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Biomedical subjects

T Osaki

Publications and source records attributed to T Osaki.

At least 91 records · Page 5Linked to original sources
PubMed1998

IFN-gamma-inducing factor/IL-18 administration mediates IFN-gamma- and IL-12-independent antitumor effects.

We evaluated the mechanism of the antitumor effects of mouse rIFN-gamma-inducing factor/IL-18 protein on the growth of mouse tumor cell lines in vivo. Mice received IL-18 before or after challenge with CL8-1, a mouse melanoma cell line. Both regimens significantly suppressed tumor growth and reduced the number of mice with growth of tumor from 60% (3/5) to 20% (1/5). Furthermore, IL-18 administered before and after tumor inoculation completely abrogated the establishment of CL8-1 in all animals. IL-18 administration also significantly suppressed the growth of MCA205, a sarcoma cell line, even when treatment was delayed to 7 days following tumor inoculation. Although IL-18/IL-12 combination therapy had the most significant and immediate antitumor effects, many mice so treated succumbed with markedly elevated serum IFN-gamma levels. The antitumor effects of IL-18 were abrogated almost completely when NK cells were eliminated using anti-asialo GM1 Ab administration, but only marginally impaired in IFN-gamma or IL-12 gene-disrupted mice. Immunohistochemical staining revealed that the number of the CD8+ T cells, but not CD4+ T cells, found at the tumor site was reduced in animals treated with IL-18. These results indicate that IL-18 has potent antitumor effects mediated by CD4+ T cells and NK cells, but in IFN-gamma- and IL-12-independent pathways.

Adjuvants, Immunologic↗
PubMed1998

Vascular endothelial growth factor expression in non-small-cell lung cancer: prognostic significance in squamous cell carcinoma.

BACKGROUND: Recently, some studies have focused on the tumor angiogenesis and its prognostic value. We studied the expression of vascular endothelial growth factor, microvessel counts, and serum concentrations of vascular endothelial growth factor to investigate their association with clinicopathologic factors and prognosis in non-small-cell lung cancer. METHODS: The expression of vascular endothelial growth factor was determined by an immunohistochemical analysis from 91 paraffin specimens of completely resected non-small-cell lung cancers using anti-growth factor polyclonal antibody. Microvessel staining was performed by immunohistochemical analysis with anti-factor VIII-related antigen polyclonal antibody. Measurement of the serum concentrations of vascular endothelial growth factor used the sandwich enzyme-linked immunosorbent assay technique. RESULTS: Expression of vascular endothelial growth factor was detected in 48 of the 91 tumors. The positive ratio was significantly higher in patients with adenocarcinoma than in those with squamous cell carcinoma. The microvessel counts were significantly higher in the patients with nodal metastasis than in those without nodal metastasis. The serum concentrations of vascular endothelial growth factor were also significantly higher in the patients with T3-4 disease than in those with T1-2 disease. The microvessel counts were closely associated with expression of vascular endothelial growth factor. The prognosis of patients with a positive growth factor ratio was significantly worse than that of the patients with a negative ratio (p = 0.002), especially in squamous cell carcinoma. According to a multivariate analysis, only nodal status and expression of vascular endothelial growth factor were found to be independent prognostic factors. CONCLUSIONS: The expression of vascular endothelial growth factor was one of the most important prognostic factors in completely resected non-small-cell lung cancer, especially in squamous cell carcinoma.

Adult↗
PubMed1998

Distinct interleukin-1beta-converting enzyme family proteases mediate cisplatin- and staurosporine-induced apoptosis of mouse proximal tubule cells.

