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Biomedical subjects

N Miyao

Publications and source records attributed to N Miyao.

At least 55 records · Page 3Linked to original sources

[Dose finding study of sparfloxacin in single-dose therapy for female acute uncomplicated cystitis].

Sparfloxacin (SPFX) is a new quinolone compound with a long half-life of 16 hours and a potent antibacterial activity (MIC90: < or = 0.025 micrograms/ml against Escherichia coli), suggesting that the agent can be effectively used in single-dose therapy for acute uncomplicated cystitis in female patients. To find the optimum dose, the present dose-finding study was conducted. A dose of either 100 mg or 200 mg of SPFX was selected by the double-blind method, and was administered only once (single dose therapy). The clinical efficacy was judged on day 3, 7 and 14 after administration. On day 3, of the 49 pts. in the 100 mg-group, the efficacy rate was 95.9% (excellent rate: 79.6%), and of the 42 pts. in the 200 mg-group, it was 100% (excellent rate: 88.1%). On day 7, of 38 pts. in the 100 mg-group, it was 94.7% (excellent rate: 78.9%), and of 28 pts. in the 200 mg-group, it was 100% (excellent rate: 92.9%). On day 14, of 27 pts. in the 100 mg-group, it was 92.6% (excellent rate: 66.7%), and of 26 in the 200 mg-group, it was 96.2% (excellent rate: 84.6%). Recurrence was observed in 4.8% (1/21) in the 200 mg-group. Therefore, there was no significant difference in the efficacy rate between the two groups, but the rate of excellent responses was higher in the 200 mg-group. Otherwise, the efficacy was estimated to be insufficient in 3 pts. and recurrent in 1 pt. they were examined the findings of detailed urological intractableness. Among 2 pts. in whom the external genitalia and urethra were closely examined, a urethral caruncle was noted in 1 pt. The results of our study indicate that 200 mg of SPFX is recommended as a single dose therapy for acute uncomplicated cystitis in females.

Acute Disease↗

[Clinical efficacy of levofloxacin (LVFX) single-dose therapy in female acute uncomplicated cystitis].

Treatment of infections by the use of antimicrobial agents should be made essentially in a dose close to the minimally required dose. Acute uncomplicated cystitis in female fits as the subject for a single-dose therapy since it is an infection reactive relatively easily to antimicrobial agents. Accordingly, an assessment has been made regarding the therapeutic results of the single-dose therapy in 76 female cases of acute uncomplicated cystitis by the use of LVFX 200 mg which is a new quinolone. The urinary concentration more than MIC90 to Escherichia coli is sustained for about 3 days by this single-dose therapy. As a result of judging the therapeutic results from the reactions of the three clinical findings of pain on micturition, pyuria and bacteriuria, excellent therapeutic results were obtained with effective rates being 100% (76/76) on the day 3, 93.9% (46/49) on the day 7 and 94.4% (34/36) on the day 14. The rate of cystitic symptoms which recurred posed no problem, being 12.5% (5/40) up to three months, as investigated by a questionnaire. As a result of performing close urological examinations such as cystoscopy on six cases with insufficient results or recurrence, we could detect mild underlying conditions which are considered to be intractable factors in the bladder in three cases. From the above results, the single-dose therapy of acute uncomplicated cystitis in the female by LVFX which is a new quinolone was considered to be an excellent therapeutic drug from its characteristics such as its therapeutic results being the same as the conventional therapy by daily administration, excellent drug compliance, low cost, hard selectiveness of resistant strains, less side effects and furthermore it gives the opportunity of detecting a latent and mild underlying condition.

Acute Disease↗

Tumor size of renal cell carcinoma: its clinical implication.

We studied the clinical implication of tumor size in renal cell carcinoma, by revealing its relation with the other histopathological and clinical features. The tumor size was well correlated with histopathological findings and metastatic status of the carcinoma. Smaller carcinomas (usually less than 60 mm) generally had a higher disease-specific survival than those of 60 mm or greater. The results indicated that the size reflected the biological character of the carcinoma. However, 10% of patients with the smaller carcinoma had lymph node metastasis or distant metastasis at the time of diagnosis, each of which contributed to a renal cell carcinoma-related death in the early follow-up period.

Carcinoma, Renal Cell↗

[Influential factors on recurrence of renal cell carcinoma].

