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Biomedical subjects

M Akimoto

Publications and source records attributed to M Akimoto.

At least 145 records · Page 8Linked to original sources
PubMed1991

[The activity of etoposide (VP16) in combination chemotherapy against human bladder cancer cells in vitro].

The activity of Etoposide (VP16) in combination chemotherapy against four human transitional cell carcinoma cell lines of bladder (TCCaB) was determined by in vitro colony formation assay. Four anti-tumor agents (methotrexate: MTX, vinblastine: VBL, adriamycin: ADM, cisplatin: DDP) were used for combination chemotherapy with VP16. The ADM + VP16 combination exhibited a strong synergistic antitumor effect against the human TCCaBs compared with other combinations in this study. The combination chemotherapy of ADM + VP16 may be useful as a new chemotherapeutic regimen for advanced bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[Clinical phase III study on TAP-144-SR, an LH-RH agonist depot formulation, in patients with prostatic cancer].

A randomized controlled phase III clinical trial comparing TAP-144-SR (TAP) and diethylstilbestrol diphosphate was conducted for patients with prostatic cancer. Patients with Stage B, C, or D disease, who were previously untreated, were enrolled. TAP-144-SR 3.75 mg was administered subcutaneously at 4-week intervals for 12 weeks (a total of 3 injections) in the TAP-144-SR group, while 100 mg of diethylstilbestrol diphosphate was administered orally three times a day (before meals) for 12 weeks in the control group. A total of 141 patients were enrolled using a centralized telephone registration system. Four of these patients were ineligible, and there were 3 drop-outs who never received drugs because they withdrew their consents to participate in the trial. These 7 were excluded from the evaluation, and as a result, 134 patients (66 in the TAP group and 68 in the control group) were evaluable in safety and efficacy. Between the two groups, there were no significant differences in patient characteristics, except the age distribution. Clinical response rates (CR+PR) in evaluable patients according to the criteria of Japanese Prostatic Cancer Study Group were 54.5% in the TAP group and 47.1% in the control group. In addition, the rates according to the criteria for Evaluating the Direct Response to Chemotherapy in Solid Carcinomas and NPCP criteria were 7.6% in the TAP group and 8.8% in the control group and 18.2% in the TAP group and 20.6% in the control group, respectively. Using any of the three criteria, there were no significant differences in response rate between the two groups. The incidence of side effects was 64.1% in the TAP group and 95.4% in the control group; the incidence being significantly higher in the control group (p less than 0.001; chi 2-test). Therefore, the overall safety was significantly greater in the TAP group than in the control group (p less than 0.001; chi 2-test). On the basis of the efficacy and safety the clinical usefulness rate of TAP-144-SR was significantly higher than that of diethylstilbestrol diphosphate (p = 0.038; U-test). In conclusion, TAP-144-SR was confirmed to be more useful than diethylstilbestrol diphosphate as a standard drug for hormonal therapy of prostatic cancer.

Aged↗
PubMed1991

[Treatment of superficial bladder tumor].

In period of April, 1982 to March, 1987 for 5 years, fifty-four patients with superficial bladder tumors were treated at the Department of Urology, Nippon Medical School. There were 42 males and 12 females with age ranged from 28 to 85 years old. All patient underwent TUR-Bt (trans urethral resection-bladder tumor) as an initial treatment. The rather long term follow-up study after initial treatment was 47 months in average. Recurrence rate at 2 years after TUR-Bt was 30%. The risk factors of recurrence were analysed in connection with sex, age, tumor number, histological grade and stage, and infiltration pattern. In conclusion, significantly higher recurrence rate were observed in G2 than G1 and G3, and in pT1b rather than pTa and pT1a. Other factors were not distinctly correlated with incidence of recurrence.

Adult↗
PubMed1991

[Improved therapeutic effect of sequential immunotherapy with cyclophosphamide, large doses of OK-432 and recombinant interleukin-2 in breast cancer patients with disseminated metastatic liver tumors].

It has been generally agreed that the prognosis of widely spreaded "surgically unresectable" metastatic liver tumor originated from breast cancer is very poor. We reported here the result of clinical efficacy of sequential immunotherapy with intra-tumoral injection of large dose OK-432, after oral administration of cyclophosphamide during 7-10 days, and continuous perfusion of purified human recombinant interleukin-2 (rIL-2) from hepatic artery for the breast cancer patients with unresectable metastatic liver tumors. In all of 3 cases, metastatic liver tumor revealed overwhelming tumor reduction more than 50% of preoperative total tumor burden evaluated by computed tomography. Only 1 day after operation, large doses of OK-432 was injected intratumorally, both activity of Natural Killer (NK) cells and lymphokine activated killer (LAK) cells in peripheral blood lymphocytes were 5-20 folds augmented in all clinical trials. Serum tumor markers, i.e., Carcinoembryonic Antigen (CEA) and CA15-3, were rapidly decreased in all cases, respectively. Our clinical data indicate that intratumoral injection of large dose OK-432 and continuous administration of rIL-2 via hepatic artery, pretreated with cyclophosphamide, were clinically effective immunotherapy for reduction of metastatic liver tumor.

