Biomedical subjects

H Kuwano

Publications and source records attributed to H Kuwano.

At least 73 records · Page 4Linked to original sources

PubMed2000

Differential expression of the LAMB3 and LAMC2 genes between small cell and non-small cell lung carcinomas.

To identify genes differentially expressed between small cell lung carcinoma (SCLC) cells and non-SCLC cells, mRNA differential display was applied to 3 SCLC cell lines and 6 non-SCLC cell lines. The LAMB3 gene was identified as being expressed only in non-SCLC cells and not in SCLC cells. The LAMB3 gene encodes the laminin beta3 chain, which is a unique component of laminin-5. Laminin-5 is a heterotrimer protein consisting of the alpha3, beta3, and gamma2 chains, and another unique component of laminin-5 is the gamma2 chain encoded by the LAMC2 gene. RT-PCR analysis of the LAMB3 and LAMC2 genes in 45 lung cancer cell lines revealed that both the LAMB3 and LAMC2 genes were co-expressed in 21 of 32 non-SCLC cell lines (66%) but only in one of 13 SCLC cell lines (8%). Coexpression of the LAMB3 and LAMC2 genes was also observed in all 4 cases of primary non-SCLC cells examined but not in the corresponding non-cancerous lung cells. Since alpha6beta4 integrin, the specific laminin-5 binding receptor, is known to be expressed only in non-SCLC cells and not in SCLC cells, it was indicated that laminin-5 is a critical microenvironmental factor for the growth of non-SCLC cells but not of SCLC cells. The differences in the expression of integrins and laminins would be critical factors to distinguish SCLC and non-SCLC cells, and such differences might be associated with the unique biological properties of SCLC cells, including metastatic potential and drug sensitivity.

Carcinoma, Non-Small-Cell Lung↗

PubMed2000

Absence of hSNF5/INI1 mutation in human lung cancer.

Frequent occurrence of chromosome 22q deletions in lung cancer indicates the presence of a tumor suppressor gene on this chromosome arm. The hSNF5/INI1 gene at chromosome 22q11.2 has recently been shown to act as a tumor suppressor in rhabdoid tumors. To investigate whether the hSNF5/INI1 gene located on chromosome 22q is involved in lung carcinogenesis, mutation analysis of the hSNF5/INI1 gene was performed using 50 lung cancer cell lines. No mutations causing amino acid substitutions or frameshifts were found by PCR-SSCP analysis of the entire coding region. The results indicated that the hSNF5/INI1 gene is not inactivated in lung cancers and suggested the presence of another tumor suppressor gene on chromosome 22q. Thus, further studies are necessary to identify the target lung tumor suppressor gene(s) on chromosome 22q.

Chromosomal Proteins, Non-Histone↗

PubMed2000

Nitrotyrosine in esophageal squamous cell carcinoma and relevance to p53 expression.

We have examined the expression of nitrotyrosine, a marker of peroxynitrite formation, in 55 esophageal cancers by immunohistochemistry. Nitrotyrosine was detected in 21 of 55 (38.2%) esophageal cancers. Comparison of nitrotyrosine expression and the pathological findings showed that there was a significant association between the expression of nitrotyrosine and each of the depth of tumor invasion (P<0.01), occurrence of metastasis (P<0.05), pathological stage (P<0.01), smoking status (P<0.05) and alcohol intake (P<0.05). The survival rate of patients with nitrotyrosine-negative cancer was significantly higher than that of patients with nitrotyrosine-positive cancer (log-rank test, P<0.01). p53 was detected in 29 of 55 (52.7%) esophageal cancers, however, p53 expression did not correlate with nitrotyrosine expression. In conclusion, nitrotyrosine, a product of nitrogen species, is expressed in esophageal squamous cell carcinoma, which suggests that exogenous risk factors, such as tobacco and alcohol, through NO, are associated with carcinogenesis and progression of esophageal squamous cell carcinoma.

