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Tetsuro Ishikawa

Publications and source records attributed to Tetsuro Ishikawa.

At least 37 records · Page 2Linked to original sources

Carcinoid tumor of the kidney presenting as a large abdominal mass: report of a case.

Carcinoid tumors are known to occur frequently in the gastrointestinal tract and they can develop in nearly every organ system. However, a carcinoid tumor of the kidney is an extremely rare entity and only 38 cases have been reported in the English literature. We herein describe the 39th case of primary renal carcinoid tumor, found in a young Japanese woman 2 months after delivery. The pathologic similarities of our case with those of previously reported cases are briefly reviewed together with some aspects of clinical features and prognostic factors of this rare disease.

Adult↗

Tumor-forming idiopathic retroperitoneal fibrosis: report of a case.

Idiopathic retroperitoneal fibrosis (IRF) is characterized by the progressive proliferation of connective tissue, but it rarely results in the formation of a mass. Herein, we report a rare case of tumor-forming IRF. A 76-year-old woman was referred to our hospital after a tumor in the right retroperitoneum was found by ultrasonography and computed tomography. Magnetic resonance imaging showed a 5 x 8 x 5-cm irregularly shaped tumor, lying adjacent to the right kidney, with a high-intensity T1-weighted image and a high-intensity T2-weighted image. Hormonal levels were within normal limits. Surgery was performed because of the possibility of an adrenal cancer. The tumor was firm, measured 7 x 8 x 4 cm, and weighed 115 g. The pathological diagnosis was retroperitoneal fibrosis. It is very difficult to distinguish tumor-forming IRF from malignancy. Several examinations, including needle aspiration cytology and biopsy, are necessary for the diagnosis and treatment of this disease.

Adrenal Gland Neoplasms↗

Telomerase activation and expression of its catalytic subunits in benign and malignant tumors of the parathyroid.

PURPOSE: Telomerase activity (TA) has been extensively studied in tumors of many organs, but not the parathyroid gland. Therefore, we investigated TA in parathyroid tumors, and examined the mRNA expression of its catalytic subunits. METHODS: We examined 17 single adenomas, one hyperplastic parathyroid gland, and one metastatic parathyroid cancer and quantified TA by fluorescence-based TRAP analysis. We also studied the expression of telomerase catalytic subunits in nine adenomas and one cancer by reverse transcription - polymerase chain reaction (RT-PCR) analysis. RESULTS: Telomerase activity was not detected in any of the adenomas or the hyperplastic gland; however, the metastatic cancer was highly positive for TA. Both human telomerase RNA ( hTR) and human telomerase-associated pretein (hTEP-1) mRNA were detected universally in every specimen tested. Conversely, human telomerase reverse transcriptase (hTERT) mRNA was not detected by the conventional electrophoresis-based technique. Faint expression of hTERT mRNA was detected by real-time RT-PCR only in the sample of parathyroid cancer. DISCUSSION: We hypothesize that TA plays a role in the malignant transformation of parathyroid disease and suggest that hTERT mRNA expression could be the key step for TA as in other malignancies. Telomerase activity and hTERT may be useful molecular targets of parathyroid cancer.

Adenoma↗

Lipoprotein lipase activator NO-1886 improves fatty liver caused by high-fat feeding in streptozotocin-induced diabetic rats.

NO-1886 is a lipoprotein lipase (LPL) activator. Administration of NO-1886 results in an increase in plasma high-density lipoprotein cholesterol (HDL-C) and a decrease in plasma triglyceride (TG) levels. The aim of this study was to ascertain whether NO-1886 improves fatty liver caused by high-fat feeding in streptozotocin (STZ)-induced diabetic rats. Administration of NO-1886 resulted in increased plasma HDL-C levels and decreased TG levels without affecting total cholesterol and glucose levels in the diabetic rats. NO-1886 dose-dependently decreased liver TG contents and cholesterol contents, resulting in improvement of fatty liver. NO-1886 also reduced plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that accompany fatty liver. The liver cholesterol contents were inversely correlated with plasma HDL-C levels (r = -0.5862, P <.001) and were positively correlated with plasma TG levels (r = 0.4083, P <.003). The liver TG contents were inversely correlated with plasma HDL-C levels (r = -0.6195, P <.001) and were positively correlated with plasma TG levels (r = 0.5837, P <.001). There was no correlation between plasma cholesterol levels, and cholesterol and TG contents in liver. These results indicate that reducing plasma TG levels and elevating in HDL-C levels may result in improving fatty liver.

