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Biomedical subjects

T Egawa

Publications and source records attributed to T Egawa.

At least 55 records · Page 3Linked to original sources

[Phase II study of a three-drug combination of ifosfamide, cisplatin and vindesine in non-small-cell lung cancer].

Between February 1986 and April 1987, we conducted a phase II clinical trial of a three-drug combination of ifosfamide, cisplatin, and vindesine in advanced non-small-cell lung cancer. The combination consisted of ifosfamide, 1,300 mg/m2, on days 1 through 5, cisplatin, 20 mg/m2, on days 1 through 5, and vindesine, 3 mg/m2, on days 1 and 8. Courses were repeated at 4-week intervals until disease progression or unacceptable toxicity occurred. Of 21 patients evaluated, one had a complete response and 12 had partial response, with an overall response rate of 62%. The projected median response duration was 30 weeks. The median survival for all patients has not been reached: 14 of 21 patients are still alive with a median follow-up period of 41 weeks (range, 12 to 73 weeks). The major toxicity was myelosuppression. One patient died of septicemia while neutropenic, but the toxicity was well tolerated in the rest. These results indicate that this three-drug combination is active against non-small-cell lung cancer and warrants further clinical trials.

Adenocarcinoma↗

Vitamin D-binding protein synthesized by a human hepatocellular carcinoma cell line.

The binding protein for 25-hydroxycholecalciferol was studied in the medium spent for the culture of HuH-7 cells, which were originally derived from a human hepatocellular carcinoma tissue. The binding protein for 25-hydroxycholecalciferol synthesized by HuH-7 cells was immunologically similar to vitamin D-binding protein in human serum and had an inter-alpha mobility. A sedimentation coefficient of 4.1 S was found on sucrose density gradient analyses. The molecular weight was estimated to be approximately 58,000 by gel filtration on a standardized column of Sephadex G-150. When mixed with filamentous actin purified from rabbit skeletal muscle, it depolymerized filamentous actin and bound to monomeric, globular actin to make a 5.5 S 1:1 molar complex with a molecular weight of approximately 100,000. These results support the conclusion that HuH-7 cells produce a functional vitamin D-binding protein.

Calcifediol↗

[Treatment of rat glioma with a beta-adrenergic agonist and a phosphodiesterase inhibitor in vivo].

Rat C 6 glioma is known to possess a beta-adrenergic receptor with which intracellular cyclic adenosine monophosphate (cAMP) levels are altered to control cell growth in vitro. In order to study the effect of beta-adrenergic agonist, isoproterenol, in growth-inhibitory action upon C 6 glioma cells, subcutaneous tumor models and meningeal gliomatisis (MG) models as a brain tumor model have been exposed to the treatment of isoproterenol. Growth of subcutaneous tumor was suppressed by the treatment of the drug, and the survival time of MG rats was prolonged by the intrathecal (i. t.) injection of isoproterenol. The addition of papaverine, phosphodiesterase inhibitor, to the treatment schedule augmented the growth-inhibitory effect of isoproterenol. Therefore, it is concluded that the survival time of the brain tumor models could be prolonged through the inhibition of the growth of C 6 glioma cells by such drugs as those which elevate intracellular cAMP levels.

Animals↗

[Treatment of a rat meningeal gliomatosis model with neocarzinostatin].

Meningeal gliomatosis (MG), pathologically, is caused by the diffuse dissemination or infiltration of glioma cells in the subarachnoid space, for which an effective, systematic treatment has not been contrived. Although, in the case of malignant leptomeningeal tumor, in general, intrathecal chemotherapy with such anticancer drugs as methotrexate and cytosine arabinoside (Ara-C) has been applied, the effect of this kind of treatment is limited, especially on MG. Therefore, the development of a new type of treatment is urgently needed. According to recent reports, neocarzinostatin (NCS) has been disclosed to have a strong cytocidal effect on glioma cells instead of injuring normal glia cells, and the intrathecal injection of NCS is suggested to be effective on MG. In order to evaluate the efficacy of intrathecal treatment with NCS on MG, a rat MG model using C 6 glioma cells has been produced and intrathecal chemotherapy with NCS was performed on this MG model. In MG rats which were treated intrathecally with NCS (1 microgram/kg) 1 day after tumor inoculation, the survival time was significantly prolonged by this treatment, where % ILS was 52.1%. Furthermore, it was more significantly prolonged with 10 micrograms/kg NCS, where 108.5% of % ILS was obtained. Contrary to these effects, this prolongation of the survival time of MG rats by the treatment with NCS showed a tendency to decrease in MG rats treated with NCS 3 days after tumor inoculation. No chemotherapeutic effect was observed in MG rats treated with even 100 micrograms/kg NCS 5 days after tumor inoculation. In conclusion, intrathecal chemotherapy with a low dose of NCS was proved to be effective in the early stages of MG.

