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N Deguchi

Publications and source records attributed to N Deguchi.

At least 55 records · Page 3Linked to original sources

Bromodeoxyuridine and deoxyribonucleic acid bivariate analysis in human renal cell carcinoma. Does flow cytometric determination predict malignant potential or prognosis of patients with renal cell carcinoma?

Sixty-one renal cell carcinomas were analyzed by simultaneous flow cytometric bivariate measurements of deoxyribonucleic acid (DNA) and bromodeoxyuridine. Bromodeoxyuridine in vitro labeling was performed by sample incubation with bromodeoxyuridine under hyperbaric oxygen. DNA ploidy status statistically correlated only with the presence or absence of distant metastasis. When the mean bromodeoxyuridine labeling index (LI) was accordingly compared with each histologic feature, architecturally solid, grade 3, high-stage (beyond pT3a) tumor, and the presence of distant metastasis showed significantly higher LI. When LI were compared with DNA ploidy, diploid tumors showed a 6.3% +/- 4.9% LI, whereas aneuploid tumors exhibited a 7.6% +/- 5.4% LI. The difference was not statistically significant. Five patients with a mean survival time of 10.2 +/- 4.1 months who had a mean LI of 11.5% +/- 7.7% died, whereas 56 patients with a mean LI of 6.7% +/- 4.8% survived. The difference was significant (P less than 0.05). However, the results did not necessarily correlate with the histologic features of the malignant potential or with the prognosis in individual patients. These data indicate that flow cytometric DNA/bromodeoxyuridine bivariate analysis remains inconsistent for predicting the malignant potential or prognosis of renal cell carcinoma.

Bromodeoxyuridine↗

SCID mice: a suitable model for experimental studies of urologic malignancies.

In vivo studies on human malignant tumors are limited because of a lack of suitable animal models. In this study, the usefulness of SCID (severe combined immunodeficiency) mice, deficient in functions of both T- and B-lymphocytes, was evaluated. Inbred SCID mice were kept in isolated cages and 2 x 10(7) cells of KU-7, an established bladder carcinoma cell line, were inoculated in the subcutaneous tissue of the flank region of six SCID mice. Athymic nude mice were inoculated by the same method and served as the controls. The KU-7 cells were taken within 14 days in the injected region in all six SCID mice, while in only five out of eight nude mice. Tumors subsequently formed at the site of inoculation in these mice were confirmed to be transitional cell carcinomas histologically and intra-abdominal metastases were noted in two SCID mice. We conclude that SCID mice provide an ideal in vivo model for experimental studies of human urologic malignant tumors.

Abdominal Neoplasms↗

Multivariate analysis of flow cytometric deoxyribonucleic acid parameters and histological features for prognosis of bladder cancer patients.

We studied whether flow cytometry provides significant prognosticators beyond the classical histological evaluation in the patient with bladder cancer. A total of 203 patients with untreated bladder cancer was evaluated using fresh bladder tumor specimens. Tumor grading and stage were the histological prognostic parameters. Deoxyribonucleic acid (DNA) index, percentage S-phase cells, percentage G2/M-phase cells and hypertetraploid cell presence were assessed as flow cytometric prognostic parameters. Multivariate survival analysis was performed using Cox's proportional regression model to study statistical individual prognostic values of histological and flow cytometric parameters. Hypertetraploid cell presence was the single most important prognostic factor (p less than 0.01), with tumor grade being nearly as important (p less than 0.01), followed by tetraploidy (p less than 0.01) and tumor stage (p less than 0.05). No other parameters, including the DNA index or cell phase fractions, contributed to the model. These results indicated that combined use of histological and flow cytometric parameters may provide additional information regarding the clinical outcome for bladder cancer patients.

Adult↗

Quantification of cell kinetic characteristics using flow cytometric measurements of deoxyribonucleic acid and bromodeoxyuridine for bladder cancer.

