Biomedical subjects

T Osaki

Publications and source records attributed to T Osaki.

At least 109 records · Page 6Linked to original sources

PubMed1997

Prognostic value of the immunohistochemical detection of p16INK4 expression in nonsmall cell lung carcinoma.

BACKGROUND: The product of the p16INK4/CDKN2/MTS1 (p16) controls the transition from the G1 phase to the S-phase in the cell cycle by inhibiting the phosphorylation of the retinoblastoma gene product. A lack of p16 expression has been reported in various cancer cell lines and tumors; however, there have been only a few reports on the prognostic significance of p16 alteration. The authors studied p16 expression in nonsmall cell lung carcinoma (NSCLC) and also examined its correlation with clinicopathologic features and prognosis. METHODS: p16 expression was determined by immunohistochemical analysis of 115 paraffin specimens of primary NSCLC that were curatively resected. The immunohistochemical study was performed using the labeled streptavidin-biotin method with anti-p16 rabbit polyclonal antibody. RESULTS: Thirty-one of 115 NSCLC specimens (27%) showed negative p16 staining. The frequency of negative p16 expression was significantly higher in squamous cell carcinoma (39.5%) than in adenocarcinoma (20.3%) (P = 0.026). There were no statistically significant differences in the p16 status with respect to age, gender, smoking history, histologic differentiation, or stage of the disease. The Kaplan-Meier survival curves demonstrated that patients with negative p16 expression survived for a significantly shorter period of time than those with positive p16 expression (P = 0.043). p16 status was a significant prognostic factor, especially in patients with early stage disease (Stages I-II) (P = 0.039). CONCLUSIONS: A lack of p16INK4 expression in NSCLC was observed more frequently in squamous cell carcinoma than in adenocarcinoma, and also was found to be closely related to prognosis, especially in patients with early stage squamous cell carcinoma.

Adenocarcinoma↗

PubMed1997

Cisplatin-induced apoptosis of immortalized mouse proximal tubule cells is mediated by interleukin-1 beta converting enzyme (ICE) family of proteases but inhibited by overexpression of Bcl-2.

Cisplatin is known to induce serious renal damage including acute renal failure, the major site of renal injury appears to be localized to the third segment of the proximal tubule (S3). Apoptosis occurs during a variety of acute injuries to tubule cell. The purpose of this study was to determine whether cisplatin induces apoptosis of immortalized mouse S3 cells, and to define the intracellular pathways leading to cell death. S3 cells exposed to cisplatin exhibited biochemical, morphological, and flow cytometric changes characteristic of apoptosis associated with slight necrosis. Cisplatin-induced apoptosis could be inhibited by overexpression of crmA, a cowpox virus gene, of which the product is known to suppress activities of the interleukin-1 beta converting enzyme (ICE) family proteases. On the other hand, overexpression of bcl-2, an antiapoptotic oncogene, rendered S3 cells partially resistant to cisplatin. These results indicate that cisplatin-induced proximal tubule damage is associated with apoptosis, which is positively modulated by the ICE family of proteases and negatively by the product of bcl-2.

Animals↗

PubMed1997

Postoperative prognosis in patients with non-small cell lung cancer with synchronous ipsilateral intrapulmonary metastasis.

BACKGROUND: Non-small cell lung cancer with intrapulmonary metastasis (PM) was recently reclassified according to the revision of the TNM classification. To determine whether the new staging system is appropriate, we analyzed the postoperative prognosis of patients with synchronously detected and resected PM lesions. METHODS: Of 509 patients with non-small cell lung cancer who underwent surgical resection, 42 patients were revealed to have synchronous and ipsilateral PM. Their survival was compared with that of matched stage groups (without PM) by Kaplan-Meier test and log rank test. RESULTS: Two patients who were classified as stage I survived 40 and 30 months after operation, respectively. One patient was determined to be stage II, and survived 100 months postoperatively. Thirty-eight patients were classified as stage IIIA/IIIB (19 each) (90.5% of all cases with PM). There was no significant difference between 3- and 5-year survival rates of the PM stage IIIA group (34.2% and 34.2%) and those of the other IIIA (144 patients; 37.9% and 31.6%). Survival rates of such stage IIIA subgroups as PM, T3 and N2, were comparable. No significant differences were observed between the 3- and 5-year survival rates of the PM stage IIIB (16.6/16.6%) and those of the other stage IIIB (45 cases; 11.7% and 0.0%). The survival rates of such stage IIIB subgroups as PM, T4 and N3 were also similar. CONCLUSIONS: The new staging system for patients with synchronous resectable PM appears to be reasonable regarding survival. Most cases of PM are categorized as locally advanced disease; however, stage IIIA/IIIB cases have become a more heterogeneous population.

