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Biomedical subjects

K Eguchi

Publications and source records attributed to K Eguchi.

At least 577 records · Page 32Linked to original sources

Phase II study of oral administration of 5'-deoxy-5-fluorouridine (5'-DFUR) for solid tumors.

A phase II trial of 5'-deoxy-5-fluorouridine (5'-DFUR), a new fluorinated pyrimidine analog which has been demonstrated to have potential superiority over 5-FU and tegafur for chemotherapy of murine tumors, was performed in patients with advanced non-small cell carcinoma of the lung and metastatic pulmonary tumors. 5'-DFUR at a dose of 800 mg/m2 was given per os every day for more than four weeks. None of 15 evaluable patients with non-small cell carcinoma of the lung and 15 evaluable patients with metastatic pulmonary tumors showed a complete or partial response. Toxic effects of 5'-DFUR included anorexia (29%), diarrhea (26%), nausea (23%), vomiting (10%), leukocytopenia (10%), general fatigue (10%), liver disorder (6%) and thrombocytopenia (6%).

Administration, Oral↗

[Multidisciplinary treatment for small cell lung cancer].

The effect of multidisciplinary treatment of small cell carcinoma of the lung was tested. The response rates to induction chemotherapy were 69.2% (9/13) and 57.1% (12/22) in small cell carcinoma of the lung with limited and extensive disease, respectively. The response rates of oat and intermediate cells were 63.6% (14/22) and 50% (5/10), respectively. Radiation therapy to primary site and mediastinum after induction chemotherapy was also effective, producing the response rates of 87.8% (7/8) and 58.3% (7/12) in limited disease and extensive disease, respectively. The non-responder and recurrent cases responded to chemotherapy with epipodophyllotoxin and/or cisplatin but not with mitomycin C and/or adriamycin. The median survival of all 37 cases was 12.2+ months, and those with limited and extensive cases were 14.8+ and 8.7 months, respectively.

Adult↗

[Randomized systemic chemotherapy using two or three drug combination for small cell lung cancer (SCLC)].

Randomized trials were sequentially performed in SCLC patients using a two-drug combination (ACNU . VCR, ADM . VCR) and a three-drug combination (ACNU . CPA . VCR, ACNU . ADM . VCR). The response rate for the two-drug regimen was 36.4% (8/22 cases) and that for the three-drug combination was 60.0% (15/25 cases). The median survival time of the two groups was 7 and 9 months, respectively. The group with PS. 0-1 showed a better prognosis than that with PS. 2-3 (p = 0.03). No fatal side effects were experienced in this protocol. These data suggest that the three-drug combination (ACNU . VCR . CPA) represents an active regimen for SCLC.

Adult↗

Correlation between drug sensitivity determined by clonogenic cell assay and clinical effect of chemotherapy in patients with primary lung cancer.

Correlation studies between the sensitivity of tumor cells determined by clonogenic cell assay and the clinical effect of chemotherapy were performed in patients with primary lung cancer. Thirty-four of 48 patients showed adequate colony formation (greater than or equal to 30 colonies) to test in vitro chemosensitivity. Colony formation of tumor specimens did not differ with regards to prognostic factors such as sex, age, stage, performance status, and prior chemotherapy. The two criteria of in vitro chemosensitivity employed were greater than 70% and 50% reduction in colony numbers. When in vitro chemosensitivity was defined as a colony reduction of greater than 50%, the true positive rate in the assay was 57%, while the true negative rate was 85%. In this case, the predictive accuracy was 79%. When in vitro chemosensitivity was defined as a colony reduction of greater than 70%, the true positive rate for the assay was 100%, while the true negative rate was 81%. In this case, the predictive accuracy was 82%. By Fisher's exact probability test, the overall in vitro/in vivo correlation was statistically significant (P = 0.042 less than 0.05) with the 50% cut-off point, but was not significant (P = 0.053 greater than 0.05) with the 70% cut-off point.

Aged↗

[Effect of CDDP administration on NK activity of human peripheral lymphocytes and its modification by corticosteroid as anti-emetic agent].

The effect of cDDP (cis-diamminedichloroplatinum) on NK (natural killer) activity of peripheral blood lymphocytes in 12 patients (7 primary lung cancer, 3 metastatic pulmonary tumor and 2 malignant mediastinal tumor) was examined with emphasis on the combination of corticosteroid. To all patients, 80 mg/m2 of CDDP was administered intravenously every 3 weeks. Four patients were treated with CDDP alone, and 8 patients received 375 mg of methylprednisolone on the same day of CDDP administration and 125 mg on each of following consecutive 5 days respectively. 1) NK activity was not suppressed for 3 weeks after CDDP administration, in the group of 4 patients without receiving corticosteroid. 2) Significant NK suppression was found 1 week after CDDP administration, and recovered 2 weeks later, in the group of 8 patients who were treated for their emesis by corticosteroid. It can be concluded that 80 mg/m2 of CDDP does not reduce NK activity at all. However, the additional administration of corticosteroid strongly inhibited NK activity. Therefore, one should be very careful when combines the corticosteroid in order to relieve emesis induced by CDDP treatment, even if it has some antiemetic effect.

