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Biomedical subjects

A Miyauchi

Publications and source records attributed to A Miyauchi.

At least 19 recordsLinked to original sources
PubMed2006

A review of 227 cases of small papillary thyroid carcinoma.

AIMS: To review differences in biological aggressiveness, clinical behaviors or selected surgical treatments between the PMC and the slightly larger PTC of 1.0<T<or=2.0 cm. METHODS: Two hundred and twenty-seven cases of papillary thyroid carcinoma not larger than 2.0 cm, diagnosed and treated at the Kuma Hospital, Kobe, Japan, with a 10-year follow-up from 1992 to 2003, were reviewed. RESULTS: The small PTCs demonstrated excellent outcomes, and persistent/recurrent disease was identified in only nine patients (4%). None of the patients died of the disease. A multivariate analysis revealed that massive extrathyroidal extension at presentation was the only independent prognostic factor for locoregional recurrence. Subdivision into PMCs and slightly larger tumors (1<T<or=2 cm) did not affect the excellent outcomes, but the patients in the latter subgroup received more lymph node surgery and displayed more aggressive clinico-histological features such as higher rates of extrathyroidal extension, lymph node metastasis, loss of polarity, invasive growth pattern and loss of cohesiveness. CONCLUSIONS: Small PTC not larger than 2.0 cm could be considered as favorable a prognosis as PMC.

Adenocarcinoma, Papillary↗
PubMed2006

Multiple activation of mitogen-activated protein kinases by purified independent CCN2 modules in vascular endothelial cells and chondrocytes in culture.

CCN2 consists of 4 distinct modules that are conserved among various CCN family protein members. From the N-terminus, insulin-like growth factor binding protein (IGFBP), von Willebrand factor type C repeat (VWC), thrombospondin type 1 repeat (TSP1) and C-terminal cysteine-knot (CT) modules are all aligned tandem therein. The multiple functionality of CCN2 is thought to be enabled by the differential use of these modules when interacting with other molecules. In this study, we independently prepared all 4 purified module proteins of human CCN2, utilizing a secretory production system with Brevibacillus choshinensis and thus evaluated the cell biological effects of such single modules. In human umbilical vascular endothelial cells (HUVECs), VWC, TSP and CT modules, as well as a full-length CCN2, were capable of efficiently activating the ERK signal transduction cascade, whereas IGFBP was not. In contrast, the IGFBP module was found to prominently activate JNK in human chondrocytic HCS-2/8 cells, while the others showed similar effects at lower levels. In addition, ERK1/2 was modestly, but significantly activated by IGFBP and VWC in those cells. No single module, but a mixture of the 4 modules provoked a significant activation of p38 MAPK in HCS-2/8 cells, which was activated by the full-length CCN2. Therefore, the signals emitted by CCN2 can be highly differential, depending upon the cell types, which are thus enabled by the tetramodular structure. Furthermore, the cell biological effects of each module on these cells were also evaluated to clarify the relationship among the modules, the signaling pathways and biological outcomes. Our present results not only demonstrate that single CCN2 modules were potent activators of the intracellular signaling cascade to yield a biological response per se, while also providing new insight into the module-wise structural and functional relationship of a prototypic CCN family member, CCN2.

Blotting, Western↗
PubMed2006

Restriction of dietary Iodine does not ameliorate the early effect of anti-thyroid drug therapy for Graves' disease in an area of excessive iodine intake.

The close relationship between iodine intake and the effects of anti-thyroid drugs (ATD) for Graves' disease (GD) has been well established. However, it remains unknown whether restriction of dietary iodine improves the effect of ATD. This study aimed to clarify this issue in Japanese patients with GD who routinely ingest large amounts of dietary iodine. We performed a prospective clinical study in 81 patients with newly diagnosed GD who were divided into an iodine restricted group and a control group. Urinary iodine, thyroid hormones and TSH receptor antibody were measured during the first 8 weeks of ATD therapy. Urinary iodine concentrations in the iodine restricted group were significantly lower than in the control group (p=0.043). However, there were no significant differences in the decrease of thyroid hormones and TSH receptor antibody between the two groups. Restriction of dietary iodine does not ameliorate the effect of ATD therapy for GD in an area of excessive iodine intake.