Interleukin-1beta converting enzyme (ICE) family proteases (caspases) are known to be implicated as important effectors of apoptotic pathways. The purpose of this study was to elucidate the role of ICE family proteases in apoptosis of mouse cells derived from the terminal proximal tubule (S3) treated with cisplatin, an anti-tumor drug, or staurosporine, a protein kinase C inhibitor. For this purpose, we measured the activities of ICE family proteases and examined the effects of tetrapeptide and viral ICE family protease inhibitors on the activities of ICE family proteases in and the degree of apoptosis of S3 cells treated with cisplatin and staurosporine. RT-PCR analysis revealed that S3 cells as well as mouse kidney express mRNA for ICE and CPP32, an ICE family protease. Results of enzymatic analysis, determination the degree of DNA fragmentation and cytotoxicity test suggest that CPP32 mediates cisplatin-induced apoptosis of S3 cells, whereas ICE family proteases other than CPP32 mediate staurosporine-induced apoptosis of S3 cells. In conclusion, distinct ICE family proteases mediate apoptosis of mouse proximal tubule cells depending on the stimuli to which the cells are exposed.

Animals↗
PubMed1998

Expression of p53 and p21 proteins in oral squamous cell carcinoma: correlation with lymph node metastasis and response to chemoradiotherapy.

p53 protein, a product of the p53 cancer suppressor gene, and p21 protein, a cyclin-dependent kinase inhibitor, were immunohistochemically investigated in 150 oral squamous cell carcinomas (SCCs) and the relationship between their expression and clinicopathological findings were evaluated. The positivity for p53 and p21 proteins was not correlated with the T-stage, mode of tumor cell invasion or tumor cell differentiation. However, the expression of p53 and p21 proteins was correlated with lymph node metastasis. Of 62 SCCs with regional lymph node metastasis, 45 SCCs (72.6%) were positive for p53 while 45 (52.9%) of 88 SCCs without metastasis expressed p53 protein (p < 0.02). In addition, p21 protein was observed in 25 (38.5%) and 18 (21.2%) SCCs with and without metastasis, respectively (p < 0.05). Furthermore, p53 protein was inversely correlated with the histopathological effect of inductive chemoradiotherapy; the rate of chemoradiotherapy-induced lethal degeneration (56.7%) in p53-negative SCCs was significantly higher than that (28.9%) in p53-positive SCCs (p < 0.005). However, no clear difference in the effect was observed between p21-positive and p21-negative SCCs. Finally, the 5-year-survival rate was highest in p53(-)-p21(+) (80.0%) followed by 76.3% in p53(-)-p21(-), 65.9% in p53(+)-p21(+) and 65.4% in p53(+)-21p(-) SCCs. These results indicate that although the expression of p21 protein is only weakly correlated with the clinico-histopathological findings, p53 protein is a useful prognostic marker and that inductive chemoradiotherapy can be successfully planned by immunohistochemical examination of p53 protein.

Adult↗
PubMed1998

Induction of differentiation in maxillary adenoid cystic carcinomas by adoptive immunotherapy in combination with chemoradiotherapy.

The successful treatment results of a case of maxillary adenoid cystic carcinoma (ACC) and the possibility of differentiation of ACC cells with chemoradioimmunotherapy are described. Combined therapy was applied to two maxillary ACCs. Adoptive immunotherapy consisted of intra-arterial injection of lymphokine-activated killer cells (total 9.0 x 10(8) cells) and recombinant interleukin-2 (1.8 x 10(5) U) and interferon-gamma (1.8 x 10(5) U) was combined with 60Co radiation (50 Gy), 5-fluorouracil (4000 mg) and peplomycin (10 mg). Immunohistochemical staining of the biopsy material obtained during the therapy revealed a marked decrease of proliferating cell nuclear antigen-positive cells and a prominent increase of Lewis Y antigen- and bone morphogenetic protein-2-positive cells. The disappearance of tumour cells and the remodeling of the sinus wall with calcification in the sinus cavity, which had been occupied by the tumour, were observed after therapy in both patients. Adoptive immunotherapy in combination with chemoradiotherapy is useful for the treatment of ACC.

Aged↗
PubMed1998

p53- and p21-independent apoptosis of squamous cell carcinoma cells induced by 5-fluorouracil and radiation.