In order to clarify factors affecting recurrence, we reviewed 115 renal cell carcinoma patients without distant metastasis at diagnosis (Mo) treated from January 1975 to March 1990 at Sapporo Medical College Hospital. Of these 115 patients, recurrence (metastasis) was found in 23 (20.0%). The non-recurrence rate was 70.6% after the 5-year and 56.5% after the 10-year follow up. In 22 out of 23 patients, recurrence appeared within 3 years following surgery. Multivariate analysis by Cox's proportional hazard model revealed that lymph node metastasis was the most significant factor for recurrence in the 115 patients followed by stage of the primary tumor and pre-operative acute phase reactant (fever, ESR and alpha 2-globulin) in this order. When the analysis was performed in the 88 patients who was in less advanced stage (pN0pV0-1a), pre-operative acute phase reactant (fever, ESR and alpha 2-globulin) was identified as the only significant factor affecting recurrence. This result suggests that pre-operative acute phase reactant is the most important risk factor for recurrence in this group of patients.

Acute-Phase Proteins↗

Clinical analysis of incidentally found renal cell carcinomas.

We reviewed 74 patients with incidentally found renal cell carcinomas (20%) out of 366 patients treated in affiliated hospitals over the past 14 years. The annual rate of the incidentally found carcinomas has increased up to 40% of the total. CT scan and/or ultrasonotomography were used in the first diagnosis in 76% of these 74 patients. The prognosis for the incidental group was more favorable than that of the classical symptom group, since the former group consisted of patients with smaller-sized carcinomas which usually tend to be confined to the kidney.

Anemia↗

[Histopathological analysis of chemical carcinogenesis process by streptozotocin in the mouse kidney].

Renal adenocarcinoma was induced in CBA/H/T6J mice by a single intraperitoneal injection of 250 mg/kg of streptozotocin (STZ). Light and electron microscopic examination revealed that the carcinoma was a granular cell type-adenocarcinoma with abundant microvilli, basal lamina and intermediate junction indicating an epithelial cell origin. In histopathological analysis of the process of this carcinogenesis, all of the kidneys examined had a dilatation of proximal tubules in the second month and thereafter. In the fifth month, one of eight kidneys developed an adenoma. The adenoma was found in all the kidneys after the ninth month. An adenocarcinoma developed in one of the 14 kidneys in the twelfth month and in all others in the fifteenth month. In vivo labeling of bromodeoxyuridine on the cells in various stages demonstrated an increase of the labeling index which paralleled with progression of the carcinogenesis process. This finding in in vivo analysis of cell proliferation also supports the idea that serial changes of the kidney which are histopathologically proven correspond to the carcinogenesis process. The original carcinoma (STZ-RCC) has serially been passed in vivo at the present. Intrasplenic injection of STZ-RCC yielded multiple macroscopic foci of metastasis in the liver. This indicates that STZ-RCC has a malignant potential. Thus, STZ-induced mouse renal adenocarcinoma can be applied to the model system to investigate carcinogenesis and biological behaviors of renal cell carcinoma.

Animals↗

[Selection of highly metastatic lines from streptozotocin-induced mouse renal adenocarcinoma and their in vivo metastatic or in vitro invasive potential].

We selected highly metastatic lines from mouse renal adenocarcinoma (STZ-RCC) chemically induced with streptozotocin. At eight weeks after an intrasplenic injections (IS injection) of original STZ-RCC, this procedure yielded metastatic foci in the liver, which we transplanted serially in syngeneic mice (STZ-HM1). STZ-HM1 was then injected into the spleen of a syngeneic mouse, which provided a source for further cycles of hepatic metastasis selection. Three cycles of selection for hepatic metastasis yielded a high hepatic metastasis line (STZ-HM3). Intravenous injection of the parent line (original STZ-RCC) yielded metastatic foci in the lung eight weeks later, which we also transplanted serially in syngeneic mice (STZ-PM1). The repeated IS injection of the cells was clearly responsible for the increase in the frequency of hepatic metastasis and the number of its nodules. In particular, STZ-HM3 was revealed to have more metastatic nodules in the liver ranging from 293 to 432 (median; 368) in all five mice at eight weeks after IS injection. STZ-PM1 had a significantly higher rate of pulmonary metastasis and more pulmonary metastatic nodules after intravenous injection than the parent line. These results confirm that the parent line, STZ-RCC, has a heterogeneity in the metastatic phenotype. In vitro invasion assay for STZ-RCC, STZ-HM1, -HM2 and -HM3 demonstrated that in vitro invasive potential was paralleled with in vivo hepatic metastasis potential. The result suggests that the invasion potential revealed by in vitro invasion assay is important in metastasis formation.

