Biomedical subjects

Yasuhiro Ito

Publications and source records attributed to Yasuhiro Ito.

At least 55 records · Page 3Linked to original sources

PubMed2005

Caveolin-1 and 14-3-3 sigma expression in follicular variant of thyroid papillary carcinoma.

There are two prominent types of thyroid carcinoma, papillary carcinoma (PC) and follicular carcinoma (FC) arising from thyroid follicular cells, which have different biological characteristics. The follicular variant of papillary carcinoma (FVPC) has a structure similar to FC, although it is classified as a subtype of PC. We have previously demonstrated that caveolin-1, a major component of caveolae and an inhibitor of growth signal transduction, and 14-3-3 sigma, a regulator of the cell cycle and signal transduction, are frequently expressed in pure PC, but not in FC. In this study, we investigated these expressions in FVPC and FC. Caveolin-1 and 14-3-3 sigma were expressed in 96.2% and 92.3% of FVPC, respectively. However, almost all FC, with only a few exceptions, were negative for these findings, indicating that these proteins were more frequently expressed in FVPC than in FC (p < 0.0001). These findings suggest that caveolin-1 and 14-3-3 sigma positively or negatively regulate the development of FVPC but not that of FC, reflecting the difference of biological characteristics of these two types of carcinoma.

14-3-3 Proteins↗

PubMed2005

S100A9 expression is significantly linked to dedifferentiation of thyroid carcinoma.

S100A9, a calcium-binding protein, is associated with myeloid cell differentiation and is expressed in some adenocarcinomas as well as in squamous epithelia and squamous cell carcinoma. In this study, we immunohistochemically investigated S100A9 expression in thyroid neoplasms. S100A9 was absent in normal follicles, follicular adenoma, and follicular and papillary carcinomas with conventional growth structures. In lesions showing a solid, trabecular, or scirrhous growth pattern, S100A9 immunoreacitivity was occasionally observed. One (5.9%) of the 17 follicular carcinomas and three (7.8%) of the 38 papillary carcinomas were regarded as positive for S100A9, but the positive cell areas always accounted for 5% or less. However, S100A9 was positive in all 19 undifferentiated carcinomas examined. Among them, the positive cell area was greater than 5% in 16 (84.2%), and greater than 25% in six (31.6%) cases. It is therefore suggested that S100A4 protein plays an important role in thyroid carcinoma dedifferentiation, and can be considered a novel characteristic of undifferentiated carcinoma.

Adenocarcinoma, Follicular↗

PubMed2005

Expression of Jun activation domain-binding protein 1 and p27 (Kip1) in thyroid medullary carcinoma.

AIMS: p27 is a prominent regulator of cell proliferation by universally inhibiting the cell cycle, while Jun activation domain-binding protein 1 (Jab1), a multifunctional cell signaling protein, contributes to carcinoma progression by degrading p27. In this study, we investigated the expression of these proteins in medullary thyroid carcinoma. METHODS: We immunohistochemically examined Jab1 and p27 expression in 64 medullary thyroid carcinomas. RESULTS: Of the 64 cases examined, decreased p27 expression was observed in 38 cases (59.4%). The p27 expression level was inversely linked to tumour size as well as plasma calcitonin level. Jab1 expression level was generally high, and 46 cases (71.9%) were classified as overexpressing Jab1. The incidence was higher than those in papillary and follicular carcinomas, which were previously reported. Jab1 expression level was inversely linked to that of p27, and all five cases with only cytoplasmic but not nuclear staining of p27 overexpressed Jab1. CONCLUSIONS: These findings suggest that (1) decrease in p27 expression may contribute to local tumour growth; (2) Jab1 expression is related to the progression of medullary carcinoma by decreasing the amount of p27 in the cell and accelerating its degradation; and (3) Jab1 may play a more vital role in the pathogenesis of medullary carcinoma than papillary and follicular carcinomas.

Adult↗

PubMed2005

Galectin-3 expression in follicular tumours: an immunohistochemical study of its use as a marker of follicular carcinoma.

