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Yuichi Sugisaki

Publications and source records attributed to Yuichi Sugisaki.

46 records · Page 3Linked to original sources
PubMed2002

SI-27, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity: detection with a variable-pressure scanning electron microscope.

OBJECTIVE: Degradation of basement membrane is one the of crucial steps in tumor angiogenesis and is performed by matrix metalloproteinases (MMPs). This study was designed to investigate the suppression of tumor angiogenesis by SI-27, an MMP inhibitor. METHODS: SI-27 was applied at noncytotoxic concentrations (1-100 micromol/L), and its effect on nonmitogenic vascular endothelial growth factor (VEGF)-enhanced cell motility and in vitro angiogenesis by human umbilical vein endothelial cells was determined. The activity of MMP-1, MMP-2, and tissue inhibitor of metalloproteinase 1 was determined by enzyme-linked immunosorbent assay. The effect of SI-27 on in vitro angiogenesis stimulated by supernatants of human glioma cell lines (U87MG, U251MG, and U373MG) also was examined. Angiogenesis was detected with variable vacuum scanning electron microscopy. RESULTS: Cell motility and in vitro angiogenesis by human umbilical vein endothelial cells were significantly increased by VEGF. The maximal effect on cell motility by VEGF was noted at 5 ng/ml (P < 0.001), and the maximal effect on the capillary network was observed at 10 ng/ml (P < 0.001), along with elevated MMP-1 and MMP-2 activity. Whereas SI-27 significantly suppressed VEGF-mediated in vitro angiogenesis (50 micromol/L; P < 0.001) and inactivated both MMP-1 and MMP-2, the expression of tissue inhibitor of metalloproteinase 1 and VEGF-mediated cell motility were not affected by SI-27. The angiogenesis promoted by glioma supernatants showed a significant reduction in the presence of SI-27 (10 micromol/L; U87MG, P < 0.01; U251MG, P < 0.01; U373MG, P < 0.01). CONCLUSION: SI-27 inhibited in vitro tumor angiogenesis by suppression of MMP. This agent may be anticipated to prevent tumor growth through an angiosuppressive effect.

Cell Division↗
PubMed2002

Peritubular capillary regression during the progression of experimental obstructive nephropathy.

Injury to the renal microvasculature may be a major factor contributing to the progression of renal disease. Although severe disruption of peritubular capillaries (PTC) could lead to marked tubulointerstitial scarring, elucidation of that process remains incomplete. This study investigated the morphologic changes in PTC and their likely regulation by vascular endothelial growth factor (VEGF) during the progression of tubulointerstitial injuries. Unilateral ureteral obstruction was induced in Wistar rats by ligation of the left ureter, and the kidneys were then collected at selected times. PTC lumina and the expression of VEGF and its receptor Flk-1 were immunohistochemically detected. Morphologic changes in PTC endothelial cells were examined by using Ki67 staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling, and electron-microscopic studies. In the first week of the disease period, immunohistochemical labeling of tubular VEGF intensified, with accompanying deformation and dilation of adjacent thrombomodulin (TM)-positive PTC lumina; an angiogenic response of endothelial cells was demonstrated with Ki67 and TM double-staining. During the subsequent 2 wk, tubular VEGF labeling decreased until it was virtually absent, an effect confirmed by Western blotting. Concomitantly, labeling of the VEGF receptor Flk-1 in PTC endothelial cells decreased and PTC lumina began to regress, demonstrating endothelial cell apoptosis (as detected in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling and electron-microscopic studies). By the end of week 4, the numbers of TM-positive PTC lumina were significantly decreased in areas of marked tubulointerstitial scarring. These results suggest that PTC regression, involving an early, unsustained, angiogenic response followed by progressive endothelial cell apoptosis, could be a potential factor contributing to tubulointerstitial scarring in this unilateral ureteral obstruction model.

Animals↗
PubMed2002

Expression of E-cadherin catenin and C-erbB-2 gene products in invasive ductal-type breast carcinomas.