A total of 56 human bladder tumors that were histologically proved to be transitional cell carcinoma was analyzed by simultaneous flow cytometric 2-color measurements of deoxyribonucleic acid (DNA) and bromodeoxyuridine. Bromodeoxyuridine in vitro labeling was performed by sample incubation with bromodeoxyuridine under high atmospheric pressure oxygen. Grade 1 tumors showed 33.3% aneuploidy with a mean bromodeoxyuridine positive stained ratio (labeling index) of 5.1 +/- 3.4%. Grade 2 tumors featured 51.7% aneuploidy with a mean labeling index of 8.9 +/- 7.7%. On the other hand, a markedly increased labeling index of 15.2 +/- 8.2% with aneuploidy was observed in all but 1 grade 3 tumors. When DNA ploidy and labeling indexes were compared according to the presence or absence of muscular invasion of tumors, all 16 muscle invasive tumors showed aneuploidy (mean labeling index 18.7 +/- 8.0%), while 17 of 40 nonmuscle invasive tumors showed aneuploidy (mean labeling index 8.6 +/- 5.4%). This labeling index difference was statistically significant (p less than 0.01). These results indicate that bromodeoxyuridine/DNA 2-color flow cytometry may provide an objective parameter for quantification of the malignant potential of bladder cancers.

Aneuploidy↗

Efficacy of gadolinium-diethylenetriaminepentaacetic acid-enhanced magnetic resonance imaging for differentiation between superficial and muscle-invasive tumor of the bladder: a comparative study with computerized tomography and transurethral ultrasonography.

Gadolinium-labeled diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) was evaluated in an effort to clarify whether MRI could replace or be proved to be superior to computerized tomography (CT) and/or transurethral ultrasonography. A total of 57 bladder cancer patients was evaluated. MRI was performed with a superconducting magnet operating at 1.5 Tesla. The images acquired were multisections, having a fast spin-echo pulse sequence of less than a 14-second breath holding. Serial scans were performed before and immediately after Gd-DTPA venous injection. The findings on different imaging techniques were compared with the histological stagings. A proper diagnosis was made in 42 of 57 cases (73.7%) by Gd-DTPA-enhanced MRI, in 27 of 57 (47.4%) by CT and in 31 of 57 (54.4%) by transurethral ultrasonography when comparing the histological findings. The sensitivity and specificity for differentiating superficial and muscle-invasive tumor of each imaging method were, respectively, 96.2 and 83.3% in Gd-DTPA-enhanced MRI, 96.0 and 58.3% in CT, and 88.0 and 66.7% in transurethral ultrasonography. These data suggest that the staging of bladder cancer by Gd-DTPA-enhanced MRI appears to be superior and more accurate than the staging obtained by CT and transurethral ultrasonography.

Adult↗

Pharmacokinetics of carumonam (AMA-1080) in patients with impaired renal function and in those undergoing hemodialysis.

The pharmacokinetics of carumonam (AMA-1080) were studied after a single intravenous 1.0-g dose was given to 26 subjects grouped according to their renal functions. Creatinine clearance (CLCR) was above 85, 50 to 84, 10 to 49, and below 10 ml/min/1.73 m2 in groups 1, 2, 3, and 4, respectively. All of the six patients in groups 4 were receiving maintenance hemodialysis, and they were studied both during and between hemodialysis sessions. Carumonam obeyed two-compartment model kinetics in all four group. The volume of distribution based on the area under serum concentration-time curve (Varea) did not differ significantly among the four groups, the mean value being 0.309 +/- 0.084 liter/kg. The elimination-phase (beta) half-lives were 1.53 +/- 0.36, 2.00 +/- 0.64, 5.08 +/- 1.85, and 12.8 +/- 4.1 h in groups 1, 2, 3, and 4, respectively. The 0- to 24-h cumulative urinary recoveries of carumonam were 83 +/- 11, 76 +/- 20, 58 +/- 25, and 12 +/- 9% of the administered dose in groups 1, 2, 3, and 4, respectively. The systemic and the renal clearances of carumonam decreased according to the severity of renal dysfunction, and the nonrenal clearance, which was calculated as the difference between renal and systemic clearances also decreased as CLCR decreased. A significant positive correlation existed between beta and CLCR (r = 0.847, P less than 0.01), and the beta of carumonam could be predicted by the following equation: beta (h-1) = 0.00460 X CLCR (ml/min/1.73 m2) + 0.049. Hemodialysis shortened the elimination-phase half-lives from 12.8 +/- 4.1 to 2.66 +/- 1.49 h in the six subjects in group 4. A 5-h hemodialysis in a hypothetical anephric subject weighing 60 kg was estimated to remove 51.4% of the drug present in the body at the start of hemodialysis.

