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N Yoshimi

Publications and source records attributed to N Yoshimi.

At least 73 records · Page 4Linked to original sources
PubMed1997

Comparison of susceptibility to apoptosis induced by rhTNF-alpha and cycloheximide between human circulating and exudated neutrophils.

To determine whether exudated neutrophils differ from circulating ones in their apoptosis, rhTNF-alpha plus cycloheximide-induced apoptosis in human salivary neutrophils was compared to that in human neutrophils in peripheral blood. Concomitant treatment of peripheral blood neutrophils with rhTNF-alpha and cycloheximide-induced apoptosis in blood neutrophils within 3 hr, as evaluated both by light microscopic changes characteristic to apoptosis and by DNA fragmentation, whereas the same treatment failed to induce any apoptosis in salivary neutrophils. These results indicate that the exudation of neutrophils from blood into tissue is associated with marked changes in their functions such as alteration in their sensitivity to apoptosis-inducing stimuli.

Apoptosis↗
PubMed1997

Expression of Bax and bcl-2 proteins, regulators of programmed cell death, in human brain tumors.

Expression of Bcl-2, a programmed cell death (PCD)-suppressing molecule, and Bax, the Bcl-2 related PCD-accelerating protein was investigated in varied human brain tumors. Thirty-six cases of human brain tumors comprising 4 astrocytomas, 3 anaplastic astrocytomas, 4 glioblastomas multiforme, 5 medulloblastomas, 1 ependymoma, 2 choroid plexus papilloma, 1 ganglioglioma, 1 central neurocytoma, 4 meningotheliomatous meningiomas, 3 transitional meningiomas, 4 fibroblastic meningiomas, 3 acoustic neurinomas and 1 craniopharyngioma were analyzed for the localization of Bax and Bcl-2 proteins. No relationship between the degree of the histological malignancy and the presence of Bax or Bcl-2 proteins was found in varied human brain tumors. However, it is suggested that reduced expression of Bax protein is necessary for the malignant transformation and progression of the brain tumors, since no histologically malignant brain tumors with positive Bax protein were present. Our findings indicate that the expression pattern of Bax and Bcl-2 may reflect histogenetic difference of each type of brain tumors.

Adolescent↗
PubMed1997

Inhibitory effect of NS-398, a selective cyclooxygenase-2 inhibitor, on azoxymethane-induced aberrant crypt foci in colon carcinogenesis of F344 rats.

Prostaglandin E2, which is produced by cyclooxygenase (COX) during arachidonic acid metabolism, is considered to be related to colon carcinogenesis. Therefore, the effect of NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide), a COX-2 inhibitor, was examined in azoxymethane (AOM)-induced colon carcinogenesis in rats in this study. In the first experiment, groups 1-3 were treated with AOM (15 mg/kg, s.c.) 3 times at intervals of a week from 5 weeks of age. Groups 2 and 3 were respectively given 1 mg/kg and 10 mg/kg of NS-398 in 5% gum arabic aqueous solution 3 times per week by oral gavage during the experiment. Six weeks after the first exposure to AOM, aberrant crypt foci (ACF) were counted in the colonic mucosa of all rats. The mean occurrence of ACF per length in rats given 1 mg/kg b.w. or 10 mg/kg b.w. of NS-398 was reduced to 65.7% or 52.8%, respectively, of that in rats treated with only AOM. Levels of COX-2 mRNA expression in groups treated with AOM, regardless of NS-398, were slightly higher than that in the group treated with NS-398 alone as judged from reverse transcription-polymerase chain reaction analysis. In the second experiment, the effect of NS-398 at different times, i.e., during initiation and post-initiation, was examined. Treatment with NS-398 in both phases significantly inhibited the appearance of ACF. The results imply that NS-398 might have a chemopreventive potential.

Animals↗
PubMed1997

Inhibitory effects of dietary protocatechuic acid and costunolide on 7,12-dimethylbenz[a]anthracene-induced hamster cheek pouch carcinogenesis.