Adult↗

PubMed2000

A novel rapid colorimetric assay of carcinoembryonic antigen levels in the abdominal cavity to detect peritoneal micrometastasis during gastric cancer surgery.

We showed that the carcinoembryonic antigen (CEA) level in a peritoneal washing is an indicator of the postoperative survival of gastric cancer patients. On the premise that the polyvinylidine difluoride membrane adsorbs a fixed quantity of protein, this study was designed to produce a rapid, colorimetric, semi-quantitative assay of peritoneal CEA levels by using anti-CEA antibodies. At the time of laparotomy, peritoneal washings were collected from 60 gastric cancer patients, and CEA levels were determined by our assay and by an enzyme immunoassay (EIA) method. The accuracy of our method corresponded with the results of the EIA method. All the cases with high levels of CEA in the peritoneal washings showed positive color changes. Our new assay had no relation to protein concentrations of the samples. The assay makes use of diluted peritoneal washings without adaptation by protein concentration. The measurement can be completed in the operating room within 30 min. As a result, this assay can detect peritoneal microdissemination easily during surgery, and it can be used as an indication of intraoperative chemotherapy against peritoneal micrometastasis.

Abdomen↗

PubMed2000

Sonographic features of acute colonic diverticulitis: the "dome sign".

PURPOSE: This study was performed to clarify the sonographic features of acute colonic diverticulitis to enable its differentiation from appendicitis. METHODS: Of 119 patients who were referred to our hospitals for lower abdominal pain between June 1997 and December 1998 and underwent sonography, 12 patients had a definitive diagnosis of acute colonic diverticulitis and 4 patients a tentative diagnosis. Seventy-eight patients were diagnosed as having acute appendicitis, confirmed by appendectomy. In the 16 patients with diagnoses of diverticulitis, the sonographic and clinical features of acute colonic diverticulitis were studied. RESULTS: Among the 12 patients with definitive diagnoses of acute colonic diverticulitis, sonographic findings included localized thickening of the colonic wall (100%) and a hemispheric mass (the "dome sign") protruding at the thickened colonic wall (100%) and consisting of a hypoechoic wall (100%) and a central echogenic area (66%). The presence of diverticula was confirmed by barium-enema x-ray study in all 12 patients. The 4 patients with tentative diagnoses of acute colonic diverticulitis all had colonic wall thickening but no dome sign. Colonoscopy revealed colitis in 3 of these patients. All 16 patients recovered with conservative treatment, without laparotomy. CONCLUSIONS: Sonography was useful for differentiating acute colonic diverticulitis from appendicitis. The sonographic finding of the dome sign seems to be specific for acute colonic diverticulitis.

Abdominal Pain↗

PubMed2000

Loss of standard type of CD44 expression in invaded area as a good indicator of lymph-node metastasis in colorectal carcinoma.

PURPOSE: Recent advances have made possible the treatment of small invasive colorectal cancer by means of polypectomy or endoscopic mucosal resection. CD44 expression in cancer cells was identified as an indicator of lymph-node metastasis, which could be evaluated in specimens removed by colonoscopy. METHODS: The correlation between lymph-node metastasis and the expression of standard-type CD44 in cancer cells was examined immunohistologically using the invaded cancer cells of 61 tissue samples of superficially invasive colorectal cancer. We defined the above as invasive cancer restricted within the colorectal wall. Of the 61 samples, 31 had submucosal invasion and 30 had muscular invasion. RESULTS: Standard-type CD44 expression in the area of invasion in cases with lymph-node metastasis was remarkably down-regulated. In 43 cases with no lymph-node metastasis, 36 (83.7 percent) of patients had CD44 expression in invaded cells, whereas only two of 18 cases (11.1 percent) with lymph-node metastasis had expression of standard-type CD44 in the same area (P < 0.0001). A total of 69.6 percent (16/23) of patients with loss of standard-type CD44 expression in invaded sites were found to have positive metastasis in the lymph nodes. These results suggest that standard-type CD44 in invasive colon cancer cells could suppress metastasis to the regional lymph nodes. CONCLUSION: In cases of invasive colorectal cancer, the loss of standard-type CD44 expression in the invaded area is a sensitive marker for metastasis to the lymph nodes. Further investigation with larger patient groups is required to clarify the reliability of loss of standard-type CD44 expression as an indicator for additional surgery after endoscopic resection of submucosal invasive colorectal carcinoma.

