibition of TA activity was attenuated by dNTP but not significantly by TS primer. These data suggest that hTg contained in thyroid follicular cells of various thyroid diseases may affect the TA activity measured in biopsied thyroid specimens, and that the reduction of the TA activity by hTg may induce slow progression and growth, and low grade malignancy of thyroid cancer, particularly differentiated carcinoma.

  19. A presença de tireoidite linfocitária crônica influencia o estadiamento tumoral do carcinoma diferenciado da tireoide? Does chronic lymphocytic thyroiditis influence the staging of differentiated thyroid carcinoma?

    Directory of Open Access Journals (Sweden)

    Marcos Antonio Nemetz

    2011-02-01

    Full Text Available A associação entre carcinoma diferenciado de tireoide (CDT e tireoidite linfocitária crônica (TLC tem sido relatada na literatura. OBJETIVO: Avaliar a incidência desta associação e determinar se a TLC pode influenciar no estadiamento tumoral do CDT quando associada a outras variáveis de risco. FORMA DE ESTUDO: Coorte histórica (retrospectiva. MATERIAL E MÉTODO: Avaliaram-se 52 prontuários e laudos de pacientes portadores de CDT, no período de 1999 a 2009, divididos em dois grupos. O primeiro, composto de 35 pacientes portadores de CDT sem TLC; o segundo, com 17 pacientes, associado à TLC. O tratamento instituído para todos os pacientes foi a tireoidectomia total. Variáveis comuns a ambos os grupos como idade, gênero, padrão histológico, diâmetro tumoral, metástase locorregional e à distância, invasão extratireoidiana, multifocalidade e presença de cápsula tumoral foram comparadas. Aplicou-se os testes t-Student e Qui-quadrado para análise dos dados. RESULTADOS: A incidência de CDT isolado foi maior do que a de CDT+TLC (p=0,0126. Nenhuma diferença estatística quanto às variáveis comuns analisadas foi observada. CONCLUSÕES: A presença de TLC ocorreu em 33% dos pacientes com CDT. Todos os casos de CDT eram em estádios iniciais.The association between differentiated thyroid carcinoma (DTC and chronic lymphocytic thyroiditis (CLT has been reported in literature. AIM: To evaluate the incidence of this association and to determine whether the CLT may influence on the early initial staging of DTC when associated with other variable risks. STUDY DESIGN: Historical (retrospective cohort. MATERIALS AND METHODS: Fifty two patients with DTC were evaluated from 1999 to 2009. They were divided into two groups. The first group had 35 patients with DTC without DLT; the second had 17 patients with CLT. Total thyroidectomy was the treatment chosen for all patients. Similarities shared in both groups such as age, gender

  20. Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties.

    Science.gov (United States)

    Godlewska, Marlena; Arczewska, Katarzyna D; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław; Czarnocka, Barbara

    2017-01-01

    Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism.

  1. Identification of new biomarkers for human papillary thyroid carcinoma employing NanoString analysis

    OpenAIRE

    Chitikova, Zhanna; Pusztaszeri, Marc; Makhlouf, Anne-Marie; Berczy, Margaret; Delucinge, Céline; Triponez, Frédéric; Meyer, Patrick; Philippe, Jacques; Dibner, Charna

    2015-01-01

    We previously reported an upregulation of the clock transcript BMAL1, correlating with TIMP1 expression in fresh-frozen samples from papillary thyroid carcinoma (PTC). Since frozen postoperative biopsy samples are difficult to obtain, we aimed to validate the application of high-precision NanoString analysis for formalin-fixed paraffin-embedded (FFPE) thyroid nodule samples and to screen for potential biomarkers associated with PTC. No significant differences were detected between fresh-froze...

  2. Spheroid formation of human thyroid cancer cells in an automated culturing system during the Shenzhou-8 Space mission.

    Science.gov (United States)

    Pietsch, Jessica; Ma, Xiao; Wehland, Markus; Aleshcheva, Ganna; Schwarzwälder, Achim; Segerer, Jürgen; Birlem, Maria; Horn, Astrid; Bauer, Johann; Infanger, Manfred; Grimm, Daniela

    2013-10-01

    Human follicular thyroid cancer cells were cultured in Space to investigate the impact of microgravity on 3D growth. For this purpose, we designed and constructed a cell container that can endure enhanced physical forces, is connected to fluid storage chambers, performs media changes and cell harvesting automatically and supports cell viability. The container consists of a cell suspension chamber, two reserve tanks for medium and fixative and a pump for fluid exchange. The selected materials proved durable, non-cytotoxic, and did not inactivate RNAlater. This container was operated automatically during the unmanned Shenzhou-8 Space mission. FTC-133 human follicular thyroid cancer cells were cultured in Space for 10 days. Culture medium was exchanged after 5 days in Space and the cells were fixed after 10 days. The experiment revealed a scaffold-free formation of extraordinary large three-dimensional aggregates by thyroid cancer cells with altered expression of EGF and CTGF genes under real microgravity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Preoperative Prediction of Cervical Lymph Node Metastasis Using Primary Tumor SUVmax on 18F-FDG PET/CT in Patients with Papillary Thyroid Carcinoma.

    Directory of Open Access Journals (Sweden)

    Ji-hoon Jung

    Full Text Available The aim of the current study was to evaluate the value of preoperative 18F-FDG (FDG PET/CT in predicting cervical lymph node (LN metastasis in patients with papillary thyroid carcinoma (PTC.One hundred and ninety-three newly diagnosed PTC patients (M: F = 25:168, age = 46.8 ± 12.2 who had undergone pretreatment FDG PET/CT and had neck node dissection were included in this study. The FDG avidity of the primary tumor and the SUVmax of the primary tumor (pSUVmax were analyzed for prediction of LN metastasis. Detectability by ultrasonography (US and FDG PET/CT for cervical LN metastasis were also assessed and compared with the pSUVmax.The FDG avidity of the primary tumor was identified in 118 patients (FDG avid group: 61.0%, M: F = 16:102, age 47.0 ± 12.7 years and pSUVmax ranged from 1.3 to 35.6 (median 4.6 in the FDG avid group. The tumor size in the FDG avid group was bigger and there was a higher incidence of LN metastasis compared to the FDG non-avid group (0.93 vs. 0.59 cm, p 4.6 was 54%; however, the detectability of central LN metastasis by US and FDG PET/CT were 10.3% and 3.6%, respectively.A high FDG avidity of the primary tumor was related to LN metastasis in PTC patients. Therefore, patients with a high pSUVmax should be cautiously assessed for LN metastasis and might need a more comprehensive surgical approach.

  4. Abnormal intracellular and extracellular distribution of basement membrane material in papillary carcinoma and hyalinizing trabecular tumors of the thyroid: implication for deregulation of secretory pathways.

    Science.gov (United States)

    Li, M; Carcangiu, M L; Rosai, J

    1997-12-01

    Papillary carcinoma (PC) and hyalinizing trabecular tumors (HTT) of the thyroid share several morphological features, including the presence of nuclear pseudoinclusions (NPI). One of the distinct characteristics of HTT is its hyalinizing stroma, which contains abundant basement membrane (BM) material. We investigated the distribution of BM material in PC and HTT. Fifteen cases of PC and nine cases of HTT were analyzed immunohistochemically with monoclonal antibodies for type IV collagen and laminin. Three stromal staining patterns were observed: (1) linear staining along the epithelium lining papillae, between trabeculae, and around follicles; (2) focal absence of staining; (3) lumpy or diffuse stromal staining. Although the latter was more commonly seen in HTT, all three patterns were present in both tumor types. More interestingly, we observed two hitherto undescribed intracellular staining patterns in both tumor types: intracytoplasmic dotlike staining and staining of NPI. Electron microscopy was performed in three cases of PC. Dilated cisternae of endoplasmic reticulum containing dense amorphous material resembling BM were observed in the cytoplasm in one case and in the NPI in another. These findings suggest the presence of a common pathway for the abnormal production of BM in both PC and HTT. Two mechanisms that may account for the abnormal intracellular detection of BM materials are proposed: (1) intracellular invagination/phagocytosis of extracellular matrix by the tumor cells; (2) abnormal production or alteration in secretory pathway in tumor cells resulting in intracellular accumulation and intranuclear invagination. The combination of immunohistochemical and electron microscopic findings favors the latter. The similar patterns of BM deposition shared by PC and HTT further support the hypothesis that PC and HTT are related to each other.

  5. cDNA immunization of mice with human thyroglobulin generates both humoral and T cell responses: a novel model of thyroid autoimmunity.

    Directory of Open Access Journals (Sweden)

    Eric M Jacobson

    2011-04-01

    Full Text Available Thyroglobulin (Tg represents one of the largest known self-antigens involved in autoimmunity. Numerous studies have implicated it in triggering and perpetuating the autoimmune response in autoimmune thyroid diseases (AITD. Indeed, traditional models of autoimmune thyroid disease, experimental autoimmune thyroiditis (EAT, are generated by immunizing mice with thyroglobulin protein in conjunction with an adjuvant, or by high repeated doses of Tg alone, without adjuvant. These extant models are limited in their experimental flexibility, i.e. the ability to make modifications to the Tg used in immunizations. In this study, we have immunized mice with a plasmid cDNA encoding the full-length human Tg (hTG protein, in order to generate a model of Hashimoto's thyroiditis which is closer to the human disease and does not require adjuvants to breakdown tolerance. Human thyroglobulin cDNA was injected and subsequently electroporated into skeletal muscle using a square wave generator. Following hTg cDNA immunizations, the mice developed both B and T cell responses to Tg, albeit with no evidence of lymphocytic infiltration of the thyroid. This novel model will afford investigators the means to test various hypotheses which were unavailable with the previous EAT models, specifically the effects of hTg sequence variations on the induction of thyroiditis.

  6. cDNA Immunization of Mice with Human Thyroglobulin Generates Both Humoral and T Cell Responses: A Novel Model of Thyroid Autoimmunity

    Science.gov (United States)

    Jacobson, Eric M.; Concepcion, Erlinda; Ho, Kenneth; Kopp, Peter; Vono Toniolo, Jussara; Tomer, Yaron

    2011-01-01

    Thyroglobulin (Tg) represents one of the largest known self-antigens involved in autoimmunity. Numerous studies have implicated it in triggering and perpetuating the autoimmune response in autoimmune thyroid diseases (AITD). Indeed, traditional models of autoimmune thyroid disease, experimental autoimmune thyroiditis (EAT), are generated by immunizing mice with thyroglobulin protein in conjunction with an adjuvant, or by high repeated doses of Tg alone, without adjuvant. These extant models are limited in their experimental flexibility, i.e. the ability to make modifications to the Tg used in immunizations. In this study, we have immunized mice with a plasmid cDNA encoding the full-length human Tg (hTG) protein, in order to generate a model of Hashimoto's thyroiditis which is closer to the human disease and does not require adjuvants to breakdown tolerance. Human thyroglobulin cDNA was injected and subsequently electroporated into skeletal muscle using a square wave generator. Following hTg cDNA immunizations, the mice developed both B and T cell responses to Tg, albeit with no evidence of lymphocytic infiltration of the thyroid. This novel model will afford investigators the means to test various hypotheses which were unavailable with the previous EAT models, specifically the effects of hTg sequence variations on the induction of thyroiditis. PMID:21559421

  7. Human Exposures to Bisphenol A, Bisphenol F and Chlorinated Bisphenol A Derivatives and Thyroid Function.

    Directory of Open Access Journals (Sweden)

    Xanthi D Andrianou

    Full Text Available Although the increasing prevalence of thyroid nodular disease (TND has been partially attributed to the more frequent usage of improved diagnostics, environmental factors, such as exposures to thyroid-disrupting chemicals may contribute to TND and altered thyroid function. We investigated the association between exposures to bisphenol A (BPA, its chlorinated derivatives (ClxBPA, and bisphenol F (BPF with TND and thyroid measures in adult women. A case-control study in Cyprus and Romania (n = 212 was conducted, where cases were those with thyroid nodules (diameter >3mm, and controls without nodules. Serum TSH and free thyroxine and urinary levels of BPA, BPF and ClxBPA were measured using immunoassays and tandem mass spectrometry, respectively. The association between exposures to BPA compounds and TND, adjusting for age, BMI, thyroid hormones and urinary iodine was assessed using logistic regression. Linear regression was used to explore associations between urinary BPA, BPF and ClxBPA and serum thyroid hormones. With the exception of a chlorinated BPA compound (30%, the rest of bisphenols were quantified in 100% of urine samples. A positive and significant (p<0.05 association was observed between urinary BPA and serum TSH that remained after adjusting for urinary creatinine, age, BMI, study site and disease status; there was no significant association between BPF or ClxBPA with TSH. None of the BPA compounds were associated with higher odds of TND. Our study found associations of urinary BPA with TSH but not with BPF or ClxBPA. A larger study would be justified.

  8. Human Exposures to Bisphenol A, Bisphenol F and Chlorinated Bisphenol A Derivatives and Thyroid Function

    Science.gov (United States)

    Andrianou, Xanthi D.; Gängler, Stephanie; Piciu, Andra; Charisiadis, Pantelis; Zira, Christina; Aristidou, Kyriacos; Piciu, Doina; Hauser, Russ; Makris, Konstantinos C.

    2016-01-01

    Although the increasing prevalence of thyroid nodular disease (TND) has been partially attributed to the more frequent usage of improved diagnostics, environmental factors, such as exposures to thyroid-disrupting chemicals may contribute to TND and altered thyroid function. We investigated the association between exposures to bisphenol A (BPA), its chlorinated derivatives (ClxBPA), and bisphenol F (BPF) with TND and thyroid measures in adult women. A case-control study in Cyprus and Romania (n = 212) was conducted, where cases were those with thyroid nodules (diameter >3mm), and controls without nodules. Serum TSH and free thyroxine and urinary levels of BPA, BPF and ClxBPA were measured using immunoassays and tandem mass spectrometry, respectively. The association between exposures to BPA compounds and TND, adjusting for age, BMI, thyroid hormones and urinary iodine was assessed using logistic regression. Linear regression was used to explore associations between urinary BPA, BPF and ClxBPA and serum thyroid hormones. With the exception of a chlorinated BPA compound (30%), the rest of bisphenols were quantified in 100% of urine samples. A positive and significant (p<0.05) association was observed between urinary BPA and serum TSH that remained after adjusting for urinary creatinine, age, BMI, study site and disease status; there was no significant association between BPF or ClxBPA with TSH. None of the BPA compounds were associated with higher odds of TND. Our study found associations of urinary BPA with TSH but not with BPF or ClxBPA. A larger study would be justified. PMID:27783680

  9. Cat Mammary Tumors: Genetic Models for the Human Counterpart

    Directory of Open Access Journals (Sweden)

    Filomena Adega

    2016-08-01

    Full Text Available The records are not clear, but Man has been sheltering the cat inside his home for over 12,000 years. The close proximity of this companion animal, however, goes beyond sharing the same roof; it extends to the great similarity found at the cellular and molecular levels. Researchers have found a striking resemblance between subtypes of feline mammary tumors and their human counterparts that goes from the genes to the pathways involved in cancer initiation and progression. Spontaneous cat mammary pre-invasive intraepithelial lesions (hyperplasias and neoplasias and malignant lesions seem to share a wide repertoire of molecular features with their human counterparts. In the present review, we tried to compile all the genetics aspects published (i.e., chromosomal alterations, critical cancer genes and their expression regarding cat mammary tumors, which support the cat as a valuable alternative in vitro cell and animal model (i.e., cat mammary cell lines and the spontaneous tumors, respectively, but also to present a critical point of view of some of the issues that really need to be investigated in future research.

  10. Validation of Reference Genes for Normalization Gene Expression in Reverse Transcription Quantitative PCR in Human Normal Thyroid and Goiter Tissue

    Directory of Open Access Journals (Sweden)

    Raquel Weber

    2014-01-01

    Full Text Available Reverse transcription quantitative polymerase chain reaction (RT-qPCR has been recognized as the most accurate method for quantifying mRNA transcripts, but normalization of samples is a prerequisite for correct data interpretation. So, this study aimed to evaluate the most stable reference gene for RT-qPCR in human normal thyroid and goiter tissues. Beta-actin (ACTB; glyceraldehyde-3-phosphate dehydrogenase (GAPDH; succinate dehydrogenase, subunit A, flavoprotein (Fp (SDHA; hypoxanthine phosphoribosyltransferase I (HPRTI; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ; and beta-2-microglobulin (B2M were evaluated in 14 thyroid tissue samples (7 normal and 7 goiter tissues by RT-qPCR. The mean Cq and the maximum fold change (MFC and NormFinder software were used to assess the stability of the genes. As a result, ACTB gene was more stable than GAPDH, SDHA, HPRTI, YWHAZ, and B2M. In conclusion, ACTB could be used to normalize RT-qPCR data in normal thyroid and goiter tissues.

  11. Triparanol suppresses human tumor growth in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Bi, Xinyu [Department of Abdominal Surgical Oncology, Lab of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021 (China); Han, Xingpeng [Department of Pathology, Tianjin Chest Hospital, Tianjin 300051 (China); Zhang, Fang [Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, Zhejiang (China); He, Miao [Life Sciences School, Sun Yat-sen University, Guangzhou 510275 (China); Zhang, Yi [Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhi, Xiu-Yi, E-mail: xiuyizhi@yahoo.com.cn [Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhao, Hong, E-mail: zhaohong9@sina.com [Department of Abdominal Surgical Oncology, Lab of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021 (China)

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Demonstrate Triparanol can block proliferation in multiple cancer cells. Black-Right-Pointing-Pointer Demonstrate Triparanol can induce apoptosis in multiple cancer cells. Black-Right-Pointing-Pointer Proved Triparanol can inhibit Hedgehog signaling in multiple cancer cells. Black-Right-Pointing-Pointer Demonstrated Triparanol can impede tumor growth in vivo in mouse xenograft model. -- Abstract: Despite the improved contemporary multidisciplinary regimens treating cancer, majority of cancer patients still suffer from adverse effects and relapse, therefore posing a significant challenge to uncover more efficacious molecular therapeutics targeting signaling pathways central to tumorigenesis. Here, our study have demonstrated that Triparanol, a cholesterol synthesis inhibitor, can block proliferation and induce apoptosis in multiple human cancer cells including lung, breast, liver, pancreatic, prostate cancer and melanoma cells, and growth inhibition can be rescued by exogenous addition of cholesterol. Remarkably, we have proved Triparanol can significantly repress Hedgehog pathway signaling in these human cancer cells. Furthermore, study in a mouse xenograft model of human lung cancer has validated that Triparanol can impede tumor growth in vivo. We have therefore uncovered Triparanol as potential new cancer therapeutic in treating multiple types of human cancers with deregulated Hedgehog signaling.

  12. Identification of new biomarkers for human papillary thyroid carcinoma employing NanoString analysis.

    Science.gov (United States)

    Chitikova, Zhanna; Pusztaszeri, Marc; Makhlouf, Anne-Marie; Berczy, Margaret; Delucinge-Vivier, Celine; Triponez, Frederic; Meyer, Patrick; Philippe, Jacques; Dibner, Charna

    2015-05-10

    We previously reported an upregulation of the clock transcript BMAL1, correlating with TIMP1 expression in fresh-frozen samples from papillary thyroid carcinoma (PTC). Since frozen postoperative biopsy samples are difficult to obtain, we aimed to validate the application of high-precision NanoString analysis for formalin-fixed paraffin-embedded (FFPE) thyroid nodule samples and to screen for potential biomarkers associated with PTC. No significant differences were detected between fresh-frozen and FFPE samples. NanoString analysis of 51 transcripts in 17 PTC and 17 benign nodule samples obtained from different donors and in 24 pairs of benign and PTC nodules, obtained from the same donor (multinodular goiters), confirmed significant alterations in the levels of BMAL1, c-MET, c-KIT, TIMP1, and other transcripts. Moreover, we identified for the first time alterations in CHEK1 and BCL2 levels in PTC. A predictive score was established for each sample, based on the combined expression levels of BMAL1, CHEK1, c-MET, c-KIT and TIMP1. In combination with BRAF mutation analysis, this predictive score closely correlated with the clinicopathological characteristics of the analyzed thyroid nodules. Our study identified new thyroid transcripts with altered levels in PTC using the NanoString approach. A predictive score correlation coefficient might contribute to improve the preoperative diagnosis of thyroid nodules.

  13. Thyroid hormone excess stimulates the synthesis of proteoglycan in human skin fibroblasts in culture

    Energy Technology Data Exchange (ETDEWEB)

    Shishiba, Yoshimasa; Ozawa, Yasunori; Shimizu, Taeko (Division of Endocrinology and Endocrine Research Laboratory, Toranomon Hospital (Japan)); Takeuchi, Yasuhiro; Yokoi, Noriko (Okinaka Memorial Institute for Medical Research, Akasaka, Tokyo (Japan))

    1990-01-01

    We previously demonstrated that proteoglycan accumulated in the affected skin of circumscribed pretibial myxedema of Graves' disease. As an underlying mechanism responsible for the accumulation, we sought to determine whether excess thyroid hormone was partially responsible for the increase in proteoglycan synthesis. Human skin fibroblasts were cultured in Ham's F-10 medium containing 1% Nutridoma with graded doses of T{sub 3}(0.184 x 10{sup -9} to 46 x 10{sup -9} mol/l) and were labelled with ({sup 35}S)sulphate and ({sup 3}H)glucosamine. Proteoglycans were purified by Sephadex G-50, Q-Sepharose chromatography with NaCl-gradient and Sepharose CL-6B chromatography. {sup 35}S and {sup 3}H incorporated into dermatan sulphate proteoglycan and heparan sulphate proteoglycan and {sup 3}H incorporated into hyaluronan were measured. {sup 35}S and {sup 3}H incorporation into dermatan sulphate proteoglycan was minimum at a T{sub 3} concentration of 0.184 x 10{sup -9} mol/l, and increased with increasing doses of T{sub 3} up to 46 x 10{sup -9} mol/l. {sup 35}S and {sup 3}H incorporation into heparan sulphate proteoglycan also increased with increasing-doses of T{sub 3}. {sup 3}H incorporation into hyaluranan was not influenced at all by T{sub 3}. The increased incorporation of {sup 35}S into proteoglycan in high-T{sub 3} culture reflects the increased synthesis of proteoglycan because 1. the extent of sulphation of disaccharides examined by thin-layer chromatography was not altered by T{sub 3}; 2. the specific activity of ({sup 35}S)sulphate was not influenced by T{sub 3}, and 3. T{sub 3} did not decrease the degradation rate of cell-associated proteoglycan. (author).

  14. Vitamin D and Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Muyesser Saykı Arslan

    2014-10-01

    Full Text Available Accumulating evidence demonstrated that the active form of vitamin D, 1,25(OH2D3, has an antiproliferative, anti-apopitotic and prodifferentiating effects in several tumour types in preclinical studies. Several studies reported the impact of vitamin D on cancer risk particularly in breast and colorectal cancer however, its effect on thyroid cancer is less known. This review focuses on the relationship of vitamin D and thyroid cancer under the light of the litherature. Thyroid cancer is the most common endocrine cancer and also vitamin D deficiency is a common condition throughout the world. Some clinical studies showed that vitamin D deficiency is higher in patients with thyroid cancer. Preclinical studies evidenced that vitamin D has an effect on differentiation, reduction in tumor burden, and prevention of metastatic growth in thyroid cancer used alone or in combination with anticancer drugs. However, further clinical studies are needed to understand its impact on prognosis of thyroid cancer.

  15. Selenium and thyroid autoimmunity

    Directory of Open Access Journals (Sweden)

    Roberto Negro

    2008-06-01

    Full Text Available Roberto NegroDepartment of Endocrinology, “V. Fazzi” Hospital, Lecce, ItalyAbstract: The trace element selenium (Se occurs in the form of the amino acid selenocysteine in selenoproteins. Selenoproteins exerts multiple physiological effects in human health, many of which are related with regulation of reduction-oxidation processes. In fact, the selenoenzyme families of glutathione peroxidase (GPx and thioredoxin reductase (TRx display the ability to act as antioxidants, protecting cells from oxidative damage. Furthermore, another class of selenoproteins are the iodothyronine deiodinase enzymes (DIO, which catalyze the conversion of thyroxine (T4 in triiodothyronine (T3, then exerting a fine tuned control on thyroid hormones metabolism. Several studies have investigated the potential positive effects of Se supplementation in thyroid diseases, characterized by increased levels of hydrogen peroxide and free radicals, like autoimmune chronic thyroiditis. These studies have supplied evidences indicating that Se supplementation, maximizing the antioxidant enzymes activity, may reduce the thyroid inflammatory status. Then, it may be postulated that Se could play a therapeutical role in thyroid autoimmune diseases. Despite the fact that recent studies seem to be concordant about Se beneficial effects in decreasing thyroid peroxidase antibodies (TPOAb titers and ameliorating the ultrasound echogenicity pattern, several doubts have to be still clarified, before advising Se supplementation in chronic autoimmune thyroiditis.Keywords: selenium, thyroid, autoimmunity

  16. Axillary lymph nodes metastasis in a patient with recurrent papillary thyroid cancer: a case report

    OpenAIRE

    Hafez, Mohamed T; Refky, Basel; Elwahab, Khaled Abd; Arafa, Mohammad; Abdou, Islam; Elnahas, Waleed

    2015-01-01

    Introduction Thyroid cancer is the most common endocrine malignancy; the most common type of thyroid cancer is papillary thyroid cancer which accounts for approximately 90% of all thyroid cancers. Previously defined prognostic factors of papillary thyroid cancer include age, gender, tumor size, extrathyroidal extension, and distant metastasis. Cervical lymph node metastases are very common in patients with papillary thyroid cancer. Although papillary thyroid cancer has an excellent prognosis,...

  17. Galectin-3 leads to attenuation of apoptosis through Bax heterodimerization in human thyroid carcinoma cells.

    Science.gov (United States)

    Harazono, Yosuke; Kho, Dhong Hyo; Balan, Vitaly; Nakajima, Kosei; Zhang, Tianpeng; Hogan, Victor; Raz, Avraham

    2014-10-30

    Cancer cells survive escaping normal apoptosis and the blocks in apoptosis that keep cancer cells alive are promising candidates for targeted therapy. Galectin-3 (Gal-3) is, a member of the lectin family, which is involved in cell growth, adhesion, proliferation and apoptosis. It remains elusive to understand the role of Gal-3 on apoptosis in thyroid carcinoma cells. Here, we report that Gal-3 heterodimerizes Bax, mediated by the carbohydrate recognition domain (CRD) of Gal-3, leading to anti-apoptotic characteristic. Gal-3/Bax interaction was suppressed by an antagonist of Gal-3, in which in turn cells became sensitive to apoptosis. The data presented here highlight that Gal-3 is involved in the anti-apoptosis of thyroid carcinoma cells. Thus, it suggests that targeting Gal-3 may lead to an improved therapeutic modality for thyroid cancer.

