Mirtha Grande

Possible bone-preserving capacity of high-dose intramuscular depot estrogen as compared to orchidectomy in the treatment of patients with prostatic carcinoma.

Treatment of prostatic disease with GnRH agonists or by orchidectomy affects bone mass negatively. Estrogen treatment has beneficial effects on bone mass in women and might hypothetically have a bone preserving capacity also in patients with prostatic cancer.

Tissue PSA from fine‐needle biopsies of prostatic carcinoma as related to serum PSA, clinical stage, cytological grade, and DNA ploidy

The mechanisms behind changes in serum PSA (S‐PSA) levels in patients with prostatic carcinoma (CAP) are not completely known. To further elucidate the factors affecting the serum levels of this important tumor marker, we measured PSA concentrations in serum and in aspiration biopsies (tissue PSA; T‐PSA) from patients with prostatic disease and correlated the values to tumor stage, cytological grade, and DNA ploidy.

Estrogens increase the endothelial nitric oxide synthase (ecNOS) mRNA level in LNCaP human prostate carcinoma cells

The endothelial cell‐specific form of nitric oxide synthases (ecNOS) may play an important role in vascular development, maintenance of vascular tone, and tumor growth in human prostate cancer. Estrogens have been shown to upregulate ecNOS expression in different human cell culture systems. Estrone sulfate (E1S) is the most abundant circulating estrogen, and may serve as a prehormone for the terminal biologically active estrogen estradiol‐17β (E2) in men.

Use of a hormone-sensitive (LNCaP) and a hormone-resistant (LNCaP-r) cell line in prostate cancer research.

In order to develop a hormone‐resistant analog to the hormone sensitive cell‐line LNCaP, different methods were tried.

Estrogens Affect Endothelin-1 mRNA Expression in LNCaP Human Prostate Carcinoma Cells

OBJECTIVE To study effects of estrogens on endothelin-1 (ET-1) mRNA expression in the androgen-sensitive LNCaP-FGC cell line and its androgen-resistant derivative LNCaP-r. Further, if effects of estrone sulfate (E1S) are mediated via conversion to estradiol-17beta (E2). Estrogens have been shown to down-regulate ET-1, a mediator of the osteoblastic response of bone to metastatic prostate cancer. METHODS Cells were grown in steroid-depleted medium and incubated for 2-4 and 48 hours with 0, 1, 10, and 100 nM of either E1S or E2. mRNA levels were measured with an RT-PCR technique. Estrogen metabolism by LNCaP-FGC cells was studied by incubation with estrone (E1) and E1S at the same conditions, followed by determination of E1 and E2. RESULTS ET-1 mRNA expression in LNCaP-FGC cells was significantly suppressed by E2 and E1S following incubation for 2-4h but after 48 h only by E2 at 1 and 10nM and in LNCaP-r cells only by E2 at 100 nM following 2-4h of incubation. ET-1 mRNA expression was significantly higher in untreated LNCaP-r than in untreated LNCaP-FGC cells. E1 was efficiently transformed into E2 by LNCaP-FGC cells but very little to E1 and no E2 was formed from E1S. CONCLUSION ET-1 mRNA expression in LNCaP-FGC can be inhibited by E2, but also by its prehormone E1S. The lack of formation of E2 from E1S suggests a mode of action not related to classical steroid receptors. The higher level of ET-1 mRNA expression found in LNCaP-r cells may reflect the capability of a hormone refractory tumor to maintain activity on its own, independently of known regulatory mechanisms such as sex steroids.

Tissue concentrations of tissue polypeptide antigen (TPA) and prostatic specific antigen (PSA) in 42 patients with prostatic carcinoma

Following development of methods to quantitate biochemical markers in aspiration biopsies we showed that tissue concentration of prostate specific antigen (T‐PSA) decreased with increasing malignancy while serum PSA increased. We also found that T‐PSA predicts the clinical outcome better than earlier used prognostic markers.

Tissue PSA is the best predicting variable for the outcome of endocrine treatment of prostatic carcinoma

In order to evaluate the prognostic value of tissue-PSA (prostatic-specific protein, measured in aspiration biopsies) 231 hormonally treated patients with verified carcinoma of the prostate (CaP) but without metastasis were studied retrospectively. T-PSA was determined at the time of diagnosis in all patients and in 52 of these also at 6, 12 and 24 months after diagnosis. Of the 231 patients, 79 died of prostatic carcinoma and 152 were still alive or had died of other diseases at the end of the observation period (more than 71 months). In a first set of evaluations the predictive value of a single analysis at the time of diagnosis was studied in 179 patients. It was found that tissue PSA was the most important factor for predicting both time to progression and time to death in CaP. Other competing factors were S-PSA, free S-PSA, age, clinical stage, grade and DNA-ploidy. Further evaluations regarding serial PSA determinations were performed in 52 patients. Tissue PSA increased during treatment in all patients who died of CaP. In all patients who survived or died for other reasons, tissue PSA decreased during treatment and remained low. The change of tissue PSA seen between 0, 6 and 12 months could in all cases predict the clinical outcome. It is concluded that a single analysis of tissue PSA at the time of diagnosis can predict the clinical outcome in most cases and that serial determinations can predict the outcome in almost all cases of a CaP without metastasis at the time of diagnosis. This requires that we use this assay when selecting between patients who will survive on hormonal treatment and those who most probably would benefit from a more aggressive treatment.

Changes in tissue prostatic acidic phosphatase during endocrine treatment of patients with prostatic carcinoma

Objective. We have previously developed methods for the quantification of different macromolecules in aspiration biopsy material and described the changes in prostate-specific antigen (T-PSA) during cancer treatment. We have now studied the changes in tissue prostatic acidic phosphatase (T-PAP) in 58 endocrine-treated patients with prostatic carcinoma and compared these data with cancer development data and tissue PSA (T-PSA) levels. Material and methods. PAP and PSA were quantified in aspiration biopsies taken before treatment and after 6 and 12 months of treatment. Patients were followed until death or for >98 months. Results. Pretreatment T-PSA was more strongly associated with survival than T-PAP. Both T-PSA and T-PAP decreased in responders during treatment. In non-responders, T-PSA and T-PAP increased after 12 months in 17/18 and 7/13 patients, respectively. Estrogen-treated responders had significantly higher T-PSA, but not T-PAP, treatment values than those treated with orchidectomy or gonadotropin-releasing hormone. Conclusions. The inferiority of serum PAP compared to PSA for monitoring cancer treatment may reflect its less pronounced changes at the tissue level, indicating different in vivo regulation of the two markers. Estrogen stimulation of PSA synthesis in vivo may underlie the higher PSA levels observed during estrogen treatment.