Biomedical subjects

Yasuhiro Ito

Publications and source records attributed to Yasuhiro Ito.

At least 109 records · Page 6Linked to original sources

PubMed2002

Activation of c-Src is inversely correlated with biological aggressiveness of breast carcinoma.

In order to investigate whether c-Src is involved in carcinogenesis and progression of breast carcinoma, we examined the expression of activated c-Src in tissue sections from surgically resected human breast specimens. First, we confirmed the specificity of the antibody against activated c-Src (Clone 28) using six cell lines established from human breast carcinomas by western blotting. As expected, activated c-Src was detected as a 60 kDa band in all cell lines tested. Immunofluorescence analysis demonstrated that the activated c-Src was mainly observed in cytoplasms of these cells. Then, we designed an immunohistochemical study with 73 human breast carcinoma tissues. Glandular epithelial and myoepithelial cells in normal mammary glands adjacent to carcinoma nests and infiltrating stromal cells were negative for activated c-Src. In contrast, 37 of the 73 breast carcinoma tested (50.7%) were positive for activated c-Src, and this positive staining was inversely correlated with Ki-67 labeling index (p < 0.0001), TNM stage (p < 0.0001), tumor size (p < 0.0001), an d histological grade (p = 0.0002). These results strongly suggest that the activation of c-Src would be related to the progression of breast carcinomas with low aggressiveness.

Adult↗

PubMed2002

Expression of p57/Kip2 protein in extrahepatic bile duct carcinoma and intrahepatic cholangiocellular carcinoma.

BACKGROUND: Evaluation of the biological character of carcinomas requires understanding of cell cycle regulators. P57 (Kip2) belongs to the Cip/Kip family and is known to be one of the universal negative regulators of cell cycle. METHODS: In the present study, therefore, we investigated p57 expression in 37 extrahepatic bile duct carcinomas (BDC) and 28 intrahepatic cholangiocellular carcinomas (CCC). RESULTS: The average p57 labeling index (LI) in BDC and CCC were 60.8 +/- 7.9 and 58.6 +/- 18.6, respectively, which were significantly lower (p = 0.0008 and p = 0.0408, respectively) than those in normal duct epithelia (73.1 +/- 7.9, 70.4 +/- 8.2). p57 LI was significantly lower in BDC and CCC cases with biological aggressive phenotypes such as poor differentiation (p = 0.0260 and p = 0.0069), lymph node metastasis (p = 0.0274 and p = 0.0214), high Ki-67 LI (p = 0.0164 and p = 0.0343) and cyclin D1 overexpression (p = 0.0359 and p = 0.0255). CONCLUSION: These findings suggest that decreased p57 expression is related to the increased activity of cell proliferation and also the progression of these carcinomas.

Adult↗

PubMed2002

Malignant mesothelioma of the pericardium: case reports and immunohistochemical studies including Ki-67 expression.

Pericardial malignant mesothelioma (PMM) is extremely rare compared with pleural cases of mesothelioma. We present the clinical and pathological features of three autopsy cases with PMM. All three cases showed rapid progress and died of heart failure. Detailed examination was obtained from the autopsy. Macroscopic appearances of each case showed a thickened pericardium due to tumor invasion. Microscopic observations of all cases led to a diagnosis of epithelial-type malignant mesothelioma (MM). The results of immunohistochemical examinations were similar to the previous published work on pleural mesothelioma. To disclose the pathological characteristics of PMM, we analyzed Ki-67 labeling index (LI) of three cases of PMM and five cases of pleural MM that died within 2 years. The difference of Ki-67 LI between PMM and pleural MM was not significant (P > 0.05). The poor prognosis of patients with PMM must be caused by restricted cardiac wall motion due to tumor involvement, in addition to the tumor proliferation itself.

Adult↗

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

Expression of the G2-M modulators in pancreatic adenocarcinoma.

