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Biomedical subjects

H Akaza

Publications and source records attributed to H Akaza.

At least 181 records · Page 10Linked to original sources

[Treatment of prostatic carcinoma with UFT and leucovorin--basic study using SRCA].

Combination effect of UFT and leucovorin against the rat prostatic carcinoma (R-3327) was evaluated by the subrenal capsular assay (SRCA) using nude mice. Anticancer effect of UFT was augmented by co-administration of both low and high dose leucovorin. These results suggest a clinical usefulness of UFT administration with leucovorin for the patients with hormonally refractory advanced prostatic carcinoma.

Animals↗

Expression of antitumor response. Role of attachment and viability of bacillus Calmette-Guérin to bladder cancer cells.

BACKGROUND: Antitumor effects of Bacillus Calmette-Guérin (BCG) against superficial urinary bladder cancer is known to be strong when BCG is directly infused into the bladder cavity. For expression of that effect, attachment of BCG to tumor cells is reported to be essential as the first step. Our study was conducted to elucidate the significance of attachment of BCG to tumor cells in inducing the antitumor effect. METHODS: BCG, Tokyo 172 strain, in the form of live bacilli, lyophilized bacilli, or autoclaved bacilli was co-cultured with MBT-2, mouse-origin transitional cell cancer cells. Various preparations of BCG were mixed with MBT-2 cells and transplanted to male C3H/He mice to see tumor growth-inhibiting effect. RESULTS: Both live and lyophilized BCG attached strongly to MBT-2 cells. The maximal attachment to the cells with live BCG occurred 24 hours earlier than with lyophilized BCG. When BCG was autoclaved, it lost the ability to attach to the cells. Lyophilized or autoclaved BCG exerted a marked tumor growth-inhibiting effects. This effect was equal to the Tokyo 172 strain and the Armand Frappier Canada strain. Histologically, a high degree of infiltration by macrophages was seen. CONCLUSIONS: The results indicated that coexistence of BCG, even as killed by autoclaving, with tumor cells activates local immunity. Accordingly, the significance of the attachment of BCG to tumor cells in intravesical infusion therapy is surmised to lie in the fact that it results in retention of the BCG at the reaction site. This may provide a clue on how to approach future development of safer and more stable BCG-derived antitumor drugs.

Animals↗

[Detection of numerical chromosome aberrations in urologic malignancies using in situ hybridization from formarin-fixed paraffin sections].

It has been shown that molecular cytogenetics in interphase nuclei is applicable to paraffin embedded sections from formarin-fixed materials utilizing in situ hybridization (ISH). This allows precise identification of numerical abnormalities of chromosome in tumor cells without disruption of tumor morphology. Thirteen cases of bladder cancer and twenty six cases of prostate adenocarcinoma were evaluated for numerical aberrations of chromosome 1, 7, 10, 11, 17, 18, X and Y utilizing biotinylated probes specific for the alpha satellite region. In two cases from total prostatectomy, one case from total cystectomy and two cases from TUR-P specimen, hybridized chromosomes could not be detected in individual tumor cells. With respect to the appearance of the ISH signal, optical concentration and time for the digestion enzyme has to be established essentially. This technique can now be applied on the detection of biological activity in various types of urological cancer.

Adenocarcinoma↗

[Histopathological comparison of prostatic adenocarcinoma in Japan and the United States].

Histopathological comparison of clinical prostatic adenocarcinoma between Japan and the United States (US) has been made with retrospective analyses on 1,037 and 987 cases, respectively. All cases were histologically evaluated by the same pathologist (M.H.) without previous knowledge of clinical information according to application of the Japanese General Rules for Prostatic Cancer (JGRPC) based on the predominant degree of histological differentiation, the nuclear grading by WHO classification and the Gleason grading systems. The age distribution of the patients was slightly different among both groups. However, this difference appeared not to be essential, because there existed difference of the date on diagnosis between two groups. Even though considering this time difference on registration, much more cases from Japan had stage D disease. The observed incidence of the histological differentiation classified by JGRPC among over-all cases did not show significant difference, however, the incidence among the cases with same stage between two groups differed with some statistical significance. Much more cases from the US fell in well differentiated adenocarcinoma and frequency of moderately differentiated adenocarcinoma was higher in the Japanese even in the cases diagnosed at advanced stages. The observed incidence of nuclear grade 3 was also higher in the Japanese. Gleason primary and secondary grade 5 and score 9-10 appeared more frequently in the cases from Japan.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Histopathological comparison of stage A prostatic adenocarcinoma in Japan and the United States].

