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Biomedical subjects

S Kudoh

Publications and source records attributed to S Kudoh.

At least 253 records · Page 14Linked to original sources
PubMed1991

Establishment and characterization of 20 human non-small cell lung cancer cell lines in a serum-free defined medium (ACL-4).

To facilitate the studies in cell biology and drug sensitivity of non-small cell lung cancer, cell samples from 55 patients have been used to establish cell lines in culture using a chemically defined medium (ACL-4). A total of 20 cell lines (36 percent) were directly established and characterized: 14 (44 percent) from pleural effusions, five (29 percent) from resected primary tumors, and one (25 percent) from ascitic fluids. They comprised 16 adenocarcinoma, two large cell carcinoma, one squamous cell carcinoma, and one malignant mesothelioma. Each cell line had distinct gross morphologic features and population doubling times from 21 to 75 h. The plating efficiency was 0.01 to 9.51 percent. The modal chromosome number varied from 45 to 108. Secretion of tumor markers (carcinoembryonic antigen, sialyl Lewis Xi, CA 50, CA 125, and CA 19-9) into the medium was also different in each cell line. Most of the cell lines have been xenografted into nude mice and found to be tumorigenic. Survival of 20 patients whose tumor cell specimens continually grew in culture at any time during their clinical course was significantly shorter than that of 35 patients with no in vitro tumour growth (median survival time of 28 weeks vs 53 weeks, p = 0.0093). Our study indicates that in vitro tumor cell growth appears to be an adverse prognostic factor in patients with non-small cell lung cancer.

Adult↗
PubMed1991

[The significance of CA-50, SLX and ST-439 in lung cancer].

Serum levels of CA-50, SLX and ST-439 were measured in 213 patients with lung cancer (92 adenocarcinomas, 63 squamous cell carcinomas, 37 small cell carcinomas and 21 large cell carcinomas) and 87 patients with benign lung disease. The overall positive rates in patients with lung cancer were 12.8% for CA-50, 29.7% for SLX and 25.3% for ST-439. The positive rates for CA-50, SLX and ST-439 in adenocarcinoma patients were 22.8%, 42.4% and 38.0%, respectively. Of the patients with benign lung disease, 4.8% were false positive for CA-50, 15.3% for SLX and 3.6% for ST-439. In the patients with adenocarcinoma of the lung, the combination assay of CEA and ST-439 had a highly accurate rate (61.9%).

Adenocarcinoma↗
PubMed1991

[High-dose Tegafur (FT) for primary lung cancer: a phase I trial].

A phase I clinical study of intravenous Tegafur was conducted in nineteen previously treated patients with primary lung cancer. The dose of Tegafur was elevated from 1.0 to 3.0 g/m2/day for five consecutive days to determine the maximum tolerated dose. The dose-limiting factors were gastrointestinal and neurological toxicity and fatigability observed with the dose level of 2.5 g/m2/day for 5 days. Hematologic, hepatic and renal toxicities were not observed. Gastrointestinal toxicity including nausea, vomiting, anorexia and diarrhea of over grade 2 were seen to result from the dose of 2.5 g/m2/day. Neurological toxicity consisted of headache, dizziness, anxiety and depression. At the dose level of 2.0 g/m2/day, one patient, who had epileptic seizures in the past, experienced a psychomotor seizure. Depression (Grade 2 CNS toxicity) was observed at the dose level of 3.0 g/m2/day. Dose limiting factors were neurological toxicities. The pharmacokinetics of tegafur and 5-FU (the active form of Tegafur) has been studied in all patients. Serum level of tegafur was measured by HPLC method, and serum level of 5-FU was analyzed by GC-MS method. At the dose level greater than 2.0 g/m2/day for 5 days, the mean serum 5-FU values appear over the therapeutic range (0.1 micrograms/ml). In conclusion, 2.5 g/m2/day for 5 days was considered to be MTD, and 2.0 g/m2/day for 5 days intravenous administration was recommended for the phase II trial of single agent chemotherapy.

