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Biomedical subjects

K Eguchi

Publications and source records attributed to K Eguchi.

At least 541 records · Page 30Linked to original sources

Chemosensitivity test for human small cell lung cancer cell lines in vitro.

The in vitro response to seven chemotherapeutic drugs of three established human small cell lung cancer (SCLC) cell lines (NCI H69, H128, N231) was tested by a double soft agar clonogenic assay. Colony formation by the three cell lines was universally reduced more than 50% by continuous exposure to peak plasma concentrations of all the drugs. However by exposure to one-tenth of the peak plasma concentrations, the colony growth of H69 was reduced to 25.6% and 37.7% by etoposide and teniposide, respectively, and that of N231 was reduced to 46.7%, 39.0%, 27.5% by carboplatin, etoposide and teniposide, respectively. On the other hand colony formation by the three cell lines was not suppressed more than 50% by one-hour exposure to any of the drugs tested at one-tenth of the peak plasma concentrations. By one-hour exposure to drugs at the peak plasma concentrations, colony formation by H69, H128 and N231 was reduced more than 50% by cisplatin, etoposide, teniposide and nimustin, by adriamycin, teniposide and ACNU, and by adriamycin, etoposide, teniposide and nimustin, respectively. It was concluded that these three cell lines have similar sensitivity to seven drugs commonly used against small cell lung cancer.

Antineoplastic Agents↗

Long-term survival in patients with small cell lung cancer.

Of the 66 patients with small cell lung cancer (SCLC) who were treated by combination chemotherapy with or without radiation therapy from July 1978 to December 1983 at the National Cancer Center Hospital, Tokyo, 12 (18%) survived over two years and nine (14%) have remained disease-free over three years. The two-year survival rates were compared according to the patient characteristics of sex, performance status (PS), extent of disease, histologic subtype, regimen of the initial chemotherapy and response to treatment. Sex, extent of disease and response to the initial chemotherapy were the most important prognostic factors. The prognosis for patients with liver or bone metastasis was poor. All disease-free survivors, except for two patients who were treated by surgical resection after chemotherapy, achieved complete response (CR) with chemotherapy with or without radiation therapy. Eleven of the 12 two-year survivors achieved CR. Because of the small number of patients in our study, it will be necessary to evaluate further the influence of prognostic factors in patients with SCLC in future studies.

Adult↗

Cytogenetic effects of multiagent chemotherapy on the peripheral lymphocytes of patients with small cell lung cancer.

Peripheral lymphocytes of 8 patients with small cell lung cancer (SCLC), who received combination chemotherapy consisting of cisplatin and VP-16 (PVP), were examined for frequency of sister chromatid exchange (SCE) and chromosomal aberrations. Three of the 8 patients were treated with the PVP regimen only; however, the others had previously been treated with multiagent chemotherapy consisting of a cyclophosphamide, adriamycin, and vincristine (CAV) regimen or a cyclophosphamide, ACNU and vincristine (CAV') regimen with or without radiotherapy. Significantly increased SCE frequency was observed in previously untreated patients 3 or 4 days after PVP treatment, compared with the pretreatment values. The earlier analysis in the previously treated patients also showed increased SCE frequency, which seemed to return to the normal value as time elapsed after PVP. In addition, abnormal chromosome count distribution and/or increased incidence of structural changes were observed in cultures from all the patients. In general, striking changes in chromosomes were observed in previously treated patients. The aberrations observed in pretreated patients consisted of chromatid gaps and breaks, exchanges, fragments and dicentric chromosomes. In addition to these abnormalities, double minutes like microchromosomes were seen irrespective of radiotherapy. Further studies are needed to elucidate whether any of the chromosomal aberrations observed in this study could participate in the induction of secondary neoplasms.

Aged↗

[The usefulness of CT in the preoperative diagnosis of metastatic lung nodules--a study with resected cases].

The reliability of the preoperative CT diagnosis was studied in patients with pulmonary metastases from osteosarcoma and colorectal cancer as compared with surgical and pathological findings. Seventy-six lesions among 111 surgically proven metastatic nodules were detected preoperatively by CT. But the predictive rate varied greatly depending upon the site and size of the lesions. CT is not so useful in subpleural and apical sites or with nodules of less than 0.2 cm in diameter.

