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Sunao Shoji,
Mayura Nakano,
Tetsuro Tomonaga,
Hakushi Kim,
Kazuya Hanai,
Yukio Usui,
Yoshihiro Nagata,
Masaki Miyazawa, Haruhiro Sato,
Xian Yang Tang,
Yoshiyuki Robert Osamura,
Toyoaki Uchida,
Toshiro Terachi,
Koichi Takeya
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ABSTRACT: KISS-1 is a metastasis-suppressor gene of human melanoma, and encodes metastin, which was identified as the ligand of a G-protein-coupled receptor (metastin receptor). The precursor protein is cleaved to 54 amino acids, which may be further truncated into carboxy-terminal fragments. Previous studies showed that lack of metastin receptor in clear cell renal cell carcinoma (RCC) is associated with tumor progression, but the prediction of metastasis in patients with pT1 clear cell RCC after radical nephrectomy is difficult. The objective of this study was to evaluate the usefulness of metastin receptor immunohistochemistry in predicting metastasis after nephrectomy for pT1 clear cell RCC. After verification of the correlation between immunostaining and mRNA expression, we evaluated the clinical value of metastin receptor immunohistochemistry. Fifty-four patients were enrolled in this study; following radical nephrectomy, seven patients were found to have lung metastasis. The sensitivity, specificity, positive predictive value, and negative predictive value with negative immunostaining of metastin receptor were 85.7, 97.6, 46.2, and 97.6 %, respectively. Metastasis-free survival rates were significantly higher in patients with positive staining (97.6 %) than in patients with negative staining (53.8 %) (P < 0.001). In univariate analysis for metastasis-free survival, negative immunostaining of metastin receptor was a significant risk factor for metastasis (P = 0.001). Furthermore, negative immunostaining of metastin receptor was an independent predictor for metastasis in multivariate analysis (hazard ratio, 3.735; 95 % CI 0.629-22.174; P = 0.002). In conclusion, our study suggests that negative expression of metastin receptor in clear cell RCC is significantly related to metastasis.
Clinical and Experimental Metastasis 01/2013; · 3.52 Impact Factor
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ABSTRACT: A 55-year-old Japanese man was referred to our hospital because of disturbance of consciousness and hyponatremia. He had been aware of general fatigue, nausea, and headache for two weeks. Tests revealed hyponatremia, plasma hypoosmolarity with urine hyperosmolarity, an elevated level of urine sodium excretion, and normal functions of the kidney, adrenal gland, and thyroid. These findings were compatible with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Head magnetic resonance imaging (MRI) demonstrated a pituitary tumor measuring 20 x 22 x 21 mm that pushed the pituitary stalk upward. Endocrinological evaluations suggested that the pituitary adenoma was non-functional. The pituitary adenoma was surgically removed, and histological examination revealed a biphasic appearance characterized by endocrine cells and a hemangiomatous stroma. After surgery, the patient developed pituitary hypothyroidism, pituitary adrenal insufficiency, and pituitary gonadal failure. Therefore, levothyroxine sodium, 50 µg per day, and hydrocortisone, 10 mg per day, were administered orally. Androgen depot, 250 mg every two months, was also injected intramuscularly. The hyponatremia did not recur, and the patient has done well for the last five years. The pituitary adenoma in this case showed two features: one was the cause of SIADH, and the other was a biphasic histological picture of endocrine cells with a hemangiomatous stroma.
The Tokai journal of experimental and clinical medicine 01/2011; 36(4):128-33.
