1/12. Numerical chromosomal changes in metastatic prostate cancer following anti-androgen therapy: fluorescence in situ hybridization analysis of 5 Japanese cases.We used fluorescence in situ hybridization with centromere-specific probes for chromosomes 7, 8, 10, and Y to determine the copy number of these chromosomes in metastatic prostate cancers of five Japanese cases. Freshly prepared samples were obtained from prostate needle biopsies at different phases of clinical treatment; pretreatment, 1 week, 4 weeks, 12 weeks, 24 weeks post-treatment (PT), and clinical relapse. Gain of chromosomes 7 and 8, as noted in pretreatment samples; however, in post-treatment specimens (four of five cases), a remarkable reduction in the number of cells with extra copies of these chromosomes was detected. This decrease in the number of cells with additional chromosome 7 and 8 signals was correlated with the clinicohistopathological findings until 4 weeks PT. chromosomes Y and 10 did not show numerical aberrations before treatment or changes in cells with aneusomy after treatment in all five cases. Our results suggest that gains of chromosomes 7 and 8 correlate with high grade and stage, and that changes in the cell number with aneusomy of chromosomes 7 and 8 reflect the clinical effects of anti-androgen therapy at an early phase, which may also indicate the androgen dependency of prostate cancer cells.- - - - - - - - - - ranking = 1keywords = androgen (Clic here for more details about this article) |
2/12. Clinical and experimental progression of a new model of human prostate cancer and therapeutic approach.We report the clinical evolution of a prostate cancer, metastasizing to lungs and bones, recurring locally, and escaping from anti-androgen therapy. Key event of biological progression of the patient's tumor was the coincidence of allelic imbalance accumulation and of bone metastases occurrence. The recurrent tumor was established as the transplantable xenograft PAC120 in nude mice, where it grew locally. PAC120 displayed the same immunophenotype of the original tumor (positive for keratin, vimentin, prostatic acid phosphatase, and Leu-7) and expressed human HOXB9, HOXA4, HER-2/neu, and prostate-specific antigen genes, as detected by reverse transcriptase-polymerase chain reaction. It formed lung micrometastases detected by mRNA expression of human genes. cytogenetic analysis demonstrated numerous alterations reflecting the tumor evolution. PAC120 was still hormone-dependent; its growth was strongly inhibited by the new gonadotropin-releasing hormone antagonist FE 200486 but weakly by gonadotropin-releasing hormone superagonist D-Trp(6)-luteinizing-hormone releasing hormone (decapeptyl). Tumor growth inhibition induced by anti-hormone therapy was linked to the hormone deprivation degree, more important and more stable with FE 200486 than with D-Trp(6)-luteinizing-hormone releasing hormone. Surgical castration of mice led to tumor regressions but did not prevent late recurrences. Transition to hormone-independent tumors was frequently associated with a mucoid differentiation or with a neuroendocrine-like pattern. Independent variations of mRNA expression of HER-2/neu and prostate-specific antigen were observed in hormone-independent tumors whereas HOXB9 gene expression was constant. In conclusion, PAC120 xenograft, a new model of hormone-dependent prostate cancer retained the progression potential of the original tumor, opening the opportunity to study the hormone dependence escape mechanism.- - - - - - - - - - ranking = 0.16666666666667keywords = androgen (Clic here for more details about this article) |
3/12. Rapid rise of serum prostate specific antigen levels after discontinuation of the herbal therapy PC-SPES in patients with advanced prostate carcinoma: report of four cases.BACKGROUND: PC-SPES is an herbal supplement whose mechanisms of action are poorly understood, but may be estrogenic. The objective of the current report is to describe the effects of discontinuing PC-SPES treatment in four patients with androgen-independent prostate carcinoma. methods: Patient charts were retrospectively reviewed. A medline search was performed to investigate whether these effects of PC-SPES had been previously reported. RESULTS: Four men whose metastatic prostate carcinoma progressed despite androgen ablation and subsequent PC-SPES treatment are described. All four patients developed a rapid increase