著者

Toru Takano

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ17-0026, (Released:2017-02-02)

被引用文献数

77

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Thyroid cancers have long been considered to arise in middle age and, after their repeated proliferation, resulting in further damage to the genome, they progress to more aggressive and lethal cancers. However, in 2014, some studies were reported that might lead to a marked change in our understanding of the natural history of thyroid cancer. A high prevalence of papillary carcinoma in the young suggested that the first initiation of thyroid cancer is likely to occur in the infantile period. Such a conclusion was also supported by a very slow growth rate of papillary microcarcinomas (PMCs) in an observation trial. The proliferation rate of PMCs was negatively correlated with the age, and surgery to remove PMCs did not contribute to reduce mortality from thyroid cancer. These findings strongly suggested the existence of self-limiting cancers, which are truly malignant but do not progress to lethal cancers, for the first time in human history. The early detection of self-limiting cancers results in overdiagnosis. Ultrasonographic screening of the thyroid in the young should be avoided. Lethal thyroid cancers, whose origin is still unknown, appear suddenly after middle age. In the elderly, thyroid cancers are a mixture of self-limiting and lethal cancers; thus, when thyroid cancer is detected, careful follow-up with examination of its growth rate is required.

著者

Toru Takano

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.64, no.3, pp.237-244, 2017 (Released:2017-03-31)

参考文献数

38

被引用文献数

58 77

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Thyroid cancers have long been considered to arise in middle age and, after their repeated proliferation, resulting in further damage to the genome, they progress to more aggressive and lethal cancers. However, in 2014, some studies were reported that might lead to a marked change in our understanding of the natural history of thyroid cancer. A high prevalence of papillary carcinoma in the young suggested that the first initiation of thyroid cancer is likely to occur in the infantile period. Such a conclusion was also supported by a very slow growth rate of papillary microcarcinomas (PMCs) in an observation trial. The proliferation rate of PMCs was negatively correlated with the age, and surgery to remove PMCs did not contribute to reduce mortality from thyroid cancer. These findings strongly suggested the existence of self-limiting cancers, which are truly malignant but do not progress to lethal cancers, for the first time in human history. The early detection of self-limiting cancers results in overdiagnosis. Ultrasonographic screening of the thyroid in the young should be avoided. Lethal thyroid cancers, whose origin is still unknown, appear suddenly after middle age. In the elderly, thyroid cancers are a mixture of self-limiting and lethal cancers; thus, when thyroid cancer is detected, careful follow-up with examination of its growth rate is required.

著者

Yasuhiro ITO Hiroshi YOSHIDA Rie MARUO Shinji MORITA Toru TAKANO Mitsuyoshi HIROKAWA Tomonori YABUTA Mitsuhiro FUKUSHIMA Hiroyuki INOUE Chisato TOMODA Minoru KIHARA Takashi URUNO Takuya HIGASHIYAMA Yuuki TAKAMURA Akihiro MIYA Kaoru KOBAYASHI Fumio MATSUZUKA Akira MIYAUCHI

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.56, no.1, pp.89-97, 2009 (Released:2009-03-12)

参考文献数

49

被引用文献数

92 176

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Recent studies have demonstrated that BRAFV600E mutation is a common event in papillary thyroid carcinoma and a majority of these lesions have shown a direct relationship between BRAFV600E mutation and aggressive characteristics, including a worse patient prognosis. However, there are no studies from Japan regarding this issue in a large series with adequate postoperative follow-up periods. We investigated BRAFV600E mutation in 631 patients with papillary carcinoma having median follow-up periods of 83 months. The prevalence of BRAFV600E mutation was 38.4%, and the rate was higher in carcinoma larger than 1.0 cm but did not successively increase with tumor size. Furthermore, the prevalence did not significantly increase in cases demonstrating high-risk biological features such as clinically apparent lymph node metastasis, massive extrathyroid extension, advanced age, distant metastasis at surgery, and advanced Stage. The disease-free survival of patients with BRAFV600E mutation did not differ from that of those without BRAFV600E mutation. These findings indicate that, although BRAFV600E mutation may play some roles in local carcinoma development, there is no evidence that BRAFV600E mutation significantly reflects the aggressive characteristics and poor prognosis of patients with papillary carcinoma in Japan.