Bone Neoplasms↗

Antiemetic efficacy of high-dose intravenous metoclopramide and dexamethasone in patients receiving cisplatin-based chemotherapy: a randomized controlled trial.

High-dose intravenous (IV) metoclopramide has shown efficacy with few side effects for the treatment of nausea and vomiting on the day of cisplatin administration. From November 1984 to January 1986, two randomized trials in an antiemetic study were conducted. In trial I, the antiemetic effect of a short course of high-dose dexamethasone was compared with that of high-dose metoclopramide in 29 patients with lung cancer receiving chemotherapy containing cisplatin (80 mg/m2 IV) in a randomized controlled trial. Dexamethasone was given IV at a dose of 16 mg 1/2 hr before and 8 mg, 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin. Metoclopramide was given IV at a dose of 2 mg/kg, 1/2 hr before and 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin. Major emetic control (0-2 episodes of vomiting) during the 24 hr after cisplatin administration was achieved in 55% (6/11) and 67% (12/18) of the patients receiving dexamethasone and metoclopramide, respectively, without serious toxicity. The duration of nausea or anorexia was similar for the two treatment groups. In trial II, the combination of metoclopramide and dexamethasone was compared with metoclopramide alone to assess the additive antiemetic effect of the two drugs in 23 patients with lung cancer receiving cisplatin at a dose of 120 mg/m2 IV in a randomized cross-over study. A major antiemetic response was observed in 27% (3/11) and 92% (11/12) of the patients receiving metoclopramide alone and metoclopramide plus dexamethasone, respectively (p less than 0.005). The duration of nausea and anorexia was similar for the two treatment groups. Patients tended to prefer the combination of metoclopramide and dexamethasone; however, the difference was not statistically significant (p = 0.14) in the small number of patients entered in this study. Despite excellent control of acute chemotherapy-induced emesis, 45% of 52 patients experienced delayed nausea and vomiting more than 24 hr after cisplatin administration even among those who had had an excellent short-term response to the antiemetic agents.

Adult↗

A trial of chemotherapy for lung cancer in short-term hospitalization.

Recently the number of patients with lung cancer who receive chemotherapy has been increasing rapidly. Therefore it has become difficult to treat all patients with advanced lung cancer on the basis of accurate protocol in long-term hospitalization. Accordingly we tried to treat patients within one week in each of a number of chemotherapy protocols (short-term hospitalization) and to follow them in the outpatient department. We were able to accept 61 admissions of 38 patients for chemotherapy from June to December 1985. Thus it was possible to take care of more than three times as many patients as could be cared for by long-term hospitalization for chemotherapy. Three patients could not be discharged within one week and eight had to be readmitted because of leucopenia, thrombocytopenia, or dehydration. It was considered to be possible to decrease the number of such patients by more careful and appropriate hydration and to detect them by appropriate intervals of examination in the outpatient department. We concluded that short-term hospitalization is one of the methods which can make chemotherapy of lung cancer more effective.

Antineoplastic Combined Chemotherapy Protocols↗

[Fundamental study and clinical testing of human tumor clonogenic assay (HTCA)].

Through our retrospective analysis of HTCA and clinical effects as well as fundamental studies, the following results were obtained: In this retrospective study, HTCA for lung cancer showed a predictive accuracy of 71%, a true positive rate of 50% and a true negative rate of 77%. To obtain good predictive accuracy, HTCA should be modified to provide conditions comparable to those in vivo with regard to drug concentration and drug exposure time. More precise analysis of the pharmacokinetics of anticancer agents might yield methodological improvement. A decrease in the chemosensitivity spectrum in vitro was observed after chemotherapy. This might be related to evidence that patients with prior chemotherapy exhibited a poor response rate to chemotherapy. There were no active anticancer agents against specimens with aplating efficiency of more than 0.04%. More extensive prospective trials will be necessary to determine the clinical value of HTCA. HTCA could be a superior assay for detecting the anti-tumor activity of new agents and a useful method for in vitro phase II study.

