Biomedical subjects

Jiro Kumagai

Publications and source records attributed to Jiro Kumagai.

10 recordsLinked to original sources

PubMed2006

High Pin1 expression is associated with tumor progression in colorectal cancer.

BACKGROUND AND OBJECTIVES: Peptidyl prolyl cis-trans isomerase (Pin1) isomerizes only phosphorylated serine or threonine residues preceding proline in certain proteins and affects the protein function. Pin1 interacts with many signaling pathways, including Wnt signaling pathway that is crucial for colorectal tumorigenesis. Pin1 promotes cyclin D1 over-expression directly or through the stabilization of beta-catenin. Pin1 is over-expressed in some cancers such as prostate and breast cancers. This study aimed to determine whether Pin1 plays a role in colorectal tumorigenesis through the upregulation of beta-catenin and cyclin D1. METHODS: Immunohistochemical analyses were performed on 105 colorectal cancer tissue samples using anti-Pin1, anti-beta-catenin, and anti-cyclin D1 antibodies. We examined the relationships between Pin1 expression and clinicopathological factors, prognosis, and beta-catenin/cyclin D1 expression. RESULTS: High Pin1 expression was observed in 40 cases (38%) and positively correlated with histological type (P=0.0240), depth of invasion (P=0.0051), and staging (P=0.0027) of colorectal tumors. High Pin1 expression was also correlated with the over-expressions of both beta-catenin (P=0.0225) and cyclin D1 (P=0.0137). CONCLUSIONS: These results suggest that Pin1 plays an important role in colorectal tumorigenesis, presumably by increasing beta-catenin and cyclin D1 expressions.

Aged↗

PubMed2006

Esophageal carcinoma: evaluation with high-resolution three-dimensional constructive interference in steady state MR imaging in vitro.

PURPOSE: To determine the usefulness of high-resolution three-dimensional (3D) constructive interference in steady state (CISS) MRI for evaluating mural invasion and morphologic features in esophageal carcinomas. MATERIALS AND METHODS: Twenty-four esophageal specimens with carcinomas were studied with a 1.5-T system using a 4-cm-diameter loop coil. High-resolution 3D-CISS MR images were obtained with a field of view (FOV) of 80 mm, matrix of 256 x 256, and section thickness of 0.5 mm (voxel size of 0.05 mm(3)). 3D-CISS MR images were compared with histopathologic findings, and virtual MR endoscopic images were compared with macroscopic findings at surgery. RESULTS: 3D-CISS MR images clearly depicted the normal esophageal wall as consisting of eight layers, which correlated well with the histologic layers. In 22 of 24 esophageal carcinomas (92%), the depth of mural invasion visualized with 3D-CISS MRI correlated well with the histopathologic staging. In all 24 carcinomas (100%), virtual MR endoscopic images clearly depicted the macroscopic types of the carcinomas, including adjacent lymph node swelling. CONCLUSION: High-resolution 3D-CISS MRI has a high diagnostic accuracy for evaluating mural invasion and macroscopic findings in esophageal carcinomas, and may be applicable to preoperative histopathologic staging and morphologic evaluation.

Aged↗

PubMed2005

An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide substitution in the 5' untranslated region of the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide exchange-factor domains.

Autosomal dominant cerebellar ataxia (ADCA) is a group of heterogeneous neurodegenerative disorders. By positional cloning, we have identified the gene strongly associated with a form of degenerative ataxia (chromosome 16q22.1-linked ADCA) that clinically shows progressive pure cerebellar ataxia. Detailed examination by use of audiogram suggested that sensorineural hearing impairment may be associated with ataxia in our families. After restricting the candidate region in chromosome 16q22.1 by haplotype analysis, we found that all patients from 52 unrelated Japanese families harbor a heterozygous C-->T single-nucleotide substitution, 16 nt upstream of the putative translation initiation site of the gene for a hypothetical protein DKFZP434I216, which we have called "puratrophin-1" (Purkinje cell atrophy associated protein-1). The full-length puratrophin-1 mRNA had an open reading frame of 3,576 nt, predicted to contain important domains, including the spectrin repeat and the guanine-nucleotide exchange factor (GEF) for Rho GTPases, followed by the Dbl-homologous domain, which indicates the role of puratrophin-1 in intracellular signaling and actin dynamics at the Golgi apparatus. Puratrophin-1--normally expressed in a wide range of cells, including epithelial hair cells in the cochlea--was aggregated in Purkinje cells of the chromosome 16q22.1-linked ADCA brains. Consistent with the protein prediction data of puratrophin-1, the Golgi-apparatus membrane protein and spectrin also formed aggregates in Purkinje cells. The present study highlights the importance of the 5' untranslated region (UTR) in identification of genes of human disease, suggests that a single-nucleotide substitution in the 5' UTR could be associated with protein aggregation, and indicates that the GEF protein is associated with cerebellar degeneration in humans.

