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K Kawaguchi,
K Yashima,
M Koda,
A Tsutsumi,
S Kitaoka,
H Andachi, A Hosoda,
Y Kishimoto,
G Shiota,
H Ito,
Y Murawaki
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ABSTRACT: The fragile histidine triad (FHIT) gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumour suppressor gene involved in a variety of tumours, including gastric carcinomas. Recently, it has been reported that the FHIT gene may be a target of damage in some of mismatch-deficient tumours. To clarify further the role of the Fhit protein in gastric carcinogenesis, we investigated whether Fhit expression in early gastric neoplasia is associated with mismatch repair protein expression and cellular phenotype. Fhit, Mlh1 and phenotypic expression were evaluated immunohistochemically in 87 early gastric neoplasias, comprising 32 adenomas and 55 intramucosal carcinomas, resected by endoscopic mucosal resection therapy. Significant loss or reduction of Fhit expression was noted in four (12.5%) of the 32 adenomas and 21 (38.2%) of the 55 intramucosal carcinomas. The rate of abnormal Fhit expression was significantly higher in intramucosal carcinomas than in adenomas (P=0.021). Moreover, reduced Fhit expression was found to be significantly associated with loss of Mlh1 expression in early gastric neoplasia (P=0.0011). Furthermore, we also detected a significant association between reduced Fhit expression and gastric phenotype (P=0.0018). These results suggested that reduced Fhit expression occurs in the early stage of gastric carcinogenesis and could be correlated with a lack of Mlh1 expression and gastric phenotype.
British Journal of Cancer 03/2004; 90(3):672-7. · 5.04 Impact Factor
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H Andachi,
K Yashima,
M Koda,
K Kawaguchi,
A Kitamura, A Hosoda,
Y Kishimoto,
G Shiota,
H Ito,
M Makino,
N Kaibara,
H Kawasaki,
Y Murawaki
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ABSTRACT: The Fragile Histidine Triad gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumour suppressor gene involved in multiple tumour types including colorectal carcinomas. Recently, it has been reported that the Fragile Histidine Triad gene may be a target of damage in a fraction of mismatch deficient tumours. To explore this hypothesis, we analysed both Fragile histidine triad and mismatch repair protein (Msh2 and Mlh1) expression using immumohistochemical methods in 52 advanced colorectal carcinomas (19 well-, 17 moderately-, and 16 poorly-differentiated). In addition, we examined whether the Fragile histidine triad and mismatch repair protein expression correlated with p53 expression and clinicopathological findings. Significant loss or reduction of Fragile histidine triad expression was noted in 18 of the 52 (34.6%) advanced colorectal carcinomas: 2 (10.5%) well-differentiated, 3 (17.6%) moderately-differentiated, 13 (81.3%) poorly-differentiated carcinomas, the frequency being significantly higher in the latter than that in the former two (P<0.0001). Loss of mismatch repair protein (mainly, Mlh1) expression was detected in 21 of the 52 (40.4%) colorectal carcinomas. Moreover, reduced Fragile histidine triad expression was significantly associated with absence of mismatch repair protein expression in the advanced colorectal carcinomas (P<0.0001). However, the Fragile histidine triad and mismatch repair protein expression was not significantly associated with p53 expression. These results suggested that reduced Fragile histidine triad expression might be correlated with mismatch repair expression, but not with p53 expression.
British Journal of Cancer 08/2002; 87(4):441-5. · 5.04 Impact Factor
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ABSTRACT: To elucidate early molecular events related to colon carcinogenesis, we examined alterations in the expression of colon cancer-related genes such as cyclooxygenase (COX)-2, APC and c-Myc, cell proliferation and apoptosis in the background colon mucosa, and K-ras mutation at aberrant crypt foci (ACF) in the colons of azoxymethane (AOM)-treated rats 4 weeks after the first exposure to AOM. About 40 ACF/colon were induced in the colons of rats treated with AOM (Group 1); however, rats not treated with AOM (Group 2) showed no ACF formation in the colon. The level of AgNORs in the colonic mucosa was significantly higher in Group 1 than in Group 2 (P<0.01). The colonic mucosa in Group 1 looked macroscopically and histologically normal, but the proliferative activity of the mucosa of rats treated with AOM was clearly elevated. COX-2 mRNA expression was not detected in normal colonic mucosa in Group 2, but 3 out of 10 rats in Group 1 showed COX-2 mRNA expression in their colons by reverse transcription (RT)-polymerase chain reaction (PCR). There was a tendency toward an increased expression level of COX-2 in the AOM-treated group. The level of APC mRNA expression in Group 1 was significantly lower than that in Group 2 (P<0.01). Moreover, the level of c-Myc mRNA expression in Group 1 was significantly higher than that in Group 2 (P<0.01). An average of 0.034+/-0.006% apoptosis in colonic mucosa was detected in Group 1; the incidence of apoptosis in Group 2 was 0.021+/-0.005%. The difference between Groups 1 and 2 was significant (P<0.01). These results indicate that apoptosis was possibly induced to eliminate cells damaged by AOM administration. Six out of 22 (27%) ACF with 4 or more crypts showed K-ras mutations at codon 12; all mutations were G to A transitions (GGT to GAT). ACF with 1-3 crypts showed no mutations in the K-ras gene. In conclusion, AOM caused an increase in COX-2 and c-Myc mRNA expression, a decrease in APC mRNA expression, induction of apoptosis in normal-appearing colonic mucosa, and a K-ras mutation in ACF with 4 or more crypts. These findings may help to identify key targets in the early steps of colon carcinogenesis, against which drugs that would be broadly effective for chemoprevention of colon cancer could be developed.