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ABSTRACT: The present study aimed to clarify decision-making factors based on imaging for laparoscopic adrenalectomy (LA) or open adrenalectomy (OA) for adrenal metastasis (AM) based on our previous experience. From November 2003 to November 2006, 11 adrenalectomies were performed for AM for malignancies such as lung cancer, renal cell carcinoma (RCC) and breast cancer at Tokai University Hospital. A diagnosis of AM for these malignancies was suspected whenever a newly diagnosed adrenal mass was located, characterized by a basal computed tomography (CT) density superior to 10 Hounsfield units, strong or heterogeneous vascular enhancement following contrast injection and/or increasing size in sequential imaging studies. There was no evidence of extra-AM. The approach to surgical management using LA or OA was determined on the basis of CT and/or magnetic resonance imaging. The patients were reviewed every 2 or 3 months by physical examination and systemic CT. We analyzed the decision-making factors based on imaging for surgical management with LA or OA from the results of oncological outcome, imaging, intraoperative and pathohistological findings. In this study, 9 patients underwent 11 adrenalectomies (9 laparoscopic and 2 open procedures). Non-small cell lung cancer was the most common primary malignancy (5 adrenalectomies of 4 patients), followed by RCC (4 adrenalectomies of 4 patients) and breast cancer (2 adrenalectomies of 1 patient). The median tumor size for the LA group was 3.1±0.7 cm (range 2.1-4.3) and for the OA group, 6.1±0.8 cm (5.5 and 6.7 cm) (p=0.001). The operative time for the LA group was 127±42 min (range 90-215) and for the OA group, 224±47 min (190 and 257 min) (p=0.018). Blood loss for the LA group was 49±63 g (range 3-207) and for the OA group, 340±10 g (333 and 347 g) (p<0.001). No complications were noted and no conversion of LA to OA occurred. All 9 adrenal tumors selected for LA were removed safely without strong adhesion to the surrounding tissue. Two adrenal tumors removed by OA had a strong adhesion to the surrounding tissue. All 9 patients had complete resection, without capsular disruption and a negative margin in the pathological findings. No port-site and local recurrences occurred. No patients presented with local relapse or port-site metastasis. Disease-free survival rate for the LA group was 57% and for the OA group, 50% (p=0.661). LA is a less invasive treatment than OA for AM. However, for complete resection, OA should be selected for cases where resection by LA is difficult. Therefore, in the decision making towards the appropriate surgical management with LA or OA, it is important to closely assess pre-operative imaging. Imaging features supporting OA include no detection of fatty tissue between the tumor and proximal organs, tumors with an irregular contour, large tumors and tumors with a cystic component.
Oncology letters 11/2010; 1(6):967-971. · 0.11 Impact Factor
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ABSTRACT: Cancer metastasis is a leading cause of death in cancer patients and is a multistep process involving complex interactions between tumor and host cells. To metastasize, tumor cells must invade or migrate from the primary tumor and be transported to close or distant secondary sites. A tumor cell should successfully accomplish each step of the pathway or metastasis may not develop. KiSS-1 is a human metastasis suppressor gene that inhibits metastasis of human melanomas and breast carcinomas without affecting tumorigenicity. KiSS-1 encodes a carboxy-terminally amidated peptide with 54 amino-acid residues. The peptide was isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor and termed 'metastin'. The literature reports metastin related to human carcinoma, such as melanoma, thyroid cancer, esophageal squamous cell carcinoma (ESCC), hepatocellular carcinoma, pancreatic carcinoma, as well as breast, ovarian, bladder and kidney cancer. These malignancies are difficult to treat and, even in early-stage cancer, a number of patients develop metastasis shortly after surgery. Studies have suggested that metastin inhibits tumor invasion or migration through focal adhesion kinase, paxillin, MAP kinase or Rho A. Additionally, metastin may be a biomarker in ESCC, pancreatic carcinoma and bladder cancer. Metastin has potential as a suitable biomarker in the identification of tumors with high metastatic potential and as a novel effective treatment modality for patients with metastasis.
Oncology letters 09/2010; 1(5):783-788. · 0.11 Impact Factor
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ABSTRACT: Nuclear genes succinate dehydrogenase B subunit and succinate dehydrogenase D subunit, which encode two mitochondrial complex II subunits, are associated with the development of familial paraganglioma (PGL). Succinate dehydrogenase B subunit gene mutation is highly associated with extraadrenal PGL and subsequent distant metastasis. We describe the case of a 29-year-old Japanese man with a 3-year history of hypertension, headache, and palpitation. Endocrinological examinations showed that the patient had elevated levels of catecholamines, and imaging studies revealed a right paraaortic PGL without distant metastases. The PGL was surgically removed. Genetic analysis of the patient showed a heterozygous thymine deletion at position 470 (c.470delT) in exon 5 of the succinate dehydrogenase B subunit gene complementary DNA. This thymine deletion changed TTG (leucine) to TGA (stop codon) at codon 157 (L157X). It remains unclear whether this mutation was associated with PGL malignancy because the patient has had no metastases for the past 3 years. It has been recently reported that L157X is associated with malignant paraaortic PGL. Thus, strict follow-up is required because this succinate dehydrogenase B subunit gene's nonsense mutation (L157X) may be related to the malignancy.
