Biomedical subjects

T Minamoto

Publications and source records attributed to T Minamoto.

At least 37 records · Page 2Linked to original sources

PubMed1996

[Comparative study on biological difference between gastric cancer and colorectal cancer].

In this study, we investigated the clinico-pathologic characteristics of patients with adenocarcinoma of the stomach and those with colorectal carcinoma to compare early progression patterns of both tumors. Histologically, gastric and colorectal adenocarcinomas showed similar progression patterns, including the incidence of submucosal invasion, lymphatic infiltration and lymph node metastasis. One striking finding was in gross appearance in born tumors. In contrast to most gastric well differentiated adenocarcinoma (DTA), which showed superficial growth, colorectal DTAs mainly showed polypoid growth. However, the superficial-type colorectal DTAs invaded the submucosal layer more frequently than did polypoid DTAs and gastric DTAs. These findings indicate that superficial-type colorectal DTAs grow more rapidly and aggressively than do polypoid DTAs and gastric DTAs. In order to elucidate growth rates between gastric cancer and colorectal cancer with hepatic metastasis doubling time was measured by exponential growth of tumor marker (CEA or AFP). The doubling time of liver metastases calculated from tumor markers was 26.6 +/- 10.8 days for stomach cancer and 57.8 +/- 35.4 days for colorectal cancer; accordingly doubling time for gastric cancer was approximately half of that for colonic cancer. However, there were no other factors (age, sex, site, histologic type in stomach, tumor marker production, etc.) influencing doubling time.

Adenocarcinoma↗

PubMed1995

Mutant K-ras in apparently normal mucosa of colorectal cancer patients. Its potential as a biomarker of colorectal tumorigenesis.

BACKGROUND: The best way to reduce the incidence of colorectal cancer mortality would be to prevent this cancer. However, none of the biomarkers proposed can accurately identify persons at increased risk of colorectal cancer or those at low risk. As a possible genetic biomarker, K-ras mutations, which are frequently found in colorectal cancers, were analyzed in apparently normal colorectal mucosa. METHODS: Nonneoplastic mucosa and tumor tissues were collected at surgery from 70 patients with colorectal cancer: one sample each from 50 patients (group A) and multiple samples from the other 20 patients (group B). Mutant K-ras codon 12 was analyzed by the enriched polymerase chain reaction (EPCR), by which one mutant can be detected among 10(3) to 10(4) normal alleles. RESULTS: Only with the aid of EPCR was mutant K-ras detected in nonneoplastic mucosa of nine patients (18%) in Group A and five patients (25%) in Group B. This increased incidence could be attributed to the multiple tissue sampling. The presence of mutant K-ras in nonneoplastic mucosae was not consistently correlated with that in the tumors. These findings suggest that the mutant K-ras identified in nonneoplastic mucosa actually represents de novo mutations, which may be initiated by different etiologic factors and at different times. CONCLUSION: Mutant K-ras detected in apparently normal mucosa should be a useful biomarker for identifying persons at higher risk of colorectal cancer. Our study also emphasizes the need for improving the method for sample collection to achieve true representation of the colorectal mucosa.

Adenocarcinoma↗

PubMed1995

Frequent and characteristic K-ras activation in aberrant crypt foci of colon. Is there preference among K-ras mutants for malignant progression?

BACKGROUND: To investigate very early lesion of colorectal cancer, K-ras activation and nuclear p53 accumulation were studied in aberrant crypt focus (ACF). METHODS: ACF were microscopically identified in grossly normal mucosa of patients with colorectal cancer who underwent surgery. Each ACF was microdissected from the surgical specimen and divided into two pieces, one for histologic and immunohistochemical examinations and the other for K-ras activation. K-ras mutations in codons 12 and 13 were sequenced after being screened by polymerase chain reaction amplification followed by restriction fragment length polymorphism analysis. Intranuclear accumulation of p53 protein was immunostained with the avidin-biotin complex method. RESULTS: ACF was predominantly distributed in the sigmoid colon and rectum, and its incidence was increased with age. Unexpectedly, ACF was very rare in colons of three patients with hereditary nonpolyposis colorectal carcinoma. K-ras mutations were detected in 58% (33 of 57) of ACF cases and in 44% (11 of 25) of adenocarcinoma cases. Although GTT mutation in codon 12 was predominantly observed in adenocarcinoma (10 of 11), GAT mutation (12 of 33) was as frequent as GTT mutation (11 of 33) in ACF together with mutation at codon 13 (7 of 33). No accumulation of p53 protein was found in any ACF. CONCLUSION: ACF were not diagnosed as neoplasms histologically, but they were considered to be neoplastic lesions, and K-ras activation is one of the key events to form ACF. The G-T substitution in K-ras codon 12 may undergo malignant growth easily compared with G-A substitution in colorectal carcinogenesis.