Adenocarcinoma↗

PubMed1997

Treatment strategy for patients with surgically discovered N2 stage IIIA non-small cell lung cancer.

BACKGROUND: The treatment strategy for patients with non-small cell lung cancer and clinically negative, but surgically detected mediastinal lymph node metastasis (surgically discovered N2 disease) is controversial. METHODS: From August 1979 through December 1994, 53 patients with non-small cell lung cancer were found to have surgically discovered N2 disease. We retrospectively studied the clinical characteristics and the factors that influenced the prognosis in these patients. RESULTS: The 3-year and 5-year survival rates and the median survival for the 53 patients with surgically discovered N2 disease were 44%, 21%, and 26 months. Two thirds of the patients had adenocarcinoma. Only complete resection affected long-term survival; adjuvant therapy had no effect on survival. In regard to lymph node status, a single metastatic focus in the aortic area was associated with long-term survival. CONCLUSIONS: Patients with adenocarcinoma may require histologic determination of N2 disease. Complete resection, including extensive and complete mediastinal lymph node dissection, is warranted in patients with surgically discovered N2 disease. In particular, when the aortic lymph node (including stations 5 and 6) alone is involved, the patients should undergo as complete a resection as possible.

Adenocarcinoma↗

PubMed1997

Micrometastatic tumor cells in the bone marrow of patients with non-small cell lung cancer.

BACKGROUND: This study was designed to evaluate the incidence and clinical implications of detection of micrometastatic cancer cells in bone marrow aspirates of patients with operable non-small cell lung cancer. The relationship between micrometastatic cells and p53 overexpression in the primary tumor was also assessed. METHODS: Thirty-nine patients with stages I through III non-small cell lung cancer who underwent curative resection were entered into this study. Immunohistochemistry with monoclonal antibody to cytokeratin 18 was used to detect tumor cells in bone marrow. Immunostaining of p53 protein in the corresponding primary tumors was also done. RESULTS: Cytokeratin 18-positive cells were detected in 15 (39%) of the 39 patients. Overexpression of p53 was associated with positivity of the tumor cells in the bone marrow at borderline significance (14/29 versus 1/10; p = 0.0574). The patients with cytokeratin 18-positive cells in bone marrow demonstrated a significantly earlier recurrence than those without such cells (p = 0.0083, log-rank test). CONCLUSIONS: Micrometastatic cancer cells were frequently present in bone marrow of patients with operable non-small cell lung cancer and may be a significant predictor of early recurrence. Further evaluation of this method may be useful in identifying patients with non-small cell lung cancer who are most likely to benefit from adjuvant chemotherapy.

Aged↗

PubMed1997

Micrometastatic P53-positive cells in the lymph nodes of non-small-cell lung cancer: prognostic significance.

