Biomedical subjects

M Takada

Publications and source records attributed to M Takada.

821 records · Page 46Linked to original sources

PubMedDate not supplied

Differing effects of staurosporine and UCN-01 on RB protein phosphorylation and expression of lung cancer cell lines.

The retinoblastoma gene product (RB protein) plays a key role in the progression of the cell cycle from G1 to S phase in normal and neoplastic cells. The activity of RB is regulated by phosphorylation and dephosphorylation with cell-cycle-dependent protein kinases. We investigated the effect of the protein kinase inhibitors, staurosporine and 7-hydroxy-staurosporine (UCN-01), on RB protein expression of N417 small cell lung cancer cells (absent RB), H209 small cell lung cancer cells (mutant RB), and Ma-31 non-small cell lung cancer cells (wild-type RB), using immunologic blotting. Staurosporine and UCN-01 each suppressed the growth of N417, H209 and Ma-31 cells in a dose-dependent manner in MTT assay. IC50 values of staurosporine for N417, H209 and Ma-31 cells were 54, 29 and 602 nM, respectively. IC50 values of UCN-01 for N417, H209 and Ma-31 cells were 737, 181 and 2,197 nM, respectively. Exposure to staurosporine and UCN-01 for 72 h each suppressed the level of expression and altered the ratio of phosphorylated/dephosphorylated RB protein (ppRB/pRB) of Ma-31 cells. Conversely, these agents increased the expression level of RB protein at concentrations less than IC50, and did not change phosphorylation status of mutant RB protein of H209 cells at the concentrations studied. A time course study demonstrated that exposure to the IC50 concentration of staurosporine for 48-72 h increased the ratio of ppRB/ pRB of Ma-31 cells, while exposure to the IC50 concentration of UCN-01 decreased that ratio. UCN-01 increased % cells in G2 + M phase and decreased % cells in S phase, while staurosporine increased % cells in G1 phase and decreased % cells in G2 + M phase. UCN-01 did not induce apoptosis (DNA content < 2 N) of Ma-31 cells, but staurosporine induced it. These findings suggest that the differing effects of staurosporine and UCN-01 on RB protein expression and cell cycle phases of lung cancer cells may explain their differing in vivo antitumor effect of staurosporine and UCN-01 despite their similar chemical structures.

Alkaloids↗

PubMedDate not supplied

Phase II study of 3-hour infusion of paclitaxel in patients with previously untreated stage III and IV non-small cell lung cancer. West Japan Lung Cancer Group.

Sixty patients with previously untreated non-small cell lung cancer of stages III and IV were treated with a 210 mg/m2 dose of paclitaxel by means of a 3-hour infusion. The objective response rate was 32% (95% confidence interval, 20-45%): 1 complete response and 18 partial responses. The median duration of response was 15 weeks, and the projected median survival duration of all patients was 30 weeks. Grade 3-4 neutropenia occurred in 73% of patients. Other grade 3-4 adverse events included anemia (5%), vomiting/nausea (8%), peripheral edema (2%), alopecia (7%), elevation of AST (2%), peripheral neuropathy (3%), allergic reaction (2%), arthralgia/myalgia (3%), and interstitial pneumonitis (3%). Paclitaxel administered at 210 mg/m2 by means of a 3-hour infusion every 3 weeks demonstrated a notable activity against previously untreated advanced non-small cell lung cancer, with a 32% major response rate. Major toxicity was neutropenia. Hypersensitivity, neurotoxicity, arthralgia/myalgia and cardiac toxicity were mild and easily managed.

Aged↗

PubMedDate not supplied

Gamma/delta T-cell receptor type granular lymphocyte proliferative disorder associated with rheumatoid arthritis.

We present here a case report of a 69-year-old female patient with T granular lymphocyte proliferative disorder (T-GLPD) expressing the gamma/delta T-cell receptor. The patient had been treated for rheumatoid arthritis for 25 years, and presented with mild anaemia. Cell-surface marker analysis was carried out using flow cytometry and natural killer function was determined using a chromium release assay. The case report is followed by a summary of the 21 other gamma/delta T-GLPD cases reported in the literature and a comparison of their clinical characteristics with those of T-GLPD cases expressing the alpha/beta T-cell receptor. The clinical symptoms and the frequency of association with rheumatoid arthritis are similar in gamma/delta and alpha/beta T-GLPD, but a prevalence of the CD8- cell-surface marker and enhanced natural killer function appear to be characteristics of gamma/delta T-GLPD.

Aged↗

PubMedDate not supplied

Binding of biotinylated thrombin receptor peptide to cloned human thrombin receptor overexpressed in baby hamster kidney cells.