Administration, Oral↗
PubMed1990

Immunohistochemical demonstration of epidermal growth factor in human gastric cancer xenografts of nude mice.

Thirty-two surgical specimens and three cell lines of human gastric cancers were used for subcutaneous transplantation into nude mice, resulting in the establishment of eight (25%) xenografts from the surgical specimens and two (67%) from the cell lines. The localization of epidermal growth factor (EGF) in the surgical specimens and cell lines of the gastric cancers and their xenografts in nude mice was then investigated immunohistochemically. Epidermal growth factor was stained in the cytoplasm of the cancer cells, being detected in 16 (50%) of the 32 surgical specimens and in all of the cell lines. Seven (44%) of the sixteen EGF-positive surgical specimens and one (6%) of the 16 EGF-negative ones were tumorigenic in nude mice. All of the xenografts in nude mice were positive for EGF. The tumorigenicity of human gastric cancer xenografts in nude mice may, therefore, be correlated with the presence of EGF in cancer cells.

Adenocarcinoma↗
PubMed1990

Papilloma of renal pelvis in childhood.

A papilloma in the renal pelvis of a five-year-old girl is reported. The transitional cell tumors of the renal pelvis in the pediatric age group are reviewed, and this is found to be the first case of a benign papilloma in childhood. We believe this pathologic entity should be included in the differential diagnosis of hematuria in a child.

Child, Preschool↗
PubMed1990

[In vitro effects of epidermal growth factor (EGF) on growth of urological malignant tumor cells].

It is well known that Epidermal Growth Factor (EGF) is a cell-regulating factor for variety of tissues in vitro including normal and malignant cells. Furthermore, Takano et al reported that a decreased expression of EGF receptor in clones of human cancer KB cell line might be one of the pleiotropic properties of multidrug-resistant cells. However, both the influence of EGF on human urological cancer cell lines and the relation between EGF receptors and sensitivities of antitumor drugs on these cell lines have not been fully described. We have studied the effects of EGF on growth of 4 transitional carcinoma cell lines of bladder (TCCaB), 1 squamous cell carcinoma cell line of bladder (SCCaB), 5 renal cell carcinoma cell lines (RCC) and 3 prostatic carcinoma cell lines (CaP), as well as the relationship between the number of EGF receptors and drug sensitivities of these cell lines in vitro against methotrexate, vinblastine, adriamycin, cisplatin and etoposide (VP16). The present results determined by the in vitro colony forming efficiency method showed that exogenous addition of EGF to cell cultures at 0.1 ng/ml stimulated the growth of SCCaB by 169.0%, and at 1 ng/ml inhibited that of RCC by 2.9%-79.0%, relative to control. The more EGF receptors by 125I-EGF binding assay, the higher inhibition of VP16 on the growth of these cell lines. These results suggested that EGF stimulated the growth of SCCaB and inhibited the growth of RCC in vitro, and we found that these phenomena were correlated with neither the number of EGF receptors nor affinities of that receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1990

[Study of cytotoxicity of recombinant interleukin-2 (rIL-2) expanded tumor infiltrating lymphocytes (TIL) in renal cell cancer].

We studied subsets and cytotoxicity of recombinant interleukin-2 (rIL-2) expanded tumor infiltrating lymphocytes (TIL) from renal cell cancer (RCC) patients. TIL were successfully expanded in 13 of 14 RCC cases using anti-CD3 during initial 48 hours of culture. Percentages of CD8 positive cells among rIL-2 expanded TIL at 1 tp 4 week(s) of culture were 56.2 +/- 15.1% (range 26.2 to 79.8%, N = 13) and not necessarily predominant over CD4 positive cells. NK and LAK activities of TIL at 3 to 6 weeks of culture were 31.6 +/- 15.8% (range 1.4 to 57.4%, N = 9) and 16.6 +/- 11.6% (range 3.8 to 35.6%, N = 6), respectively. Autologous and allogeneic RCC cytotoxicity of TIL at 3 to 4 weeks of culture were 17.9 +/- 19.7% (range 0 to 47.6%, N = 4) and 18.9 +/- 14.8% (range 0 to 47.3%, N = 12), respectively. Since there was no statistical difference between them, autologous specific cytotoxicity was not demonstrated. From these results of present study, it is unlikely that most of effector cells of rIL-2 expanded TIL in autologous RCC lysis are major histocompatibility complex restricted cytotoxic T cells. And we concluded that it is doubtful that TIL is significantly superior over LAK cells in immunotherapy of human RCC.

