The Experts below are selected from a list of 8721 Experts worldwide ranked by ideXlab platform
Sheue-yann Cheng - One of the best experts on this subject based on the ideXlab platform.
-
Genomic profiling of genes contributing to metastasis in a mouse model of Thyroid Follicular Carcinoma.
American journal of cancer research, 2011Co-Authors: Alok Mishra, Paul S. Meltzer, Yuelin J. Zhu, Sheue-yann ChengAbstract:Metastasis is the major cause of Thyroid cancer-related death. However, little is known about the genes involved in the metastatic spread of Thyroid Carcinomas. We have created a mouse that spontaneously develops metastatic Follicular Thyroid Carcinoma (FTC). This mouse harbors a targeted mutation (denoted TRβPV) in the Thyroid hormone receptor β gene (ThrbPV/PV mice). Our recent studies show that the highly elevated level of Thyroid stimulating hormone (TSH) in ThrbPV/PV mice promotes proliferation of Thyroid tumor cells, but requires the collaboration of the oncogenic action of TRβPV to empower the tumor cells to undergo distant metastasis. To uncover genes destined to drive the metastatic process, we used cDNA microarrays to compare the genomic expression profile of laser capture microdissected Thyroid tumor lesions of ThrbPV/PV mice with that of hyperplastic Thyroid cells of wild-type mice having elevated TSH induced by treatment with the anti-Thyroid drug propylthiouracil (WT-PTU mice). Analyses of microarray data indicated that the expressions of 150 genes were significantly altered between ThrbPV/PV and WT-PTU mice (87 genes had higher expression and 63 genes had lower expression in ThrbPV/PV mice than in WT-PTU mice). Thirty-six percent of genes with altered expression function as key regulators in metastasis. The remaining genes were involved in various cellular processes including metabolism, intracellular trafficking, transcriptional regulation, post-transcriptional modification, and cell-cell/extracellular matrix signaling. The present studies have uncovered novel genes responsible for the metastatic spread of FTC and, furthermore, have shown that the metastatic process of Thyroid cancer requires effective collaboration among genes with diverse cellular functions. Importantly, the present studies indicate that the tumor cells in the primary lesions are endowed with the genes destined to promote metastasis. Thus, our study has provided new insights into the understanding of the metastatic spread of human Thyroid cancer.
-
PPARγ insufficiency promotes Follicular Thyroid carcinogenesis via activation of the nuclear factor-κB signaling pathway
Oncogene, 2006Co-Authors: Y Kato, Hao Ying, Li Zhao, Mark C. Willingham, F Furuya, O Araki, Sheue-yann ChengAbstract:The molecular genetic events underlying Thyroid carcinogenesis are poorly understood. Mice harboring a knock-in dominantly negative mutant Thyroid hormone receptor β (TR β ^PV/PV mouse) spontaneously develop Follicular Thyroid Carcinoma similar to human Thyroid cancer. Using this mutant mouse, we tested the hypothesis that the peroxisome proliferator-activated receptor γ (PPAR γ ) could function as a tumor suppressor in Thyroid cancer in vivo . Using the offspring from the cross of TR β ^PV/+ and PPAR γ ^+/− mice, we found that Thyroid carcinogenesis progressed significantly faster in TR β ^PV/PV mice with PPAR γ insufficiency from increased cell proliferation and reduced apoptosis. Reduced PPAR γ protein abundance led to the activation of the nuclear factor- κ B signaling pathway, resulting in the activation of cyclin D1 and repression of critical genes involved in apoptosis. Treatment of TR β ^PV/PV mice with a PPAR γ agonist, rosiglitazone, delayed the progression of Thyroid carcinogenesis by decreasing cell proliferation and activation of apoptosis. These results suggest that PPAR γ is a critical modifier in Thyroid carcinogenesis and could be tested as a therapeutic target in Thyroid Follicular Carcinoma.