Animals↗

[Study on in vitro invasive potential of renal cell carcinoma cell lines and effect of growth factors (EGF and TGF-beta 1) on their in invasions].

Renal cell carcinomas (RCCs) frequently metastasize to distant organs in their clinical course. However, the mechanism of the metastasis had not been fully elucidated. In vitro invasion assay has been reported to be a rapid method for the evaluation of the invasive potential of various malignant cells. In vitro invasive potential of RCC has not been investigated by this method. Thus, in the present study, we first attempted to characterize the in vitro invasive potential of four human RCC cell lines which had been established in our institute. Secondly, we investigated the influence of two growth factors (EGF, TGF-beta 1) on the invasive potential of these cell lines when the two factors were applied as chemoattractants. SMKT-R-3 and R-4 cell lines showed more cell penetration through Matrigel than SMKT-R-1 and R-2 cell lines, suggesting that the former cell lines have higher invasive potential. While invasive potential varied in each cell line, it was enhanced by EGF in all cell lines. However, TGF-beta 1 suppressed the invasive potential of all four cell lines. These results suggest that two factors have different actions on the invasion of RCCs.

Carcinoma, Renal Cell↗

[Studies on pulmonary metastasis of renal cell carcinoma--pulmonary embolism revealed by lung-perfusion imaging and metastasis].

Invasion of renal cell carcinoma to veins is known to have a close relation with pulmonary metastasis. We speculated that a tumor thrombus would lodge in the pulmonary artery before establishment of a clinically apparent pulmonary metastasis. This may be particularly true in patients with renal vein or vena cava involvement of renal cell carcinoma. In this instance, it is crucial to know the clinical consequence of tumor thrombi in the pulmonary artery. Thus, we investigated these issues with the aid of lung-perfusion imaging in 22 renal cell carcinoma patients with and without vein involvement. The lung-perfusion imaging revealed positive in 8 of the patients examined prior to treatment. The incidence of positive finding was well correlated with an extensive vein invasion. Patients with positive imaging prior to treatment were associated with pulmonary metastasis at a higher rate than those with negative findings. These findings have indicated that vein invasion should be related with tumor thrombus formation in the pulmonary artery, and such a status in the lung would, in part, result in pulmonary metastasis. Two different clinical courses were found by an analysis of patients with the positive imaging prior to treatment. One is the clinical course in which positive findings were correlated with a newly developed metastasis in the lung. Thus, care should be taken in development of the metastasis during the follow-up when patients show the positive lung-perfusion imaging prior to treatment. On the other hand, we found two patients in whom the positive findings disappeared during the follow-up.

Adult↗

[Clinical efficacy of modified M-VAC chemotherapy for advanced urothelial carcinoma and influence of squamous cell carcinoma-associated antigen on efficacy of the chemotherapy].

The efficacy of modified M-VAC chemotherapy was evaluated in twenty-two patients with advanced urothelial carcinoma (18 cases of transitional cell carcinoma, 3 of transitional cell associated with squamous cell carcinoma and 1 of squamous cell carcinoma). Among the 22 patients, 14 underwent two or more courses of modified M-VAC chemotherapy and had lesions suitable for the evaluation. Three of the 14 patients achieved complete response and 6 partial response, resulting in a 64.3% response rate. With regard to the direct effect according to the site of the lesion, the response rate was 75% for the urinary bladder, 100% for lung, 100% for subcutaneous tissues, and 75% for lymph nodes metastasis, whereas the chemotherapy was ineffective for metastasis in the bone and muscle. With this neoadjuvant chemotherapy the primary tumor of the urinary bladder was downstaged from T2 to T0 in one patient who showed complete response. In 4 of 5 patients achieving partial response, the primary tumors were downstaged from T2 to T1. Of 9 patients given this chemotherapy for metastatic lesions, 2 achieved complete response and are alive, whereas all 3 without response died of cancer within the 1 year following the chemotherapy. Since most of the cases associated with the squamous cells carcinoma component showed no response to the therapy, it seems that the level of serum squamous cell carcinoma-associated antigen may be helpful for predicting the efficacy of modified M-VAC chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Immunosuppressive acidic protein (IAP) and immunosuppressive substance (ISS) in patients with renal cell carcinoma].

