HSV-tk gene therapy for human renal cell carcinoma in nude mice.

We have treated Caki-2 human renal cell carcinoma in vivo using herpes simplex virus thymidine kinase (HSV-tk) gene therapy. Both stably transduced Caki-2 tumors, generated using retrovirus-mediated ex vivo HSV-tk gene transfer and direct intratumoral adenovirus-mediated HSV-tk gene transfer of wild type tumors, were tested. Similar treatments with LacZ containing retro- and adenoviruses were used as controls. The outcome was evaluated by imaging the tumors before and after the treatment with magnetic resonance imaging, and using histology, immunocytochemistry, and survival analysis. When implanted orthotopically into nude mouse kidneys, Caki-2 cells formed reproducible cystic papillary kidney carcinomas. In vivo magnetic resonance imaging provided an important tool for the evaluation of tumor growth. Transduction efficiency of wild-type tumors in vivo with adeno-LacZ was 22+/-14%. Significant tumor regression was achieved with direct intratumoral adeno-HSV-tk transduction followed by intraperitoneal ganciclovir (GCV) (P<.001). Also, the treatment of stably transduced Caki-2 tumors with intraperitoneal GCV resulted in a significant treatment response in the HSV-tk group as compared to the LacZ group (P<.009). Increased apoptosis and macrophage infiltrations, reduced proliferation, and degenerative changes were observed in the tumors treated with HSV-tk and GCV. Also, significant prolongation in survival was achieved with adeno-HSV-tk- and GCV-treated mice as compared to the controls. It is concluded that adeno-HSV-tk gene therapy may be useful for the treatment of renal cell carcinoma in vivo.

The prognostic value of inducible nitric oxide synthase in local prostate cancer.

OBJECTIVE: To compare the clinical and histological data from patients with prostate cancer with the results of the immunohistochemical analysis of inducible nitric oxide synthase (iNOS), and thus determine the prognostic value of iNOS. PATIENTS AND METHODS: The study included 82 patients (mean age 64.6 years, SD 6.1) with local prostate cancer treated by radical prostatectomy in two Finnish hospitals. Their mean (SD) follow-up was 3.3 (2.2) years. An immunohistochemical method was used to detect the expression of iNOS in these specimens, and the expression graded according to staining intensity as none, weak or strong. RESULTS: There was weak or strong expression of iNOS in 25 (31%) and 56 (68%) of the patients, respectively, and one specimen was negative for iNOS. Strong expression of iNOS was related to high a preoperative prostate specific antigen (PSA) level (P = 0.006) and high pT classification (P < 0.001), but not to nodal status, grade, seminal vesicle or capsular invasion, surgical margin status, perineural infiltration, tumour infiltrating lymphocytes or proliferation rate of cancer cells. A PSA failure was detected in 29 patients but was not predicted by iNOS expression. A Cox multivariate analysis showed that surgical margin positivity, seminal vesicle involvement and number of tumour infiltrating lymphocytes predicted the PSA failure. CONCLUSION: A high expression of iNOS was related to a high pT classification and the preoperative PSA level but not to other established prognostic factors; iNOS expression was not a predictor of PSA failure in patients with local prostate cancer.

Characterization of a new animal model for human renal cell carcinoma.

BACKGROUND: Human renal cell carcinoma (RCC) is the most common kidney malignancy with significant mortality. Human tumor xenograft models are important tools for cancer research. MATERIALS AND METHODS: We have established and characterized a new animal model for human RCC using Caki-2 cells implanted into the renal subcapsule (RSC) of nude mice. Histology, immunocytochemistry, in situ hybridization and magnetic resonance imaging (MRI) were used to analyze the tumors. RESULTS: The implantations generated reproducible carcinomas which closely resemble human RCC. The tumors showed cystic-papillary structures, rich capillary network and fibro-septa formations. Proliferation varied from 0-5% and from 1-60% in cystic and solid areas, respectively. Apoptosis was less than 1%. Macrophages and other inflammatory cell infiltrations were detected in the tumors. VEGF-A and angiopoietin I were expressed in a small number of cells in large tumors. Tumors did not metastasize outside peritoneal cavity. Survival of the tumor bearing animals was 23 +/- 3 weeks. CONCLUSIONS: It is concluded that Caki-2 carcinomas implanted into renal subcapsule of nude mice resemble human RCC in several aspects and represent a good animal model for studies regarding the pathogenesis and treatment of human RCC.

Blood loss in long-term aspirin users undergoing transurethral prostatectomy.

As aspirin is now widely used for preventing recurrence of cardiovascular and cerebrovascular disorders, many men selected for transurethral resection of the prostate (TURP) are aspirin users. The previous indication for aspirin as a preoperatively administered antithrombotic agent is no longer common. In this study we investigated the blood loss in long-term aspirin users (250 mg/day) undergoing TURP. The mean blood loss in the 40 aspirin users was 358 (range 50-1550) ml, and in a control group of 42 men it was 478 (40-2400) ml. When mean blood loss was correlated to operating time and prostatic weight, the intergroup difference was not significant. In the late postoperative period two aspirin-treated men had bleeding with tamponade of the urinary bladder requiring emptying in the operating room. As blood loss was not enhanced by aspirin use, avoidance of aspirin before TURP appears to be unnecessary.

Multilocular renal cyst. Report of two cases and review of the literature.

Multilocular renal cyst (MRC), or cystic nephroma (CN), is a rare tumour of the kidney. Approximately one hundred cases have been reported, half of these in children. Normally these lesions have been confirmed to be benign cystic lesions, but it is possible for them to transform into malignancy. In children this type of tumour may simulate Wilms' tumour. We report two cases of MRC disease with clinical findings, pathology, treatment and survival.

Evaluation of immediate and late results of transurethral resection of the prostate.

A total of 401 men who underwent transurethral resection of the prostate (TURP) between 1983 and 1986, were prospectively evaluated in 1987, 167 of them were sent a questionnaire about their ability to pass urine 1990. Our results showed that TURP was safe with no immediate mortality. The hospital stay was, however, long (median 7.0 days). It should be possible to shorten the hospital stay of those in the age group 60 and 70 years. After a mean of 6.5 years, 92% of patients were satisfied with their ability to pass urine.

Leiomyoma of the bladder. Case report.

A 33-year-old woman was incidentally noted to have a benign bladder leiomyoma on pelvic ultrasonography during pregnancy. This was resected and she made an uneventful recovery. Leiomyomas of the bladder are rare and usually asymptomatic; the treatment is excision.

Ultrasonography for diagnosis of obstructing ureteral calculus.

The reliability of ultrasonography in diagnosing ureteral obstruction caused by calculus was prospectively investigated. In 60 consecutive cases sonograms were compared with excretory urograms. The sonographic diagnosis was correct in 27 (79%) of the 34 cases shown by urography to have ureteral obstruction, and the sonograms showed the causal calculus in 17. The rate of false negative sonographic diagnosis was thus 21%. In two patients with no urographic abnormality, the sonograms indicated ureteral calculus without signs of obstruction. Ultrasonography may be used as an alternative to emergency urography for initial imaging in cases of suspected ureteral obstruction, but urography remains the standard method for evaluating the obstructed urinary tract, due to its greater accuracy and ability to assess renal function.