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Biomedical subjects

N Takigawa

Publications and source records attributed to N Takigawa.

At least 55 records · Page 3Linked to original sources
PubMed1993

Antitumor activity of platinum analogs against human lung cancer cell lines and tumor specimens.

Antitumor activities of five platinum analogs, including cisplatin, carboplatin, 254-S, DWA2114R, and NK121, were compared using five human lung cancer cell lines and 19 tumor specimens obtained from lung cancer patients. The antitumor activity was evaluated by determining the ratio of the maximum tolerated dose of each drug to the 70% tumor growth inhibitory concentration in a colony assay. Cisplatin was the most potent agent, followed by 254-S and carboplatin. DWA2114R and NK121 were less potent than cisplatin and 254-S. Cross-resistance to adriamycin was also investigated using an adriamycin-resistant small cell lung cancer subline, SBC -3/ADM30. SBC-3/ADM30 was 1.7- to 4.0-fold more resistant to cisplatin, carboplatin, NK121, and DWA2114R, than was the parent line, SBC-3, and the subline was 2.0-fold more sensitive to 254-S. Using SBC-3, in vitro combination effects of etoposide and cisplatin, carboplatin, or 254-S were evaluated by the median-effect principle. Synergism was noted when cisplatin and etoposide were combined at a fixed molar ratio of 1:1. Combination of carboplatin and etoposide showed an additive effect. The combination of 254-S and etoposide was antagonistic at low concentrations, but was markedly synergistic at higher concentrations. These data suggested the efficacy of 254-S in the treatment of lung cancer.

Antineoplastic Agents↗
PubMed1993

[In vitro comparison of podophyllotoxin analogues; etoposide, teniposide and NK 611 using human lung cancer cell lines].

In an attempt to predict the antitumor activity of a new podophyllotoxin analogue, NK 611, in the treatment of lung cancer, we compared the drug with etoposide and teniposide using four human small cell lung cancer (SCLC) cell lines, SBC-2, -3, -4, -7, and two non-small cell lung cancer cell lines, ABC-1, EBC-1. In terms of the fifty percent tumor growth inhibitory concentration (IC 50) determined by MTT assay, teniposide was most potent among the drugs. The degree of cross-resistance of each drug was investigated using an etoposide-resistant SCLC subline (SBC-3/ETP), an adriamycin-resistant subline (SBC-3/ADM 100), and a cisplatin-resistant subline (SBC-3/CDDP). As for relative resistant (the ratio of IC 50 for resistant subline to that for the parent subline), NK 611 was least cross-resistant to etoposide, adriamycin, and cisplatin among drugs tested. These results indicate that NK 611 may play a role in a salvage chemotherapy for patients with resistant SCLC.

Adenocarcinoma↗
PubMed1993

[Cytotoxic effect of topoisomerase II inhibitors against adriamycin- and etoposide-resistant small cell lung cancer sublines].

Using reverse transcription polymerase chain reaction, we determined mRNA expression of topoisomerase (topo) II alpha and beta in adriamycin- and etoposide-resistant small cell lung cancer sublines, SBC-3/ADM 100 and SBC-3/ETP. The expression of topo II alpha mRNA decreased substantially in SBC-3/ADM 100 and SBC-3/ETP as compared with the parent cell line, SBC-3; 0.71-fold in the former and 0.38-fold in the latter. Similarly, that of topo II beta mRNA decreased to an extent of 0.68-fold in SBC-3/ADM 100 and 0.28-fold in SBC-3/ETP as compared with the parent cell line. SBC-3/ADM 100 and SBC-3/ETP were highly resistant to topo II inhibitors such as daunorubicin, epirubicin, pirarubicin, mitoxantrone, and teniposide. However, SBC-3/ADM 100 showed a less resistance to aclarubicin, and SBC-3/ETP was as sensitive to the drug as was in the parent cell line. The resistance to topo II inhibitors excluding for aclarubicin might be partially explained by the decreased expression of topo II alpha and beta mRNA.

Carcinoma, Small Cell↗
PubMed1993

[A case of small cell lung cancer associated with diabetes insipidus and Cushing's syndrome].

A 62-year-old male with small cell lung cancer (SCLC) associated with Cushing's syndrome and diabetes insipidus (DI) is reported. The patient was referred to our hospital for treatment of SCLC. A diagnosis of paraneoplastic Cushing's syndrome was made on the basis of an elevated serum ACTH (623.5 pg/ml) level, elevated excretion of urinary 17-OHCS (18.01 mg/day), obesity, hypertension, hyperglycemia, persistent hypokalemia, alkalosis, and no history of diabetes mellitus. He was also diagnosed as having DI based on polyuria and polydipsia, low specific gravity of the urine (1.007-1.010), low serum ADH (1.4 pg/ml) level, normal plasma osmolarity (29 mOsm/kg H2O), and the results of water deprivation test. DI and a left visual field defect was suggestive of metastasis to the pituitary region, but no lesion was detected by either CT scan or MRI scan. The patient failed to show a good response to intensive chemotherapy, and died of the tumor five months after commencing chemotherapy. Post-mortem examination revealed metastases to the hypothalamic-neurohypophyseal region, lungs, liver, adrenal glands, bone, bone marrow, and hilar and mediastinal lymph nodes.