AIMS: Galectin-3, a member of the beta-galactoside binding family of lectins, has been regarded as a useful tool for discriminating malignant tumours from benign nodules of the thyroid, including the distinction between follicular carcinoma and adenoma. However, there are follicular tumours with unclear vascular or capsular invasion, which makes diagnosis more difficult. In this study, we investigated the relationship between galectin-3 expression and the degree of vascular or capsular invasion of follicular tumours. METHODS: We immunohistochemically investigated galectin-3 expression in 260 cases of follicular tumour with various degrees of vascular or capsular invasion classified into four categories. RESULTS: The galectin-3 expression level significantly increased with the degree of vascular or capsular invasion (p<0.0001). However, its diagnostic value for follicular carcinoma was not high because the sensitivity and specificity were 68.7% and 57.5%, respectively. CONCLUSIONS: Our findings suggest that galectin-3 plays a role in the transformation of follicular tumours from benign to malignant; however, when diagnosing follicular tumours, the presence of this protein should not be required for diagnosing malignant transformation in all cases. Therefore, we must conclude that galectin-3 should only be considered an adjuvant marker for follicular carcinoma.

Adenocarcinoma, Follicular↗

PubMed2005

Lower-limb asymmetries in early and late middle age.

The present study examined the relationship between upper- and lower-limb laterality and the difference in kinaesthetic function between lower limbs. A total of 360 early and late middle-aged people from rural areas in Japan participated in the study. The first purpose was to describe upper- and lower-limb lateral preferences. Approximately 80% of the population showed uncrossed lateral preference between hand and foot (i.e., right-handed and right-footed or left-handed and left-footed). Furthermore, the proportions of uncrossed type population were similar among the four age groups (30s-40s, 50s, 60s, and 70s). The second purpose was to examine the lateral differences in leg muscle strength in order to seek possible reasons for a leftward bias in the occurrence of hip fractures. Leg muscle strength was measured by a strengthergometer. The muscle strength of the left leg (non-preferred) was stronger than that of the right (preferred) leg in the 50s age group, whereas there was no significant difference between the two lower limbs in the other age groups (30s-40s, 60s, 70s). This finding suggests that greater fatigue on the left leg bone system might induce the high occurrence of left hip fractures.

Adult↗

PubMed2005

Transcutaneous iodine absorption in adult patients with thyroid cancer disinfected with povidone-iodine at operation.

Povidone-iodine is used as disinfection in patients undergoing many kinds of operations. Several cases of thyroid dysfunction induced by transcutaneous absorption of povidone-iodine have been reported in small infants. However, transcutaneous absorption was not clearly reported in adults. The aim of this study was to assess transcutaneous absorption of iodine in patients who received single topical application with povidoneiodine and serial changes of urinary iodine excretion under the condition with a simple iodine-restricted diet in Japan, an iodine-sufficient area. Sixty-eight patients with thyroid carcinoma undergoing total thyroidectomy received single skin disinfection with either povidone-iodine (group A; n = 47) or chlohexidine gluconate, a noniodine containing biguanide (group B; n = 21). In group A, urinary iodine excretion on the first day after operation increased up to 7 times that of the preoperative value. The amounts of urinary iodine correlated positively with operating time. Increased urinary iodine, however, returned to preoperative values on the third or fifth day after operation. In group B, there was no increase in urinary iodine excretion and urinary iodine excretion was ranged from 54 to 193 microg/g of creatinine on the third day of operation. In conclusion, a large amount of povidone-iodine was absorbed through healthy skin even in adults. This may possibly interfere with scintigraphy or radioactive iodine treatment, or cause thyroid disinfection in susceptible patients.

Administration, Cutaneous↗

PubMed2005

Postoperative tomographic assessment of veneer bone grafting with implant placement in the maxillary anterior region.