The modifying effects of dietary exposure to two natural products, protocatechuic acid (PCA) and costunolide during the development of neoplasms in oral carcinogenesis initiated with 7,12-dimethylbenz[a]anthracene (DMBA) were investigated in male Syrian golden hamsters. All hamsters except those in the test chemical alone and control groups received DMBA (0.5%) in mineral oil to the right buccal pouch 3 times per week for 4 or 6 weeks. At 13 weeks of age, the groups exposed to DMBA were fed diet containing PCA or costunolide at a dose of 0.2 g/kg diet (200 ppm) for 17 weeks. The other groups consisted of hamsters given mineral oil alone for 6 weeks, or given 200 ppm PCA or costunolide alone, or untreated. All animals were necropsied at the termination of the experiment (week 24). PCA or costunolide significantly decreased the tumor burden (P < 0.001-P < 0.05) and the extent of dysplastic areas (%) (P < 0.001-P < 0.05). PCA significantly decreased the mean number of AgNORs/nucleus (P < 0.05). The BrdUrd-labeling index was reduced by dietary administration of test compounds, though not significantly. These results suggest that PCA and costunolide inhibited hamster buccal pouch carcinogenesis and such inhibition may be related to suppression of cell proliferation in the buccal mucosa. It was also found that telomerase activity expressed in neoplastic and preneoplastic lesions of hamster buccal pouch epithelium after DMBA treatment correlated with the histopathological degree of malignancy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Apoptosis induced by NS-398, a selective cyclooxygenase-2 inhibitor, in human colorectal cancer cell lines.

Recent studies have suggested that apoptosis is a key phenomenon in the chemopreventive action of nonsteroidal antiinflammatory drugs (NSAIDs), which exhibit cancer-preventive and tumor-regressive effects in the human colon. The effect of NS-398, N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide, which is a selective inhibitor of cyclooxygenase-2 (COX-2), on the induction of apoptosis in two human colorectal cancer cell lines (Colo320 and THRC) was determined. The apoptotic ratios (-fold vs. control value) of Colo320 in the presence of 100 microM indomethacin and NS-398 were 3.3 +/- 1.5 and 9.0 +/- 0.94, and those of THRC were 2.3 +/- 0.46 and 7.4 +/- 0.87, respectively. The ability of NS-398 to induce apoptosis is greater than that of indomethacin. Both indomethacin and NS-398 reduced the cell proliferation in a concentration-dependent manner. The IC50 values of NS-398 (54.8 +/- 3.6 and 77.2 +/- 4.9 microM) were significantly lower than those of indomethacin (206.3 +/- 43.0 and 180.3 +/- 22.6 microM) at P < 0.01 in Colo320 and THRC cell lines, respectively. These findings suggest that NS-398, a selective inhibitor of COX-2, is a possible candidate for a chemopreventive agent with a potent apoptosis-inducing effect and low ulcerogenic activity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Inhibitory effects of diallyl disulfide or aspirin on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mammary carcinogenesis in rats.

Modifying effects of diallyl disulfide (DAD), aspirin or DL-alpha-difluoromethylornithine (DFMO) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in SD rats were investigated. A total of 166 female rats, 6 weeks old, were divided into 8 groups. They were fed a high fat diet throughout the experiment. Starting at 7 weeks of age, groups 1-4 were given PhIP (85 mg/kg body weight in corn oil) by gavage 8 times in 10 days, and groups 5-8 were given corn oil alone. For the beginning 4 weeks, groups 2 and 5 were given DAD at 200 ppm in diet. Similarly groups 3 and 6, and groups 4 and 7 were given aspirin (400 ppm) and DFMO (400 ppm), respectively. Mammary carcinomas were only recognized in groups 1-4 at the termination (25 weeks after the start of experiment). Multiplicity (mean number/rat) of neoplasms in group 2 (PhIP+DAD, 0.90/rat) and group 3 (PhIP+aspirin, 1.37/rat) was significantly smaller than that in group 1 (PhIP alone, 2.45/ rat) (P < 0.005 and P < 0.05, respectively). These results indicate that dietary intake of DAD or aspirin during the time corresponding to initiation phase has chemopreventive potential on PhIP-induced mammary carcinogenesis in rats.

Administration, Oral↗
PubMed1997

Regressive effects of various chemopreventive agents on azoxymethane-induced aberrant crypt foci in the rat colon.