Drug Administration Schedule↗
PubMed1990

Direct determination of the antihypertensive agent Cromakalim and its major metabolites in human urine by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of Cromakalim, a novel antihypertensive agent, and its urinary metabolites including diastereomeric glucuronides. The HPLC system employed a strong cation-exchange precolumn (Senshu Pak SCX-2051-N) to allow direct injection of urine samples. The unchanged drug and its three major metabolites were simultaneously separated on a reversed-phase column (Develosil ODS-5) and fluorometrically detected (excitation, 254 nm; emission, 306 nm) by the aid of their native fluorescence. The calibration curves for Cromakalim and a metabolite were linear in the range from 10 to 200 ng ml-1, while those for the diastereomeric glucuronides were linear in the range from 20 to 400 ng ml-1. The detection limits (signal-to-noise ratio = 3) of these compounds were 0.3 ng ml-1 or less in all cases.

Antihypertensive Agents↗
PubMed1990

Evaluation of high-dose etoposide combined with cisplatin for treating relapsed small cell lung cancer.

The synergism of combined high-dose etoposide with standard dose cisplatin (HD-EP) was evaluated in 20 patients who had relapsed after treatment of small cell lung cancer. Each patient was given etoposide at 500 mg/m2/day on days 1 to 3 and cisplatin at 80 mg/m2 (two patients given 120 mg/m2) on day 1; autologous bone marrow was not transplanted. Five patients were given recombinant human granulocyte colony-stimulating factor (rhG-CSF, 50 micrograms/m2) in an attempt to reduce HD-EP induced neutropenia. The overall response was 50% (9 of 18); one complete response (6%), eight partial responses (44%), seven no change (39%), and two progressions of disease (11%). Of the 18 evaluable patients, 12 had been treated with regimens of conventional doses of etoposide with conventional doses of cisplatin or carboplatin, and of these, five (42%) achieved a partial response. The median duration of response was 8.4 weeks (range, 5.3 to 17.7) and the median survival time was 20.3 weeks (range, 1.6 to 91). All of the patients developed severe myelosuppression; rhG-CSF did not shorten the period of the leukopenia. Mucositis and liver dysfunction were the major nonhematologic manifestations of toxicity. Two treatment-related deaths resulted from sepsis. These results suggest that the activities of high doses etoposide with standard doses of cisplatin are synergistic against small cell lung cancer.

Aged↗
PubMed1990

Combination chemotherapy with or without radiation therapy in small cell lung cancer. An analysis of a 5-year follow-up.

From January 1978 to March 1984, a series of 159 patients with newly diagnosed small cell lung cancer (SCLC) was treated with combination chemotherapy with or without chest radiation at the Osaka Prefectural Habikino Hospital. By March 31, 1989, ten patients (6.3%) had survived for 5 years or more after the initial chemotherapy, including nine of 95 patients (9.5%) with limited disease and one of 64 patients (1.6%) with extensive disease. All these 5-year disease-free survivors, except for one patient whose response could not be assessed by chest radiograph because of radiation fibrosis, had a complete response. Nine of the 71 patients (12.7%) treated with combination regimens containing doxorubicin survived 5 years or more, and only one of the 88 (1.1%) treated with regimens without doxorubicin had long-term survival (P less than 0.01). The sex, performance status (PS), and chest radiation after systemic chemotherapy did not correlate statistically with long-term survival (P greater than 0.05). Three of the ten patients died free of SCLC. Two of the ten patients (20%) developed second malignancies and died. The remaining patient died of pneumonia. The Cox regression analysis identified the PS and doxorubicin-containing regimens as important factors indicating improved survival. Combination regimens containing doxorubicin have, therefore, been found to be very effective in improving survival and achieving long-term survival.

Adult↗
PubMed1990

Patient with pyruvate kinase deficiency developed acute myelogenous leukemia.

A 44-year-old previously healthy male was diagnosed as anemic and treated at a nearby hospital. A year later, he was admitted to our hospital for precise examination of the progression of refractory anemia. Blood examination showed hemolytic anemia and more detailed examination of this hemolysis revealed pyruvate kinase deficiency. The activity was 15.1% of a normal control. Pyruvate kinase activities of his family members were normal or slightly decreased. Ten months after admission to our hospital, 2% of blast cells with Auer's body in the peripheral blood were noted which increased progressively. The bone marrow contained 17.3% of blast cells with a subsequent diagnosis of acute myelogenous leukemia being made. Although intensive chemotherapy was performed, the patient achieved a brief remission and died 2 years after admission to our hospital.

Adult↗
PubMed1990

Analysis of HLA antigens in patients with diffuse panbronchiolitis.