Biomarkers, Tumor↗

PubMed2000

Malignant proliferating trichilemmal tumor in the skin over the breast: a case report.

A proliferating trichilemmal tumor is relatively uncommon. It is composed of multiple cysts consisting of squamous epithelium with trichilemmal keratinization without granular layer interposition. This lesion usually occurs in the scalp of elderly women. We describe a 67-year-old woman with a malignant proliferating trichilemmal tumor in the skin over the breast. We first misdiagnosed the disease as a primary squamous cell carcinoma of the breast with a metastatic lymph node in the axilla because of the disease site and our unfamiliarity with the disease. The patient underwent radical mastectomy with axillary dissection. Eight months postoperatively, a tumor appeared in her right axilla and progressively enlarged. We subsequently excised the tumor. She is healthy as of 8 months postoperatively. To the best of our knowledge, only one case of a proliferating trichilemmal tumor occurring in the skin over the breast has been reported.

Aged↗

PubMed2000

Tumor cells as the origin of elevated serum alpha1,3fucosyltransferase in association with malignancy.

We have previously reported that the elevated activities of serum alpha 1,3fucosyltransferase reverted to normal levels after curative removal of the tumors. To determine the origin of elevated serum alpha 1,3fucosyltransferase, blood samples were obtained from both the drainage vein and the artery in patients with different stages of colorectal cancer at surgery. The enzyme levels in all samples from the drainage vein were found to be higher than the levels in the artery that fed the tumor. Hence, the origin of elevated alpha1,3fucosyltransferase in serum was thought to be the tumor rather than the liver that is the normal source of serum alpha1,3fucosyltransferase. When serum samples not only from colorectal cancer patients but also from patients with gastric, liver, lung, pancreas, bladder and esophagus cancer were treated with anti-FUTVI antibody, the measured activities of alpha1,3fucosyltransferase were markedly reduced. Further, secretion of alpha1,3fucosyltransferase from human colorectal carcinoma cells was also detected in the culture medium by Western immuno-blot analysis with anti-FUTVI antibody.

Aged↗

PubMed2000

A new method for assaying adhesion of cancer cells to the greater omentum and its application for evaluating anti-adhesion activities of chemically synthesized oligosaccharides.

A new ex vivo method for assaying adhesion of cancer cells to the greater omentum has been developed using mouse greater omentum and [3H]labelled human gastric and mouse colorectal cancer cells. Since the adhesion rates were found to increase up to 18 h and labelled cells seemed to be stable during the period, the present method could be useful for investigating adhesion of cancer cells to the greater omentum, which must occur at the first step of the peritoneal dissemination. The adhesion of cancer cells to the greater omentum was inhibited by a series of chemically synthesized oligosaccharides and Gal beta1,3[3OMeGal beta1,4GlcNAc beta1,6]alphaBn was found to be the best inhibitor. The anti-tumor effect of this novel tetrasaccharide in vivo was shown in preliminary experiments using Balb/c mice and colon26 cells.

Animals↗

PubMed2000

Prostaglandin E2 stimulates motilin release via a cholinergic muscarinic pathway in the dog.

