Kanaji Hospital

Kita-ku, Japan

Kanaji Hospital

Kita-ku, Japan
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Yamazaki K.,Kanaji Hospital | Tanigawa K.,Japan National Institute of Infectious Diseases | Suzuki K.,Japan National Institute of Infectious Diseases | Yamada E.,Kanaji Hospital | And 4 more authors.
Thyroid | Year: 2010

Background: It is well known that iodide exacerbates thyroid function in subclinical hypothyroid patients with autoimmune thyroiditis. To investigate the immunological mechanism of iodine-induced thyroid dysfunction, we studied the effect of iodide in cultured human thyroid follicles, which respond to physiological concentrations of human thyrotropin (TSH) (0.3-10μU/mL) and maintain the Wolff-Chaikoff effect. Materials and Methods: Thyroid follicles obtained from Graves' patients at subtotal thyroidectomy were precultured in medium containing 0.5% fetal calf serum and 10-8 M iodide for 5 days, and then cultured with the medium containing bovine TSH (30μU/mL) and low (10-8M) or high (10-5M) concentrations of iodide. After 3-72 hours of culture, the effect of iodide on thyroid cell mRNA expression was analyzed by microarray and reverse transcriptase-polymerase chain reaction. Results: After 48 hours of culture, iodide nearly doubled the mRNA expression levels of the immunity-associated genes (intercellular adhesion molecule-1, transforming growth factor beta 1-induced protein, early growth response gene 1, guanylate-binding protein 1, and annexin A1) and decreased the mRNA expression of sodium-iodide symporter to less than 20%. Further, the mRNA expression levels of chemokines (CCL2, CXCL8, and CXCL14) increased nearly twofold, whereas their receptors did not show any significant response. Real-time polymerase chain reaction analyses confirmed that iodide increased the mRNA expression levels of these genes in a time- and concentration-dependent manner. Immunohistochemical studies revealed that the chemokines were expressed mainly in the thyroid follicular cells in addition to the immune cells. The iodide-induced increase in CCL2 was greater in thyroid follicles obtained from thyroid gland that had been moderately infiltrated with the immunocompetent cells. Conclusion: We have demonstrated that iodide stimulates thyroid follicular cells to produce chemokines, particularly CCL2, CXCL8, and CXCL14. These chemokines and intercellular adhesion molecule-1 would attract immunocompetent cells into thyroid gland. These in vitro findings suggest that iodide at high concentrations may induce thyroid dysfunction through not only biochemical but also immunological mechanisms, particularly in patients with autoimmune thyroid disorders. © Mary Ann Liebert, Inc.


Onoda N.,Nippon Medical School | Onoda N.,Osaka City University | Sugitani I.,Nippon Medical School | Sugitani I.,Cancer Institute Hospital | And 18 more authors.
BMC Cancer | Year: 2015

Background: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, often demonstrating resistance to multimodal therapeutic approaches. The median survival of ATC patients after initial diagnosis was reported to be < 6 months due to the rapid progression of disease by dissemination and/or invasion. There have been several reports describing possible effective chemotherapies, but these studies might be biased by the nature of retrospective accumulations of clinical experiences, and thus reliable data concerning the efficacies of the treatment efforts are required. Design: In 2009, we established the research organization Anaplastic Carcinoma Research Consortium Japan (ATCCJ) to investigate this highly malignant disease. Using this nationwide organization, we conducted a prospective clinical study to investigate the feasibility, safeness, and efficacy of chemotherapy with weekly paclitaxel for ATC patients. This trial is registered on the clinical trials site of the University Hospital Medical Information Network Clinical Trials Registry Web site (UMIN000008574). The study was started in 2012, and enrollment was closed in March 2014 after accumulating 71 patients from 28 registered institutes. The follow-up data will be available in April 2015. Discussion: Important information concerning the management of this disease is expected to be revealed by this study. The concept and design of the study are described herein. © Onoda et al.


Sugishita Y.,Kanaji Hospital | Kammori M.,Kanaji Hospital | Yamada O.,Tokyo Women's Medical University | Poon S.S.S.,British Columbia Cancer Research Center | And 9 more authors.
International Journal of Oncology | Year: 2013

The human epidermal growth factor receptor 2 (HER2) proto-oncogene plays an important role in the development and progression of breast and gastric cancer. Monitoring of the HER2 status and treatment with trastuzumab was performed initially in breast cancer, and subsequently in gastric cancer. However, the HER2 status of thyroid cancer remains unexplored. Telomere alteration and telomerase activity have been observed in most human cancers and are known to be a feature of malignancy. The aims of this study were to clarify the HER2 status of thyroid cancer and to examine any correlations to various characteristics of malignancy. We investigated 69 cases of differentiated thyroid cancers with reference to: i) telomere length as measured using tissue quantitative fluorescence in situ hybridization (Q-FISH), ii) expression of human telomerase reverse transcriptase (hTERT) as determined by immunohistochemistry (IHC), and iii) overexpression of the HER2 protein as determined by IHC and amplification of the HER2 gene as determined by fluorescence in situ hybridization (FISH). The telomeres of thyroid cancers, especially follicular carcinomas, were significantly shorter compared to those of adjacent normal tissues. Positivity for hTERT expression and HER2 amplification were observed in approximately 70 and 22% of thyroid cancers, respectively. Our data demonstrated that telomeres in HER2-positive cancers were significantly shorter compared to those in HER2-negative cancers. These results suggest that highly malignant differentiated thyroid cancer can be detected by monitoring HER2 status and telomere shortening, and that trastuzumab therapy may be effective for refractory thyroid cancer.