Adenocarcinoma↗

PubMed1995

Frequent and characteristic K-ras activation and absence of p53 protein accumulation in aberrant crypt foci of the colon.

BACKGROUND/AIMS: The relationship of aberrant crypt foci (ACF) to colorectal carcinogenesis is still controversial. Histological examination and analyses of K-ras mutations and p53 gene expression were performed to characterize ACF. METHODS: ACF were identified microscopically in grossly normal colorectal mucosa. The ACF were separated into two pieces, one for histological and immunohistochemical examinations and the other for molecular analysis. K-ras mutations in codons 12 and 13 were analyzed by polymerase chain reaction amplification, followed by restriction fragment length polymorphism and sequencing analyses. Intranuclear p53 protein was immunostained by the avidin-biotin complex method. RESULTS: Histologically, elongation and apical branching of the crypts in ACF were striking. K-ras mutations were detected in 58% of ACF (33 of 57; 46% [26 of 57] in codon 12, and 12% [7 of 57] in codon 13) and in 44% of adenocarcinomas (11 of 25; all in codon 12). In ACF, GAT mutations (12 of 26) were as frequent as GTT mutations (11 of 26) in codon 12, although GTT mutations in codon 12 were predominant in adenocarcinomas (10 of 11). No accumulation of p53 protein was detected in any ACF, although it was detected in 52% (13 of 25) of the colorectal carcinomas. CONCLUSIONS: ACF do not seem histologically to be neoplasms, although genetically they are monoclonal lesions. K-ras mutation is critical in the formation of ACF, but p53 alteration could play a causal role in tumor progression.

Adult↗

PubMed1995

Sampling method as a key factor in identifying K-ras oncogene mutations in preneoplastic colorectal lesions.

The development of sensitive polymerase chain reaction (PCR)-based techniques in recent years has enabled us to verify the possible presence of mutated oncogenes and tumor suppressor genes in stages preceding tumor formation. Early detection of mutants serves as a powerful tool for detecting exposure to carcinogens and can assist in diagnosis. In studies performed in the past few years, we have identified mutant ras alleles in preneoplastic samples of patients with and without colorectal cancer. Our studies have shown (i) that mutant ras alleles are present at low incidence in normal appearing tissues of patients with colorectal cancer. Such mutations are also found in colonic effluents of patients at risk for developing this tumor type; and (ii) that the method of sampling is critical to ensure true representation of the entire colonic mucosa. The implications of identifying ras mutations in patients without evidence for neoplasma are discussed.

Biomarkers, Tumor↗

PubMed1994

Effect of docosahexaenoic acid on azoxymethane-induced colon carcinogenesis in rats.

The effect of intragastric gavage administration of docosahexaenoic acid (DHA) on azoxymethane (AOM)-induced colon carcinogenesis in rats was studied. Male F344 rats were treated s.c. with 15 mg/kg of AOM once a week for 2 weeks and were given either 0.7 ml of DHA or water intragastrically twice a week starting the day before the first carcinogen treatment. The number of crypt multiplicity (number of crypts/focus) of aberrant crypt foci (ACF) in the colon were measured after 4, 12, and 36 weeks. The numbers and average crypt multiplicities of ACF induced by AOM were significantly lower after 12 and 36 weeks in animals given DHA. DHA also reduced the incidence of spontaneous ACF in animals without carcinogen treatment. Colorectal tumor incidence and number of tumors per rat after 36 weeks were slightly, but not significantly, lower in the DHA-treated group. These results suggest that DHA slightly suppresses colon carcinogenesis, and a possibility that warrants further study.

Animals↗

PubMed1994

Infrequent K-ras activation in superficial-type (flat) colorectal adenomas and adenocarcinomas.