Carcinoma, Small Cell↗
PubMed1993

[A case of small cell bronchogenic carcinoma accompanied by polyneuropathy and SIADH].

A 77-year-old man with small cell lung cancer (SCLC) accompanied by polyneuropathy and SIADH is reported. The patient first developed peripheral hyperesthesia and muscle weakness 6 months before admission. He was diagnosed as having SCLC by sputum cytology and supraclavicular lymph node biopsy. On admission, chest radiography and CT scan revealed a mediastinal mass, and the conduction velocity in peripheral nerves was delayed. He was also found to have SIADH, on the basis of an extremely low level of serum Na (114 mEq/l) and osmotic pressure (251 mOsm/kg) but with normal urinary Na and osmotic pressure. In association with complete disappearance of the mediastinal mass after intensive chemotherapy, SIADH and polyneuropathy also improved remarkably. When SCLC relapsed in the abdominal lymph nodes 11 months after complete disappearance of the mediastinal mass, polyneuropathy and SIADH also reappeared. These results indicate that both SIADH and polyneuropathy comprised a paraneoplastic syndrome.

Aged↗
PubMed1993

[Assessment of antitumor activity rhizoxin for human lung cancer cell lines: a potent new drug for drug-resistant lung cancer].

Rhizoxin is a new macrocyclic lactone isolated from the fungus Rhizopus chinensis. In an attempt to predict the effectiveness of rhizoxin in the treatment of lung cancer, we compared the antitumor activity of rhizoxin with those of cisplatin and etoposide using four small cell lung cancer (SCLC) cell lines, SBC-2, -3, -4, and -7, and two non-small cell lung cancer (NSCLC) cell lines, ABC-1 and EBC-1. The concentrations producing 50% inhibition of the growth of these cell lines (IC50) for each drug were obtained by MTT assay. The IC50 of rhizoxin for these cell lines ranged 0.408 nM to 1.56 nM, which were significant lower than those of cisplatin (660 nM to 16,300 nM) and etoposide (275 nM to 31,300 nM). The ratio of IC50 for the most sensitive cell line, SBC-3, to that for the most resistant cell line was less than 4-fold in rhizoxin, in contrast to more than 20-fold in cisplatin and 100-fold in etoposide. Cross-resistance of rhizoxin to cisplatin and etoposide was investigated using a cisplatin-resistant SCLC subline, SBC-3/CDDP, and an etoposide-resistant SCLC subline, SBC-3/ETP. Of interest, the parent cell line, and the resistant sublines were equally sensitive to rhizoxin, indicating rhizoxin being non-cross-resistant to cisplatin and etoposide. In conclusion, rhizoxin may be beneficial in the salvage chemotherapy of drug-resistant SCLC and non-SCLC.

Antibiotics, Antineoplastic↗
PubMed1992

Comparison of antitumor activity of new anthracycline analogues, ME2303, KRN8602, and SM5887 using human lung cancer cell lines.

In an attempt to predict the clinical activity of newly developed anthracycline analogues, ME2303, KRN8602, and SM5887 in the treatment of lung cancer, we compared antitumor activity of these drugs with that of adriamycin, using six human lung cancer cell lines and two drug-resistant human lung cancer sublines. Taking the pharmacokinetic data into consideration, we evaluated the relative antitumor activity: the ratio of area under the concentration-time curve of each drug to the 50% inhibitory concentration of the drug. Regarding this ratio, ME2303 was more potent than adriamycin, SM5887, and KRN8602. Cross-resistance of the new analogues to adriamycin was investigated using an adriamycin-resistant small cell lung cancer subline, SBC-3/ADM100 and an etoposide-resistant subline, SBC-3/ETP. SBC-3/ADM100 being 106-fold more resistant to adriamycin than the parent SBC-3 showed less resistance to the analogues: 1.80-fold to KRN8602, 3.80-fold to SM5887, and 8.60-fold to ME2303. SBC-3/ETP which was 52.1-fold more resistant to etoposide and 39.5-fold more resistant to adriamycin were also less resistant to the new analogues: 3.27-fold to KRN8602, 9.07-fold to SM5887, and 17.3-fold to ME2303. In conclusion, ME2303 was found to be the most potent agent among drugs tested for the treatment of lung cancer, and KRN8602 can be expected to be beneficial for the treatment of drug-resistant small cell lung cancer.

Anthracyclines↗
PubMed1992

Establishment and characterization of an etoposide-resistant human small cell lung cancer cell line.

