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M Koutsilieris

Publications and source records attributed to M Koutsilieris.

At least 55 records · Page 3Linked to original sources
PubMed1989

Human uterus-derived growth substances for rat bone cells and fibroblasts.

The effects of extracts from normal human uteri on tritiated thymidine incorporation and cell number were studied in primary cultures of isolated fetal rat calvarial osteoblasts and fetal rat skin fibroblasts. In this study crude uterine extracts were shown to stimulate tritiated thymidine incorporation into cellular deoxyribonucleic acid in osteoblast-like and fibroblast-like cell cultures above controls levels. This effect, which began after 6 hours, was maximal after 24 hours of incubation. In addition, the number of osteoblast-like and fibroblast-like cells increased above control levels after 1, 3, and 5 days of incubation. The above effects were dose-dependent, and maximal stimulation of uterine extracts was comparable with the stimulation achieved by 10% fetal bovine serum. The degree of stimulation by uterine extracts, expressed as percent above controls, was not dependent on the concentration of fetal bovine serum in cell culture medium. The above results are consistent with the view that uterine extracts contain mitogen(s) for bone cells and fibroblasts. These mitogens could play an important role in bone physiology and uterine pathophysiology.

Adult↗
PubMed1988

Application of octadecylsilyl-silica in purification studies related to the nontransformed rat ventral prostate androgen receptor.

We investigated the application of octadecylsilyl (ODS)-silica in studies related to characterization and purification of the nontransformed rat ventral prostate androgen receptor. The results indicated that ODS-silica successfully separates the free [3H]R1881 from the labeled [3H]R1881 transformed (4-5S) and nontransformed (8-9S) rat ventral prostate androgen receptors. Partial purification of the 8-9S receptor form was performed by the fractionation of rat cytosol using cartridges of the ODS-silica and fast-flow-rate phosphocellulose chromatography. Further purification was accomplished by differential chromatography (DEAE-cellulose and slow-flow-rate phosphocellulose chromatography). This partially purified 8-9S receptor, when analyzed on a gel permeation high-performance liquid chromatography column, resulted in a three-peak pattern of UV absorbance. One of these peaks corresponded to a 59-kD non[3H]R1881-binding protein and the remaining two corresponded to 270-kD and 190-kD[3H]R1881-binding proteins. These results demonstrate the usefulness of ODS-silica in androgen receptor studies. The association of a 59-kD nonsteroid binding protein with the nontransformed rat ventral prostate androgen receptor is discussed.

Animals↗
PubMed1987

Complete response of lung metastases caused by prostatic cancer after chronic administration of a gonadotropin-releasing hormone analog, buserelin (HOE 766).

A stage D2 prostate cancer patient with biopsy-proven lung metastases and negative work-up for metastases is discussed. Treatment consisted of hormonal therapy in the form of chronic administration of an analog of gonadotropin-releasing hormone (GnRH-A), Buserelin, with follow-up for 24 months. The complete response of the patient to GnRH-A therapy provides an interesting and unusual case in the understanding of the biological behavior of prostate cancer.

Adenocarcinoma↗
PubMed1987

Characteristics of prostate-derived growth factors for cells of the osteoblast phenotype.

We examined the characteristics of mitogens extracted from human benign prostatic hyperplasia and prostatic adenocarcinoma tissue. Although mitogens for fetal rat skin fibroblasts as well as for rat calvarial osteoblasts and osterosarcoma cells were found, distinct entities that acted selectively in cells of the osteoblast phenotype could be obtained by sequential reverse-phase high performance liquid chromatography. Two peptides with apparent molecular weights of 10,000 and 13,000 D were derived from hyperplastic tissue, whereas a single moiety of 10,000 D was obtained from malignant tissue. These entities increased cell numbers and alkaline phosphatase activity in osteoblastlike cells consistent with effects on both growth and differentiation. Prostatic peptides did not stimulate adenylate cyclase in osteosarcoma cells. Mitogenic activity selective for osteoblastlike cells was identified in postpubertal but not prepubertal normal prostate. The results demonstrate the existence of osteoblastic growth factors in prostatic tissue whose presence may accompany postpubertal development.