Clinicopathological evidence is accumulating that a superficial-type (flat) colorectal tumor is a distinct neoplastic entity. To clarify the genetic characteristics of this tumor, we investigated the K-ras gene mutations and morphological features of 43 tumors of this type. A mutation of the K-ras codon 12 was detected in only 5 (16%) of 31 adenomas and 2 (17%) of 12 adenocarcinomas. The presence or absence of this mutation was not correlated with the tumor size or stage or with histopathological findings. None of these tumors had a mutation in codon 13 or exon 2, including codon 61. This low incidence of K-ras mutations (16%) suggests that superficial-type colorectal tumors are etiologically distinct from ordinary colorectal polypoid tumors and that there may be an alternative pathway of colorectal tumorigenesis.

Adenocarcinoma↗

PubMed1994

Renal cell carcinoma producing alpha-fetoprotein (AFP) with a unique lectins-affinity profile.

Renal cell carcinoma (RCC) producing alpha-fetoprotein (AFP) is a rare entity and merely 7 cases have been reported so far. The present case, a 71-year-old woman, showed a high serum AFP level of 204 ng/ml. The RCC of the autopsied right kidney consisted mainly of spindle-shaped or bizarre sarcomatous tumor cells. AFP was immunolocalized only in the concomitant clear cell component. Concanavalin A (Con A)-nonadsorption rate of serum AFP was 42%, which was an intermediate value between those of yolk sac tumors and metastatic liver carcinomas. Lens culinalis agglutinin (LCA)-affinity study of the patient's AFP showed an unknown peak X, which was eluted between the known peaks 2 and 3. These results suggest a certain structural alteration in carbohydrate moieties of the AFP derived from this RCC. A review of the clinicopathologic features of 8 patients with AFP-producing RCC was made to understand the pathophysiology of AFP-producing neoplasms.

Aged↗

PubMed1994

Superficial-type adenomas and adenocarcinomas of the colon and rectum: a comparative morphological study.

BACKGROUND/AIMS: It has been uncertain whether colorectal carcinomas preferentially arise on preexisting adenomas or de novo. However, from a morphological viewpoint, it seems unlikely that pedunculated or exophytic malignant polyps progress to the deeply ulcerated advanced carcinomas usually found clinically. METHODS: The morphological features of 26 nonpolypoid, superficial-type colorectal tumors (17 adenomas and 9 adenocarcinomas) were compared to clarify the developmental route of colorectal carcinomas. RESULTS: The adenomas and adenocarcinomas were very similar in size and gross appearance; however, examination of the surface appearances of unsectioned tumors by dissecting microscopy was helpful for distinguishing the two. Histologically, no adenomatous tissue was found in any case of superficial-type adenocarcinoma. Five of the nine adenocarcinomas, even including those of small size, invaded the submucosal layer, and two showed lymph node metastasis. CONCLUSIONS: These findings suggest that superficial-type adenocarcinomas show rapid growth and aggressive behavior. We suggest that this type of carcinoma may not progress by the adenoma-to-carcinoma pathway but that it may arise from a very small superficial-type adenoma.

Adenocarcinoma↗

PubMed1994

Increased cell proliferation of azoxymethane-induced aberrant crypt foci of rat colon.

Aberrant crypt foci (ACF) were induced in the colon of F344 rats by s.c. injection of azoxymethane (AOM) twice in a three day-interval and examined after 4 and 12 weeks. The number and crypt multiplicity of ACF in each section of rat colon increased during this period. Histologically, aberrant crypts consisted of proliferating atypical epithelial cells. Cell proliferation of ACF consisting of 4 aberrant crypts [ACF(4)] and 2 aberrant crypts [ACF(2)], and normal crypts in the colon of rats treated with AOM [normal crypts/AOM(+)] or saline [normal crypts/AOM(-)] was investigated by measurement of the mitotic index, proliferating cell nuclear antigen-labeling index (PCNA-LI), and 5-bromo-2'-deoxyuridine-labeling index (BrdU-LI). All three parameters of the cell proliferative activity of ACF(4) were higher than those of normal crypts/AOM(+) and normal crypts/AOM(-). The PCNA-LI and BrdU-LI in ACF(2) were the same as those in ACF(4). These findings suggest that ACF have increased cell proliferative activity. The correlation of these three parameters confirmed that the PCNA-LI is also a useful parameter for evaluating cell proliferative activity in ACF. The presence of many cells stained by PCNA in the upper portion of ACF suggested that ACF have more G1 phase cells, which readily respond to mitogenic stimulation, than G0 phase cells, which are predominant in normal crypts.