Antineoplastic Agents↗

Naloxone-reversible respiratory inhibition induced by muscular thin-fiber afferents in decerebrated cats.

Stimulation of muscular thin-fiber afferents of cats causes two types of respiratory suppression: one is stimulus-locked suppression which is not affected by naloxone, and the other is naloxone-reversible respiratory suppression after cessation of the stimulation. Both types of respiratory suppression could still be evoked after decerebration of cats at the midcollicular level. The present experiment revealed that muscular thin-fiber afferents, presumably polymodal receptor afferents, caused respiratory inhibition mediated through an opiate system in the brain structure below the caudal part of the brain stem.

Animals↗

Suppression of natural killer activity in patients treated with cisplatin and methylprednisolone.

The achievable concentrations of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl-3-nitrosourea (ACNU), adriamycin, mitomycin C, vindesine, and epipodophyllotoxin suppressed the natural killer (NK) activity of human peripheral blood lymphocytes in vitro, whereas NK activity was not decreased 24 h after incubation with the maximum achievable concentration of cisplatin (cDDP). NK activity of patients treated with 80 mg per square meter of cDDP alone was not decreased for 3 weeks after cDDP administration. In contrast, NK activity of patients treated with the same dose of cDDP and methylprednisolone was significantly decreased 1 week after cDDP administration. It was concluded that methylprednisolone, used as an antiemetic agent, had an immunosuppressive effect.

Adult↗

Stimulus-response relation of tooth pulp units in rat trigeminal nucleus.

Electrical stimulation of the rat tooth pulp evokes a slow mass potential (SMP) in the trigeminal spinal nucleus. Single units in the SMP field were examined for their stimulus-response relation. The response profile of most single units differed from that of background SMPs in that the former tended to give a greater gradient or exponent when they were approximated by linear or power function, respectively. Most of single units with a short and stable latency could be described rather well by power function, while a majority of units with a longer and unstable latency had a relatively wide dynamic range to varied stimulus intensities and could be approximated more closely by linear function.

Animals↗

Concentrations of polyamines in umbilical blood.

Red blood cell and plasma polyamines in umbilical and maternal blood at delivery were measured using high performance liquid chromatography. The concentration of each polyamine in red blood cells and plasma of umbilical blood was significantly higher than in maternal blood. Spermidine and spermine concentrations in fetal red blood cells decreased markedly with the progress of pregnancy. In addition, younger red blood cells contained more polyamines than older cells. Red blood cell polyamines are closely associated with the cell membrane. Plasma polyamine in umbilical blood reflect active fetal metabolism, whereas red blood cell polyamines mainly reflect alterations in erythropoiesis in bone marrow and may indicate the proliferation of the bone marrow.

Embryonic and Fetal Development↗

Hormonal regulation of ornithine decarboxylase and polyamines in primary cultured rat hepatocytes--differences in hormonal response between adult and fetal hepatocytes.

Polyamines are polycationic substances which are widely distributed in living organisms and have a close relation to rapid growth phenomena. We examined ornithine decarboxylase (ODC), which is the rate limiting enzyme of polyamine biosynthesis, and polyamine induction in primary cultured rat hepatocytes by various hormones which increase during pregnancy, and revealed differences in hormonal responses between adult and fetal rat hepatocytes. Thirteen hormones, including estrone, estradiol, progesterone, testosterone, human chorionic gonadotropin (HCG), cortisol, dexamethasone, insulin, glucagon, epinephrine and epidermal growth factor (EGF), were tested. Among these hormones, only insulin, dexamethasone and EGF induced ODC activity and polyamine biosynthesis, especially that of putrescine, in both adult and fetal hepatocytes. The effects of EGF were the most significant. The combined effect of insulin and dexamethasone was additive, while that of insulin and EGF was synergistic. The rate of ODC induction was higher in adult hepatocytes than in fetal hepatocytes, however, the reaction was earlier in fetal hepatocytes. These observations suggest that ODC and polyamines in the fetal stage of development are regulated by a mechanism different from that in the adult liver.

Animals↗