Alanine Transaminase↗

Change in von Willebrand factor and carotid intima-media thickness in hypothyroid patients with normal thyroid function after levothyroxine replacement therapy.

OBJECTIVE: This study examined whether levothyroxine (L-T4) replacement might affect serum markers of endothelium injury, including von Willebrand factor (vWF), factor VIII activity and thrombomodulin (TM), during normalization of increased intima-media thickness (IMT) in the common carotid artery (CCA) in hypothyroid patients after L-T4 replacement therapy. PATIENTS AND METHODS: Thirty-three hypothyroid patients were examined for vWF, factor VIII, TM and CCA IMT before and after 1 year of normalization of thyroid function by L-T4 replacement. CCA IMT was measured from digitized still images taken during scanning by high-resolution ultrasonography as an indicator of early atherosclerosis. RESULTS: Serum factor VIII and vWF increased significantly during 1 year of normalization of thyroid function (from 122.7+/-9.4 to 151.3+/-18.8% (P<0.05) and from 109.9+/-9.6 to 135.2+/-12.4% (P<0.005) respectively), although these values all fell within the respective normal range. Serum TM, in contrast, did not change appreciably in response to L-T4 treatment, moving from 2.57+/-0.15 to 2.74+/-0.18 ng/ml (P=0.086). During 1 year of a euthyroid state, all patients showed a significant decrease in CCA IMT (P<0.0001). Change in serum vWF, but not in factor VIII or TM, showed a positive correlation with that of CCA IMT during L-T4 replacement therapy. Furthermore, the change in serum vWF was significantly and independently associated with change in CCA IMT (r=0.490, P=0.0038). CONCLUSIONS: The present study demonstrated that the improvement of CCA IMT during L-T4 treatment might have the potential to attenuate an elevation of vWF and to attenuate vascular injury by the cardiovascular effects of thyroid hormone in hypothyroid patients.

Biomarkers↗

[A case of gastric cancer with umbilical metastasis that responded to TS-1 with low-dose cis-platinum].

An umbilical metastasis of gastric cancer is known as Sister Mary Joseph's nodule. It ordinarily indicates a poor prognosis because umbilical metastasis often develops with peritoneal dissemination. Herein, we report a case of umbilical metastasis of gastric cancer that showed good response to chemotherapy, including the oral anticancer agent TS-1. The patient was a 55-year-old man in which gastric cancer was found by upper gastrointestinal series. Physical examination revealed an umbilical nodule that had an irregular surface and a hard consistency. Ultrasonography showed a 15 x 10 mm hypoechoic mass under the umbilicus. Core needle biopsy of the umbilical mass revealed adenocarcinoma. Peritoneal dissemination was proved by diagnostic laparoscopy. Oral anticancer agent TS-1 was administered with low-dose cis-platinum. The gastric lesion and umbilical nodule showed marked response to the chemotherapy and the response continued for 20 months. The patient died of disease progression 31 months after the initiation of the treatment.

Adenocarcinoma↗

Correlation between vascular endothelial growth factor C expression and lymph node metastasis in T1 carcinoma of the colon and rectum.

PURPOSE: Vascular endothelial growth factor C (VEGF-C) is known to be associated with the development of the lymphatic vessel system. Recently, VEGF-C is thought to be correlated with lymph node metastasis in some malignant tumors. In this study, we investigated the correlation between VEGF-C expression and lymph node metastasis in early carcinoma of the colon and rectum. METHODS: Two hundred and twenty-one endoscopically biopsied specimens from patients with T1 colorectal carcinoma prior to operation were investigated by an immunohistochemical study. RESULTS: VEGF-C expression was more frequently observed in the tumors with nodal metastasis than in those without metastasis. Moreover, a multivariate analysis indicated that VEGF-C expression is an independent predictor of lymph node metastasis. CONCLUSION: VEGF-C staining using endoscopically biopsied specimens prior to operation could be of use in the prediction of lymph node metastasis and in preoperative selection of treatment in patients with T1 colorectal carcinoma.