5' Untranslated Regions↗

PubMed2005

Clonality analysis for normal and cancerous colon tissues with human androgen receptor gene polymerase chain reaction.

We assessed the feasibility of clonality analysis with human androgen receptor gene polymerase chain reaction in terms of the sensitivity and specificity for normal and cancerous colonic tissues taken from fourteen informative cases selected from 22 women with colonic adenocarcinoma. Ten crypts microdissected from each 10-microm-thick cryostat sections and whole tissues were used as samples. DNA was extracted from the samples and amplified with and without prior enzyme digestion. These products were analyzed by capillary electrophoresis for clonality. Of the whole-tissue DNA, none of the normal tissues and seven (50.0%) of the cancerous tissues showed monoclonality. Of the microdissected samples, monoclonality was found in 88.4% (107/121) of normal crypts and 95.9% (117/122) of cancerous crypts. Samples composed of crypts with short and long alleles were found in eight of the 14 normal colonic mucosae, but in none of the cancerous tissues. We concluded that the sensitivity of this method is limited for both whole-tissue DNA and microdissected-tissue DNA, because monoclonality from small samples does not always indicate monoclonality of the entire lesion. The high specificity of this method, however, allows polyclonal results in whole tissues to be confirmed by additional analysis of microdissected tissues.

Adenocarcinoma↗

PubMed2004

Mucin core protein expression by colorectal mucinous carcinomas with or without mucus hyperplasia.

BACKGROUND: In the categorization of colorectal mucinous carcinomas, much attention has been paid to the amount of extracellular mucin, but little to that of intracellular mucin. Perhaps this factor would be useful in further categorization. METHODS: We estimated the amount of intracellular mucin morphologically, and classified colorectal tumors (tubular adenomas, mucinous carcinomas, and nonmucinous carcinomas) into two categories each, those with and without intracellular mucus hyperplasia. From preliminary results, we chose a range of 50% or more for the ratio of intracellular mucus to the total area of tumor cells for our definition of such hyperplasia. Then, mucin expression in the different categories was examined immunochemically with antibodies to the mucin core proteins MUC1, MUC2, MUC5AC, and MUC6. RESULTS: MUC1 expression was found in none of the 40 adenomas, 8 (17%) of the 48 mucinous carcinomas (with little difference in those with and without mucus hyperplasia), and 4 (16%) of the 25 nonmucinous carcinomas. MUC2 was found in all mucinous carcinomas. MUC5AC was found in 18 (86%) of the 21 mucinous carcinomas with mucus hyperplasia and 18 (90%) of the 20 adenomas with mucus hyperplasia, but in only 9 (33%) of the 27 mucinous carcinomas without mucus hyperplasia, 5 (20%) of the 25 nonmucinous carcinomas, and 2 (10%) of the 20 adenomas without mucus hyperplasia. CONCLUSIONS: Mucinous carcinomas with and without mucus hyperplasia may arise from adenomas with and without mucus hyperplasia, respectively. The amount of intracellular mucin may be a morphologic reflection of the origin of colorectal mucinous carcinomas.

Adenocarcinoma, Mucinous↗

PubMed2004

Liver metastasis from rectal cancer with prominent intrabile duct growth.

Intrabiliary growth of liver metastases from colorectal cancer has rarely been studied. A surgically resected case of a metastatic liver tumor with prominent intrabiliary growth derived from rectal cancer is reported. The patient was a 62-year-old man who had received a low anterior resection for rectal cancer in March 2000. He was re-admitted due to obstructive jaundice in January 2003, and was diagnosed with hepatic malignancy in segment II of the liver with an intrabiliary tumor extending from the intrahepatic bile duct of segment II to the common hepatic duct. He underwent a left hepatectomy, a partial resection of segment VI, and an extrahepatic bile duct resection with reconstruction of the biliary tract. In the resected specimen, there were whitish tumors of 3 cm and 1.5 cm in diameter in segments II and VI, respectively, and an intrabiliary tumor originating from the main tumor in segment II extended to the common hepatic duct. Both the liver tumors and the intrabiliary tumor consisted of a well- to moderately differentiated adenocarcinoma, which showed the same histological features as the rectal cancer. The immunohistochemical findings strongly supported that these tumors, including the intrabiliary growth, were liver metastasis from the rectal cancer. The intrabiliary invasion and growth of metastatic liver tumors has generally been overlooked, notwithstanding their frequently observed biological behavior. The present case is informative, and further investigation into this type of metastatic liver tumor may be warranted.

Adenocarcinoma↗

PubMed2003

Endoscopic, histological and serologic findings of gastric hyperplastic polyps after eradication of Helicobacter pylori: comparison between responder and non-responder cases.