  18. Thyroid Disorders Overview

    Science.gov (United States)

    ... Hyperthyroidism Hypothyroidism Thyroid Nodules Pregnancy and Thyroid Disease Thyroid Disorders The thyroid is a small butterfly-shaped ... consumes less oxygen and produces less body heat. Thyroid Nodules A thyroid nodule is a small lump ...

  19. Oxidative stress and apoptosis induction in human thyroid carcinoma cells exposed to the essential oil from Pistacia lentiscus aerial parts.

    Directory of Open Access Journals (Sweden)

    Simona Catalani

    Full Text Available Essential oils from the aerial parts (leaves, twigs and berries of Pistacia lentiscus (PLEO have been well characterized for their antibacterial and anti-inflammatory properties; however, poor information exists on their potential anticancer activity.Increasing concentrations of PLEO (0.01-0.1% v/v, 80-800 μg/ml were administered to a wide variety of cultured cancer cells from breast, cervix, colon, liver, lung, prostate, and thyroid carcinomas. Fibroblasts were also included as healthy control cells. Cell viability was monitored by WST-8 assay up to 72 hours after PLEO administration. The intracellular formation of reactive oxygen species (ROS, the induction of apoptosis, and the enhancement of chemotherapeutic drug cytotoxicity by PLEO were further investigated in the most responsive cancer cell line.A dose-dependent reduction of tumor cell viability was observed upon PLEO exposure; while no cytotoxic effect was revealed in healthy fibroblasts. FTC-133 thyroid cancer cells were found to be the most sensitive cells to PLEO treatment; accordingly, an intracellular accumulation of ROS and an activation of both the extrinsic and intrinsic apoptotic pathways were evidenced in FTC-133 cells after PLEO administration. Furthermore, the cytotoxic effect of the antineoplastic drugs cisplatin, 5-fluorouracil and etoposide was enhanced in PLEO-exposed FTC-133 cells.Taking into account its mode of action, PLEO might be considered as a promising source of natural antitumor agents which might have therapeutic potential in integrated oncology.

  20. Oxidative stress and apoptosis induction in human thyroid carcinoma cells exposed to the essential oil from Pistacia lentiscus aerial parts.

    Science.gov (United States)

    Catalani, Simona; Palma, Francesco; Battistelli, Serafina; Benedetti, Serena

    2017-01-01

    Essential oils from the aerial parts (leaves, twigs and berries) of Pistacia lentiscus (PLEO) have been well characterized for their antibacterial and anti-inflammatory properties; however, poor information exists on their potential anticancer activity. Increasing concentrations of PLEO (0.01-0.1% v/v, 80-800 μg/ml) were administered to a wide variety of cultured cancer cells from breast, cervix, colon, liver, lung, prostate, and thyroid carcinomas. Fibroblasts were also included as healthy control cells. Cell viability was monitored by WST-8 assay up to 72 hours after PLEO administration. The intracellular formation of reactive oxygen species (ROS), the induction of apoptosis, and the enhancement of chemotherapeutic drug cytotoxicity by PLEO were further investigated in the most responsive cancer cell line. A dose-dependent reduction of tumor cell viability was observed upon PLEO exposure; while no cytotoxic effect was revealed in healthy fibroblasts. FTC-133 thyroid cancer cells were found to be the most sensitive cells to PLEO treatment; accordingly, an intracellular accumulation of ROS and an activation of both the extrinsic and intrinsic apoptotic pathways were evidenced in FTC-133 cells after PLEO administration. Furthermore, the cytotoxic effect of the antineoplastic drugs cisplatin, 5-fluorouracil and etoposide was enhanced in PLEO-exposed FTC-133 cells. Taking into account its mode of action, PLEO might be considered as a promising source of natural antitumor agents which might have therapeutic potential in integrated oncology.

  1. Inhibitory effects of retinoic acid on invasiveness of human thyroid carcinoma cell lines in vitro.

    Science.gov (United States)

    Lan, L; Cui, D; Luo, Y; Shi, B Y; Deng, L L; Zhang, G Y; Wang, H

    2009-10-01

    The prognosis of patients with metastasized thyroid carcinoma is not optimistic, necessitating the search for new treatment options. Beneficial effects of retinoic acid (RA) have been suggested in thyroid cancer differentiation and the present study was performed to investigate the anti-metastatic potential of RA in respect of important determinants of metastatic behavior in thyroid carcinoma, focusing on the role of invasion-associated proteins. Differentiated thyroid carcinoma cell lines FTC- 133 and XTC.UC1, and anaplastic thyroid cancer cell lines C643 and HTH74 were studied. All cell lines were cultured with alltrans- RA (ATRA) or the solvent ethanol. Invasion and adhesion potency in vitro was studied by transwell experiment and short-term adhesion assay. The involvement of invasion-associated proteins, urokinase type plasminogen activator (uPA), uPA receptor (uPAR), matrix metalloproteinase-2 (MMP-2) and E-cadherin, were investigated by semi-quantitative RT-PCR and Western blot. In vitro invasion assay revealed that ATRA treatment could reduce the invasive potency in all the thyroid cancer cell lines, with the most significant effect in anaplastic cancer cells. Short-term adhesion assay suggested that ATRA increases cancer cell adhesion to extracellular matrix (ECM) in C643, HTH74 and XTC.UC1, probably through a transcriptional and translational regulation of some attachment molecules. RT-PCR andWestern blot both revealed diminished expression of uPAR in all four carcinoma cell lines. In C643 and HTH74 cell lines, the expression of uPA was reduced and the expression of E-cadherin was increased, whereas the MMP-2 expression was not significantly down-regulated in ATRA-treated group. In ATRA-treated FTC-133 and XTC.UC1 cell lines, MMP-2 expression was decreased, but no significant changes in uPA and E-cadherin expression were observed. The present study demonstrates the influence of ATRA on both important determinants of metastatic behavior ("de-adhesion" and

  2. Molecular signatures of thyroid follicular neoplasia

    DEFF Research Database (Denmark)

    Borup, R.; Rossing, M.; Henao, Ricardo

    2010-01-01

    The molecular pathways leading to thyroid follicular neoplasia are incompletely understood, and the diagnosis of follicular tumors is a clinical challenge. To provide leads to the pathogenesis and diagnosis of the tumors, we examined the global transcriptome signatures of follicular thyroid...

  3. Parathyroid involvement in thyroid cancer: an unforeseen event

    Directory of Open Access Journals (Sweden)

    Chrisoulidou Alexandra

    2012-06-01

    Full Text Available Abstract Background Parathyroid metastatic disease from thyroid cancer has not been studied extensively, mainly due to the need for parathyroid preservation during thyroid surgery. Methods We reviewed files from 1,770 patients with thyroid cancer followed up in our department and 10 patients with parathyroid metastases (0.5% were identified. Patient and tumor characteristics were recorded. Results Six out of ten patients had metastases from papillary thyroid cancer, three from follicular thyroid cancer and one from anaplastic thyroid cancer. In nine patients parathyroid infiltration from thyroid cancer was found in direct contact with the thyroid cancer, and in one patient metastatic foci were observed not in continuity with the thyroid cancer. Conclusions Parathyroid involvement, although infrequent, may occur in thyroid cancer independently of patient age and tumor size. The clinical significance of such event is not clear. The influence on disease outcome remains to be elucidated.

  4. Label-free electrochemical detection of human methyltransferase from tumors.

    Science.gov (United States)

    Furst, Ariel L; Muren, Natalie B; Hill, Michael G; Barton, Jacqueline K

    2014-10-21

    The role of abnormal DNA methyltransferase activity in the development and progression of cancer is an essential and rapidly growing area of research, both for improved diagnosis and treatment. However, current technologies for the assessment of methyltransferase activity, particularly from crude tumor samples, limit this work because they rely on radioactivity or fluorescence and require bulky instrumentation. Here, we report an electrochemical platform that overcomes these limitations for the label-free detection of human DNA(cytosine-5)-methyltransferase1 (DNMT1) methyltransferase activity, enabling measurements from crude cultured colorectal cancer cell lysates (HCT116) and biopsied tumor tissues. Our multiplexed detection system involving patterning and detection from a secondary electrode array combines low-density DNA monolayer patterning and electrocatalytically amplified DNA charge transport chemistry to measure selectively and sensitively DNMT1 activity within these complex and congested cellular samples. Based on differences in DNMT1 activity measured with this assay, we distinguish colorectal tumor tissue from healthy adjacent tissue, illustrating the effectiveness of this two-electrode platform for clinical applications.

  5. Adoptively transferred human lung tumor specific cytotoxic T cells can control autologous tumor growth and shape tumor phenotype in a SCID mouse xenograft model

    Directory of Open Access Journals (Sweden)

    Ferrone Soldano

    2007-06-01

    Full Text Available Abstract Background The anti-tumor efficacy of human immune effector cells, such as cytolytic T lymphocytes (CTLs, has been difficult to study in lung cancer patients in the clinical setting. Improved experimental models for the study of lung tumor-immune cell interaction as well as for evaluating the efficacy of adoptive transfer of immune effector cells are needed. Methods To address questions related to the in vivo interaction of human lung tumor cells and immune effector cells, we obtained an HLA class I + lung tumor cell line from a fresh surgical specimen, and using the infiltrating immune cells, isolated and characterized tumor antigen-specific, CD8+ CTLs. We then established a SCID mouse-human tumor xenograft model with the tumor cell line and used it to study the function of the autologous CTLs provided via adoptive transfer. Results The tumor antigen specific CTLs isolated from the tumor were found to have an activated memory phenotype and able to kill tumor cells in an antigen specific manner in vitro. Additionally, the tumor antigen-specific CTLs were fully capable of homing to and killing autologous tumors in vivo, and expressing IFN-γ, each in an antigen-dependent manner. A single injection of these CTLs was able to provide significant but temporary control of the growth of autologous tumors in vivo without the need for IL-2. The timing of injection of CTLs played an essential role in the outcome of tumor growth control. Moreover, immunohistochemical analysis of surviving tumor cells following CTL treatment indicated that the surviving tumor cells expressed reduced MHC class I antigens on their surface. Conclusion These studies confirm and extend previous studies and provide additional information regarding the characteristics of CTLs which can be found within a patient's tumor. Moreover, the in vivo model described here provides a unique window for observing events that may also occur in patients undergoing adoptive cellular

  6. Phase transitions in tumor growth: IV relationship between metabolic rate and fractal dimension of human tumor cells

    Science.gov (United States)

    Betancourt-Mar, J. A.; Llanos-Pérez, J. A.; Cocho, G.; Mansilla, R.; Martin, R. R.; Montero, S.; Nieto-Villar, J. M.

    2017-05-01

    By the use of thermodynamics formalism of irreversible processes, complex systems theory and systems biology, it is derived a relationship between the production of entropy per unit time, the fractal dimension and the tumor growth rate for human tumors cells. The thermodynamics framework developed demonstrates that, the dissipation function is a Landau potential and also the Lyapunov function of the dynamical behavior of tumor growth, which indicate the directional character, stability and robustness of the phenomenon. The entropy production rate may be used as a quantitative index of the metastatic potential of tumors. The current theoretical framework will hopefully provide a better understanding of cancer and contribute to improvements in cancer treatment.

  7. Clinical Features and Treatment Outcomes of 41 Dogs with Sublingual Ectopic Thyroid Neoplasia

    National Research Council Canada - National Science Library

    Broome, M.R; Peterson, M.E; Walker, J.R

    2014-01-01

    ... cervical location results in ectopic cranial mediastinal, heart base thyroid tissue, or both. Thyroid tumors in dogs are relatively common, representing approximately 1–3% of all neoplasia in the dog. Tumors arising from ectopic thyroid tissue are considered relatively rare, but such ectopic thyroid neoplasia has been documented in ...

  8. Thyroid cancer

    Science.gov (United States)

    ... neck (especially in childhood) Radiation exposure from nuclear plant disasters Other risk factors are a family history ... Cough Difficulty swallowing Enlargement of the thyroid gland Hoarseness or changing voice Neck swelling Thyroid lump (nodule) ...

  9. Thyroid Cancer

    Science.gov (United States)

    ... body work normally. There are several types of cancer of the thyroid gland. You are at greater ... imaging tests, and a biopsy to diagnose thyroid cancer. Treatment depends on the type of cancer you ...

  10. Telomere length modulation in human astroglial brain tumors.

    Directory of Open Access Journals (Sweden)

    Domenico La Torre

    Full Text Available BACKGROUND: Telomeres alteration during carcinogenesis and tumor progression has been described in several cancer types. Telomeres length is stabilized by telomerase (h-TERT and controlled by several proteins that protect telomere integrity, such as the Telomere Repeat-binding Factor (TRF 1 and 2 and the tankyrase-poli-ADP-ribose polymerase (TANKs-PARP complex. OBJECTIVE: To investigate telomere dysfunction in astroglial brain tumors we analyzed telomeres length, telomerase activity and the expression of a panel of genes controlling the length and structure of telomeres in tissue samples obtained in vivo from astroglial brain tumors with different grade of malignancy. MATERIALS AND METHODS: Eight Low Grade Astrocytomas (LGA, 11 Anaplastic Astrocytomas (AA and 11 Glioblastoma Multiforme (GBM samples were analyzed. Three samples of normal brain tissue (NBT were used as controls. Telomeres length was assessed through Southern Blotting. Telomerase activity was evaluated by a telomere repeat amplification protocol (TRAP assay. The expression levels of TRF1, TRF2, h-TERT and TANKs-PARP complex were determined through Immunoblotting and RT-PCR. RESULTS: LGA were featured by an up-regulation of TRF1 and 2 and by shorter telomeres. Conversely, AA and GBM were featured by a down-regulation of TRF1 and 2 and an up-regulation of both telomerase and TANKs-PARP complex. CONCLUSIONS: In human astroglial brain tumours, up-regulation of TRF1 and TRF2 occurs in the early stages of carcinogenesis determining telomeres shortening and genomic instability. In a later stage, up-regulation of PARP-TANKs and telomerase activation may occur together with an ADP-ribosylation of TRF1, causing a reduced ability to bind telomeric DNA, telomeres elongation and tumor malignant progression.

  11. The role of Arg445 and Asp498 in the human thyroid hormone transporter MCT8

    NARCIS (Netherlands)

    S. Groeneweg (Stefan); E.C.H. Friesema (Edith); S. Kersseboom (Simone); W. Klootwijk (Willem); W.E. Visser (Wil Edward); R.P. Peeters (Robin); T.J. Visser (Theo)

    2014-01-01

    textabstractMonocarboxylate transporter 8 (MCT8) facilitates cellular influx and efflux of the thyroid hormones (THs) T4 and T3. Mutations in MCT8 lead to severe psychomotor retardation. Here, we studied the importance of 2 highly conserved residues (Arg445 in transmembrane domain 8 and Asp498 in

  12. Tumor environmental factors glucose deprivation and lactic acidosis induce mitotic chromosomal instability--an implication in aneuploid human tumors.

    Directory of Open Access Journals (Sweden)

    Chunyan Dai

    Full Text Available Mitotic chromosomal instability (CIN plays important roles in tumor progression, but what causes CIN is incompletely understood. In general, tumor CIN arises from abnormal mitosis, which is caused by either intrinsic or extrinsic factors. While intrinsic factors such as mitotic checkpoint genes have been intensively studied, the impact of tumor microenvironmental factors on tumor CIN is largely unknown. We investigate if glucose deprivation and lactic acidosis--two tumor microenvironmental factors--could induce cancer cell CIN. We show that glucose deprivation with lactic acidosis significantly increases CIN in 4T1, MCF-7 and HCT116 scored by micronuclei, or aneuploidy, or abnormal mitosis, potentially via damaging DNA, up-regulating mitotic checkpoint genes, and/or amplifying centrosome. Of note, the feature of CIN induced by glucose deprivation with lactic acidosis is similar to that of aneuploid human tumors. We conclude that tumor environmental factors glucose deprivation and lactic acidosis can induce tumor CIN and propose that they are potentially responsible for human tumor aneuploidy.

  13. Tumor Environmental Factors Glucose Deprivation and Lactic Acidosis Induce Mitotic Chromosomal Instability – An Implication in Aneuploid Human Tumors

    Science.gov (United States)

    Zhu, Chunpeng; Hu, Xun

    2013-01-01

    Mitotic chromosomal instability (CIN) plays important roles in tumor progression, but what causes CIN is incompletely understood. In general, tumor CIN arises from abnormal mitosis, which is caused by either intrinsic or extrinsic factors. While intrinsic factors such as mitotic checkpoint genes have been intensively studied, the impact of tumor microenvironmental factors on tumor CIN is largely unknown. We investigate if glucose deprivation and lactic acidosis – two tumor microenvironmental factors – could induce cancer cell CIN. We show that glucose deprivation with lactic acidosis significantly increases CIN in 4T1, MCF-7 and HCT116 scored by micronuclei, or aneuploidy, or abnormal mitosis, potentially via damaging DNA, up-regulating mitotic checkpoint genes, and/or amplifying centrosome. Of note, the feature of CIN induced by glucose deprivation with lactic acidosis is similar to that of aneuploid human tumors. We conclude that tumor environmental factors glucose deprivation and lactic acidosis can induce tumor CIN and propose that they are potentially responsible for human tumor aneuploidy. PMID:23675453

  14. The humanized anti-human AMHRII mAb 3C23K exerts an anti-tumor activity against human ovarian cancer through tumor-associated macrophages.

    Science.gov (United States)

    Bougherara, Houcine; Némati, Fariba; Nicolas, André; Massonnet, Gérald; Pugnière, Martine; Ngô, Charlotte; Le Frère-Belda, Marie-Aude; Leary, Alexandra; Alexandre, Jérôme; Meseure, Didier; Barret, Jean-Marc; Navarro-Teulon, Isabelle; Pèlegrin, André; Roman-Roman, Sergio; Prost, Jean-François; Donnadieu, Emmanuel; Decaudin, Didier

    2017-11-21

    Müllerian inhibiting substance, also called anti-Müllerian hormone (AMH), inhibits proliferation and induces apoptosis of AMH type II receptor-positive tumor cells, such as human ovarian cancers (OCs). On this basis, a humanized glyco-engineered monoclonal antibody (3C23K) has been developed. The aim of this study was therefore to experimentally confirm the therapeutic potential of 3C23K in human OCs. We first determined by immunofluorescence, immunohistochemistry and cytofluorometry analyses the expression of AMHRII in patient's tumors and found that a majority (60 to 80% depending on the detection technique) of OCs were positive for this marker. We then provided evidence that the tumor stroma of OC is enriched in tumor-associated macrophages and that these cells are responsible for 3C23K-induced killing of tumor cells through ADCP and ADCC mechanisms. In addition, we showed that 3C23K reduced macrophages induced-T cells immunosuppression. Finally, we evaluated the therapeutic efficacy of 3C23K alone and in combination with a carboplatin-paclitaxel chemotherapy in a panel of OC Patient-Derived Xenografts. In those experiments, we showed that 3C23K significantly increased the proportion and the quality of chemotherapy-based in vivo responses. Altogether, our data support the potential interest of AMHRII targeting in human ovarian cancers and the evaluation of 3C23K in further clinical trials.

  15. [Beneficial effects of retinoic acid on in vitro invasiveness of human thyroid carcinoma cell lines].

    Science.gov (United States)

    Lan, Ling; Cui, Dai; Luo, Yong; Shi, Bing-yin; Deng, Li-li; Zhang, Guo-ying; Deng, Wei; Wang, Hong

    2010-09-14

    To investigate the anti metastatic potential of retinoic acid as an important determinant of metastatic behavior in thyroid carcinoma and understand the role of invasion associated proteins. Differentiated thyroid carcinoma cell lines FTC-133 and XTC.UC1, anaplastic thyroid cancer cell lines C643 and HTH74 were studied. All cell lines were cultured with all-trans-RA (ATRA) or solvent ethanol. The in vitro invasion and adhesion potency were studied by transwell experiment and short-term adhesion assay. The functions of invasion associated proteins, urokinase type plasminogen activator (uPA), uPA receptor (uPAR), MMP2 and E-cadherin were investigated by semi-quantitative RT-PCR and Western blot. In vitro invasion assay revealed that ATRA treatment could reduce the invasive potency in all the thyroid cancer cell lines. On Day 5 of ATRA treatment, the numbers of cells that migrated through extracellular matrix were as follows, in contrast to control group, FTC-133: 91±9 vs 118±10, C643: 92±17 vs 164±21, HTH74: 87±18 vs 169±15, and XTC.UC1: 95±23 vs 136±15, respectively (all PXTC.UC1. RT-PCR and Western blot both revealed diminished expression of uPAR in all four carcinoma cell lines. In C643 and HTH74 cell lines, the expression of uPA was reduced and the expression of E-Cadherin was increased; whereas the MMP2 expression was not significantly down-regulated in ATRA treated group. In ATRA treated FTC-133 and XTC.UC1 cell lines, MMP2 expression was decreased, but no significant changes in uPA and E-Cadherin expression were observed. The present study demonstrates the influence of ATRA on two important determinants of metastatic behavior ("de adhesion" and proteolysis) in thyroid carcinoma cell lines.

  16. Thyroid function in multidrug-resistant tuberculosis patients with or without human immunodeficiency virus (HIV) infection before commencement of MDR-TB drug regimen.

    Science.gov (United States)

    Ige, Olusoji Mayowa; Akinlade, Kehinde Sola; Rahamon, Sheu Kadiri; Edem, Victory Fabian; Arinola, Olatunbosun Ganiyu

    2016-06-01

    Mycobacterium tuberculosis and human immunodeficiency virus (HIV) are known to cause abnormal thyroid function. There is little information on whether HIV infection aggravates alteration of thyroid function in patients with MDR-TB. This study was carried out to determine if HIV co-infection alters serum levels of thyroid hormones (T3, T4) and thyroid stimulating hormone (TSH) in patients with MDR-TB patients and to find out the frequency of subclinical thyroid dysfunction before the commencement of MDR-TB therapy. This observational and cross-sectional study involved all the newly admitted patients in MDR-TB Referral Centre, University College Hospital, Ibadan, Nigeria between July 2010 and December 2014. Serum levels of thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were determined using ELISA. Enrolled were 115 patients with MDR-TB, out of which 22 (19.13%) had MDR-TB/HIV co-infection. Sick euthyroid syndrome (SES), subclinical hypothyroidism and subclinical hyperthyroidism were observed in 5 (4.35%), 9 (7.83%) and 2 (1.74%) patients respectively. The median level of TSH was insignificantly higher while the median levels of T3 and T4 were insignificantly lower in patients with MDR-TB/HIV co-infection compared with patients with MDRT-TB only. It could be concluded from this study that patients with MDR-TB/HIV co-infection have a similar thyroid function as patients having MDR-TB without HIV infection before commencement of MDR-TB drug regimen. Also, there is a possibility of subclinical thyroid dysfunction in patients with MDR-TB/HIV co-infection even, before the commencement of MDR-TB therapy.

  17. Pretargeted 177Lu radioimmunotherapy of carcinoembryonic antigen-expressing human colonic tumors in mice

    National Research Council Canada - National Science Library

    Schoffelen, R; Graaf, W.T.A. van der; Franssen, G.M; Sharkey, R.M; Goldenberg, D.M; McBride, W.J; Rossi, E.A; Eek, A; Oyen, W.J.G; Boerman, O.C

    2010-01-01

    ... (CEA)-expressing human tumors. METHODS: To obtain the optimal therapeutic efficacy, several strategies were evaluated to increase the total amount of radioactivity targeted to subcutaneous LS174T colon cancer tumors in BALB/c nude mice...

  18. Radioactivity and thyroid cancer.

    Science.gov (United States)

    Reiners, Christopher

    2009-01-01

    There is no evidence that natural radiation (cosmic radiation or from natural radioiosotopes) increases the risk for thyroid diseases. Moreover, while it has been proven that exposure to external medical radiation or to external and internal radiation by atomic bomb explosions leads to an increased risk for thyroid cancer, the medical use of radioiodine, namely diagnostic and therapeutic application of (1)(3)(1)I, is safe and does not induce thyroid cancer. Exposure of children aged less than 4 years to fallout from the Chernobyl reactor accident has led to a substantial increase of childhood cancer incidence in the countries affected (Belarus, Ukraine and Western parts of Russia). Up to now, the total number of cases in children and adolescents adds up to approximately 5,000; in the next 50 years, approximately 15,000 additional thyroid cancer cases in this age group are expected. With respect to the Chernobyl effects on adults, there is no proven radiation related increase of the thyroid cancer incidence. As can be proven by a therapy project in 247 children with advanced thyroid cancer from Belarus, the prognosis for this tumor, even when metastasized, is good, this being in accordance with literature data indicating mortality rates between 1 and 2%.

  19. Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention.

    Directory of Open Access Journals (Sweden)

    Liying Gu

    Full Text Available The aim of this current study was to investigate the expression of the tumor necrosis factor (TNF-like weak inducer of apoptosis (TWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14 in human malignant ovarian tumors, and test TWEAK's potential role on tumor progression in cell models in-vitro. Using immunohistochemistry (IHC, we found that TWEAK and its receptor Fn14 were expressed in human malignant ovarian tumors, but not in normal ovarian tissues or in borderline/benign epithelial ovarian tumors. High levels of TWEAK expression was detected in the majority of malignant tumors (36 out of 41, 87.80%. Similarly, 35 out of 41 (85.37% malignant ovarian tumors were Fn14 positive. In these malignant ovarian tumors, however, TWEAK/Fn14 expression was not corrected with patients' clinical subtype/stages or pathological features. In vitro, we demonstrated that TWEAK only inhibited ovarian cancer HO-8910PM cell proliferation in combination with tumor necrosis factor-α (TNF-α, whereas either TWEAK or TNF-α alone didn't affect HO-8910PM cell growth. TWEAK promoted TNF-α production in cultured THP-1 macrophages. Meanwhile, conditioned media from TWEAK-activated macrophages inhibited cultured HO-8910PM cell proliferation and invasion. Further, TWEAK increased monocyte chemoattractant protein-1 (MCP-1 production in cultured HO-8910PM cells to possibly recruit macrophages. Our results suggest that TWEAK/Fn14, by activating macrophages, could be ovarian tumor suppressors. The unique expression of TWEAK/Fn14 in malignant tumors indicates that it might be detected as a malignant ovarian tumor marker.

  20. Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model.

