Biomedical subjects

Kanji Kuma

Publications and source records attributed to Kanji Kuma.

At least 91 records · Page 5Linked to original sources

PubMed2003

Decreased expression of catalase mRNA in thyroid anaplastic carcinoma.

BACKGROUND: A decreased expression of glutathione peroxidase mRNA, an antioxidant enzyme, was previously observed in thyroid anaplastic carcinomas. METHODS: To clarify the expression of antioxidant-related enzymes in thyroid anaplastic carcinomas, the expression levels of catalase, copper and zinc superoxide dismutase and manganese superoxide dismutase mRNA in 85 benign and malignant thyroid tissues were measured by means of real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Decreased expression levels of catalase and copper and zinc superoxide dismutase mRNAs, but not manganese mRNA, were observed in five anaplastic carcinomas compared with normal thyroid tissues and differentiated tumors. CONCLUSION: These results suggest the possibility that anaplastic carcinoma cells are more likely to suffer damage by oxygen free radicals than normal thyroid cells or differentiated tumor cells.

Adenoma↗

PubMed2003

Overexpression of human tumor-associated antigen, RCAS1, is significantly linked to dedifferentiation of thyroid carcinoma.

OBJECTIVE: Counterattack by RCAS1 on carcinoma to cytotoxic T cells and natural killer (NK) cells has been suggested as a contribution to carcinoma progression, because RCAS1 can inhibit their proliferation and induce apoptosis. In this study, we examined RCAS1 expression in various thyroid neoplasms in order to clarify its clinical significance. METHODS: We studied RCAS1 expression by means of immunohistochemistry using a mouse monoclonal antibody against RCAS1 for normal thyroid epithelium, follicular adenoma, follicular carcinoma, papillary carcinoma and undifferentiated (anaplastic) carcinoma. RESULTS: Normal epithelium and follicular adenoma did not express or only faintly expressed RCAS1. In thyroid carcinomas. RCAS1 overexpression was more frequently observed in anaplastic (undifferentiated) carcinomas than papillary (p < 0.0001) and follicular carcinomas (p = 0.0018). In follicular carcinoma, the widely invasive type more frequently overexpressed RCAS1 than the minimally invasive type (p = 0.0488). Furthermore, the incidences of RCAS1 overexpression increased with carcinoma dedifferentiation (p < 0.0001). CONCLUSION: These results suggest that RCAS1 may contribute to the progression of thyroid carcinoma with high biological aggressiveness.

Adenocarcinoma, Follicular↗

PubMed2003

Expression of TRbeta1 mRNAs with functionally impaired mutations is rare in thyroid papillary carcinoma.

A previous study reported the expression of functionally impaired thyroid hormone receptor (TR)beta1 mutants in almost all papillary thyroid carcinomas. To confirm this, we analyzed the sequence of the entire coding region of TRbeta1 cDNAs expressed in 16 papillary carcinomas. Among the 48 clones analyzed, we found no mutations with an amino acid substitution, which represents a clear discrepancy between our findings and those in the previous study. Our findings suggest that the expression of functionally impaired mutants in papillary carcinomas is rare, and they raise a question about the possible role of mutated TRbeta1 in the tumorigenesis of papillary carcinoma.

Adult↗

PubMed2003

Changes in serum TSH receptor antibody (TRAb) values in patients with Graves' disease after total or subtotal thyroidectomy.