Adult↗
PubMed2006

Two cases of subacute thyroiditis presenting in pregnancy.

Subacute thyroiditis (SAT) is an extremely rare cause of thyrotoxicosis in pregnant women. Untreated, thyrotoxicosis may result in complications, such as prematurity and congenital malformations in the fetus. We report two cases of first trimester subacute thyroiditis, one mild and one severe. The severe case, as demonstrated by laboratory and ultrasound findings, was successfully treated with prednisolone. In this case, it was thought that the benefits of pharmacological therapy outweighed the risk of potential teratogenesis by the medication. In contrast, the milder case was managed conservatively and resolved without treatment. These cases illustrate how laboratory and ultrasound findings can be used to determine whether treatment should be initiated and, once begun, if medication levels need to be adjusted. In both cases, the pregnancies resulted in healthy full-term infants.

Adult↗
PubMed2005

Expression of S100A2 and S100A6 in thyroid carcinomas.

AIMS: S100 calcium-binding proteins are known to play multiple roles in carcinoma development. In this study, we focused on two kinds of these proteins, S100A2 and S100A6, and investigated their expression in thyroid neoplasms. METHODS AND RESULTS: We investigated S100A2 and S100A6 expression in 141 thyroid neoplasms by immunohistochemistry. S100A2 was not expressed in normal follicles or follicular tumours, with one exception. Although 89.5% of papillary carcinoma were positive for S100A2, the expression was heterogeneous except in two cases. In anaplastic carcinoma, 78.5% of cases expressed S100A2 diffusely, while the remaining cases were negative. In normal follicles, S100A6 expression was always low, while 8.3% of follicular adenomas and 39.5% of follicular carcinomas showed increased expression. In papillary carcinomas, S100A6 expression was increased in 75% of cases, but in anaplastic carcinomas it was decreased, with only 14.3% showing high expression. CONCLUSIONS: The expression patterns of S100A2 and S100A6 in thyroid neoplasms are unique compared with those of other carcinomas, suggesting that: (i) S100A2 and S100A6 contribute to certain events in papillary carcinoma progression, and (ii) S100A2 expression is one of the biological characteristics of anaplastic carcinoma.

Adenocarcinoma, Follicular↗
PubMed2004

High-throughput differential screening of mRNAs by serial analysis of gene expression: decreased expression of trefoil factor 3 mRNA in thyroid follicular carcinomas.

To find mRNAs whose expression differs between thyroid follicular adenomas and carcinomas, a high-throughput analysis of mRNAs in these two tumours was performed. This method, named high-throughput differential screening by serial analysis of gene expression (HDSS), combines a modified method of serial analysis of gene expression (SAGE) and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). A total of 40 candidate tag sequences that showed extremely different expression levels between a follicular carcinoma and a follicular adenoma in the SAGE analysis were analysed by real-time quantitative RT-PCR, using RNAs from an additional four typical follicular carcinomas and adenomas. One sequence tag that represents trefoil factor 3 (TFF3) mRNA showed a clear difference in its expression level between adenomas and carcinomas. The expression levels of TFF3 mRNA in 48 follicular adenomas and 29 follicular carcinomas were measured by real-time quantitative RT-PCR using a specific probe for TFF3. They were significantly decreased in follicular carcinomas, especially in widely invasive types and those with evident metastases. These results indicate that the decreased expression of TFF3 mRNA is a marker of follicular carcinomas, especially those with a high risk of invasion or metastasis.

Adenocarcinoma, Follicular↗
PubMed2004

Polo-like kinase 1 overexpression is an early event in the progression of papillary carcinoma.