in serum prostate specific antigen (PSA) within one month of stopping PC-SPES, ranging from 345% to 880%. Two patients increased their PSA levels to 1300% and 1400% after 7 weeks. Compared to the rate of rise of PSA levels prior to and during PC-SPES therapy, the rise after stopping this treatment was much higher than expected. Clinical symptoms remained relatively stable despite the serologic changes. CONCLUSIONS: Discontinuing PC-SPES therapy can be associated with a rapid rise in PSA. To the authors' knowledge, this effect has not been reported previously. This effect should be considered in the design of clinical trials as well as in the standard management of androgen-independent prostate carcinoma patients.- - - - - - - - - - ranking = 0.5keywords = androgen (Clic here for more details about this article) |
4/12. Virilizing adrenal tumor in a child suppressed with dexamethasone for three years. Effect of o,p'-DDD on serum and urinary androgens.Extensive hormonal evaluation was performed in a girl with adrenal carcinoma during the primary tumor stage, following adrenalectomy, during the period when metastases were evident and while on treatment with o,p'-DDD. At the age of 14 months a diagnosis of congenital adrenal hyperplasia was made and treatment with dexamethasone (0.125 to 0.25 mg/day) resulted in a fall-off in growth rate, normal advancement in bone age, decrease in virilization and suppression of 17- ketosteroid excretion which continued until 4 3/12 years of age when virilization increased. At five years of age elevated serum and urinary androgen levels unsuppressible with dexamethasone were noted. Following removal of a large right adrenal carcinoma, serum and urinary hormone levels returned to normal. There months following surgery, liver metastases were documented associated with elevated levels of serum androgens. With o,p'-DDD treatment, serum dehydroepiandrosterone sulfate (DS) and urinary 17-ketosteroid (17-KS) excretion fell rapidly while there was a delay in the fall of free androgens. The persistence of free steroid secretion with decreased formation of DS suggests that the o,p'-DDD may have altered sulfatase activity before causing tumor necrosis and total decrease in steroidogenesis.- - - - - - - - - - ranking = 1.1666666666667keywords = androgen (Clic here for more details about this article) |
5/12. A malignant aldosteronoma.OBJECTIVE: To describe a case of primary aldosteronism due to an adrenocortical carcinoma (ACC) and highlight the need for thorough long-term follow-up. methods: We present the clinical, laboratory, radiologic, and pathologic findings in a patient with ACC and review the related literature. RESULTS: A 52-year-old woman with a history of hypertension and hypokalemia was referred for evaluation of a 6-cm adrenal mass. Her biochemical studies revealed a serum aldosterone-to-renin ratio of 52 without evidence of cortisol, catecholamine, or androgen excess. She underwent surgical resection of this mass, and histologic analysis showed a focally brisk mitotic rate but no evidence of capsular or vascular invasion. In light of these findings, the biologic nature of the tumor was difficult to predict. Thus, it was thought to be an adrenocortical neoplasm. The patient underwent follow-up clinically, biochemically, and with interval computed tomography. Nine years later, hypertension and hypokalemia redeveloped, and she was found to have metastatic ACC. CONCLUSION: ACC can generally be reliably diagnosed; however, in some cases, the true biologic behavior is difficult to predict. We emphasize the importance of careful clinical, biochemical, and radiologic surveillance in these difficult cases because surgical resection provides the best opportunity for cure in patients with adrenal cancer.- - - - - - - - - - ranking = 0.16666666666667keywords = androgen (Clic here for more details about this article) |
6/12. male breast cancer: two cases with objective regressions from calusterone (7 alpha, 17 beta-dimethyltestosterone) after failure of orchiectomy.Calusterone (7 alpha, 17beta-dimethyltestosterone) is an orally effective weakly androgenic steroid. The antitumor efficacy of calusterone, 200 mg per day against objectively progressing advanced breast cancer in females has already been reported. In the present study calusterone was used in metastatic breast cancer in two male patients. Both had failed to continue respond to orchiectomy and had measurable lesions one in the lungs, the other in the bones. Both patients showed objective regression (blastic response of osteolytic lesions and disappearance of lung metastases) lasting five months in one patients and more than seven months in the other, who is still in regression. Further experience is necessary for statistically adequate results.- - - - - - - - - - ranking = 0.16666666666667keywords = androgen (Clic here for more details about this article) |