Animals↗

[Intrathecal ACNU for the treatment of a meningeal gliomatosis model].

A nitrosourea derivative, ACNU (nimustine hydrochloride), is often used in the chemotherapy of brain tumors and shows considerable efficacy, since it crosses the blood-brain barrier (B.B.B.). This drug is also considered to be useful for intrathecal treatment of meningeal gliomatosis (MG) because of its short half-life in the blood or cerebrospinal fluid (CSF) and its strong cytotoxicity for glioma cells. In order to evaluate the efficacy of intrathecal therapy of MG with ACNU, MG models, which were produced by intracisternal inoculation of rat C6 glioma, were treated with intrathecal or intravenous administration of ACNU. When intrathecally administered 1 day or 3 days after tumor inoculation, ACNU (1 mg/kg) significantly prolonged the survival time of MG rats, where ILS was 35.7 to 42.9% and 24.1 to 25.0%, respectively. In MG rats which were treated intrathecally with ACNU (1 mg/kg) 5 days after tumor inoculation or intravenously with ACNU (15 mg/kg), ACNU failed to prolong survival time compared with the controls. It might therefore be suggested that intrathecal chemotherapy with a low dose of ACNU is effective in the early stages of MG, in which intravenous treatment with a high dose of ACNU is ineffective.

Animals↗

[Possibility of overcoming ACNU resistance in ACNU-resistant sublines of rat brain tumors in vitro by a calmodulin inhibitor].

A calmodulin inhibitor, trifluoperazine, was found to enhance the cytotoxicity of ACNU in vitro in rat C6 glioma, 9L gliosarcoma and their ACNU-resistant sublines (C6/ACNU and 9L/ACNU). Uptake and retention of ACNU in these cells were studied with [14C]ACNU in the absence or presence of trifluoperazine. The results indicated that intracellular uptake and retention of ACNU in C6 and 9L cells were larger than those in C6/ACNU and 9L/ACNU cells, and that trifluoperazine increased the cellular uptake and retention of ACNU in C6 and 9L, especially in C6/ACNU and 9L/ACNU cells. The amounts of ACNU in C6/ACNU and 9L/ACNU cells reached almost the same level as those detected in C6 and 9L cells. When trifluoperazine were added along with ACNU to the culture in vitro at a concentration of 10 and 20 microM, ACNU resistance was completely overcome. Furthermore, treatment of C6 and C6/ACNU cells with 20 microM trifluoperazine did not change the cellular uptake rate of [14C]AIB (alpha-aminoisobutyric acid), which might indicate that the membrane permeability of the cells was kept intact during the drug treatment. The same phenomenon was observed in 9L and 9L/ACNU cells. It might be concluded that the enhanced effect of cytotoxicity of ACNU in ACNU-resistant rat brain tumor cells presented in this study is presumably due to the increase of intracellular concentration of ACNU resulting from the inhibition of the efflux of ACNU by trifluoperazine from the resistant cells. It was also suggested that ACNU resistance in malignant brain tumors could be overcome by combination chemotherapy with ACNU and calmodulin inhibitors.

Animals↗

[Overcoming of ACNU resistance in an ACNU-resistant subline of rat C6 glioma in vivo through enhanced effect of ACNU by calmodulin inhibitor].

A calmodulin inhibitor, trifluoperazine, was found to enhance the cytotoxic action of ACNU in C6, especially in ACNU-resistant (C6/ACNU) glioma cells in vitro. In order to clarify the efficacy of trifluoperazine in vivo, 1 X 10(7) C6 or C6/ACNU cells were percutaneously implanted into the cisterna magna of Wistar rats to produce meningeal gliomatosis (MG) models as a chemosensitivity assay system. MG rats were treated with ACNU and trifluoperazine according to a variety of schedules. Trifluoperazine in doses of 250 to 500 micrograms/kg intrathecally (it) administered with 1 mg/kg ACNU 1 day after the tumor inoculation significantly increased the life span of the C6/ACNU bearing (C6/ACNU MG) rats. At doses of 250 and 500 micrograms/kg of trifluoperazine in the C6/ACNU MG rats, values of increased life span of 22 and 30% were obtained with a 1 mg/kg dose of ACNU, respectively. These values were statistically significant compared with that obtained in the C6/ACNU MG rats treated with ACNU alone at 1 mg/kg. It might be concluded that the combination chemotherapy with ACNU and such a calmodulin inhibitor as trifluoperazine could overcome ACNU resistance in malignant brain tumors.