Polo-like kinase 1 (PLK1) is one of the serine threonine kinases that contributes to cell mitosis and is regarded as a marker of cellular proliferation. However, its protein expression in human carcinoma has not been studied in depth. We investigated PLK1 expression in various thyroid neoplasms in order to elucidate its physiological significance in thyroid carcinoma. Normal follicular cells only occasionally expressed PLK1. In follicular tumours and anaplastic carcinoma, PLK1 overexpression was not a common event and only 5.9% of follicular adenoma, 7.1% of follicular carcinoma, and 11.8% of anaplastic carcinoma overexpressed this protein. However, 43.7% of papillary carcinoma overexpressed PLK1. Polo-like kinase 1 overexpression was more frequently observed in smaller papillary carcinoma lesions, and 62.5% of microcarcinoma (ranging from 4 mm to 1.0 cm) and even 66.7% of incidental carcinoma (less than 4 mm) overexpressed it, whereas this phenomenon could only be seen in 20.0% of lesions larger than 4.0 cm. Furthermore, PLK1 overexpression was not related to cell-proliferating activity evaluated by Ki-67 labelling index, but it was inversely linked to UICC stage, extrathyroidal invasion, and the presence of poorly differentiated lesion as proposed by Sakamoto et al. These findings strongly suggest that, unlike other carcinomas previously studied, PLK1 does not act as a cell cycle regulator but plays a constitutive role in papillary carcinoma especially in the early phase, and may contribute to the malignant transformation of this carcinoma.

Blotting, Western↗
PubMed2004

PGP9.5 mRNA could contribute to the molecular-based diagnosis of medullary thyroid carcinoma.

The protein gene product 9.5 (PGP9.5) is a ubiquitin hydrolase that is widely expressed in neuronal tissues at all stages of neuronal differentiation and is a known neuroendocrine marker. Medullary thyroid carcinoma (MTC) arises from parafollicular cells and is reported to overexpress several mRNAs such as RET, calcitonin, and CEA. These markers are thought to be useful in determining a molecular-based diagnosis of MTC. We examined the expression levels of PGP9.5 mRNA in 80 thyroid tissues using real-time quantitative reverse transcription (RT-PCR) and found that PGP9.5 mRNA was overexpressed in all 11 MTCs examined, both hereditary and sporadic, but not in other histological tumour types. Furthermore, by RT-PCR, PGP9.5 mRNA was detected only in aspirates from three medullary carcinomas, and not in aspirates from other tumour types. These results demonstrate that, in addition to the expression of RET, calcitonin and CEA, PGP9.5 mRNA expression may contribute to the molecular-based diagnosis of MTCs.

Adolescent↗
PubMed2004

Decrease of CD154 intensity on peripheral CD4+ T cells in autoimmune thyroid disease.

To clarify immunological differences among patients with Graves' disease (GD) and Hashimoto's disease (HD) at various levels of severity, we examined the expression of the CD154 molecules on peripheral T cells, which regulate B cell activation, B cell differentiation, and T-cell survival. We found decreases in the intensities of CD154 on peripheral CD4(+) cells from euthyroid patients with GD and HD, but we did not find any differences between patients with different disease severities. CD8(+) cells did not express CD154 molecules. Thus, CD154 expression on CD4(+) cells may be related to the pathogenesis of the autoimmune thyroid diseases, not to the disease severity.

Adult↗
PubMed2004

Lower concentration of serum soluble CD8 in severe Hashimoto's disease.

To investigate the roles of soluble CD4 (sCD4) and CD8 (sCD8) in the severity of autoimmune thyroid diseases, we examined serum concentrations of sCD4 and sCD8 in various degrees of severity of Hashimoto's disease (HD) and Graves' disease (GD) by enzyme immunoassay. The serum concentration of sCD8 was lower in euthyroid patients with HD undergoing treatment for hypothyroidism (severe HD) than in untreated, euthyroid patients with HD (mild HD), but the sCD4 concentration did not differ between patients with severe and mild HD. The serum sCD8 concentration was negatively correlated with the proportion of CD25(+) cells in CD8(+) cells in patients with severe HD. Serum sCD4 and sCD8 concentrations did not differ between euthyroid patients with GD in remission and those with intractable GD. These results indicate that serum sCD8 is involved in the severity of HD, possibly by down-regulating the function of cytotoxic T cells.