Apoptosis-inducing therapy is becoming a new strategy in cancer therapy. We investigated the influence of 5-fluorouracil (5-FU) and radiation (gamma-ray) on the cell cycle of tumor cells, and their apoptosis-inducing activity using four oral squamous cell carcinoma lines (OSC-1 and OSC-4 with wild type p53; OSC-2 and OSC-3 with mutant type p53). The expression of p53 and cyclin-dependent kinase 2 (Cdk2) proteins was not increased even after cell treatment with 5-FU and gamma-rays in any cell lines. Although the promoter of p21 gene was not activated, p21-mRNA expression was increased by 5-FU and gamma-rays. p21 protein was expressed by irradiation in parallel with the increase in the messages but not by 5-FU in any OSC lines. Despite the increased p21 protein expression, cyclin E/Cdk2 kinase activity was not suppressed in irradiated cells. With the increased expression of cyclin E protein, 5-FU augmented the kinase activity in OSC-1, OSC-2 and OSC-3 cells. However, with a constant cyclin E level the kinase activity in OSC-4 was not increased by 5-FU. Without correlation to the kinase activity, 5-FU strongly induced apoptosis in OSC-2, OSC-3 and OSC-4 accumulating cells in the S phase, but 5-FU only very weakly induced apoptosis in OSC-1. While irradiated cells were in the G2/M phase, they exhibited apoptosis, to the same degree, in all OSC lines. Furthermore, the expression of Bax protein was not increased by 5-FU or gamma-rays, although apoptosis was induced by both treatments. These findings indicate that 5-FU and gamma-rays induce apoptosis of squamous cell carcinoma cells in p53- and p21-independent manners, in the S and G2/M phases, respectively.

Antimetabolites, Antineoplastic↗
PubMed1998

A virulence factor of Helicobacter pylori: role of heat shock protein in mucosal inflammation after H. pylori infection.

Among the various virulence factors of Helicobacter pylori the role of its heat shock protein 60 (HSP60, HspB) in mucosal inflammation after H. pylori infection was examined. In flow cytometric analysis, the expression of HSP60 on the cell surface was different, depending on the H. pylori strain used. The HSP60 epitope was also detected on the surface of both human gastric cancer cells (MKN45, KATOIII, and MKN28) and human gastric biopsy specimens. The intensity of the expression of HSP60 on the cell surface correlated significantly with the adhesion of H. pylori to MKN45 cells, but not with urease activity and production of vacuolating cytotoxin. A monoclonal antibody to H. pylori HSP60 inhibited the adhesion of H. pylori to MKN45 cells. These results suggest that HSP60 of H. pylori might act as an important virulence factor after H. pylori infection.

Antibodies, Monoclonal↗
PubMed1998

Establishment and characterisation of a monoclonal antibody to inhibit adhesion of Helicobacter pylori to gastric epithelial cells.

Monoclonal antibodies (MAbs) that inhibit adhesion of Helicobacter pylori to human gastric cancer (MKN45) cells were established to clarify the mechanism of adhesion of H. pylori. Of 53 hybridoma clones screened by the primary inhibition assay for adhesion, MAb A20 of IgM class was selected on the basis of both its reactivity to whole cells of H. pylori by ELISA and its inhibitory effect on adhesion of H. pylori. The adhesion of H. pylori strain TK1029 to MKN45 cells was inhibited by MAb A20, depending on the concentration of the MAb. The MAb recognised the surface antigen, lipopolysaccharide (LPS) of H. pylori, suggesting that LPS is associated with adhesion of H. pylori to human gastric epithelial cells.

Antibodies, Bacterial↗
PubMed1998

Effects of interleukin-12 on the induction of cytotoxic T lymphocytes from the regional lymph node lymphocytes of patients with lung adenocarcinoma.