Prostaglandins are well known to be widely distributed in mammalian gastrointestinal tissues and to play a role in the regulation of gastrointestinal hormones and contractions. The present study was undertaken to determine whether prostaglandins have an effect on the endogenous release of motilin in the dog. In six conscious dogs, gastrointestinal contractions were monitored by means of chronically implanted force transducers. Prostaglandin E2 (PGE2; 3, 10, 30 microgram kg-1) was given intravenously during the interdigestive phase I period with or without a muscarinic or nicotinic receptor antagonist. Blood samples were collected from 10 min before, to 30 min after, prostaglandin injection. Indomethacin (5 mg kg-1) was given intravenously to investigate the effect of endogenous prostaglandins on motilin release. PGE2 significantly stimulated motilin release but not gastric contractions. Atropine, but not hexamethonium, blocked PGE2-induced motilin release. Motilin release in response to PGE2 was significantly increased by pretreatment with hexamethonium. Indomethacin inhibited the cyclic release of motilin and gastric phase III contractions. We conclude that PGE2 appears to stimulate motilin release via cholinergic muscarinic pathways, and nicotinic receptors modulate this reaction. PGE2 may be involved in part in the regulation of the cyclic release of motilin and the occurrence of gastric phase III.

Animals↗

PubMed2000

The role of activin and transforming growth factor-beta in the regulation of organ mass in the rat liver.

The present study was conducted to assess the role of activin(s) in the regulatory mechanism to maintain constant liver mass. To this end, we infused follistatin, an activin antagonist, into the portal vein of the rat. Follistatin induced DNA synthesis, as assessed by bromodeoxy uridine labeling, in intact livers. Small peaks of bromodeoxy uridine labeling were observed after 3 and 18 hours of infusion, and a large peak was observed after 48 hours. In follistatin-treated rats, the DNA content of the liver was significantly elevated after 72 hours and returned to the basal value within 120 hours. Likewise, liver weight increased significantly after 60 and 72 hours, but returned to the control value within 120 hours. Apoptosis of hepatocytes, assessed by the Tdt-mediated, dUTP-biotin nick end labeling method was observed after 72 hours or later. Messenger RNA (mRNA) expression of hepatocyte growth factor, transforming growth factor-alpha, tumor necrosis factor-alpha, and interleukin-6 did not increase after the addition of follistatin. The mRNA expression and immunoreativity of transforming growth factor-beta increased after the administration of follistatin. These results suggest that the blockade of activin action leads to the initiation of DNA synthesis in the intact liver. Activins may tonically inhibit hepatocyte growth in the intact liver. Transforming growth factor-beta may also act to maintain constant liver mass when activin action is blocked.

Activins↗

PubMed2000

Prognostic factors in patients with submucosal carcinoma of the oesophagus.

To clarify the prognostic factors in patients with submucosal carcinoma of the oesophagus, we examined the results of surgical treatment for 78 cases over the last decade. The clinicopathological factors including age, sex, location of the tumour, length of the tumour, histological differentiation, subclassification of depth, lymphatic or blood vessel invasion, intramural metastasis and lymph node metastasis were all analysed. Then the correlation between these factors and prognosis was investigated. As a result, significant differences were observed in the survival rates between the groups regarding lymphatic vessel invasion (P = 0.0003), intramural metastasis (P = 0.0051) and lymph node metastasis (P = 0.0026). According to a multivariate analysis, intramural metastasis (P = 0.0038, relative risk 9.17), vessel invasion (P = 0.0033, relative risk 6.25) and lymph node metastasis (P = 0.0187, relative risk 3.62) were found to be independent prognostic factors. The prognosis of the patients with at least one of these factors was significantly poorer than that without. The five-year survival rate of the patients without these factors was as good as that with mucosal carcinoma of the oesophagus. Based on our findings, vessel invasion, intramural metastasis and lymph node metastasis are thus considered to be significant prognostic factors in patients with submucosal carcinoma of the oesophagus.

Age Factors↗

PubMed2000

p53 expression in squamous dysplasia associated with carcinoma of the oesophagus: evidence for field carcinogenesis.