Regressive effects of four chemopreventive agents [5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone (KYN-54), S-methyl methanethiosulfonate (MMTS), chlorogenic acid (CA), and piroxicam] on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in the colon of male F344 rats were examined by dietary exposure. At six weeks of age, 60 rats of groups 1 through 5 received subcutaneous injections of AOM (15 mg/kg body weight) once a weeks. Twelve weeks after the first carcinogen injection, when the occurrence of ACF was maximal, the rats in groups 2 through 5 were started on diet containing the test chemicals as follows: group 2, KYN-54 (0.02%); group 3, MMTS (0.01%); group 4, CA (0.025%); and group 5, piroxicam (0.0125%). Group 1 (20 rats) was kept on the basal diet alone, and group 6 (12 rats) served as an untreated control. Rats in each group were killed at 6, 12, 18, or 24 weeks after the start of the experiment, and the yield of ACF in the colon of each group at 18 or 24 weeks was compared with that at 12 weeks. The number of ACF per rat colon of each group at 18 or 24 weeks was smaller than that at 12 weeks. The reduction rates at 18 weeks were 7% in group 1 (AOM alone), 11% in group 2 (AOM + KYN-54), 10% in group 3 (AOM + MMTS), 51% in group 4 (AOM + CA) (P < 0.01), and 33% in group 5 (AOM + piroxicam) (P < 0.02), while at 24 weeks they were 12%, 26%, 51% (P < 0.002), 43% (P < 0.05), and 70% (P < 0.001), respectively. These results indicate that chemopreventive agents for large bowel carcinogenesis, i.e., KYN-54, MMTS, CA, and piroxicam, are not only able to prevent the development of ACF, but also can regress ACF, which are regarded as precursor lesions of colorectal cancer.

4-Butyrolactone↗
PubMed1997

No involvement of APC gene mutations in ulcerative colitis-associated rat colon carcinogenesis induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate.

A rat model for human ulcerative colitis (UC) has been developed by using 1-hydroxyanthraquinone (1-HA) to cause severe inflammation of colonic mucosa. 1-HA also has synergistic effects on the carcinogenicity of methylazoxymethanol (MAM) acetate in the rat colon. In this study, four adenomas and 16 adenocarcinomas induced in male F344 rats by 1-HA and MAM acetate were examined for mutations in the entire coding regions and introns flanking coding exons of the APC gene by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and PCR-restriction-SSCP analyses. No mutations were found. These results, together with our previous observations of a relative lack of Ki-ras gene mutations in the same tumors, are similar to those found in human UC-associated colon cancer, suggest a common pathway in these two systems, although they are different in their implication of p53 mutations. Therefore, this model may have some relevance and application to the study of colon cancer in human inflammatory bowel disease, which is not associated with APC mutations or with Ki-ras or p53 mutations.

Animals↗
PubMed1997

Chemoprevention by naturally occurring and synthetic agents in oral, liver, and large bowel carcinogenesis.

A number of naturally occurring compounds and several related synthetic agents were confirmed to exert chemopreventive properties against carcinogenesis in the digestive organs. Phenolic compounds, widely distributed as plant constituents, possess chemopreventive activities in tongue, liver, and large bowel of rodents. Of them, a simple phenolic protocatechuic acid seems to be a promising compound. Organosulfur compounds contained in the cruciferous vegetables and known to activate detoxifying enzymes are regarded as a candidate group for cancer preventive agents. We proved a strong protective effect of S-methylmethanethiosulfonate, a constituent in these vegetables, on azoxymethane (AOM)-induced large bowel carcinogenesis. Some oxygenated carotenoids (xanthophylls) are reported to have antitumor effects. Naturally occurring xanthophylls astaxanthin and canthaxanthin have considerable preventive activities on 4-nitroquinoline-1-oxide (4-NQO)-induced tongue carcinogenesis and AOM-induced large bowel carcinogenesis. A novel synthesized retinoidal butenolide, KYN-54, which suppresses large bowel as well as tongue carcinogenesis could be a useful agent for prevention of digestive organ cancers. Some trace elements are known to have anticarcinogenic effects. Magnesium hydroxide, a protective agent in colorectal carcinogenesis, inhibits c-myc expression and ornithine decarboxylase activity in the mucosal epithelium of the intestine. Our results show that many agents with preventive effects in tongue, liver, and large bowel control carcinogen-induced hyperproliferation of cells in these organs. Carcinogens used to induce large bowel cancers also induce apoptosis in the target sites. Telomerase activity is increased in the tissues of preneoplastic as well as neoplastic lesions in experimental models such as dimethylbenz[a]anthracene-induced oral carcinogenesis in hamsters. These could be useful biomarkers in studies for cancer chemoprevention.