Endocrine 08/2010; 38(1):18-23. · 1.42 Impact Factor
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ABSTRACT: Functioning black adrenal adenoma (BAA) rarely causes preclinical Cushing's syndrome (CS). In the present case, a 46-year-old Japanese Peruvian woman presented with left flank pain and hypertension. Abdominal computed tomography showed that she had a 15-mm in diameter, round, left adrenal adenoma. She had no physical features of CS, such as moon face, buffalo hump, truncal obesity, or purple striae. Endocrinological examination showed that the plasma adrenocorticotropic hormone (ACTH) level was below the detectable level, despite a serum cortisol level within the normal range. A normal cortisol circadian rhythm was not present. Dexamethasone (1 mg and 8 mg) suppression testing did not decrease serum cortisol levels to the reference levels. These findings were compatible with preclinical CS. The left adrenal adenoma was laparoscopically removed. Examination of the surgical specimen revealed unilateral double adrenal adenomas of the left adrenal gland, one of which was a BAA. The BAA measured 20 × 11 × 10 mm. Microscopically, the BAA showed proliferation of compact cells containing numerous brown-pigmented granules. There were also foci of myelolipomatous degenerative changes in the tumor. The compact cell zones remained in the adrenal cortex adjacent to the BAA showed atrophic change. These findings indicated that BAA appeared to have caused preclinical CS in this patient.
The Tokai journal of experimental and clinical medicine 01/2010; 35(2):57-61.
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Haruhiro Sato
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ABSTRACT: A 34-year-old Japanese woman was referred to the hospital because of general fatigue and palpitations. She was diagnosed as having resistance to thyroid hormone (RTH) and Hashimoto's thyroiditis at the age of 28. She felt general fatigue, palpitations, heat intolerance, and sweating for 6 months. Thyroid function tests demonstrated elevated levels of free triidothyronine (T3) and free thyroxine (T4) that were above detectable ranges and a completely suppressed level of TSH that was below the detectable range. Titers of anti-TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb) were positive. A 20-minute Technetium-m99 pertechnetate thyroid uptake imaging study showed an elevated value of 39.53% and a normal-shaped thyroid gland. These results indicated that Graves' disease (GD) caused primary hyperthyroidism. Pituitary and peripheral tissues responded to the presence of excess thyroid hormone in the patient. Oral administration of methimazole was started and continued for 1 year 10 months, after which it was ceased. Two years after the cessation of methimazole treatment, level of free T4 was elevated compared to reference range, but levels of TSH and free T3 were within normal reference ranges. Titers of TRAb and TSAb remained negative for 2 years. These findings indicated that the patient's GD was in remission. In conclusion, it is difficult to make a differential diagnosis between GD with RTH and GD alone if RTH is not diagnosed before the onset of GD. An antithyroid drug is able to cause the remission of GD with RTH.
Endocrine Journal 01/2010; 57(8):687-92. · 2.03 Impact Factor
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ABSTRACT: A 56-year-old Japanese woman with adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) was admitted to hospital, where she was diagnosed as having a mediastinal tumor with ectopic ACTH production. The tumor and associated lymph node metastases were resected endoscopically, and the pathological diagnosis was atypical thymic carcinoid. Radiation therapy and administration of metyrapone, an inhibitor of 11b-hydroxylase to decrease the cortisol level, were attempted, but the levels of ACTH and cortisol were unresponsive. Bilateral adrenalectomy and hydrocortisone replacement were performed to ameliorate the patient's hypercortisolism. She subsequently developed multiple vertebral metastases, but was unwilling to undergo chemotherapy. Her condition deteriorated progressively, and she died of heart and respiratory failure 3 years and 6 months after the first admission. Immunostaining for ACTH, chromogranin A, synaptophysin, and neuron-specific enolase was positive in the carcinoid cells. Since somatostatin (SS) and SS analogues inhibit the growth of carcinoid via the SS receptor (SSTR) 2, we evaluated the expression of SSTR2 in the carcinoid cells using reverse transcription-polymerase chain reaction, and this confirmed the expression of SSTR2 in the carcinoid cells. Our experience of this patient with CS due to an ectopic ACTH-producing atypical thymic carcinoid suggests that SS analogues may be useful for treatment of carcinoid showing expression of SSTR2.