Animals↗

PubMed1993

Reduction in formation and growth of 1,2-dimethylhydrazine-induced aberrant crypt foci in rat colon by docosahexaenoic acid.

The effect of intragastric gavage administration of docosahexaenoic acid (DHA) on the formation of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci in rat colon was investigated. Male F344 rats were treated three times s.c. with 20 mg/kg of DMH and were given either 0.7 ml of DHA or water intragastrically 5 times a week for 4, 8, or 12 weeks from the day before the first carcinogen treatment. The numbers of DMH-induced aberrant crypt foci per colon after 4, 8, and 12 weeks of DHA treatment were approximately 40% of those in the respective control groups, and the differences were statistically significant. The numbers of foci reached plateau levels at 8 weeks in both the DHA-treated and control groups. The mean number of aberrant crypts per focus was also significantly smaller in the group given DHA than that in the control group at each time. These results suggest that DHA suppresses the formation and growth of aberrant crypt foci and has a preventive effect on colon carcinogenesis.

1,2-Dimethylhydrazine↗

PubMed1993

High frequency and low specificity of ras gene mutations in rat Zymbal's gland tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline.

The activating mutations of all three ras genes in rat Zymbal's gland tumors induced by a food mutagen, 2-amino-3-methylimidazo[4,5- f]quinoline (IQ) were analyzed. DNA fragments of the Ha-ras, Ki-ras and N-ras oncogenes were amplified from formalin-fixed and paraffin-embedded tissues by the polymerase chain reaction (PCR) and analyzed for activating mutations involving codons 12, 13 and 61 by oligonucleotide differential hybridization. All nine Zymbal's gland tumors examined, including three papillomas, were found to contain either an Ha-ras or Ki-ras mutation. These mutations were located in either codon 13 or 61 of Ha-ras, and in either codon 12 or 13 of Ki-ras. Of the nine mutations, three were G-->T, three were G-->C, two were G-->A and one was A-->T. Of the nine mutations, eight occurred at guanine bases and seven were transversions. There was no correlation between the types of mutations and the histological types of the tumors. These results suggest that ras gene activation is an important early event in the tumorigenesis induced by IQ in rat Zymbal's gland and that mutations at guanine bases are frequent, though the locations and types of the mutations are not highly specific.

Animals↗

PubMed1993

Rapidly growing mucinous cholangiocarcinoma.

A 65-year-old man was hospitalized due to an abdominal tumor. Several imaging studies showed multilocular tumors in the right hepatic lobe and in the pancreatic head, 4 and 7 cm in size, respectively. The hepatic tumor rapidly grew to 9 cm in 4 weeks, associated with a rapid increase in the serum carcinoembryonic antigen level from 125 ng/ml to 1,000 ng/ml. The pathologic diagnosis of the resected liver tumor was mucinous cholangiocarcinoma. This hepatic tumor produced a large amount of mucin, but did not secrete mucin into the bile ducts. Therefore, there was no obstructive jaundice. The incidentally accompanied pancreatic tumor was a typical serous cystadenoma. The present case suggested that mucinous cholangiocarcinoma could present rapid growth of the tumor. The clinicopathological features of mucinous cholangiocarcinoma are demonstrated for the first time, and the differences between mucinous cholangiocarcinoma and mucin-producing papillary adenocarcinoma of duct-spreading type are discussed.

Adenoma, Bile Duct↗

PubMed1993

Early invasive colorectal carcinomas metastatic to the lymph node with attention to their nonpolypoid development.

Clinicopathologic study of six cases of early invasive colorectal carcinoma metastatic to lymph node was performed in order to elucidate possible characteristics relating to the risk of metastasis, with particular attention to the growth pattern of the primary tumor. All of the cases had at least one of the well-known risk factors for lymph node metastasis, including moderately or poorly differentiated histologic characteristics, considerable degree of submucosal invasion, and lymphatic invasion. An interesting finding of the present study was the identification of a nonpolypoid growth pattern with no concomitant adenomatous tissue, which seemed to be different from that of "malignant polyps" of previously reported cases showing adenoma-carcinoma sequence. This unique growth feature was found in all of the cases. Therefore, in addition to the accepted risk factors, nonpolypoid growth pattern and absence of adenomatous component may be risk factors predictive of nodal metastasis in patients with early invasive colorectal carcinoma.