Baby hamster kidney (BHK) cells transfected with an expression vector for the human thrombin receptor, and then treated with basic fibroblast growth factor, were found to express specific and saturable binding sites for biotinylated thrombin receptor peptide (SFLLRNPNDKYEPF). Analysis of the binding to live BHK cells yielded an equilibrium dissociation constant (Kd) of 3.0 +/- 0.3 mu mol/l and a maximal binding capacity (Bmax) of 31.0 +/- 0.5 nmol/mg of protein. In competitive binding experiments, the thrombin receptor agonist peptide (SFLLRN), which is a strong inducer of human platelet aggregation, was the most potent competitor. In contrast, position 1 to 2 inverted peptides such as FSLLRNPNDKYEPF and FSLLRNP, which fail to induce for the platelet aggregation, were less potent. This simple and convenient binding assay system using the biotinylated thrombin receptor peptide as a labeled ligand and the cloned thrombin receptor overexpressed in BHK cells may be useful for exploring specific antagonists of the receptor.

Amino Acid Sequence↗

PubMedDate not supplied

RB protein status and chemosensitivity in non-small cell lung cancers.

The retinoblastoma gene product (RB protein), one of the tumor suppressor proteins has been found as wild-type in most non-small cell lung cancer (NSCLC) cells, usually showing multidrug chemoresistance. Recently, carboplatin (CBDCA) and etoposide (VP-16) have been introduced for the treatment of NSCLC as well as small cell lung cancer (SCLC). We examined the correlation of RB protein expression levels and chemosensitivities of a panel of NSCLC cell lines with wild-type RB for CBDCA and VP-16 in order to clarify the role of RB protein in chemoresistance of NSCLC cells. There was significant correlation between chemosensitivity and high level of RB protein expression (P=0.049 for VP-16, P=0.016 for CBDCA). We next examined the effect of VP-16 on RB protein status and cell cycle phases of two NSCLC cell lines (Ma-12, the most chemosensitive cell line; Ma-31, the most chemoresistant cell line). VP-16 suppressed RB protein expression level of Ma-12 cells but did not suppress that of Ma-31 cells, following 24 h exposure at 0.1-10 microM. And the alteration of phosphorylation status of Rb protein expression were quite different in these cells. After the treatment of VP-16, dephosphorylated RB protein became dominant in Ma-12 cells, but phosphorylated RB protein became dominant in Ma-31. High sensitive non-small lung cancer Ma-12 cells were accumulated in G2/M phases of the cell cycle. But no major changes were found in low sensitive non-small lung cancer Ma-31 cells. This shows that phosphorylation status of RB protein might be useful for the assessment for the sensitivity to VP-16 and for the cell cycle inhibition.

Adult↗

PubMedDate not supplied

Prognostic significance of telomeric repeat length alterations in pathological stage I-IIIA non-small cell lung cancer.

This study was performed to evaluate the prognostic significance of alteration in telomere length in pathological stage (p-stage) I-IIIA non-small cell lung cancer (NSCLC). Paired cancer and normal lung tissues were obtained from 72 patients with histologically confirmed p-stage I-IIIA NSCLC. Terminal restriction fragment (TRF) length, which indicates telomere length, was measured by Southern blot analysis. Tumor telomerase activity was also assayed by non-radioactive PCR-ELISA in 55 patients. TRF length (mean +/- SD) in normal tissue was 6.2 +/- 1.1 Kb. Therefore, upper and lower limits of normal range in TRF length was set at 8.4 (mean + 2SD) Kb and 4.0 (mean-2SD) Kb, respectively. A tumor showing TRF length over normal range was defined as positive for the alteration. In 72 patients, 25 (34.7%) with alteration in TRF length had significantly shorter survival durations than those of the others. Telomerase activity did not correlate with survival duration. In multivariate analysis, alteration in TRF length (P = 0.0033) was second to p-stage (P = 0.0004) in importance among the various parameters.

Adult↗

PubMedDate not supplied

Bcl-2-independent induction of apoptosis by neuropeptide receptor antagonist in human small cell lung carcinoma cells.

The broad-spectrum antagonist of neuropeptide receptor, [D-Arg1, D-Phe5, D-Trp7,9, Leu11]substance P, induced apoptosis selectively in human small cell lung carcinoma (SCLC) cells, which express gastrin-releasing peptide receptor, but not in other types of tumor cells as well as normal cells. The addition of gastrin-releasing peptide or bombesin and the inhibitor of caspase-3 suppressed [D-Arg1, D-Phe5, D-Trp7,9, Leu11]substance P-induced apoptosis. Moreover, [D-Arg1, D-Phe5, D-Trp7,9, Leu11]substance P-induced apoptosis was not suppressed by Bcl-2 over-expression. Thus, blockage of gastrin-releasing peptide receptor-mediated signaling may provide a novel therapeutic option in SCLC which has become resistant to conventional chemotherapeutic agents.