Histopathological characteristics of stage A prostatic adenocarcinoma from Japan (137 cases) and the United States (51 cases) were comparatively evaluated by retrospective analysis. All cases were examined by one referee pathologist (MH) using classification based on Japanese General Rules for Prostatic Cancer (JGRPC), nuclear grading by Mostofi-WHO system and Gleason grading. The incidences of the cases with well differentiated, low nuclear anaplasia and Gleason grade 1 or 2 on primary and secondary grades as well as histologic score 2-4 were much more higher in the cases from Japan as compared with those from the US. In the cases from the US proportion of the cases with moderately differentiated adenocarcinoma and grade 2 nuclear anaplasia exceeded those with well differentiated and grade 1 anaplasia. Adenocarcinomas with Gleason grade 3 in primary and secondary grade and 6-8 of histologic score were also more frequently observed in the cases from the US. No different distribution of each histologic grade could be obtained among the Japanese cases classified stage A2 and entire cases from the US. These results suggest that much more stage A adenocarcinoma in the US might fall into A2 if strict criteria was applied for subcalssification of stage A, which may reflected in the remarkable difference in the incidence of clinical prostatic carcinoma.

Adenocarcinoma↗

[Phenotypic difference of lymphocytes circulating in tumorous renal artery and renal vein in patients with renal cell carcinoma].

Phenotypic difference of lymphocytes circulating in tumorous renal artery and renal vein in patients with renal cell carcinoma was studied. Fifteen patients with no prior treatment were studied, from whom blood samples were taken at the time of radical nephrectomy. Mononuclear cells separated from tumorous renal arterial and venous blood were analyzed for cell surface markers. CD3, CD4, CD8, CD11b, CD16, CD25, CD57, Leu8 HLA-DR were compared. CD25 positive cells were significantly increased in venous blood than in arterial blood in the kidneys with tumor. No significant difference was found regarding the other surface markers.

Carcinoma, Renal Cell↗

[A case report of an ectopic ureter in a patient treated for chronic prostatitis].

A male aged 20 had been treated for anal and lower abdominal pain after ejaculation for about 2 years under the diagnosis of chronic prostatis. Because of worsening of the pain, he was admitted to our hospital in September 24, 1991. On the rectal examination, a cystic tumor was palbable on the left side of the prostate. The left kidney was not detected by IVP and ultrasonography. CT revealed two retrovesical cystic lesions in the left side. Cystourethroscopy showed an absence of ureteral orifice and ureteral ridge on the left side. Left uretero-seminal vesiculectomy was performed on October 3rd, under the diagnosis of an ectopic ureter entering into the seminal vesicle or ejaculatory duct. Histopathologically, the left ectopic ureter entering into the lower portion of the seminal vesicle or ejaculatory duct and the left renal agenesis were diagnosed. It was remarkable that ureteral epithelium was not transitional but columnar epithelium.

Adult↗

[Assessment of the quality of life of prostate cancer patients].

Assessing the QOL in cancer clinical trials is becoming increasingly important. However, a suitable device of assessment of QOL has not been developed yet for prostate cancer patients in Japan. We tried to assess the QOL of prostate cancer patients using the EORTC questionnaire translated in Japanese, and examined its validity and reliability. Thirty-six patients filled in a questionnaire. The reliability of this device was confirmed by the results of test-retest reproducibility. Good correlation was shown between the results and patients performance status, and between the results and clinical stages, which support the validity of the device. As for the results of assessment of QOL, these patients were severely damaged in sexuality. Those factors of functional status, physical symptoms and fatigue/malaise were closely related to disease activity and clinical stage.

Aged↗

[Retroperitoneal liposarcoma with intrarenal metastases which was difficult to distinguish from angiomyolipoma. A case report].