Adenocarcinoma↗
PubMed1987

Effects of human prostatic mitogens on rat bone cells and fibroblasts.

We examined several characteristics of the mitogenic activity of extracts of human prostatic adenocarcinoma and human benign prostatic hyperplasia in fetal rat calvarial cells, cloned rat osteosarcoma cells and rat skin fibroblasts. Prostatic moieties produced maximal stimulation of [3H]thymidine incorporation at 24 h, were mitogenic in the absence or presence of various concentrations of serum, and were active in calvarial cells enriched with osteoblasts, skin fibroblasts and the cloned rat osteosarcoma cell line UMR 108. The known growth-promoting agents insulin, insulin-like growth factor, fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, interleukin-1 alpha and beta and transforming growth factor beta were also mitogenic in the indicator systems employed; however, maximally stimulating effects of these peptides in cells of the osteoblast phenotype were further enhanced with prostatic material. Prostatic activity was acid-stable and could be enriched with respect to osteoblast stimulation by hydrophobic and carboxymethyl ion-exchange chromatography. The results demonstrate the presence of potent mitogenic activity in hyperplastic and malignant prostatic tissue which appears to include unique osteoblast-stimulating activity.

Adenocarcinoma↗
PubMed1986

Selective osteoblast mitogens can be extracted from prostatic tissue.

Extracts of human prostatic carcinoma and of human benign prostatic hyperplasia were found to exhibit mitogenic activity in freshly isolated rat osteoblasts, rat fibroblasts, and osteoblast-derived osteosarcoma cells. This activity was markedly reduced by tryptic digestion of extracts, indicating its protein nature. Results of bioassay studies suggested that the prostatic material was different from a number of known growth factors. Analysis by reversed-phase high performance liquid chromatography revealed that extracts contained mitogenic activity for osteoblasts that was distinct from fibroblast-stimulating activity. Such osteoblast growth factors could form the basis of the skeletal osteogenic response to metastatic prostatic adenocarcinoma.

Adenocarcinoma↗
PubMed1986

Objective response and disease outcome in 59 patients with stage D2 prostatic cancer treated with either Buserelin or orchiectomy. Disease aggressivity and its association with response and outcome.

A comparative study was done in 59 recently diagnosed Stage D2 prostatic cancer patients treated with either long-term GnRH-A (Buserelin) (N = 42) or with orchiectomy (N = 17) and followed up for three years. The suppressed limits of plasma testosterone and estradiol levels after eight-week follow-up as well as the objective clinical response and disease outcome were found to be similar with either treatment. Hot flushes and loss of libido were noticed in both groups throughout the follow-up period; however, there were no other side effects. Analysis of Stage D2 patients based on their time of death enables us to identify nonhormonal variables which, in the form of an aggressiveness score, correlated well with both clinical response and disease outcome. These data confirm that (1) Buserelin is an effective and safe alternative to orchiectomy in advanced prostatic cancer, and (2) in clinical studies a multifactor aggressiveness score is useful for analyzing clinical efficacy data. Prospective application of that score may enable predictability of patient response and influence patient management.

Buserelin↗
PubMed1985

Long-term follow-up of patients with advanced prostatic carcinoma treated with either buserelin (HOE 766) or orchiectomy: classification of variables associated with disease outcome.