Adenocarcinoma↗

[Cis-dichlorodiammine platinum (II) CDDP in the treatment of non-small cell lung cancer].

The effect of CDDP was evaluated in 44 cases of non-small cell lung cancer (squamous cell ca. 11 cases, adeno-large cell ca. 33 cases). Administered dosage of CDDP was in the range of 60-100 mg/m2 (60 mg/m2, 80 mg/m2, 100 mg/m2 per individual). 23 cases were treated with CDDP chemotherapy alone while the other 21 cases were combined with Vindesine (VDS). Three cases out of 18 receiving the CDDP monochemotherapy achieved partial response and the response rate was 16.7%. Six cases out of 15 receiving the CDDP + VDS cases achieved partial response and the response rate was 40.0%. Because of slow shrinkage of the lesion as revealed by chest X-ray film, evaluation of CDDP efficacy could only be done after two administrations at 3-4 week intervals. Values of serum creatine and BUN were transiently elevated with a dose-dependent tendency in the monochemotherapy cases. In combination chemotherapy cases bone marrow toxicity was the main dose-limiting factor. This regimen was tolerable and it was concluded that CDDP is a useful agent for combination chemotherapy of non-small cell lung cancer.

Adenocarcinoma↗

Sister chromatid exchanges induced in human lymphocytes by cis-diamminedichloroplatinum (II).

Sister chromatid exchanges (SCE) frequency in cultured lymphocytes from seven patients with lung cancer receiving cis-Diamminedichloroplatinum(II) (Pt(II] for chemotherapy was studied. Significantly increased SCE frequency was observed in all the patients, six of whom received intravenous infusion of Pt(II) and one of whom received the agent as an intrapleural infusion. In addition, a dose-dependent increase in the frequency of SCE was observed in lymphocytes from healthy subjects upon exposure to Pt(II) in vitro. The results of the present study revealed that Pt(II) is a potent inducer of SCE in human lymphocytes in vivo and in vitro. It thus appears that follow-up study of the long-term survivors who have been treated with this agent for cancer is necessary because of the possible occurrence of secondary neoplasms.

Aged↗

[Effect of 7-N-(P-hydroxyphenyl)-mitomycin C (KW-2083) against pleuritis carcinomatosa].

Fourteen cases of adenocarcinoma with pleuritis carcinomatosa (lung cancer 10 cases, ovarian cancer 2 cases, colon cancer 2 cases) were treated with intra-pleural instillation of 7-N-(p-hydroxyphenyl)-mitomycin C (KW-2083), a derivative of mitomycin C. KW-2083 was administered at a dose of 40 mg once or twice weekly. In 14 evaluable patients, the rate of decrease of pleural fluid was 79%, and that of disappearance of tumor cells in pleural fluid was 64%. Median survival time (MST) from the beginning of treatment in all cases was 163 days. The toxicities of intrapleural instillation of KW-2083 were chest pain (86%), transient fever (64%), anorexia (64%), fatigability (29%), nausea (21%), vomiting (21%) and thrombocytopenia (nadir: 3.5 X 10(4)/mm3; 7%). Serum and pleural fluid KW-2083 concentrations have been measured in 3 patients after intrapleural administration of KW-2083. The mean half life of KW-2083 in serum and pleural fluid was 74 min (69-78 min) and 56 min (33-70 min), respectively. The peak serum KW-2083 concentration was 0.18 microgram/ml (0.06-0.24 microgram/ml).

Adenocarcinoma↗

Membrane characterization of cultured human keratinocytes by freeze-fracture electron microscopy.

Human skin explants obtained from 2 to 5-year-old patients with harelips were cultured in NCTC 168 medium at 37 degrees C, in a humidified atmosphere of 5% CO2 in air. After a 2-week incubation period, plasma membranes of the newly grown cells were characterized by freeze-fracture electron microscopy. Desmosomal diameter in cultured keratinocytes was much smaller, ranging from 0.08 to 0.19 micron, than that in vivo, where it ranged from 0.3 to 0.7 micron in diameter. On the E-face of the plasma membranes, attached to the bottom of the culture dish, small particle aggregations were observed. These were thought to be half-desmosomes, each consisting of 10 to 30 particles. Small gap junctions were also observed. These ranged in size from 0.05 to 0.1 micron in diameter. Membranous structures were found adhering to the plasma membrane from the intercellular spaces. These membranous structures may be lipid vesicles, since they are similar in freeze-fracture electron-microscopic features to lamellar lipid structures seen in the intercellular spaces of horny cells in vivo.

Cell Membrane↗

Tight junctions of human keratinocytes in primary culture: a freeze-fracture study.