Carcinoma, Renal Cell↗
PubMed1990

[Therapy on pulmonary metastasis of renal cell carcinoma].

We reviewed the results of therapy on pulmonary metastasis of renal cell carcinoma performed in our hospital between 1979 and 1988. Eighty patients of renal cell carcinoma were treated during the period. Of those patients 13 (10 males and 3 females) had pulmonary metastasis and their ages were between 52 and 74 (average 61.6). The therapies we performed were surgical resection, cytotoxic chemotherapy, BRM (biological response modifier) therapy, hormone therapy and irradiation therapy. Four patients became tumor free by administration of medroxyprogesterone acetate, interferon-alpha, UFT (a compound combining tegafur and uracil) and surgical resection respectively. In 1 patient, administration of UFT resulted in partial remission. Cytotoxic chemotherapy using cisplatin, vinblastine and doxorubicin, and irradiation therapy were not effective. These findings suggest that BRM therapy, UFT therapy and hormone therapy are effective in eliminating pulmonary metastasis of renal cell carcinoma, particularly in the patients with excellent performance status whose original lesions had been resected.

Aged↗
PubMed1990

[Effect of endothelin on gastric mucosal lesion in rats].

Gastric mucosal blood flow and gastric mucosal prostaglandin E2 (PGE2) and prostacyclin (PGI2) were investigated in male Wistar rats intraarterially injected with endothelin (ET), an endothelium-derived vasoconstrictor peptide. Immediately following ET (4 nmol/kg) administration, gastric mucosal blood flow decreased. Then 30 min later, the blood flow reached the minimum, but PGE2 and PGI2 showed the highest value. PGE2 showed a tendency to decrease 90 min later, while PGI2 continued to show high value. There were redness and hemorrhagic damage in the gastric mucosa. Endogenous PGs were presumed to be relate to the regulation of the development of the mucosal damage owing to decrease in the blood flow after ET administration.

Animals↗
PubMed1990

Stable isotope 15N-urea and clinical research in nephrology.

Stable isotope 15N-compound, 15N-urea, is useful marker to investigate nitrogen metabolism in clinical nephrology, particularly in chronic renal failure or dialysis. 15N-urea incorporation into plasma albumin in addition to plasma 15N disappearance was studied in 6 patients with endstage chronic renal failure. As a result, only minor fraction of administered 15N-urea was incorporated into albumin in this study. In addition, it was also confirmed that high energy diet may promote protein synthesis through 15N incorporation to plasma amino acids, such as alanine, in these patients with low protein meal. Therefore, administration of 15N-compound to human subjects may contribute to provide us the important informations on nitrogen metabolism. For instance, urea kinetics are described in the endstage chronic renal failure in this review. However, less expensive 15N-compounds should be provided and more simple but accurate measurement of 15N activity should be developed for the further clinical application of the stable isotope.

Adult↗
PubMed1989

Transurethral enucleation of benign prostatic hyperplasia.

A prostatic detaching blade for a new endoscopic method has been devised for transurethral resection of the prostate along the cleavage plane at the surgical capsule. After partial resection of the adenoma with the loop the remaining adenoma, except for a portion at the bladder neck, is detached from the surgical capsule under direct vision with the detaching blade. The remaining adenoma then is removed by the electric loop down to the detached surgical capsule. This method of resection has been performed in 200 patients with improvement of symptoms in all. Detachment of the adenoma along the surgical capsule always is possible, thereby defining the depth of resection and minimizing the risk of capsular perforation compared to standard transurethral prostatectomy.

Aged↗
PubMed1989

[The analysis of the difference in anti-cancer drug sensitivity of 3 clones separated from bladder cancer cell line].

One of the major problems with cancer chemotherapy is the development of drug resistance during treatment. Two mechanisms are considered as the cause of drug resistance, natural and acquired. It is now considered that cancers can be composed of multiple clonal subpopulations of cancer cells. In this study, we separated three clones (C1, C3 and C8) from NBT-2 (human bladder cancer cell line) by limiting dilution. We examined the growth rate and the transplantability to nude mice and performed chromosomal analysis of three clones. The doubling time of C1 is 22 hours, and those of C3 and C8 were 25 and 36 hours, respectively. Each clone was transplantable to nude mice, but we could not find out any histological difference among them. The chromosome numbers of C1 was 66, and those of C3 and C8 were 68 and 63, respectively. We could also find out karyotypic difference among them. We could therefore consider that these three clones had different biological features and studied the difference in drug sensitivity among these three clones and the parent cell line. Cells (1 x 10(4)/well) were incubated in microplates with ten different chemotherapeutic agents for 72 hours. Then 3H-thymidine (1 microCi/ml) was added to each. After 24 hours, cells were harvested and the uptake of 3H thymidine was counted with a liquid scintillation counter. According to the reaction pattern, these chemotherapeutic agents were divided into three groups. 1. The radio isotope uptake of three clones and parent cell line was proportionally inhibited by increasing the drug concentration (carboplatin, (glycolato-o, o-) diammine platinum (II), ifosfamide).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Metastasis into the paracystium of urinary bladder carcinoma--the rate position and morphology of metastasis].