An etoposide-resistant subline, SBC-3/ETP, from a human small cell lung cancer cell line, SBC-3, was developed by continuous exposure to increasing concentrations of etoposide in culture. The SBC-3/ETP was 52.1-fold more resistant to etoposide than the parent cell line. The SBC-3/ETP was highly cross-resistant to teniposide, adriamycin, vinca alkaloids, 4-hydroperoxycyclophosphamide, CPT-11 and mitomycin C, and marginally cross-resistant to cisplatin, while the subline showed a collateral sensitivity to bleomycin. Topoisomerase I activity in the SBC-3/ETP was reduced to an extent of one half and topoisomerase II activity to an extent of one eighth in comparison with those of the SBC-3. Intracellular accumulation of [3H]-etoposide in the SBC-3/ETP was significantly lower in comparison to the SBC-3. An overexpression of MDR1 mRNA, and the presence of its product, P-glycoprotein, were detected in the SBC-3/ETP by Northern blotting and flowcytometry using a monoclonal antibody of the protein, MRK16. These results indicate that a decreased activity of topoisomerase II is the major factor for the development of etoposide resistance, and that an overexpression of the MDR1 gene is responsible, in part, for the development of resistance to the drug and some structurally unrelated compounds such as adriamycin and vinca alkaloids.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

[Serum neuron specific enolase (NSE) levels in patients with non small cell lung cancer].

Serum NSE levels were measured in 126 patients with previously untreated NSCLC. The NSE level was greater than 10 ng/ml in 29 patients (23.0%) and this was considered to be positive. Elevation of serum NSE levels correlated closely with clinical stage except stage I and II. The effect of chemotherapy was evaluated in 74 cases included 22 NSE-positive cases. The response rate was 50% in positive cases and 34.6% in negative cases. However, the median duration of response in positive cases (2.2 months) was significantly shorter than that in negative cases (6.6 months). The median survival time of 6.0 months in positive cases was brief compared with 9.6 months in negative cases. These results indicate that elevation of serum NSE level in patients with NSCLC may be a marker of poor prognosis.

Adenocarcinoma↗
PubMed1992

An adriamycin-resistant subline is more sensitive than the parent human small cell lung cancer cell line to lonidamine.

Lonidamine, a unique new type of anticancer agent, has been shown to exert marginal activity in patients with resistant small cell lung cancer. We have assessed cytotoxic activity using seven human small cell lung cancer cell lines and the drug resistant small cell lung cancer sublines, Adriamycin-resistant SBC-3/ADM100, etoposide-resistant SBC-3/ETP and cisplatin-resistant SBC-3/CDDP. Although lonidamine had only a minimal activity in seven human small cell lung cancer cell lines, SBC-3/ADM100 cells were more sensitive to lonidamine than the parent SBC-3 cells to a 1.6-fold extent in terms of IC50. SBC-3/CDDP and SBC-3/ETP had no cross-resistance to lonidamine at all. These observations may be of potential clinical significance in treating small cell lung cancer.

Antineoplastic Agents↗
PubMed1992

[Immunohistochemical detection of carcinoembryonic antigen and P-glycoprotein in small cell lung cancer at diagnosis and relapse, with special reference to the tissue expression of CEA and response to chemotherapy].

Small cell lung cancer (SCLC) is one of the most sensitive tumors to drug therapy; however, the majority of patients eventually relapse within a few years. Emergence of drug resistance is thought to play a major role in the dismal course of this disease. However, the mechanism of drug resistance in SCLC still remains obscure. Based on the clinical observation that a significant proportion of patients with relapsing tumor show an elevated serum carcinoembryonic antigen (CEA) concentration while serum neuron-specific enolase (NSE) concentration remains normal, we attempted to determine whether the tissue of CEA is indicative of a clonal change in SCLC, in contrast with the tissue expression of NSE and P-glycoprotein (P-gp). We examined 22 SCLC patients with tumor specimens available both at diagnosis and at relapse. Of the 22 patients, two had CEA expression at diagnosis, and a further three patients showed CEA expression at relapse. It is of note that there were two patients whose tumors expressed NSE alone at diagnosis but expressed CEA alone at relapse. Serum CEA concentration was concordant with the tissue expression of CEA; however, serum NSE concentration was not concordant with the tissue expression of NSE. Tumors with CEA expression at relapse were generally resistant to salvage chemotherapy, while there was no close relationship between the tissue expression of P-gp and refractoriness to drugs at relapse. These findings indicate that the tissue expression of CEA in SCLC is a marker of a clonal change during chemotherapy, and such a clonal change would play a role in the emergence of drug resistance in SCLC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

[Double cancer in small cell lung cancer patients treated with intensive chemotherapy with or without radiation therapy].

Development of double cancer was evaluated in 311 small cell lung cancer patients who had received intensive chemotherapy with or without radiotherapy. Of those, 10 patients (3.2%) developed a second malignancy:stomach cancer in four, non-small cell lung cancer in three, acute myelogenous leukemia in two, and liver cancer in one. The cumulative risk for the development of double cancer was 1.0% at 1-year, 17.0% at 3-years, and 100% at 8.1 years. The relative risk for the development of double cancer calculated by person-year method utilizing age and sex adjusted cancer incidence in Japan was 2.96-fold (p less than 0.01). The risk of non-small cell lung cancer (6.65-fold) and acute myelogenous leukemia (54.9-fold) was particularly high. Of 21 patients who survived disease-free for more than 2 years, 8 patients died; four patients (50%) died of second malignancy, two died of infectious disease, and only two patients died from recurrent small cell lung cancer. These results indicate that a cautious follow-up program for the detection of double cancer is indicated in patients surviving small cell lung cancer.

Adult↗