CD4 Antigens↗
PubMed2004

Tie-1 tyrosine kinase expression in human thyroid neoplasms.

AIMS: To investigate tie-1 expression in human thyroid neoplasms. Recent studies have demonstrated that receptor-type tyrosine kinases (RTKs) contribute to carcinoma progression. Tie-1 is one of the RTKs and plays a role in angiogenesis, although its pathophysiological significance in human carcinoma is still to be elucidated. METHODS AND RESULTS: Immunohistochemical expression of tie-1 was studied in various thyroid neoplasms. Tie-1 immunoreactivity was only occasionally observed in normal follicular cells. In papillary carcinoma, tie-1 was classified as positive in carcinoma cells in 55.7% of the cases and was more frequently expressed in those of smaller size with an absence of a poorly differentiated lesion. In contrast, tie-1 was positive in only 8.3% of anaplastic carcinoma and no cases of follicular carcinoma or adenoma were positive. CONCLUSIONS: These results suggest that tie-1 has a role in thyroid tumorigenesis, especially in the early phase of papillary carcinoma, but it is not important in the progression of anaplastic carcinoma or follicular tumour.

Carcinoma↗
PubMed2004

Parathyroid invasion, nodal recurrence, and lung metastasis by papillary carcinoma of the thyroid.

AIMS: Parathyroid invasion by papillary thyroid carcinoma (PTC) is found in a small proportion of surgical specimens, but the clinicopathological relevance of this phenomenon is not well understood. This study investigated the possible prognostic relevance of parathyroid invasion in PTC. METHOD: Parathyroid involvement was seen in 14 patients with PTC, and the clinicopathological characteristics and follow up data of these patients were analysed and compared with 164 patients without parathyroid involvement, in whom histological parathyroid examination had been undertaken, and 177 other patients without parathyroid examination (341 patients without parathyroid involvement in total). RESULTS: Parathyroid invasion was found in older patients and there were more male patients in this group than in those without parathyroid invasion. These patients had more extrathyroid extension and were frequently in an advanced stage of disease. Lung metastasis was seen in two of the 14 patients, which was significantly more than that seen in control cases. Moreover, male patients with parathyroid invasion and those who were older than 55 years had reduced disease free survival compared with those without parathyroid invasion. CONCLUSION: Parathyroid invasion seen in thyroid carcinoma may be an important histological feature indicating a greater chance of nodal recurrence and lung metastasis.

Age Factors↗
PubMed2004

Papillary carcinoma of the thyroid in Japan: subclassification of common type and identification of low risk group.

AIMS: Papillary thyroid carcinoma (PTC) is classified into two subgroups-common type and other histological variants. Correlations between further subgrouping of the common type and patient prognosis are not well documented. AIMS: To introduce two novel histological parameters to characterise PTC-loss of cellular polarity and loss of cellular cohesiveness. To investigate a new subgroup of common type PTC with possible prognostic value. METHODS: In total, 213 patients with PTCs larger than 1 cm were studied. Histological characteristics of these PTCs, including tumour growth pattern, encapsulation, extrathyroidal invasion, loss of cellular polarity, and loss of cellular cohesiveness were examined and correlated with disease free survival (DFS). RESULTS: Multivariate analysis revealed that invasive growth of unencapsulated PTC, in addition to sex (male) and tumour size (>4 cm) were significant and independent parameters for poor DFS, whereas loss of cellular polarity and cohesiveness, old age (>60 years), extrathyroid invasion, and completeness of surgery were significant only in univariate analysis. PTCs that showed expansive growth and retained cellular polarity had a favourable course, with no recurrence and no cancer related deaths. In contrast, PTCs exhibiting loss of cellular polarity and/or invasive growth with no tumour capsule had a higher risk of recurrence. CONCLUSION: Cytological features alone cannot predict patient outcome in PTC. This study indicates for the first time that loss of cellular polarity and the tumour growth pattern are useful parameters for identifying the so called low risk group in common type PTC and in predicting patient outcome in terms of tumour recurrence and cancer related death.

