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Biomedical subjects

Y Sakamoto

Publications and source records attributed to Y Sakamoto.

At least 559 records · Page 31Linked to original sources
PubMed1987

[Combination chemotherapy with 3 or 4 drugs on human breast and gastrointestinal cancer xenografts in nude mice (II)].

Because of the limited effects of single-agent chemotherapy for solid tumors, combination therapy was employed in an attempt to enhance the clinical effects. Following our former report in which the combination effects of mitomycin C (MMC) and 5'-deoxy-5-fluorouridine (5'-DFUR) were clarified, combined applications of 4 drugs, vindesine (VDS), methotrexate (MTX), cisplatin (CDDP) and 5'-DFUR against 3 lines of human breast cancer (H-62, H-31, H-71), and one line each of gastric cancer (H-55) and colon cancer (H-110) xenografted into nude mice were evaluated in comparison with CAF (cyclophosphamide, adriamycin and 5-FU) therapy which is commonly used for breast cancer. Treatment was initiated in groups of 7 mice each when the mean tumor volume of subcutaneous tumors had reached about 100mm3, and the therapeutic effect was evaluated in terms of the inhibition rate (I.R.). A synergistic effect is said to exist when the combination therapy is superior to each single drug therapy at the maximal tolerated dose. Combination therapy with 3 drugs (VDS, CDDP and 5'-DFUR) or 4 drugs (VDS, CDDP, MTX and 5'-DFUR) achieved an I.R. of over 98%, i.e., a marked effect with tumor shrinkage, in 3 lines of tumors (H-55, H-31 and H-62). Moreover, remarkable effects were shown even in the other 2 lines which were insensitive to every single-agent therapy, the I.R. values being 85.7% (H-71) and 78.5% (H-110). A synergistic effect was obtained in 3 of the 5 lines examined. These combination therapies were histologically superior to therapies employing each single-drug therapy or CAF therapy. The side effects for combination of these 3 or 4 drugs evaluated by body weight loss were transient and equivalent to maximal dose of VDS or CDDP. Clinically, it is thought that these combined therapies of 3 or 4 drugs will bring about a considerable response in practice.

Animals↗
PubMed1987

[Effects of alternating chemotherapy with 2 non-cross-resistant drug combinations on human alimentary and breast cancer xenografts in nude mice].

Despite the recent advances made in the development of anticancer drugs, any single chemotherapy treatment has only limited effects on cancers of the stomach, colon and breast, so that the combined use of multiple drugs is necessary for the treatment of solid tumors. In our previous studies with human gastrointestinal and breast cancers xenografted into nude mice, combination therapy with mitomycin C (MMC) and 5'-deoxy-5-fluorouridine (5'-DFUR) [I] or cisplatin (CDDP), vindesine (VDS) and 5'-DFUR [II] produced higher response rates than single-agent therapy with any one of these drugs. In the present study, the effectiveness of alternating chemotherapy with the combination regimens I and II was evaluated using 3 lines of cancer xenografts with special emphasis on relapse-free survival. Even in untreated controls, different influences of these cancers on the host as well as differences in their growth rates resulted in delayed tumor death in breast cancer (H-31) compared with pancreas (H-48) and colon (H-110) cancers. Four cycles of the regimen I drug combination failed to prolong life due to toxic side effects in every cancer line. In H-48 cancer, although regimen I alternated with regimen II achieved an inhibition rate (IR) of 96% with tumor shrinkage, 2 of 7 mice died of toxicity. In H-110 cancer, which is only sensitive to VDS, 4 cycles of regimen II alone produced an IR of 83.5%, which was slightly superior to alternating chemotherapy. In H-31 cancer, which retains considerable sensitivity to CDDP, MMC and 5'-DFUR, mice treated with alternating chemotherapy starting from regimen I for a total of 5 cycles attained a maximal IR of over 99% including disappearance of the tumor in 6 of 7 mice during the treatment course, and at the end of the experiment (20th week), all had survived with one in a relapse-free state, compared with the control group which had only 2 survivors. Thus, cyclic delivery of two non-cross-resistant drug combinations with optimal treatment doses and timing prevented toxic effects and induced long-term survival without relapse. Also, this appears to be the first study that has evaluated the effects of cancer chemotherapy in a human solid tumor-nude mouse system according to survival rate.

Animals↗
PubMed1987

[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↗
PubMed1987

[A parallel comparative double blind study of cefixime with cefroxadine in the treatment of acute lacunar tonsillitis].

The clinical efficacy and safety of cefixime (CFIX), a new oral cephalosporin, were compared with those of cefroxadine (CXD) in patients suffering from acute lacunar tonsillitis in a double blind study. Two hundred and fifty two patients were given each orally 100 mg of CFIX b.i.d. or 250 mg of CXD t.i.d. for, in principle, 7 days. Number of patients evaluated for clinical efficacy was 202 (103 treated with CFIX and 99 treated with CXD). As for the backgrounds of patients, more severe cases were found in the CFIX group than in the CXD group (P less than 0.01). Efficacy rates evaluated by individual doctors were 88.3% in the CFIX group and 91.9% in the CXD group. There was no significant difference between the 2 groups. Efficacy rates on the third day after the initiation of treatment evaluated by the committee were 40.8% in the CFIX group and 47.9% in the CXD group with no significant difference. Efficacy rate on the 7th day, however, was 79.8% in the CFIX group and 93.4% in the CXD group, showing a significant difference (P less than 0.05). Bacteriological effectiveness were satisfactory for both groups with eradication rates of 93.4% for the CFIX and 96.9% for the CXD group. Number of patients evaluated for safety was 226 (110 treated with CFIX and 116 treated with CXD). No significant difference was observed between the 2 drug groups in incidences of side effects; gastrointestinal disturbances or rashes were noted in 6 patients (5.5%) of the CFIX group and in 5 patients (4.3%) of the CXD group. As for the abnormal laboratory findings, elevation of GOT & GPT was observed in 1 patients of the CFIX group. From these results, it was concluded that 100 mg b.i.d. of CFIX was as useful as 250 mg t.i.d. of CXD in the treatment of acute lacunar tonsillitis.