The Tokai journal of experimental and clinical medicine 01/2010; 35(2):78-84.
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ABSTRACT: Small-cell carcinoma (SCC) of neuroendocrine type is an uncommon tumor of the endometrium. No previous report has documented Cushing's syndrome due to ectopic ACTH production by SCC of the endometrium. We describe a 56-year-old Japanese woman with SCC of the endometrium and multiple lung metastases presenting as Cushing's syndrome. The patient was referred to our hospital because of general fatigue with facial and leg edema, and multiple nodular lesions in the bilateral lungs on chest X-ray examination. A physical examination revealed that the patient had moon face, buffalo hump, and truncal obesity. Endocrinological examinations confirmed ACTH-dependent Cushing's syndrome. Thoracic computed tomography imaging showed multiple nodular lesions in the bilateral lungs. Abdominal magnetic resonance imaging suggested a malignant tumor of the uterus. The patient received a lung tumor biopsy and surgical hysterectomy. The endometrial carcinoma was histologically a SCC admixed with endometrioid adenocarcinoma. The SCC of the endometrium showed immunoreactivity for pro-opiomelanocortin, ACTH, and vimentin, but not for thyroid transcription factor-1. The lung biopsy specimen had the same features. These findings indicated that the SCC originated from the endometrium, and the ectopic ACTH-producing tumor caused Cushing's syndrome. This study provides the evidence that SCC of endometrial origin was an ectopic ACTH-producing tumor causing Cushing's syndrome.
Endocrine Journal 10/2009; 57(1):31-8. · 2.03 Impact Factor
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ABSTRACT: We report a 44-year-old Japanese man who showed a reversible blunted response of growth hormone (GH) to GH-releasing hormone (GRH) stimulation test and reversible chronic thyroiditis accompanied by isolated ACTH deficiency. He was admitted to our hospital because of severe general malaise, hypotension, and hypoglycemia. He showed repeated attacks of hypoglycemia, and his serum sodium level gradually decreased. Finally, he was referred to the endocrinology division, where his adrenocorticotropic hormone (ACTH) and cortisol values were found to be low, and his GH level was slightly elevated. An increased value of thyroid stimulating hormone (TSH) and decreased values of free triidothyronine and free thyroxine were observed along with anti-thyroglobulin antibody, suggesting chronic thyroiditis. Pituitary stimulation tests revealed a blunted response of ACTH and cortisol to corticotropin-releasing hormone, and a blunted response of GH to GRH. Hydrocortisone replacement was then started, and this improved the patient's general condition. His hypothyroid state gradually ameliorated and his titer of anti-thyroglobulin antibody decreased to the normal range. Pituitary function was re-evaluated with GRH stimulation test under a maintenance dose of 20 mg/day hydrocortisone and showed a normal response of GH to GRH. It is suggested that re-evaluation of pituitary and thyroid function is useful for diagnosing isolated ACTH deficiency after starting a maintenance dose of hydrocortisone in order to avoid unnecessary replacement of thyroid hormone.
The Tokai journal of experimental and clinical medicine 01/2009; 34(2):34-8.
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ABSTRACT: Currently there are various discussions on the upper limit of FPG (Fasting Plasma Glucose) levels. In Japan, when abnormal levels of FPG are detected at general health checkups or complete physical examinations, 75g Oral Glucose Tolerance Tests (75g OGTT) are often conducted in follow-up examinations. Therefore we investigated the appropriate upper limit of FPG levels to decide whether 75g OGTT are actually necessary.
Based on the FPG levels of 256,309 women with an age range of 20 to 79, we established the upper limits of FPG levels by 5-year intervals, using a method equivalent to the National Committee for Clinical Laboratory Standards (NCCLS) used in the U. S. [4]. We also obtained the ROC curve from the 75g OGTT results from 160 women aged 20 to 39. We then divided those 160 women into four categories based on their 75g OGTT results, and compared the abnormal rates of their 2-hour post-75g OGTT glucose levels, HOMA-R and Insulin Index using the Kruskal-Wallis test.