A 40-year-old man was admitted to our hospital with a fat-density extrarenal tumor and intrarenal nodules which were detected by ultrasonography (US) and CT scan obtained the general health check. After his admission, US, CT, MRI and angiography were performed. As the final diagnostic procedure, we performed a US-guided percutaneous needle biopsy of the extrarenal tumor, because this tumor was difficult to distinguish from liposarcoma and angiomyolipoma (AML). The pathological study revealed a well-differentiated liposarcoma, and the extrarenal tumor and the left kidney were removed en bloc. Pathologically, the tumor not only invaded into the renal parenchyma directly but also have metastasized independently to the intrarenal region. Postoperatively, he received a tumor dose of irradiation of 50 Gy. Liposarcoma arising in the perirenal space should be considered in the differential diagnosis of exophytic AML. If radiological studies can not confirm the appropriate diagnosis, we consider that biopsy of the tumor should be selected as an alternative diagnostic approach. And, we think that this is the first case report dealing with intrarenal metastases of liposarcoma.

Adult↗

A randomized phase II trial of flutamide vs chlormadinone acetate in previously untreated advanced prostatic cancer. The Japan Flutamide Study Group.

We have conducted a double-blind comparative study of flutamide and chlormadinone acetate (CMA) on patients with stage C or D prostatic cancer and with no prior experience of hormone therapy. This is believed to be the first such trial entered in the medical literature, fifty-four patients were randomly selected to undergo flutamide (p.o.) monotherapy at a daily dose of 375 mg, which was determined as the optimal dose in Japan in our previous phase II study. Forty-nine others were randomly selected to undergo CMA (p.o.) monotherapy at a daily dose of 100 mg, which is the most commonly used dosage in Japan for patients with prostatic cancer. Ultimately, 47 patients from the flutamide group and 40 patients from the CMA group were judged eligible, with efficacy being evaluated after 12 weeks of treatment. Similar objective responses were seen in both groups: 48.9% (95% confidence limits 34.1-63.9%) in the flutamide group, 45% (95% confidence limits 29.3-61.5%) in the CMA group. The response at each organ site was also similar between the groups. Serum prostatic specific antigen decreased by more than 50% of the abnormal pretreatment level in 87.5% of the flutamide group and in 85.7% of the CMA group. Serum luteinizing hormone, follicle-stimulating hormone, testosterone and 5 alpha-dihydrotestosterone decreased significantly in the CMA group, but increased significantly in the flutamide group. The serum testosterone level after 12 weeks of treatment was 0.955 +/- 0.13 ng/ml in the CMA group and 6.64 +/- 0.38 ng/ml in the flutamide group. The serum estradiol level also increased significantly in patients in the flutamide group. The serum prolactin level decreased significantly in the flutamide group, but increased significantly in the CMA group. Eight patients on flutamide manifested gynecomastia. Diarrhea and hepatic toxicity were observed in both groups, but only rarely, and were well tolerated. We have thus concluded that flutamide is as effective as CMA in maintaining libido and potency without decreasing testosterone levels.

Aged↗

[Young's syndrome].

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Constriction, Pathologic↗

[Subrenal capsule assay of nude mice for testing the effectiveness of UFT for rat prostatic carcinoma (R3327)].

Combination effect of UFT and CDDP against the rat prostatic carcinoma (R3327) was evaluated by the subrenal capsule assay in nude mice. The tumor growth of R3327 was inhibited in proportion to the UFT concentration. Anticancer effect of UFT was elevated by co-administration of CDDP. These data suggest a clinical usefulness of UFT administration with CDDP for hormonally refractory advanced prostatic carcinoma.

Animals↗

[Phase I study of flutamide, a nonsteroidal antiandrogen, in patients with prostatic cancer].