-
Mutant Thyroid Hormone Receptor β Represses the Expression and Transcriptional Activity of Peroxisome Proliferator-activated Receptor γ during Thyroid Carcinogenesis
Cancer research, 2003Co-Authors: Hao Ying, Hideyo Suzuki, Li Zhao, Mark C. Willingham, Paul S. Meltzer, Sheue-yann ChengAbstract:The molecular genetics underlying Thyroid carcinogenesis is not clear. Recent identification of a PAX8-peroxisome proliferator-activated receptor γ ( PPAR γ) fusion gene in human Thyroid Follicular Carcinoma suggests a tumor suppressor role of PPARγ in Thyroid carcinogenesis. Mice harboring a knockin mutant Thyroid hormone β receptor ( TRβPV ) spontaneously develop Thyroid Follicular Carcinoma through pathological progression of hyperplasia, capsular invasion, vascular invasion, anaplasia, and eventually, distant organ metastasis. This mutant mouse ( TR β PV/PV mouse) provides an unusual opportunity to ascertain the role of PPARγ in Thyroid carcinogenesis. Here, we show that the expression of PPAR γ mRNA was repressed in the Thyroid gland of mutant mice during carcinogenesis. In addition, TRβPV acted to abolish the ligand (troglitazone)-mediated transcriptional activity of PPARγ. These results indicate that repression of PPARγ expression and its transcriptional activity are associated with Thyroid carcinogenesis and raise the possibility that PPARγ could be tested as a therapeutic target in Thyroid Follicular Carcinoma.
Toru Takano - One of the best experts on this subject based on the ideXlab platform.
-
Trefoil factor 3 (TFF3): a promising indicator for diagnosing Thyroid Follicular Carcinoma.
Endocrine journal, 2008Co-Authors: Toru Takano, Hiroya YamadaAbstract:Since the introduction of fine needle aspiration biopsy (FNAB) in the 1970's, a preoperative diagnostic technique for Thyroid Follicular Carcinoma has long been awaited. Many markers that distinguish Follicular Carcinomas from adenomas have been reported; however, most of them have not been confirmed to be beneficial for clinical use. Trefoil factor 3 (TFF3) is a relatively new family of peptides that bears the three-loop trefoil domain. Several groups have reported that the suppression of TFF3 mRNA expression is related to malignant characteristics of Thyroid Follicular cell-derived tumors and the expression level of TFF3 mRNA is the most promising indicator for diagnosing Follicular Carcinoma. Development of TFF3-based diagnostic methods is now ongoing and it may not be long before Thyroid Follicular Carcinoma can be diagnosed preoperatively using an aspirated sample from the tumor.
-
Decreased relative expression level of trefoil factor 3 mRNA to galectin-3 mRNA distinguishes Thyroid Follicular Carcinoma from adenoma
Cancer letters, 2005Co-Authors: Toru Takano, Akira Miyauchi, Hiroshi Yoshida, Kanji Kuma, Nobuyuki AminoAbstract:Abstract The expression level of trefoil factor 3 (TFF3) mRNA is a marker for distinguishing Thyroid Follicular adenomas from Carcinomas. However, when measuring the expression level of TFF3 mRNA in fine needle aspiration biopsies, an appropriate internal control mRNA, of which expression is restricted in Thyroid epithelial—derived cells, is necessary, since they are often contaminated with a considerable number of blood cells, which do not express TFF3 mRNA. In this study, we evaluated the efficiency of molecular-based diagnosis of Thyroid Follicular Carcinoma by measuring the relative expression of TFF3 mRNA by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using galectin-3 mRNA as an internal control. The TFF3/galectin-3 mRNA ratio (T/G ratio) was measured in 54 Follicular adenomas and 29 Follicular Carcinomas. It was markedly decreased in 7 Follicular Carcinomas of widely invasive type and with evident distant metastases. When the cutoff point was set at 16.0 by a receiver operator characteristic curve, the TG ratio showed good agreement with the pathological diagnosis [ κ =0.55; 95% confidence interval (CI), 0.34–0.77]. This agreement was better when the pathologically questionable cases were excluded ( κ =0.72; 95% CI, 0.49–0.95). Quantification of the T/G ratio may be a useful tool for the distinction between Follicular adenomas and Carcinomas, which is the most difficult in Thyroid pathology.