Adult↗

Removal of imipenem and cilastatin by hemodialysis in patients with end-stage renal failure.

The removal of imipenem and cilastatin by hemodialysis was studied in 14 (for imipenem) and 6 (for cilastatin) subjects. Following intravenous infusion of imipenem and cilastatin at a combined concentration of 10 mg/kg of body weight, drug levels in plasma were determined serially during off- and on-hemodialysis periods, which were 2 and 4 h, respectively. The biexponential decay of the drug levels in plasma was evident in each subject for both imipenem and cilastatin. Hemodialysis accelerated the elimination of both imipenem and cilastatin: the mean elimination-phase half-life of imipenem was shortened from 200 to 78 min, and that of cilastatin was shortened from 445 to 115 min. Hemodialysis clearance of imipenem and cilastatin was calculated by five different methods, each with intrinsic assumptions. The mean hemodialysis clearance of imipenem was estimated to be 74.08 +/- 13.29 ml/min, and that of cilastatin was estimated to be 65.0 +/- 8.6 ml/min, after consideration of various methodological limitations. It was estimated that in a hypothetical anephric patient weighing 60 kg, a 4-h hemodialysis treatment would remove 54.8% of the imipenem and 62.9% of the cilastatin present in the body at the start of dialysis.

Cilastatin↗

Antitumor effects of interleukin 2 against renal cell carcinoma: basic study and clinical application.

In order to determine an optimum mode for systemic administration of recombinant interleukin 2 (rIL2), the effects of rIL2 on lymphocyte-mediated cytotoxicity against renal carcinoma cells were studied in vitro. Augmentation of the cytotoxicity by rIL2 was dose- and time-dependent. The optimum dose of rIL2 was 100-500 units (Jurkat units)/ml, and cytotoxicity increased significantly even at a low concentration such as 4 units/ml. We thus chose daily administration of multiple repeated dose for inpatients. To prevent withdrawal from the therapy as a result of untolerable adverse effects, the daily dose was set at 1 X 10(6) units, and rIL2 was given to 12 patients with metastatic renal cell carcinoma. Two-hour intravenous drip infusions containing 5 X 10(5) units of rIL2 was given daily 2 times to inpatients and after at least 28 days of this mode of administration, subcutaneous injection at a dose of 1 X 10(6) units was given 6 days a week to outpatients. Three patients showed complete response, 7 patients no change, and 2 patients progressive disease. Serious adverse effects due to capillary leak syndrome were not observed. We conclude that low-dose rIL2 is safe and has potential antitumor effects.

Aged↗

[Effects of recombinant interleukin 1 beta on peripheral blood cells and induction of lymphokine-activated killer activity in patients with urological malignancies].