OBJECTIVES: Approximately one fourth of all patients with stage I non-small-cell lung cancer die of tumor recurrence, despite radical removal of their tumors. We thus tried to detect micrometastasis in the regional lymph nodes indicated to be tumor free by conventional histopathologic methods in patients with non-small-cell lung cancer by using immunohistochemical staining for p53 protein. We also investigated the relation between micrometastatic p53-positive cells in the lymph nodes and the prognosis of the patients. METHODS: Samples from 480 regional lymph nodes were taken from 47 patients who underwent pulmonary resection for non-small-cell lung cancer and whose primary lesions were positive for p53 immunohistochemical staining. These samples were fixed in formalin and embedded in paraffin. We used p53 immunohistochemical staining to detect micrometastatic tumor cells in the lymph nodes. RESULTS: Cells positive for p53 protein were found in 14 of 31 (45%) patients with a negative pathologic lymph node status and in 26 of 315 (8.3%) lymph nodes in these patients. The proportion of patients with micrometastasis who survived was also significantly lower than the proportion of patients without micrometastasis who survived (p = 0.0001). CONCLUSIONS: Immunohistochemical staining for the p53 protein offers a rapid, sensitive, and useful way of detecting for micrometastasis to the regional lymph nodes in patients with non-small-cell lung cancer that is positive for p53 staining. The patients with such micrometastases have a poor prognosis and thus need to be carefully followed up after the initial pulmonary resection.

Carcinoma, Non-Small-Cell Lung↗

PubMed1997

Influence of SNN-6010, an elemental diet, on the generation of cytokines, NO, and chemiluminescence from leukocytes and umbilical vein endothelial cells in man.

AIMS: There is insufficient information on the influence of elemental diet (ED) on leukocytes and endothelial cells although ED has been used increasingly for debilitated and post-operative patients. We here aimed to show the influence of SNN-6010 (Twinline; TL), which contains medium-chain triglycerides, on the generation of cytokines and nitric oxide (NO) and chemiluminescence in human umbilical vein endothelial cells (HUVEC) and leukocytes. METHODS: Leukocytes were obtained from 10 healthy volunteers and 10 patients with jaw fractures who underwent TL for 30 days after intermaxillary fixation. Luminol-dependent chemiluminescence and NO generation were measured in polymorphonuclear leukocytes (PMN) and HUVEC and generation of interleukin-1 beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), and prostaglandin E2 (PGE2) as well as expression of these cytokines' mRNA were examined in lymphocytes, monocytes, PMN, and HUVEC. RESULTS: TL dose-dependently suppressed generation of IL-1beta, TNF-alpha, PGE2, and NO in all kinds of cells from healthy individuals. Lymphocytes from patients who underwent TL feeding for 30 days showed reduced generation of IL-1beta and TNF-alpha, and the suppressed cytokine generation corresponded with the decreased expression of mRNA of these cytokines. Chemiluminescence by PMN from healthy individuals was suppressed by TL dose-dependently, and PMN from TL-fed patients showed reduced chemiluminescence. CONCLUSION: These results appear to indicate that TL suppresses the functions of leukocytes and endothelial cells by down-regulating the generation of reactive oxygen intermediates, NO, and cytokines.

Adult↗

PubMed1997

Adenoid basal carcinoma of the uterine cervix: immunohistochemical study and literature review.

Adenoid basal carcinoma of the uterine cervix is rare and its cell origin is still obscure. We report a case of adenoid basal carcinoma of the uterine cervix discovered incidentally in a 69-year-old woman who had been hysterectomized due to endometrial adenocarcinoma of the uterine corpus. Histologically, small round-to-oval cancer cell nests with peripheral cell palisading were seen budding from the basal cell layer of the uterine cervix showing carcinoma in situ. Immunohistochemically, the basaloid cells of the adenoid basal carcinoma were positive for keratins 14, 17 and 19 and resembled reserve cells of the cervical epithelium. The results of this study clearly demonstrated that adenoid basal carcinoma shows a phenotype similar to reserve cells of the uterine cervix. A review of the literature indicated that this tumor has a favorable prognosis and should be clearly separated from adenoid cystic carcinoma, which has a much poorer outcome.

Aged↗

PubMed1997

Combined carboplatin and cisplatin therapy in patients with advanced non-small cell lung cancer.