7/12. Androgen producing adrenocortical carcinoma.Two cases of androgen secreting adrenocortical carcinoma have been described by light and electron microscopy. The histological and ultrastructural features of the tumour cells were similar to those of compact cells of zona reticularis and to those described in virilizing adenomas. They possess numerous mitochondria with lamellar and tubular cristae, abundant smooth endoplasmic reticulum, lipofuscin bodies and scanty lipid. Irregularly shaped, crenated mitochondria, with outpouchings of the outer limiting membrane have also been observed. The clusters of neoplastic cells were surrounded by basement membrane which demonstrated a focal discontinuity, probably reflecting malignancy of the tumours. hyperplasia of smooth endoplasmic reticulum and the presence of outpouchings of the mitochondrial outer limiting membrane might be the morphological manifestation of endocrine activity of the tumours.- - - - - - - - - - ranking = 0.16666666666667keywords = androgen (Clic here for more details about this article) |
8/12. Indications for use of ketoconazole in management of metastatic prostate cancer.Newer methods of androgen ablation for the treatment of metastatic prostatic carcinoma have been developed as alternatives to the standard forms of therapy, oral estrogens and surgical castration. The purpose of this review is to elucidate the indications and to determine the role of ketoconazole in the management of metastatic prostatic cancer. Eighteen patients have been treated with ketoconazole. The indications for usage have included: prompt therapeutic response, when orchiectomy is contraindicated, when estrogens are contraindicated, initial empirical therapy, and hormonally refractory disease. It can also be used in conjunction with luteinizing hormone-releasing hormone analogues. ketoconazole is excellent for short-term usage prior to bilateral orchiectomy and when prompt therapeutic response is needed but orchiectomy cannot be performed. However, it is not particularly useful for long-term hormonal therapy.- - - - - - - - - - ranking = 0.16666666666667keywords = androgen (Clic here for more details about this article) |
9/12. aldosterone-producing adrenocortical carcinoma. Preoperative recognition and course in three cases.Three patients with primary aldosteronism due to adrenocortical carcinoma were studied, two with hyperaldosteronism alone and one also with hypercortisolism; in the later stages all three had hypersecretion of glucocorticoid and androgenic hormones. Although clinical presentations were similar to those of patients with benign adenoma, all had significantly higher concentrations of deoxycorticosterone and aldosterone and more profound hypokalemia. Stimulation with adrenocorticotropin in two patients showed a good cortisol response but no aldosterone response. The circadian rhythm for cortisol was normal but absent for aldosterone and deoxycorticosterone. Sequential 24-hour circadian studies in one patient showed that as the disease progressed, corticosterone and finally cortisol lost their circadian rhythms. Treatment with spironolactone, mitotane, or aminoglutethimide had transient clinical effects. The patients died 2 to 13 years later.- - - - - - - - - - ranking = 0.16666666666667keywords = androgen (Clic here for more details about this article) |
10/12. Dramatic prostate specific antigen decrease in response to discontinuation of megestrol acetate in advanced prostate cancer: expansion of the antiandrogen withdrawal syndrome.We report a dramatic decrease in prostate specific antigen in response to the discontinuation of megestrol acetate in a patient with progressive metastatic prostate cancer. Our case demonstrates that withdrawal responses may occur with steroidal and nonsteroidal antiandrogens.- - - - - - - - - - ranking = 0.83333333333333keywords = androgen (Clic here for more details about this article) |
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