TSH receptor antibodies (TRAb) are generally regarded as mediators of thyroid stimulation in Graves' disease. In addition, a high serum TRAb value during pregnancy is one of the risk factors for intrauterine death, prematurity, and fetal or neonatal hyperthyroidism. Recently, correlations between a high serum TRAb value and endocrine opthalmopathy were also suggested. Surgical resection of the thyroid is usually followed by a reduction of serum TRAb levels in variable degrees. The relation between the extent of the thyroidectomy and the degree of reduction is still controversial. In addition, the changes in the TRAb value after total thyroidectomy (TT) over a long period of time have never been studied. We studied the changes in serum TRAb values after TT and subtotal thyroidectomy (ST) for more than 7 years. Forty-one patients with Graves' disease underwent TT, and 99 patients underwent ST. The serum TRAb values and the ratio of the patients who achieved normal values among each group (normalization rates of TRAb) at 3 and 6 months, 1, 3, 5 and 7 years after surgery were compared between the TT group and ST group. The mean preoperative TRAb values were not significantly different between the TT and ST groups, and the mean TRAb values measured 3, 6 and 12 months after surgery were not significantly different between the groups. However, the TRAb values measured 3, 5 and 7 years after surgery were significantly (p<0.05) lower in the TT group than in the ST group (16.7 +/- 3.3% vs 28.0 +/- 2.6%, 12.6 +/- 3.4% vs 29.3 +/- 3.8%, 5.6 +/- 0.9% vs 25.4 +/- 4.1%, respectively). The normalization rates of TRAb were not significantly different between the groups until 1 year after surgery. However, the normalization rates 3, 5 and 7 years after surgery were significantly (p<0.05) higher in the TT group than in the ST group (65.7% vs 42.4%, 77.3% vs 46.7%, 100% vs 59.1%, respectively). The surgical complication rates of TT were similar to ST except for permanent hypoparathyroidism. TT is a treatment option for Graves' disease, especially in patients with a high TRAb value who wish to have children or who have Graves' opthalmopathy.

Adolescent↗

PubMed2003

Successful management of a patient with pseudomalabsorption of levothyroxine.

Pseudomalabsorption of levothyroxine is a factitious disorder. Despite the administration of large doses of levothyroxine, patients with this disorder show hypothyroidism due to noncompliance. These patients are different from the patients with simple noncompliance in that they have a psychiatric disorder. Because their psychological identities are rooted in their being a "patient," they go to great lengths to become and stay a patient. We report a case of pseudomalabsorption of levothyroxine. A 28-year-old woman was referred to us because she was believed to have unusual malabsorption of levothyroxine. We diagnosed the patient as having this factitious disorder, and as treatment, had her visit a hospital twice a week to take medicine under the observation of nurses so that she would not lose her status as a "patient." Her serum free T4 level normalized during three years with twice weekly dosing of thyroxine after hospital discharge. Our approach could be a therapeutic choice for this intractable disorder. To our knowledge, this is the first report of successful management of a patient with pseudomal-absorption of levothyroxine.

Adult↗

PubMed2003

[A case with poorly differentiated follicular carcinoma of the thyroid produced and secreted CEA].

Detection of thyroglobulin, CEA, and calcitonin in serum and tissue is very useful to make differential diagnosis among papillary, follicular, and medullary carcinoma of the thyroid. The case was a 70-year-old woman with a nodule of the thyroid, presenting elevated serum level of thyroglobulin and CEA (22.0 ng/ml). Both serum level of thyroglobulin and CEA decreased after surgery. One year and nine months after surgery, she died from systemic metastases of thyroid carcinoma. Histological examination of the tumor presented to be poorly differentiated type of follicular carcinoma, presenting positive of both thyroglobulin and CEA, and negative of calcitonin in the cytoimmunochemistry. This case was identified to be a rare case that tumor cells of poorly differentiated follicular carcinoma produced and secreted both thyroglobulin and CEA.

Adenocarcinoma, Follicular↗

PubMed2002

Decreased expression of glutathione peroxidase mRNA in thyroid anaplastic carcinoma.

Our recent study using serial analysis of gene expression show the decreased expression of glutathione peroxidase (GPx), an antioxidant enzyme, in an anaplastic carcinoma. To clarify the expression of GPx in various kinds of thyroid tumors, the expression levels of GPx mRNA in 79 benign and malignant thyroid tissues were measured by means of real-time quantitative reverse transcription-polymerase chain reaction. A decreased expression of GPx mRNA was observed in all of five anaplastic carcinomas and some of the papillary carcinomas. A molecular-based therapy which produces O(2) radical may be considered as an alternative choice for the treatment of anaplastic carcinomas.

Carcinoma↗

PubMed2002

Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutations.