    Science.gov (United States)

    Park, Jeong Won; Han, Cho Rong; Zhao, Li; Willingham, Mark C; Cheng, Sheue-yann

    2016-01-01

    Compelling epidemiologic studies indicate that obesity is a risk factor for many human cancers, including thyroid cancer. In recent decades, the incidence of thyroid cancer has dramatically increased along with a marked rise in obesity prevalence. We previously demonstrated that a high fat diet (HFD) effectively induced the obese phenotype in a mouse model of thyroid cancer (Thrb(PV/PV)Pten(+/-) mice). Moreover, HFD activates the STAT3 signal pathway to promote more aggressive tumor phenotypes. The aim of the present study was to evaluate the effect of S3I-201, a specific inhibitor of STAT3 activity, on HFD-induced aggressive cancer progression in the mouse model of thyroid cancer. WT and Thrb(PV/PV)Pten(+/-) mice were treated with HFD together with S3I-201 or vehicle-only as controls. We assessed the effects of S3I-201 on HFD-induced thyroid cancer progression, the leptin-JAK2-STAT3 signaling pathway, and key regulators of epithelial-mesenchymal transition (EMT). S3I-201 effectively inhibited HFD-induced aberrant activation of STAT3 and its downstream targets to markedly inhibit thyroid tumor growth and to prolong survival. Decreased protein levels of cyclins D1 and B1, cyclin dependent kinase 4 (CDK4), CDK6, and phosphorylated retinoblastoma protein led to the inhibition of tumor cell proliferation in S3I-201-treated Thrb(PV/PV)Pten(+/-) mice. Reduced occurrence of vascular invasion and blocking of anaplasia and lung metastasis in thyroid tumors of S3I-201-treated Thrb(PV/PV)Pten(+/-) mice were mediated via decreased expression of vimentin and matrix metalloproteinases, two key effectors of EMT. The present findings suggest that inhibition of the STAT3 activity would be a novel treatment strategy for obesity-induced thyroid cancer. © 2016 Society for Endocrinology.

  1. [E1A gene transfection of human undifferentiated thyroid cancer cell line HTC/3 by nanoparticles].

    Science.gov (United States)

    He, Xiang-Liang; He, Dong-Hua; Liao, Xiao-Xing; Zhan, Hong; Ma, Zhong-Fu; Wang, Xi-Fu; Li, Qing; Li, Xin; Li, Yu-Jie

    2007-12-01

    To prepare nanoparticles containing E1A gene and observe the efficiency and feasibility of transfecting E1A gene into human undifferentiated thyroid cancer cell line HTC/3. To examine the sensitivity of transgene cells to X-ray and X-ray-induced apoptosis in those cells. Nanoparticle-DNA complex was prepared with PLGA coating adenoviral early expression gene E1A, and the package efficiency, release progress in vitro, and size of the complex were determined. The nanoparticle-DNA was transfected into the HTC/3 cells. Lipofectamine was used to transfect E1A gene as a control. RT-PCR was used to examine E1A gene mRNA expression in the transfected cells. The survival ratio of HTC/3-E1A and control cells, and the growth inhibition ratio induced by different doses of X-ray in HTC/3-E1A cells were examined by MTT assay. The apoptosis in HTC/3-E1A cells induced by 2 Gy X-ray iradiation was examined by flow cytometry and DNA electrophoresis. The package efficiency, release progress in vitro, and size of the nanoparticle-DNA complex were 0.78%, 18 days, and 150-280 nm, respectively when transfected the plasmid at the same level, the nanoparticle group got more positive transgene cell clones than that in lipofectamine group, with a statistically significant difference (P HTC/3-E1A cells grew slowly, and their doubling time was prolongated (1.44 times in comparison with that in parental cells). According to IC50, the sensitivity of HTC/3-E1A cells to X-ray was improved 2.9 and 2.8 times, respectively, in comparison with that in HTC/3-Vect and HTC/3 cells. The ratio of subG0/G1 phase of HTC/3-E1A cells was significantly higher than that in HTC/3-Vect and HTC/3 cells (P HTC/3-E1A cells was significantly lower than that in HTC/3-Vect and HTC/3 cells (P HTC/3-E1A cells was observed by electrophoresis, but not found in HTC/3-Vect and HTC/3 cells. A nanoparticle-DNA complex has been successfully prepared, and it may carry a foreign gene into cells. The sensitivity of HTC/3-E1A cells

  2. [Thyroid cancer].

    Science.gov (United States)

    Nagayama, Yuji

    2012-03-01

    The thyroid glands are a vulnerable organ to ionizing radiation. Indeed the epidemiological studies have revealed an increase in the incidences of thyroid cancer among atomic bomb survivors in Hiroshima and Nagasaki and radiation casualties in Chernobyl. The carcinogenic risk for the thyroids is dependent on radiation dose, and higher in younger people. Recent advances in molecular biology contribute to clarify the mechanisms for thyroid carcinogenesis at genetic and molecular levels. Here radiation-induced thyroid carcinogenesis is reviewed from epidemiological data to basic research.

  3. p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer

    Science.gov (United States)

    McFadden, David G.; Vernon, Amanda; Santiago, Philip M.; Martinez-McFaline, Raul; Bhutkar, Arjun; Crowley, Denise M.; McMahon, Martin; Sadow, Peter M.; Jacks, Tyler

    2014-01-01

    Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. PMID:24711431

  4. Humanized mouse model of ovarian cancer recapitulates patient solid tumor progression, ascites formation, and metastasis.

    Directory of Open Access Journals (Sweden)

    Richard B Bankert

    Full Text Available Ovarian cancer is the most common cause of death from gynecological cancer. Understanding the biology of this disease, particularly how tumor-associated lymphocytes and fibroblasts contribute to the progression and metastasis of the tumor, has been impeded by the lack of a suitable tumor xenograft model. We report a simple and reproducible system in which the tumor and tumor stroma are successfully engrafted into NOD-scid IL2Rγ(null (NSG mice. This is achieved by injecting tumor cell aggregates derived from fresh ovarian tumor biopsy tissues (including tumor cells, and tumor-associated lymphocytes and fibroblasts i.p. into NSG mice. Tumor progression in these mice closely parallels many of the events that are observed in ovarian cancer patients. Tumors establish in the omentum, ovaries, liver, spleen, uterus, and pancreas. Tumor growth is initially very slow and progressive within the peritoneal cavity with an ultimate development of tumor ascites, spontaneous metastasis to the lung, increasing serum and ascites levels of CA125, and the retention of tumor-associated human fibroblasts and lymphocytes that remain functional and responsive to cytokines for prolonged periods. With this model one will be able to determine how fibroblasts and lymphocytes within the tumor microenvironment may contribute to tumor growth and metastasis, and will make it possible to evaluate the efficacy of therapies that are designed to target these cells in the tumor stroma.

  5. Human melanoma immunotherapy using tumor antigen-specific T cells generated in humanized mice.

    Science.gov (United States)

    Hu, Zheng; Xia, Jinxing; Fan, Wei; Wargo, Jennifer; Yang, Yong-Guang

    2016-02-09

    A major factor hindering the exploration of adoptive immunotherapy in preclinical settings is the limited availability of tumor-reactive human T cells. Here we developed a humanized mouse model that permits large-scale production of human T cells expressing the engineered melanoma antigen MART-1-specific TCR. Humanized mice, made by transplantation of human fetal thymic tissue and CD34+ cells virally-transduced with HLA class I-restricted melanoma antigen (MART-1)-specific TCR gene, showed efficient development of MART-1-TCR+ human T cells with predominantly CD8+ cells. Importantly, MART-1-TCR+CD8+ T cells developing in these mice were capable of mounting antigen-specific responses in vivo, as evidenced by their proliferation, phenotypic conversion and IFN-γ production following MART-1 peptide immunization. Moreover, these MART-1-TCR+CD8+ T cells mediated efficient killing of melanoma cells in an HLA/antigen-dependent manner. Adoptive transfer of in vitro expanded MART-1-TCR+CD8+ T cells induced potent antitumor responses that were further enhanced by IL-15 treatment in melanoma-bearing recipients. Finally, a short incubation of MART-1-specific T cells with rapamycin acted synergistically with IL-15, leading to significantly improved tumor-free survival in recipients with metastatic melanoma. These data demonstrate the practicality of using humanized mice to produce potentially unlimited source of tumor-specific human T cells for experimental and preclinical exploration of cancer immunotherapy. This study also suggests that pretreatment of tumor-reactive T cells with rapamycin in combination with IL-15 administration may be a novel strategy to improve the efficacy of adoptive T cell therapy.

  6. Administration of interferon-gamma in healthy subjects does not modulate thyroid hormone metabolism

    NARCIS (Netherlands)

    de Metz, J.; Romijn, J. A.; Endert, E.; Corssmit, E. P.; Sauerwein, H. P.

    2000-01-01

    Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL-2), IL-6, and interferon-alpha (IFN-alpha), alter human thyroid hormone metabolism and may be involved in the pathogenesis the euthyroid sick syndrome. Experimental data suggest that interferon-gamma (IFN-gamma) could be

  7. Mathematical modeling of a survey-meter used to measure radioactivity in human thyroids: Monte Carlo calculations of the device response and uncertainties

    Science.gov (United States)

    Khrutchinsky, Arkady; Drozdovitch, Vladimir; Kutsen, Semion; Minenko, Victor; Khrouch, Valeri; Luckyanov, Nickolas; Voillequé, Paul; Bouville, André

    2012-01-01

    This paper presents results of Monte Carlo modeling of the SRP-68-01 survey meter used to measure exposure rates near the thyroid glands of persons exposed to radioactivity following the Chernobyl accident. This device was not designed to measure radioactivity in humans. To estimate the uncertainty associated with the measurement results, a mathematical model of the SRP-68-01 survey meter was developed and verified. A Monte Carlo method of numerical simulation of radiation transport has been used to calculate the calibration factor for the device and evaluate its uncertainty. The SRP-68-01 survey meter scale coefficient, an important characteristic of the device, was also estimated in this study. The calibration factors of the survey meter were calculated for 131I, 132I, 133I, and 135I content in the thyroid gland for six age groups of population: newborns; children aged 1 yr, 5 yr, 10 yr, 15 yr; and adults. A realistic scenario of direct thyroid measurements with an “extended” neck was used to calculate the calibration factors for newborns and one-year-olds. Uncertainties in the device calibration factors due to variability of the device scale coefficient, variability in thyroid mass and statistical uncertainty of Monte Carlo method were evaluated. Relative uncertainties in the calibration factor estimates were found to be from 0.06 for children aged 1 yr to 0.1 for 10-yr and 15-yr children. The positioning errors of the detector during measurements deviate mainly in one direction from the estimated calibration factors. Deviations of the device position from the proper geometry of measurements were found to lead to overestimation of the calibration factor by up to 24 percent for adults and up to 60 percent for 1-yr children. The results of this study improve the estimates of 131I thyroidal content and, consequently, thyroid dose estimates that are derived from direct thyroid measurements performed in Belarus shortly after the Chernobyl accident. PMID:22245289

  8. Pathways Regulating Spheroid Formation of Human Follicular Thyroid Cancer Cells under Simulated Microgravity Conditions: A Genetic Approach.

    Science.gov (United States)

    Riwaldt, Stefan; Bauer, Johann; Wehland, Markus; Slumstrup, Lasse; Kopp, Sascha; Warnke, Elisabeth; Dittrich, Anita; Magnusson, Nils E; Pietsch, Jessica; Corydon, Thomas J; Infanger, Manfred; Grimm, Daniela

    2016-04-08

    Microgravity induces three-dimensional (3D) growth in numerous cell types. Despite substantial efforts to clarify the underlying mechanisms for spheroid formation, the precise molecular pathways are still not known. The principal aim of this paper is to compare static 1g-control cells with spheroid forming (MCS) and spheroid non-forming (AD) thyroid cancer cells cultured in the same flask under simulated microgravity conditions. We investigated the morphology and gene expression patterns in human follicular thyroid cancer cells (UCLA RO82-W-1 cell line) after a 24 h-exposure on the Random Positioning Machine (RPM) and focused on 3D growth signaling processes. After 24 h, spheroid formation was observed in RPM-cultures together with alterations in the F-actin cytoskeleton. qPCR indicated more changes in gene expression in MCS than in AD cells. Of the 24 genes analyzed VEGFA, VEGFD, MSN, and MMP3 were upregulated in MCS compared to 1g-controls, whereas ACTB, ACTA2, KRT8, TUBB, EZR, RDX, PRKCA, CAV1, MMP9, PAI1, CTGF, MCP1 were downregulated. A pathway analysis revealed that the upregulated genes code for proteins, which promote 3D growth (angiogenesis) and prevent excessive accumulation of extracellular proteins, while genes coding for structural proteins are downregulated. Pathways regulating the strength/rigidity of cytoskeletal proteins, the amount of extracellular proteins, and 3D growth may be involved in MCS formation.

  9. Screening between normal and cancer human thyroid cells through comparative adhesion studies using the Quartz Crystal Microbalance

    Directory of Open Access Journals (Sweden)

    Dimitra Chronaki

    2016-12-01

    Full Text Available In this work, the Quartz Crystal Microbalance with Dissipation monitoring (QCM-D was used to distinguish the dynamic cell adhesion behavior of human normal (Nthy thyroid epithelial cells from poorly differentiated anaplastic carcinoma cells (ARO. The surfaces used to facilitate cell adhesion were bare titanium (Ti, gold (Au and fibrinogen-coated gold (Fg-Au. The pattern of cell adhesion for both cell lines was that the largest acoustic signals were observed on Ti, followed by Au and last by Fg-Au; in addition, ARO cells always produced smaller acoustic signals than Nthy cells on the same surface and for the same number of cells in suspension. Moreover, the calculated acoustic ratio of energy dissipation over frequency change suggests a higher ability of Nthy cells to spread and potentially form more attachment points on the surface than the ARO cells, something observed in SEM images. Finally, we demonstrated that the application of two surfaces for cell adhesion experiments, one of which is Au and the other either Ti or Fg-Au, can discriminate with accuracy between the two particular cell types and potentially form a platform for differentiation between normal and cancer thyroid cell types.

  10. Overexpression of thyroid hormone beta1 nuclear receptor is associated with an increased proliferation of human hepatoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, K.; Lin, Y.; McPhie, P. [Chang-Gung College of Medicine and Technology, Graduate Institute of Clinical Medicine, Taoyuan (Taiwan, Province of China); Cheng, S. [National Cancer Inst., Bethesda, MD (United States)

    1994-12-31

    It is evaluated the expression of thyroid hormone nuclear receptors (TRs) and their possible roles in the carcinogenesis of human hepatocarcinoma. The expression of TR{beta}1 and TR{alpha} genes was evaluated at both the mRNA and protein levels. The expression of TR{beta}1 and TR{alpha}1 mRNAs is similar to those found in normal liver. However, the expression of TR isoform proteins depends on the cell-type. The expression of TRaplha1 protein is low in all cell lines examined. However, TR{Beta}1 protein is overexpressed in Mahlavu, SK-Hep-1, and HA22T, moderately expressed in J5, J7, and J328 and is very low HepG2, Hep3B, and PLC/PRF/5 cells. The proliferation of cells in which TR{beta}1 is overexpressed is stimulated by the thyroid hormone, 3,3`,5- triiodo-L-thyronine. These results suggest that TR{beta}1, not TR{alpha}1, is probably involved in the prolifaration of hepatoma cells.

  11. Development of a screening approach to detect thyroid disrupting chemicals that inhibit the human sodium iodide symporter (NIS).

    Science.gov (United States)

    Hallinger, Daniel R; Murr, Ashley S; Buckalew, Angela R; Simmons, Steven O; Stoker, Tammy E; Laws, Susan C

    2017-04-01

    The U.S. EPA's Endocrine Disruptor Screening Program aims to use high-throughput assays and computational toxicology models to screen and prioritize chemicals that may disrupt the thyroid signaling pathway. Thyroid hormone biosynthesis requires active iodide uptake mediated by the sodium/iodide symporter (NIS). Monovalent anions, such as the environmental contaminant perchlorate, are competitive inhibitors of NIS, yet limited information exists for more structurally diverse chemicals. A novel cell line expressing human NIS, hNIS-HEK293T-EPA, was used in a radioactive iodide uptake (RAIU) assay to identify inhibitors of NIS-mediated iodide uptake. The RAIU assay was optimized and performance evaluated with 12 reference chemicals comprising known NIS inhibitors and inactive compounds. An additional 39 chemicals including environmental contaminants were evaluated, with 28 inhibiting RAIU over 20% of that observed for solvent controls. Cell viability assays were performed to assess any confounding effects of cytotoxicity. RAIU and cytotoxic responses were used to calculate selectivity scores to group chemicals based on their potential to affect NIS. RAIU IC50 values were also determined for chemicals that displayed concentration-dependent inhibition of RAIU (≥50%) without cytotoxicity. Strong assay performance and highly reproducible results support the utilization of this approach to screen large chemical libraries for inhibitors of NIS-mediated iodide uptake. Published by Elsevier Ltd.

  12. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft

    NARCIS (Netherlands)

    Nagengast, Wouter B.; Hospers, Geke A.; Mulder, Nanno H.; de Jong, Johan R.; Hollema, Harry; Brouwers, Adrienne H.; van Dongen, Guns A.; Perk, Lars R.; Lub-de Hooge, Marjolijn N.

    Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. The humanized monoclonal antibody bevacizumab blocks VEGF-induced tumor angiogenesis by binding, thereby neutralizing VEGF. Our aim was to develop radiolabeled bevacizumab for

  13. Study of the correlation between immunohistochemistry of the initial tumor and PET/CT after recombining TSH (RHTSH) in case of tumor recurrence in differentiated thyroid carcinomas; Etude de la correlation entre l'immunohistochimie de la tumeur initiale et la TEP-FDG/TDM apres TSH recombinante (RHTSH) en cas de recidive tumorale dans les carcinomes thyroidiens differencies

    Energy Technology Data Exchange (ETDEWEB)

    Lansoy-Kuhn, C.; Mechken, F.; Edet-Sanson, A.; Vera, P. [Centre Becquerel and QuantIF LITIS EA4108, Service de medecine nucleaire, 76 - Rouen (France); D' anjou, J.; Cornic, M. [Centre Henri-Becquerel, service anatomopathologie, 76 - Rouen (France)

    2010-07-01

    Purpose: In patients with differentiated thyroid carcinoma, the correlation between the value of thyroglobulin and the positivity of F.D.G.-PET remains controversial. We looked at whether the immunohistochemical criteria of the original tumor could be predictive of a positive PET in cases of tumor recurrence. Conclusions: on a larger series, we have not confirmed the results of Hooft (JCEM 2005). This study did not reveal immunohistochemical marker, present in the original tumor, which would be predictive of a positive PET-F.D.G. in the search for a recurrence. The study of NIS and GLUT1 expression is underway. (N.C.)

  14. Thyroid Disease and Teens

    Science.gov (United States)

    ... Situations Talking to Your Parents - or Other Adults Thyroid Disease KidsHealth > For Teens > Thyroid Disease Print A ... other parts of your body. continue What Is Thyroid Disease? Thyroid disease occurs when the thyroid gland ...

  15. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses ... the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is a ...

  16. Thyroid Scan and Uptake

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses ... the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is a ...

  17. Thyroid Disorders (For Kids)

    Science.gov (United States)

    ... Dieting OK for Kids? Your Teeth Heart Murmurs Thyroid Disorders KidsHealth > For Kids > Thyroid Disorders Print A ... the world is a thyroid? What Is the Thyroid? The thyroid (say: THYE-royd) is a gland, ...

  18. Thyroid cancer - medullary carcinoma

    Science.gov (United States)

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. ... and adults. Unlike other types of thyroid cancer, MTC is less ...

  19. Thyroid Disease (for Parents)

    Science.gov (United States)

    ... Late for the Flu Vaccine? Eating Disorders Arrhythmias Thyroid Disease KidsHealth > For Parents > Thyroid Disease Print A ... many other parts of the body. What Is Thyroid Disease? Thyroid disease is when the thyroid gland ...

  20. Modification of the hypoxic fraction of a xenografted human colon tumor by differentiation-inducing agents

    Energy Technology Data Exchange (ETDEWEB)

    Leith, J.T.

    1988-05-18

    Xenografted tumors were produced in nude mice by injection of HCT-15 human colon tumor cells. The hypoxic fractions of control tumors as determined from x-ray survival curves were approximately 18%. Other tumors were treated (every day X 9) with daily injections of N-methylformamide (150 mg/kg) or sodium butyrate (2,000 mg/kg). For both agents, it was found that the hypoxic fractions were less than 0.05% and less than 1.7%, respectively. These data indicate that selected differentiation-inducing agents could be of value for treatment of human solid tumors that contain hypoxic cells.

  1. Arterial supply to the thyroid gland and the relationship between the recurrent laryngeal nerve and the inferior thyroid artery in human fetal cadavers.

    Science.gov (United States)

    Ozgüner, G; Sulak, O

    2014-11-01

    The aim of this study was to identify the arterial supply to the thyroid gland and the relationship between the inferior thyroid artery (ITA) and the recurrent laryngeal nerve (RLN) in fetal cadavers using anatomical dissection. The anterior necks of 200 fetuses were dissected. The origins of the superior thyroid artery (STA) and the ITA and location of the ITA in relation to the entrance of the thyroid lobe were examined. The relationship between the ITA and the RLN was determined. The origins of the STA were classified as: external carotid artery, common carotid artery (CCA), and the thyrolingual trunk. The origins of the ITA were the thyrocervical trunk and the CCA. The ITA was absent on the left side in two cases. The relationship of the RLN to the ITA fell into seven different types. Type 1: the RLN lay posterior to the artery; right (42.5%), left (65%). Type 2: the RLN lay anterior to the artery; right (40.5%), left (22.5%). Type 3: the RLN lay parallel to the artery; right (11.5%), left (7%). Type 4: the RLN lay between the two branches of the artery; right (1%), left (3.5%). Type 5: The extralaryngeal branch of the RLN was detected before it crossed the ITA; right (4.5%), left (0%). Type 6: the ITA lay between the two branches of the RLN; right (0%), left (0.5%). Type 7: the branches of the RLN lay among the branches of the ITA; right (0%), left (0.5%). The results from this study would be useful in future thyroid surgeries. © 2014 Wiley Periodicals, Inc.

  2. A Large Nonmetastatic Anaplastic Thyroid Cancer with Complete Thyroidal Confinement

    Directory of Open Access Journals (Sweden)

    Jeffrey C. Xing

    2011-01-01

    Full Text Available Anaplastic thyroid cancer (ATC is rare but extremely aggressive, which accounts for about 2% of all thyroid cancers yet nearly 50% of thyroid-cancer-associated deaths in the United States. The median survival time from diagnosis is 5 months, with a 1-year survival rate of only 20%. We report here a case of ATC in a 56-year-old man who survived a large ATC. Preoperative fine-needle aspiration biopsy study to a large right thyroid mass suggested ATC. Total thyroidectomy with radical lateral neck and central neck dissection removed a well-circumscribed 9.5 cm tumor without extrathyroidal extension or lymphovascular invasion. All 73 lymph nodes removed were negative for metastasis. The tumor consisted of highly pleomorphic, undifferentiated cells with large zones of necrosis and loss of thyroid transcription factor-1 and thyroglobulin expression. A focal well-differentiated component and PAX8 expression confirmed its thyroid follicular cell origin. Nine months after postsurgical adjuvant concurrent radiation therapy and chemotherapy, the patient remained well without clinical, biochemical, and radiographical evidence for cancer recurrence. This is an unusual case of ATC in that it is one of the largest ATC tumors reported to display mild pathologic behavior and relatively long-term patient survival.

  3. Mouse x human heterohybridomas as fusion partners with human B cell tumors.

    Science.gov (United States)

    Carroll, W L; Thielemans, K; Dilley, J; Levy, R

    1986-05-01

    Surface idiotype (Id) of B cell malignancies is an excellent tumor-specific marker. We have, however, recently described heterogeneity of tumor Id in some cases. We therefore sought a way to isolate, reliably and efficiently, different species of idiotype from a potentially heterogeneous population. In this report we demonstrate our success using a series of mouse X human heterohybridomas as fusion partners with human B cell tumors. Three lines (K6H6/B5, K6H9/G12, SBC/H20) demonstrated excellent fusion efficiency with 75%-85% of wells plated containing hybrids. Two cell lines, K6H9/G12 and SBC/H20 had a tendency to secrete a single Ig chain (heavy or light chain), whereas the K6H6/B5 cell line secreted whole immunoglobulin (Ig) in greater than 80% of the hybrids. This line secreted significant amounts of Ig (2.73 micrograms/ml/10(6) cells) and was relatively stable in culture. Since this line has such a high fusion efficiency the products of normal B cells admixed with tumor may be recovered, allowing the opportunity of isolating host anti-tumor antibodies. In order to prove that hybrids were derived from the tumor, Southern blot analysis of rearranged DNA was performed in selected cases. Fusions with this line provide the potential for recovering many different species of idiotype in a mixed population. This will facilitate the production of mouse monoclonal anti-idiotype antibodies against many variants and against different idiotopes.

  4. WISP-2 expression in human salivary gland tumors.

    Science.gov (United States)

    Kouzu, Yukinao; Uzawa, Katsuhiro; Kato, Masaki; Higo, Morihiro; Nimura, Yoshinori; Harada, Koji; Numata, Tsutomu; Seki, Naohiko; Sato, Mitsunobu; Tanzawa, Hideki

    2006-04-01

    This study was designed to disclose detailed genetic mechanisms in salivary gland tumors (SGTs) for development of novel independent marker. We constructed an in-house cDNA microarray carrying 2,201 cDNA clones derived from SGT and oral squamous cell carcinoma cDNA libraries. Four cell lines that originated from the SGT-derived cell lines were analyzed using this microarray system. The genes identified by our microarray system were further analyzed at the mRNA or protein expression level in other types of human cancer cell lines and clinical samples (ten normal salivary glands [NSGs], eleven pleomorphic adenomas, ten adenoid cystic carcinomas and three adenocarcinomas). Two up-regulated genes and six down-regulated genes were identified in common when compared with the control RNA. Of the up-regulated genes, WISP-2, which plays an important role in breast carcinogenesis, was selected for further analyses. We found a higher expression of the WISP-2 gene in the SGT-derived cell lines compared with other types of human cancer cell lines. Furthermore, WISP-2 mRNA and protein expression levels in NSGs were significantly higher than those in SGTs. These results suggest that WISP-2 could be a reliable independent marker and that down-regulation or loss of the WISP-2 gene may be associated with the development of SGTs.