Animals↗
PubMed1996

Immunohistochemical detection of Bax and Bcl-2 proteins in gerbil hippocampus following transient forebrain ischemia.

Time-course expression of Bax and Bcl-2 proteins, identified as apoptosis-regulating molecules, was assessed in gerbil hippocampus following transient forebrain ischemia. Brain sections from animals sacrificed at 48, 72, 96 h and 7 days following 5 min ischemia were immunohistochemically evaluated using polyclonal antibodies specific for Bax and Bcl-2 proteins, respectively. The intensity of Bax expression in CA1 neurons increased with time and peaked at 72 h, and immediately disappeared at 96 h following 5 min ischemia. No expression of Bcl-2 in the CA1 neurons was recognized in all the time evaluated.

Animals↗
PubMed1996

Telomerase activity of normal tissues and neoplasms in rat colon carcinogenesis induced by methylazoxymethanol acetate and its difference from that of human colonic tissues.

Telomerase activity in tissues may be related to tumor development, especially malignant conversion, in humans. However, there are few reports about telomeres and telomerase activity in animals. In this study, we examined telomerase activity in rat colon carcinogenesis and in normal rat liver tissue and compared it with that of human colon cancer tissues. This is the first report concerning telomerase activity in rats. F344 rats were used, and colon neoplasms were induced with methylazoxymethanol acetate. There was telomerase activity in not only the induced colon neoplasms but also the colon mucosa and livers of untreated rats, in contrast with the results from normal human somatic tissues in previous reports. Indeed, we also observed negative results in normal human mucosa, despite the positive results in colon-cancer tissues. These findings suggest that there is a difference in the telomerase activities in humans and rats. Because rat telomeres are very long (20-100 kp, average 50 kp) compared with human telomeres (5-15 kp, average 12 kp), the difference in the telomere lengths of rats and humans might be related to their enzyme activities, although this is still unclear. Furthermore, because the inhibition of telomerase has been proposed as a novel cancer therapy for humans, the rat model presented here, in which telomerase is expressed in somatic tissues, may be useful for studies of telomerase inhibition, including inhibition by chemopreventive agents.

Adenocarcinoma↗
PubMed1996

Localization of Bax and Bcl-2 proteins, regulators of programmed cell death, in the human central nervous system.

Bax and Bcl-2 proteins are identified as regulating molecules for programmed cell death. In the central nervous system, programmed cell death or apoptosis is considered to be an important phenomenon that is related to neuron vulnerability to a variety of toxic effects, including ischaemic insult. In this study, localization of Bax and Bcl-2 proteins was investigated in the human central nervous system using autopsy cases without any neurological disorder. Results were compared with findings in the rat. Most neurons in human cerebral cortex, basal ganglia and brain stem were positive for both Bax and Bcl-2 proteins, whereas Purkinje cells in cerebellum and neurons in hippocampal CA1, CA2 and CA3 regions were positive for Bax but negative or weakly positive for Bcl-2. Glial cells examined in all sections were negative for both proteins. Choroid plexus, ependymal cells and arachnoid villi showed positive reactivity for both proteins. A possible relationship between the localization of Bax or Bcl-2 proteins and the cell vulnerability in central nervous system is discussed.

Animals↗
PubMed1996

Different expression patterns of cyclins A, D1 and E in human colorectal cancer.

The expressions of cyclins A, D1 and E at the protein level were investigated by Western blotting in human colorectal carcinomas and in adjacent non-neoplastic colorectal mucosas. Cyclin E was higher in the cancer tissue than in the non-neoplastic mucosa in 92% patients (35 out of 38 cases). However, the cyclin A expression of the mucosa was higher than that of the cancer tissue in 63% (25 out of 40 cases) cases, and only 4 (10%) cancers had higher cyclin A expression. Eleven cancers (27%) demonstrated expression equivalent to that in the mucosa. Equal expression of cyclin D1 in cancer and mucosal tissues was found in 51% cases (20/39), lower expression of cyclin D1 by cancer tissues was demonstrated in 41% cases (16/39) and only three cancers showed higher expression than the mucosa. Proliferating-cell nuclear antigen immunohistochemistry revealed that the labeling index of the cancer tissue was 43.5 +/- 8.3% while that of the mucosa was only 14.8 +/- 5.1%. These results proved that colorectal cancers express high levels of cyclin E, consistent with a high rate of cell proliferation, whereas most of such cancer lose control of cyclin A and cyclin D1 expression.