著者

Toru Takano

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.61, no.4, pp.311-320, 2014 (Released:2014-04-29)

参考文献数

57

被引用文献数

5 30 7

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Thyroid cancer cells were believed to be generated by multi-step carcinogenesis, in which cancer cells are derived from thyrocytes, via multiple incidences of damage to their genome, especially in oncogenes or anti-oncogenes that accelerate proliferation or foster malignant phenotypes, such as the ability to invade the surrounding tissue or metastasize to distant organs, until a new hypothesis, fetal cell carcinogenesis, was presented. In fetal cell carcinogenesis, thyroid tumor cells are assumed to be derived from three types of fetal thyroid cell which only exist in fetuses or young children, namely, thyroid stem cells (TSCs), thyroblasts and prothyrocytes, by proliferation without differentiation. Genomic alternations, such as RET/PTC and PAX8-PPARγ1 rearrangements and a mutation in the BRAF gene, play an oncogenic role by preventing thyroid fetal cells from differentiating. Fetal cell carcinogenesis effectively explains recent molecular and clinical evidence regarding thyroid cancer, including thyroid cancer initiating cells (TCICs), and it underscores the importance of identifying a stem cells and clarifying the molecular mechanism of organ development in cancer research. It introduces three important concepts, the reverse approach, stem cell crisis and mature and immature cancers. Further, it implies that analysis of a small population of cells in a cancer tissue will be a key technique in establishing future laboratory tests. In the contrary, mass analysis such as gene expression profiling, whole genomic scan, and proteomics analysis may have definite limitations since they can only provide information based on many cells.

著者

Toru TAKANO

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.51, no.6, pp.509-515, 2004 (Released:2005-01-12)

参考文献数

34

被引用文献数

19 20

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Since the 1980s, cancer cells have been considered to be generated from well-differentiated benign cells by transformation caused by accumulating damage in their genomes. However, recent progress in gene expression analysis in thyroid malignancies has raised the possibility of another model of thyroid carcinogenesis. We propose a novel hypothesis of thyroid carcinogenesis, the fetal cell carcinogenesis hypothesis, in which cancer cells are derived from the remnants of fetal thyroid cells, instead of from normal thyroid follicular cells. This hypothesis explains well the clinical and biological features and recent molecular evidence of thyroid carcinoma. It suggests the importance of clarifying the molecular mechanism of thyroid development and the identification of fetal thyroid cells such as thyroid stem cells (TSCs), since such data will lead to a better understanding of thyroid carcinogenesis and thyroid regeneration.

著者

Toru Takano

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ13-0517, (Released:2014-01-22)

被引用文献数

5 30

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Thyroid cancer cells were believed to be generated by multi-step carcinogenesis, in which cancer cells are derived from thyrocytes, via multiple incidences of damage to their genome, especially in oncogenes or anti-oncogenes that accelerate proliferation or foster malignant phenotypes, such as the ability to invade the surrounding tissue or metastasize to distant organs, until a new hypothesis, fetal cell carcinogenesis, was presented. In fetal cell carcinogenesis, thyroid tumor cells are assumed to be derived from three types of fetal thyroid cell which only exist in fetuses or young children, namely, thyroid stem cells (TSCs), thyroblasts and prothyrocytes, by proliferation without differentiation. Genomic alternations, such as RET/PTC and PAX8-PPARgamma1 rearrangements and a mutation in the BRAF gene, play an oncogenic role by preventing thyroid fetal cells from differentiating. Fetal cell carcinogenesis effectively explains recent molecular and clinical evidence regarding thyroid cancer, including thyroid cancer initiating cells (TCICs), and it underscores the importance of identifying a stem cells and clarifying the molecular mechanism of organ development in cancer research. It introduces three important concepts, the reverse approach, stem cell crisis and mature and immature cancers. Further, it implies that analysis of a small population of cells in a cancer tissue will be a key technique in establishing future laboratory tests. In the contrary, mass analysis such as gene expression profiling, whole genomic scan, and proteomics analysis may have definite limitations since they can only provide information based on many cells.