We tested the clinical efficacy of a biologically active dose (BAD) of interferon (IFN)-gamma for treatment of progressive renal cell carcinoma (RCC). Twenty-two RCC patients with disease progression subsequent to nephrectomy were entered on a phase II clinical trial. During an initial dose-finding phase, biochemical responses to repeated once-weekly subcutaneous injections of 10, 100, or 500 micrograms of recombinant IFN-gamma were tested in 16 patients. Results indicated that 100 micrograms IFN-gamma applied once weekly was biologically active with induction of serum beta 2-microglobulin and neopterin. Such a dose induced a nearly maximum response of both markers lasting more than 4 days. This dose was also associated with minimal side effects. A dose of 100 micrograms IFN-gamma given once weekly was, therefore, subsequently given weekly for long-term treatment. During a median time of therapy of 10 months (range, 2 to 32 months) two complete (CR; 20+, 20+ months) and four partial tumor responses (PR; 6+, 7+, 8+, 24+ months) were seen (30% CR plus PR; 95% confidence limits, 12% to 54%) among 20 patients evaluable for response. Patients with refractory disease had significantly lower IFN-gamma-induced increments of serum beta 2-microglobulin than those who achieved clinical remission or stable disease.
The present study assesses the clinical outcome of microsurgical subinguinal varicocelectomy in infertile men, especially with regard to sperm count, motility and fertility. Between June 1990 and October 1998, 272 patients had subinguinal microsurgical varicocelectomy operations for clinical varicoceles, and their long-term results were assessed. In nearly all the patients there was a significant improvement in sperm count and sperm motility after 3 and 6 months. Very few complications arose from this procedure. We concluded that microsurgical subinguinal varicocelectomy is an effective treatment for clinical varicoceles in infertile men. The significant improvement in the quality of spermatozoa, the low complication rates and the remarkably high pregnancy rates make this a valuable alternative to in vitro reproduction techniques.
The presence of the prostate is universal in mammals; when compared among species the prostate is marked by variations in its anatomy, biochemistry and pathology. The epithelial cells provide secretions that empty through ducts into the urethra to form a major component of the seminal plasma of the ejaculate. The prostate is stimulated to grow and is maintained in size and function by the presence of serum testosterone. Several protein-type growth factors, such as urogastrone and prostatropin, may also affect prostatic growth. After testosterone from the plasma has entered the prostatic cell through diffusion it is metabolized to other steroids by a series of enzymes. Over 95% of testosterone is converted to the most important prostatic androgen dihydrotestosterone. DHT then binds to the activated androgen receptor. The hormone receptor complex undergoes transformation and translocation into the nucleus. In the nucleus RNA-polymerase is activated followed by the synthesis of mRNA. The noncellular stroma and connective tissue compose the extracellular matrix. The extracellular matrix plays an important role in development and control of cellular functions.
(i) Like normal kidney, virtually all primary human renal cell carcinomas express MHC class I antigens and retain this phenotype even during tumor progression and metastasis; (ii) class II expression on normal and RCC cells appears more limited but occurs frequently in both primary and metastatic lesions; and (iii) in most continuous RCC cell lines expression of MHC class I and II can effectively be stimulated by IFN-gamma. Since expression of MHC molecules might determine the immunogenicity of human RCC, its constitutive expression and augmentation could play an important role for the immunotherapy and prognosis of human renal cancer.
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