BACKGROUND: Cell-proliferating activity is one of the prominent parameters for evaluating the biological aggressiveness of carcinomas. Pancreatic adenocarcinoma has been studied to identify modulators of the G1-S boundary. In the present study we investigated the modulators of another important checkpoint, the G2-M checkpoint. METHODS: We immunohistochemically studied three representative G2-M modulators, cdc2, cyclin A and cyclin B1 in 62 pancreatic adenocarcinomas and 7 cystadenomas. RESULTS: Overexpression of cdc2, cyclin A and cyclin B1, was observed in 54.8, 54.9 and 56.4%, respectively, of the pancreatic adenocarcinomas. cdc2 overexpression was directly related to lymph node metastasis, Ki-67 labeling index (LI), and cyclin A overexpression which was significantly linked to the stage, carcinoma differentiation, tumor size, and lymphatic invasion. On the other hand, cyclin B1 was not linked to clinicopathological parameters including Ki-67 LI and cdc2 overexpression, except for tumor size. CONCLUSION: The findings suggest that cdc2 and cyclin A play a role in the progression of pancreatic adenocarcinoma, while the clinical significance of cyclin B1 remains to be clarified because of its more random expression.

Adenocarcinoma↗

PubMed2002

OsRALyase1, a putative F-box protein identified in rice, Oryza sativa, with enzyme activity identical to that of wheat RALyase.

A rice gene, OsRALyase1, encoding a product similar to wheat ribosomal RNA apurinic site specific lyase (RALyase), was isolated and expressed in vitro. An open reading frame of the gene predicted a protein of 476 amino acid residues with 75% identity to RALyase and contained an F-box-like motif in its amino terminal region. The rice gene product expressed in a wheat-germ protein expression system had the same characteristics as its wheat counterpart, cleaving a specific depurinated site of the 28S rRNA sarcin-ricin domain.

Amino Acid Motifs↗

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↗

PubMed2001

Expression of Heparin-Binding Epidermal Growth Factor-like Growth Factor in Pancreatic Adenocarcinoma.

Heparin-binding epidermal growth factor-likegrowth factor (HB-EGF) belongs to the EGF familyand was originally identified in the conditionedmedium of a human histiotic lymphoma cell line, U937 (1). This protein is synthesized as a preproformof 208 amino acids (2), is expressed as amembrane-anchored HB-EGF, and is released as asoluble form of 87 amino acids after being processedby protease (1,2). HB-EGF binds to the EGF receptor(EGF-R) in competition with EGF (3), and exogenoussoluble HB-EGF is known to stimulateDNA synthesis in primary rat hepatocytes in a dosedependentmanner (4).

Journal Article↗

PubMedDate not supplied

Fatal delayed esophageal rupture following aortic clamping for treatment of Stanford type B dissection.

A 65-year-old man underwent a thromboexclusion operation for management of chronic Stanford type B dissecting aneurysm in 1991. However, long-term follow-up CT scans after the operation revealed that the ascending aorta gradually enlarged and was eventually complicated by recurrent aortic dissection. The patient complained of frequent bloody sputum, whereas chest roentogenography showed no pulmonary abnormalities. Subsequent swallow esophagogram demonstrated that the upper esophagus was deviated to the right and the middle esophagus was greatly compressed by the aortic clamp. Esophageal endoscopy showed a bloody inner surface and marked swelling of the middle esophagus. The patient eventually died of massive hematemesis in 2001. We describe the imaging features of unanticipated complications such as recurrent dissecting aneurysm or impending esophageal rupture. Furthermore, we discuss the cause of hematemesis and document that the aortic clamp migrated and resulted in development of a recurrent aneurysmal dissection, which in turn resulted in esophageal rupture with aneurysmal disruption.

Aortic Dissection↗

PubMedDate not supplied

Ets-2 overexpression contributes to progression of pancreatic adenocarcinoma.

Ets-2, a transcriptional factor, has been linked to carcinoma progression but in-depth studies on its expression in human carcinoma have not been done. The present study investigated ets-2 expression in pancreatic adenocarcinoma. The ets-2 labeling index (LI) in normal pancreatic duct and pancreatic adenocarcinoma averaged 33.1+/-8.4 and 43.1+/-18.6, respectively. No statistical significance was found between the LI of normal duct and that of carcinoma with low biological aggressiveness. However, in cases with highly aggressive phenotypes such as stage IV, moderate or poor differentiation, lymph node metastasis, larger size, vascular invasion, lymphatic invasion, perineural invasion, retropancreatic invasion and capsular invasion, the ets-2 LI was significantly higher than in normal ducts and in cases with lower biological aggressiveness. Also, ets-2 transfected pancreatic carcinoma cells, when injected into athymic mice caused the formation of large tumors. These results suggest that ets-2 plays a role in the progression of pancreatic adenocarcinoma predominantly in the late phase.