Acute Disease↗
PubMed1987

[Expression of Thomsen-Friedenreich antigen (T-Ag) in gynecologic cancer tissues].

The expression of Thomsen-Friedenreich antigen (T-Ag), the precursor of MN blood group antigen, was studied by the ABC method with Arachys Hypogaea lectin (PNA) and the relationship of the results to the histology and clinical behavior of primary gynecologic cancers were examined. The results were as follows: 1. In cervical squamous cell tumors, the incidence of the expression of T-Ag in invasive cancers (52.9%, 37/70) was significantly higher (p less than 0.05) than that in intraepithelial tumors (28.6%, 8/28). No cryptic T-Ag(-) tissue was found in intraepithelial tumors or microinvasive cancers. 2. In squamous cell carcinomas of the cervix, the incidence of cryptic T-Ag(-) tissue was high (36.4%, 4/11) in tissue of the small cell non-keratinizing type, the most undifferentiated type, whereas it was not found in 5 cases of well-differentiated keratinizing carcinoma examined. 3. In stage Ib and II cervical cancers, no relationship was recognized between the expression of T-Ag in primary lesion and extension to the parametrium or the pelvic lymph nodes. 4. The incidence of T-Ag(+) tissue in adenocarcinomas of the uterine cervix (62.5%, 5/8), the endometrium (91.7%, 11/12), and the ovarian (80%, 8/10) was higher than that in squamous cell carcinoma of the uterine cervix (52.5%, 32/61). 5. In endometrial cancers, no relationship was recognized between the expression of T-Ag and hormone receptor status.

Adenocarcinoma↗
PubMed1987

[Report of two cases of advanced renal cell carcinoma and our experience at Mito Saiseikai General Hospital].

A tumor thrombus in the vena cava (infrahepatic) was identified in a 70-year-old male with chronic obstructive lung disease, and right nephrectomy and thrombectomy were performed successfully. Therefore, he enjoyed good health for 6 months until he developed bone metastasis in the vertebrae and upper gastrointestinal bleeding. In another case of a 51-year-old male who presented with a mass in the posterior part of the chest; the biopsy specimen of the mass was reported to at least resemble renal-cell carcinoma. Subsequently, he underwent right nephrectomy and thoracotomy to remove the mass. He has since led an uneventful life without tumor recurrence. In our hospital from 1971 to 1980, 9 cases of renal-cell carcinoma have been experienced, including the above 2 cases. Their average age was 49.4 years, with ages ranging from 34 to 70 years. Seven patients presented with gross hematuria, and 2 patients, with flank pain. All 9 cases, all of whom underwent radical nephrectomy, were diagnosed pathologically as having renal cell carcinoma. The right side was involved in 3 cases, and the left, in 6 cases. The upper pole of the kidney was involved in 2 cases the middle in 1 case, and the lower in 5 cases. The mean 5-year survival rate was 69.2% and was closely associated with the tumor stage.

Adult↗
PubMed1987

[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↗
PubMed1987

[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↗
PubMed1987

[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↗
PubMed1987

Effects of adenosine and theophylline on canine tracheal smooth muscle tone.

The postulated mechanisms by which theophylline induces relaxation of airway smooth muscle include, among others, inhibition of cyclic nucleotide phosphodiesterase(s) and antagonism of adenosine-induced contraction. This latter possibility was examined by investigation of the interaction of theophylline and adenosine in canine tracheal smooth muscle preparations. Adenosine did not alter basal tone i.e. there is no evidence of a contractile response. However, when contraction was induced with methacholine, adenosine caused relaxation. It appears that this relaxation occurred as a consequence of the combination of adenosine with a site within the smooth muscle cell. The prior addition of theophylline (10(-6)-10(-3) M) did not alter adenosine-induced relaxation and in the reverse experiment, the prior addition of adenosine (10(-6)-10(-3) M) did not alter the relaxation produced by theophylline. It is concluded that adenosine relaxes canine tracheal smooth muscle by combination with an intracellular site, rather than a receptor on the cell surface. The hypothesis that theophylline relaxes airways smooth muscle by antagonism of adenosine or that adenosine antagonizes theophylline was not supported by our data.

Adenine↗
PubMed1987

[The effect of physical exercise in experimental osteoporosis rats].

The effect of physical exercise on the growth of bones was studied. Male rats 8 weeks old were divided into 3 groups, a sedentary group and 2 exercise groups (RUN 1, RUN 2). Rats in the exercised groups were conditioned by a treadmill running program for 8 weeks (RUN 1, 1 hr X 1/day; RUN 2, 1 hr X 2/day). Animals in the RUN 2 group showed remarkably increased cortical thickness and density by the microdensitometry method and greater dry weight. Female rats in the similar running program showed the effective change in only RUN 1 group. To evaluate the protective effect of physical exercise on the loss of bone mass in experimental osteoporosis, 6 week old rats were bilaterally ovariectomized, fed a low Ca diet and exercised on a treadmill. Ovariectomized-exercised bones were higher in cortical thickness, density, area and dry weight than the ovariectomized-unexercised group. These results support the view that suitable physical exercise may be a valuable treatment for postmenopausal osteoporosis in human beings.

Animals↗