Various ridge augmentation and sinus lift procedures were performed in severely resorbed alveolar crests of a maxilla to provide some volume for implant treatment. It was reported that the outcome of maxillary sinus lift procedures was evaluated with conventional tomography or computerized tomography, and that grafted bone around implants markedly progressed in resorption, particularly at the implant apex. However, veneer bone grafting with implant placement has not been evaluated after treatment with imaging techniques. Therefore, the purpose of this study was to assess veneer bone grafting after maxillary anterior implant treatment. Seven patients with a mean age of 24 years, with implants placed in the maxillary anterior region with or without autogenous veneer bone grafting were postoperatively examined using conventional tomography. On tomograms, the ratio of bone-to-implant contact and the area of bone were measured in labial bones with bone grafts, and they were compared with the values without bone grafts. In cases with bone grafting, the average ratio of bone-to-implant contact was 63.6%, whereas 81.8% was formed in cases without bone grafting. The average area of bone was 12.9 mm and 23.4 mm in patients with and without bone grafting, respectively. No significant difference was found between the implants with and without bone grafts. Resorbed labial bone was observed in the maxillary anterior region with and without veneer bone grafting.

Adolescent↗

PubMed2005

Polo-like kinase 1 expression in medullary carcinoma of the thyroid: its relationship with clinicopathological features.

OBJECTIVE: 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. In this study, we investigated PLK1 expression in medullary thyroid carcinoma by means of immunohistochemistry. METHODS: We immunohistochemically investigated PLK1 expression in 67 cases of medullary thyroid carcinoma. RESULTS: The PLK1 expression level was elevated in 43 of the 67 cases (64.1%). Furthermore, the expression level was directly linked to lymph node metastasis, advanced stage and male sex. All patients who were negative for PLK1 expression are currently alive without tumor recurrence, while 6 of the 43 PLK1-positive patients showed recurrence and 3 have already died of this disease. CONCLUSIONS: These findings suggest that PLK1 expression significantly reflects aggressive characteristics of medullary thyroid carcinoma.

Adolescent↗

PubMed2005

Reevaluation of stringent low iodine diet in outpatient preparation for radioiodine examination and therapy.

To decrease total body iodine is a key point in preparation for radioiodine study and therapy. We introduced a stringent self-managed low iodine diet (LID) and compared the outcome to that of the conventional restricted iodine diet (RID) for outpatients. We measured urine iodine to creatinine ratios (I/Cr) in patients prepared with RID for one week, LID for one week, or LID for two weeks. Mean urinary iodine excretion after RID for one week (n = 210) was 182.2 microg/gCr (range, 13-986 microg/gCr; standard deviation (SD) = 158.5) not reaching below the recommended level (I/Cr<100 microg/gCr). Urinary iodine excretion after LID for one week (n = 15) showed a lower mean urinary iodine level (I/Cr 119.4 microg/gCr; range, 23-218 microg/gCr; SD = 55.9) than RID for one-week, and two-week LID (n = 17) showed an even lower mean level (I/Cr 63.1 microg/gCr; range, 7-134 microg/gCr; SD = 38.7). The one-week LID period adequately (recommended level of I/Cr being less than 100 microg/gCr) prepared 26% of the patients, while two-weeks on the diet adequately prepared 70% of the patients. Furthermore, none of the two-week LID patients had I/Cr>150 microg/gCr, although a significantly greater number of one-week LID patients (19%) did. Our self-managed, outpatient LID successfully induced iodine deficiency, and two-week LID may be recommended for preparation in radioiodine study and therapy for thyroid cancer.

Adult↗

PubMed2004

Activated protein C induces endothelial cell proliferation by mitogen-activated protein kinase activation in vitro and angiogenesis in vivo.