Squamous epithelial dysplasia is often observed multifocally in the cancerous oesophagus and is presumably considered to be a pre-cancerous lesion. A mutation of the p53 tumour suppressor gene is commonly identified in oesophageal cancer and dysplasia. p53 mutations can be anticipated immunohistochemically. In order to confirm the biological and clinical significance of p53 expressions in oesophageal field carcinogenesis, immunostaining for p53 in cancerous and multifocal precancerous lesions from resected human oesophagus was systematically investigated, while paying special attention to the contiguity of these lesions. Lesions expressing p53 were detected in 46.5% (20 of 43 lesions) of the invasive carcinoma, and in 51.0% (46 of 90 lesions) of the carcinoma in situ, and in 51.4% (92 of 179 lesions) of the dysplasia. Next, the p53 expression in dysplasia was compared with that in carcinoma for the same case. 37 of 39 (94.8%) dysplasias contiguous to p53-positive carcinomas also expressed p53 (P<0.0001). On the other hand, the isolated dysplasias without contiguity to p53-positive carcinomas, only expressed p53 protein in 44.0% (11 of 25 lesions). No significant correlations were found between the p53 staining and either the clinicopathological features or prognosis. Discordant p53 alterations, such as those seen in cancerous and isolated precancerous lesions, may thus demonstrate further evidence for a multicentric or field carcinogenesis of the human oesophagus.

Aged↗

PubMed2000

Effect of uric acid on liver injury during hemorrhagic shock.

BACKGROUND: It remains unproven whether nitric oxide (NO) exerts a toxic effect on hepatocytes directly or through the formation of a more toxic compound during hemorrhagic shock (HS). NO reacts at a very high rate constant with superoxide to give peroxynitrite, a potentially toxic molecule. In this study, we investigated whether or not peroxynitrite contributed to tissue injury in the liver during HS. METHODS: Male Sprague-Dawley rats were subjected to decompensated HS followed by resuscitation. In addition to the time course of tissue injury and inducible NO synthase (iNOS) messenger RNA (mRNA) expression in the liver during HS, we investigated the effect of N6-(iminoethyl)-L-lysine(LNIL) (a specific inhibitor of iNOS) and also that of uric acid (a natural scavenger of peroxynitrite) on tissue injury and nitrotyrosine formation (a footprint of peroxynitrite) in the liver. RESULTS: The liver injury, evaluated by plasma aminotransferase levels and histology, became evident at the end of the shock period and had significantly increased 1 hour after the start of resuscitation (Shock-1 h). There was no iNOS mRNA expression in the liver at baseline, and it had clearly increased by Shock-1 h. Treatment with LNIL or uric acid significantly attenuated the tissue injury with a prominent reduction in nitrotyrosine formation in the liver. CONCLUSIONS: These lines of evidence suggest that one of the mechanisms by which NO production causes liver injury during HS may be its reaction with superoxide to form peroxynitrite.

Animals↗

PubMed2000

Relation among portal segmentation, proper hepatic vein, and external notch of the caudate lobe in the human liver.

OBJECTIVE: To identify portal segmentation and a portal fissure in the caudate lobe of the human liver in relation to the hepatic venous system and the external notch at the caudal edge of the caudate lobe. SUMMARY BACKGROUND DATA: Although the anatomy of the caudate lobe has been studied, the detailed anatomy has not yet been clarified; this is necessary to develop safe procedures for caudate lobe resection. METHODS: A total of 88 formalin-fixed human livers were dissected to visualize the portal vein and hepatic vein systems of the caudate lobe in relation to the external notch. RESULTS: The patterns of portal branching were classified into two types. In 58 livers (67.4%), the territories of the first-order portal branches were clearly divided into two areas (the Spiegel lobe and the paracaval portion). In the remaining 28 livers (32.6%), the territories of the second-order portal branches were clearly divided into two areas. These two areas were distinctly separated by an internal plane, which was coincident with the external notch. The caudate lobe had a systematized hepatic venous system that consisted of one (87.5%) or two (11.4%) proper hepatic veins and plural accessory hepatic veins. The proper hepatic veins laid along the internal plane between these two portal areas. CONCLUSION: The caudate lobe exhibited distinct portal segmentation with a portal fissure that was indicated internally by the proper hepatic vein and externally by the notch at the caudal edge of the caudate lobe.