The upper limits of FPG levels were 99 mg/dl in the 20-29 age range, 101 mg/dl in the 30-34 age range, and 104 mg/dl in the 35-39 age range. The upper limits of the FPG reference intervals increased almost proportionally up to the age 50, and showed little difference thereafter. The point on the ROC curve where the total value of sensitivity plus specificity reached the highest had an FPG level of 99.5 mg/dl. For 2-hour post-75g OGTT glucose levels and HOMA-R, there was a significant difference in abnormal rates between the categories of FPG ≤ 99 mg/dl and 100 ≤ FPG ≤ 109 mg/dl, but not in Insulin Index.
We believe that 75g OGTT are necessary for Japanese women aged 20 to 39 with FPG levels of 100 mg/dl or above.
The Tokai journal of experimental and clinical medicine 01/2009; 34(1):15-20.
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ABSTRACT: We describe a 59-year-old Japanese woman with post-parathyroidectomy transient thyrotoxicosis and atrial fibrillation. She underwent parathyroidectomy for secondary hyperparathyroidism due to chronic renal failure. Three days after surgery, she complained of palpitation and chest pain due to atrial fibrillation. Results of thyroid function tests were compatible with thyrotoxicosis. Twelve days after parathyroidectomy, the elevated level of free thyroxine decreased spontaneously to the normal range. These features were compatible with post-parathyroidectomy transient thyrotoxicosis. No further recurrences of thyrotoxicosis or atrial fibrillation were observed for one year. This is the first report of atrial fibrillation induced by post-parathyroidectomy transient thyrotoxicosis.
Internal Medicine 02/2008; 47(20):1807-11. · 0.94 Impact Factor
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ABSTRACT: Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of variable tissue hyporesponsiveness to thyroid hormone (TH). Its characteristics are a high level of TH and inappropriate lack of TSH suppression. RTH is mainly categorized as generalized RTH (GRTH), pituitary RTH (PRTH), and peripheral tissue RTH (PTRTH). Untreated subjects with GRTH usually achieve a normal metabolic state. We describe a 21-year-old Japanese woman with GRTH and coincidental chronic thyroiditis. Physical examination revealed palpable goiter, congenital alopecia on top of the head, and short stature. She showed elevated levels of free triiodothyronine (FT3) and free thyroxine (FT4), and an inappropriately normal level of TSH. Anti-thyroglobulin and anti-thyroid peroxidase antibodies were positive. A TRH stimulation test showed a normal TSH response. The patient received the standardized diagnostic protocol, administration of incremental doses of liothyronine (L-T3). The peak TSH level after the TRH stimulation test gradually decreased. The patient showed low sensitivity to TH in terms of bone metabolism, protein catabolism, lipid metabolism, and urine magnesium metabolism. Sequence analysis of the TR beta gene was performed with informed consent, and this revealed a novel heterozygous mutation at codon 347 resulting in a GGG (glycine) to GCG (alanine) substitution (G347A). The patient was diagnosed as having GRTH with chronic thyroiditis, and carrying a novel mutation, G347A, of the TR beta gene.
Endocrine Journal 01/2008; 54(5):727-32. · 2.03 Impact Factor
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ABSTRACT: Rupture of adrenal pheochromocytoma is extremely rare and can be lethal because of dramatic changes in the circulation. We describe a 58-year-old Japanese man who suffered rupture of a pheochromocytoma. The patient was referred to our hospital because of severe hypertension (256/127 mmHg) and a left adrenal tumor. T2-weighted magnetic resonance imaging showed high signal intensity in the 50-mm left adrenal tumor. Endocrinological examinations showed elevated plasma and urinary catecholamine levels. These findings suggested that the left adrenal tumor was a pheochromocytoma. Phentolamine mesilate was administered intravenously. This resulted in a decrease of the systolic blood pressure to 100 mmHg. On the third hospital day, the patient complained of left back pain, and abdominal computed tomography showed rupture of the pheochromocytoma. Pulmonary congestion and effusion, and paralytic small-intestinal ileus occurred. Blood pressure was controlled, small-intestinal decompression was done with a Miller-Abbot tube, and body water was controlled by fluid replacement. After the general condition of the patient had became stable, laparoscopic adrenalectomy was performed. Phentolamine mesilate is a useful α-adrenergic blocker. However, care is needed with its administration, because rupture of pheochromocytoma may be related to a decrease in blood pressure induced by phentolamine mesilate.