A new clinicopathologic entity, diffuse panbronchiolitis, was recently reported in Japan. This disorder is characterized by recurrent sinopulmonary infection and respiratory bronchiolitis. We identified cases of familial diffuse panbronchiolitis and found that many siblings of the patients had paranasal sinusitis. Because of this, we performed HLA analysis of the patients with diffuse panbronchiolitis. In HLA Class I and Class II antigens, Bw54 significantly increased (frequency: 63.2%; RR = 13.30; corrected p value less than 1.08 x 10(-10], whereas Cw1 and MC1 (a new HLA-DR-related antigen) slightly increased. These increases might be explained by the fact that these two antigens, Cw1 and MC1, formed a haplotype with Bw54, which suggests that one or some of the genes controlling the susceptibility and/or immune responsiveness of diffuse panbronchiolitis might be located near HLA loci. In addition, Bw54, or its related haplotype, exists only in Japanese, Chinese, and Korean populations. This may explain why a similar disease had not been reported in the English literature.

Asian People↗
PubMed1990

Human granulocyte colony formation in serum-free cultures stimulated with purified recombinant granulocyte colony-stimulating factor.

Granulocyte colony formation by human bone marrow cells in serum-free cultures was studied using purified recombinant granulocyte colony-stimulating factor (rG-CSF). The cloning efficiency of the serum-free cultures was about 80% that of the serum-containing cultures. In addition to purified G-CSF, four ingredients were found to be essential to granulocyte colony formation: bovine serum albumin (BSA), iron-saturated human transferrin, cholesterol, and L-alpha-phosphatidylcholine. Their optimal concentrations were also investigated. Insulin was not indispensable for granulocyte colony formation, but its addition did increase the number of granulocyte colonies. Hydrocortisone was found to be inhibitory to granulocyte colony formation at high concentrations.

Blood↗
PubMed1990

[Analysis of peripheral lymphocyte subsets and changes due to erythromycin therapy in patients with diffuse panbronchiolitis].

It is well known that patients with diffuse panbronchiolitis (DPB) have various immunological abnormalities. The authors evaluated the peripheral lymphocyte subsets using two-color analysis by FACS. Convening percentages of activated CD3+, CD8+, and CD4+ cells in DPB patients, all, especially that of CD8+ cell, were greater in number before therapy compared to healthy controls. After erythromycin therapy, all three parameters decreased in all patients. Therapy with other antibiotics did not obtain any effects. These results suggested that patients with DPB had some immunological hyperreactivity and that erythromycin was effective in these patients by suppressing this activity. From these results, together with the fact that DPB is a type of sino-bronchial syndrome, the possible pathogenesis of DPB was thought to be related to some immunological defect and hyperreactivity in the respiratory system.

Adult↗
PubMed1989

Establishment of tumor cell lines from a patient with head and neck cancer and their different sensitivities to anti-cancer agents.

The authors established five cell lines from a human head and neck tumor. The five cell lines (HC-2, HC-3, HC-4, HC-7, and HC-9) exhibited different sensitivities to Adriamycin, cisplatin, bleomycin, 5-fluorouracil, vincristine, and daunomycin. The D50 was 200 ng/ml Adriamycin (doxorubicin) for HC-7 and 45 ng/ml for HC-2. At the inception of long-term culture (11 months) in the absence of any drug, the sensitivity to Adriamycin of HC-7-5 (subcloned from HC-7) was 3.4 times greater than that of HC-2-6 (subcloned from HC-2); by 11 months, it decreased to 1.6 times that of HC-2-6. The cytocidal action of Adriamycin on HC-2-6 and HC-7-5 was potentiated when Adriamycin was combined with verapamil or cepharanthine. Cepharanthine also potentiated daunomycin and vincristine (VCR) against HC-2-6 and HC-7-5 cells, and it almost completely overcame drug-resistance to daunomycin and vincristine in HC-7-5/VCR, a multidrug-resistant variant isolated after long exposure to vincristine of HC-7-5 cells in culture. The cellular accumulation of [3H]-daunomycin by HC-7-5 cells was about 70% that of HC-2-6 cells. By Northern blot analysis, using a multidrug-resistance gene (mdr-1) probe, neither HC-2-6 nor HC-7-5 expressed the mdr-1 gene, but HC-7-5/VCR or other multidrug-resistant variants showed active expression of the mdr-1 gene. Differential sensitivities among the five cell lines to 5-fluorouracil, cisplatinum, and bleomycin appear to be mediated through other mechanism beside the mdr-1 gene.

Alkaloids↗
PubMed1989

[Bone formation in the bilateral kidneys of a chronic renal failure patient. A case report].