We compared the clinical efficacy and safety of Buserelin treatment versus orchiectomy in 29 patients with newly diagnosed advanced prostatic cancer. There was no significant difference between the two treatment modalities in 1) reduction of plasma testosterone to below 100 ng/dl after 8 weeks, 2) objective clinical response rates in patients with stage D2 carcinoma, 3) induction of complete remission in patients with stages C and D1 carcinoma, or 4) relapse rates and death rates in patients with stage D2 carcinoma. After scoring stage D2 disease according to our aggressiveness analysis system, we found that patients with less aggressive neoplasms displayed a qualitatively better response and more prolonged remission. These data and the absence of estrogenic effects confirm Buserelin as a favorable alternative to orchiectomy in the treatment of prostatic cancer. Additionally, the study demonstrates the importance of considering the heterogeneity of the aggressiveness of stage D2 disease in assessing the benefits of clinical trials in prostatic carcinoma.

Acid Phosphatase↗
PubMed1984

Advanced prostatic adenocarcinoma: biological aspects and effects of androgen deprivation achieved by castration or agonistic analogues of LHRH.

Twenty-nine patients with advanced prostatic adenocarcinoma were evaluated clinically, biochemically and radiologically and randomly assigned either to orchiectomy or to medical treatment. The latter consisted of the chronic administration of an LHRH agonistic analogue by parenteral and/or intranasal routes. Plasma testosterone levels fell to castrate values and remained so for as long as the follow-up lasted (24 months); estrogen levels fell as well. No change in basal cortisol, thyroxine or prolactin levels was noticed. A decrease in prostate size and improvement in prostatism occurred in all. Bone pain and radiology conventionally or by isotopic scanning, did not parallel the improvement seen in the primary disease locus. Similarly, the changes in alkaline phosphatase were minimal when compared to that of prostatic acid phosphatase. Both enzymes increased prior to or concurrently with relapse of the disease. The longest remission and survival was seen in patients with low enzyme levels, non diffuse bone metastases and high degree of tumor differentiation. Chronic use of agonistic analogues of LHRH induces effective castration in men with prostatic carcinoma and can replace orchiectomy or estrogen administration. The quantitative analysis of androgen receptors (AR) in subcellular fractions of tumor cells; the use of techniques to enhance the number of AR in the cytosol; and the determination of the type II/I regulatory subunit of protein kinase may be used to identify hormone independent clones and spare patients of unnecessary procedures.

Acid Phosphatase↗
PubMed1983

Gonadotropin-releasing hormone agonistic analogues in the treatment of advanced prostatic carcinoma.

Orchiectomy or chronic administration of the gonadotropin releasing hormone agonistic analogue D, Ser (TBU)6, des Gly-NH2(10) ethylamide (HOE 766) were employed as therapeutic maneuvers in 25 patients with advanced prostatic carcinoma. HOE 766 administration effectively suppressed plasma testosterone to castrate levels that persisted for as long as treatment continued. Surgical and medical castration resulted in a significant decrease in prostatic size; this became evident earlier for surgically than medically treated patients (P less than .05), but no difference existed after the third month of treatment. Symptoms and signs of prostatism improved in practically all the patients. Among patients with stage D2 disease, there was an improvement in five as far as bone radiological assessment was concerned. Alkaline phosphatase levels did not show appreciable changes in patients showing objective stable disease or partial response according to National Prostatic Cancer Project criteria. Radioimmunoassayable prostatic acid phosphatase levels became normal in two of two stage C, five of five stage D1, and eight of seventeen patients with stage D2 disease, a rise in prostatic acid phosphatase (PAP), in alkaline phosphatase, and deterioration in bone radiology were associated with clinical evidence of relapse; this occurred despite persistently low levels of plasma testosterone. Serum thyroxine, cortisol, and prolactin levels remained unchanged following orchiectomy or chronic administration of HOE 766. Practically all patients complained of hot flashes and experienced a decrease in libido and potency, but none developed gynecomastia or thromboembolic episodes. The data indicate that HOE 766 can be used safely as an alternative to castration or estrogens for the treatment of patients with androgen-dependent prostatic cancer.

Acid Phosphatase↗
PubMed1983

Transabdominal ultrasonography in the evaluation of patients with advanced prostatic carcinoma: effects of castration and of chronic administration of a gonadotropin releasing hormone agonistic analogue.