Combining cisplatin and carboplatin may eliminate some of the toxic effects of each agent and permit the use of higher doses, because these agents have different pharmacodynamics and dose-limiting toxicities. We investigated the safety and efficacy of these agents in combination. The toxicity profile was evaluated in a Phase I trial in 18 patients with advanced non-small cell lung cancer (NSCLC). Carboplatin was administered in doses ranging from 200 to 400 mg/m2 on day 1 and cisplatin at a dose of 80 mg/m2 on day 3. Only one cycle of chemotherapy was administered. Thrombocytopenia was the dose-limiting toxic effect. The maximal tolerated dose of carboplatin was 350 mg/m2. We then investigated the efficacy of the optimal dose of this combined chemotherapy in a Phase II trial in 13 patients. We used a carboplatin dose of 300 mg/m2 for safety in the Phase II trial. Three of 13 patients developed grade 3-4 hematologic toxicity, which was improved without major complications. A partial response was observed in 5 of 13 patients (38.5%). Combination chemotherapy with carboplatin (day 1, 300 mg/m2) and cisplatin (day 3, 80 mg/m2) showed promising effects in patients with advanced NSCLC.

Aged↗

PubMed1997

Cytotoxicity and motility of Helicobacter pylori.

To clarify the relationship between interleukin-8 (IL-8) production and virulent factors, we examined the motility and cytotoxicity of H. pylori, suggested to be a major cause of chronic gastritis and peptic ulcers. Our results demonstrated that among cytotoxic strains of H. pylori, high-motility strains induced more IL-8 than low-motility strains. There was no correlation between cytotoxicity and motility of H. pylori. Four restriction fragment length polymorphism (RFLP) patterns were observed in the flaA PCR products. There was no correlation between flaA RFLP and motility. In conclusion, our findings suggest that both cytotoxicity and motility are virulent factors in the pathogenesis of gastric mucosal injury.

Animals↗

PubMed1997

Effect of sofalcone on adherence, production of vacuolating toxin, and induction of interleukin-8 secretion by Helicobacter pylori.

We examined the effect of sofalcone, a mucosal protective agent that has been reported to inhibit growth of Helicobacter pylori, on adherence, production of vacuolating toxin (VT), and induction of interleukin-8 (IL-8) secretion by H. pylori. Mixing VT with various concentrations (1.5-100 micrograms/ml) of sofalcone resulted in a 50% decrease in the VT titer. When toxigenic H. pylori strains were incubated in the presence of sofalcone (20 and 40 micrograms/ml), although bacterial growth was not inhibited significantly there was significant inhibition of VT production. Notable inhibition of IL-8 secretion by human gastric cancer cells (MKN 45) was detected in the presence of sofalcone (20-100 micrograms/ml) after co-incubation with H. pylori strains. In flow cytometric analysis, adherence of H. pylori strains to MKN 45 cells was significantly inhibited by treatment with sofalcone (20-60 micrograms/ml), indicating at least one reason for the inhibition of IL-8 secretion. These results show that sofalcone is an effective mucosal protective agent that inhibits both production of VT and induction of IL-8 secretion.

Anti-Ulcer Agents↗

PubMed1997

Production and characterisation of monoclonal antibodies to heat-shock protein 60 of Helicobacter pylori.

Two monoclonal antibodies (MAbs), designated as H9 (IgG2a) and H20 (IgM), directed against heat-shock protein 60 (HSP60) of Helicobacter pylori strain TK1029 were established. Affinity-purified antigens cross-reacted in immunoblots with MAb H9 and MAb H20 respectively. These antigens also reacted with the 3C8 MAb previously established in this laboratory, which recognised Yersinia enterocolitica HSP60. By amino-acid sequence analysis, the N-terminal amino-acid sequence of the protein recognised by both H9 and H20 MAbs was confirmed as the amino-acid sequence of H. pylori HSP60 reported previously. Both MAbs reacted with nine strains of H. pylori in enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. In addition, MAb H9 reacted with extracts of other bacteria including H. mustelae, Pseudomonas aeruginosa, Vibrio cholerae, Serratia marcescens, Proteus mirabilis, Escherichia coli and Shigella sonnei. In contrast, MAb H20 reacted only with strains H. pylori. These results suggest that both the species-specific epitope recognised by MAb H20 and the common epitope recognised by MAb H9 exist on HSP60 of the bacterial cell. Both MAbs also reacted with the 60-kDa protein in the lysate of human gastric carcinoma (MKN45) cells. It was shown by immunohistochemical staining that gastric epithelial cells of four out of six biopsy specimens examined stained positively with MAb H20. These results suggest that there is a common epitope in H. pylori HSP60 and human gastric epithelial cells.