  5. DNA Methylation in Thyroid Tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Stephen, Josena K., E-mail: jstephe2@hfhs.org [Department of Otolaryngology/Head and Neck Surgery, Henry Ford Hospital, Detroit, MI 48202 (United States); Chitale, Dhananjay [Department of Pathology, Henry Ford Hospital, Detroit, MI 48202 (United States); Narra, Vinod [Essex Surgical Associates, PC, Beverly, MA 01915 (United States); Chen, Kang Mei; Sawhney, Raja; Worsham, Maria J. [Department of Otolaryngology/Head and Neck Surgery, Henry Ford Hospital, Detroit, MI 48202 (United States)

    2011-03-29

    Thyroid cancer is the most common endocrine cancer with 1,690 deaths each year. There are four main types of which the papillary and follicular types together account for >90% followed by medullary cancers with 3% to 5% and anaplastic carcinomas making up <3%. Epigenetic events of DNA hypermethylation are emerging as promising molecular targets for cancer detection. Our immediate and long term goal is to identify DNA methylation markers for early detection of thyroid cancer. This pilot study comprised of 21 patients to include 11 papillary thyroid cancers (PTC), 2 follicular thyroid cancers (FTC), 5 normal thyroid cases, and 3 hyperthyroid cases. Aberrant promoter methylation was examined in 24 tumor suppressor genes using the methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) assay and in the NIS gene using methylation-specific PCR (MSP). The frequently methylated genes were CASP8 (17/21), RASSF1 (16/21) and NIS (9/21). In the normal samples, CASP8, RASSF1 and NIS were methylated in 5/5, 4/5 and 1/5 respectively. In the hyperthyroid samples, CASP8, RASSF1 and NIS were methylated in 3/3, 2/3 and 1/3 respectively. In the thyroid cancers, CASP8, RASSF1, and NIS were methylated in 9/13, 10/13, and 7/13 respectively. CASP8, RASSF1 and NIS were also methylated in concurrently present normal thyroid tissue in 3/11, 4/11 and 3/11 matched thyroid cancer cases (matched for presence of both normal thyroid tissue and thyroid cancer), respectively. Our data suggests that aberrant methylation of CASP8, RASSF1, and NIS maybe an early change in thyroid tumorigenesis regardless of cell type.

  6. Tropomyosin-1, A Putative Tumor-Suppressor and a Biomarker of Human Breast Cancer

    Science.gov (United States)

    2004-10-01

    cDNA. Lobular carcinoma - 2 A polyclonal pan-TM antibody that recognizes multiple TM Phyllodes tumor - 1 Not determined from the initial pathology...AD Award Number: DAMD17-98-1-8162 TITLE: Tropomyosin-1, A Putative Tumor -Suppressor and a Biomarker of Human Breast Cancer PRINCIPAL INVESTIGATOR...4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Tropomyosin-l, A Putative Tumor -Suppressor and a Biomarker DAMD17-98-1-8162 of Human Breast Cancer 6. A UTHOR

  7. Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells

    Directory of Open Access Journals (Sweden)

    Massade L.

    2011-10-01

    Full Text Available RET/PTC1 fusion oncogene is the most common genetic alteration identified to date in thyroid papillary carcinomas (PTC and represents a good target for small interfering RNA (siRNA. Our aim was: i to target the RET/PTC1 oncogene by siRNAs, ii to assess the knockdown effects on cell growth and cell cycle regulation and iii to vectorize it in order to protect it from degradation. Methods. Human cell lines expressing RET/PTC1 were transfected by siRNA RET/PTC1, inhibition of the oncogene expression was assessed by qRT-PCR and by Western blot. Conjugation of siRNA RET/PTC1 to squalene was performed by coupling it to squalene. In vivo studies are performed in nude mice. Conclusion. In this short communication, we report the main published results obtained during last years.

  8. Human breast adipose tissue: characterization of factors that change during tumor progression in human breast cancer.

    Science.gov (United States)

    Fletcher, Sabrina Johanna; Sacca, Paula Alejandra; Pistone-Creydt, Mercedes; Coló, Federico Andrés; Serra, María Florencia; Santino, Flavia Eliana; Sasso, Corina Verónica; Lopez-Fontana, Constanza Matilde; Carón, Rubén Walter; Calvo, Juan Carlos; Pistone-Creydt, Virginia

    2017-02-07

    Adipose microenvironment is involved in signaling pathways that influence breast cancer. We aim to characterize factors that are modified: 1) in tumor and non tumor human breast epithelial cell lines when incubated with conditioned media (CMs) from human breast cancer adipose tissue explants (hATT) or normal breast adipose tissue explants (hATN); 2) in hATN-CMs vs hATT-CMs; 3) in the tumor associated adipocytes vs. non tumor associated adipocytes. We used hATN or hATT- CMs on tumor and non-tumor breast cancer cell lines. We evaluated changes in versican, CD44, ADAMTS1 and Adipo R1 expression on cell lines or in the different CMs. In addition we evaluated changes in the morphology and expression of these factors in slices of the different adipose tissues. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post-hoc tests were performed within each individual treatment. hATT-CMs increase versican, CD44, ADAMTS1 and Adipo R1 expression in breast cancer epithelial cells. Furthermore, hATT-CMs present higher levels of versican expression compared to hATN-CMs. In addition, we observed a loss of effect in cellular migration when we pre-incubated hATT-CMs with chondroitinase ABC, which cleaves GAGs chains bound to the versican core protein, thus losing the ability to bind to CD44. Adipocytes associated with the invasive front are reduced in size compared to adipocytes that are farther away. Also, hATT adipocytes express significantly higher amounts of versican, CD44 and Adipo R1, and significantly lower amounts of adiponectin and perilipin, unlike hATN adipocytes. We conclude that hATT secrete a different set of proteins compared to hATN. Furthermore, versican, a proteoglycan that is overexpressed in hATT-CMs compared to hATN-CMs, might be involved in the tumorogenic behavior observed in both cell lines employed. In addition, we may conclude that adipocytes from the tumor microenvironment show a less differentiated

  9. Expression of CD44 splice variants in human primary brain tumors

    NARCIS (Netherlands)

    Kaaijk, P.; Troost, D.; Morsink, F.; Keehnen, R. M.; Leenstra, S.; Bosch, D. A.; Pals, S. T.

    1995-01-01

    Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastatic potential in a number of different animal and human cancers. Although differential expression of CD44 standard epitopes (CD44s) in human brain tumors has been reported, the expression of

  10. Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

    NARCIS (Netherlands)

    van Bree, Chris; Castro Kreder, Natasja; Loves, Willem J. P.; Franken, Nicolaas A. P.; Peters, Godefridus J.; Haveman, Jaap

    2002-01-01

    Purpose: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel,

  11. Regulation of Thyroid Hormone Bioactivity in Health and Disease

    NARCIS (Netherlands)

    R.P. Peeters (Robin)

    2005-01-01

    textabstractTThyroid hormone plays an essential role in a variety of metabolic processes in the human body. Examples are the effects of thyroid hormone on metabolism and on the heart. The production of thyroid hormone by the thyroid is regulated by thyroid stimulating hormone (TSH) via the TSH

  12. Thyroid abnormalities in survivors of childhood cancer.

    Science.gov (United States)

    Çağlar, Ayla Akca; Oğuz, Aynur; Pınarlı, Faruk Güçlü; Karadeniz, Ceyda; Okur, Arzu; Bideci, Aysun; Koçak, Ülker; Bora, Hüseyin

    2014-09-01

    To investigate the late side effects of childhood cancer therapy on the thyroid gland and to determine the risk factors for development of thyroid disorder among childhood cancer survivors. One hundred and twenty relapse-free survivors of childhood cancer (aged 6-30 years) were included in this study. The diagnoses of patients were lymphoma, leukemia, brain tumor, rhabdomyosarcoma and nasopharyngeal carcinoma (NPC). The patients were divided into two groups depending on the treatment: group 1-chemotherapy (ChT) only (n=52) and group 2-combination therapy of ChT + radiotherapy (RT) (head/neck/thorax) (n=68). Thyroid function tests, urinary iodine levels, and thyroid gland ultrasound examinations were evaluated in both groups. Incidence of thyroid disease was 66% (n=79) in the survivors. The thyroid abnormalities were: hypothyroidism (HT) (n=32, 27%), thyroid nodules (n=27, 22%), thyroid parenchymal heterogeneity (n=40, 33%), autoimmune thyroiditis (n=36, 30%), and thyroid malignancy (n=3, 2%). While the incidence of HT and thyroid nodules in group 2 was significantly higher than in group 1, the incidence of thyroid parenchymal heterogeneity and autoimmune thyroiditis was similar in the two patient groups. HT and thyroid malignancy were seen only in group 2. In multivariate logistic regression analysis, a history of Hodgkin lymphoma (HL), brain tumor and NPC, as well as cervical irradiation and 5000-5999 cGy doses of radiation were found to constitute risk factors for HT. History of HL and 4000-5999 cGy doses of radiation were risk factors for thyroid nodules. Head/neck irradiation and treatment with platinum derivatives were risk factors for autoimmune thyroiditis. In univariate analysis, a history of NPC, cervical + nasopharyngeal irradiation, and treatment with platinum derivatives were risk factors for thyroid parenchymal heterogeneity. Our results indicate that there is especially an increased risk of HT and thyroid nodules in patients treated with combination

  13. The role of podoplanin in the biology of differentiated thyroid cancers.

    Directory of Open Access Journals (Sweden)

    Magdalena Rudzińska

    Full Text Available Podoplanin (PDPN, a mucin-type transmembrane glycoprotein specific to the lymphatic system is expressed in a variety of human cancers, and is regarded as a factor promoting tumor progression. The purpose of this study was to elucidate the molecular role of PDPN in the biology of thyroid cancer cells. PDPN expression was evaluated in primary thyroid carcinomas and thyroid carcinoma cell lines by RT-qPCR, Western blotting, IF and IHC. To examine the role of podoplanin in determining a cell's malignant potential (cellular migration, invasion, proliferation, adhesion, motility, apoptosis, a thyroid cancer cell line with silenced PDPN expression was used. We observed that PDPN was solely expressed in the cancer cells of 40% of papillary thyroid carcinoma (PTC tissues. Moreover, PDPN mRNA and protein were highly expressed in PTC-derived TPC1 and BcPAP cell lines but were not detected in follicular thyroid cancer derived cell lines. PDPN knock-down significantly decreased cellular invasion, and modestly reduced cell migration, while proliferation and adhesion were not affected. Our results demonstrate that PDPN mediates the invasive properties of cells derived from papillary thyroid carcinomas, suggesting that podoplanin might promote PTC progression.

  14. PPARγ Promotes Growth and Invasion of Thyroid Cancer Cells

    Directory of Open Access Journals (Sweden)

    William M. Wood

    2011-01-01

    Full Text Available Undifferentiated (anaplastic thyroid cancer (ATC is one of the most aggressive human malignancies and no effective therapy is currently available. We show here that PPARγ levels are elevated in cells derived from ATC. Depletion of PPARγ in HTh74 ATC cells resulted in decreased cell growth, cell cycle arrest and a reduction in pRb and cyclin A and B1 levels. We further showed that both flank and orthotopic thyroid tumors derived from PPARγ-depleted cells grew more slowly than PPARγ-expressing cells. When PPARγ was overexpressed in more differentiated thyroid cancer BCPAP cells which lack PPARγ, there was increased growth and raised pRb and cyclin A and B1 levels. Finally, PPARγ depletion in ATC cells decreased their invasive capacity whereas overexpression in PTC cells increased invasiveness. These data suggest that PPARγ may play a detrimental role in thyroid cancer and that targeting it therapeutically may lead to improved treatment of advanced thyroid cancer.

  15. Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells.

    Science.gov (United States)

    Niwa, Andressa Megumi; D Epiro, Gláucia Fernanda Rocha; Marques, Lilian Areal; Semprebon, Simone Cristine; Sartori, Daniele; Ribeiro, Lúcia Regina; Mantovani, Mário Sérgio

    2016-06-01

    The search for anticancer drugs has led researchers to study salinomycin, an ionophore antibiotic that selectively destroys cancer stem cells. In this study, salinomycin was assessed in two human cell lines, a breast adenocarcinoma (MCF-7) and a non-tumor breast cell line (HB4a), to verify its selective action against tumor cells. Real-time assessment of cell proliferation showed that HB4a cells are more resistant to salinomycin than MCF-7 tumor cell line, and these data were confirmed in a cytotoxicity assay. The half maximal inhibitory concentration (IC50) values show the increased sensitivity of MCF-7 cells to salinomycin. In the comet assay, only MCF-7 cells showed the induction of DNA damage. Flow cytometric analysis showed that cell death by apoptosis/necrosis was only induced in the MCF-7 cells. The increased expression of GADD45A and CDKN1A genes was observed in all cell lines. Decreased expression of CCNA2 and CCNB1 genes occurred only in tumor cells, suggesting G2/M cell cycle arrest. Consequently, cell death was activated in tumor cells through strong inhibition of the antiapoptotic genes BCL-2, BCL-XL, and BIRC5 genes in MCF-7 cells. These data demonstrate the selectivity of salinomycin in killing human mammary tumor cells. The cell death observed only in MCF-7 tumor cells was confirmed by gene expression analysis, where there was downregulation of antiapoptotic genes. These data contribute to clarifying the mechanism of action of salinomycin as a promising antitumor drug and, for the first time, we observed the higher resistance of HB4a non-tumor breast cells to salinomycin.

  16. Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

    Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

  17. Apoptosis and tumor cell death in response to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

    Science.gov (United States)

    Hallgren, Oskar; Aits, Sonja; Brest, Patrick; Gustafsson, Lotta; Mossberg, Ann-Kristin; Wullt, Björn; Svanborg, Catharina

    2008-01-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human milk that kills tumor cells by a process resembling programmed cell death. The complex consists of partially unfolded alpha-lactalbumin and oleic acid, and both the protein and the fatty acid are required for cell death. HAMLET has broad antitumor activity in vitro, and its therapeutic effect has been confirmed in vivo in a human glioblastoma rat xenograft model, in patients with skin papillomas and in patients with bladder cancer. The mechanisms of tumor cell death remain unclear, however. Immediately after the encounter with tumor cells, HAMLET invades the cells and causes mitochondrial membrane depolarization, cytochrome c release, phosphatidyl serine exposure, and a low caspase response. A fraction of the cells undergoes morphological changes characteristic of apoptosis, but caspase inhibition does not rescue the cells and Bcl-2 overexpression or altered p53 status does not influence the sensitivity of tumor cells to HAMLET. HAMLET also creates a state of unfolded protein overload and activates 20S proteasomes, which contributes to cell death. In parallel, HAMLET translocates to tumor cell nuclei, where high-affinity interactions with histones cause chromatin disruption, loss of transcription, and nuclear condensation. The dying cells also show morphological changes compatible with macroautophagy, and recent studies indicate that macroautophagy is involved in the cell death response to HAMLET. The results suggest that HAMLET, like a hydra with many heads, may interact with several crucial cellular organelles, thereby activating several forms of cell death, in parallel. This complexity might underlie the rapid death response of tumor cells and the broad antitumor activity of HAMLET.

  18. Diagnostic usefulness of Galectin-3 in thyroid gland nodular lesions

    Directory of Open Access Journals (Sweden)

    D. I. Kebalo

    2015-12-01

    Full Text Available Aim. The objective of this study was to evaluate the diagnostic usefulness of Galectin-3 marker in the diagnosis of thyroid nodules. Methods and results. results of immunocytochemical method for the expression of a tumor marker of galectin-3 in samples taken with the suction puncture biopsy of the thyroid gland in 230 patients were studied. It was established that immunocytochemical method of survey in material malignantion of thyroid tumors in 90–95% of cases observed bright reaction to galectin-3 in foulliculy and papillary thyroid cancer. In benign tumors this reaction was weak or was absent. Conclusion. This gives rise to the application of this method to identify malignant tumors of the thyroid gland or in the differential diagnostics of malignant and benign tumors of the thyroid gland.

  19. Human Organotypic Lung Tumor Models: Suitable For Preclinical 18F-FDG PET-Imaging.

    Directory of Open Access Journals (Sweden)

    David Fecher

    Full Text Available Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and -testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future.

  20. Thyroid Duplication and Papillary Carcinoma in an Ectopic Thyroid. A Case Presentation

    Directory of Open Access Journals (Sweden)

    José Alberto Puerto Lorenzo

    2012-05-01

    Full Text Available We present the case of a patient with a palpable tumor located in midline of the anterior neck above the hyoid bone, initially diagnosed as a thyroglossal duct cyst. Preliminary study of the lesion was conducted, both clinically and radiologically and cytologically. The tumor was removed through surgery by conventional technique. The paraffin biopsy defined the existence of thyroid papillary carcinoma. Despite this condition, the patient had thyroid gland in normal location. It is considered to be a curious case, combining the concepts of thyroid duplication and ectopic thyroid, with the presence, in this last one, of papillary carcinoma.

  1. Constitutive phosphorylation of Shc proteins in human tumors

    DEFF Research Database (Denmark)

    Pelicci, G; Lanfrancone, L; Salcini, A E

    1995-01-01

    cells. In tumor cells with known TK gene alterations Shc proteins were constitutively phosphorylated and complexed with the activated TK. No constitutive Shc phosphorylation was found in primary cell cultures and normal tissues. In 14 of 27 tumor cell lines with no reported TK alterations, Shc proteins...... activated TKs and that the analysis of Shc phosphorylation allow the identification of tumors with constitutive TK activation....

  2. Warthin-like papillary thyroid carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Haeri H

    2013-02-01

    Full Text Available Background: Warthin tumor- like papillary carcinoma of thyroid is a rare variant of papillary thyroid carcinoma. It is characterized by distinct papillary structures lined by oncocytic tumor cells with nuclear features of papillary carcinoma and marked lymphoplasmocytic infiltrate in the papillary stalks. This tumor derives its name from its resemblance to Warthin tumor of major salivary glands.Case presentation: We report a 54- year- old man presented with bilateral thyroid masses. Histopathological study showed papillary structures lined by cells with eosinophilic granular cytoplasm and ground- glass nuclei with lymphoplasmacytic infiltration of the stalks.Conclusion: Warthin tumor-like papillary thyroid carcinoma could be mistaken for benign lymphoepithelial lesions such as Hashimoto thyroiditis, Hurthle cell tumors and tall cell variant of papillary carcinoma. Follow- up information on the previously reported cases has suggested that these tumors behave similarly to usual papillary carcinoma.

  3. Viruses and thyroiditis: an update

    Directory of Open Access Journals (Sweden)

    Hober Didier

    2009-01-01

    Full Text Available Abstract Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40 in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment.

  4. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-12-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  5. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-01-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  6. The expression of Egfl7 in human normal tissues and epithelial tumors.

    Science.gov (United States)

    Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

    2013-04-23

    To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

  7. Thyroid Surgery

    Science.gov (United States)

    ... has had a previous neck operation (thyroid surgery, parathyroid surgery, spine surgery, carotid artery surgery, etc.) and/or who has had a suspected invasive thyroid cancer should have their vocal cord function evaluated routinely before surgery. This is necessary to ...

  8. Thyroid Tests

    Science.gov (United States)

    ... hypothyroidism —when thyroid hormones levels are too low Hashimoto’s disease , of the most common cause of hypothyroidism ... disease —the most common cause of hyperthyroidism—and Hashimoto’s disease —the most common cause of hypothyroidism. Thyroid ...

  9. INTERNALIZATION OF ANTIMICROBIAL PEPTIDE ACIPENSIN 1 INTO HUMAN TUMOR CELLS

    Directory of Open Access Journals (Sweden)

    E. S. Umnyakova

    2016-01-01

    Full Text Available Search for new compounds providing delivery of drugs into infected or neoplastic cells, is an important direction of biomedical research. Cell-penetrating peptides are among those compounds, due to their ability to translocate through membranes of eukaryotic cells, serving as potential carriers of various therapeutic agents to the target cells. The aim of present work was to investigate the ability of acipensin 1, an antimicrobial peptide of innate immune system, for in vitro penetration into human tumor cells. Acipensin 1 is a cationic peptide that we have previously isolated from leukocytes of the Russian sturgeon, Acipenser gueldenstaedtii. Capability of acipensin 1 to enter the human erytroleukemia K-562 cells has been investigated for the first time. A biotechnological procedure for producing a recombinant acipensin 1 peptide has been developed. The obtained peptide was conjugated with a fluorescent probe BODIPY FL. By means of confocal microscopy, we have shown that the tagged acipensin 1 rapidly enters into K-562 cells and can be detected in the intracellular space within 5 min after its addition to the cell culture. Using flow cytometry technique, penetration kinetics of the labeled peptide into K-562 cells (at nontoxic micromolar concentrations has been studied. We have observed a rapid internalization of the peptide to the target cells, thus confirming the results of microscopic analysis, i.e, the labeled acipensin was detectable in K-562 cells as soon as wihin 2-3 seconds after its addition to the incubation medium. The maximum of fluorescence was reached within a period of approx. 45 seconds, with further “plateau” at the terms of >100 seconds following cell stimulation with the test compound. These data support the concept, that the antimicrobial peptides of innate immunity system possess the features of cell-penetrating peptides, and allow us to consider the studied sturgeon peptide a promising template for development of new

  10. [Autoimmune diseases of the thyroid gland].

    Science.gov (United States)

    Allelein, S; Feldkamp, J; Schott, M

    2017-01-01

    Autoimmune diseases of the thyroid gland are considered to be the most frequent cause of thyroid gland disorders. Autoimmune thyroid diseases consist of two subgroups: autoimmune thyroiditis (AIT) and Graves' disease. The AIT is the most common human autoimmune disease. Infiltration of the thyroid gland with cytotoxic T‑cells can lead to an initial thyrotoxicosis und during the course to hypothyroidism due to destruction of the thyroid gland. Substitution with Levothyroxine is indicated for manifest hypothyroidism and subclinical hypothyroidism with increased thyroid antibodies with the intention of normalizing the serum thyroid stimulating hormone (TSH). Graves' disease is characterized by the appearance of stimulating TSH receptor antibodies leading to hyperthyroidism. Endocrine ophthalmopathy may also occur. Ablative therapy with radioiodine therapy or thyroidectomy is administered to patients with Graves' disease without remission after at least 1 year of antithyroid drug therapy.

  11. Molecular diagnostics and predictors in thyroid cancer.

    Science.gov (United States)

    Nikiforova, Marina N; Nikiforov, Yuri E

    2009-12-01

    The accuracy of cancer detection in thyroid nodules by fine-needle aspiration (FNA) cytology and prognostication of thyroid cancer needs further improvement and can benefit from testing for molecular alterations known to occur in thyroid tumors. Recent studies have demonstrated the feasibility of mutation detection in clinical FNA samples from thyroid nodules and their contribution to improving the diagnostic accuracy of FNA cytology. It appears that molecular testing is most beneficial for thyroid FNA samples with indeterminate cytology, where it can resolve the diagnosis in a significant number of cases. In addition to BRAF mutation, which has been studied most extensively, detection of RAS, RET/PTC, and PAX8/PPARgamma mutations also contribute substantially to cancer diagnosis. Some of these molecular markers, particularly BRAF, can also be used for tumor prognostication. In clinical setting, molecular testing of thyroid FNA samples and surgically removed tumors should utilize a restricted number of techniques that provide high accuracy and specificity of mutation detection. Testing for cancer-specific mutations in thyroid FNA samples and surgically removed tumor tissues increases diagnostic accuracy of FNA cytology and offers better prognostication of thyroid cancer.

  12. Thyroid cancer imaging in vivo by targeting the anti-apoptotic molecule galectin-3.

    Directory of Open Access Journals (Sweden)

    Armando Bartolazzi

    Full Text Available BACKGROUND: The prevalence of thyroid nodules increases with age, average 4-7% for the U.S.A. adult population, but it is much higher (19-67% when sub-clinical nodules are considered. About 90% of these lesions are benign and a reliable approach to their preoperative characterization is necessary. Unfortunately conventional thyroid scintigraphy does not allow the distinction among benign and malignant thyroid proliferations but it provides only functional information (cold or hot nodules. The expression of the anti-apoptotic molecule galectin-3 is restricted to cancer cells and this feature has potential diagnostic and therapeutic implications. We show here the possibility to obtain thyroid cancer imaging in vivo by targeting galectin-3. METHODS: The galectin-3 based thyroid immuno-scintigraphy uses as radiotracer a specific (99mTc-radiolabeled mAb. A position-sensitive high-resolution mini-gamma camera was used as imaging capture device. Human galectin-3 positive thyroid cancer xenografts (ARO and galectin-3 knockout tumors were used as targets in different experiments in vivo. 38 mice with tumor mass of about 1 gm were injected in the tail vein with 100 microCi of (99mTc-labeled mAb to galectin-3 (30 microg protein/in 100 microl saline solution. Tumor images were acquired at 1 hr, 3 hrs, 6 hrs, 9 hrs and 24 hrs post injection by using the mini-gamma camera. FINDINGS: Results from different consecutive experiments show an optimal visualization of thyroid cancer xenografts between 6 and 9 hours from injection of the radiotracer. Galectin-3 negative tumors were not detected at all. At 6 hrs post-injection galectin-3 expressing tumors were correctly visualized, while the whole-body activity had essentially cleared. CONCLUSIONS: These results demonstrate the possibility to distinguish preoperatively benign from malignant thyroid nodules by using a specific galectin-3 radio-immunotargeting. In vivo imaging of thyroid cancer may allow a better

  13. Expression of cyclooxygenase-2 and inducible nitric oxide synthase in human ovarian tumors and tumor-associated macrophages

    NARCIS (Netherlands)

    Klimp, AH; Hollema, H; Kempinga, C; van der Zee, AGJ; de Vries, EGE; Daemen, T

    2001-01-01

    This study investigates whether and to what extent cyclooxygenase type-2 (COX-2) and inducible nitric oxide-synthase (iNOS), both known to have an immunosuppressive effect, are expressed in human ovarian tumors. Because COX-2 and iNOS can be expressed by activated macrophages, the presence of

  14. Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy.

    Science.gov (United States)

    Ji, Minbiao; Lewis, Spencer; Camelo-Piragua, Sandra; Ramkissoon, Shakti H; Snuderl, Matija; Venneti, Sriram; Fisher-Hubbard, Amanda; Garrard, Mia; Fu, Dan; Wang, Anthony C; Heth, Jason A; Maher, Cormac O; Sanai, Nader; Johnson, Timothy D; Freudiger, Christian W; Sagher, Oren; Xie, Xiaoliang Sunney; Orringer, Daniel A

    2015-10-14

    Differentiating tumor from normal brain is a major barrier to achieving optimal outcome in brain tumor surgery. New imaging techniques for visualizing tumor margins during surgery are needed to improve surgical results. We recently demonstrated the ability of stimulated Raman scattering (SRS) microscopy, a nondestructive, label-free optical method, to reveal glioma infiltration in animal models. We show that SRS reveals human brain tumor infiltration in fresh, unprocessed surgical specimens from 22 neurosurgical patients. SRS detects tumor infiltration in near-perfect agreement with standard hematoxylin and eosin light microscopy (κ = 0.86). The unique chemical contrast specific to SRS microscopy enables tumor detection by revealing quantifiable alterations in tissue cellularity, axonal density, and protein/lipid ratio in tumor-infiltrated tissues. To ensure that SRS microscopic data can be easily used in brain tumor surgery, without the need for expert interpretation, we created a classifier based on cellularity, axonal density, and protein/lipid ratio in SRS images capable of detecting tumor infiltration with 97.5% sensitivity and 98.5% specificity. Quantitative SRS microscopy detects the spread of tumor cells, even in brain tissue surrounding a tumor that appears grossly normal. By accurately revealing tumor infiltration, quantitative SRS microscopy holds potential for improving the accuracy of brain tumor surgery. Copyright © 2015, American Association for the Advancement of Science.