Lung cancer-specific cytotoxic T lymphocytes (CTL) were induced by repeated stimulations of regional lymph node lymphocytes (RLNL) in lung cancer patients with either autologous or HLA-A-locus-matched tumor cells. To investigate the effect of interleukin-12 (IL-12), IL-12 was added during the stimulation of RLNL from HLA A24/adenocarcinoma patients with either autologous tumor cells or HLA A24-positive adenocarcinoma cells (PC-9) in combination with, or instead of interleukin-2 (IL-2), and then the cytotoxic activity, cytokine production and populations of the lymphocyte subsets were examined. The addition of IL-12, or the substitution of IL-2 by IL-12 was found to enhance the cytotoxic activity and the cytokine production (IFN-gamma, GM-CSF) of the CTL as compared with IL-2 alone. The cytotoxic activity and cytokine production were both partially inhibited by anti-MHC-class I monoclonal antibody. The CTL thus induced by IL-12 had a higher proportion of CD3+/CD56+ cells than the CTL induced with IL-2 alone. The positively selected CD8+/CD56- lymphocytes showed PC-9-specific cytotoxic activity, because the population did not show any cytotoxicity to K562 or A549 (HLA-A26/A30). However, the CD3+/CD56+ lymphocytes were cytotoxic to both PC-9 and K562. In conclusion, IL-12 is considered to be a useful cytokine for both the induction of lung-cancer specific CTL and the augmentation of non-MHC-restricted cytotoxicity against tumor cells, and may be applicable for adoptive immunotherapy using CTL.

Adenocarcinoma↗
PubMed1998

Lung cancer patients have increased 8-hydroxydeoxyguanosine levels in peripheral lung tissue DNA.

The 8-hydroxydeoxyguanosine (8-OH-dG) levels in the peripheral parts of human lung tissues were compared between lung cancer patients (n=70) and non-cancer patient controls (n=15). An increased level of 8-OH-dG was observed in the lung cancer group, in both the adenocarcinoma and non-adenocarcinoma (mainly squamous cell carcinoma) groups, as compared to the non-cancer control group. This result suggests that reactive oxygen species are partly involved in the induction of lung carcinomas (both adenocarcinoma and non-adenocarcinoma).

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Influence of twinline, an elemental diet, on the generation of nitric oxide and reactive-oxygen intermediates from mouse peritoneal macrophages and polymorphonuclear leukocytes.

The influence of Twinline (SNN-6010), an elemental diet containing medium-chain triglycerides, on the generation of nitric oxide (NO) and superoxide (O2.-) has been examined in mouse peritoneal macrophages and polymorphonuclear leukocytes (PMN). When PMN and peritoneal macrophages obtained from untreated mice were cultured in medium containing 0.1% and 1% (v/v) Twinline for 48h and stimulated with phorbol myristate acetate or N-formyl-methionyl-leucyl-phenylalanine, their chemiluminescence and O2.- generation were strongly suppressed, as was NO generation from peritoneal macrophages. PMN and peritoneal macrophages obtained from mice fed Twinline for 30 days generated much smaller amounts of 02.- and NO compared with PMN and peritoneal macrophages from control mice. In conjunction with this suppressed NO generation, inducible NO synthase and its mRNA expression in peritoneal macrophages were suppressed by Twinline both in-vivo and ex-vivo. Although phagocytosis of PMN and peritoneal macrophages was not suppressed by Twinline; their candida-killing activity was markedly suppressed. These results indicate that Twinline suppresses the host-defence function of PMN and peritoneal macrophages by down-regulating their generation of reactive-oxygen intermediates and NO.

Animals↗
PubMed1998

[The role of heat shock protein 60 (HSP60) of Helicobacter pylori in adhesion of H. pylori to human gastric epithelial cell].

Adhesion of Helicobacter pylori to both human gastric carcinoma cell lines (MKN45, MKN28 and KATO III) and prepared primary human gastric epithelial cells were analyzed with flow-cytometry. All strains adhered to human gastric carcinoma cells. Especially, these strains strongly adhered to MKN45 cells. Adhesion of H. pylori strains to prepared primary human gastric epithelial cells was also observed. However, the adherence rates of H. pylori to these cells were different among the cells used. These results suggested that the host factor might be important for adhesion of the bacteria to human gasgric cells. In addition, H20 monoclonal antibody directed to H. pylori HSP60 inhibited the adhesion of H. pylori to both cells. These results indicate that H. pylori HSP60 might be associated with the adhesion of the bacteria to human gastric epithelial cells.