Activated protein C (APC), a natural anticoagulant, has recently been demonstrated to activate the mitogen-activated protein kinase (MAPK) pathway in endothelial cells in vitro. Because the MAPK pathway is implicated in endothelial cell proliferation, it is possible that APC induces endothelial cell proliferation, thereby causing angiogenesis. We examined this possibility in the present study. APC activated the MAPK pathway, increased DNA synthesis, and induced proliferation in cultured human umbilical vein endothelial cells dependent on its serine protease activity. Antibody against the endothelial protein C receptor (EPCR) inhibited these events. Early activation of the MAPK pathway was inhibited by an antibody against protease-activated receptor-1, whereas neither late and complete activation of the MAPK pathway nor endothelial cell proliferation were inhibited by this antibody. APC activated endothelial nitric oxide synthase (eNOS) via phosphatidylinositol 3-kinase-dependent phosphorylation, followed by activation of protein kinase G, suggesting that APC bound to EPCR might activate the endothelial MAPK pathway by a mechanism similar to that of VEGF. APC induced morphogenetic changes resembling tube-like structures of endothelial cells, whereas DIP-APC did not. When applied topically to the mouse cornea, APC clearly induced angiogenesis in wild-type mice, but not in eNOS knockout mice. These in vitro events induced by APC might at least partly explain the angiogenic activity in vivo. This angiogenic activity of APC might contribute to maintain proper microcirculation in addition to its antithrombotic activity.

Animals↗

PubMed2004

Preoperative ultrasonographic examination for lymph node metastasis: usefulness when designing lymph node dissection for papillary microcarcinoma of the thyroid.

Papillary microcarcinoma has an excellent prognosis after surgical treatment, but how to dissect the lymph nodes remains an open question. In this study, we investigated whether modified radical neck dissection (MND) affected the lymph node recurrence-free survival (LN-RFS) rate for 590 patients with papillary microcarcinoma and recurrence in the lateral compartment who underwent surgery in our hospital between 1993 and 2001. MND was performed in 316 patients, and metastasis in lateral compartment was preoperatively detected on ultrasonography in 67. These 67 patients showed significantly worse LN-RFS (p = 0.0038) than the remaining 249 patients without preoperatively detectable lateral node metastasis. Of the 523 patients (590 minus the 67 patients) whose lateral node metastasis was not detected preoperatively, 249 underwent MND; the remaining 274 patients did not. There was no significant difference in LN-RFS between these two groups. Our preliminary data suggest that with papillary microcarcinoma: (1) MND is not necessary in patients without lateral node metastasis detected on ultrasonography preoperatively, and (2) patients with preoperatively detected lateral node metastasis are more likely to develop recurrence in the lymph nodes so careful MND should be performed.

Adolescent↗

PubMed2004

Angiopoietin-related growth factor (AGF) promotes angiogenesis.

We report here the identification of angiopoietin-related growth factor (AGF) as a positive mediator for angiogenesis. To investigate the biologic function of AGF in angiogenesis, we analyzed the vasculature in the dermis of transgenic mice expressing AGF in mouse epidermal keratinocytes (K14-AGF). K14-AGF transgenic mice were grossly red, especially in the ears and snout, suggesting that hypervascularization had occurred in their skin. Histologic examination of ear skin from K14-AGF transgenic mice revealed increased numbers of microvessels in the dermis, whereas the expression of several angiogenic factors, such as basic fibroblast growth factor (bFGF), vascular endothelial growth factors (VEGFs), and angiopoietin-1 (Ang-1), was decreased. We showed that AGF is a secreted protein and does not bind to tyrosine kinase with immunoglobulin and EGF-homology domain (Tie1) or Tie2 receptors. An in vitro chamber assay revealed that AGF directly promotes chemotactic activity of vascular endothelial cells. Both mouse corneal and matrigel plug assays showed that AGF induces neovascularization in vivo. Furthermore, we found that plasma leakage occurred after direct injection of AGF into the mouse dermis, suggesting that AGF directly induces a permeability change in the local vasculature. On the basis of these observations, we propose that AGF is a novel angiogenic factor and that handling of its biologic functions could lead to novel therapeutic strategies for control of angiogenesis.

Angiogenesis Inducing Agents↗

PubMed2004

SP3 acts as a positive regulator on the core promoter of human ZPK gene.