  15. Somatostatin receptors in human adrenal gland tumors--immunohistochemical study.

    OpenAIRE

    Tomasz Stepień; Hanna Pisarek; Robert Kubiak; Marek Pawlikowski

    2008-01-01

    Somatostatin receptors subtypes (SSTR 1-5) were demonstrated in surgically obtained adrenal gland tumors by means of immunohistochemistry (IHC). Results of the present study demonstrate that somatostatin receptors are expressed in adrenal tumors in a varied manner which is specific in each case. It provides different diagnostic and therapeutic possibilities.

  16. Somatostatin receptors in human adrenal gland tumors--immunohistochemical study.

    Directory of Open Access Journals (Sweden)

    Tomasz Stepień

    2008-12-01

    Full Text Available Somatostatin receptors subtypes (SSTR 1-5 were demonstrated in surgically obtained adrenal gland tumors by means of immunohistochemistry (IHC. Results of the present study demonstrate that somatostatin receptors are expressed in adrenal tumors in a varied manner which is specific in each case. It provides different diagnostic and therapeutic possibilities.

  17. P53 MUTATIONS IN HUMAN LUNG-TUMORS

    NARCIS (Netherlands)

    MILLER, CW; ASLO, A; KOK, K; YOKOTA, J; BUYS, CHCM; TERADA, M; KOEFFLER, HP; Simon, K.

    1992-01-01

    Mutation of one p53 allele and loss of the normal p53 allele [loss of heterozygosity (LOH)] occur in many tumors including lung cancers. These alterations apparently contribute to development of cancer by interfering with the tumor suppressor activity of p53. We directly sequenced amplified DNA in

  18. [Silent thyroiditis and postpartum thyroiditis].

    Science.gov (United States)

    Díez, J J

    1995-01-01

    Six cases of silent thyroiditis are described. Clinical, analytical, therapeutical and prognostical features are reviewed. Descriptive and retrospective study. Outpatient endocrinological clinic of a General Hospital Six women (age 26-41 years) that fulfil clinical and analytical criteria of silent thyroiditis. In 4 patients thyroiditis was diagnosed in the postpartum period and in the remaining 2 there was no relationship with pregnancy. Serum levels of thyroid hormones and thyroglobulin and thyroid peroxidase antibodies were measured in all patients. Follow-up period was between 12 and 41 months. The 2 patients with the sporadic form of silent thyroiditis showed clinical and analytical data of thyrotoxicosis that spontaneously resolved. The remaining 4 patients presented with hypothyroidism. In one of them the hypothyroidism spontaneously resolved, in 2 it became permanent and in a further one it developed to subclinical hypothyroidism. Silent thyroiditis (sporadic or postpartum) is a frequent disorder, usually benign and transient. It can present in different clinic forms and evolve to resolution of permanent thyroid dysfunction.

  19. Steroid Tumor Environment in Male and Female Mice Model of Canine and Human Inflammatory Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sara Caceres

    2016-01-01

    Full Text Available Canine inflammatory mammary cancer (IMC shares clinical and histopathological characteristics with human inflammatory breast cancer (IBC and has been proposed as a good model for studying the human disease. The aim of this study was to evaluate the capacity of female and male mice to reproduce IMC and IBC tumors and identify the hormonal tumor environment. To perform the study sixty 6–8-week-old male and female mice were inoculated subcutaneously with a suspension of 106 IPC-366 and SUM149 cells. Tumors and serum were collected and used for hormonal analysis. Results revealed that IPC-366 reproduced tumors in 90% of males inoculated after 2 weeks compared with 100% of females that reproduced tumor at the same time. SUM149 reproduced tumors in 40% of males instead of 80% of females that reproduced tumors after 4 weeks. Both cell lines produce distant metastasis in lungs being higher than the metastatic rates in females. EIA analysis revealed that male tumors had higher T and SO4E1 concentrations compared to female tumors. Serum steroid levels were lower than those found in tumors. In conclusion, IBC and IMC male mouse model is useful as a tool for IBC research and those circulating estrogens and intratumoral hormonal levels are crucial in the development and progression of tumors.

  20. Human xenografts are not rejected in a naturally occurring immunodeficient porcine line: a human tumor model in pigs.

    Science.gov (United States)

    Basel, Matthew T; Balivada, Sivasai; Beck, Amanda P; Kerrigan, Maureen A; Pyle, Marla M; Dekkers, Jack C M; Wyatt, Carol R; Rowland, Robert R R; Anderson, David E; Bossmann, Stefan H; Troyer, Deryl L

    2012-04-01

    Animal models for cancer therapy are invaluable for preclinical testing of potential cancer treatments; however, therapies tested in such models often fail to translate into clinical settings. Therefore, a better preclinical model for cancer treatment testing is needed. Here we demonstrate that an immunodeficient line of pigs can host and support the growth of xenografted human tumors and has the potential to be an effective animal model for cancer therapy. Wild-type and immunodeficient pigs were injected subcutaneously in the left ear with human melanoma cells (A375SM cells) and in the right ear with human pancreatic carcinoma cells (PANC-1). All immunodeficient pigs developed tumors that were verified by histology and immunohistochemistry. Nonaffected littermates did not develop tumors. Immunodeficient pigs, which do not reject xenografted human tumors, have the potential to become an extremely useful animal model for cancer therapy because of their similarity in size, anatomy, and physiology to humans.

  1. Genetic and Epigenetic of Medullary Thyroid Cancer

    Science.gov (United States)

    Khatami, Fatemeh; Tavangar, Seyed Mohammad

    2017-11-11

    Medullary thyroid carcinoma (MTC) is an infrequent, calcitonin producing neuroendocrine tumor and initiates from the parafollicular C cells of the thyroid gland. Several genetic and epigenetic alterations are collaterally responsible for medullary thyroid carcinogenesis. In this review article, we shed light on all the genetic and epigenetic hallmarks of MTC. From the genetic perspective, RET, HRAS, and KRAS are the most important genes that are characterized in MTC. From the epigenetic perspective, Ras-association domain family member 1A, telomerase reverse transcriptase promoter methylations, overexpression of histone methyltransferases, EZH2 and SMYD3, and wide ranging increase and decrease in non-coding RNAs can be responsible for medullary thyroid carcinogenesis.

  2. Antitumor activity of irofulven against human ovarian cancer cell lines, human tumor colony-forming units, and xenografts.

    Science.gov (United States)

    van Laar, E S; Izbicka, E; Weitman, S; Medina-Gundrum, L; Macdonald, J R; Waters, S J

    2004-01-01

    The objective of this study was to investigate the cytotoxic activity of irofulven (HMAF, MGI 114), a unique chemotherapeutic agent currently under clinical investigation, in various preclinical models of ovarian cancer. Antiproliferative effects of irofulven in ovarian cancer cell lines and ovarian tumor specimens were characterized in vitro using sulforhodamine B and human tumor colony-forming assays, respectively. Irofulven demonstrated marked activity against a panel of ovarian tumor cell lines, including IGROV1, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, and SK-OV-3, all of which exhibit various drug resistance mechanisms. In human tumor cloning assays, irofulven inhibited colony formation in surgically derived ovarian tumors at concentrations as low as 0.001 micro g /ml and indicated superior activity in comparison with paclitaxel when tested against the same tumor specimens. The antitumor activity of irofulven compared to that of paclitaxel was also examined using the SK-OV-3 xenograft model. In mice bearing subcutaneously implanted SK-OV-3 tumors, treatment with paclitaxel failed to inhibit tumor growth; whereas mice treated with maximum tolerated doses of irofulven had a 25% partial shrinkage rate, and the remaining animals had a mean tumor growth inhibition of 82%. The potent activity of irofulven against ovarian tumors in vitro and in vivo supports the evaluation of its clinical activity in ovarian cancer.

  3. Environmental chemicals and thyroid function: an update

    DEFF Research Database (Denmark)

    Boas, M.; Main, K.M.; Feldt-Rasmussen, U.

    2009-01-01

    PURPOSE OF REVIEW: To overview the effects of endocrine disrupters on thyroid function. RECENT FINDINGS: Studies in recent years have revealed thyroid-disrupting properties of many environmentally abundant chemicals. Of special concern is the exposure of pregnant women and infants, as thyroid...... thyroid effects through a variety of mechanisms of action, and some publications have focused on elucidating the mechanisms of specific (groups of) chemicals. SUMMARY: A large variety of ubiquitous chemicals have been shown to have thyroid-disrupting properties, and the combination of mechanistic......, epidemiological and exposure studies indicates that the ubiquitous human and environmental exposure to industrial chemicals may impose a serious threat to human and wildlife thyroid homeostasis. Currently, available evidence suggests that authorities need to regulate exposure to thyroid-disrupting chemicals...

  4. Lingual thyroid

    Directory of Open Access Journals (Sweden)

    Marina Đorđe

    2007-01-01

    Full Text Available Lingual thyroid is a rare congenital malformation that occurs more frequently in the female population. It occurs because of the error in transcriptional factors, the key for the normal differentiation of thyrocyte, so the thyroid gland tissue does not descend normally down the thyroglossal duct to the final position in the neck. Due to that, it can entirely or partially remain at the base of the tongue. This is the most frequent localization of the ectopic tissue while it can remain in the sublingual, suprahyoid and infrahyoid area as well. This disease can be diagnosed in the asymptomatic phase, as well as in the phase of compensatory and manifest hypothyroidism. In the ectopic thyroid gland, all diseases of the thyroid gland can occur as in the usual localization in the neck. The authors show a 6-year old patient, who had a routine medical examination for the inflamed throat, during which a vascular tumefaction was discovered at the base of the tongue. A cyst at the base of the tongue was suspected, but additional examination showed that it was an ectopic thyroid tissue marked as a lingual thyroid gland. Diagnosis of this disease starts with the laboratory analysis of the thyroid status. The next step involves scintigraphy of the thyroid gland with technetium-pertechnetate (99mTc or radioactive iodine (123I. The therapy of the compensatory hypothyroidism is suppressive therapy with levothyroxine and in the manifest hypothyroidism it is hormone substitution therapy with levothyroxine. Although there are recommended age-related daily doses, they should not be accepted as final, but rather prescribed according to the individual thyroid status. .

  5. HMGB1-Induced Cross Talk between PTEN and miRs 221/222 in Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    S. Mardente

    2015-01-01

    Full Text Available High mobility group box 1 (HMGB1 is an ubiquitous protein that plays different roles in the nucleus, cytoplasm, and extracellular space. It is an important DAMP molecule that allows communication between damaged or tumor cells and the immune system. Tumor cells exploit HMGB1’s ability to activate intracellular pathways that lead to cell growth and migration. Papillary thyroid cancer is a well-differentiated tumor and is often used to study relationships between cells and the inflammatory microenvironment as the latter is characterized by high levels of inflammatory cells and cytokines. Anaplastic thyroid cancer is one of the most lethal human cancers in which many microRNAs and tumor suppressor genes are deregulated. Upregulation of microRNAs 221 and 222 has been shown to induce the malignant phenotype in many human cancers via inhibition of PTEN expression. In this study we suggest that extracellular HMGB1 interaction with RAGE enhances expression of oncogenic cluster miR221/222 that in turn inhibits tumor suppressor gene PTEN in two cell lines derived from human thyroid anaplastic and papillary cancers. The newly identified pathway HMGB1/RAGE/miR221/222 may represent an effective way of tumor escape from immune surveillance that could be used to develop new therapeutic strategies against anaplastic tumors.

  6. Antibody directed against human YKL-40 increases tumor volume in a human melanoma xenograft model in scid mice

    DEFF Research Database (Denmark)

    Salamon, Johannes; Hoffmann, Tatjana; Elies, Eva

    2014-01-01

    Induced overexpression of the secretory protein YKL-40 promotes tumor growth in xenograft experiments. We investigated if targeting YKL-40 with a monoclonal antibody could inhibit tumor growth. YKL-40 expressing human melanoma cells (LOX) were injected subcutenously in Balb/c scid mice. Animals...

  7. Use of recombinant, human TSH radioiodine therapy in patients with differentiated thyroid carcinoma; Radioiodtherapie des differenzierten Schilddruesenkarzinoms nach Vorbehandlung mit rekombinantem, humanem TSH

    Energy Technology Data Exchange (ETDEWEB)

    Luster, M. [Wuerzburg Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin

    2001-12-01

    We describe the use of recombinant human TSH (rhTSH) in conjunction with ablative radioiodine therapy (RIT) in 11 patients (16 total treatments) with advanced and/or recurrent DTC (5 papillary, 6 follicular) for whom withdrawal of thyroid hormone suppressive therapy (THST) to increase serum TSH was not an option. Indications for rhTSH use in these patients included inability to tolerate withdrawal of thyroid hormones due to poor physical condition or inability to achieve sufficient serum TSH levels after THST withdrawal. All patients had undergone thyroidectomy and most (9/11) had received prior radioablative therapy after THST withdrawal. In 7 cases (5 patients), post-therapy Tg levels assessed at a mean of 4.3 months (range 2-10 months) after I-131 therapy were decreased by at least 30% compared to pre-therapy levels. In an additional 3 patients, whole body scans performed at follow-up indicated decreased or stabilized tumor burden compared to pre-therapy scans or marked clinical improvement was found. Three patients died of progressive disease within 2 months of therapy before follow-up assessments occurred. No adverse events were reported among the 8 surviving patients. The results suggest that rhTSH offers a promising alternative to THST withdrawal to allow radioablative therapy under maximal TSH stimulation in patients with advanced recurrent DTC who would not otherwise be able to receive this treatment. This therapeutic indication extends the clinical potential of the new agent, already demonstrated to be effective for use with I-131 for diagnostic purposes. However in some patients suffering from highly aggressive tumors the poor prognosis will not be improved. (orig.) [German] An unserer Klinik liegen bislang Erfahrungen mit 16 Radioiodtherapien (RIT) (z.T. mehrfache Anwendung) unter rhTSH vor. Die ueberwiegende Mehrzahl der Patienten wurde wegen einer fortgeschrittenen Tumorerkrankung mit dem Risiko einer lebensbedrohlichen Verschlechterung in

  8. Drug-induced thyroiditis and papillary carcinoma in a minocycline-pigmented black thyroid gland.

    Science.gov (United States)

    Tacon, Lyndal; Tan, Charles T K; Alvarado, Raul; Gill, Anthony J; Sywak, Mark; Fulcher, Greg

    2008-07-01

    We describe a 31-year-old woman who had ingested minocycline for 18 months prior to presenting with hyperthyroidism and a palpable thyroid nodule. There was no evidence of Graves' disease or autonomous nodule on thyroid scintigraphy, and a clinical diagnosis of thyroiditis was made. Fine-needle aspiration biopsy of the palpable lesion suggested papillary carcinoma, and the patient underwent a total thyroidectomy. Intraoperatively, the thyroid gland was found to have a striking black discoloration. Subsequent histological examination revealed the accumulation of pigment globules within the apical cytoplasm of the follicular cells, and associated findings of a drug-induced thyroiditis. The tumor nodule showed features of infarction and was felt to represent a necrotic papillary microcarcinoma. We postulate that in addition to causing black thyroid pigmentation, chronic minocycline use in our patient resulted in thyroiditis and subsequent hyperthyroidism. The papillary microcarcinoma was probably a coincidental finding.

  9. Phenotypic characterization of drug resistance and tumor initiating cancer stem cells from human bone tumor osteosarcoma cell line OS-77

    Directory of Open Access Journals (Sweden)

    Yue Zhang

    2014-08-01

    Full Text Available The cancer stem cell theory suggest that presence of small subpopulation of cancer stem cells are the major implication in the cancer treatment and also responsible for tumor recurrence. Based on Hoechst 33342 dye exclusion technique, we have identified about 3.3% of cancer stem like side population (SP cells from human osteosarcoma OS-77 cell line whose prevalence is significantly reduced to 0.3% after treatment with verapamil. The sphere formation assay revealed that osteosarcoma SP cells are highly capable to form tumor spheres (sarcospheres. Further by immunocytochemistry and RT-PCR, we show that OS-77 SP cells have enhanced expression of stem cell surface markers such as CD44, Nanog and ATP-binding cassette (ABC transporter gene (ABCG2 which contributes to self-renewal and drug resistance, respectively. Our findings help to designing a novel therapeutic drug which could effectively target the cancer stem cells and prevent the tumor relapse.

  10. HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.

    Science.gov (United States)

    Aits, Sonja; Gustafsson, Lotta; Hallgren, Oskar; Brest, Patrick; Gustafsson, Mattias; Trulsson, Maria; Mossberg, Ann-Kristin; Simon, Hans-Uwe; Mograbi, Baharia; Svanborg, Catharina

    2009-03-01

    HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.

  11. Thyroid and Weight

    Science.gov (United States)

    ... thyroid hormones are elevated, such as in the toxic phase of thyroiditis (see Thyroiditis brochure ) and if ... discontinued. HYPOTHYROIDISM AND THYROID HORMONE WHAT IS THE RELATIONSHIP BETWEEN HYPOTHYROIDISM AND WEIGHT GAIN? Since the BMR ...

  12. Pediatric Thyroid Cancer

    Science.gov (United States)

    ... Marketplace Find an ENT Doctor Near You Pediatric Thyroid Cancer Pediatric Thyroid Cancer Patient Health Information News ... and neck issues, should be consulted. Types of thyroid cancer in children: Papillary : This form of thyroid ...

  13. Anaplastic thyroid cancer

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000352.htm Anaplastic thyroid cancer To use the sharing features on this page, ... of cancer of the thyroid gland. Causes Anaplastic thyroid cancer is an invasive type of thyroid cancer that ...

  14. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... limitations of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... top of page What are some common uses of the procedure? The thyroid scan is used to ...

  15. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... of page What are some common uses of the procedure? The thyroid scan is used to determine ...

  16. Chronic thyroiditis (Hashimoto disease)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000371.htm Chronic thyroiditis (Hashimoto disease) To use the sharing features on this page, ... Hashimoto Images Endocrine glands Thyroid enlargement - scintiscan Hashimoto's disease (chronic thyroiditis) Thyroid gland References Amino N, Lazarus JH, ...

  17. Pregnancy and Thyroid Disease

    Science.gov (United States)

    ... People Who Were Treated with hGH Thyroid Disease & Pregnancy Thyroid disease is a group of disorders that ... prescribes. What role do thyroid hormones play in pregnancy? Thyroid hormones are crucial for normal development of ...

  18. Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor-Associated Macrophages

    Science.gov (United States)

    Allavena, P.; Chieppa, M.; Bianchi, G.; Solinas, G.; Fabbri, M.; Laskarin, G.; Mantovani, A.

    2010-01-01

    Tumor-Associated Macrophages (TAMs) are abundantly present in the stroma of solid tumors and modulate several important biological processes, such as neoangiogenesis, cancer cell proliferation and invasion, and suppression of adaptive immune responses. Myeloid C-type lectin receptors (CLRs) constitute a large family of transmembrane carbohydrate-binding receptors that recognize pathogens as well as endogenous glycoproteins. Several lines of evidence demonstrate that some CLRs can inhibit the immune response. In this study we investigated TAM-associated molecules potentially involved in their immune suppressive activity. We found that TAMs isolated from human ovarian carcinoma samples predominantly express the CLRs Dectin-1, MDL-1, MGL, DCIR, and most abundantly the Mannose Receptor (MR). Components of carcinomatous ascites and purified tumoral mucins (CA125 and TAG-72) bound the MR and induced its internalization. MR engagement by tumoral mucins and by an agonist anti-MR antibody modulated cytokine production by TAM toward an immune-suppressive profile: increase of IL-10, absence of IL-12, and decrease of the Th1-attracting chemokine CCL3. This study highlights that tumoral mucin-mediated ligation of the MR on infiltrating TAM may contribute to their immune suppressive phenotype. PMID:21331365

  19. Absence of tumor growth stimulation in a panel of 16 human tumor cell lines by mistletoe extracts in vitro.

    Science.gov (United States)

    Maier, Gerhard; Fiebig, Heinz-Herbert

    2002-04-01

    Extracts of Viscum album (mistletoe) are widely used as complementary cancer therapies in Europe. The mistletoe lectins have been identified as the main active principle of mistletoe extracts. They have been shown to exhibit cytotoxic effects as well as immunomodulatory activities. The latter is exemplified by induction of cytokine secretion and increased activity of natural killer cells. Recent reports, however, indicated possible tumor growth stimulation by mistletoe extracts. Therefore, the three aqueous mistletoe extracts (Iscador M special, Iscador Qu special and Iscador P) were evaluated for antiproliferative and/or stimulatory effects in a panel of 16 human tumor cell lines in vitro using a cellular proliferation assay. The results show no evidence of stimulation of tumor growth by any of the three Iscador preparations, comprising central nervous system, gastric, non-small cell lung, mammary, prostate, renal and uterine cancer cell lines, as well as cell lines from hematological malignancies and melanomas. On the contrary, Iscador preparations containing a high lectin concentration (Iscador M special and Iscador Qu special) showed antitumor activity in the mammary cancer cell line MAXF 401NL at the 15 microg/ml dose level with a more than 70% growth inhibition compared to untreated control cells. In addition, a slight antitumor activity (growth inhibition 30-70%) was found in three tumor cell lines for Iscador M special and in seven tumor cell lines for Iscador Qu special, respectively. Iscador P, which contains no mistletoe lectin I, showed no antiproliferative activity.

  20. GT198 Expression Defines Mutant Tumor Stroma in Human Breast Cancer.

    Science.gov (United States)

    Yang, Zheqiong; Peng, Min; Cheng, Liang; Jones, Kimya; Maihle, Nita J; Mivechi, Nahid F; Ko, Lan

    2016-05-01

    Human breast cancer precursor cells remain to be elucidated. Using breast cancer gene product GT198 (PSMC3IP; alias TBPIP or Hop2) as a unique marker, we revealed the cellular identities of GT198 mutant cells in human breast tumor stroma. GT198 is a steroid hormone receptor coactivator and a crucial factor in DNA repair. Germline mutations in GT198 are present in breast and ovarian cancer families. Somatic mutations in GT198 are present in ovarian tumor stromal cells. Herein, we show that human breast tumor stromal cells carry GT198 somatic mutations and express cytoplasmic GT198 protein. GT198(+) stromal cells share vascular smooth muscle cell origin, including myoepithelial cells, adipocytes, capillary pericytes, and stromal fibroblasts. Frequent GT198 mutations are associated with GT198(+) tumor stroma but not with GT198(-) tumor cells. GT198(+) progenitor cells are mostly capillary pericytes. When tested in cultured cells, mutant GT198 induces vascular endothelial growth factor promoter, and potentially promotes angiogenesis and adipogenesis. Our results suggest that multiple lineages of breast tumor stromal cells are mutated in GT198. These findings imply the presence of mutant progenitors, whereas their descendants, carrying the same GT198 mutations, are collectively responsible for forming breast tumor microenvironment. GT198 expression is, therefore, a specific marker of mutant breast tumor stroma and has the potential to facilitate diagnosis and targeted treatment of human breast cancer. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Thyroid gland removal

    Science.gov (United States)

    Total thyroidectomy; Partial thyroidectomy; Thyroidectomy; Subtotal thyroidectomy; Thyroid cancer - thyroidectomy; Papillary cancer - thyroidectomy; Goiter - thyroidectomy; Thyroid nodules - thyroidectomy

  2. Thyroid Antibodies

    Science.gov (United States)

    ... Factor Antibody Iron Iron Tests JAK2 Mutation Kidney Stone Analysis Kidney Stone Risk Panel KRAS Mutation Lactate Lactate Dehydrogenase (LD) ... gain Fatigue Dry skin Hair loss Intolerance to cold Constipation A high level of thyroid hormone ( hyperthyroidism ) ...

  3. Cholesterol masks membrane glycosphingolipid tumor-associated antigens to reduce their immunodetection in human cancer biopsies.

    Science.gov (United States)

    Novak, Anton; Binnington, Beth; Ngan, Bo; Chadwick, Karen; Fleshner, Neil; Lingwood, Clifford A

    2013-11-01

    Glycosphingolipids (GSLs) are neoplastic and normal/cancer stem cell markers and GSL/cholesterol-containing membrane rafts are increased in cancer cell plasma membranes. We define a novel means by which cancer cells can restrict tumor-associated GSL immunoreactivity. The GSL-cholesterol complex reorients GSL carbohydrate to a membrane parallel, rather than perpendicular conformation, largely unavailable for antibody recognition. Methyl-β-cyclodextrin cholesterol extraction of all primary human tumor frozen sections tested (ovarian, testicular, neuroblastoma, prostate, breast, colon, pheochromocytoma and ganglioneuroma), unmasked previously "invisible" membrane GSLs for immunodetection. In ovarian carcinoma, globotriaosyl ceramide (Gb3), the GSL receptor for the antineoplastic Escherichia coli-derived verotoxin, was increased throughout the tumor. In colon carcinoma, Gb3 detection was vastly increased within the neovasculature and perivascular stroma. In tumors considered Gb3 negative (neuroblastoma, Leydig testicular tumor and pheochromocytoma), neovascular Gb3 was unmasked. Tumor-associated GSL stage-specific embryonic antigen (SSEA)-1, SSEA-3, SSEA-4 and globoH were unmasked according to tumor: SSEA-1 in prostate/colon; SSEA-3 in prostate; SSEA-4 in pheochromocytoma/some colon tumors; globoH in prostate/some colon tumors. In colon, anti-SSEA-1 was tumor cell specific. Within the GSL-cholesterol complex, filipin-cholesterol binding was also reduced. These results may relate to the ill-defined benefit of statins on cancer prognosis, for example, prostate carcinoma. We found novel anti-tumor GSL antibodies circulating in 3/5 statin-treated, but not untreated, prostate cancer patients. Lowering tumor membrane cholesterol may permit immune recognition of otherwise unavailable tumor-associated GSL carbohydrate, for more effective immunosurveillance and active/passive immunotherapy. Our results show standard immunodetection of tumor GSLs significantly under assesses

  4. Thyroid and Glucocorticoid Hormones Promote Functional T-tubule Development in Human-Induced Pluripotent Stem Cell Derived Cardiomyocytes.