Adenocarcinoma↗

PubMed1992

Collagens in human atherosclerosis. Immunohistochemical analysis using collagen type-specific antibodies.

This study represents a systematic analysis of the distribution of collagen types in human atherosclerotic lesions. Formalin-fixed, paraffin-embedded aortic tissues of 40 lesions from 16 different individuals ranging in age from 1 month to 84 years were examined immunohistochemically using antibodies to type I, III, IV, V, and VI collagens. Preembedding immunoelectron microscopy was used to simultaneously localize type V and VI collagens within the lesions. Localization of type III collagen was very similar to that of type I, and type VI collagen appeared together with these two types of collagen in the thickened intimas of all stages of the lesion. Type V collagen was not detected in either fatty streaks or the mild intimal thickening of the aortas of children. With advancing age and lesion progression, the immunoreactivity with anti-type V collagen antibody became more intense. Type IV collagen was detected in the basement membrane region of intimal cells. In advanced lesions thick deposits of type IV collagen were found around the elongated smooth muscle cells. Using immunoelectron microscopy, type V collagen was found to be localized to cross-banded collagen fibers, and type VI collagen was found to be localized to beaded filaments present throughout the interstitium of the thickened intima. These findings suggest that collagens preserve the pathophysiological and functional integrity of the vascular wall by providing mechanical support as well as assuring the proper interaction of cells during the formation of atherosclerotic lesions.

Adult↗

PubMed1992

[Controversy between endoscopic and surgical treatment against early gastric and colorectal cancer].

Although endoscopic treatment against the patients with early cancer in gastrointestinal tract is an excellent method especially in high aged or poor risk patients, there still exists controversy about the indication for endoscopic treatment because of deeper invasion of the cancer or lymph node metastases. In order to clarify whether the patient has a possibility of nodal involvement or not, we made the clinicopathological analysis concerning 220 cases with early gastric cancers and 118 cases with colorectal cancers. Our retrospective analysis shows that endoscopic resection can be indicated for small polypoid cancer less than 10 mm in size, excluding IIa + IIc type. As to small depressed type, this procedure should be applied for IIc type which is well differentiated adenocarcinoma without ulcer formation (U1 (-)). Regarding early colorectal cancer there has been many discussion how to treat the patients with sm-cancer. Based on our analysis of 39 cases with sm-cancer, we led to the conclusion that the characteristics of sm-cancer with lymph node metastases are i) massive invasion into submucosal layer, ii) positive lymphatic permeation, or iii) "de novo" cancer. As a result, a decision of further surgery should be made even in small lesions less than 10 mm, taking the fact into consideration of the possibility of nodal involvement of sm-cancer.

Adult↗

PubMed1991

Anisakiasis of the colon: report of two cases with emphasis on the diagnostic and therapeutic value of colonoscopy.

Anisakiasis of the colon is a rare entity as compared with gastric anisakiasis, and its diagnosis is very difficult. We present here two cases--a 42-year-old woman and a 30-year-old woman--of anisakiasis of the colon treated by colonoscopic removal of the worm without surgery. The importance of colonoscopy for the diagnosis and treatment of this disease is briefly discussed.

Adult↗

PubMed1991

A limitation of endoscopic ultrasound: an unusual case of early gastric cancer overlying a pancreatic rest.

Endoscopic ultrasonography (EUS) has been developed as a valuable tool for examining the depth of carcinoma invasion and evaluating the submucosal tumors of the gastrointestinal tract. In the present case, that of a 60-yr-old woman, the work-up of radiography and conventional endoscopy revealed an ulcerating cancer of the stomach. Subsequent EUS showed a solid high-echoic mass occupying the third (submucosal) and fourth (muscularis propria) layers of gastric wall, suggestive of an advanced cancer invading the muscularis propria. However, histologic examination of the surgical specimen showed that this tumor was early submucosal carcinoma confined to the surface of a pancreatic rest. Retrospective evaluation of EUS pictures proved that the mass had tubular or circular echoless structures associated with thickening of the fourth layer, suggesting the pancreatic rest. Our experience in reviewing EUS findings of this tumor seems noteworthy, inasmuch as EUS indicates that EUS may provide certain characteristic features of gastric pancreatic rest that should be differentiated from invading carcinoma.

Carcinoma↗