Adult↗

Decrease in carotid intima-media thickness in hypothyroid patients after normalization of thyroid function.

OBJECTIVE: This case-control study was carried out to assess whether levothyroxine (L-T4) replacement might cause regression of the enhanced atherosclerosis seen in hypothyroid patients. PATIENTS AND METHODS: Intima-media thickness (IMT) in the common carotid artery (CCA) was measured from digitalized still images taken during scanning by high-resolution ultrasonography as an indicator of early atherosclerosis. Thirty-five hypothyroid patients were examined for their CCA IMT before and 1 year after normalization of thyroid function by L-T4 replacement. As control, 35 healthy subjects were enrolled from among the participants in a local health-check programme conducted at the Osaka City University Hospital. RESULTS: Basal CCA IMT was significantly higher in hypothyroid patients [0.635 +/- 0.018 (mean +/- SE) mm] than in control subjects (0.559 +/- 0.021 mm, P < 0.005). After 1 year of euthyroidism, 34 out of 35 patients showed a significant decrease of CCA IMT, to 0.552 +/- 0.015 mm (P < 0.0001), a level comparable to normal controls. CCA IMT change was closely associated with basal levels of total cholesterol (r = -0.472, P= 0.0031), low-density lipoprotein (LDL) cholesterol (r = -0.441, P= 0.0076) and the total/HDL cholesterol ratio (r =-0.435, P= 0.0057), but not with any of the other variables measured except for age (r = -0.353, P= 0.0296). CONCLUSIONS: This study demonstrated that L-T4 treatment might have the potential to reverse the progression of atherosclerosis in hypothyroid patients. Furthermore, it suggests that increased levels of LDL cholesterol and the total/HDL cholesterol ratio have an important role in the increased common carotid intima-media thickness in hypothyroid patients.

Carotid Artery Diseases↗

Identification of a trypsinogen activity stimulating factor produced by pancreatic cancer cells: its role in tumor invasion and metastasis.

Trypsinogen/trypsin is one of the major serine proteases and is produced by pancreatic acinar cells. Tumor-associated trypsinogen (TAT) has been reported to be produced by several cancer cell lines. The biological roles and activation mechanisms of both TAT and pancreatic acinar trypsinogen (PAT) have not been elucidated in the context of cancer extension, in particular at the stage of invasion and metastasis. In this study, we investigate the roles played by PAT and TAT in pancreatic cancer invasion. In addition, we determined their mechanisms of activation and identified a trypsinogen activity-stimulating factor (TASF) produced by pancreatic cancer cells. TAT expression and high TAT activity were associated with high invasive and liver metastatic potential in SW1990 and CAPAN-2 cells. Moreover, a trypsinogen activating effect and activity prolonging effect was observed in a mixture of these supernatants with trypsinogen. These cells revealed significantly enhanced invasiveness upon invasion assay and in the presence of PAT. TAT and PAT were activated by TASF, active u-PA, produced by pancreatic cancer cells. Activated TAT and PAT can degrade not only ECM proteins but they can also activate other latent proteases. This ECM-protease-network may form a vicious cycle, thereby promoting tumor cell invasion.

Enzyme Activators↗

Very low incidence of microsatellite instability in intraductal papillary-mucinous neoplasm of the pancreas.