Kawashima A.,Japan National Institute of Infectious Diseases | Yamazaki K.,Kanaji Hospital | Hara T.,Japan National Institute of Infectious Diseases | Akama T.,Japan National Institute of Infectious Diseases | And 9 more authors.
Thyroid | Year: 2013

Background: Autoimmune thyroid disease is an archetypal organ-specific autoimmune disorder that is characterized by the production of thyroid autoantibodies and lymphocytic infiltration into the thyroid. However, the underlying mechanisms by which specific thyroid antibodies are produced are largely unknown. Recent studies have shown that innate immune responses affect both the phenotype and the severity of autoimmune reactions. Moreover, it appears that even non-immune cells, including thyroid cells, have an ability to launch such responses. The aim of this study was to conduct a more detailed analysis of innate immune responses of the thyroid upon stimulation with various "non-self" and "self" factors that might contribute to the initiation of autoimmune reactions. Methods: We used rat thyroid FRTL-5 cells, human thyroid cells, and mice to investigate the effects of various pathogen-Associated molecular patterns (PAMPs), danger-Associated molecular patterns (DAMPs), and iodide on gene expression and function that were related to innate immune responses. Results: RT-PCR analysis showed that both rat and human thyroid cells expressed mRNAs for Toll-like receptors (TLRs) that sensed PAMPs. Stimulation of thyrocytes with TLR ligands resulted in activation of the interferon-beta (IFN-β) promoter and the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)-dependent promoter. As a result, pro-inflammatory cytokines, chemokines, and type I interferons were produced. Similar activation was observed when thyroid cells were stimulated with double-stranded DNA, one of the typical DAMPs. In addition to these PAMPs and DAMPs, treatment of thyroid cells with high concentrations of iodide increased mRNA expression of various cytokines. Conclusion: We show that thyroid cells express functional sensors for exogenous and endogenous dangers, and that they are capable of launching innate immune responses without the assistance of immune cells. Such responses may relate to the development of thyroiditis, which in turn may trigger autoimmune reactions. © Copyright 2013, Mary Ann Liebert, Inc. 2013.


PubMed | Kanaji Hospital
Type: Journal Article | Journal: Thyroid : official journal of the American Thyroid Association | Year: 2010

It is well known that iodide exacerbates thyroid function in subclinical hypothyroid patients with autoimmune thyroiditis. To investigate the immunological mechanism of iodine-induced thyroid dysfunction, we studied the effect of iodide in cultured human thyroid follicles, which respond to physiological concentrations of human thyrotropin (TSH) (0.3-10 microU/mL) and maintain the Wolff-Chaikoff effect.Thyroid follicles obtained from Graves patients at subtotal thyroidectomy were precultured in medium containing 0.5% fetal calf serum and 10(-8) M iodide for 5 days, and then cultured with the medium containing bovine TSH (30 microU/mL) and low (10(-8)M) or high (10(-5)M) concentrations of iodide. After 3-72 hours of culture, the effect of iodide on thyroid cell mRNA expression was analyzed by microarray and reverse transcriptase-polymerase chain reaction.After 48 hours of culture, iodide nearly doubled the mRNA expression levels of the immunity-associated genes (intercellular adhesion molecule-1, transforming growth factor beta 1-induced protein, early growth response gene 1, guanylate-binding protein 1, and annexin A1) and decreased the mRNA expression of sodium-iodide symporter to less than 20%. Further, the mRNA expression levels of chemokines (CCL2, CXCL8, and CXCL14) increased nearly twofold, whereas their receptors did not show any significant response. Real-time polymerase chain reaction analyses confirmed that iodide increased the mRNA expression levels of these genes in a time- and concentration-dependent manner. Immunohistochemical studies revealed that the chemokines were expressed mainly in the thyroid follicular cells in addition to the immune cells. The iodide-induced increase in CCL2 was greater in thyroid follicles obtained from thyroid gland that had been moderately infiltrated with the immunocompetent cells.We have demonstrated that iodide stimulates thyroid follicular cells to produce chemokines, particularly CCL2, CXCL8, and CXCL14. These chemokines and intercellular adhesion molecule-1 would attract immunocompetent cells into thyroid gland. These in vitro findings suggest that iodide at high concentrations may induce thyroid dysfunction through not only biochemical but also immunological mechanisms, particularly in patients with autoimmune thyroid disorders.

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