Adult↗
PubMed1996

Early alterations of apoptosis and cell proliferation in azoxymethane-initiated rat colonic epithelium.

Alterations of apoptosis and cell proliferation in the colonic epithelium of rats after exposure to azoxymethane (AOM) were estimated by means of the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method, measurement of 5-bromo-2'-deoxyuridine (BrdU) incorporation, immunohistochemical staining for proliferating cell nuclear antigen (PCNA), and counting of mitotic cells. F344 male rats were given a single s.c. injection of AOM (15 mg/kg body weight) at 6 week of age, and killed 4 h, 8 h, 3 days, and 7 days after the AOM treatment. At 4 h after the treatment, many damaged cells were already observed in the colonic epithelium, and they were positive by TUNEL staining. At 8 h, the number of TUNEL-positive cells was largest. The reduction of DNA synthesis in the colonic epithelium, confirmed by BrdU incorporation, was not distinct in comparison with the mitotic inhibition. There was no remarkable change in PCNA labeling index, except that strong expression of PCNA was detected in many damaged cells. On the 3rd day, the appearance of cell death became infrequent and an increase of cell proliferation occurred. On the 7th day, the expression of TUNEL and the cell proliferation biomarkers were at almost normal levels. These findings suggest that AOM induces apoptosis, which is associated with synchronous inhibition of mitosis. The data also indicate that PCNA immunostaining does not reflect the true proliferation state in the early phase after AOM exposure, probably due to the occurrence of cell cycle arrest or DNA repair.

Animals↗
PubMed1996

[Correlation between an enzyme (glutathione S-transferase-pi) and effects of chemotherapy (cisplatin + etoposide)].

OBJECTIVES: We studied the correlation between cisplatin and etoposide chemotherapy and GST-pi staining in patients with untreated primary non-small cell lung cancer. METHODS: Of patients diagnosed as having primary lung cancer, 27 patients (26 men, 1 woman; median age 74.9 years) with stage III b or over were studied. Histological types included squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. A course of treatment consisted of cisplatin 100 mg/m2/day x one day and etoposide 100 mg/m2/day x 3 days during 28 days. After 2 courses of treatment, the therapeutic effects were judged and examined in relation to immunostaining levels obtained with anti-GST-pi antibody. RESULTS: Of patients with PR (14), 11 showed GST-pi (-) staining. CONCLUSION: There is a correlation between GST-pi staining and the effects of cisplatin and etoposide chemotherapy.

Aged↗
PubMed1996

[A case of mucosa associated lymphoid tissue (MALT) lymphoma].

We examined a 63-year-old female, who was referred to our hospital for a thorough examination of abnormal findings on the X-ray which were first detected in May, 1992, and suggested a tumor. After hospital admission, a bracheobronchial lymph node biopsy was performed, and the results suggested a pseudo-lymphoma. However, because the possibility of a malignant tumor was not completely negated and the patient, as well as her family, hoped to receive surgical treatment, we performed the tumor resection. The tumor had a clear border. S6 was 3 x 3.5 x 4 cm, S8 was 2 x 2.5 x 3 cm, and evaluation according to the tumor node metastasis (TNM) classification was T1 N0 M0, i.e., Stage I. In addition to an ordinary histopathological examination, an immunohistochemical examination was conducted for CD19+, CD20+, CD22+, IgD-, CD5-, CD10-. Overall, the tumor was diagnosed as a MALT lymphoma. Investigated IgH, TCR beta, bcl-1 and bcl-2 genes did not show reconstitution. Because it is difficult to differentiate a malignant lymphoma, primarily developed in the lung, from a MALT lymphoma on a morphological examination of a tissue specimen, immunohistochemical and genetic examinations are helpful for making a diagnosis.

Female↗
PubMed1995

DNA fragmentation in granular cells of human cerebellum following global ischemia.

Vulnerability of human cerebellum in two autopsy cases following global brain ischemia was examined histologically by using a specific in situ nick-end labeling method for DNA breaks. In both cases, DNA fragmentation was observed in approximately one-third of the granular cells in cerebellar cortex, whereas Purkinje cells were still alive and no DNA fragmentation was recognized in the nuclei. The present study suggests that some granular cells of cerebellar cortex are more vulnerable to transient ischemia than Purkinje cells and death of granular cells is induced by an apoptotic DNA fragmentation following global brain ischemia.

Adult↗