Although sporadic medullary thyroid carcinoma (MTC) tends to be unicentric and confined to one lobe, total thyroidectomy is usually performed because of the risk of a hereditary or bilateral process. Germline RET mutation analysis can discriminate hereditary MTC and truly sporadic, nonhereditary MTC. We analyzed 72 of 94 patients with MTC to establish the genetic nature and the clinical features of nonhereditary MTC. Since 1996 we have prospectively treated 15 patients with nonhereditary MTC (prospective study group, or PSG) according to a unilateral surgery policy. A group of 22 previously operated patients in whom the nonhereditary nature was established served as controls (retrospective study group, or RSG). Systematic central and ipsilateral neck dissection was performed in both groups. Outcome was assessed using postoperative stimulated serum calcitonin levels; a normal value was considered a biochemical cure. All 24 hereditary MTC patients carried germline RET mutations: 8 of 48 patients with apparently sporadic MTC had the mutations, and 6 of the 8 had bilateral MTC. All 40 patients without mutations had a unilateral tumor. In the RSG group 15 of 22 (68%) patients underwent total thyroidectomy, and the biochemical cure rate was 68%. Although only 3 of 15 (20%) of the PSG patients underwent total thyroidectomy, 12 of the 15 (80%) achieved biochemical cure. Univariate analyses revealed that pathologic node involvement- high T and N stages-was adversely related to biochemical cure. The extent of thyroid resection was not related to biochemical cure. Of 20 patients with node involvement, 10 achieved biochemical cure, indicating the importance of systematic neck dissection. Hemithyroidectomy with systematic central and ipsilateral neck dissection is appropriate surgery for nonhereditary MTC.

Adult↗

PubMed2002

Excessive survivin expression in thyroid lymphomas.

Thyroid lymphoma occurs most commonly in the thyroid glands with a background of Hashimoto's thyroiditis. Therefore, it is occasionally difficult to distinguish lymphoma from Hashimoto's thyroiditis because of some cellular and histologic similarities. We have examined whether survivin or human telomerase reverse transcriptase (hTERT) expression can differentiate between the 2 disorders. Surgically removed tissue samples from 6 patients with thyroid lymphoma and 6 patients with Hashimoto's thyroiditis were analyzed for mRNA levels of survivin and hTERT by real-time quantitative reverse-transcription polymerase chain reaction. Expression of survivin protein was examined by immunohistochemical stain using a polyclonal antibody. Survivin mRNA levels were greater in thyroid lymphoma than in Hashimoto's thyroiditis: 49.1 +/-36.4 versus 6.6 +/-2.7 pg/ng rRNA (mean +/- SD) (P <0.005). Immunohistochemical stain confirmed an abundance of survivin protein in lymphoid cells of thyroid lymphoma. The amount of hTERT mRNA did not differ in the 2 disorders. Our study shows that measuring survivin mRNA levels or immunohistochemistry of the protein expression can be useful to aid the diagnosis of thyroid lymphoma when histologic diagnosis is difficult.

Biomarkers, Tumor↗

PubMed2002

Expression of G2-M modulators in thyroid neoplasms: correlation of cyclin A, B1 and cdc2 with differentiation.

Previous studies have demonstrated that cell proliferating activity accurately reflects the biological aggressiveness of thyroid neoplasms. In this study, we focused on the G2-M boundary regulators of the cell cycle and investigated the expression of three proteins, cyclin A, cyclin B1 and cdc2. The incidence of cyclin A overexpression was significantly linked to carcinoma differentiation (p < 0.0001) and, in particular, all 21 cases of undifferentiated carcinoma overexpressed this protein. On the other hand, cyclin B1 was overexpressed in four undifferentiated carcinomas (19.0%), but not in carcinomas of other types. Cdc2 overexpression was also related to carcinoma differentiation (p < 0.0001), and was directly linked to cyclin A overexpression (p < 0.0001), but not to cyclin B1 overexpression. No significant relationship could be established between the overexpression of these proteins and the histological type of follicular tumor. These results suggest that cyclin A, rather than cyclin B1, contributes significantly to the aggressive character of thyroid carcinoma, together with cdc2.

Adenoma↗

PubMed2002

Acute suppurative thyroiditis caused by an infected piriform sinus fistula with thyrotoxicosis.