Adult↗

PubMed2000

Roles of cyclooxygenase-2 in tissue injury during hemorrhagic shock.

Prostaglandins (PGs), which play a pivotal role in the cytokine network, have been implicated in the pathophysiology of circulatory shock, but the precise role of cyclooxygenase-2 (COX-2) in circulatory shock is still not known. This study investigated whether or not COX-2 affects liver and bowel injury during hemorrhagic shock (HS). Male Sprague-Dawley rats were subjected to decompensated HS followed by resuscitation. Besides the time course of tissue injury and mRNA expression of COX-2 in the liver and bowel during HS, we investigated the effect of N-(2-cyclohexyloxy-4-nitrophenyl)methane sulfonamide (NS398), a specific inhibitor of COX-2, on injury to these organs. The liver injury, evaluated by plasma aminotransferase levels and histology, was evident at the end of the shock period (Shock-0h) and had significantly increased 1 h after the start of resuscitation (Shock-1h) (P < 0.01). The bowel injury, assessed by histological findings in the terminal ileum, was scarcely detectable at Shock-0h but became noticeable at Shock-1h (P < 0.01). COX-2 mRNA expression was up-regulated in the liver during HS whereas it did not change in the bowel. NS398 treatment significantly exacerbated both liver and bowel injury. These lines of evidence suggest that COX-2-derived PGs provide protection against HS-induced liver and bowel injury.

Actins↗

PubMed2000

Genetic variations of the midkine (MK) gene in human sporadic colorectal and gastric cancers.

Midkine (MK), a retinoic acid responsible protein, is regulated during development and may play an important role in tumorigenesis. A search for genetic variations of the MK gene, located on chromosome 11q11.2 in humans, has not yet been conducted in cancers. To examine the entire coding region, as well as 4 regions of the promoter covering all functional motifs, 8 sets of intron-based and promoter region primers were designed. Using these primers, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis of genomic DNA samples from 60 sporadic colorectal and 37 sporadic gastric cancer patients was carried out. This analysis, followed by DNA sequencing, revealed a heterozygous g/t polymorphism at the 62nd base on intron 3 in five colorectal tumors (8.3%) and one gastric tumor (2.7%). In the promoter region, a heterozygous CTT deletion, creating a (CTTTT)2 repeat, in one colorectal cancer sample (1.67%) and a heterozygous 2-bp deletion in the G7 tract in another colorectal cancer patient were detected. A/G and A/A alleles were also detected at nt. -1741 in 36 (97.3%) and one (2.7%) gastric cancer samples, respectively. The A/G alleles were observed in all colorectal cancer patients (100%). All variations observed in the promoter region showed polymorphism. These results suggest that in sporadic colorectal and gastric cancers some gene alterations are present in the MK promoter region, but alterations in the coding region are rare.

Alleles↗

PubMed2000

Mutation analysis of transforming growth factor beta type II receptor, Smad2, Smad3 and Smad4 in esophageal squamous cell carcinoma.

Mutations of the transforming growth factor beta type II receptor (TGFbetaRII) gene and Smad family genes have been observed in several human cancers. However, there has been no report on mutation analysis of the entire coding regions of these genes in esophageal cancer, and the role of these genes in the development of esophageal cancer remains unknown. We performed polymerase chain reaction-single strand conformation polymorphism analysis of TGFbetaRII, Smad2, Smad3 and Smad4 genes and microsatellite assay in 20 esophageal squamous cell carcinomas (ESCC). We detected polymorphisms at exon 2 of Smad3 and intron 6 of Smad4. No mutation was found in TGFbetaRII, Smad2, Smad3 and Smad4 genes. These results suggest that mutation of TGFbetaRII, Smad2, Smad3 and Smad4 genes is a rare event in ESCC.

Base Sequence↗