Age Factors↗
PubMed2003

Cyclooxygenase-2 expression in thyroid neoplasms.

AIMS: Previous studies have demonstrated that cyclooxygenase-2 (COX-2) plays a role in carcinogenesis and carcinoma development. In this study, we investigated its expression in thyroid neoplasms in order to elucidate its role. METHODS AND RESULTS: COX-2 expression was studied immunohistochemically in 20 anaplastic (undifferentiated) carcinomas, 49 papillary carcinomas, 22 follicular carcinomas and 15 follicular adenomas. Positive staining was only occasionally seen in normal follicles or stromal cells. COX-2 over-expression was found in only 20.0% of follicular adenomas and 40.9% of follicular carcinomas. In papillary carcinomas, the incidence (81.3%) was significantly higher (P < 0.0001) than in follicular carcinomas, although COX-2 expression was reduced in cases with old age (P = 0.0190), large size (P = 0.0028), advanced stage (P = 0.0225), satellite tumours (P = 0.0363), and the presence of solid, scirrhous or trabecular growth patterns (P = 0.0018). Undifferentiated carcinomas less frequently over-expressed COX-2 (P = 0.0004), with an incidence of 40.0%. CONCLUSIONS: These results indicate that the up-regulation of COX-2 may contribute predominantly in the early phase of papillary carcinoma progression, whereas it plays a more adjuvant role in follicular carcinoma progression.

Carcinoma↗
PubMed2003

Syndecan-1 expression in thyroid carcinoma: stromal expression followed by epithelial expression is significantly correlated with dedifferentiation.

AIM: To investigate the expression of syndecan-1 in thyroid neoplasia. Syndecan-1 is a proteoglycan regulating cell adhesion. Previous studies have demonstrated that decreased expression of syndecan-1 is linked to malignant progression. METHODS AND RESULTS: Syndecan-1 expression in thyroid neoplasia was studied immunohistochemically. Syndecan-1 was expressed in stromal cells as well as neoplastic epithelial cells. Stromal syndecan-1 expression was observed more frequently in papillary carcinomas larger than 10 mm in size than in microcarcinomas and in widely invasive than in minimally invasive follicular carcinomas. Furthermore, poorly differentiated carcinomas showed this phenomenon more than well-differentiated carcinomas, but the expression in undifferentiated carcinomas was similar to that of poorly differentiated carcinomas. Epithelial syndecan-1 expression was more frequently observed in anaplastic (undifferentiated) carcinomas than in papillary and follicular carcinomas. No significant difference in epithelial expression was found between well and poorly differentiated carcinomas, but undifferentiated carcinomas expressed epithelial syndecan-1 more frequently than did poorly differentiated carcinomas. CONCLUSIONS: These results are in contrast to those previously reported for carcinomas at other sites. It is suggested that the role of syndecan-1 in thyroid carcinomas might be unique. Stromal syndecan-1 expression followed by its epithelial expression is significantly related to progression, including dedifferentiation of thyroid carcinoma.

Adenocarcinoma↗
PubMed2002

Expression of cdc25A and cdc25B proteins in thyroid neoplasms.

Cdc25B and cdc25A phosphates are prominent stimulators of cell cycle progression and recent studies have also suggested their oncogenic roles. To elucidate the role of these proteins in thyroid neoplasms, we immunohistochemically investigated their expression, and neither protein was expressed in normal follicular cells. Cdc25B was frequently overexpressed in follicular adenoma and minimally invasive follicular carcinoma, but the incidence was significantly lower in widely invasive follicular carcinoma. Furthermore, the cdc25B expression level significantly decreased with the dedifferentiation of thyroid carcinoma. Cdc25A overexpression was observed in high incidences in all types of thyroid neoplasms. These results suggest that cdc25B and cdc25A play oncogenic roles in thyroid follicules and that cdc25B works predominantly in the early phase of the progression of thyroid carcinoma, whereas cdc25A plays a fundamental role in the development of thyroid neoplasms.

Adenoma↗