ZPK (zipper protein kinase)/MUK/DLK/MAP3K12, a member of mixed-lineage kinases (MLKs), is expressed in a tissue-specific manner, particularly in developing brain, and likely to contribute to cytodifferentiation, apoptotic elimination, and migration. To understand the preferential expression of ZPK in neuronal tissues, we have analyzed the putative core promoter region upstream of the first exon of the human ZPK gene. The core promoter region is TATA-less, but contains several potential transcription factor-binding motifs such as a GC-box, all of which are well conserved between human and mouse. Reporter assays and 'gel-shift' analysis using SH-SY5Y cells revealed that a xenobiotic responsive element (XRE)-like motif (GGGCGTGTCC) was preferentially recognized by Sp3, and enhanced the core promoter activity. However, the core promoter activity was still potent even in HeLa cells which barely express ZPK. Our results suggest that, for the selective expression of ZPK gene, cell-specific negative regulatory element(s) which locate outside of the core promoter region repress the potent basic promoter activity.

Amino Acid Motifs↗

PubMed2004

Expression of cdc25A and cdc25B phosphatase in breast carcinoma.

BACKGROUND: Previous studies have indicated that cdc25B and cdc25A phosphatase stimulate cell cycle progression and also play a role in malignant transformation of cells. In this study, we investigated the expression of these phosphatases in breast carcinoma to elucidate their significance. METHODS: We immunohistochemically examined cdc25B and cdc25A expression in 46 cases of breast carcinoma. RESULTS: Cdc25B and cdc25A were negative or only equivocally expressed in glandular epithelial cells. In breast carcinoma, 56.5% of cases had high levels of cdc25B expression. Interestingly, the expression of cdc25B was significantly lower in cases with biologically aggressive phenotypes. The cdc25A level was high in 69.6% of cases, but we could not find any relationship between cdc25A expression and clinicopathological parameters. CONCLUSION: These results suggest that cdc25B is important especially in the early phase of breast carcinoma progression.

Adult↗

PubMed2004

Cribriform-morular variant of papillary thyroid carcinoma: clue to early detection of familial adenomatous polyposis-associated colon cancer.

The cribriform-morular variant (CMV) of papillary thyroid carcinoma (PTC) is a rare histologic subtype of PTC that shows a combination of growth patterns including cribriform and spindle cell areas. The thyroid cancer with this unique histology was originally reported in patients with familial adenomatous polyposis (FAP), although it was later found in patients without polyposis as well. Because of its rarity, its clinical features are not clear. We reviewed seven patients with CMV-PTC who were found among 4194 patients with PTC in our pathology files between June 1991 and March 2003. The prevalence of CMV was 0.16% among all PTCs. We invited these patients to our hospital so we could obtain a detailed family history and recommend colonoscopic examination and germline APC gene analysis. Two patients without subjective symptoms had polyposis of the colon and colon cancers. Germline APC gene mutations were found in both patients. The father of a patient who refused the invitation was revealed to have undergone surgery for colon polyposis. In the remaining four patients, neither polyposis nor APC gene mutation was found. Common clinical features included a young age (mean 25 years), predominance of females, circumscribed tumors, negative node metastasis, and no recurrence of the thyroid cancer after surgery. Two of the three patients with colon polyposis had bilateral multiple thyroid tumors, whereas the remaining four (without polyposis) had a solitary tumor. The histopathology of CMV in patients with PTC should arouse a suspicion of FAP, especially if there are multiple tumors. This finding can lead to early detection of colon cancer.

Adenomatous Polyposis Coli↗

PubMed2004

Papillary microcarcinoma of the thyroid: how should it be treated?