A phase I study of orally administered flutamide (a pure anti-androgen) was performed in 26 patients with prostatic cancer. No side effects were observed in 11 patients receiving single doses of either 125, 250, 375 or 500 mg. However, in the daily dosing schedule of 375, 750, 1125 and 1,500 mg/day doses, where medication was taken in three divided doses, discomfort in the stomach, nausea, vomiting and anorexia were experienced in one of the four patients receiving the highest dose of 1,500 mg. Nine patients receiving the other doses did not complain of toxic symptoms. Laboratory values did not change in the three patients receiving the lowest 375 mg/day dose, but elevation of transaminase was observed in five of the nine patients given higher doses. This elevation was observed in all the three patients receiving 1,500 mg/day dose. Among the serum hormone levels, significant increases of luteinizing hormone were observed. As for efficacy, objective responses were observed in two of the three patients in each of the four daily dosing groups. Improvement of pain, voiding obstruction symptoms, and performance status were also observed. Flutamide was found to be absorbed rapidly and to exist as a hydroxylated form (hydroxy-flutamide) in the plasma. The half-life of hydroxy-flutamide was similar in the single and daily administration, but the peak concentration and area under the concentration versus time curve in the daily administration became greater than those in the single administration. In conclusion, flutamide should be examined for efficacy and safety using doses of 375 to 1,125 mg/day in the phase II study.

Administration, Oral↗

[Clinical evaluation of flutamide, a pure antiandrogen, in prostatic cancer phase II dose-finding study].

The phase II study of flutamide, a pure anti-androgen, was performed to estimate the clinical doses on 165 hormone untreated or treated patients with prostatic cancer. The hormone-untreated patients were given orally flutamide of 90, 375, 750 or 1,125 mg/day in three divided doses daily for 12 weeks. Responses were not observed at the 90 mg/day dose except for improvement of clinical symptoms. However, an objective response rate of 48.8-46.7% was obtained at 375-1,125 mg/day doses. In hormone-treated patients including cases refractory to the previous hormonal treatment, the objective response rates were 13.3 and 8.3% in 375 and 750 mg/day flutamide groups, respectively. Side effects such as gynecomastia, nausea, vomiting, diarrhea, and abnormal laboratory findings such as the elevation of hepatic transaminases were observed. The incidence increased dose-dependently. Determinations of serum hormone levels revealed an increase in testosterone levels by the use of flutamide. In conclusion 375 mg/day of flutamide is the optimal dose in monotherapy for hormone-untreated patients with prostatic cancer, where the quality of life can be maintained compared with therapies involving testosterone suppression. This dose is also expected to show some efficacy in cases refractory to hormone treatment.

Administration, Oral↗

Enhancement of chemotherapeutic effects by recombinant human granulocyte colony-stimulating factor on implanted mouse bladder cancer cells (MBT-2).

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered intraperitoneally in combination with multidrug chemotherapy using methotrexate (M), vinblastine (V), doxorubicin (A), and cisplatin (C, or for the combination, MVAC) to C3H/He mice (5-week-old females) after experimental carcinoma, MBT-2, a transplantable transitional cell carcinoma of the urinary bladder had been implanted. The effects of therapy were studied. The animal groups consisted of: (1) control (no drug administration), (2) rhG-CSF (100 micrograms/kg/d, from days 8 through 42 after MBT-2 implantation, except for the days when MVAC was administered), (3) high-dose MVAC (2 mg/kg of M, 0.2 mg/kg of V, 2 mg/kg of A, and 4 mg/kg of C once a week for 3 weeks), (4) low-dose MVAC (one-quarter of the high dose), (5) high-dose MVAC with rhG-CSF, and (6) low-dose MVAC with rhG-CSF. In an in vitro system, rhG-CSF did not show any effect on the proliferation of MBT-2 cells or exert any influences on A's tumor proliferation-suppressing action on MBT-2. However, in an in vivo system, concomitant administration of rhG-CSF significantly enhanced the tumor-suppressing effect of the MVAC therapy, as did rhG-CSF alone. The greatest effect was observed in the group receiving high-dose MVAC plus rhG-CSF. These result suggested that rhG-CSF-stimulated granulocytes may exert antitumor activity on tumor cells severely damaged by chemotherapeutic agents at a relatively high concentration. The survival rate was improved to some degree even by administration of rhG-CSF alone. Although further study is required to elucidate the action mechanism of rhG-CSF, these results suggest that rhG-CSF may be useful clinically to enhance the activity of antitumor agents and not only through its ability to alleviate granulocytopenia or prevent its development.

Agranulocytosis↗