To clarify their usefulness as markers for renal cell carcinoma, serum immunosuppressive acidic protein (IAP) and serum immunosuppressive substance (ISS) were evaluated by TIA (turbidometric immunoassay) for IAP and by SRID (single radial immunodiffusion) for ISS. The mean level of IAP and ISS was beyond each upper normal limit (500, 700 micrograms/ml) in every stage, and especially high in the M1 group. The levels of IAP and ISS were significantly correlated with each other. The determination of IAP and ISS levels after treatment showed a good correlation to the clinical course of the disease. The positive rates of IAP and ISS increased as the stages progressed, respectively. When the influences of pretreatment IAP and ISS level on survival period were investigated, the low IAP or ISS level group (less than two times of the upper normal limit) tended to have a better prognosis than the high level group (more than two times of the upper normal limit) in the M1 patients. These findings suggested that IAP and ISS could be used as markers for monitoring a disease and predicting the prognosis in patients with renal cell carcinoma. As for the positive rate in the combination assay for IAP, TPA and ferritin, or ISS, TPA and ferritin, more than 80% of the patients with low stage renal cell carcinoma had at least one positive marker. This suggested that the combination assay of these three markers was clinically valuable as a disease monitor in patients with renal cell carcinoma.

Adult↗

Regional lymph node metastasis in renal cell carcinoma: incidence, distribution and its relation to other pathological findings.

Extended ipsilateral lymphadenectomy performed on 102 patients with renal cell carcinoma revealed 21 patients (21%) having regional lymph node metastasis. Of the 21 patients, 6 (6%) had single-node metastasis and 15 (15%) multiple-node metastasis. PT, pV, pM, cell type and grade were all correlated with regional node metastasis. The metastatic lymph node foci were distributed along the pathways of normal lymphatic drainage. The recurrence of the disease was correlated with lymph node metastasis, indicating that metastasis is one of the prognostic factors. The very close correlation of node metastasis with vein invasion suggests that removal at least of the ipsilateral lymph node might be necessary when removal of a thrombus in the renal vein or vena cava is indicated.

Carcinoma, Renal Cell↗

[Studies on incidental carcinoma of the prostate].

We reviewed 157 patients retrospectively with incidental carcinoma of the prostate who had been treated at our collaborating hospitals during the past ten years. Of 5212 patients with benign prostatic hyperplasia who received subcapsular prostatectomy or transurethral resection of the prostate (TUR-P), 157 (3.0%) were diagnosed as having an incidental carcinoma of the prostate, which was somewhat lower than that in previously published reports. Of these, 30 and 127 patients were in stage A1 and A2, respectively. Well, moderately and poorly differentiated carcinomas were found in 44.6%, 36.7% and 18.5% of the patients, respectively. The incidence of poorly differentiated carcinoma in the study seemed to be higher than that in the previous reports. A positive correlation was identified in TUR-P specimens between the carcinoma differentiation and its extension which was evaluated by cancer-positive chip ratio. Atypical adenomatous hyperplasia and intraductal dysplasia were identified in 36.9% and 85.3% of the patients with incidental carcinoma, respectively. These incidences tended to become lower as the carcinoma became less differentiated or more extended. Further studies will be necessary to define the significance of these pathological findings as a direct biological precursor of prostatic carcinoma. Six out of the 157 patients with incidental carcinoma showed a progression during the follow-up period. All of these patients were in stage A2 and all but one showed a histology of moderately or poorly differentiated carcinoma at the time of diagnosis. Radical prostatectomy or radiation therapy as well as endocrine therapy should be considered as treatment modalities for stage A2 patients, when staging lymphadenectomy shows no pelvic lymph node metastasis.

Humans↗

[Clinical study of penile cancer].