    Science.gov (United States)

    Parikh, Shan S; Blackwell, Daniel J; Gomez-Hurtado, Nieves; Frisk, Michael; Wang, Lili; Kim, Kyungsoo; Dahl, Christen P; Fiane, Arnt E; Tønnessen, Theis; Kryshtal, Dmytro O; Louch, William E; Knollmann, Bjorn C

    2017-10-02

    Rationale: Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) are increasingly being used for modeling heart disease and are under development for regeneration of the injured heart. However, incomplete structural and functional maturation of hiPSC-CM including lack of t-tubules, immature excitation-contraction (EC) coupling, and inefficient Ca-induced Ca release (CICR) remain major limitations. Objective: Thyroid and glucocorticoid hormones are critical for heart maturation. We hypothesized that their addition to standard protocols would promote t-tubule development and mature EC coupling of hiPSC-CM when cultured on extracellular matrix with physiological stiffness (Matrigel mattress). Methods and Results: HiPSC-CM were generated using a standard chemical differentiation method supplemented with triiodo-L-thyronine (T3) and/or dexamethasone (Dex) during days 16-30 followed by single-cell culture for 5 days on Matrigel mattress. HiPSC-CM treated with T3+Dex, but not with either T3 or Dex alone, developed an extensive t-tubule network. Notably, Matrigel mattress was necessary for t-tubule formation. Compared to adult human ventricular CM, t-tubules in T3+Dex-treated hiPSC-CM were less organized and had more longitudinal elements. Confocal line scans demonstrated spatially and temporally uniform Ca release that is characteristic of EC coupling in the heart ventricle. T3+Dex enhanced elementary Ca release measured by Ca sparks as well as promoted ryanodine receptor (RyR2) structural organization. Simultaneous measurements of L-type Ca current and intracellular Ca release confirmed enhanced functional coupling between L-type Ca channels and RyR2 in T3+Dex cells. Conclusions: Our results suggest a permissive role of combined thyroid and glucocorticoid hormones during the cardiac differentiation process which, when coupled with further maturation on Matrigel mattress, is sufficient for t-tubule development, enhanced CICR, and more ventricular-like EC

  5. Substernal Thyroid Masses

    Directory of Open Access Journals (Sweden)

    Mohamed A.H. Regal

    2010-10-01

    Full Text Available A thyroid mass, most often a non toxic colloid goiter or occasionally an adenoma, is not an unusual finding below the level of the thoracic inlet.1 In 1992 Creswell and Wells estimated that these tumors comprise 5.8% of all mediastinal lesions.1 There is no standard definition for thyroid glands extending below the thoracic inlet, but such masses descend from their original cervical location for more than 2 or 3 cm below the thoracic inlet, and are not truly primary tumors of the mediastinum. They preserve the connection between the thoracic and cervical portion and receive their blood supply from the neck.2,3 In 1940, the seminal report of Wakeley and Mulvany divided intrathoracic thyroid masses into 3 types; (1”Small substernal extension” of a mainly cervical mass, (2 “Partial” intrathoracic, in which the major portion of the mass is situated within the thorax, and (3”Complete” in which all of the mass lies within the thoracic cavity.

  6. Primary thyroid paraganglioma presenting with double thyroid nodule: a case report.

    Science.gov (United States)

    Erem, Cihangir; Kocak, Mustafa; Nuhoglu, İrfan; Cobanoglu, Umit; Ucuncu, Ozge; Okatan, Burcu Kemal

    2009-12-01

    Paragangliomas (PGs) are exceptionally rare tumors. Only 24 cases have previously been reported. Both preoperative and postoperative differential diagnosis is very difficult. Due to interesting nature in diagnosis and differential diagnosis, we describe the case 58-year-old euthyroid woman with a thyroid PG. The patient had presented with euthyroid multinodular goiter to a secondary hospital. The patient was treated with right lobectomy, isthmectomy, and left partial lobectomy without any imaging procedures. No complication had been developed during and following the operation. Initial pathological examination suggested medullar thyroid carcinoma (MTC) in a nodule of 4.5 cm in diameter on right thyroid lobe and a nodule of 2.5 cm in diameter on the left thyroid lobe without amyloid stroma and referred to our third-stage hospital. Repeated pathological examination involving immunohistochemistry revealed that the tumor was stained positively to neuron-specific enolase, chromogranin A, synaptophysin, and S-100 protein. No immunoreactivity was detected against thyroglobulin, calcitonin, parathormone, carcino-embryonic antigen, thyroid transcription factor-1, and cytokeratin. A diagnosis of thyroid PG was finally made. Laboratory analyses and imaging procedures excluded any neck or extracervical tissues metastasis or multiple endocrine neoplasia. In conclusion, thyroid PG is an elusive tumor. We present this interesting nature thyroid PG case to highlight importance of careful evaluation of clinical and pathological findings to correctly identify paragangliomas which anatomically mimic MTCs. This report is the first case of thyroid PG presenting with multinodular goiter in the literature.

  7. Tumor-infiltrating plasmacytoid dendritic cells promote immunosuppression by Tr1 cells in human liver tumors

    NARCIS (Netherlands)

    Pedroza-Gonzalez, A.; Zhou, G.; Vargas-Mendez, E.; Boor, P.P.; Mancham, S.; Verhoef, C.; Polak, W.G.; Grunhagen, D.; Pan, Q.; Janssen, H.; Garcia-Romo, G.S.; Biermann, K.; Tjwa, E.T.; Ijzermans, J.N.M.; Kwekkeboom, J.; Sprengers, D.

    2015-01-01

    CD4+ type 1 T regulatory (Tr1) cells have a crucial role in inducing tolerance. Immune regulation by these cells is mainly mediated through the secretion of high amounts of IL-10. Several studies have suggested that this regulatory population may be involved in tumor-mediated immune-suppression.

  8. Characterization of acylfulvene histiospecific toxicity in human tumor cell lines.

    Science.gov (United States)

    Kelner, M J; McMorris, T C; Montoya, M A; Estes, L; Uglik, S F; Rutherford, M; Samson, K M; Bagnell, R D; Taetle, R

    1998-01-01

    Acylfulvene derivatives demonstrate marked efficacy in xenograft carcinoma models as compared with the parent illudin compounds. To elucidate the increased therapeutic efficacy of acylfulvene analogs, we compared them with the illudin compounds in terms of their in vitro cytotoxicity, cellular accumulation and DNA incorporation. The cytotoxicity of various acylfulvene analogs was tested in vitro against a variety of tumor cell lines. Radiolabelled acylfulvene analog was prepared and used for cellular accumulation and DNA incorporation studies. The prototype acylfulvene analog retained selective histiospecific toxicity towards myeloid leukemia and various carcinoma cell lines. In vitro killing of tumor cells by acylfulvene required up to a 30-fold increase in molecules per cell, as compared with illudin S, indicating that acylfulvene was less toxic on a cellular level. At equitoxic concentrations, acylfulvene incorporation into genomic tumor cell DNA was equivalent to illudin S suggesting that cellular metabolism has a role in acylfulvene cytotoxicity. Analysis of cellular accumulation of acylfulvene into tumor cells revealed a markedly higher Vmax for tumor cells, and a lower Vd for diffusion accumulation into other cells. The combination of higher Vmax and lower Vd may explain the increased in vivo efficacy of acylfulvene.

  9. Effects of charged particles on human tumor cells

    Directory of Open Access Journals (Sweden)

    Kathryn D Held

    2016-02-01

    Full Text Available The use of charged particle therapy in cancer treatment is growing rapidly, in large part because the exquisite dose localization of charged particles allows for higher radiation doses to be given to tumor tissue while normal tissues are exposed to lower doses and decreased volumes of normal tissues are irradiated. In addition, charged particles heavier than protons have substantial potential clinical advantages because of their additional biological effects including greater cell killing effectiveness, decreased radiation resistance of hypoxic cells in tumors and reduced cell cycle dependence of radiation response. These biological advantages depend on many factors such as endpoint, cell or tissue type, dose, dose rate or fractionation, charged particle type and energy, and oxygen concentration. This review summarizes the unique biological advantages of charged particle therapy and highlights recent research and areas of particular research needs, such as quantification of Relative Biological Effectiveness (RBE for various tumor types and radiation qualities, role of genetic background of tumor cells in determining response to charged particles, sensitivity of cancer stem-like cells to charged particles, role of charged particles in tumors with hypoxic fractions and importance of fractionation, including use of hypofractionation, with charged particles.

  10. Roles of F-box proteins in human digestive system tumors (Review).

    Science.gov (United States)

    Gong, Jian; Lv, Liang; Huo, Jirong

    2014-12-01

    F-box proteins (FBPs), the substrate-recognition subunit of E3 ubiquitin (Ub) ligase, are the important components of Ub proteasome system (UPS). FBPs are involved in multiple cellular processes through ubiquitylation and subsequent degradation of their target proteins. Many studies have described the roles of FBPs in human cancers. Digestive system tumors account for a large proportion of all the tumors, and their mortality is very high. This review summarizes for the first time the roles of FBPs in digestive system tumorige-nesis and tumor progression, aiming at finding new routes for the rational design of targeted anticancer therapies in digestive system tumors.

  11. Correlation between serum lead and thyroid diseases: papillary thyroid carcinoma, nodular goiter, and thyroid adenoma.

    Science.gov (United States)

    Li, Hui; Li, Xiang; Liu, Jie; Jin, Langping; Yang, Fan; Wang, Junbo; Wang, Ouchen; Gao, Ying

    2017-10-01

    Studies have showed that lead was associated with human health. However, the effects of lead on thyroid functions are inconsistent, and studies based on Chinese population are fragmentary. To evaluate the correlation between lead and thyroid functions of Chinese with different thyroid diseases, we conducted a hospital-based study. Ninety-six papillary thyroid carcinoma (PTC), 10 nodular goiter (NG), and 7 thyroid adenoma (TA) patients were recruited from the First Affiliated Hospital of Wenzhou Medical University, China. Serum triiodothyronine (T3), free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone (TSH) were evaluated with chemiluminescent microparticle immunoassay. Serum lead was assessed with ICP-MASS. Partial correlation was used to explore the correlations of serum lead and thyroid diseases. Compared to PTC, the level of lead was significantly higher in TA, and lower in NG (p lead was negatively correlated with TSH (r s  =  - 0.27, p lead at quartile4 (r s  = 0.61, p lead and FT3 or FT4 in any group. The results suggested that lead might have different etiological roles in these three thyroid diseases.

  12. A Role for T-Lymphocytes in Human Breast Cancer and in Canine Mammary Tumors

    Directory of Open Access Journals (Sweden)

    Maria Isabel Carvalho

    2014-01-01

    Full Text Available Chronic inflammation in the tumor microenvironment has a prominent role in carcinogenesis and benefits the proliferation and survival of malignant cells, promoting angiogenesis and metastasis. Mammary tumors are frequently infiltrated by a heterogeneous population of immune cells where T-lymphocytes have a great importance. Interestingly, similar inflammatory cell infiltrates, cytokine and chemokine expression in humans and canine mammary tumors were recently described. However, in both species, despite all the scientific evidences that appoint for a significant role of T-lymphocytes, a definitive conclusion concerning the effectiveness of T-cell dependent immune mechanisms has not been achieved yet. In the present review, we describe similarities between human breast cancer and canine mammary tumors regarding tumor T-lymphocyte infiltration, such as relationship of TILs and mammary tumors malignancy, association of ratio CD4+/ CD8+ T-cells with low survival rates, promotion of tumor progression by Th2 cells actions, and association of great amounts of Treg cells with poor prognostic factors. This apparent parallelism together with the fact that dogs develop spontaneous tumors in the context of a natural immune system highlight the dog as a possible useful biological model for studies in human breast cancer immunology.

  13. Analysis of Recurrence Factor of Postoperative Papillary Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    XING Lan-lan;CHEN Song;LI Ya-ming

    2014-02-01

    Full Text Available To investigate the factors that influences the recurrence of papillary thyroid cancer,69 patients with papillary thyroid cancer since January 1, 2011 to march 30, 2013 were analyzed respectively. They meet the inclusion criteria and complete clinical data, 18 males and 51 females,average age: 40.17±12.97.Thyroid ultrasonography, thyroid function test, thyroglobulin and antibody measurement were performed on all patients and thyroid function were checked three or more times on the premise of continuously levothyroxine. Single factor analysis were performed using SPSS17.0 in these respects including patients' gender, age, tumor size, type of opetation, the inhibition degree of TSH with taking levothyroxine postoperative and whether to perform 131I thyroid remnant ablation. Binary Logistic regression analysis were used for studying recurrence factors in multivariate analysis. The ROC curve were drawn, and then determine the threshold of TSH to evaluate tumor recurrence using Youden index method. Unvaried analysis showed that there was no statistically significance between papillary thyroid cancer recurrence and patients' age, surgical approach (P =0.373, P = 0.226,but were related to patient's gender, tumor size, postoperative TSH suppression degree and the removal of residual thyroid tissue postoperative(P= 0.031, P = 0.004, P = 0.000 01, P = 0.000 05. Males, large tumors, high postoperative TSH values and patients who didn't remove the residual thyroid tissue after surgery had higher recurrence rate. Logistic regression analysis showed that tumor size, postoperative TSH suppression degree and whether to remove the residual thyroid tissue were the influencing factors of tumor recurrence. The postoperative TSH supressive degree evaluation of critical point of tumor recurrence was determined by 0.223 5 mU/L using the Yueden index method. Large tumors, high postoperative TSH values,and no removal of the residual thyroid tissue had more influence

  14. Comprehensive allelotype and genetic anaysis of 466 human nervous system tumors

    DEFF Research Database (Denmark)

    von Deimling, A; Fimmers, R; Schmidt, M C

    2000-01-01

    Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However, a considera...... may provide a valuable framework for future studies to delineate molecular pathways in many types of human central nervous system tumors.......Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However......, a considerable number of affected genes remain to be identified. We present here a comprehensive allelotype analysis of 466 nervous system tumors based on loss of heterozygosity (LOH) studies with 129 microsatellite markers that span the genome. Specific alterations of the EGFR, CDK4, CDKN2A, TP53, DMBT1, NF2...

  15. Oncolytic Virotherapy Synergism with Signaling Inhibitors: Rapamycin Increases Myxoma Virus Tropism for Human Tumor Cells▿

    OpenAIRE

    Stanford, Marianne M.; Barrett, John W.; Nazarian, Steven H.; Werden, Steven; McFadden, Grant

    2006-01-01

    Myxoma virus is a rabbit-specific poxvirus pathogen that also exhibits a unique tropism for human tumor cells and is dramatically oncolytic for human cancer xenografts. Most tumor cell lines tested are permissive for myxoma infection in a fashion intimately tied to the activation state of Akt kinase. A host range factor of myxoma virus, M-T5, directly interacts with Akt and mediates myxoma virus tumor cell tropism. mTOR is a regulator of cell growth and metabolism downstream of Akt and is spe...

  16. Modeling of light propagation in the human neck for diagnoses of thyroid cancers by diffuse optical tomography.

    Science.gov (United States)

    Fujii, H; Yamada, Y; Kobayashi, K; Watanabe, M; Hoshi, Y

    2017-05-01

    Diffuse optical tomography using near-infrared light in a wavelength range from 700 to 1000 nm has the potential to enable non-invasive diagnoses of thyroid cancers; some of which are difficult to detect by conventional methods such as ultrasound tomography. Diffuse optical tomography needs to be based on a physically accurate model of light propagation in the neck, because it reconstructs tomographic images of the optical properties in the human neck by inverse analysis. Our objective here was to investigate the effects of three factors on light propagation in the neck using the 2D time-dependent radiative transfer equation: (1) the presence of the trachea, (2) the refractive-index mismatch at the trachea-tissue interface, and (3) the effect of neck organs other than the trachea (spine, spinal cord, and blood vessels). There was a significant influence of reflection and refraction at the trachea-tissue interface on the light intensities in the region between the trachea and the front of the neck surface. Organs other than the trachea showed little effect on the light intensities measured at the front of the neck surface although these organs affected the light intensities locally. These results indicated the necessity of modeling the refractive-index mismatch at the trachea-tissue interface and the possibility of modeling other neck organs simply as a homogeneous medium when the source and detectors were far from large blood vessels. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib.

    Science.gov (United States)

    Wei, Wei-Jun; Shen, Chen-Tian; Song, Hong-Jun; Qiu, Zhong-Ling; Luo, Quan-Yong

    2016-09-01

    Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has markedly changed the therapeutic landscape, side-effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of the present study was to identify the antitumor property of the non-selective β-adrenergic receptor antagonist propranolol for thyroid cancers. Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used in the present study. Broad β-blocker propranolol and β2-specific antagonist ICI118551, but not β1-specific antagonist atenolol, inhibited the growth of 8505C and K1 cells. Propranolol treatment inhibited growth and induced apoptosis of 8505C cells in vitro and in vivo, which are closely associated with decreased expressions of cyclin D1 and anti-apoptotic Bcl-2. Expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) also decreased following propranolol intervention. 18F-FDG PET/CT imaging of the 8505C xenografts validated shrinkage of the tumors in the propranolol-treated group when compared to the phosphate‑buffered saline treated group. Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib. Our present results suggest that propranolol has potential activity against thyroid cancers and investigation of the combination with targeted molecular therapy for progressive thyroid cancers could be beneficial.

  18. Human saliva as route of inter-human infection for mouse mammary tumor virus.

    Science.gov (United States)

    Mazzanti, Chiara Maria; Lessi, Francesca; Armogida, Ivana; Zavaglia, Katia; Franceschi, Sara; Al Hamad, Mohammad; Roncella, Manuela; Ghilli, Matteo; Boldrini, Antonio; Aretini, Paolo; Fanelli, Giovanni; Marchetti, Ivo; Scatena, Cristian; Hochman, Jacob; Naccarato, Antonio Giuseppe; Bevilacqua, Generoso

    2015-07-30

    Etiology of human breast cancer is unknown, whereas the Mouse Mammary Tumor Virus (MMTV) is recognized as the etiologic agent of mouse mammary carcinoma. Moreover, this experimental model contributed substantially to our understanding of many biological aspects of the human disease. Several data strongly suggest a causative role of MMTV in humans, such as the presence of viral sequences in a high percentage of infiltrating breast carcinoma and in its preinvasive lesions, the production of viral particles in primary cultures of breast cancer, the ability of the virus to infect cells in culture. This paper demonstrates that MMTV is present in human saliva and salivary glands. MMTV presence was investigated by fluorescent PCR, RT-PCR, FISH, immunohistochemistry, and whole transcriptome analysis. Saliva was obtained from newborns, children, adults, and breast cancer patients. The saliva of newborns is MMTV-free, whereas MMTV is present in saliva of children (26.66%), healthy adults (10.60%), and breast cancer patients (57.14% as DNA and 33.9% as RNA). MMTV is also present in 8.10% of salivary glands. RNA-seq analysis performed on saliva of a breast cancer patient demonstrates a high expression of MMTV RNA in comparison to negative controls. The possibility of a contamination by murine DNA was excluded by murine mtDNA and IAP LTR PCR. These findings confirm the presence of MMTV in humans, strongly suggest saliva as route in inter-human infection, and support the hypothesis of a viral origin for human breast carcinoma.

  19. Criteria to define HLA haplotype loss in human solid tumors

    NARCIS (Netherlands)

    Ramal, LM; van der Zwan, AW; Collado, A; Lopez-Nevot, MA; Tilanus, M; Garrido, F

    Short tandem repeat (STR) markers are currently used to define loss of heterozygosity (LOH) of genes and chromosomes in tumors. Chromosome 6 and chromosome 15 STR markers are applied to define loss of HLA and related genes (e.g. TAP and beta(2)m) The number of STR identified in the HLA region is

  20. Analysis of molecular changes during human melanocytic tumor progression

    NARCIS (Netherlands)

    Wit, Nicole Johanna Wilhelmina de

    2005-01-01

    Melanoma is one of the most aggressive types of cancer, due to its potency to disseminate early in tumor progression. The incidence is still rising, even though the rate of change has leveled off in the last decade. As melanoma cells are relatively insensitive to classical systemic therapies, like

  1. Application of new therapies in Graves' disease and thyroid-associated ophthalmopathy: animal models and translation to human clinical trials

    DEFF Research Database (Denmark)

    Banga, J Paul; Nielsen, Claus H; Gilbert, Jacqueline A

    2008-01-01

    Most current approaches for treating Graves' disease are based essentially upon regimes developed nearly 50 years ago. Moreover, therapeutic approaches for complications such as thyroid-associated ophthalmopathy (TAO) and dermopathy are singularly dependent on conventional approaches of nonspecif...

  2. Effects of recombinant human thyrotropin administration on 24-hour arterial pressure in female undergoing evaluation for differentiated thyroid cancer

    National Research Council Canada - National Science Library

    Rentziou, Gianna; Saltiki, Katerina; Manios, Efstathios; Stamatelopoulos, Kimon; Koroboki, Eleni; Vemmou, Anastasia; Mantzou, Emily; Zakopoulos, Nikolaos; Alevizaki, Maria

    2014-01-01

    ...) in premenopausal women with well-differentiated thyroid carcinoma (DTC). Designs. Thirty euthyroid DTC female patients were evaluated by rhTSH stimulation test (mean age 40.4 ± 8.6 years). A 24...

  3. Effects of Recombinant Human Thyrotropin Administration on 24-Hour Arterial Pressure in Female Undergoing Evaluation for Differentiated Thyroid Cancer

    National Research Council Canada - National Science Library

    Rentziou, Gianna; Saltiki, Katerina; Manios, Efstathios; Stamatelopoulos, Kimon; Koroboki, Eleni; Vemmou, Anastasia; Mantzou, Emily; Zakopoulos, Nikolaos; Alevizaki, Maria

    2014-01-01

    ...) in premenopausal women with well-differentiated thyroid carcinoma (DTC). Designs. Thirty euthyroid DTC female patients were evaluated by rhTSH stimulation test (mean age 40.4±8.6 years). A 24...

  4. Anaplastic Thyroid Carcinoma: Computed Tomographic Differentiation from Other Thyroid Masses

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jun Won; Yoon, Dae Young; Choi, Chul Soon; Chang, Suk Ki; Yun, Eun Joo; Seo, Young Lan; Rho, Young-Soo; Jin Cho, Sung; Kim, Keon Ha (Depts. of Radiology, Otorhinolaryngology, and Pathology, Kangdong Seong-Sim Hospital, Hallym Univ. College of Medicine, Seoul (KR))

    2008-04-15

    Background: Anaplastic thyroid carcinoma is rare but is one of the most aggressive malignancies. Therefore, accurate diagnosis is important in order to provide appropriate therapy. Purpose: To establish useful computed tomographic (CT) criteria for differentiating anaplastic carcinoma from other thyroid masses. Material and Methods: The CT scans of nine patients with anaplastic carcinomas were retrospectively reviewed and compared with those of 32 patients with papillary carcinomas (n = 12) or benign lesions (n = 20) exceeding a maximum diameter of 2.0 cm. Image analysis was performed according to the following CT parameters: size, margin (well defined or ill defined), composition (cystic, mixed, or solid), mean attenuation value, ratio of attenuation of the mass to that of the adjacent muscle (M/m attenuation ratio), necrosis (present or absent), and calcification (stippled, nodular, or absent) of the thyroid mass; and tumor-spreading patterns including the presence of surrounding normal thyroid tissue in the involved lobe, involvement of the contralateral thyroid lobe, extension into the adjacent structures, and cervical lymphadenopathy. Results: Anaplastic carcinomas appeared as large (average 4.6 cm), solid (100%), and ill-defined (88.9%) masses accompanied by necrosis (100%), nodular calcification (44.4%), direct invasion into the adjacent organs (55.6%), and cervical lymph node involvement (77.8%). Tumor necrosis was the most valuable parameter in differentiating anaplastic carcinomas from other thyroid masses. Patient age (>70 years) and low attenuation value on postcontrast scan (attenuation value <100 HU, or M/m attenuation ratio <1.3) are also helpful predictors for anaplastic carcinoma. Conclusion: If a patient is older than 70 years of age and has a large necrotic thyroid mass of low attenuation, anaplastic carcinoma should be included in the differential diagnosis

  5. Over-expression of HOX-8, the human homologue of the mouse Hox-8 homeobox gene, in human tumors.

    Science.gov (United States)

    Suzuki, M; Tanaka, M; Iwase, T; Naito, Y; Sugimura, H; Kino, I

    1993-07-15

    A human ovarian yolk sac tumor cDNA library was screened for homeobox genes with an oligonucleotide probe under low stringent condition. Three homeobox genes were isolated, two of which were identified as HHO.c1 and HB24. The third was highly homologous with the mouse Hox-8 gene and was designated as HOX-8. Studies on RNAs from 25 human tumor tissues and cell lines showed that the profile of HOX-8 expression was different from those of HHO.c1 and HB24. The expression of HOX-8 was not detected in hematopoietic tumor cells, in which HHO.c1 and HB24 were highly expressed. HOX-8 was expressed at higher levels in a variety of tumors of epithelial origin than in their corresponding normal tissues more frequently than HHO.c1 and HB24. All three homeobox genes were highly expressed in a yolk sac tumor, an immature tumor of gonadal origin. These results suggest that HOX-8 plays a more important role in human tumors of epithelial origin than those of hematopoietic origin.

  6. Targeting Homologous Recombination in Notch-Driven C. elegans Stem Cell and Human Tumors.

    Directory of Open Access Journals (Sweden)

    Xinzhu Deng

    Full Text Available Mammalian NOTCH1-4 receptors are all associated with human malignancy, although exact roles remain enigmatic. Here we employ glp-1(ar202, a temperature-sensitive gain-of-function C. elegans NOTCH mutant, to delineate NOTCH-driven tumor responses to radiotherapy. At ≤20°C, glp-1(ar202 is wild-type, whereas at 25°C it forms a germline stem cell⁄progenitor cell tumor reminiscent of human cancer. We identify a NOTCH tumor phenotype in which all tumor cells traffic rapidly to G2⁄M post-irradiation, attempt to repair DNA strand breaks exclusively via homology-driven repair, and when this fails die by mitotic death. Homology-driven repair inactivation is dramatically radiosensitizing. We show that these concepts translate directly to human cancer models.

  7. Cysteine-rich domain of human ADAM 12 (meltrin alpha) supports tumor cell adhesion

    DEFF Research Database (Denmark)

    Iba, K; Albrechtsen, R; Gilpin, B J

    1999-01-01

    The ADAMs (A disintegrin and metalloprotease) comprise a family of membrane-anchored cell surface proteins with a putative role in cell-cell and/or cell-matrix interactions. By immunostaining, ADAM 12 (meltrin alpha) was up-regulated in several human carcinomas and could be detected along the tumor...... cell membranes. Because of this intriguing staining pattern, we investigated whether human ADAM 12 supports tumor cell adhesion. Using an in vitro assay using recombinant polypeptides expressed in Escherichia coli, we examined the ability of individual domains of human ADAM 12 and ADAM 15 to support...... tumor cell adhesion. We found that the disintegrin-like domain of human ADAM 15 supported adhesion of alphavbeta3-expressing A375 melanoma cells. In the case of human ADAM 12, however, recombinant polypeptides of the cysteine-rich domain but not the disintegrin-like domain supported cell adhesion...

  8. Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue.

    NARCIS (Netherlands)

    Brown, L.M.; Helmke, S.M.; Hunsucker, S.W.; Netea-Maier, R.T.; Chiang, S.A.; Heinz, D.E.; Shroyer, K.R.; Duncan, M.W.; Haugen, B.R.