Special attention has focused on E-cadherin and the invasiveness of breast carcinoma because E-cadherin was suggested to be the major cell adhesion molecule in the mammary gland. In the cytoplasm, E-cadherin is linked to beta-catenin and alpha-catenin which mediate the connection of the cytoskeleton. In addition, c-erbB-2 oncoprotein causes disruption of this cell adhesion system through beta-catenin phosphorylation. We investigated the expression of E-cadherin, alpha-catenin and c-erbB-2 gene products in 66 invasive ductal carcinomas by immuno-histochemistry to examine the relation between the E-cadherin mediated cell adhesion system and histological subtypes used in Japan as well as histological grading. The series included 21 papillotubular carcinomas, 16 solid-tubular carcinomas and 29 scirrhous carcinoma. There were 33 cases of grade I, 20 cases of grade II and 13 cases of grade III. We defined P&P&N as E-cadherin positive and alpha-catenin positive and c-erbB-2 negative cases to evaluate the preservation of the E-cadherin mediated cell adhesion system. There were only 13 cases (19.7%) of P&P&N in total. As for the frequency of E-cadherin/alpha-catenin/c-erbB-2 expression and P&P&N, no significant difference between histological subtypes was found. However, those in the grade I group tended to be higher than in the other two grade groups. Regarding the rates of alpha-catenin positive cases and P&P&N cases, there were significant differences between the grade I group and a combination group consisting of the grade II and grade III groups. These results suggest that the E-cadherin-mediated cell adhesion system is frequently lost in invasive ductal-type breast cancers by random loss of E-cadherin/catenins or c-erbB-2 overexpression, and that the preservation of this system correlates with well differentiated morphological features.

Breast Neoplasms↗
PubMed2002

[A clinicopathologic study of autopsy cases with myocardial infarction treated with coronary intervention (PTCA/Stenting)].

A clinicopathologic study was made in 28 patients who died after acute myocardial infarction (AMI) treated with coronary intervention (CI: Percutaneous transluminal coronary angioplasty (PTCA) or Stenting). Nineteen patients received PTCA (12 men and 7 women, 42 to 85 years of age, mean 71.4 years), and 9 patients received stenting after PTCA (8 men and 1 woman, 49 to 86 years of age, mean 67.7 years). Hemorrhagic infarction was found in 23 cases. Compared to direct PTCA, more severe hemorrhage was found in cases treated with PTCA after intracoronary thrombolytic therapy (rescue PTCA: r-PTCA). Also, severe hemorrhage in the infarct area was found in cases treated with percutaneous cardiopulmonary support (PCPS) after AMI. Hemorrhagic infarction was found even in patients treated with CI in the early phase after AMI, and also in some patients who recovered from initial heart failure after AMI. Compared to usual ischemic infarct, healing was greatly delayed in the hemorrhagic infarct area. We conclude that special care is required in the treatment of patients who received CI, because of a high possibility of hemorrhage in the infarct area after CI and the delay in healing in the hemorrhagic infarction area.

Adult↗
PubMed2002

Immunohistochemical study of CYP2E1 in hepatocellular carcinoma carcinogenesis: examination with newly prepared anti-human CYP2E1 antibody.

Cytochrome P450 2E1 (CYP2E1) is known as a heme-containing enzyme that produces abundant free radicals, and its involvement in carcinogenesis has been suggested in several organs in vivo. In this study, to clarify the involvement of CYP2E1 in liver cancer and its carcinogenesis process, we investigated the expression of CYP2E1 in 42 surgically resected or biopsied specimens of hepatocellular carcinomas (HCC) and 26 cases with other liver lesions immunohistochemically using a newly prepared anti-human CYP2E1 antibody. When intracellular CYP2E1 expression was investigated in three different regions of HCC specimens, the expression in hepatocytes of the peri-tumor region was the highest (p<0.001) compared with those in the tumor and non-peri-tumor regions. Histologically, the expression of CYP2E1 in tumor cells tended to decrease as the cells were less differentiated (p<0.0001) and was the lowest in poorly differentiated HCC (p<0.01). CYP2E1 expression was highest in the pseudo-glandular type and low in the thick trabecular and solid types of HCC (p<0.0001). In mature regenerative nodules of liver cirrhosis, adenomatous hyperplasia (AH) and atypical adenomatous hyperplasia (AAH) to early-HCC, CYP2E1 expression was notably high as compared with other legions. CYP2E1 has a strong free radical-producing ability, and the cell injury and DNA damages by the free radicals are considered to be involved in carcinogenesis. Therefore, our results suggest that the different expression of CYP2E1 in hepatocytes may play important roles in the multistep carcinogenic process and the histogenesis of hepatocellular carcinoma.