3T3 Cells↗

PubMedDate not supplied

Differential expression of RAGE in human pancreatic carcinoma cells.

BACKGROUND/AIMS: Amphoterin is a key protein in normal neurite outgrowth and that its receptor on the cell surface, RAGE, is an important molecule for invasion. RAGE induces neurite outgrowth and regulate gene expression through NF-kappa B. Because the pancreatic cancer shows the constitutively activated NF-kappa B, the involvement of RAGE could be possible as a determinant for the metastatic ability. METHODOLOGY: To see the involvement of RAGE in pancreatic cancer, three representative human pancreatic carcinoma cells were rendered for the study which have different metastatic potential, PANC-1 and MIA PaCa-2 as the cells with high ability, BxPC-3 as those with low. The expression of RAGE (receptor for advanced glycation end-products) was examined by Western blot. RESULTS: The expression of RAGe was strong in MIA PaCa-2 and PANC-1 that have high metastatic ability. On the contrary, RAGE is expressed little in BxPC-3 whose ability is low. CONCLUSIONS: RAGE is expressed in concordant to the metastatic ability of the human pancreatic cancer cells. Control of this molecule could be a key to regulate the metastatic ability of pancreatic cancer.

Blotting, Western↗

PubMedDate not supplied

Prognostic significance of serum p53 antibodies in squamous cell carcinoma of the lung.

BACKGROUND: The prognostic significance of serum p53-Abs positivity for non-small cell lung cancer (NSCLC) is still unknown. PATIENTS AND METHODS: To determine the prognostic value of serum p53-Abs status, we determined serum p53-Abs and immunohistochemistry in 140 patients with stage I-IIIA NSCLC. RESULTS: p53-Abs were detected in 12.1% of all patients and in 17.6% of those with squamous cell carcinoma (SCC). Neither p53-Abs nor p53 overexpression alone was correlated with survival for all patients. When these factors were combined for SCC, seronegative patients with tumors overexpressing p53 survived significantly longer than did those with p53-Abs or p53-nonexpressing tumors. In multivariate analysis, p53-Abs status and p53 overexpression were independent prognostic factors for SCC (p = 0.0337). CONCLUSIONS: These findings suggest that the combination of p53Abs seropositivity and p53 overexpression may be a prognostic factor for SCC.

Aged↗

PubMedDate not supplied

Laparoscopic partial hepatectomy.

This article describes the surgical techniques and indications of laparoscopic partial hepatectomy, which is not as widely available as laparoscopic cholecystectomy. Three patients with hepatocellular carcinoma and associated severe liver cirrhosis were candidates for this technique from July 1993 to August 1994. The tumor size was 4 cm or less and all the tumors were located in segment 5 or 8 which had grown nodularly and protruded from the liver surface. A microwave tissue coagulator was used for parenchymal dissection under ultrasonographic guidance in a gas-less method with or without low-pressure pneumoperitoteum of 4 mmHg. The principle of dissection consists of tissue coagulation and fragmentation with dissecting forceps. Three hepatectomies were performed uneventfully without blood transfusion and the patients rapidly returned to their preoperative conditions. The laparoscopic partial hepatectomy can be an option of treatment in selected cases where the tumor can be removed by minor, superficial resection.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Prognostic significance of CYFRA 21-1 in non-small cell lung cancer.

Between July 1991 and February 1993, CYFRA 21-1 levels of 149 newly diagnosed patients with histologically proven non-small cell lung cancer (NSCLC) at Osaka Prefectural Habikino Hospital were measured with an enzyme immunoassay method developed by Boeringer Mannheim (Enzymun-Test CYFRA 21-1). NSCLC patients with CYFRA 21-1 serum levels over 3.5 ng/ml had a significantly poorer prognosis than did patients with normal CYFRA 21-1 levels (P < 0.001). Univariate analysis revealed that CYFRA 21-1 levels above 3.5 ng/ml, poor PS, advanced stage and serum LDH over 450 U/l strongly correlated with survival period. In multivariate analysis, however, only CYFRA 21-1 was found to be an independent prognostic factor compatible with Stage and PS (P = 0.0040 for CYFRA 21-1, P < 0.001 for PS, P = 0.0052 for Stage).

Adult↗