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1/6. role of herbal compounds (PC-SPES) in hormone-refractory prostate cancer: two case reports.

    PURPOSE: Herbal therapies are unconventional treatments that have been used for several different diseases. PC-SPES is an herbal mixture, composed of eight different herbs (chrysanthemum, isatis, licorice, ganoderma lucidum, panax pseudo-ginseng, rabdosia rubescens, saw palmetto, and scutellaria), which has been used as an alternative in the treatment of prostate cancer. We report two cases of hormone-refractory prostate cancer patients, who showed a favorable response to therapy with this herbal combination, controlling the progression of the disease. methods: We report two cases of biopsy proven prostate cancer patients with metastatic disease, treated with total androgen blockade, progressing to an androgen-independent status. These patients were offered traditional therapies for hormone-resistant prostate cancer, and they chose to take PC-SPES. The follow-up as well as their evolution are described. RESULTS: PC-SPES extract decreased the prostate-specific antigen (PSA) value for both patients from an initial value of 100 and 386 ng/mL to 24 and 114 ng/mL after 1 year and 4 months, respectively, remaining stable until now. No gynecomastia or hot flashes were observed in these patients and the treatment was well tolerated. CONCLUSION: PC-SPES has shown a strong estrogenic in vitro and in vivo activity as an alternative tool in the management of prostate cancer patients. These cases suggest that PC-SPES might have some potential activity against hormone-independent prostate cancers.
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2/6. Expression of glucocorticoid receptor and 11beta hydroxysteroid dehydrogenase in a case of pulmonary epithelioid haemangioendothelioma.

    This report describes a case of pulmonary epithelioid haemangioendothelioma in which the tumour cells expressed the glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase. The patient, a 15 year old girl, who had no other complaints or past illnesses, was found to have an abnormal shadow on a chest roentgenogram obtained at a school medical examination. Multiple nodular shadows in the bilateral lungs were also confirmed by computerised axial tomography scan. A diagnosis of pulmonary epithelioid haemangioendothelioma was made on the basis of lung biopsy specimens. The tumour cells were immunohistochemically positive for factor viii related antigen, CD31, and CD34, but not surfactant apoprotein A. In addition, almost all of the tumour cells showed simultaneous expression of the glucocorticoid receptor and 11beta hydroxysteroid dehydrogenase, suggesting that steroid treatment would be effective.
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3/6. Orbital metastasis from prostate cancer: an atypical case of neuroendocrine dedifferentiation during progression from hormone-sensitive to refractory stage.

    We report a case of orbital metastasis from a neuroendocrine dedifferentiated prostate cancer during progression from hormone-sensitive to hormone refractory stage. A patient receiving androgen deprivation for hormone-sensitive prostate cancer presented with sudden-onset right-sided ptosis and an increasing serum prostate-specific antigen level. Imaging studies revealed a mixed blastic and lytic lesion involving the right orbital wall and the right cavernous sinus. Comparison of the metastatic histology with the original pathology confirmed a histologic change to poorly differentiated prostate adenocarcinoma with neuroendocrine features. Local radiation of the lesion and palliative systemic chemotherapy resulted in marked short-term improvement of all presenting symptoms. Because prostate cancer metastasis involves hematogenous and lymphatic routes, we also evaluated expression of the vascular endothelial growth factor (VEGF) and receptors (VEGFR-1, VEGFR-2, and VEGFR-3) in the metastatic deposit by immunohistochemistry. Strong expression of VEGFR-2 and VEGFR-3 restricted to the malignant epithelium was noted. We recommend a second biopsy of atypical prostate metastasis associated with sudden change to aggressive clinical behavior in order to evaluate for dedifferentiation features before planning appropriate treatment interventions especially in patients who are candidates for systemic chemotherapy.
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4/6. Complete response, as determined by prostate-specific antigen level, to chlormadinone acetate withdrawal persisting longer than 2 years in patients with advanced prostate cancer: two case reports.