Amino Acid Sequence↗

PubMed1997

Heat-shock protein 60 homologue of Helicobacter pylori is associated with adhesion of H. pylori to human gastric epithelial cells.

A previous study reported a relationship between the expression of heat-shock protein 60 (HSP60) by Helicobacter pylori and its adhesion to human gastric carcinoma (MKN45) cells. To examine whether the HSP60 homologue of H. pylori is associated with the adhesion of H. pylori to human gastric epithelial cells, an inhibition assay of adhesion of H. pylori to MKN45 cells was performed by flow cytometric analysis with monoclonal antibody (MAb) designated as H20 recognising HSP60 of H. pylori. The rate of adhesion of H. pylori pretreated with MAbH20 to MKN45 cells was lower than that of untreated H. pylori. Primary human gastric epithelial cells from a patient with gastric cancer were also prepared for comparison in the inhibition assay with MAbH20. H. pylori adhered to the primary human gastric epithelial cells, and this adhesion was significantly inhibited by MAbH20. These results suggest that the H. pylori HSP60 homologue recognised by MAbH20 might be associated with the adhesion of H. pylori to primary human gastric epithelial cells as well as to cultured gastric cancer cells.

Adhesins, Bacterial↗

PubMed1997

Studies on the relationship between adhesive activity and haemagglutination by Helicobacter pylori.

The adhesion of Helicobacter pylori to gastric carcinoma cells (MKN45, KatoIII and MKN28) and Intestine-407 cells was tested by flow cytometric analysis. The mean adhesion rates of H. pylori strains to MKN45, KatoIII and Intestine-407 cells were 90.5, 42.7 and 15.1%, respectively. There was no statistical correlation between the adhesion rates to MKN45 cells and haemagglutination (HA) activity of H. pylori strains, although H. pylori strains with high HA activity with human type O erythrocytes tended to adhere effectively to MKN45 cells. No correlation between adhesion and production of vacuolating toxin was observed.

Animals↗

PubMed1997

Growth inhibition of Helicobacter pylori by monoclonal antibody to heat-shock protein 60.

The H20mAb recognizing the 60-kilodalton protein, which existed in the outer membrane and was induced by heat shock at 42 C, was established. The molecule recognized with the mAb was a heat-shock protein 60 (HSP60) of Helicobacter pylori. To understand the role of HSP60 on the cell surface of H. pylori, whether or not H20mAb affects the growth of H. pylori was investigated. When bacteria were cultured with H20mAb, growth was markedly inhibited after 24 hr, although an initial 5 hr-incubation with the mAb induced no significant inhibition of H. pylori growth. The 24- and 48 hr growth of the bacteria after washing to remove the mAb at 5 hr was also inhibited though the inhibitory effect was not strong. In electron microscopical analysis, the spots with high electron density in the cytoplasm of the bacteria treated with H20mAb were increased, depending on the length of incubation time from 5 to 24 hr. After 24 hr treatment with H20mAb, bacterial destruction was also observed, indicating bactericidal activity by H20mAb. These results suggest that the HSP60 on the cell surface of H. pylori might have an essential role in the growth of the bacteria.

Amino Acid Sequence↗

PubMed1997

The induction of cytotoxic T lymphocytes against HLA-A locus-matched lung adenocarcinoma in patients with non-small cell lung cancer.