Intraductal papillary-mucinous carcinoma (IPMC) of the pancreas, a new entity of pancreatic cancer with a favorable prognosis, has shown a gradual increase in the number of reported cases. Patients with high-frequency microsatellite instability (MSI-H) tumors have been shown to survive longer than those with low-frequency MSI (MSI-L) or microsatellite stable (MSS) tumors in colorectal and gastric cancer. We investigated whether MSI-H in patients with IPMC can contribute to a good prognosis. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from 10 patients with IPMCs and 16 with intraductal papillary-mucinous adenomas (IPMAs) were provided for DNA extraction after microdissection. Polymerase chain reaction (PCR) was carried out using 8 microsatellite primer marker sets. The mixed PCR samples were analyzed using a genetic analyzer. MSI-H was determined by assessment of microsatellite variations in 3 or more of the 8 tested markers. Immunohistochemical staining of the MSI-responsible proteins hMLH1 and hMSH2 was conducted for both the IPMC and IPMA samples. Ten percent of IPMC harbored MSI-H tumors, whereas no MSI-H tumors were detected in the IPMAs. Thirty percent of IPMC tumors and 25% of IPMA tumors showed MSI-L. All IPMCs and IPMAs showed normal expression of both hMLH1 and hMSH2. MSI-H and loss of hMLH1 and hMSH2 are very rare events in both IPMCs and IPMAs. We conclude that a good prognosis for patients with IPMC is not associated with MSI-H.

Adaptor Proteins, Signal Transducing↗

Establishment and characterization of OCUT-1, an undifferentiated thyroid cancer cell line expressing high level of telomerase.

BACKGROUND & OBJECTIVES: Undifferentiated thyroid cancer is one of the most aggressive human malignancies, and the prognoses that have been reported are extremely poor. A number of studies have described the clinicopathologic features of this tumor and analyzed its biologic background to explain the extraordinarily aggressive nature of the tumor. Still the mechanism of cellular aggressiveness in undifferentiated thyroid cancer is not yet fully understood. METHODS: We established and characterized an undifferentiated thyroid cancer cell line, OCUT-1, derived from the surgical specimen obtained from a 74-year-old Japanese woman with advanced undifferentiated thyroid cancer. RESULTS: The cell line had already maintained over 100 passages and was stably cultured for more than a year. The cell line was observed to maintain not only its morphologic similarity to the primary cancer cells, but also its aggressive nature, including high proliferative activity, numerous genetic abnormalities, and cytokine production. Further, we have demonstrated the expression of telomerase activity in the cell, which could represent one of the responsible mechanisms for the cellular aggressiveness of this type of tumor. CONCLUSIONS: This cell line might be useful for further study concerning the correlation between telomerase activation and disease progression or anaplastic change in thyroid cancer.

Aged↗

Primary leiomyosarcoma of the breast: report of a case.

We describe herein a case of primary leiomyosarcoma of the breast in a 59-year-old woman. Preoperative clinical examination and cytology findings indicated a benign breast tumor, but intraoperative histopathological examination of the tumor revealed malignant spindle cells, and a modified radical mastectomy was performed. Immunohistochemical analysis subsequently confirmed a diagnosis of leiomyosarcoma. Primary leiomyosarcoma of the breast is extremely rare and difficult to diagnose before surgery because of the need for mitotic figures and immunohistochemical staining to confirm the diagnosis. When pre- and intraoperative examinations indicate the possibility of a leiomyosarcoma, an extended excision with sufficient margins should be performed to remove all of the affected tissue. A review of the literature on this unusual tumor of the breast is presented.

Breast Neoplasms↗

Thoracoscopic excision for ectopic mediastinal parathyroid tumor.

Ectopic parathyroid adenoma or hyperplasia in the mediastinum are seen in a percentage of patients with hyperparathyroidism and have generally been treated by conventional open surgery. However, due to recent improvements in the ability of diagnostic imaging such as 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy to identify these lesions, we have been obtaining favorable results from thoracoscopic excision of mediastinal parathyroid tumors. In thoracoscopic surgery, three to four trocars were inserted between the fourth and seventh ribs from a lateral approach. Based on diagnostic imaging, tumors were identified and excised by the shortest possible route. Surgery time for four consecutive patients ranged from 50 to 140 min, and hemorrhage volumes were small. No intra- or postoperative complications were observed, and the postoperative course for these patients has been uneventful. Analgesia was required only a few times for each patient. In the most recent patient, radioisotope-navigated thoracoscopic excision was performed using 99mTc-MIBI. When thoracoscopic excision was combined with radioisotope navigation, tumor identification took less time, cutting the surgery time in half and ultimately placing less stress on the patient.

Adult↗

Peroxisome proliferator-activated receptor gamma activation induces cell cycle arrest via the p53-independent pathway in human anaplastic thyroid cancer cells.