    Antiandrogen withdrawal syndrome (AWS) is a well-established phenomenon in prostate cancer. However, responses to AWS are usually of limited duration, and a complete response (CR) is extremely rare. We present two patients who exhibited a chemical CR for more than 2 years after the discontinuation of steroidal antiandrogen chlormadinone acetate use. Whether patients who respond to antiandrogen withdrawal include a group of patients with a better prognosis remains uncertain. However, considering that the usual survival period of patients with hormone-resistant prostate cancer is approximately 12 months, both of the patients reported here, who are present in excellent physical condition, exhibiting an improved quality of life, and attending their hospital as outpatients, obviously acquired a prolonged survival because of AWS.
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5/6. Effects of intermittent androgen suppression on androgen-dependent tumors. apoptosis and serum prostate-specific antigen.

    BACKGROUND. Since postcastration progression of tumors to an androgen-independent state appears to be linked to the cessation of androgen-induced differentiation of tumorigenic stem cells, the authors hypothesized that the replacement of androgens at the end of a period of apoptotic regression might result in the regeneration of differentiated tumor cells with further apoptotic potential. methods AND RESULTS. To determine the effect of intermittent exposure of androgens on the androgen-dependent Shionogi carcinoma, the tumor was transplanted into a succession of male mice, each of which was castrated when the estimated tumor weight became about 3 g. After the tumor had regressed to 30% of the original weight, it was transplanted into the next noncastrated male. This cycle of transplantation and castration-induced apoptosis was repeated successfully four times before growth became androgen-independent during the fifth cycle. In four of Stage C and three of Stage D patients with prostate cancer, androgen withdrawal was initiated with cyproterone acetate (100 mg/d) and diethylstilbestrol (0.1 mg/d) and then maintained with cyproterone acetate in combination with the luteinizing hormone-releasing hormone agonist, goserelin acetate (3.6 mg/month). After 6 or more months of suppression of serum prostate-specific antigen (PSA) into the normal range, treatment was interrupted for 2 to 11 months. After recovery of testicular function, androgen-withdrawal therapy was resumed when serum PSA increased to a level of about 20 micrograms/l. This cycle was repeated sequentially to a total of two to four times over treatment periods of 21 to 47 months with no loss of androgen dependence. CONCLUSIONS. These results demonstrate that intermittent androgen suppression can be used to induce multiple apoptotic regressions of a tumor; they also suggest that the cyclic effects of such treatment on prostate cancer can be followed by the sequential measurement of serum PSA levels.
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6/6. Are pancreatic tumors hormone dependent?: A case report of unusual, rapidly growing pancreatic tumor during pregnancy, its possible relationship to female sex hormones, and review of the literature.

    The occurrence of a pancreatic tumor in a young patient is rare. However, when one identifies a pancreatic mass during pregnancy and particularly when the lesion is located in the tail of the pancreas, "unusual tumors" of the pancreas should be considered. The management of these tumors during pregnancy presents unusual challenges because of rapid tumor growth probably related to elevated levels of sex hormones. An immunohistochemical study was done to evaluate for hormone receptors of the tissue removed from the tumor. We present a case of a 37-year-old female patient in her 4th week of pregnancy who was found to have a pancreatic mass; she was followed with ultrasonography. At the 23rd week of gestation, the tumor increased in size to more than 12 cm and required resection. Immunohistochemical studies were done to evaluate receptors for progesterone, estrogen, PS2-estrogen-related protein, pancreatic polypeptide antigen, flow cytometry, dna ploidy, and proliferative activity in tumor cells. pathology showed a low-grade multiloculated mucinous cystic neoplasm of the pancreas. There was a positivity for progesterone receptor and PS2-estrogen-related protein but not for estrogen receptor in the tumor. We conclude that a pancreatic mass detected during pregnancy requires a different consideration for its management. Early tissue diagnosis with CT or ultrasound-guided biopsy is essential. Even those lesions diagnosed as benign would require early intervention because of their rapid growth, probably influenced by female sex hormones.
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