To induce cytotoxic T lymphocytes (CTL) against non-small cell lung cancer (NSCLC) efficiently, the induction of CTL was attempted using HLA-A locus-shared allogeneic NSCLC cells. T cells derived from either tumor tissue specimens or the regional lymph nodes of patients with NSCLC were stimulated twice or three times with an HLA-A2/A24-positive NSCLC cell line (PC-9), and thereafter the cytotoxic activity was examined by 51Cr-release assay. In patients with HLA-A24/ adenocarcinoma, anti-PC-9 cytotoxicity was induced in all 6 patients tested. Anti-PC-9 cytotoxicity was induced in 2 out of 5 patients with HLA-A2 (A24-)/adenocarcinoma, in 2 out of 4 patients with HLA-A24/squamous cell carcinoma, and 1 of 2 patients with HLA-A2/squamous cell carcinoma. The cytotoxic activity was observed to kill PC-9 selectively, not other NSCLC lines, and the activity was substantially blocked by anti-MHC class I antibody, but not by anti-MHC class II antibody. The PC-9-specific CTL produced gamma-interferon in response to autologous tumor cells. These results indicated that the anti-PC-9 cytotoxicity was mediated by cytotoxic T lymphocytes that may recognize the T cell epitope(s) shared and presented by HLA-A2 and/or HLA-A24-positive NSCLC.

Adenocarcinoma↗

PubMed1997

Hemostatic treatment after tooth extraction in a patient with factor V deficiency.

BACKGROUND: Factor V deficiency is a very rare hereditary coagulation disorder and tooth extraction in the patient with factor V deficiency has not been reported except in one case. PATIENTS AND TREATMENT: A 38-year-old woman with factor V deficiency was referred for extraction of the impacted lower third molar. After intravenous administration of frozen fresh plasma (FFP) and recognition of an increase of factor V level from 1-31%, upper and lower third molars were extracted. Eighteen and 48 h after the extraction, factor V was intermittently supplemented by injection of 4 and 2 units of FFP, respectively, and factor V was maintained above 12%. To form fast coagula and to protect the wound, the lower extraction socket was filled with a fibrin glue composed of factor XIII and fibrinogen (Beriplast P) and a plastic splint was applied. The wound was healed and epithelized within 2 weeks after the extraction without any bleeding or infectious consequences. CONCLUSION: Extraction in the patient with factor V hereditary deficiency is safely performed by both supplementation of factor V and application of local hemostasis.

Adult↗

PubMed1997

Intranodal injection of anticancer drugs into fixed cervical metastatic lymph nodes.

OBJECTIVE: In patients with head and neck carcinoma, fixed enlarged metastatic lymph nodes (LNs) are sometimes inoperable and carry an increased risk of mortality. To control metastatic LNs, we attempted intranodal injection of anticancer agents. SUBJECTS AND METHODS: Fifteen patients with squamous cell carcinoma arising in the gingiva (8), tongue (3), floor of the mouth (1), or maxillary sinus (3) were enrolled. These patients consisted of two groups, those in the early era in which the fixed LNs of six patients were treated with 60Co (RA group) and those in the late era in which both radiation and intranodal injection of anticancer agents were administered to nine patients (IN group). Intranodal injection consisted of peplomycin, 5-fluorouracil, and cis-diamminedichloroplatinum. RESULTS: In the IN group, LNs regressed from about 40% to nearly 100%, although two patients showed no appreciable response. The LNs treated by combination therapy regressed considerably while LNs in the same patients treated with 60Co alone showed a minor response or grew gradually. In three patients, the LNs regressed sufficiently to be extirpated safely. The good clinical response in the locally injected LNs was histologically associated with distinct evidence of tumor cell degeneration. In the RA group, none of the LNs responded to radiation with 60Co; one LN exhibited slight regression, but the others enlarged during and soon after the radiation. Compatible with the clinical effects, many patients in the IN group demonstrated a good prognosis; three are alive without disease, and four survived for prolonged periods. However, all patients in the RA group died due to progression of the positive LNs or pulmonary complication within 10 months. CONCLUSION: These results indicate that intranodal injection of anticancer drugs is useful for the management of fixed enlarged LNs.

Aged↗