Anaplastic thyroid carcinoma is one of the most aggressive human malignancies. Outcomes of intensive multimodal therapy have been far from satisfactory. Furthermore, p53 gene dysfunction, often found in this type of cancer, is known to impair the efficacy of the therapeutic agents. Specific ligands for peroxisome proliferator activated receptor gamma (PPAR-gamma) induce growth suppression in some tumor cells. In this study, we investigated the role of PPAR-gamma in anaplastic thyroid cancer cell lines (OCUT-1, ACT-1). PPAR-gamma was expressed and functional in both cell lines. Activation of PPAR-gamma with its specific ligands, troglitazone and 15-deoxy-delta 12,14-prostaglandin J2, inhibited cell growth in a dose-dependent manner through inducing G1 cell cycle arrest. P53 protein expression differed in OCUT-1 and in ACT-1, though the levels stayed constant irrespective of ligand exposure in both cell lines. In contrast, p21 and p27 proteins were induced in a dose-dependent manner in both situations. This study showed that PPAR-gamma ligands were able to induce growth suppression in anaplastic thyroid cancer cells via a p53-independent, but p21- and p27-dependent cytostatic pathway. These tumor-suppressive effects of PPAR-gamma may provide a novel approach to the treatment of anaplastic thyroid cancer.

Cell Cycle↗

Prognostic value of microsatellite instability in resectable pancreatic cancer.

The significance of microsatellite instability (MSI) as a prognostic predictor for resectable pancreatic cancer patients was examined. Forty-six histologically confirmed pancreatic cancer patients who had undergone resection were studied. DNA was extracted from the paraffin block sections by means of the microdissection method. PCR was performed using eight microsatellite primer marker sets. The mixed PCR sample was analyzed by a genetic analyzer. The number of MSI-positive patients was eight (17.4%) as determined by assessment of microsatellite variations in three or more of the eight tested markers. Univariate analysis revealed that patients with MSI-positive tumors had significantly longer survival times than patients with MSI-negative tumors, although there were no significant differences in clinicopathological factors between the two groups (median survival term, 62 months versus 10 months, respectively; P = 0.011). According to univariate survival analysis, patients with T3/T4, N1, or M1 tumors, as classified by Union Internationale Contre le Cancer staging, had significantly shorter survival times than patients with less progressive tumors. Multivariate survival analysis indicated that MSI status had an independent predictive value (hazard ratio = 5.577; P = 0.007). The tumor-infiltrating leukocyte intensity in MSI-positive tumors was significantly larger than that in MSI-negative tumors, suggesting that MSI-positive tumors may induce stronger antitumor immunity. In conclusion, a patient with MSI-positive pancreatic cancer may have a comparatively better prognosis after resection, possibly due to intensive immunoreaction to the tumor.

Aged↗

Genetic alterations in adenoma-carcinoma sequencing of intraductal papillary-mucinous neoplasm of the pancreas.

We investigated the adenoma-carcinoma sequence in intraductal papillary-mucinous neoplasm from the aspect of genetic changes. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from patients with 16 intraductal papillary-mucinous adenoma of the pancreas (IPMA) and 10 intraductal papillary-mucinous carcinoma of the pancreas (IPMC) were provided for DNA extraction after microdissection. SSCP-DNA sequencing analysis demonstrated K-ras mutations at codon 12 in 75% of IPMA and 70% of IPMC, while those at codon 13 were observed neither in IPMA nor IPMC. There were no characteristic K-ras mutation types in IPMA and IPMC and no significant differences in incidence of K-ras mutations between the two categories. The frequencies of p53 mutations analyzed by SSCP-DNA sequencing were not high in IPMA (18.8%) and IPMC (30%), showing no significant difference between them. LOHs of APC in IPMA and IPMC were infrequent (6.3 and 20%, respectively) and showed no significant difference in incidence between the two categories. The LOH frequencies of DCC in IPMA and IPMC were 31.3 and 40%, respectively, and were not statistically different from each other. Taken together, genetic changes such as K-ras, p53, APC and DCC mutations may not be associated with adenoma-carcinoma sequence in intraductal papillary-mucinous neoplasm of pancreas.

Adenocarcinoma, Mucinous↗