The Tokai journal of experimental and clinical medicine 01/2008; 33(3):110-5.
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ABSTRACT: Multiple endocrine neoplasia (MEN) type 2B is a rare hereditary disorder characterized by medullary thyroid carcinoma, pheochromocytoma, and neuroma. Early signs of MEN 2B are usually neuroma, gastrointestinal problems, and medullary thyroid carcinoma. Noncardiogenic pulmonary edema is rare as a presenting symptom. We report a 31-year-old male who was admitted to our hospital because of noncardiogenic pulmonary edema. He was 168 cm in height, weighed 55 kg, and had an arm span of 166 cm. No marfanoid habitus was evident, but thickened lips and tongue neuroma were present. Chronic constipation had been present since childhood, and the patient had a two-year history of untreated hypertension. Noncardiogenic pulmonary edema and toxic megacolon were noted, and abdominal computed tomography revealed bilateral adrenal tumors. Ultrasonography of the thyroid showed two mass lesions. Intubation and mechanical ventilation were performed because of severe hypoxemia. Endocrinological examinations showed high levels of serum and urinary fractionated catecholamines, serum calcitonin, serum carcinoembryonic antigen, and serum intact parathyroid hormone. It was suggested that the high level of catecholamine from pheochromocytoma had caused the pulmonary edema. RET gene analysis showed a codon 918 mutation in exon 16 resulting in an ATG (methionine) to ACG (threonine) substitution, but analysis of the patient's parents showed the wild type. Therefore, the patient was diagnosed as having de novo MEN 2B. He underwent laparoscopic bilateral adrenectomy and total thyroidectomy. However, the values of serum calcitonin and CEA did not decrease to the normal ranges. Patients with early-stage MEN 2B have distinct characteristics that can aid early detection of the disease, thus possibly allowing them to be saved.
Endocrine Journal 09/2006; 53(4):523-9. · 2.03 Impact Factor
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ABSTRACT: Resistance to thyroid hormone (RTH) is characterized by decreased tissue responsiveness to thyroid hormone, due mainly to mutation of the thyroid hormone receptor (TR) beta gene. It has been reported that serum of patients with RTH lacks autoantibodies against thyroglobulin (Tg) and thyroid peroxidase (TPO), except in rare cases where there is co-occurrence of coincidental autoimmune thyroiditis. Here we describe the five-year medical history of a Japanese woman and her father with RTH and coincidental chronic thyroiditis. The woman, aged 28 years, was referred to our hospital because of suspected hyperthyroidism. She showed a normal level of TSH and elevated levels of free triiodothyronine (FT3) and free thyroxine (FT4). Anti-Tg and anti-TPO antibodies were slightly positive. Since RTH was suspected, her parents were investigated with informed consent. Her father showed elevated levels of TSH, FT3 and FT4, and was positive for both anti-Tg antibody and anti-TPO antibody. Her mother had hypothyroidism caused by chronic thyroiditis. Sequencing of the TR beta gene showed that the patient and her father had a codon 453 mutation resulting in a CCT (proline) to ACT (threonine) substitution. The patient gradually developed emotional disturbance, and was admitted to a psychiatry ward for two months, where she was treated with lorazepam and her condition improved. Her father, on the other hand, has been doing well for five years. The patient and the father showed different clinical courses, even though they carried the same mutation of the TR beta gene. The fact that the father showed an elevated TSH level, whereas the patient did not, was thought to be due to decreased thyroid function caused by chronic thyroiditis.
Endocrine Journal 07/2006; 53(3):421-5. · 2.03 Impact Factor
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ABSTRACT: Thyroid incidentalomas are common, often less than 1.5 cm in size, and frequently benign. It is recommended that low-risk patients with incidentalomas be followed up ultrasonographically in 6 to 12 months and not be subjected to routine testing with ultrasonographically guided fine-needle aspiration biopsy (US-FNA). In patients who have nodules larger than 1.5 cm in size, a history of head and neck irradiation, a strong family history of thyroid carcinoma, or ultrasonographic findings that suggest malignancy, US-FNA should be done. A patient with hypercalcemia caused by ectopic production of parathyroid hormone in papillary thyroid carcinoma was reported. It is known that medullary thyroid carcinoma rarely shows production of adrenocorticotropic hormone or serotonin. However, ectopic hormone productive tumors in the thyroid are extremely rare.