A 28-year-old man with back pain visited a near hospital on October, 1987. Afterwards he was referred to our hospital on November 11 for detailed examination of the kidneys. The blood chemical analysis showed marked renal hypofunction. The abdominal USG and CT showed bilateral calcification of the cortices. Biopsy specimens of the kidneys revealed bone formation containing bone marrow tissue. Afterwards he had been treated as an outpatients, but he admitted again on June 3, 1988. He is now being hemodialyzed.

Adult↗
PubMed1989

[A case of the bare lymphocyte syndrome with clinical manifestations of diffuse panbronchiolitis].

Touraine et al reported some cases lacking HLA-class I antigens on the cell surface of their lymphocytes as "Bare lymphocyte syndrome" (BLS). Recently we experienced a case of BLS the clinical features of which are very similar to those of diffuse panbronchiolitis (DPB). Namely, she had chronic pansinusitis, diffuse nodular shadows on her chest X-ray film, obstructive impairment of pulmonary function tests and continuous increase of cold hemagglutinin titer. The pathogenesis of DPB is not confirmed. However, this case and other cases with sino-bronchial syndrome suggest that patients with DPB may have some immunodeficiencies. In addition the immunosuppressive action of erythromycin and its effectiveness on DPB were interesting. From these points of view, we discussed the relationship between this case and DPB, and the pathogenesis of DPB.

Adult↗
PubMed1989

[A case of chronic obstructive pulmonary disease associated with central alveolar hypoventilation diagnosed by exercise test].

We report a case of chronic obstructive pulmonary disease associated with central alveolar hypoventilation diagnosed by exercise test. A 61-year-old man with chronic obstructive pulmonary disease was admitted to our hospital because of respiratory failure caused by bacterial pneumonia. After recovery from pneumonia, we examined his functional ventilatory response to incremental exercise. Exercise was discontinued because of his maximal target heart rate, and there was no complaint of dyspnea throughout the exercise test. Although the patient had enough ventilatory reserve during exercise (VEmax/MVV = 50%), there was a marked progressive retention of carbon dioxide disproportionate to the extent of his air flow obstruction. Moreover the patient was able to reduce the carbon dioxide tension to a subnormal level by voluntary hyperventilation, and his ventilatory response to carbon dioxide and mouth occlusion pressure at rest was significantly diminished as compared with normal subjects. These findings suggest that this patient has several features compatible with central alveolar hypoventilation. Exercise test was useful for the diagnosis as well as exercise prescription because the patient could develop dangerous hypoxemia without alarming symptoms like dyspnea.

Exercise Test↗
PubMed1989

Effect of recombinant human granulocyte colony-stimulating factor on Pneumocystis carinii infection in nude mice.

Repeated subcutaneous (s.c.) injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to Pneumocystis carinii (P. carinii)-infected balb/c nude (nu/nu) mice had no effects on the number of the P. carinii cysts in the lungs, despite neutrophilic infiltration in the tissues and a marked increase in blood neutrophil count. This finding indicates that neutrophils in the absence of T cells do not play an important role in the killing of P. carinii. However, survival periods of the rhG-CSF treated mice seemed to extend to some extent compared with the controls presumably because of the prevention of mixed bacterial infections.

Animals↗
PubMed1988

[Subrenal capsule assay (SRCA) using human lung cancer].

SRCA was performed using surgically removed fresh tissues in 26 cases of lung cancer. The histological examination of day 6 xenograft showed that only a few xenografts contained tumor cells because of the host cell infiltration and stroma. For the assay considered as evaluable, we defined that control mice needed to show delta tumor size larger than -0.5 OMU and histological presence of tumor cell more than 50% in the day 6 xenograft. The evaluable assay rate (EAR) was no more than 25% (4/16). By the pretreatment with X-ray irradiation of 3 Gy, host cell infiltration was significantly suppressed. With this procedure however, only 40% (4/10) of EAR was gained. The reason for this low EAR was due to the difficulty to obtain the specimens enriched with tumor cells because of stroma and necrotic tissue. Then we used specimen obtained from the human lung cancer line xenografted in nude mice, which resulted in a high EAR of 84% (16/19). We concluded that SRCA for fresh surgical materials was still difficult. However SRCA for lung cancer line was feasible, especially for in vivo preclinical chemosensitivity test for new agents and decision for new drug combination. SRCA as a disease oriented chemosensitivity test is expected to develop in the future.

Animals↗