-
molecular based diagnosis of Thyroid Carcinoma germ cell carcinogenesis and aspiration biopsy nucleic acid diagnosis abnd
The Japanese journal of clinical pathology, 2004Co-Authors: Toru Takano, Nobuyuki AminoAbstract:Recent data have shown the existence of specific changes in mRNAs in Thyroid Carcinomas. It has not been clarified, however, why these changes clearly distinguish benign tissues from Carcinomas, while genomic alternation such as mutations in the RAS or P53 genes do not. Further, the widely believed hypothesis, multi-step carcinogenesis, does not explain some clinical and experimental evidence of Thyroid Carcinomas. Considering these facts, we propose a new idea for Thyroid carcinogenesis called "germ-cell carcinogenesis", in which cancer cells are derived from the remnant of fetal Thyroid germ cells(thyroblasts) instead of normal Thyroid Follicular cells. Utilizing such mRNAs, we have established a new method for preoperative molecular-based diagnosis of Thyroid Carcinomas, Aspiration Biopsy Nucleic Acid Diagnosis(ABND). ABND allows us to perform preoperative nucleic acid analyses of the tumors by extracting RNAs or DNAs from tumor cells obtained by fine needle aspiration biopsies(FNABs). Pathological diagnosis of Thyroid Follicular Carcinoma is quite difficult, and the establishment of preoperative molecular-based diagnosis of Follicular Carcinoma has been long expected. We found that quantification of the trefoil factor 3(TFF3)/galectin-3 mRNA ratio in Thyroid tumor cells is a useful tool for distinction between Follicular adenomas and Carcinomas. Because ABND can be performed without any severe invasion to the patients, in the near future, when more reliable systems of quantitative RNA analysis have been developed, ABND will probably become one of the standard tests for preoperative diagnosis of Thyroid Carcinoma.
Hiroya Yamada - One of the best experts on this subject based on the ideXlab platform.
-
Trefoil factor 3 (TFF3): a promising indicator for diagnosing Thyroid Follicular Carcinoma.
Endocrine journal, 2008Co-Authors: Toru Takano, Hiroya YamadaAbstract:Since the introduction of fine needle aspiration biopsy (FNAB) in the 1970's, a preoperative diagnostic technique for Thyroid Follicular Carcinoma has long been awaited. Many markers that distinguish Follicular Carcinomas from adenomas have been reported; however, most of them have not been confirmed to be beneficial for clinical use. Trefoil factor 3 (TFF3) is a relatively new family of peptides that bears the three-loop trefoil domain. Several groups have reported that the suppression of TFF3 mRNA expression is related to malignant characteristics of Thyroid Follicular cell-derived tumors and the expression level of TFF3 mRNA is the most promising indicator for diagnosing Follicular Carcinoma. Development of TFF3-based diagnostic methods is now ongoing and it may not be long before Thyroid Follicular Carcinoma can be diagnosed preoperatively using an aspirated sample from the tumor.
Toyotsugu Kiku - One of the best experts on this subject based on the ideXlab platform.
-
Separation of I-131-positive juxtagastric metastatic Thyroid Carcinoma from the stomach by simultaneous dual-isotope imaging with I-131 and Tc-99m pertechnetate.
Clinical nuclear medicine, 1999Co-Authors: Shinsaku Tsuchimochi, Masayuki Nakajo, Yuichi Hino, Yoshiaki Nakabeppu, Noboru Fukushima, Toyotsugu KikuAbstract:1-131 whole-body imaging was performed in a 72-year-old woman with multiple metastases from Thyroid Follicular Carcinoma. Increased activity in the left lower chest mimicked physiologic gastric uptake. To determine whether it was a true-positive lesion, dual-isotope imaging was performed after intravenous administration of Tc-99m pertechnetate. This imaging clearly separated the 1-131 in the chest wall metastasis from the physiologic accumulation of Tc-99m pertechnetate in the stomach.