    2006-01-01

    In order to better understand basic mechanisms of tumor development and identify potential new biomarkers, we have performed difference gel electrophoresis (DIGE) and peptide mass fingerprinting on pooled protein extracts from patients with papillary thyroid carcinoma (PTC) compared with matched

  9. Suppressive effects of tumor cell-derived 5'-deoxy-5'-methylthioadenosine on human T cells.

    Science.gov (United States)

    Henrich, Frederik C; Singer, Katrin; Poller, Kerstin; Bernhardt, Luise; Strobl, Carolin D; Limm, Katharina; Ritter, Axel P; Gottfried, Eva; Völkl, Simon; Jacobs, Benedikt; Peter, Katrin; Mougiakakos, Dimitrios; Dettmer, Katja; Oefner, Peter J; Bosserhoff, Anja-Katrin; Kreutz, Marina P; Aigner, Michael; Mackensen, Andreas

    2016-08-01

    The immunosuppressive tumor microenvironment represents one of the main obstacles for immunotherapy of cancer. The tumor milieu is among others shaped by tumor metabolites such as 5'-deoxy-5'-methylthioadenosine (MTA). Increased intratumoral MTA levels result from a lack of the MTA-catabolizing enzyme methylthioadenosine phosphorylase (MTAP) in tumor cells and are found in various tumor entities. Here, we demonstrate that MTA suppresses proliferation, activation, differentiation, and effector function of antigen-specific T cells without eliciting cell death. Conversely, if MTA is added to highly activated T cells, MTA exerts cytotoxic effects on T cells. We identified the Akt pathway, a critical signal pathway for T cell activation, as a target of MTA, while, for example, p38 remained unaffected. Next, we provide evidence that MTA exerts its immunosuppressive effects by interfering with protein methylation in T cells. To confirm the relevance of the suppressive effects of exogenously added MTA on human T cells, we used an MTAP-deficient tumor cell-line that was stably transfected with the MTAP-coding sequence. We observed that T cells stimulated with MTAP-transfected tumor cells revealed a higher proliferative capacity compared to T cells stimulated with Mock-transfected cells. In conclusion, our findings reveal a novel immune evasion strategy of human tumor cells that could be of interest for therapeutic targeting.

  10. Human T cell crosstalk is induced by tumor membrane transfer.

    Directory of Open Access Journals (Sweden)

    Ronny Uzana

    Full Text Available Trogocytosis is a contact-dependent unidirectional transfer of membrane fragments between immune effector cells and their targets, initially detected in T cells following interaction with professional antigen presenting cells (APC. Previously, we have demonstrated that trogocytosis also takes place between melanoma-specific cytotoxic T lymphocytes (CTLs and their cognate tumors. In the present study, we took this finding a step further, focusing on the ability of melanoma membrane-imprinted CD8+ T cells to act as APCs (CD8+ T-APCs. We demonstrate that, following trogocytosis, CD8+ T-APCs directly present a variety of melanoma derived peptides to fraternal T cells with the same TCR specificity or to T cells with different TCRs. The resulting T cell-T cell immune synapse leads to (1 Activation of effector CTLs, as determined by proliferation, cytokine secretion and degranulation; (2 Fratricide (killing of CD8+ T-APCs by the activated CTLs. Thus, trogocytosis enables cross-reactivity among CD8+ T cells with interchanging roles of effectors and APCs. This dual function of tumor-reactive CTLs may hint at their ability to amplify or restrict reactivity against the tumor and participate in modulation of the anti-cancer immune response.

  11. Thyroid hormone differentially modulates Warburg phenotype in breast cancer cells.

    Science.gov (United States)

    Suhane, Sonal; Ramanujan, V Krishnan

    2011-10-14

    Sustenance of cancer cells in vivo critically depends on a variety of genetic and metabolic adaptations. Aerobic glycolysis or Warburg effect has been a defining biochemical hallmark of transformed cells for more than five decades although a clear molecular basis of this observation is emerging only in recent years. In this study, we present our findings that thyroid hormone exerts its non-genomic and genomic actions in two model human breast cancer cell lines differentially. By laying a clear foundation for experimentally monitoring the Warburg phenotype in living cancer cells, we demonstrate that thyroid hormone-induced modulation of bioenergetic profiles in these two model cell lines depends on the degree of Warburg phenotype that they display. Further we also show that thyroid hormone can sensitize mitochondria in aggressive, triple-negative breast cancer cells favorably to increase the chemotherapeutic efficacy in these cells. Even though the role of thyroid hormone in modulating mitochondrial metabolism has been known, the current study accentuates the critical role it plays in modulating Warburg phenotype in breast cancer cells. The clinical significance of this finding is the possibility to devise strategies for metabolically modulating aggressive triple-negative tumors so as to enhance their chemosensitivity in vivo. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Primary thyroid angiosarcoma: an unusual localization

    Directory of Open Access Journals (Sweden)

    Petronella Pasquale

    2012-05-01

    Full Text Available Abstract The finding of thyroid nodules is a very common occurrence in routine clinical practice. Approximately 5% to 7% of the entire population have thyroid nodules. Vascular lesions are one of the most controversial issues in thyroid pathology. These include benign lesions such as hemangiomas and, rarely, malignant tumors such as angiosarcomas or undifferentiated angiosarcomatoid carcinomas. In particular, angiosarcoma of the thyroid gland is a rare, highly aggressive malignant vascular tumor and in Italy the greatest geographical incidence of this lesion is witnessed near the Alps. Here, a case of thyroid angiosarcoma in a 71-year-old man with a history of goiter for about 20 years is described. The unusual localization of this lesion, the difficulties in reaching a definitive diagnosis for this particular histological type of primary tumor and a history of long-standing multinodular goiter in thyroid of an older man from outside the Alpine region prompted us to report this case of thyroid angiosarcoma mainly to discuss surgical, histopathological and immunohistochemical features.

  13. Thyroid Nodules and Thyroid Cancer: Surgical Aspects

    OpenAIRE

    Clark, Orlo H.

    1980-01-01

    Patients with thyroid nodules must be treated selectively because these nodules develop far more frequently than does thyroid cancer. A thorough clinical history, family history and history of radiation, as well as an accurate physical examination, are very important in determining whether surgical treatment is indicated. Thyroid function tests, a radioactive isotope scan, a thyroid echogram and fine-needle biopsy are also useful.

  14. Oncolytic virotherapy synergism with signaling inhibitors: Rapamycin increases myxoma virus tropism for human tumor cells.

    Science.gov (United States)

    Stanford, Marianne M; Barrett, John W; Nazarian, Steven H; Werden, Steven; McFadden, Grant

    2007-02-01

    Myxoma virus is a rabbit-specific poxvirus pathogen that also exhibits a unique tropism for human tumor cells and is dramatically oncolytic for human cancer xenografts. Most tumor cell lines tested are permissive for myxoma infection in a fashion intimately tied to the activation state of Akt kinase. A host range factor of myxoma virus, M-T5, directly interacts with Akt and mediates myxoma virus tumor cell tropism. mTOR is a regulator of cell growth and metabolism downstream of Akt and is specifically inhibited by rapamycin. We report that treatment of nonpermissive human tumor cell lines, which normally restrict myxoma virus replication, with rapamycin dramatically increased virus tropism and spread in vitro. This increased myxoma replication is concomitant with global effects on mTOR signaling, specifically, an increase in Akt kinase. In contrast to the effects on human cancer cells, rapamycin does not increase myxoma virus replication in rabbit cell lines or permissive human tumor cell lines with constitutively active Akt. This indicates that rapamycin increases the oncolytic capacity of myxoma virus for human cancer cells by reconfiguring the internal cell signaling environment to one that is optimal for productive virus replication and suggests the possibility of a potentially therapeutic synergism between kinase signaling inhibitors and oncolytic poxviruses for cancer treatment.

  15. Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors

    National Research Council Canada - National Science Library

    Salmon, Hélène; Franciszkiewicz, Katarzyna; Damotte, Diane; Dieu-Nosjean, Marie-Caroline; Validire, Pierre; Trautmann, Alain; Mami-Chouaib, Fathia; Donnadieu, Emmanuel

    2012-01-01

    .... Studies using fixed tumor samples from human patients have shown that T cells accumulate more efficiently in the stroma than in tumor islets, but the mechanisms by which this occurs are unknown...

  16. Epigenetic modulators of thyroid cancer.

    Science.gov (United States)

    Rodríguez-Rodero, Sandra; Delgado-Álvarez, Elías; Díaz-Naya, Lucía; Martín Nieto, Alicia; Menéndez Torre, Edelmiro

    2017-01-01

    There are some well known factors involved in the etiology of thyroid cancer, including iodine deficiency, radiation exposure at early ages, or some genetic changes. However, epigenetic modulators that may contribute to development of these tumors and be helpful to for both their diagnosis and treatment have recently been discovered. The currently known changes in DNA methylation, histone modifications, and non-coding RNAs in each type of thyroid carcinoma are reviewed here. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Ectopic Thyroid Tissue With Hashimoto's Thyroiditis.

    Science.gov (United States)

    Garcia-Rodriguez, Laura; Dharia, Rahil; Massey, Becky

    2016-02-01

    Ectopic thyroid gland is a rare occurrence with a prevalence of 1 per 100,000 to 300,000 people. Hashimoto's thyroiditis involving ectopic thyroid tissue is particularly unusual. We describe the presentation, workup, surgical management, and brief review of the literature. Retroactive review of an 83-year-old white female patient record. As a case report, this project was exempt from institutional review board approval. We present a case of ectopic thyroid tissue located in the strap muscles with concurrent Hashimoto's thyroiditis. This tissue initially was believed to represent metastatic follicular thyroid carcinoma. Whenever ectopic thyroid tissue is encountered, the gravest concern is metastatic thyroid cancer. The possibility of benign thyroid tissue should not be excluded even if the thyroid histology initially appears to be malignant in nature.

  18. Oncolytic vaccinia virotherapy of anaplastic thyroid cancer in vivo.

    Science.gov (United States)

    Lin, Shu-Fu; Price, Daniel L; Chen, Chun-Hao; Brader, Peter; Li, Sen; Gonzalez, Lorena; Zhang, Qian; Yu, Yong A; Chen, Nanhai; Szalay, Aladar A; Fong, Yuman; Wong, Richard J

    2008-11-01

    Anaplastic thyroid carcinoma (ATC) is a fatal disease with a median survival of only 6 months. Novel therapies are needed to improve dismal outcomes. A mutated, replication-competent, vaccinia virus (GLV-1h68) has oncolytic effects on human ATC cell lines in vitro. We assessed the utility of GLV-1h68 in treating anaplastic thyroid cancer in vivo. Athymic nude mice with xenograft flank tumors of human ATCs (8505C and DRO90-1) were treated with a single intratumoral injection of GLV-1h68 at low dose (5x10(5) plaque-forming unit), high dose (5x10(6) plaque-forming unit), or PBS. Virus-mediated marker gene expression (luciferase, green fluorescent protein, and beta-galactosidase), viral biodistribution, and flank tumor volumes were measured. Luciferase expression was detected 2 d after injection. Continuous viral replication within tumors was reflected by increasing luciferase activity to d 9. At d 10, tumor viral recovery was increased more than 50-fold as compared with the injected dose, and minimal virus was recovered from the lung, liver, brain, heart, spleen, and kidneys. High-dose virus directly injected into normal tissues was undetectable at d 10. The mean volume of control 8505C tumors increased 50.8-fold by d 45, in contrast to 10.5-fold (low dose) and 2.1-fold (high dose; P=0.028) increases for treated tumors. DRO90-1 tumors also showed significant growth inhibition by high-dose virus. No virus-related toxicity was observed throughout the study. GLV-1h68 efficiently infects, expresses transgenes within, and inhibits the growth of ATC in vivo. These promising findings support future clinical trials for patients with ATC.

  19. Steady-state properties of sodium channels from healthy and tumorous human brain

    NARCIS (Netherlands)

    Frenkel, C.; Wartenberg, H. C.; Duch, D. S.; Urban, B. W.

    1998-01-01

    This extensive bilayer study of unpurified human brain channels from non-diseased and tumorous human brain involves more than 300 lipid bilayer experiments. Single channel conductances and subconductances, single channel fractional open times, the voltage-dependence of tetrodotoxin (TTX) block and

  20. Expression of metastasis-associated protein 3 in human brain glioma related to tumor prognosis.

    Science.gov (United States)

    Shan, Shouqin; Hui, Guangyan; Hou, Fanggao; Shi, Hua; Zhou, Guoqing; Yan, Han; Wang, Lu; Liu, Jinfeng

    2015-10-01

    Glioma represents a disparate group of tumors characterized by high invasion ability, and therefore it is of clinical significance to identify molecular markers and therapeutic targets for better clinical management. Previously, metastasis-associated protein family (MTA) is considered to promote tumor cell invasion and metastasis of human malignancies. Recently, the newly identified MTA3 has been shown to play conflicting roles in human malignancies, while the expression pattern and potential clinical significance of MTA3 in human glioma have not been addressed yet. In the present study, we investigated the protein expression of MTA3 by immunohistochemistry assay and analyzed its association with glioma prognosis in 186 cases of patients. Results showed that MTA3 expression was decreased in glioma compared with that in normal brain (P human glioma and negatively associated with prognosis of patients, suggesting that MTA3 may play a tumor suppressor role in glioma.

  1. Alvocidib (Flavopiridol) suppresses tumor growth in SCID mice with human esophageal cancer xenografts without inducing apoptosis.

    Science.gov (United States)

    Sato, Shinsuke; Kajiyama, Yoshiaki; Sugano, Masahiko; Iwanuma, Yoshimi; Sonoue, Hiroshi; Matsumoto, Toshiharu; Tsurumaru, Masahiko

    2006-08-01

    Alvocidib (Flavopiridol, HMR1275) is a potent inhibitor of multiple cyclin-dependent kinases and has been identified recently as an antitumor agent in several cancers. Previous studies have shown that alvocidib could potentially treat esophageal cancer in vitro. This study evaluates alvocidib for its ability to suppress tumor growth in severe combined immunodeficiency (SCID) mice bearing TE8 human esophageal squamous cell carcinoma (SCC) xenografts. Alvocidib treatment of 10mg/kg body weight reduced tumor volume significantly. Immunohistochemistry analysis of alvocidib-treated tumor sections showed significant reductions in cyclin D1, VEGF, and Rb levels. Alvocidib treatment did not cause a marked increase in apoptotic tumor cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis, yet hematoxylin and eosin staining revealed tumor necrosis. In vivo investigation of alvocidib treatment confirmed antitumor activity in TE8 esophageal xenografts. These findings suggest that alvocidib could be a useful anti-cancer agent for esophageal cancer.

  2. Growth curves of three human malignant tumors transplanted to nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Nielsen, A; Visfeldt, J

    1980-01-01

    Experimental growth data for three human malignant tumors transplanted to nude mice of BALB/c origin are analyzed statistically in order to investigate whether they can be described according to the Gompertz function. The aim is to set up unequivocal standards for planned therapeutic experiments...... and to develop an essential part of the determination of proliferation parameters for the tumors. The results indicate that the course of tumor growth can be described with good approximation by the Gompertz function. A transformation of this function depicts the growth rectilinearly and appears to be suitable...... as a standard, e.g. in therapeutic experiments. The course of tumor growth is independent of the size of the transplant, and whether tumors are transplanted in the right or left or both flanks of the recipient mice. Furthermore, the growth does not vary in a systematic way with the number of passages in nude...

  3. Study of potential inhibitors of thyroid iodide uptake by using CHO cells stably expressing the human sodium/iodide symporter (hNIS) protein.

    Science.gov (United States)

    Agretti, P; Dimida, A; De Marco, G; Ferrarini, E; Rodrìguez Gonzàlez, J C; Santini, F; Vitti, P; Pinchera, A; Tonacchera, M

    2011-03-01

    Thyroid gland is highly dependent on dietary intake of iodine for normal function, so it is particularly subjected to "endocrine disruptor" action. The human sodium/iodide symporter (hNIS) is an integral plasma membrane glycoprotein mediating the active transport of iodide into thyroid follicular cells, a crucial step for thyroid hormone biosynthesis. Beyond to perchlorate and thyocianate ions a few other inhibitors of iodide uptake have been described. The aim of this study was to investigate if 10 substances usually used as drugs in clinical practice were able to inhibit NIS-mediated iodide uptake in vitro. A CHO cell line stably expressing hNIS was used to test any inhibition of NIS-mediated iodide uptake exerted by drugs. Perchlorate and thyocianate ions were used as positive controls. None of the analyzed substances was able to significantly inhibit iodide uptake in our system. As we expected, perchlorate and thyocianate ions were able to inhibit iodide uptake in a dose-dependent manner. In conclusion, we carried out an in vitro assay to evaluate the potential inhibitory effect of common drugs on NISmediated iodide uptake by using CHO-hNIS cells. None of the analyzed substances was able to inhibit iodide uptake; only perchlorate and thyocianate were able to inhibit iodide uptake in a dose-dependent manner.

  4. Method of conjugate gamma camera image to determine tumor uptake in other thyroid treatments with I-131; Metodo de la imagen conjugada en Gammacamara para determinar la captacion en resto tumoral tiroideo en tratamientos con I-131

    Energy Technology Data Exchange (ETDEWEB)

    Barquero, R.; Sainz, A.; Tortosa, R.; Mari, A.

    2011-07-01

    The efficacy of ablation of thyroid remnants with 1-131 in the treatment of CDT depends on the activity captured in these remains, the optimal method for quantifying this activity is based on the gamma camera imaging with in the course of treatment. However, due to saturation of the image with high activities and time-cost optimization of machine, not usually get those images, except in a post-treatment scan. In our service MN tracking each patient is between 6 and 9 after administration. A method of quantification of the activity captured in other thyroid screening using this image.

  5. Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms.

    Science.gov (United States)

    Stewart, Daniel C; Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S

    2017-01-01

    While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17-16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.

  6. Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms.

    Directory of Open Access Journals (Sweden)

    Daniel C Stewart

    Full Text Available While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17-16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.

  7. Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms

    Science.gov (United States)

    Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S.

    2017-01-01

    While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17–16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models. PMID:28582392

  8. Bioinformatics Analysis of the Human Surfaceome Reveals New Targets for a Variety of Tumor Types

    Directory of Open Access Journals (Sweden)

    André L. Fonseca

    2016-01-01

    Full Text Available It is estimated that 10 to 20% of all genes in the human genome encode cell surface proteins and due to their subcellular localization these proteins represent excellent targets for cancer diagnosis and therapeutics. Therefore, a precise characterization of the surfaceome set in different types of tumor is needed. Using TCGA data from 15 different tumor types and a new method to identify cancer genes, the S-score, we identified several potential therapeutic targets within the surfaceome set. This allowed us to expand a previous analysis from us and provided a clear characterization of the human surfaceome in the tumor landscape. Moreover, we present evidence that a three-gene set—WNT5A, CNGA2, and IGSF9B—can be used as a signature associated with shorter survival in breast cancer patients. The data made available here will help the community to develop more efficient diagnostic and therapeutic tools for a variety of tumor types.

  9. Expression profiles of SnoN in normal and cancerous human tissues support its tumor suppressor role in human cancer.

    Directory of Open Access Journals (Sweden)

    Nadine S Jahchan

    Full Text Available SnoN is a negative regulator of TGF-β signaling and also an activator of the tumor suppressor p53 in response to cellular stress. Its role in human cancer is complex and controversial with both pro-oncogenic and anti-oncogenic activities reported. To clarify its role in human cancer and provide clinical relevance to its signaling activities, we examined SnoN expression in normal and cancerous human esophageal, ovarian, pancreatic and breast tissues. In normal tissues, SnoN is expressed in both the epithelium and the surrounding stroma at a moderate level and is predominantly cytoplasmic. SnoN levels in all tumor epithelia examined are lower than or similar to that in the matched normal samples, consistent with its anti-tumorigenic activity in epithelial cells. In contrast, SnoN expression in the stroma is highly upregulated in the infiltrating inflammatory cells in high-grade esophageal and ovarian tumor samples, suggesting that SnoN may potentially promote malignant progression through modulating the tumor microenvironment in these tumor types. The overall levels of SnoN expression in these cancer tissues do not correlate with the p53 status. However, in human cancer cell lines with amplification of the snoN gene, a strong correlation between increased SnoN copy number and inactivation of p53 was detected, suggesting that the tumor suppressor SnoN-p53 pathway must be inactivated, either through downregulation of SnoN or inactivation of p53, in order to allow cancer cell to proliferate and survive. These data strongly suggest that SnoN can function as a tumor suppressor at early stages of tumorigenesis in human cancer tissues.

  10. Predictive Value of Sphingosine Kinase 1 Expression in Papillary Thyroid Carcinoma.

    Science.gov (United States)

    Do, Sung-Im; Kim, Hyun-Soo; Kim, Kyungeun; Lee, Hyunjoo; Do, In-Gu; Kim, Dong-Hoon; Chae, Seoung Wan; Sohn, Jin Hee

    2017-10-01

    Sphingolipid metabolites are emerging as key signaling molecules in cancer. Sphingosine kinase 1 is up-regulated in many different types of human malignancies and plays a crucial role in cancer development and progression. The utility of sphingosine kinase 1 to act as a predictive biomarker in thyroid cancer remains unclear. Sphingosine kinase 1 expression was evaluated using immunohistochemical staining in 110 formalin-fixed, paraffin-embedded papillary thyroid carcinoma tissue samples. Sphingosine kinase 1 expression in papillary thyroid carcinoma tissue was significantly higher than in nodular goiter (pcarcinomas exhibited high sphingosine kinase 1 expression, that was significantly associated with tumor multiplicity (p=0.004), extrathyroidal extension (p=0.013), presence of lymph node metastasis (pcarcinoma development and progression and can serve as a potential biomarker predictive of lymph node metastasis. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. PCR Expression Analysis Of the Estrogeninducible Gene Bcei in Gastrointestinal and Other Human Tumors

    Directory of Open Access Journals (Sweden)

    Iris Wundrack

    1994-01-01

    Full Text Available A polymerase chain reaction (PCR assay was developed to test for tumor cell specific expression of the BCEI gene. This new marker gene, reported at first for human breast cancer, was found specifically active in various gastrointestinal carcinomas by previously applying immunohistochemistry and RNA (Northern blot analysis. Presently, by using reverse transcription -PCR analysis, a series of primary tumor tissues and established tumor cell lines were testcd for BCEI transcription. This approach was compared to immunostaining achieved by an antibody directed against the BCEI gene’s product. The result demonstrate the superior sensitivity of PCR by indicating the gene’ s expression in cases where immunohistochemical testing remained negative.

  12. Circadian clocks and tumor biology: what is to learn from human skin biopsies?

    Science.gov (United States)

    Lengyel, Zsuzsanna; Battyáni, Zita; Szekeres, György; Csernus, Valér; Nagy, András D

    2013-07-01

    Some of the components of the circadian molecular clock have been shown to link directly to tumor suppression. Most studies on human tumorous biopsies with consistently down-regulated clock gene expression suggested a protective role for these genes against cancer formation. To highlight some limitations of this hypothesis we review these data in light of recent evidences from animal research, epidemiologic studies, and clinical data on skin tumors. We emphasize the role of circadian rhythmic orchestration in cellular metabolism with a potential in cancer development. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. A multi-class predictor based on a probabilistic model: application to gene expression profiling-based diagnosis of thyroid tumors.

    Science.gov (United States)

    Yukinawa, Naoto; Oba, Shigeyuki; Kato, Kikuya; Taniguchi, Kazuya; Iwao-Koizumi, Kyoko; Tamaki, Yasuhiro; Noguchi, Shinzaburo; Ishii, Shin

    2006-07-27

    Although microscopic diagnosis has been playing the decisive role in cancer diagnostics, there have been cases in which it does not satisfy the clinical need. Differential diagnosis of malignant and benign thyroid tissues is one such case, and supplementary diagnosis such as that by gene expression profile is expected. With four thyroid tissue types, i.e., papillary carcinoma, follicular carcinoma, follicular adenoma, and normal thyroid, we performed gene expression profiling with adaptor-tagged competitive PCR, a high-throughput RT-PCR technique. For differential diagnosis, we applied a novel multi-class predictor, introducing probabilistic outputs. Multi-class predictors were constructed using various combinations of binary classifiers. The learning set included 119 samples, and the predictors were evaluated by strict leave-one-out cross validation. Trials included classical combinations, i.e., one-to-one, one-to-the-rest, but the predictor using more combination exhibited the better prediction accuracy. This characteristic was consistent with other gene expression data sets. The performance of the selected predictor was then tested with an independent set consisting of 49 samples. The resulting test prediction accuracy was 85.7%. Molecular diagnosis of thyroid tissues is feasible by gene expression profiling, and the current level is promising towards the automatic diagnostic tool to complement the present medical procedures. A multi-class predictor with an exhaustive combination of binary classifiers could achieve a higher prediction accuracy than those with classical combinations and other predictors such as multi-class SVM. The probabilistic outputs of the predictor offer more detailed information for each sample, which enables visualization of each sample in low-dimensional classification spaces. These new concepts should help to improve the multi-class classification including that of cancer tissues.

  14. A multi-class predictor based on a probabilistic model: application to gene expression profiling-based diagnosis of thyroid tumors

    Directory of Open Access Journals (Sweden)

    Noguchi Shinzaburo

    2006-07-01

    Full Text Available Abstract Background Although microscopic diagnosis has been playing the decisive role in cancer diagnostics, there have been cases in which it does not satisfy the clinical need. Differential diagnosis of malignant and benign thyroid tissues is one such case, and supplementary diagnosis such as that by gene expression profile is expected. Results With four thyroid tissue types, i.e., papillary carcinoma, follicular carcinoma, follicular adenoma, and normal thyroid, we performed gene expression profiling with adaptor-tagged competitive PCR, a high-throughput RT-PCR technique. For differential diagnosis, we applied a novel multi-class predictor, introducing probabilistic outputs. Multi-class predictors were constructed using various combinations of binary classifiers. The learning set included 119 samples, and the predictors were evaluated by strict leave-one-out cross validation. Trials included classical combinations, i.e., one-to-one, one-to-the-rest, but the predictor using more combination exhibited the better prediction accuracy. This characteristic was consistent with other gene expression data sets. The performance of the selected predictor was then tested with an independent set consisting of 49 samples. The resulting test prediction accuracy was 85.7%. Conclusion Molecular diagnosis of thyroid tissues is feasible by gene expression profiling, and the current level is promising towards the automatic diagnostic tool to complement the present medical procedures. A multi-class predictor with an exhaustive combination of binary classifiers could achieve a higher prediction accuracy than those with classical combinations and other predictors such as multi-class SVM. The probabilistic outputs of the predictor offer more detailed information for each sample, which enables visualization of each sample in low-dimensional classification spaces. These new concepts should help to improve the multi-class classification including that of cancer tissues.