Adenocarcinoma↗

PubMedDate not supplied

Expression of ets-1 and ets-2 in colonic neoplasms.

BACKGROUND: Investigation of transcription regulators in carcinoma can contribute greatly to clarifying the biological character of the carcinoma. In this study, we examined the expression of ets-1 and ets-2, prominent transcription regulators belonging to the ets family, in various colonic tissues. MATERIALS AND METHODS: We investigated the expression of ets-1 and ets-2 in normal colon, hyperplastic polyps, adenomas, carcinoma-in-adenoma and colonic adenocarcinomas by means of immunohistochemistry. RESULTS: Expression of ets-1 and ets-2 was not observed in normal colon and hyperplastic polyp. The ets-1 labeling index significantly increased with the successive events of colonic carcinogenesis. A similar tendency was observed for ets-2 expression in colonic neoplasms. In adenocarcinoma, ets-1 and ets-2 expression was directly linked to lymph node metastasis. CONCLUSION: These results suggest that ets-1 and ets-2 may act as transcription regulators of the genes related to colonic carcinogenesis and the progression of colonic adenocarcinoma.

Adenocarcinoma↗

PubMedDate not supplied

Linkage of elevated ets-2 expression to hepatocarcinogenesis.

BACKGROUND: Previous studies have shown that ets-2, a transcription factor, is linked to carcinoma progression. In the present study, we investigated the expression and clinical significance of ets-2 in hepatocellular carcinoma (HCC) and malignant transformation of the liver. MATERIALS AND METHODS: The expression of ets-2 was immunohistochemically investigated with 91 HCC, 46 noncancerous lesions, 8 atypical adenomatous hyperplasias and 14 normal liver controls. RESULTS: The ets-2 labeling index (LI) in normal liver was significantly lower than in noncancerous lesion (p<0.0001). The LI in atypical adenomatous hyperplasia tended to be higher than in noncancerous lesion (p=.0779). In HCC, the LI was significantly lower (p<0.0001) than that in noncancerous lesion and atypical adenomatous hyperplasia. In HCC, the ets-2 expression level was significantly lower in cases with advanced stage (p=0.0085), large size (p=0.0441), high proliferating activity (p<0.0001), poor differentiation (p=0.0005), the presence of portal invasion (p=0.0009) and intrahepatic metastasis (p=0.0236) and shorter disease-free survival (p=0.0372). CONCLUSION: These findings suggest that ets-2 plays an important role predominantly in malignant transformation of the liver.

Carcinoma, Hepatocellular↗

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↗

PubMedDate not supplied

Decreased expression of cyclin G2 is significantly linked to the malignant transformation of papillary carcinoma of the thyroid.

BACKGROUND: Cyclin G2 is a novel cyclin negatively regulating the cell cycle progression, contrary to the characteristics of conventional cyclins. However, little is known about the cyclin G2 expression in human carcinomas. We thus investigated cyclin G2 expression in human thyroid neoplasms. MATERIALS AND METHODS: We immunohistochemically examined cyclin G2 expression in 40 normal thyroids and 80 thyroid neoplasms. RESULTS: Normal thyroids expressed cyclin G2 in more than 5% of follicular cells. Of 30 papillary carcinomas including 6 microcarcinoma, cyclin G2 expression was not, or only occasionally, observed in carcinoma cells, indicating its expression decreased in all these cases. On the other hand, in 16 of the 24 follicular adenomas (66.7%) and 5 of the 23 follicular carcinomas (21.7%), cyclin G2 expression was retained (more than 5% of neoplastic cells were positive), and adenomas more frequently (p = 0.0032) retained cyclin G2 expression than carcinomas. CONCLUSION: Our results suggest that lack of cyclin G2 plays an important role in the malignant transformation of papillary carcinoma. Also, it may play an adjuvant role in the transformation of follicular adenoma to carcinoma. This is the first study of the expression of cyclin G2, a novel cyclin having a role opposite to that of conventional cyclins, in human carcinoma.