We previously demonstrated that (1) most papillary microcarcinomas can be followed without surgical treatment and (2) when surgery is performed, patients with lateral lymph node metastasis detected on preoperative ultrasonography (US) are more likely to develop recurrence. In this study, we further investigated the application of these strategies. To date, we have observed 211 patients (average follow-up 47.9 months). In more than 70% of these patients the tumor size did not increase during the follow-up period. There were no clinicopathologic features linked to tumor enlargement except in tumors > or = 7 mm, which tended to enlarge in patients followed for 4 years. To evaluate not only whether observation can continue but also how to dissect the lymph nodes optimally at surgery, US diagnosis for lateral node metastasis is essential because the presence of US-diagnosed lateral metastasis is an even stronger predictive marker for recurrence than the presence of pathologically confirmed node metastasis. The positive predictive value (PPV) was 80.6% for US but reached 100% if fine-needle aspiration biopsy (FNAB) of nodes or FNAB-thyroglobulin measurement is added. Furthermore, carcinomas occupying the upper region of the thyroid more frequently showed US-diagnosed and pathologically confirmed lateral metastasis, and those measuring > or = 7 mm were more likely to show pathologically confirmed lateral metastasis. These findings suggest that, for papillary microcarcinoma: (1) US-diagnosed lateral metastasis is a strong marker predicting a worse relapse-free survival; (2) FNAB of nodes and FNAB-thyroglobulin measurement are useful tools for evaluating lymph node metastasis; and (3) careful US evaluation for lateral metastasis is necessary in patients with a tumor measuring > or = 7 mm or that is located in the upper region of the thyroid both during observation and preoperatively.

Adult↗

PubMed2004

Prognosis after reoperation for local recurrence of papillary thyroid carcinoma.

PURPOSE: To investigate the factors associated with a favorable prognosis after reoperation for local recurrent papillary thyroid carcinoma (PTC), we reviewed 45 patients who underwent surgery for first local recurrence of PTC. METHODS: We divided the patients into two groups. Group A (n = 28) had no second recurrence, and group B (n = 17) had second local recurrence after surgery for recurrence. RESULTS: The mean follow-up period after reoperation was 56.9 months. The mean age at the time of reoperation in group A was significantly lower than that in group B, at 48.1 years versus 62.3 years, respectively (P = 0.0007). The mean age at the time of the initial operation in group A was also significantly lower than that in group B, at 40.1 years versus 55.1 years, respectively (P = 0.0006). Patients with recurrent tumors only outside the area dissected at the initial operation (n = 27) had a better outcome than those with recurrence within the dissected area (n = 18; P = 0.0127). Patients who underwent systematic partial or modified neck dissection (n = 36) had a better outcome than those who underwent only simple local resection (n = 9; P = 0.0169). CONCLUSION: For local recurrent PTC, systematic neck dissection is recommended over local resection of recurrent tumors.

Adult↗

PubMed2004

Maspin expression is directly associated with biological aggressiveness of thyroid carcinoma.

Maspin belongs to the serpin superfamily and has been identified as a tumor suppressor because it inhibits cell motility, invasion, and angiogenesis. However, its physiological activity in carcinoma tissues seems to differ according to the origin of the carcinoma. In this study, we investigated maspin expression in thyroid neoplasms originating in follicular cells by means of immunohistochemistry. Neither normal follicular cells nor stromal cells expressed maspin. Follicular adenomas were all negative for maspin, but 12.5% of follicular carcinomas and 30.5% of papillary carcinomas were positive for it. However, the staining pattern was only focal in all positive specimens except for one and maspin-expressing cells were present mainly at the edge of carcinoma nests. Widely invasive follicular carcinomas tended to be more frequently positive for maspin than minimally invasive ones. In papillary carcinoma, maspin expression was directly linked to stage, tumor size, and extrathyroidal invasion. Papillary and follicular carcinomas involving lesions with solid, trabecular, or scirrhous growth patterns (poorly differentiated carcinoma as designated by Sakamoto et al.) expressed maspin in significantly higher incidence than those with pure papillary or follicular patterns. Furthermore, 48.2% of anaplastic (undifferentiated) carcinomas diffusely expressed maspin, and the rest were completely negative. These findings indicate that, in contrast to other carcinomas, maspin expression is directly associated with the biological aggressiveness of thyroid carcinoma. Further studies regarding the function of maspin in this carcinoma are required.

Cysteine Proteinase Inhibitors↗