Subcutaneous injection of human recombinant interleukin 1 (IL-1) beta was given to 9 patients with urological malignancies (5 renal cell carcinoma, 2 bladder carcinoma, 1 renal pelvic tumor, and 1 testicular tumor), at an initial dose of 1 x 10(4) units on days 1 and 2, and there after weekly for 4 weeks. The dose was increased by 1 x 10(4) units weekly up to final dose of 4 x 10(4) units. Peripheral blood mononuclear cells (PBMC) were isolated from patients on day 3 in week 2 and week 4, and lymphokine-activated killer (LAK) activity against Daudi cells was measured using 4 hr 51Cr-release assay, after incubation with human recombinant interleukin 2 (IL-2) of 50 units/ml for 72 hours. Proliferation of lymphocytes was measured by tritiated thymidine incorporation after incubation with IL-2 for 72 hours. IL-1 beta increased the number of peripheral blood granulocytes and lymphocytes, but did not increase the numbers of monocytes and platelets. IL-1 beta significantly augmented IL-2-induced LAK activity in vitro, but this augmentation was neither accompanied by the increase of IL-2 receptor-positive cell ratio in peripheral blood lymphocytes nor enhancement of IL-2-induced proliferation of lymphocytes. Administration of IL-1 beta increased LAK activity of the patients, despite the fact that IL-1 beta did not increase LAK activity in vitro. The result suggests that IL-1 beta-stimulated LAK activity may be mediated by the induction of some cytokines in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Transurethral microwave thermotherapy of benign prostatic hypertrophy].

Transurethral microwave thermotherapy using Prostatron was performed in 31 patients with benign prostatic hypertrophy, and the clinical effectiveness was evaluated by analyzing the subjective and objective responses following the treatment. The 22F balloon catheter to be placed in the prostatic urethra incorporates the microwave antenna, a cooling system and a fiberoptic thermosensor which allow an effective delivery of microwave energy to the center of the prostate, while preserving the mucosa and periurethral tissue. The maximum urethral temperature during the treatment ranged from 43.3 to 45.5 degrees C (44.7 +/- 0.96 degrees C: mean +/- S.D.) and the average power output was 27.4 Watt. The treatment was performed in a single session of an hour on the outpatient basis. In one patient who could not be relieved of the indwelling catheter underwent a transurethral resection, and the histological effect of thermotherapy on the resected specimen was examined. In the prostatic tissue, heat-induced necrotic change of the interstitial tissue as well as degenerative change of the acinar epithelium were remarkable, whereas the urethral mucosa was well preserved. In the remaining 30 patients, the clinical effects were evaluated 8 weeks after the treatment by a score scale for subjective symptoms, residual urine and maximum urinary flow rate, which was compared with the pretreatment score. Improvement of both subjective symptoms and objective findings was observed in 13 subjects (43.3%), that of subjective symptoms only in 14 cases, and that of objective findings only in 2 cases, resulting in a notable improvement in total 29 cases (97.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Kidney preserving surgery for renal cell carcinoma in patients with a solitary kidney or bilateral tumors--with special regard to indication and limitation of enucleation].

We performed kidney preserving surgery for renal cell carcinoma in 10 patients with a solitary kidney or bilateral tumors. Two had cancer in a solitary kidney (contralateral kidney was nephrectomized for benign disease) and 8 had bilateral renal tumors, 3 and 5 of the latter 8 patients being asynchronous and synchronous, respectively. The kidney preserving surgery included partial nephrectomy in 3 patients and enucleation in 7 patients and was performed in situ and ex vivo followed by renal autotransplantation in 4 and 6 patients, respectively. Of the 10 patients, 4 are still alive after 2 years and 11 months-5 years and 6 months. Death occurred in 6 patients. Excluding one non-resectable patient and 2 patients of non-cancer death, 3 patients survived for 3 years-8 years and 8 months. The 10 patients, excluding one non-resectable, showed actuarial survival rates of 89, 89 and 63.3% for 1, 3 and 5 years, respectively, and excluding patients of non-cancer death, the above rates were 100, 100 and 85.7%, respectively. Postoperative local recurrence was found in 1 of 3 patients of partial resection and 2 of 7 patients of enucleation, and the latter 2 patients were those who had synchronous bilateral tumors and underwent renal autotransplantation following enucleation of a number of tumor nodules from seemingly less involved kidneys and contralateral radical nephrectomy; recurrence in the grafted kidney was already observable in the early postoperative period, which indicated re-growth of the residual tumor rather than recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Clinicopathological studies and flow cytometric analysis on renal cell carcinoma after incidental finding].