Twenty-two patients with advanced prostatic carcinoma were subjected either to orchiectomy (group I, n = 5) or to chronic administration of a gonadotropin releasing hormone agonistic analogue D, Ser (TBU)6, des Gly-NH2(10) LHRH nonapeptide (HOE 766) (group 2, n = 17). Plasma testosterone was similar in both groups prior to treatment (group 1: 636 +/- 129.29, group 2: 580.85 +/- 37.57; X +/- SE). The levels attained in group I were significantly lower (P less than .05) than those of group 2 through eight weeks of follow-up but were similar by the third month. Prostatic size (cm2) as estimated by transabdominal ultrasonography did not differ between the two groups prior to treatment (group 1: 23.6 +/- 3.35, group 2: 21.4 +/- 1.97; X +/- SE). Both therapies resulted in a decrease of prostatic size that was significantly more pronounced (P less than .05) in group I compared with group 2 by the first and third month; by the six month, there was no statistical difference in the prostatic size attained with either therapeutic modality. Persistent suppression of prostatic size was documented in all patients of group 2 chronically (up to 24 months) treated with HOE 766 even when there was evidence of uninhibited or progressive bony metastases. The above data 1) indicate the efficacy of the HOE 766 in inducing medical castration and prostatic shrinkage in advanced carcinoma of the prostate, 2) document the usefulness of transabdominal ultrasound in the follow-up of such patients, and 3) suggest a relationship between the rapidity of tumor shrinkage and Leydig cell suppression.

Buserelin↗
PubMed1983

Suppression of testicular steroidogenesis by the GnRH agonistic analogue Buserelin (HOE-766) in patients with prostatic cancer: studies in relation to dose and route of administration.

Forty-six patients with prostatic carcinoma received the gonadotropin releasing hormone agonistic analogue (GnRH-A) Buserelin at doses ranging from 0.05 to 1.5 mg subcutaneously and/or 0.4 to 1.2 mg intranasally (i.n.) daily for 12-120 weeks. An increase in plasma testosterone (T) was seen in 19% of patients on day 7 of therapy; with continuation of treatment plasma T as well as DHT and E2 levels fell by more than 50% within 2-4 weeks in those patients receiving greater than or equal to 50 micrograms s.c. and/or greater than or equal to 1 mg in daily dose. Persistently low plasma T levels (less than 1 ng/ml) were reached in 60% of patients receiving 50 micrograms s.c. in 89% of those treated with 1.2 mg i.n. and in 100% of patients who received initially 1.5 mg s.c. X 7 days followed by 1.2 mg i.n. daily. The above data indicate the importance of dose and route of administration in achieving significant suppression of plasma sex steroids in patients with prostate cancer in whom Buserelin can be used as an alternative to castration or estrogens.

Aged↗
PubMedDate not supplied

Surgical stress induces a marked and sustained increase of adrenal androgen secretion in postmenopausal women.

We analyzed the secretion of adrenal androgens in response to surgical stress in eight (8) postmenopausal women. ACTH, cortisol (F) and adrenal androgens, such as dehydroepiandrosterone (DHEA), delta 4-androstendione (delta 4-A), dehydroepiandrosterone sulfate (DHEA-S) and testosterone (T) were measured at 08:00 and 20:00 hr the day before and for three consecutive days after operation, as well as at 0, 15, 30, 60, 120 minutes during cholocystectomy. Basal levels of ACTH, F, DHEA, delta 4-A, DHEA-S and T were found within the normal range for this age group before surgery. During surgery the ACTH was significantly increased, reaching a peak value at 30 min after surgery initiation. F, DHEA and delta 4-A were significantly increased during and after surgery, returning to pre-surgery levels by the third day post-surgery. DHEA-S levels did not increase during surgery but was found significantly increased the day after surgery, returning to presurgical levels two days later. We conclude that surgical stress can induce adrenal androgen hypersecretion during and within the early days post-surgery. Because the adrenal androgens levels are declining and respond suboptimally to exogenous corticotropin releasing hormone (CRH) or ACTH bolus injection in aging women, it is conceivable that this remarkable response of adrenal androgens to surgical stress is probably of biological significance and conceivably mediated by a CRH/ACTH-independent mechanism.