Carcinoma↗

PubMedDate not supplied

Jun activation domain-binding protein 1 expression in malignant lymphoma of the thyroid: its linkage to degree of malignancy and p27 expression.

BACKGROUND: Jab1 (Jun activation domain-binding protein 1) is known as a coactivator of the AP1 transcription factor, which contributes to carcinoma progression by degrading the p27/Kip1 protein. To date, the clinical significance of jab1 in human carcinoma, including malignant lymphoma, has not been studied in depth. In this study, we investigated jab1 expression in malignant lymphoma of the thyroid. MATERIALS AND METHODS: We immunohistochemically studied jab1 expression for 50 cases of thyroid lymphoma, as well as 10 cases of chronic thyroiditis. RESULTS: Although jab1 was only occasionally expressed in follicular cells in normal follicules, it was diffusely positive in those forming small follicules typical of chronic thyroiditis and malignant lymphoma. In infiltrating lymphocytes in chronic thyroiditis, jab1 was not overexpressed. On the other hand, in malignant lymphomas, jab1 overexpression was observed in 24 cases (48.0%). It was directly linked to MIB-1 labeling index (p < 0.0001), grade of malignancy (p = 0.0130) and aberrant p53 expression (p = 0.0145). Furthermore, an inverse relationship was observed between jab1 and p27 overexpression (p = 0.0130). CONCLUSION: These results suggest that: 1) jab1 plays a role in the regenerating of follicular cells attacked by lymphocytes in chronic thyroiditis and malignant lymphoma, and 2) jab1 contributes to the progression of malignant lymphoma especially with aggressive phenotypes, possibly by degrading p27.

COP9 Signalosome Complex↗

PubMedDate not supplied

Decreased expression of p107 is correlated with anaplastic transformation in papillary carcinoma of the thyroid.

BACKGROUND: Previous studies have demonstrated that two members of the Rb family, pRb and p130, are expressed in thyroid neoplasms. However, our knowledge about the expression and physiological role of the third member of this family, p107, remains poor. We therefore investigated p107 expression in various thyroid neoplasms. MATERIALS AND METHODS: We immunohistochemically investigated p107 expression in 16 anaplastic carcinomas, 50 papillary carcinomas, 15 follicular carcinomas and 17 follicular adenomas using a rabbit polyclonal antibody against p107. RESULTS: Normal follicular cells only occasionally expressed p107. In papillary carcinoma, p107 was positive in 84.0% of the cases, regardless of various biological characteristics. Follicular carcinoma less frequently expressed p107 than follicular adenoma (p = 0.0278). Furthermore, only 12.5% of anaplastic carcinomas were p107-positive and the incidence was significantly less than that in papillary carcinoma (p < 0.0001). CONCLUSION: Our findings suggest that p107 plays a constitutive role in the progression of papillary carcinoma and that decreased p107 expression may contribute to the transformation from follicular adenoma to follicular carcinoma and anaplastic transformation.

Carcinoma↗

PubMedDate not supplied

Polo-like kinase 1 (PLK1) expression is associated with cell proliferative activity and cdc2 expression in malignant lymphoma of the thyroid.

BACKGROUND: Polo-like kinase 1 (PLK1) is one of the serine threonine kinases that plays a role in cellular proliferation by activating the CDC25C-CDK1 (cdc2) loop. We recently demonstrated that cdc2 expression is associated with the biological aggressiveness of malignant lymphoma of the thyroid. In this study, we investigated PLK1 expression in thyroid lymphoma in order to elucidate its physiological significance in this disease. MATERIALS AND METHODS: We immunohistochemically investigated PLK1 expression in 46 cases of thyroid lymphoma and 10 cases of chronic thyroiditis. RESULTS: Normal follicular cells did not express PLK1, whereas follicular cells in those in chronic thyroiditis and malignant lymphoma demonstrated a high level of PLK1 expression. In lymphocytes in chronic thyroiditis with strong lymphocyte infiltration, PLK1 was weakly expressed. In malignant lymphoma, PLK1 expression was observed in all cases, but PLK1 was more strongly expressed in cases with high cell proliferative activity and with cdc2 expression. CONCLUSION: These results suggest that PLK1 regulates the cell cycle progression of thyroid lymphoma cells in the G2-M-phase.

CDC2 Protein Kinase↗