Twenty-three patients, who underwent radical cystectomy and pelvic lymph node dissection for bladder carcinoma from November 1985 to November 1987, were studied pathologically. We evaluated the rate, position and morphology of metastasis into the neurovascular corridor or paracystium. The stages of the twenty-three patients were G1 1, G2 10, G3 12 and pT1a 1, pT1b 4, pT2 8, pT3a 2, pT3b 7, pT4 1. Of the 23 specimens, 22 (95%) were found to contain metastasis in the connective tissue of the paracystium. Lymph node metastasis was recognized in four patients (17%). Metastasis in connective tissue around the iliac lymph node was recognized in 5 patients (22%). Of these 5 patients, 3 were free from lymph node metastasis. The morphological pattern of metastasis was ranged from a few tumor cells to massive tumor cells with proliferation of fibroblasts. The existence of metastasis in the paracystium should be evaluated morphologically for urinary bladder carcinoma.

Adult↗
PubMed1989

[Production of monoclonal antibody to renal cell carcinoma].

We report a novel way of obtaining a monoclonal antibody to renal cell carcinoma (RCC). BALB/c mice were immunized with RCC cells (ACHN, ATCC CRL1611) and hyperimmunized spleen cells were fused with Sp/2 murine myeloma cell line by PEG 2000. Many hybridoma supernatants were screened by enzyme linked immunosorbent assay (ELISA). After the cloning by limiting dilution, we established a hybridoma reactive to RCCs and named it A25. It belonged to the IgG1 subclass of immunoglobulins. According to our results using ELISA, 4 of 5 RCC cell lines were reactive to A25, while the remaining 23 non RCC cell lines did not react. The supernatant from A25 was used as a primary antibody preparation for avidin-biotin complex immuno peroxidase staining of multiple cases of RCC, normal tissue, and other tumors. This antibody reacted with 3 of 3 grade 1 RCC, 10 of 11 grade 2 RCC and 0 of 3 grade 3 RCC. Proximal tubules of the kidney shared this antigen. However, cross reactivity of this antibody was observed to pyloric glands of the stomach and adenocarcinoma of the colon. The epitope of A25 seemed to originate from normal kidney tubules. Low grade tumors preserved this epitope well, but this character of the original tissue seemed to disappear as tumor grade increased.

Animals↗
PubMed1989

[Subrenal capsule assay for chemosensitivity test of urinary tract cancers].

Subrenal capsule assay as a chemosensitivity test was performed on 8 renal cell carcinomas and 7 transitional cell carcinomas using athymic mice. Twelve of the 15 trials were considered suitable for evaluable assay. In 2 of the 3 non-evaluable trials the histological examination showed fibroblasts without cancer cells in the implants of the control group while the implants grew macroscopically. No host cell infiltration was observed microscopically in any implant of the control groups of evaluable assays. Mice were treated with several anticancer agents and sensitivities were evaluated by the tumor growth inhibition rate (TGIR) on the day 10 or 12 and by histological changes. No correspondence was observed between TGIR and histological changes. The characteristic histological finding of the treated groups of transitional cell carcinomas was cystic degeneration and it seemed to be a factor of the discordance between TGIR and the histological changes.

Animals↗
PubMed1989

[Reduction of 5-FU toxicity with improved nutritional status in tumor bearing mice].

This study was performed to determine the role of nutritional status as a determinants of 5 fluorouracil (5-FU) toxicity in a tumor bearing mice. After subcutaneous inoculation, of mammary tumor (81 B) mice were assigned randomly to two nutritional regimens, (1) 8% casein: D-mice, (2) 27% casein: N-mice. Mortality was increased significantly in D-mice (100%) compared with N-mice (0%) by administration of 5-FU (20 mg/kg). Intratumoral 5-FU concentration of D-mice was significantly lower than that of N-mice, 1 hour after i.p injection of 5-FU (100 mg/kg, 300 mg/kg). Both growth rate and intratumoral protein content of transplanted tumor was equivalent in two dietary group, N-mice and D-mice. Protein depleted status was associated with a significant reduction in Interferon production of spleen cells. Inhibition of cell proliferation in bone marrow and cytokine production were recognized in hypo-nutritional status. Thus, improved nutritional status reduced the morbidity and mortality associated with 5-FU treatment in tumor bearing mice.

Animals↗