Antibodies↗
PubMed2002

Immunohistochemical, biochemical and immunoelectron microscopic analysis of antigenic proteins on neuroendocrine cell tumors using monoclonal antibody HISL-19.

The monoclonal antibody HISL-19 was originally generated after immunizing BALB/c mice with human islet cells. We used this antibody to study a wide variety of neuroendocrine (NE) and non-NE tumors by immunohistochemical, immunoelectron microscopic, and biochemical (Western blotting) techniques. Of the thyroid tumors, HISL-19 specifically immunoreacted with medullary carcinoma of the thyroid (MCT); of the pancreatic tumors, it reacted with islet cell tumors such as insulinomas and a gastrinoma; of the adrenal tumors, it reacted with pheochromocytoma. HISL-19 showed particularly strong immunoreactivity to a gross granular material at the perinuclear area in the MCT and malignant pheochromocytoma but not in the benign pheochromocytoma, although the latter cells showed a faint and homogenous positive reactivity in the cytoplasm. The strongly HISL-19-positive material was found to consist of newly synthesized antigenic proteins with a molecular weight between 60 and 65 kilodaltons (kDa) by Western blotting. Immunoelectron microscopic analysis revealed that this antigenic protein was located in the secretory granules that appear markedly in malignant endocrine tumors, usually located close to the nucleus. Thus, HISL-19 is a useful and specific marker for the immunohistochemical diagnosis of NE cell tumors. The specific antigenic proteins of HISL-19 were defined in MCT and malignant pheochromocytoma. These proteins are speculated to be actively synthesized and more highly produced in the secretory granules of malignant endocrine tumors than benign ones. Thus, a preoperative immunohistochemical study using HISL-19 might be useful for predicting the grade of malignancy of endocrine malignant tumors and thus help determine an appropriate operative procedure, in addition to being a useful marker of neuroendocrine cell tumors.

Adenoma, Islet Cell↗
PubMed2002

Expression and accumulation of lumican protein in uterine cervical cancer cells at the periphery of cancer nests.

Lumican is a member of a small leucine-rich proteoglycan (SLRP) family and is reported to be overexpressed during the wound healing process of the cornea, and ischemic and reperfused heart. In the carcinomatous tissues, lumican is overexpressed in human breast and pancreatic cancer tissues. In the present study, we aimed to clarify the expression of lumican mRNA and its protein in human cervical cancer cell lines (CaSki, ME-180 and HeLa cells) and their localization in normal and cancerous human cervical tissues. Reverse transcription-polymerase chain reaction and Western blot analysis revealed the expression of lumican mRNA and its protein in CaSki, ME-180 and HeLa cells. No or weak immunoreactivity of the lumican protein was observed in stroma but not in squamous and ductal cells of non-cancerous uterine cervical tissues. In 21 of 28 (75%) cervical cancer cases, the lumican protein was strongly expressed in cancer cells, and accumulated particularly in cancer cells at the periphery of the cancer nests. It was also expressed in the fibroblasts adjacent to the cancer cells. In situ hybridization analysis revealed that lumican mRNA was not expressed in squamous or ductal epithelial cells in non-cancerous tissues, but was expressed in most cancer cells and stromal fibroblasts in uterine cervical cancer tissues. The lumican protein was not localized in normal squamous or ductal cells close to cancer cells, but its mRNA was strongly expressed in the same cells. To our knowledge, this is the first report on lumican synthesized by squamous cell carcinomas. These findings may indicate that the accumulated lumican protein in cancer cells at the periphery of cancer nests may play roles in the growth or invasion of human cervical cancer cells.