Journal of experimental & clinical cancer research: CR 06/2002; 21(2):203-11. · 1.50 Impact Factor
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ABSTRACT: The FHIT gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene involved in multiple tumors, including esophageal carcinoma. We analyzed Fhit expression using an immunohistochemical method in invasive carcinoma, carcinoma in situ (CIS) and dysplasia, in paraffin sections of 75 esophageal squamous cell carcinomas (ESCs) to further elucidate the role of Fhit protein in esophageal carcinogenesis. In addition, we also examined whether Fhit expression correlated with p53 expression and apoptosis. Compared to adjacent normal mucosa, significant loss or reduction of Fhit expression was noted in 67 of 75 (89.3%) invasive ESCs, in 13 of 19 (68.4%) CIS lesions, and in 10 of 23 (43.5%) dysplastic lesions. There was a progressive loss or reduction of Fhit expression with progressive increases in the severity of histopathological changes (p < 0.001). However, there was no association between Fhit expression and clinicopathological findings, including tumor stage, lymph node metastasis, or overall survival. Moreover, Fhit expression was not significantly associated with p53 expression and apoptosis. These results indicate that abnormal Fhit expression is a common event in the early stage of ESC development and may occur independently of p53 expression and apoptosis mechanisms.
Oncology 01/2001; 61(3):205-11. · 2.27 Impact Factor
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ABSTRACT: A case of elastofibroma occurring in the sigmoid colon of a 69 year-old woman is reported. The woman presented for survey of her gastrointestinal tract. Colonoscopy disclosed two polyps in the sigmoid colon, one of which was clinically considered to be recurrent adenoma. Histologically, the lesion had characteristic eosinophilic fibers and globules, termed elastofibroma fibers with hematoxylin and eosin stain. In addition, these elastinophilic materials were digested by elastase. Histological evaluation confirmed the diagnosis of elastofibroma. Our case might suggest that it is the result of long-term fibrosis after previous endoscopic resection of a sigmoid colonic adenoma.
Pathology - Research and Practice 02/2000; 196(3):205-7. · 1.21 Impact Factor
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G Shiota,
M Ishida,
N Noguchi,
K Oyama,
Y Takano,
M Okubo,
S Katayama,
Y Tomie,
K Harada,
K Hori, [......],
T Suou,
T Kanbe,
K Tanaka,
K Nosaka,
O Tanida,
H Kojo,
K Miura,
H Ito,
N Kaibara,
H Kawasaki
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ABSTRACT: The presence of serum anti-p53 antibody has been reported to be associated with survival of patients with breast cancer, ovarian cancer, and hepatocellular carcinoma. To clarify prognostic significance of p53 antibody in colorectal cancer, serum p53 antibody was measured in patients with colorectal cancer. The 89 patients included 71 with colorectal cancer and 18 with colon polyp. An enzyme-linked immunosorbent assay was used to detect p53 antibodies in serum. Clinicopathological parameters such as age, sex, degree of differentiation of cancer, location of tumor, liver metastasis, stage classification, Dukes classification, CEA, CA19-9, and immunostaining of p53 and anti-p53 antibody were evaluated as prognostic factors of colorectal cancer. p53 antibody was positive in 18 of 71 (25%) with colorectal cancer, whereas it was positive in only 1 of 18 (6%) with colon polyp. The patients with p53 antibody had higher CEA and CA19-9 levels, higher positive rates of p53 protein expression in cancer cells, and higher liver metastasis rates. The p53 antibody positivity at stage classification I-IIIb/ Dukes classification A-C was significantly lower than that at stage classification IV/Dukes classification D. Overall survival in colorectal cancer patients with p53 antibody was significantly shorter than in those without p53 antibody. A Cox regression analysis showed that liver metastasis, stage classification, Dukes classification, CA19-9, and p53 antibody were significant prognostic factors in colorectal cancer. Serum anti-p53 antibody could serve as one of the prognostic factors in patients with colorectal cancer.