  15. Human tumor-associated viruses and new insights into the molecular mechanisms of cancer.

    Science.gov (United States)

    Martin, D; Gutkind, J S

    2008-12-01

    The study of acute-transforming retroviruses and their oncogenes and of the multiple mechanisms deployed by DNA viruses to circumvent the growth-suppressive and proapoptotic function of tumor suppressor genes has provided the foundation of our current understanding of cancer biology. Unlike acute-transforming animal viruses, however, human tumor-associated viruses lead to malignancies with a prolonged latency and in conjunction with other environmental and host-related cooperating events. The relevance of viral infection to human cancer development has often been debated. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), human T-cell lymphotropic virus (HTLV-1) and Kaposi's associated sarcoma virus (KSHV) contribute to 10-15% of the cancers worldwide. Hence, the opportunity exists to fight cancer at the global scale by preventing the spread of these viruses, by the development and distribution of effective and safe antiviral vaccines, and by identifying their oncogenic mechanism. Here, we discuss the molecular events underlying the neoplastic potential of the human tumor-associated viruses, with emphasis on the enigmatic KSHV and its numerous virally hijacked proangiogenic, immune-evasive and tumor-promoting genes. The emerging information may facilitate the development of new molecular-targeted approaches to prevent and treat virally associated human malignancies.

  16. Cerebral glial tumors and human immunodeficiency virus-1 infection. More than a coincidental association.

    Science.gov (United States)

    Moulignier, A; Mikol, J; Pialoux, G; Eliaszewicz, M; Thurel, C; Thiebaut, J B

    1994-07-15

    The authors describe the clinical and morphologic patterns in four patients with acquired immune deficiency syndrome (AIDS) who developed intracranial glial tumors. This retrospective study reports 70 patients at various stages of human immunodeficiency virus-1 (HIV-1) infection who underwent stereotactic brain biopsy for an intracerebral space-occupying lesion. Of these patients, four had glial tumors: one astroblastoma, two astrocytomas, and one glioblastoma. Glial tumors probably arise from a complex interplay of factors; possibilities include the activation of a dominant oncogene or viral inactivation of a tumor suppressor gene by a viral promoter (like the tat protein), impairment of immune defenses (which facilitates the growth of astrocytomas in acute lymphoblastic leukemia), production of cellular growth factors, cytokines, possible infection of glial cells by HIV, and the potentiation of a coinfectious agent. These cases illustrate that glial tumors should be considered in the differential diagnosis of brain masses in HIV-1 infection, especially because specific treatment for these tumors is available. Moreover, the occurrence of glial tumors in AIDS patients is not only an important event from a clinical point of view, but may also have implications for the pathogenesis of tumors in AIDS.

  17. Immunohistochemical profiling of the ultimobranchial remnants in the rat postnatal thyroid gland.

    Science.gov (United States)

    Vázquez-Román, Victoria; Utrilla, José C; Fernández-Santos, José M; Martín-Lacave, Inés

    2017-08-01

    Ultimobranchial (UB) remnants are a constant presence in the thyroid throughout rat postnatal life; however, the difficulty in identifying the most immature forms from the surrounding thyroid tissue prompted us to search for a specific marker. With that objective, we applied a panel of antibodies reported to be specific for their human counterpart, solid cell nests (SCNs), using double immunohistochemistry and immunofluorescence. Our results demonstrated that cytokeratin 34βE12 and p63 are highly sensitive markers for the immunohistologic screening of UB-remnants, independently of their maturity or size. Furthermore, rat UB-follicles (UBFs) coincided with human SCNs in the immunohistochemical pattern exhibited by both antigens. In contrast, the pattern displayed for calcitonin and thyroglobulin differs considerably but confirm the hypothesis that rat UB-cells can differentiate into both types of thyroid endocrine cells. This hypothesis agrees with recent findings that thyroid C-cells share an endodermic origin with follicular cells in rodents. We suggest that the persistence of p63-positive undifferentiated cells in UB-remnants may constitute a reservoir of basal/stem cells that persist beyond embryogenesis from which, in certain unknown conditions, differentiated thyroid cells or even unusual tumors may arise. © 2017 Wiley Periodicals, Inc.

  18. Strategies for Human Tumor Virus Discoveries: From Microscopic Observation to Digital Transcriptome Subtraction.

    Science.gov (United States)

    Mirvish, Ezra D; Shuda, Masahiro

    2016-01-01

    Over 20% of human cancers worldwide are associated with infectious agents, including viruses, bacteria, and parasites. Various methods have been used to identify human tumor viruses, including electron microscopic observations of viral particles, immunologic screening, cDNA library screening, nucleic acid hybridization, consensus PCR, viral DNA array chip, and representational difference analysis. With the Human Genome Project, a large amount of genetic information from humans and other organisms has accumulated over the last decade. Utilizing the available genetic databases, Feng et al. (2007) developed digital transcriptome subtraction (DTS), an in silico method to sequentially subtract human sequences from tissue or cellular transcriptome, and discovered Merkel cell polyomavirus (MCV) from Merkel cell carcinoma. Here, we review the background and methods underlying the human tumor virus discoveries and explain how DTS was developed and used for the discovery of MCV.

  19. Human pancreatic tumors grown in mice release tissue factor-positive microvesicles that increase venous clot size.

    Science.gov (United States)

    Hisada, Y; Ay, C; Auriemma, A C; Cooley, B C; Mackman, N

    2017-11-01

    Essentials Tumor-bearing mice have larger venous clots than controls. Human tissue factor is present in clots in tumor-bearing mice. Inhibition of human tissue factor reduces clot size in tumor-bearing mice. This new mouse model may be useful to study mechanisms of cancer-associated thrombosis. Background Pancreatic cancer patients have a high rate of venous thromboembolism. Human pancreatic tumors and cell lines express high levels of tissue factor (TF), and release TF-positive microvesicles (TF+ MVs). In pancreatic cancer patients, tumor-derived TF+ MVs are present in the blood, and increased levels are associated with venous thromboembolism and decreased survival. Previous studies have shown that mice with orthotopic human or murine pancreatic tumors have circulating tumor-derived TF+ MVs, an activated clotting system, and increased incidence and mean clot weight in an inferior vena cava stenosis model. These results suggest that TF+ MVs contribute to thrombosis. However, the specific role of tumor-derived TF+ MVs in venous thrombosis in mice has not been determined. Objectives To test the hypothesis that tumor-derived TF+ MVs enhance thrombosis in mice. Methods We determined the contribution of TF+ MVs derived from human pancreatic tumors grown orthotopically in nude mice to venous clot formation by using an anti-human TF mAb. We used an inferior vena cava stasis model of venous thrombosis. Results Tumor-bearing mice had significantly larger clots than control mice. Clots from tumor-bearing mice contained human TF, suggesting the incorporation of tumor-derived MVs. Importantly, administration of an anti-human TF mAb reduced clot size in tumor-bearing mice but did not affect clot size in control mice. Conclusions Our results indicate that TF+ MVs released from orthotopic pancreatic tumors increase venous thrombosis in mice. This new model may be useful for evaluating the roles of different factors in cancer-associated thrombosis. © 2017 International Society on

  20. Consensus on the management of advanced medullary thyroid carcinoma on behalf of the Working Group of Thyroid Cancer of the Spanish Society of Endocrinology (SEEN) and the Spanish Task Force Group for Orphan and Infrequent Tumors (GETHI).

    Science.gov (United States)

    Galofré, Juan C; Santamaría Sandi, Javier; Capdevila, Jaume; Navarro González, Elena; Zafón Llopis, Carles; Ramón Y Cajal Asensio, Teresa; Gómez Sáez, José Manuel; Jiménez-Fonseca, Paula; Riesco Eizaguirre, Garcilaso; Grande, Enrique

    2015-04-01

    In Spain medullary thyroid carcinoma (MTC) would not exceed 80 new cases per year and less than half of them would be good candidates for systemic treatment with novel agents. Relevant literature was reviewed, including PubMed searches supplemented with additional articles. The consensus summarizes the clinical outcomes in terms of activity and toxicity of each of the available drugs. A brief summary of the minimum requirements in terms of follow up and genetic counseling around MTC is also included. Only those patients with objective imaging progression in the last 12-14 months with large volume of disease are clear candidates to start systemic treatment. However, those patients with low disease volume should be considered for 'wait and see' strategy until symptoms of the disease appear. Multidisciplinary approach for the management of MTC patient is mandatory nowadays. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  1. Metastasis of colon cancer to medullary thyroid carcinoma: a case report.

    Science.gov (United States)

    Yeo, So-Jung; Kim, Kyu-Jin; Kim, Bo-Yeon; Jung, Chan-Hee; Lee, Seung-Won; Kwak, Jeong-Ja; Kim, Chul-Hee; Kang, Sung-Koo; Mok, Ji-Oh

    2014-10-01

    Metastasis to the primary thyroid carcinoma is extremely rare. We report here a case of colonic adenocarcinoma metastasis to medullary thyroid carcinoma in a 53-yr old man with a history of colon cancer. He showed a nodular lesion, suggesting malignancy in the thyroid gland, in a follow-up examination after colon cancer surgery. Fine needle aspiration biopsy (FNAB) of the thyroid gland showed tumor cell clusters, which was suspected to be medullary thyroid carcinoma (MTC). The patient underwent a total thyroidectomy. Using several specific immunohistochemical stains, the patient was diagnosed with colonic adenocarcinoma metastasis to MTC. To the best of our knowledge, the present patient is the first case of colonic adenocarcinoma metastasizing to MTC. Although tumor-tumor metastasis to primary thyroid carcinoma is very rare, we still should consider metastasis to the thyroid gland, when a patient with a history of other malignancy presents with a new thyroid finding.

  2. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Suhail Mahmoud M

    2011-12-01

    Full Text Available Abstract Background Gum resins obtained from trees of the Burseraceae family (Boswellia sp. are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. Methods Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 oC for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231 and an immortalized normal human breast cell line (MCF10-2A. Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. Results More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 oC hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil

  3. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

    Science.gov (United States)

    2011-01-01

    Background Gum resins obtained from trees of the Burseraceae family (Boswellia sp.) are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. Methods Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 oC for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231) and an immortalized normal human breast cell line (MCF10-2A). Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. Results More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 oC hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil treatment. Boswellia sacra

  4. A potential diagnostic application of magnetization transfer contrast: an in vitro NMR study of excised human thyroid tissues

    Science.gov (United States)

    Callicott, C.; Goode, A. W.

    1998-03-01

    A series of freshly excised thyroid tissues was analysed using a nuclear magnetic resonance spectrometer and then subjected to routine histo-pathology examination. Whilst simple values for normal tissue and goitre are not significantly different, the degree of intra-subject and variability is shown to be an indicator of benign thyroid disease. Using data collected from an inversion-recovery sequence performed with and without magnetization transfer, a magnetization transfer rate constant was calculated for each tissue sample. These data suggest that this parameter may provide in vivo discrimination between follicular cancer and follicular adenoma.

  5. Sulfation of thyroid hormone by estrogen sulfotransferase

    NARCIS (Netherlands)

    M.H.A. Kester (Monique); T.J. Visser (Theo); C.H. van Dijk (Caren); D. Tibboel (Dick); A.M. Hood (Margaret); N.J. Rose; W. Meinl; U. Pabel; H. Glatt; C.N. Falany; M.W. Coughtrie

    1999-01-01

    textabstractSulfation is one of the pathways by which thyroid hormone is inactivated. Iodothyronine sulfate concentrations are very high in human fetal blood and amniotic fluid, suggesting important production of these conjugates in utero. Human estrogen

  6. Radioimmunoassay in the diagnosis of thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kashkadamov, A.V.; Komissarenko, I.V. (Kievskij Nauchno-Issledovatel' skij Inst. Ehndokrinologii i Obmena Veshchestv (Ukrainian SSR))

    1983-08-01

    The paper is concerned with a study of the concentration of thyrotropic hormone (TTH), thyroxine, triidothyronine, thyroxine-binding globulin (TBG), thyroglobulin (TG) and carcinoembryonic antigen (CEA) in the blood plasma of 69 patients with benign and malignant thyroid tumors. It has been established that the determination of TTH and TBG level can be used as an additional criterion to define the nature of a tumor process in the thyroid gland. A study of TTH and TG levels is of diagnostic importance in patients with recurrences and metastases of thyroidal cancer to the lungs. A study of the level of CEA in the blood is an important parameter in the control over the efficacy of thyroid cancer treatment.

  7. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    Energy Technology Data Exchange (ETDEWEB)

    Erez, Neta, E-mail: netaerez@post.tau.ac.il [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Glanz, Sarah [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Raz, Yael [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Avivi, Camilla [Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Barshack, Iris [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  8. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... code: Phone no: Thank you! Do you have a personal story about radiology? Share your patient story ...

  9. American Thyroid Association

    Science.gov (United States)

    ... Professionals Thyroid Information Find out more information on Thyroid Disease. learn more Meetings ATA meeting dates, information, and education. learn more Publications/News Thyroid, Clinical Thyroidology, VideoEndocrinology and NEWS. learn more Guidelines ...

  10. Thyroid gland removal - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000293.htm Thyroid gland removal - discharge To use the sharing features ... surgery. This will make your scar show less. Thyroid Hormone Replacement You may need to take thyroid ...

  11. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... typically performed on people who have or had thyroid cancer. A physician may perform these imaging tests to: ... such as lumps (nodules) or inflammation determine whether thyroid cancer has spread beyond the thyroid gland evaluate changes ...

  12. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... taking our brief survey: Survey Do you have a personal story about radiology? Share your patient story ...

  13. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... the limitations of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid ... body converts food to energy. top of page What are some common uses of the procedure? The ...

  14. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... scan and thyroid uptake provide information about the structure and function of the thyroid. The thyroid is ... computer, create pictures offering details on both the structure and function of organs and tissues in your ...

  15. Thyroid Function Tests

    Science.gov (United States)

    ... a patient with hypothyroidism make a diagnosis of Hashimoto’s thyroiditis. If the antibodies are positive in a ... Thyroid Nodules Goiter Graves’ Disease Graves’ Eye Disease Hashimoto’s Thyroiditis Hyperthyroidism (Overactive) Hypothyroidism (Underactive) Iodine Deficiency Low ...

  16. Systemic uptake of diethyl phthalate, dibutyl phthalate, and butyl paraben following whole-body topical application and reproductive and thyroid hormone levels in humans

    DEFF Research Database (Denmark)

    Janjua, Nadeem Rezaq; Mortensen, Gerda Krogh; Andersson, Anna-Maria

    2007-01-01

    In vitro and animal studies have reported endocrine-disrupting activity of chemicals used commonly as additives in cosmetics and skin care products. We investigated whether diethyl phthalate (DEP), dibutyl phthalate (DBP), and butyl paraben (BP) were systemically absorbed and influenced endogenous...... reproductive and thyroid hormone levels in humans after topical application. In a two-week single-blinded study, 26 healthy young male volunteers were assigned to daily whole-body topical application of 2 mg/cm2 basic cream formulation each without (week one) and with (week two) the three 2% (w/w) compounds...

  17. Evaluation of Antiproliferative Potential of Cerium Oxide Nanoparticles on HeLa Human Cervical Tumor Cell

    Directory of Open Access Journals (Sweden)

    Zoriţa Diaconeasa

    2015-05-01

    Full Text Available Cerium oxide nanoparticles (CeO2 nanoparticles as nanomaterials have promising biomedical applications. In this paper, the cytotoxicity induced by CONPs human cervical tumor cells was investigated. Cerium oxide nanoparticles were synthesized using the precipitation method. The nanoparticles were found to inhibit the proliferation of HeLa human cervical tumor cells in a dose dependent manner but did not showed to be cytotoxic as analyzed by MTT assay. The administrated treatment decreased the HeLa cell viability cells from 100% to 65% at the dose of 100 μg/mL.

  18. [Risk factors and the progression of thyroid malignancies].

    Science.gov (United States)

    Giannoula, Evanthia; Iakovou, Ioannis; Chatzipavlidou, Vasiliki

    2015-01-01

    Thyroid cancer is the most common endocrine malignancy and the fifth most common malignant neoplasm of the female sex. During the past several decades, an increasing incidence of thyroid cancer has been reported. The mortality from thyroid cancer is comparatively low and remains almost stable showing a slight increase. It is currently unclear whether the observed increase in thyroid cancer is real or is due to overdiagnosis, as clinical and pathology findings may be sometimes doubtful in diagnosing the incidence and mortality of thyroid cancer. The cancer has different distribution depending on gender, race, age and environmental conditions. Despite considerable progress in the understanding of the biology and molecular pathways of carcinogenesis in the thyroid gland, less progress has been made in terms of defining a risk profile for thyroid cancer. The only risk factor which is systematically documented as carcinogenic for thyroid is exposure to ionizing radiation during childhood. Recently several studies are examining as risk factors diet and exercise, benign thyroid diseases as well as a genetic factors that influence the incidence and mortality of the disease. To the best of our knowledge there are only few epidemiological studies examining the effects of exposure to chemical agents on thyroid cancer's "behavior". The effect of risk factors for the onset and progression of malignant thyroid tumors constitutes a field that requires further study in order to provide answers on the pathogenesis of the disease, so as to take preventing measures and finally manage to decrease thyroid cancer incidence and mortality.

  19. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models

    Science.gov (United States)

    Liu, Huiping; Patel, Manishkumar R.; Prescher, Jennifer A.; Patsialou, Antonia; Qian, Dalong; Lin, Jiahui; Wen, Susanna; Chang, Ya-Fang; Bachmann, Michael H.; Shimono, Yohei; Dalerba, Piero; Adorno, Maddalena; Lobo, Neethan; Bueno, Janet; Dirbas, Frederick M.; Goswami, Sumanta; Somlo, George; Condeelis, John; Contag, Christopher H.; Gambhir, Sanjiv Sam; Clarke, Michael F.

    2010-01-01

    To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44+ cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy. PMID:20921380

  20. High hydrostatic pressure induces immunogenic cell death in human tumor cells.

    Science.gov (United States)

    Fucikova, Jitka; Moserova, Irena; Truxova, Iva; Hermanova, Ivana; Vancurova, Irena; Partlova, Simona; Fialova, Anna; Sojka, Ludek; Cartron, Pierre-Francois; Houska, Milan; Rob, Lukas; Bartunkova, Jirina; Spisek, Radek

    2014-09-01

    Recent studies have identified molecular events characteristic of immunogenic cell death (ICD), including surface exposure of calreticulin (CRT), the heat shock proteins HSP70 and HSP90, the release of high-mobility group box protein 1 (HMGB1) and the release of ATP from dying cells. We investigated the potential of high hydrostatic pressure (HHP) to induce ICD in human tumor cells. HHP induced the rapid expression of HSP70, HSP90 and CRT on the cell surface. HHP also induced the release of HMGB1 and ATP. The interaction of dendritic cells (DCs) with HHP-treated tumor cells led to a more rapid rate of DC phagocytosis, upregulation of CD83, CD86 and HLA-DR and the release of interleukin IL-6, IL-12p70 and TNF-α. DCs pulsed with tumor cells killed by HHP induced high numbers of tumor-specific T cells. DCs pulsed with HHP-treated tumor cells also induced the lowest number of regulatory T cells. In addition, we found that the key features of the endoplasmic reticulum stress-mediated apoptotic pathway, such as reactive oxygen species production, phosphorylation of the translation initiation factor eIF2α and activation of caspase-8, were activated by HHP treatment. Therefore, HHP acts as a reliable and potent inducer of ICD in human tumor cells. © 2014 UICC.

  1. Rapid spread of mouse mammary tumor virus in cultured human breast cells

    Directory of Open Access Journals (Sweden)

    Günzburg Walter H

    2007-10-01

    Full Text Available Abstract Background The role of mouse mammary tumor virus (MMTV as a causative agent in human breast carcinogenesis has recently been the subject of renewed interest. The proposed model is based on the detection of MMTV sequences in human breast cancer but not in healthy breast tissue. One of the main drawbacks to this model, however, was that until now human cells had not been demonstrated to sustain productive MMTV infection. Results Here, we show for the first time the rapid spread of mouse mammary tumor virus, MMTV(GR, in cultured human mammary cells (Hs578T, ultimately leading to the infection of every cell in culture. The replication of the virus was monitored by quantitative PCR, quantitative RT-PCR and immunofluorescence imaging. The infected human cells expressed, upon cultivation with dexamethasone, MMTV structural proteins and released spiked B-type virions, the infectivity of which could be neutralized by anti-MMTV antibody. Replication of the virus was efficiently blocked by an inhibitor of reverse transcription, 3'-azido-3'-deoxythymidine. The human origin of the infected cells was confirmed by determining a number of integration sites hosting the provirus, which were unequivocally identified as human sequences. Conclusion Taken together, our results show that human cells can support replication of mouse mammary tumor virus.

  2. Hersintuzumab: A novel humanized anti-HER2 monoclonal antibody induces potent tumor growth inhibition.

    Science.gov (United States)

    Amiri, Mohammad Mehdi; Golsaz-Shirazi, Forough; Soltantoyeh, Tahereh; Hosseini-Ghatar, Reza; Bahadori, Tannaz; Khoshnoodi, Jalal; Navabi, Shadi Sadat; Farid, Samira; Karimi-Jafari, Mohammad Hossein; Jeddi-Tehrani, Mahmood; Shokri, Fazel

    2017-10-06

    Humanized monoclonal antibodies (mAbs) against HER2 including trastuzumab and pertuzumab are widely used to treat HER2 overexpressing metastatic breast cancers. These two mAbs recognize distinct epitopes on HER2 and their combination induces a more potent blockade of HER2 signaling than trastuzumab alone. Recently, we have reported characterization of a new chimeric mAb (c-1T0) which binds to an epitope different from that recognized by trastuzumab and significantly inhibits proliferation of HER2 overexpressing tumor cells. Here, we describe humanization of this mAb by grafting all six complementarity determining regions (CDRs) onto human variable germline genes. Humanized VH and VL sequences were synthesized and ligated to human γ1 and κ constant region genes using splice overlap extension (SOE) PCR. Subsequently, the humanized antibody designated hersintuzumab was expressed and characterized by ELISA, Western blot and flow cytometry. The purified humanized mAb binds to recombinant HER2 and HER2-overexpressing tumor cells with an affinity comparable with the chimeric and parental mouse mAbs. It recognizes an epitope distinct from those recognized by trastuzumab and pertuzumab. Binding of hersintuzumab to HER2 overexpressing tumor cells induces G1 cell cycle arrest, inhibition of ERK and AKT signaling pathways and growth inhibition. Moreover, hersintuzumab could induce antibody-dependent cell cytotoxicity (ADCC) on BT-474 cells. This new humanized mAb is a potentially valuable tool for single or combination breast cancer therapy.

  3. Thyroid effects of endocrine disrupting chemicals

    DEFF Research Database (Denmark)

    Boas, Malene; Feldt-Rasmussen, Ulla; Main, Katharina M

    2012-01-01

    In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert...... thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth...... and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have...

  4. New developments in the diagnosis and treatment of thyroid cancer.

    Science.gov (United States)

    Schneider, David F; Chen, Herbert

    2013-01-01

    Thyroid cancer exists in several forms. Differentiated thyroid cancers include those with papillary and follicular histologies. These tumors exist along a spectrum of differentiation, and their incidence continues to climb. A number of advances in the diagnosis and treatment of differentiated thyroid cancers now exist. These include molecular diagnostics and more advanced strategies for risk stratification. Medullary cancer arises from the parafollicular cells and not the follicular cells. Therefore, diagnosis and treatment differs from those of differentiated thyroid tumors. Genetic testing and newer adjuvant therapies have changed the diagnosis and treatment of medullary thyroid cancer. This review will focus on the epidemiology, diagnosis, workup, and treatment of both differentiated and medullary thyroid cancers, focusing specifically on newer developments in the field. © 2013 American Cancer Society, Inc.

  5. Spatial distribution of mast cells and macrophages around tumor glands in human breast ductal carcinoma.

    Science.gov (United States)

    Tamma, Roberto; Guidolin, Diego; Annese, Tiziana; Tortorella, Cinzia; Ruggieri, Simona; Rega, Serena; Zito, Francesco A; Nico, Beatrice; Ribatti, Domenico

    2017-10-01

    Macrophages and mast cells are usually present in the tumor microenvironment and play an important role as regulators of inflammation, immunological response and angiogenesis in the tumor microenvironment. In this study, we have evaluated macrophage, mast cell, and microvessel density in a selected group of different grade of invasive breast carcinoma tumor specimens. Furthermore, we have investigated the pattern of distribution of CD68-positive macrophages and tryptase-positive mast cells around tumor glands. Results have shown that: A) Macrophages are more numerous in G2 and G3 breast cancer stages respect to controls, the per cent of macrophages in G1 samples was comparable to the controls, and the spatial relationship between macrophages and glands (as indicated by the mean cell-to-gland distance) correlated with CD31-positive vessels. B) Mast cells in G2 and G3 tumor specimens show a significant increase in their number as compared to control samples, and their spatial distribution around the glands did not show any significant difference among groups. Overall, the results of this study confirm the important role of macrophages and mast cells in tumor progression and angiogenesis in human ductal breast cancer, and pointed out the spatial relationship between tumor macrophages and glands, and its correlation with microvascular density. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Stemness is Derived from Thyroid Cancer Cells

    Science.gov (United States)

    Ma, Risheng; Bonnefond, Simon; Morshed, Syed A.; Latif, Rauf; Davies, Terry F.

    2014-01-01

    Background: One hypothesis for thyroid cancer development is its derivation from thyroid cancer stem cells (CSCs). Such cells could arise via different paths including from mutated resident stem cells within the thyroid gland or via epithelial to mesenchymal transition (EMT) from malignant cells since EMT is known to confer stem-like characteristics. Furthermore, EMT is a critical process for epithelial tumor progression, local invasion, and metastasis formation. In addition, stemness provides cells with therapeutic resistance and is the likely cause of tumor recurrence. However, the relevance of EMT and stemness in thyroid cancer progression has not been extensively studied. Methods: To examine the status of stemness in thyroid papillary cancer, we employed a murine model of thyroid papillary carcinoma and examined the expression of stemness and EMT using qPCR and histochemistry in mice with a thyroid-specific knock-in of oncogenic Braf (LSL-Braf(V600E)/TPO-Cre). This construct is only activated at the time of thyroid peroxidase (TPO) expression in differentiating thyroid cells and cannot be activated by undifferentiated stem cells, which do not express TPO. Results: There was decreased expression of thyroid-specific genes such as Tg and NIS and increased expression of stemness markers, such as Oct4, Rex1, CD15, and Sox2 in the thyroid carcinoma tissue from 6-week-old BRAFV600E mice indicating the dedifferentiated status of the cells and the fact that stemness was derived in this model from differentiated thyroid cells. The decreased expression of the epithelial marker E-cadherin and increased EMT regulators including Snail, Slug, and TGF-β1 and TGF-β3, and the mesenchymal marker vimentin demonstrated the simultaneous progression of EMT and the CSC-like phenotype. Stemness was also found in a cancer thyroid cell line (named Marca cells) derived from one of the murine tumors. In this cell line, we also found that overexpression of Snail caused up-regulation of