Nobuyuki Amino - One of the best experts on this subject based on the ideXlab platform.
-
Decreased relative expression level of trefoil factor 3 mRNA to galectin-3 mRNA distinguishes Thyroid Follicular Carcinoma from adenoma
Cancer letters, 2005Co-Authors: Toru Takano, Akira Miyauchi, Hiroshi Yoshida, Kanji Kuma, Nobuyuki AminoAbstract:Abstract The expression level of trefoil factor 3 (TFF3) mRNA is a marker for distinguishing Thyroid Follicular adenomas from Carcinomas. However, when measuring the expression level of TFF3 mRNA in fine needle aspiration biopsies, an appropriate internal control mRNA, of which expression is restricted in Thyroid epithelial—derived cells, is necessary, since they are often contaminated with a considerable number of blood cells, which do not express TFF3 mRNA. In this study, we evaluated the efficiency of molecular-based diagnosis of Thyroid Follicular Carcinoma by measuring the relative expression of TFF3 mRNA by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using galectin-3 mRNA as an internal control. The TFF3/galectin-3 mRNA ratio (T/G ratio) was measured in 54 Follicular adenomas and 29 Follicular Carcinomas. It was markedly decreased in 7 Follicular Carcinomas of widely invasive type and with evident distant metastases. When the cutoff point was set at 16.0 by a receiver operator characteristic curve, the TG ratio showed good agreement with the pathological diagnosis [ κ =0.55; 95% confidence interval (CI), 0.34–0.77]. This agreement was better when the pathologically questionable cases were excluded ( κ =0.72; 95% CI, 0.49–0.95). Quantification of the T/G ratio may be a useful tool for the distinction between Follicular adenomas and Carcinomas, which is the most difficult in Thyroid pathology.
-
molecular based diagnosis of Thyroid Carcinoma germ cell carcinogenesis and aspiration biopsy nucleic acid diagnosis abnd
The Japanese journal of clinical pathology, 2004Co-Authors: Toru Takano, Nobuyuki AminoAbstract:Recent data have shown the existence of specific changes in mRNAs in Thyroid Carcinomas. It has not been clarified, however, why these changes clearly distinguish benign tissues from Carcinomas, while genomic alternation such as mutations in the RAS or P53 genes do not. Further, the widely believed hypothesis, multi-step carcinogenesis, does not explain some clinical and experimental evidence of Thyroid Carcinomas. Considering these facts, we propose a new idea for Thyroid carcinogenesis called "germ-cell carcinogenesis", in which cancer cells are derived from the remnant of fetal Thyroid germ cells(thyroblasts) instead of normal Thyroid Follicular cells. Utilizing such mRNAs, we have established a new method for preoperative molecular-based diagnosis of Thyroid Carcinomas, Aspiration Biopsy Nucleic Acid Diagnosis(ABND). ABND allows us to perform preoperative nucleic acid analyses of the tumors by extracting RNAs or DNAs from tumor cells obtained by fine needle aspiration biopsies(FNABs). Pathological diagnosis of Thyroid Follicular Carcinoma is quite difficult, and the establishment of preoperative molecular-based diagnosis of Follicular Carcinoma has been long expected. We found that quantification of the trefoil factor 3(TFF3)/galectin-3 mRNA ratio in Thyroid tumor cells is a useful tool for distinction between Follicular adenomas and Carcinomas. Because ABND can be performed without any severe invasion to the patients, in the near future, when more reliable systems of quantitative RNA analysis have been developed, ABND will probably become one of the standard tests for preoperative diagnosis of Thyroid Carcinoma.