Animals↗

Randomized trial comparing chemotherapy alone and chemotherapy plus chest irradiation in limited stage small cell lung cancer: a preliminary report.

In order to assess the effectiveness of chest irradiation in addition to intensive chemotherapy in limited stage small cell lung cancer, 50 patients were randomized to receive either chemotherapy alone or chemotherapy plus chest irradiation, between April 1981 and October 1985. The chemotherapy regimen consisted of a four-drug combination of cyclophosphamide, vincristine, methotrexate, and procarbazine, and a three-drug combination of etoposide, adriamycin, and nimustine, given alternately every 8 weeks. One group of 26 patients received the chemotherapy alone, and another group of 24 patients received chest irradiation with 40 Gy between cycles 1 and 2 of the chemotherapy. Complete response rates were quite similar in the two groups; 50% for those receiving chemotherapy alone, and 59% for those receiving chemotherapy plus chest irradiation. There were no significant differences in median survival (15 months versus 12 months) and in long-term survival rates between the two groups with a median follow-up period of 26 months. The combined modality treatment was more toxic than chemotherapy alone; two patients receiving such treatment died of radiation pneumonitis. It is concluded that chest irradiation combined with chemotherapy does not affect the response rate, survival, or pattern of recurrence in patients with limited stage small cell lung cancer.

Actuarial Analysis↗

Mesenchymal hamartoma of the liver in infant: its roentgen diagnosis.

A case of mesenchymal hamartoma of the liver in an 18-month-old boy is reported. CT and US revealed a large, cystic tumour surrounded by a thick wall. In the lower portion of the tumour, a small solid component was recognized on CT. Angiography revealed marked arterial displacement, fine tumour vessels and a large radiolucent area. CT, US and angiography were helpful to make a diagnosis of mesenchymal hamartoma of the liver.

Angiography↗

Duplication of the thumb. A retrospective review of two hundred and thirty-seven cases.

Over a twenty-two-year period, 237 patients (261 hands) with duplication of the thumb were seen in the Hand Clinic of Osaka University Hospital. Two groups were identified: Group A, 141 patients without previous surgical treatment, and Group B, ninety-six patients with residual deformity despite previous surgical treatment. Using a modification of Wassel's classification, seven types of deformity were defined. In Group A these types were identified on the basis of the observed duplications of bone and soft tissue. In all but ten of the Group-B patients preoperative roentgenograms were not available and the type of deformity had to be deduced from the residual duplicated bone, the surgical scar, and the residual deformity. Surgery, performed on 193 hands (125 in Group A and sixty-eight in Group B), attempted to restore normal anatomical relationships. The results could be evaluated in 130 hands according to the range of motion, joint stability, and alignment of the remaining thumb after an average follow-up of 35.0 months. According to the rating system described, the results were rated as good in 75.5 per cent, fair in 20.2 per cent, and poor in 4.3 per cent of the ninety-four hands in Group-A patients who were followed. In the thirty-six hands of Group-B patients who could be followed, the preoperative and postoperative scores were compared. Thirteen were not improved while the other twenty-three, sixteen improved from fair to good and seven improved from poor to fair, to give a good result in 63.9 per cent of the Group-B patients who were followed. The results in these 130 Group-A and B hands emphasize the importance of providing muscle balance and, in young patients, of performing an arthroplasty of the interphalangeal or metacarpophalangeal joint when indicated, although arthrodesis was indicated as a salvage operation for Group-B patients who were more than fifteen years old.

Adolescent↗

The carpus in congenital anomalies of the hand.

Congenital anomalies of the carpus associated with congenital hand and upper limb anomalies were investigated from the point of view of the development of the hand. Defects of the carpus were categorized as follows: 1) Radial ray defect: loss of the scaphoid, trapezium and trapezoid. 2) Central ray defect: loss of the capitate and loss of a part of the trapezium and hamate. 3) Ulnar ray defect: loss of the triguetrum, pisiformis and hamate. Deficiencies of the carpus and more distal parts of the hand proved to be secondary to defects of the forearm bones in both the radial and ulnar ray. On the other hand deficiency of the carpus was secondary to defects of the phalanx and metacarpal of the middle finger in the central ray. Thus, from the standpoint of the development of the carpus, bipolar development of the bones of the hand originates proximally in both the radial and ulnar rays and distally in the central ray.

Adolescent↗