Human skin explants obtained from 2- to 5-yr-old patients with harelips were cultured in NCTC 168 medium at 37 degrees C, in a humidified atmosphere containing 5% CO2 in air. After a 2-week incubation period, the newly grown cells were studied with special reference to tight junctions by freeze-fracture electron microscopy. Many completely formed tight junctions were observed between the uppermost living cells of migrating epithelium, and fragmented tight junctions were seen between the lower layer cells. The tight junctions in the uppermost cells developed so well that they formed a belt-like network consisting of two to six rows of strands. This observation may suggest that human keratinocytes have the ability to produce tight junctions perfectly enough to serve as a barrier, although no complete tight junctions were formed in situ.

Cells, Cultured↗

Effect of peplomycin plus carbazilquinone and mitomycin on non-small cell carcinoma of the lung.

The effects of two chemotherapeutic regimens, peplomycin (PLM) plus carbazilquinone and PLM plus mitomycin, on non-small cell carcinoma of the lung were evaluated by a randomized controlled trial. Seven partial responses were observed in 53 evaluable patients, for an overall response rate of 13.2%. There was no difference in response rate or in median survival time between PLM plus carbazilquinone (11.5% and 32 weeks) and PLM plus mitomycin (14.8% and 25 weeks). Seven patients developed interstitial pneumonitis, and four died of pulmonary fibrosis. It was concluded that the chemotherapeutic regimens that include PLM are only marginally effective against non-small cell carcinoma of the lung, with relatively frequent pulmonary fibrosis.

Adenocarcinoma↗

Pulmonary toxicity induced by pepleomycin 3-[(S)-1'-phenylethylamino] propylamino-bleomycin.

Chemotherapy regimens containing pepleomycin, a derivative of bleomycin, were used for 81 patients with advanced primary lung cancer and 32 patients with metastatic pulmonary tumors. Among the patients with non-small cell carcinoma of the lung, partial responses were observed in three of 27 patients treated with pepleomycin + carbazilquinone and four of 26 patients treated with pepleomycin + mitomycin C (published in Cancer Treatment Reports, 1983). Five partial responses (primary organ: larynx, esophagus, lung, pancreas and uterus; one patient each) in 23 evaluable patients with metastatic pulmonary tumors were observed during treatment, for an overall response rate of 21.7%. In patients with primary lung cancer, no correlation between the incidence of the decrease in partial arterial oxygen tension (PaO2) during treatment and age was observed. Decrease in PaO2 during treatment was found more frequently in patients with abnormal pulmonary function before treatment than in patients with normal pulmonary function, but the mean lowest values of PaO2 in the two groups were the same. Intravenous weekly injection of pepleomycin is less likely to result in a decrease in PaO2 than two daily intramuscular injections. Definite pulmonary toxicity occurred in seven of the 113 patients (6.2%). Each of the seven received a total dose of over 60 mg and their ages were over 60 yr, although no correlation between the incidence of pulmonary fibrosis and total cumulative dose of pepleomycin was observed. Six of the seven patients died of pulmonary fibrosis in spite of prednisone treatment. Clinical, radiologic and histopathologic findings associated with pepleomycin were the same as those of bleomycin pulmonary toxicity. Further studies are needed to determine the appropriate dose schedule and route of administration of pepleomycin with regard to its benefit and toxicity.

Age Factors↗

[31P-NMR analysis of high energy phosphorous compounds (ATP and phosphocreatine) in the living rat brain--effects of halothane anesthesia and a hypoxic condition].

31phosphorus nuclear magnetic resonance (31P-NMR) measurements have provided new and valuable insights for studying the metabolism of living systems. The aim of this paper is to introduce a technique of application of 31P-NMR measurements using a surface coil method, and to discuss the effects of halothane anesthesia and hypoxic hypoxia on the energetic metabolism of intact rat brains. All measurements were made using a JEOL FX 270 spectrometer with a super conducting magnet of 54-mm bore diameter. The magnetic field intensity of this machine is 6.3 tesla, and the resonance frequency used for 31P was 109.14 MHz. We remodelled an ordinary probe to take a live rat, and the animals were made to inhale anesthetic halothane or mixture of oxygen and nitrogen at various concentrations controlled by a flow regulator. The best conditions for measurements with our surface coil method were determined in this study as follows: (1) 90 degrees pulse width and selectivity, Fig. 1 shows signal selectivity in depthwise direction changed with 90 degrees pulse width, which was set to 20 microseconds. (2) Sensitivity and resolution; To obtain a spectrum of 31P-NMR from a rat brain 500 accumulations of free induction decays were considered suitable for both time and space resolution. Fig. 2 shows variations of signal intensity with pulse repetition time, which was set to 2 sec. It took about 17 min for averaging to get a spectrogram. (3) Quantitative accuracy and qualification; As shown in Fig. 3, a linear relationship was found between the signal intensity of beta-phosphate of ATP and the concentration of ATP solutions, thus proving the quantitative accuracy of our systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