BACKGROUND: Evidence indicates that eradication of Helicobacter pylori leads to the disappearance of hyperplastic polyps in the stomach. However, there are some exceptions. We have compared endoscopic and serologic findings of responder and non-responder cases with hyperplastic polyps to try to identify the cause(s), other than H. pylori infection, of the formation or growth of gastric hyperplastic polyps. METHODS: We retrospectively studied 33 patients whose hyperplastic polyps disappeared after eradication of H. pylori and 10 patients whose hyperplastic polyps did not disappear after eradication. The patients were examined both endoscopically and serologically before, 1-3 months after and 12-15 months after the eradication. RESULTS: The responder and non-responder groups were similar with respect to age, sex, coexisting diseases, and histologic findings. The number and maximum size of polyps tended to be larger before treatment in the non-responder group than in the responder group. The serum gastrin level was higher in the non-responder group than in the responder group before, 1-3 months after and 12-15 months after the eradication (p=0.0096, p>0.2, p=0.0014). On histologic examination, similar reductions in the degree of inflammatory cell infiltration in the gastric mucosa of the antrum and body were seen in both the responder and non-responder groups. In the non-responders, the size and numbers of the polyps regressed in 5 of the 10 patients. The score of glandular atrophy in the antrum and the serum gastrin levels in the non-regressed cases was higher than those in the regressed cases at 1-3 and 12-15 months after eradication. CONCLUSION: Persistent high gastrin levels were found in the non-responder cases with gastric hyperplastic polyps.

Adult↗

PubMed2003

Absence of either gastric or intestinal phenotype in microscopic differentiated gastric carcinomas.

Differentiated gastric carcinoma (DGC) corresponds roughly to the intestinal type of gastric carcinoma described by Laurén. It has been suggested that DGCs arise from intestinalized gastric mucosa, but recent findings regarding their mucin expression do not support this hypothesis. To evaluate the histogenetic relationship between DGCs and intestinal metaplasia, lesions that are as small as possible should be examined. Twenty-five DGCs, ranging in their greatest dimension from 0.4 to 2.7 mm, were collected and divided into two groups by size. Group A consisted of 13 lesions less than 1.4 mm across, and group B of 12 lesions 1.4 mm or more. The presence of mucin and a brush border was assessed by immunostaining with antibodies against human gastric mucin, pyloric-gland-type mucin, Muc-2 glycoprotein, and CD10 antigen, and the lesions were classified as having the gastric phenotype (G-type), intestinal phenotype (I-type), mixed gastric and intestinal phenotype (M-type), or null phenotype (N-type). Thirteen (52%) of the 25 lesions were N-type, 5 (20%) lesions were G-type, 5 (20%) were I-type, and 2 (8%) were M-type. Group A had a larger proportion of N-type lesions than B (10/13, or 77%, vs. 3/12, or 25%; p = 0.027, chi-square test for proportions). Group B had a larger proportion of G-type lesions than A (5/12, or 42%, vs. 0/13, or 0%; p = 0.033). The phenotypes of the carcinomas and their surrounding mucosa were unrelated. Therefore, DGCs may arise from gastric mucosa affected by intestinal metaplasia or not, without having either the gastric or intestinal phenotype.

Aged↗

PubMed2002

A directional electron transfer regulator based on heme-chain architecture in the small tetraheme cytochrome c from Shewanella oneidensis.

The macroscopic and microscopic redox potentials of the four hemes of the small tetraheme cytochrome c from Shewanella oneidensis were determined. The microscopic redox potentials show that the order of reduction is from hemes in the C-terminal domain (hemes 3 and 4) to the N-terminal domain (heme 1), demonstrating the polarization of the tetraheme chain during reduction. This makes heme 4 the most efficient electron delivery site. Furthermore, multi-step reduction of other redox centers through either heme 4 or heme 3 is shown to be possible. This has provided new insights into the two-electron reduction of the flavin in the homologous flavocytochrome c-fumarate reductase.

Binding Sites↗

PubMed2002

[Resection of pancreatic cancer and simultaneous lung metastasis--a case report of successful in tumor dormancy mainly by postoperative 5-fluorouracil-based chemotherapy].

A 48-year-old male patient was admitted to our institution with left hypochondralgia. Preoperative serum CEA was 504 ng/ml. Under a radiological diagnosis of simultaneous double cancer of the pancreas and lung, resection was performed. Pathological study revealed primary pancreatic cancer with lung metastasis. After the operation, serum CEA fell to 55 ng/ml. Seventeen months later, bowel obstruction occurred and serum CEA was 140 ng/ml. One course of systemic chemotherapy, using the combination of CDDP, 5-FU and Leucovorin, was successful. After another three months, however, the same clinical symptoms occurred. With no response to the prior chemotherapy regimen, surgery was undertaken and a mass at the mesentery was removed. Fifty-nine months have passed since the initial operation and the patient is free of disease, though his serum CEA is around 50 ng/ml. In conclusion, there are cases of pancreatic cancer in which tumor dormancy can be achieved by postoperative 5-FU based chemotherapy.

Antimetabolites, Antineoplastic↗