[Biological response modifiers and urological cancer].
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Carcinoma, Renal Cell↗
Biomedical subjects
H Tazaki
Publications and source records attributed to H Tazaki.
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↗
Embolization in high-flow arteriovenous malformations of the face.
Five patients with arteriovenous malformations of the face (4 males and 1 woman; age range, 11-38 years) were treated by selective embolization through the feeding arteries with polyvinyl alcohol particles. Immediate gross angiographical obliteration was obtained in 4 patients, with pronounced reduction of the arteriovenous shunt in the fifth. Clinical symptoms including bleeding, swelling, pulsations, bruit, and disfigurement improved in all the patients followed up for a period of 6 to 21 months. Polyvinyl alcohol particle embolization, without surgical resection, though palliative could be useful in select patients. The classification and diagnosis of congenital vascular malformations is briefly reviewed and treatment discussed.
Adolescent↗
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↗
Adrenocorticotropic hormone-independent bilateral adrenocortical macronodular hyperplasia as a distinct subtype of Cushing's syndrome. Enzyme histochemical and ultrastructural study of four cases with a review of the literature.
Four patients with adrenocorticotropic hormone (ACTH)-independent bilateral adrenocortical macronodular hyperplasia (AIMAH) were examined. All of them were men whose ages ranged from 37 to 52 years. Plasma cortisol levels were high, with a loss of diurnal rhythmicity, and plasma ACTH was undetectable. Adrenal cortisol secretion was not suppressed by dexamethasone, but it was ACTH responsive. Test results for corticotropin-releasing hormone (CRH) also were negative. Image analyses revealed a normal sella turcica and significantly enlarged adrenal glands, which showed enhanced uptake of isotope. Both adrenal glands in all cases were between 72 and 176 g in combined weight and were composed of, and distorted by, yellow nodules. Histologically, small cortical cells with or without lipid, occasional clear cells, and rare compact cells of the usual size were increased in number in the glandular cords. Enzyme histochemically, cortical cells showed weaker activity for 3 beta hydroxysteroid dehydrogenase and other enzymes than did usual cortisol-producing adenomas. Ultrastructurally, they had moderately to poorly developed smooth endoplasmic reticulum. Nonnodular areas of the cortex consisting of nonproliferating cells were atrophic and contained no compact cell zone. This is similar to the adrenal cortices attached to cortisol-producing adenomas. These features are unique to AIMAH and suggest the presence of a distinct subtype of Cushing's syndrome.
Adrenal Cortex↗
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↗
[Studies on in vitro anti-tumor activity of tumor necrosis factor alpha against human renal carcinoma cell line (KU-2)].
We attempted to clarify the anti-tumor activity and its mechanism of human recombinant tumor necrosis factor alpha (rTNF alpha). The established cell line KU-2, derived from human renal cell carcinoma, was treated with rTNF alpha alone or in combination with the following anti-cancer agents in vitro: actinomycin D (ACD), vinblastine sulfate (VLB), nimustine hydrochloride (ACNU), and methotrexate (MTX). In vitro studies, including cytotoxic assay, colony forming assay and flow cytometric DNA analysis were performed. By cytotoxic assay, 21.4 +/- 4.0% and 34.8 +/- 4.7% of the cells were killed by 72 hour incubation with 100 ng/ml of rTNF alpha alone, and 1 ng/ml of ACD alone, respectively. An augmented cytotoxicity of 75.3 +/- 0.3% was observed by simultaneously adding 1 ng/ml of rTNF alpha and 1 ng/ml ACD. However, when KU-2 was treated with both 100 ng/ml of rTNF alpha and 3 micrograms/ml of ACNU or 2.5 ng/ml of MTX, no significant increase in cytotoxicity was noted. In the colony forming assay study, the colony forming efficiency (CE) of the control cultures was 31.8 +/- 8.1%. A 92.3 +/- 1.8% reduction in CE was demonstrated when 100 ng/ml of rTNF alpha was added to the cultures. No augmented effects were seen between rTNF alpha and chemotherapeutic agents in this study. In flow cytometric DNA analysis, no cell cycle specific effects of rTNF alpha were demonstrated, regardless of whether or not chemotherapeutic agents were added. These results indicate that the cytotoxic and cytostatic activities of rTNF alpha may be mediated by separate mechanisms of action and that rTNF alpha affects more markedly KU-2 cells having clonogenic potentials.(ABSTRACT TRUNCATED AT 250 WORDS)
Antineoplastic Agents↗
[Studies on anti-tumor activity of tumor necrosis factor alpha against human renal cell carcinoma cells heterotransplanted into nude mice].
The anti-tumor activity of recombinant tumor necrosis factor alpha (rTNF alpha) against the renal cell carcinoma cell line KU-2 was studied in vivo, employing athymic nude mice. The nude mice were divided into six groups and each group was composed of six mice. Group I underwent no treatment, Groups II and III were injected with 5 and 10 micrograms of rTNF alpha intraperitoneally, respectively. Group IV received 5 micrograms of rTNF alpha intravenously and Groups V and VI were administered 2.5 and 5 micrograms of rTNF alpha six times, given intravenously every other day, respectively. Evaluation of the study was performed according to Battelle Colombus Laboratories Protocol. Tumor regression was defined as RW less than 1; inhibition of tumor proliferation was defined as TRW/CRW less than or equal to 42%. Other results were defined as no effect. No obvious anti-tumor activity was observed in group II and III. Though inhibition of tumor proliferation was noted in Group IV, death of two nude mice in this group was noted. When rTNF alpha was administered to the mice in Group V, complete disappearance of the heterotransplanted tumor in two nude mice and tumor regression in four were observed. No death of mice in this group occurred. When the dose of rTNF alpha was raised to 5 micrograms (Group VI), however, five mice died. The histopathological study revealed remarkable necrosis in the tumor tissue and congestion around the white pulps of the spleen 24 hours after intravenous administration of 5 micrograms of rTNF alpha, although no obvious changes were noted in the liver, kidney and digestive organs.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[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↗
Haemodialysis and platelet activation.
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Animals↗
[Treatment of benign prostatic hypertrophy using balloon dilation].
Balloon dilation of the prostatic urethra was performed for the management of benign prostatic hypertrophy. The patients selected were mainly high risk patients who were poor surgical candidates for transurethral resection of the prostate. Ten patients between 61 and 87 years old with a mean age of 77.8 years were treated. Of the 10 patients 6 had urinary retention. The procedures were performed under spinal anesthesia, using 75 Fr dilation balloon for 10 minutes twice at 3 atmospheres. In a couple of months after treatments, 5 patients showed improvement in both uroflowmetry and clinical symptoms. Three patients revealed improvement of clinical symptoms only and 2 were in vain. One year after treatment, 3 out of 6 patients had persistent improvement. Balloon dilation of prostatic urethra was safe and showed promising effectiveness for high risk patients.
Aged↗
[Enucleation performed to treat renal cell carcinoma associated with chronic nephritis: a case report].
We performed enucleation on a patient with renal cell carcinoma associated with nephritis to preserve renal function. The patient was a 40-year-old man diagnosed with chronic nephritis. Ultrasonography performed during brief hospitalization for a check-up revealed a tumor in the left kidney. Enucleation was performed to treat stage 1 renal cell carcinoma. Pathological study revealed that the patient had IgA nephropathy and grade 1 clear cell carcinoma.
Adult↗