Nippon rinsho. Japanese journal of clinical medicine 06/2004; 62(5):935-9.
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ABSTRACT: Dysadherin is a cancer-associated cell membrane glycoprotein. Its cDNA encodes 178 amino acids, including a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Dysadherin is believed to down-regulate the expression of E-cadherin, the prime mediator of cell-cell adhesion in epithelial cells, by a posttranscriptional mechanism and promote the metastasis of carcinoma cells. To evaluate the association between dysadherin expression and E-cadherin expression in thyroid carcinoma, immunostaining for dysadherin and E-cadherin was performed in 51 papillary, 10 follicular, and 31 undifferentiated carcinomas. Immunoreactivity for dysadherin, localized at cell-cell boundaries, was detected in 39 of the 51 papillary carcinomas and all 31 undifferentiated carcinomas but not in the follicular carcinomas or normal thyroid tissue controls. Dysadherin expression was significantly higher in undifferentiated carcinoma than in papillary carcinoma and follicular carcinoma and showed significant negative correlation with E-cadherin expression. The degree of dysadherin expression was significantly associated with the prognosis, occurrence of secondary undifferentiated carcinomas, size of the primary tumor, and metastasis to the regional lymph nodes and lungs. In conclusion, a process involving increased dysadherin expression may lead to an adverse clinical outcome.
Journal of Clinical Endocrinology & Metabolism 10/2003; 88(9):4407-12. · 6.50 Impact Factor
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ABSTRACT: The c-met protein, encoded by the c-met oncogene and its ligand, the hepatocellular growth factor/scatter factor, are known to be responsible for the motility and mitogenesis of epithelial cells including cancer cells. Recent studies have reported the prognostic significance of the c-met protein in malignant tumors. Papillary thyroid carcinoma, the most common histological type of thyroid carcinoma, can easily metastasize to regional lymph nodes, reflecting the activated motility and invasiveness of the carcinoma cells. We examined the expression of c-met protein in papillary thyroid carcinomas to assess its significance. Immunohistochemical staining of the c-met protein was performed on archival materials. The c-met protein was expressed in 10 cases of papillary thyroid carcinoma with recurrence, and in 5 of 10 cases without recurrence. Normal thyroids were negative for c-met protein. Expression of the c-met protein was statistically associated with recurrence of the thyroid carcinoma (p = 0.016). It is suggested that expression of the c-met protein plays a role in the recurrence of papillary thyroid carcinoma.
The Tokai journal of experimental and clinical medicine 09/2002; 27(2):43-9.
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ABSTRACT: E-cadherin, the major intercellular adhesion molecule of epithelial cells, is important in determining the architecture of sarcomas, especially those showing epithelioid features. In addition to its role in cell adhesion, #-catenin, a cadherin undercoat protein, has been shown to function as a downstream transcriptional activator of the Wnt/Wingless signaling pathway. In order to evaluate the significance of the cadherin cell adhesion system and the Wnt/Wingless signaling pathway in the morphogenesis and/or tumorigenesis of synovial sarcoma (a major type of sarcoma with epithelioid features), immunoreactivity for pan-cadherin, E-cadherin, and their undercoat proteins (!-, #- ,and %-catenins and p120) was evaluated in 15 synovial sarcomas. Immunoreactivity for pan-cadherin, E-cadherin, !-catenin, #-catenin, and p120 was observed in all 15 specimens. Immunoreactivity for pan-cadherin was stronger than that for E-cadherin. Expression of %-catenin was detected in ten specimens. Although #-catenin was observed only at the cell-cell boundaries in four specimens, it was present in the nucleus and cytoplasm and at the cell-cell boundaries in the other 11, suggesting constitutional activation of the Wnt/Wingless signaling pathway in synovial sarcoma. Direct sequencing for exon 3 of the #-catenin gene, however, revealed no mutations in any of the 15 specimens. In conclusion, other types of cadherin besides E-cadherin, together with cadherin undercoat proteins, may play a role in cell adhesion in synovial sarcoma. Furthermore, mechanisms other than mutation of exon 3 of the #-catenin gene may activate the Wnt/Wingless signaling pathway in this type of tumor.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 12/2000; 438(1):23-30. · 2.49 Impact Factor