Blotting, Western↗
PubMed2002

[An autopsy case with subacute spinal cord disease showing progressive paraplegia].

We report a 72-year-old woman who died of respitory failure. History included onset of diabetes mellitus at the age of 67 years and hypertension at the age of 72 years. The patient had been in good health otherwise until 2000, when she had onset of numbness or tingling of the bilateral lower limbs. On December 3, 2000, she was admitted to a hospital in the vicinity of her home because of the above-mentioned complaints. Neurological examinations revealed progressive paraplegia. Symptoms and signs suggested Guillain-Barré syndrome. Examinations of cerebrospinal fluids revealed cell count of 338/3 (mono 72%, poly 18%) and protein value of 100 mg/dl. Later the patient course deteriorated. On December 15, 2000, she was admitted to Hakujikai Memorial Hospital for the second time. Ten days later, MRI examination showed diffuse swelling of the spinal cord from the cervical (C 3/4) level to the thoracic level. Gd-enhanced T 1-weighted MRI performed 22 days later showed a partially enhanced lesion at the thoracic (Th 5/6) level of the spinal cord. The patient was treated with steroid therapy (methylprednisolone 500 mg/dl). She died of respiratory failure on January 6, 2001. The patient was presented in a neurological CPC. Neurological and imaging findings suggested a transverse myelopathy. However, there were several points in this case that were unusual for a typical transverse myelopathy, such as total sensory loss below spinal segments of thoracic level (Th 5) and motor weakness of the upper limbs of upper segment of the same level. A clinical neurologist concluded that the patient had subacute transverse myelopathy with fused multiple pathy pathologic lesions. We discussed whether this case was a transverse myelopathy or multiple sclerosis. Post mortem examination revealed acute necrotic myelopathy affecting the spinal cord from the second cervical to the tenth thoracic vertebrae, with conspicuous infiltration of CD 68-positive macrophages involving both gray and white matter, partially necrotic associated with scattered UCHL-1 dominants lymphocytic infiltration of T cells around vessels. There were relatively older lesions with demyelinating features in the spinal roots that were particularly dominant in the anterior roots. No demyelinated plaques in the optic chiasm, tracts and nerves, or in the cerebero-cerebellar white matter were found. Systemic pathological diagnosis was lung edema with fresh hemorrhage, pancreatic atrophy consistent with diabetes mellitus and choleductlithiasis.

Aged↗
PubMedDate not supplied

Fine needle aspiration cytology of primary epithelioid sarcoma. A report of 2 cases.

BACKGROUND: Epithelioid sarcoma is a rare soft part tumor, the cytologic features of which have not been fully elucidated to date. We describe the cytologic features in 2 cases of primary epithelioid sarcoma with samples obtained by fine needle aspiration (FNA). CASES: Case 1 was a 50-year-old male who complained of a small mass in his left palm. Case 2 was a 56-year-old female who presented with a mass on the medial aspect of her right forearm. Preoperative FNA smears in both cases showed loose, aggregated and isolated tumor cells that were round to polygonal, with eccentrically located nuclei, against a background of inflammation and necrosis. The tumor cells showed moderate atypia, irregularity in size and many mitoses. In case 1 a presumptive diagnosis of epithelioid sarcoma was made by FNA cytology, while in case 2, FNA cytology revealed a high grade sarcoma with abundant matrix mimicking osteoids, difficult to differentiate from an extraskeletal osteosarcoma. CONCLUSION: Epithelioid sarcoma may be difficult to differentiate from an extraskeletal osteosarcoma in cases with abundant hyalinized collagen on FNA cytology.

Biopsy, Fine-Needle↗