We report herein an unusual case of thyrotoxicosis caused by acute suppurative thyroiditis (AST) infected through a piriform sinus fistula (PSF). A 28-year-old man presented with pain over the thyroid gland and elevated serum thyroid hormone levels, a picture similar to subacute thyroiditis. A fine-needle aspiration biopsy from the left lobe showed neutrophil infiltration, and culture from the aspirate grew anaerobic peptostreptococcus. A neck computed tomography (CT) scan showed an abscess in the thyroid gland, and barium swallow revealed the presence of PSF. Appropriate antibiotic treatment ameliorated his symptoms of infection, followed by normalization of thyroid function. Three months later, he underwent fistulectomy and partial left lobectomy. The end of the PSF track was found in the left thyroid lobe. Thus infection of the thyroid gland through the infected PSF was likely the cause of supprative thyroiditis. The unusual clinical features of AST in this patient include the presence of severe thyrotoxicosis, relatively late onset (28-years-old) of infection despite the presence of congenital PSF, and the lack of acute inflammatory signs on the overlying skin of the thyroid gland. It is important to recognize this type of AST, since fistulectomy is required to prevent recurrent AST.

Acute Disease↗

PubMed2002

Quantitative analysis of thymosin beta-10 messenger RNA in thyroid carcinomas.

BACKGROUND: Genes that are differentially expressed in benign and malignant tissues are important for the establishment of molecular-based diagnosis of carcinomas. Our recent study on the gene expression profile of thyroid carcinomas revealed an increased expression of thymosin beta-10 mRNA. METHODS: To confirm this, we measured the expression levels of thymosin beta-10 mRNA in 84 thyroid benign and malignant thyroid tissues, including five anaplastic carcinomas, by means of real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: We found an increased expression of thymosin beta-10 mRNA in thyroid carcinomas, especially in anaplastic carcinomas. Expression levels of thymosin beta-10 mRNA relative to thyroglobulin mRNA in anaplastic carcinomas were greatly increased compared with those in differentiated carcinomas. CONCLUSION: These results suggest the usefulness of the quantitative measurement of thymosin beta-10 mRNA in molecular-based diagnosis of thyroid anaplastic carcinomas, but not of differentiated carcinomas.

Biomarkers, Tumor↗

PubMed2002

Quantitative analysis of osteonectin mRNA in thyroid carcinomas.

Our recent study of the gene expression profile in thyroid carcinoma showed an overexpression of osteonectin mRNA, an extracellular matrix protein, in an anaplastic carcinoma. To confirm this, we measured the expression levels of osteonectin mRNA in 84 thyroid normal and tumor tissues, including five anaplastic carcinomas by realtime quantitative reverse-transcription PCR. Increased expression of osteonectin mRNA was observed in anaplastic carcinoma tissue. However, in five anaplastic carcinoma cell lines, no increase was observed in the expression levels of osteonectin mRNA. These findings suggest the possibility that increased expression of osteonectin mRNA in anaplastic carcinoma tissue may be due to its overexpression in stromal cells, but not in anaplastic carcinoma cells.

Carcinoma↗

PubMed2002

Expression of p57/Kip2 protein in normal and neoplastic thyroid tissues.

p57 (Kip2) belongs to the Cip/Kip family and is one of the universal negative regulators of the cell cycle. In this study, we investigated the p57 expression of various types of thyroid neoplasm. p57 overexpression was observed in only 4.2% of normal thyroid tissues. In follicular adenoma and minimally invasive follicular carcinoma, p57 was overexpressed in 100% and 91.7% of the cases, respectively. However, its incidence was significantly lower (p<0.0001) in widely invasive follicular carcinoma, of which only 36.4% overexpressed p57. This phenomenon was seen in 63.1% of papillary carcinoma and 13.3% of anaplastic (undifferentiated) carcinoma. Furthermore, poorly differentiated and undifferentiated carcinoma more frequently lacked p57 expression (p<0.0001). These results suggest that the down-regulation of p57 may play a role in the dedifferentiation of thyroid carcinoma and in follicular carcinoma mutating to be more invasive.

Cell Differentiation↗

PubMed1995

Immunoreactive Characteristics and Classification of Hyperparathyroidism.