Recent progress in molecular biology suggests a certain relationship between penile cancer and human papilloma virus infection. However, the treatment for penile cancer has not been established since each institute has experienced only a small number of patients. We analyzed the result of our treatment for 14 penile cancer patients during past twenty years. Ten of the 14 patients were initially treated for the primary lesion with a combination of peplomycin (PEP) or bleomycin (BLM) and radiation therapy. Of these, 9 were found not to have residual viable cancer cells in their primary lesions. No local recurrence was found in all 7 patients in whom the penis was preserved. This result suggests that combination of PEP (BLM) and radiation preserves the penis without increasing the risk of local recurrence. Penile cancer-related death did not occur in patients without lymph node metastasis. However, this cancer death did occur in 4 out of 7 patients with lymph node metastasis, suggesting that metastasis is one of the important prognostic factors. PEP (BLM) and radiation therapy with or without regional lymph node dissection did not improve the prognosis of patients with advanced penile carcinoma, such as with pN2, pN3 or distant metastasis. More effective management may be necessary for these patients.

Antineoplastic Combined Chemotherapy Protocols↗

Establishment of three human renal cell carcinoma cell lines (SMKT-R-1, SMKT-R-2, and SMKT-R-3) and their characters.

We have established three new cell lines of human renal cell carcinoma (RCC), designated as SMKT-R-1, SMKT-R-2 and SMKT-R-3. These cell lines were derived from a primary lesion of the tumor or a tumor initially xenotransplanted in nude mice. These cell lines have maintained a stable growth in vitro for more than a year. They also exhibited characteristics showing a lack of contact inhibition of cells, colony formation in soft agarose and tumor formation in nude mice by a xenotransplantation of cells, all of which suggested an epithelial origin. The tumors produced in nude mice by the inoculation of cell lines were demonstrated by light an electron microscopy to be derived from RCC. The doubling time of these cell lines were 180.0 h, in SMKT-R-1, 56.4 h in SMKT-R-2 and 55.7 h in SMKT-R-3. The cell lines were aneuploid in their chromosomal analysis, and SMKT-R-2 and SMKT-R-3 also had three and two marker chromosomes, respectively. The different biological characters of these cell lines from the others so far established would be of benefit in the future study of human RCC.

Animals↗

[In vitro antiproliferative effect of cancer chemotherapeutic agents and their combination with interferon in renal cell carcinoma].

We studied an antiproliferative effect of cancer chemotherapeutic agents, interferon (IFN) and, in particular, their combination effect on renal cell carcinoma. Either of colony formation assay (CFA) or [3H]-thymidine incorporation assay ([3H]-TdR assay) was employed as an in vitro chemosensitivity testing system. When compared, these two systems produced similar results with a good correlation (r = 0.97, p less than 0.01), in the antiproliferative effect of 30 drugs for 4 primary renal cell carcinomas and 5 xenotransplantable renal cell carcinomas. In vitro chemosensitivity test (CFA or [3H]-TdR assay) screened successfully only 5 "sensitive" drugs (7.9%) out of a total 63 cancer chemotherapeutic agents for 24 human renal cell carcinoma. This confirmed the findings reported by others. In the study of the antiproliferative effect of a cancer chemotherapeutic agent, human lymphoblastoid interferon (HLBI) and their combination on human renal cel carcinoma cell line (SMK-R2). Each of VBL, MTX or HLBI tended to suppress [3H]-TdR uptake in a dose-dependent manner. The combination of VBL (0.05 microgram/ml) and HLBI (10(2) or 10(3) IU/ml) produced a subadditive effect, and that of MTX (0.1 microgram/ml) and HLBI 10(2) IU/ml produced a synergistic effect on the human renal cell carcinoma cell line, the effect which is evaluated by Valeriote and Lin's criteria of combination. In particular, the synergistic effect by MTX and HLBI under the clinically achievable drug concentration seems important, when its clinical application is considered.

Antineoplastic Agents↗

[Two cases of so-called extragonadal germinal tumor with "probable" retroperitoneal origin].

In a rare case of germinal tumor, the patient usually presents complaining of an abdominal mass as an initial symptom without an apparent tumor in his testis. Clinical strategy for such patients is based on that for testicular cancer. However, it often fails to produce a satisfactory response. The poor response may contribute to several "poor prognostic feature" found in most of these patients.

Adult↗