Of 173 patients with renal cell carcinoma treated at the Keio University Hospital between 1979 and 1989, 48 cases were found to have their tumors incidentally (group 1), and the remaining patients presented with signs and/or symptoms related to their tumors (group 2). In this study we attempted to define the clinicopathological and ploidy characteristics of the tumors in the patients of the two groups. The number of patients having tumor stages not exceeding pT2NOMOV- was significantly higher in group 1 (81.3%) than in group 2 (36.0%) (p less than 0.001), and the median tumor size was significantly smaller in group 1 (4.32 +/- 2.38 cm) than in group 2 (7.86 +/- 4.07 cm) (p less than 0.001). The survival rate in group 1 was significantly favorable when compared with group 2 (p less than 0.005). And even in the same stage (pT1-2NOMOV-) there were statistical significance in the survival and relapse rate between the two groups (p less than 0.05), which indicate that renal cell carcinomas detected incidentally are associated with biologically low malignant potential. From 1985, flow cytometric DNA analysis was performed in 32 tumors from the group 1 and in 50 from the group 2. The frequency of occurrence of aneuploid pattern was significantly lower in tumors from the group 1 (25.0% in the overall patients and 16.0% in those with stage pT1-2NOMOV- tumors of group 1) than in those from the group 2 (52.0% in the overall patients and 42.9% in those with stage pT1-2NOMOV- tumors) (p less than 0.05). These results also suggest that renal cell carcinomas detected incidentally are associated with low malignant potential biologically.

Adult↗

[A randomized trial of PVB, VAB-6, BVP regimen versus PEB chemotherapy in patients with disseminated testicular tumors].

During 2 years and 7 months from June, 1985 to December, 1987, a randomized multi-center trial of PVB, VAB-6, BVP regimen (group A) without etoposide versus PEB chemotherapy (bleomycin, etoposide and cisplatinum) (group B) was given to patients with disseminated testicular tumors. Of 34 patients registered, 10 patients were with minimal disease in stages IIA, IIIO and IIIA and 24 with extensive disease in IIB, IIIB2 and IIIC. Seminomas were found in 10 patients, while non-seminomatous tumors in 24. Among groups A and B, there was no statistical difference in clinicopathological profiles. A group patients were given either PVB, VAB-6 or BVP according to the physician's discretion. In groups A and B, 35% and 43% of the patients achieved complete response, and 45% and 50% achieved partial response, respectively. The difference in CR rates among both groups was not statistically significant even when calculated according to the stage or histologic grouping. Salvage treatments mainly with surgical resection of residual tumors after the chemotherapy, however, were more successful in group B (88%) than group A (61%). It appears likely that the higher response of induction chemotherapy in patients with extensive disease made the salvage surgery more successful in group B than in group A. The 3 year survival rate was 100% in group B, whereas it was 76% in group A. Although the incidence of myelosuppression and alopecia was significantly higher in group B, neuropathy was significantly more frequent in group A. From the above results, PEB seems to be a better induction chemotherapy than the conventional one for advanced testicular tumors.

Antineoplastic Combined Chemotherapy Protocols↗

Immunologic effects of recombinant interferon-gamma in patients with renal cell carcinoma.

Immunologic and antitumor effects of human recombinant interferon-gamma were studied in patients with renal cell carcinoma. A daily dose of 6 to 12 x 10(6) units/m2 of interferon-gamma was given by intravenous drip infusion or intramuscular injection to nine patients over a period varying from two to 16 weeks. Antibody-dependent cell-mediated cytotoxicity and OKIa1-positive monocytes count increased significantly after the therapy was started. Interferon-gamma transiently increased OKT3- and OKT4- positive lymphocyte count. Tumor regression was not observed when clinical response was evaluated in seven patients. Two others, who had no measurable metastases, were not evaluated, because interferon-gamma were given to them as post-operative adjuvant therapy. Our results indicate that interferon-gamma stimulated monocytes and enhanced cell-mediated cytotoxicity; they also suggest the necessity of combining monoclonal antibodies and other biological response modifiers that effect tumor-associated antigens.