Bacterial Adhesion↗
PubMed1998

Detection of Helicobacter pylori in fecal samples of gnotobiotic mice infected with H. pylori by an immunomagnetic-bead separation technique.

By an immunomagnetic-bead (IMB) separation technique, isolation of Helicobacter pylori from gastrointestinal and fecal samples of gnotobiotic mice infected with the microorganism was tried. The isolation rate of H. pylori from stomach samples after IMB separation was not higher than that of direct culture of the samples. After IMB separation of feces, H. pylori was detectable by PCR, although H. pylori was not culturable.

Animals↗
PubMed1998

p53 alteration, proliferating cell nuclear antigen, and nucleolar organizer regions in thymic epithelial tumors.

We examined p53 protein expression, p53 gene mutation, proliferating cell nuclear antigen (PCNA), and argyrophilic nuclear organizer regions (AgNOR), in 30 patients with surgically-treated thymic tumors (26 thymoma and 4 thymic carcinoma cases). p53 expression ratio with DO-1 was divided as p53 negative (0% positivity), low expressor (<10% positivity), high expressor (>10% positivity). The incidence of p53 low and high expressor in thymoma were 19% (5/26) and 8% (2/26), respectively. p53 immunopositivity in thymoma was significantly correlated with PCNA labeling index (LI). p53 expression ratio in invasive thymoma (33%) tended to be higher than that in non-invasive thymoma (18%). p53 expression was detected in one of the thymic carcinoma. There were no p53 gene mutations in 15 invasive thymoma, although one of four (25%) thymic carcinomas showed two point mutations. p53 gene alterations seem to be associated with malignant activity of tumor cells, and therefore detection of p53 gene mutations is useful as a diagnostic factor.

Adult↗
PubMed1998

Relationship between expression of HSP60, urease activity, production of vacuolating toxin, and adherence activity of Helicobacter pylori.

The relationship between the expression of heat shock protein 60 (HSP60) of Helicobacterpylori on the bacterial surface and its pathogenic factors of urease activity, production of vacuolating toxin, and adherence to human gastric carcinoma cells was examined. There was no correlation between urease activity, production of vacuolating toxin, and the expression of HSP60. However, there was a significant correlation between the adherence activity to human gastric carcinoma MKN45 cells and the expression of HSP60 (correlation coefficient; r = 0.68). In an inhibition assay with anti-HSP60 antibody, we examined the adhesion of H. pylori to MKN45 cells. The adherence of 3 of 13 H. pylori strains was inhibited by anti-HSP60 antibody. The results suggest that H. pylori HSP60 may be associated with the adhesion of H. pylori to human gastric cells.

Bacterial Adhesion↗
PubMed1998

Characteristics of Helicobacter pylori strains isolated from patients with different gastric diseases.

The pathogenesis of chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and remnant gastritis is considered to be related to infection by Helicobacter pylori. The purpose of this study was to investigate the characteristics of H. pylori strains isolated from patients with various gastric diseases. Fifty strains of H. pylori were clinically isolated at Keio University Hospital and were assessed for (i) vacuolating cytotoxin (VT) production, by cytotoxic assay using rabbit kidney (RK) 13 cells; (ii) the expression of cytotoxin associated gene (cagA), by polymerase chain reaction; and (iii) motility on a semi-solid plate. Positivity for VT production by H. pylori strains isolated from patients with chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and remnant gastritis, was 100%, 89%, 92%, 100%, and 60%, respectively. There was no significant difference in the incidence of positivity for cagA among the strains isolated from different gastric diseases. Swarming distances, which indicate motility of H. pylori strains, were 12.7, 13.2, 12.8, 16.6 and 9.2mm in strains from chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and remnant gastritis, respectively, with H. pylori isolated from remnant gastritis showing significantly less motility than H. pylori isolates from other diseases. There were no significant differences in VT production and cagA positivity among the H. pylori strains.

Animals↗