Hyperparathyroidism is caused mainly by three different conditions: namely, secondary hyperplasia, primary hyperplasia, and adenoma with only a few cases due to carcinomas. Histological distinction among these diseases is still difficult. In an attempt to characterize the three conditions, 17 cases from patients with hyperparathyroidism and 12 with normal glands were investigated immunohistochemically using antibodies against PTH, PTHrP, Ki-67 (MIB-1), and chromogranin A. The normal glands showed a diffuse staining pattern for PTH, and focal staining for PTHrP and for chromogranin A. Secondary hyperplasia demonstrated either focal, diffuse, or mixed staining in one gland with the three antibodies. For the primary hyperplasias and adenomas, the cases could be divided into two groups. The first group (group I), including 1 case of primary hyperplasia and 3 cases of adenoma, showed a homogeneous staining pattern with all three antibodies. A heterogeneous staining pattern similar to secondary hyperplasia was found in the other 8 cases that formed the second group (group II). There were five types of cytologic staining patterns after immunostaining. In secondary hyperplasia and group II, several patterns appeared simultaneously. On the contrary, only one pattern was found in group I. The proliferative index (P1) from Ki-67 staining of group I was also significantly higher than in group II. A lower P1 was observed in the normal glands. The present results indicate that different immunohistochemical characteristics exist in primary hyperplasias and in adenomas.

Journal Article↗

PubMed1995

Immunolocalization of Parathyroid Hormone in Human Parathyroid Glands with Special References to Microwave Antigen Retrieval.

The subcellular localization of parathyroid hormone (PTH) in the normal human parathyroid glands with particular reference to microwave antigen retrieval was investigated using peroxidase-labeled PTH antibody, immunohistochemical, and immunoelectron microscopic methods. The results revealed that PTH granules existed mainly as pro-PTH on the trans side of Golgi and in the regions adjacent to Golgi apparatus. Only a small proportion of secretory granules were stored near the plasma membrane. Microwave irradiation was essential for the immunodetection of PTH. As the irradiative time extended from 1 to 30 min, the staining intensity increased, and the subcellular preservation decreased. Microwave irradiation for 15 mm (with the sections in citrate buffer) with a power output of 500 W is the most ideal for PTH antigen retrieval, as well as for subcellular preservation.

Journal Article↗

PubMedDate not supplied

Bag-1 expression in thyroid neoplasm: its correlation with Bcl-2 expression and carcinoma dedifferentiation.

BACKGROUND: Apoptosis, programmed cell death, is one of the promnent factors in the evaluation of carcinoma characteristics. It is well-known that bcl-2 and its related proteins significantly modulate apoptosis. Bag-1 is a recently identified bcl-2-related protein and is known to be linked to the biological aggressiveness of some carcinomas. MATERIALS AND METHODS: We immunohistochemically investigated bag-1 and bcl-2 expression in various thyroid neoplasms using monoclonal antibodies. RESULTS: High bag-1 expression was observed in 66.7% of follicular adenoma and 75.0% of follicular carcinoma, and no statistical difference was established between them. In papillary carcinoma, 60.7% were classified with high bag-1 expression, whereas only 4.5% of anaplastic (undifferentiated) carcinoma highly expressed bag-1, and the incidence was significantly lower (p < 0.0001) than in papillary and follicular carcinomas. Furthermore, in thyroid neoplasm, bag-1 expression was directly linked (p < 0.0001) to bcl-2 expression. CONCLUSION: These findings suggest that bag-1 may interact with bcl-2 to play an important role in thyroid neoplasm before anaplastic transformation, and the disruption of events mediated by bag-1 and bcl-2 may be a typical characteristic of undifferentiated carcinoma.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

Survivin expression is significantly linked to the dedifferentiation of thyroid carcinoma.

Survivin is a novel member of the apoptosis protein inhibitors, but according to previous reports, it is also significantly linked to cell proliferating activity. In this study, we investigated the expression of survivin in thyroid neoplasms. Survivin was only occasionally expressed in normal follicular cells, whereas in follicular and papillary carcinomas, about 20% of cases were positive for survivin. The incidence was significantly higher in advanced stage papillary carcinoma (p=0.0080) and papillary and follicular carcinomas with poorly differentiated lesions (p=0.0150). In anaplastic carcinoma, survivin positivity was observed in 84% of the cases, which was in significantly higher incidence than in papillary or follicular carcinoma (p<0.0001). These results suggest that survivin is strongly related to the dedifferentiation of thyroid carcinoma.

Adenocarcinoma, Follicular↗