Digestive Diseases and Sciences 02/2000; 45(1):122-8. · 2.12 Impact Factor
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G Shiota,
M Ishida,
N Noguchi,
Y Takano,
K Oyama,
M Okubo,
S Katayama,
K Harada,
K Hori,
K Ashida,
Y Kishimoto, A Hosoda,
T Suou,
H Ito,
H Kawasaki
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ABSTRACT: The presence of serum p53 antibody has been reported to have prognostic significance in patients with breast and ovarian cancers. In order to clarify clinical and prognostic significance of p53 antibody in serum, we measured p53 antibody in patients with gastric cancer. Twenty-five patients with gastric cancer were examined as well as 9 patients with gastric polyp as controls. Eight of 25 patients (32%) with gastric cancer were positive for p53 antibody, while no patients with gastric polyp were positive in gastric polyp group (p < 0.05). The presence of p53 antibody was significantly associated with histology, liver metastasis and stage classification in gastric cancer (p < 0.05, respectively). Presence of liver metastasis, type of histology and presence of p53 antibody are independent prognostic factors (p < 0.05, respectively). The overall survival in patients with p53 antibody was significantly shorter survival than for those without antibody (p < 0.05%). These data suggest that p53 antibody serves as one of the prognostic factors in gastric cancer.
Research communications in molecular pathology and pharmacology 01/1998; 99(1):41-51.
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ABSTRACT: The present study investigated the relationship between the concentration of the reduced form of glutathione (GSH) and GSH-dependent enzyme activities in the gastric mucosa during chronic liver injury caused by carbon tetrachloride (CCl4) in rats. There were significant decreases in the mucosal GSH concentration and glutathione S-transferase (GST) activity as well as a significant increase in gamma glutamyltransferase (GGT) activity in rats exposed to CCl4 (all p < 0.001). However, no significant change was observed in glutathione peroxidase (GSH-Px) activity. A negative correlation was seen between the mucosal GSH concentration and GGT activity (p < 0.05) and a positive correlation between the GSH concentration and GST activity (p < 0.01). No correlation was noted between the GSH concentration and GSH-Px activity. Gastric mucosal damage, as evaluated by macroscopic observation and light microscopy, was more damaged in the rats exposed to CCl4 than in the control group. There was a significant correlation between histologic mucosal damage and GGT activity (p < 0.05) as well as a negative correlation between the number of macroscopic lesions and GSH and between the number of macroscopic lesions and GST (p < 0.01). From the observed abnormalities of GSH and GSH-dependent enzymes in the gastric mucosa of the rats exposed to CCl4, GSH content and the activities of GSH-dependent enzymes might play a role in the gastric mucosal defense mechanism during chronic liver injury.
Research communications in chemical pathology and pharmacology 08/1993; 81(2):209-20.
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ABSTRACT: The present study investigated the relationship between the concentration of the reduced form of glutathione (GSH) and GSH-dependent enzyme activities in the gastric mucosa during acute liver injury caused by carbon tetrachloride (CCl4) in rats. Transient decreases in glutathione S-transferase (GST) activity and in glutathione peroxidase (GSH-Px) activity was observed (p < 0.01). GSH concentration also decreased (p < 0.01) but then transiently increased (p < 0.05). Gamma-glutamyltransferase (GGT) activities in rats killed 6, 12, and 24 hr after exposure to CCl4 were all higher than in the control group (p < 0.01). There was a significant correlation between GSH concentration and GST activity (p < 0.05) and between GSH concentration and GSH-Px activity (p < 0.01). However, there was no correlation between GSH concentration and GGT activity. The gastric mucosa, as judged by light microscopy, was slightly more damaged in the rats exposed to CCl4 than in the control group. From the observed abnormalities of GSH and GSH-dependent enzymes in the gastric mucosa of the rats exposed to CCl4, changes in GSH content and GSH-related enzymes in gastric mucosa may be important in gastric protection during acute liver injury.
Research communications in chemical pathology and pharmacology 02/1993; 79(2):141-50.
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ABSTRACT: A 76-year-old female was admitted to our hospital because of anemia. Complete blood count was as follows: RBC 2.37 X 10(6)/microliters, Hb 7.7 g/dl, WBC 2,600/microliters, Plt 105 X 10(3)/microliters. A bone marrow aspirate revealed 40.8% plasmacytoid cells showing the characteristics of plasma cells by electron microscopy. Total serum protein was 5.4 g/dl. Monoclonal protein was not observed by electrophoresis. On immunoelectrophoresis, M-bow was not observed in the serum or in 50-fold concentrated urine. The plasma cells were negative for cytoplasmic IgG, M, A, E, D, kappa or lambda by immunoperoxidase studies. Although radiologic studies of the bones did not reveal destructive or punched out lesions, we diagnosed this case as a nonproducing myeloma and the patient responded to MP therapy. This case was considered interesting as regards the pathological entity of myeloma.
[RinshÅ ketsueki] The Japanese journal of clinical hematology 07/1990; 31(6):842-6.