Adult↗

[Long-term bioeffects of extracorporeal shock waves on renal tissue and blood pressure in normotensive and spontaneously hypertensive rats].

In order to examine chronic effects of shock waves on renal structure and blood pressure, normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were uninephrectomized and shock waves were given on the lower half of the residual kidney by Piezolith with the focus pressure of 1020 bar. In the first experiment, 36 WKY were divided into 6 groups; Group 1 served as control, Group 2, 4 and 6 received a single session of 1250, 2500 and 5000 shocks, respectively, whereas the animals in Group 3 and 5 received repeated dose of 1250 or 2500 shocks within 3 days after the first session. All the animals in Group 6 died within 48 hours due to remarkable renal hemorrhage, leaving only 5 Groups for the evaluation of long-term study. The blood pressure, measured by tail-cuff method 60 days after shock wave administration, was not significantly different between the control and shock-waved WKY. Neither was there any remarkable difference between the blood pressures measured prior to and 60 days after the intervention in each Group. At 16th week after the shock wave administration, the animals were sacrificed. There was a slight but statistically significant increase in serum creatinine level in Groups 2, 4 and 5, as compared to the level of control animals in Group 1. On light microscopic sections, there was no remarkable histological change in the kidney of Group 2, however, the renal parenchyma was frequently replaced with interstitial fibrosis in Groups 3, 4 and 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Chromosome analysis of renal cell carcinoma].

Of 8 tumors surgically extirpated from 8 patients with renal cell carcinoma, 7 were successfully processed in short-term culture by collagenase method, and 130 metaphases were extracted from these 7 tumors and were subjected to chromosomal analysis according to the G banding technique. As for karyotype, 4, 2 and 1 cases were mainly diploid, hypodiploid and aneuploid, respectively. The highest incidence of chromosome aberration was marked by #3 chromosome (5 of 7 cases of which 4 and 1 showed monosomy as clonal aberration and trisomy as non-clonal aberration, respectively). The commonest gain of chromosome was noted for #7 trisomy (4 of 7 cases). Two cases had already had metastases at the time of surgery, each showing #7 trisomy. Marker chromosome was noted in 6 of 7 cases. Structural chromosome aberration had a lesser incidence compared with numerical aberration; only clonal aberrations were long-arm aberrations (2q+, 6q+) of #2 and #6 chromosomes. Short-arm aberrations (3p-, 8p-) of #3 and #8 chromosomes were noted in one case each. 3p deletion, which is reported to be predominant in the literature, was noted only in one case. This was observed in triploid cells. However, all of metaphases showing 2q+ and 6q+ had concomitant #3 monosomy, and excess portions of #2 and #6 chromosomes were in good agreement with the band pattern of #3 chromosomal long-arm. Therefore, translocation of 3q12-qter in #2 and #6 chromosomes is supposed to lead to 3p deletion. A similar mechanism seems to be involved in the formation of marker chromosomes, suggesting the involvement of deleted #3 chromosome in marker chromosomes.

Aged↗

[Discriminant analysis of quantification theory on prognostic factors of chemotherapeutic effects on advanced testicular cancer. East Japan Testicular Tumor Study Group].

Prognostic factors of chemotherapy against advanced testicular cancer were analysed in 33 cases studied by East Japan Testicular Tumor Study Group. In this study a discriminant analysis of quantification theory (a multivariate analysis) was adapted, taking 7 factors as comparative variables. The significant factors for complete tumor response were clinical stage, histology, and tumor markers (HCG-beta, AFP). Prognostic score was calculated in each case by quantification theory, which correctly discriminated the group with CR from that without CR, at a probability of 90.1%. The results of our study indicate that the outcome of chemotherapy on advanced testicular cancer may be predicted with probability, by patients' status and adopted treatment. It may enable one to make an adequate treatment schedule for each patient.

Antineoplastic Combined Chemotherapy Protocols↗