Adrenal Glands↗
PubMedDate not supplied

Response of PC-3 prostate cancer cells to combination therapy using irradiation with glucocorticoids or doxorubicin.

OBJECTIVES: We evaluated the effects of irradiation, doxorubicin and dexamethasone on human PC-3 prostate cancer cells, investigating whether dexamethasone and doxorubicin can alter the irradiation cytotoxicity of PC-3 cells. METHODS: We used the human PC-3 prostate cancer cells, analyzing cell growth with trypan blue exclusion, indices of the cell cycle with flow cytometry and apoptosis with flow cytometry and analysis of DNA fragmentation on simple agarose gel. RESULTS: Doxorubicin (100 nM) arrested cell cycle at the G2/M phase, decreased cell growth and produced apoptosis of PC-3 cells in a time-dependent manner. Dexamethasone (100 nM) increased the distribution of PC-3 cells at G0/G1 phase in the cell cycle, exerting an inhibitory effect on the proliferation of PC-3 cells after 48 and 72 hr, but it did not produce apoptosis. Irradiation (4 Gy) initially arrested cells at the G2/M phase in the cell cycle (24 hr) which was gradually overcome and the PC-3 cells were shifted into G0/G1 phase or apoptosis after 48 and 72 hr. Irradiation decreased the PC-3 cell growth by 40-50% after 48 and 72 hr, respectively. Treatment with doxorubicin (100 nM) for 24, 48, and 72 hr after irradiation potentiated irradiation cytotoxicity of PC-3 cells. Dexamethasone treatment 24 hr before and 24, 48 and 72 hr after irradiation increased the number of surviving PC-3 cells and partially neutralized the irradiation effects on cell cycle. CONCLUSION: Doxorubicin potentiated while dexamethasone partially reversed the irradiation cytotoxicity of PC-3 cells. These data may be of clinical importance for the treatment of hormone refractory prostate cancer.

Cell Cycle↗
PubMedDate not supplied

Conversion of nested reverse-transcriptase polymerase chain reaction from positive to negative status at peripheral blood during androgen ablation therapy is associated with long progression-free survival in stage D2 prostate cancer patients.

BACKGROUND: Nested reverse-transcriptase polymerase chain reaction (nested rt-PCR) for the detection of mRNA of prostate specific antigen (PSA) and prostate specific membrane antigen (PSMA) in peripheral blood samples (PB) and bone marrow biopsies (BM) can assess the extraprostatic growth of prostate cells. MATERIALS AND METHODS: Nested rt-PCR for PSA and PSMA at PB and BM was performed (a) at diagnosis, (b) after 6 months from the initiation of combined androgen blockade [(CAB); triptorelin 3.75 mg, i.m., q28 days plus flutamide 250 mg, per os, tid] and, (c) at progression to androgen refractory stage in 28 patients with newly-diagnosed stage D2 prostate cancer. RESULTS: At diagnosis, all patients were found to be rt-PCR positive for PSA and PSMA at BM while 7 (25%) were rt-PCR negative for PSA and PSMA at PB. Nine out of 21 patients with rt-PCR-positive status have converted to rt-PCR-negative status at PB during CAB while they remained rt-PCR-positive at BM. The rt-PCR-negative status at PB during CAB was associated with progression-free survival >12 months (p=0.029). At progression to androgen refractory stage all but 2 patients were rt-PCR-positive at PB for PSA and PSMA, among them 3 who were rt-PCR-negative at diagnosis. CONCLUSION: Our data suggest that conversion to rt-PCR-negative status at PB for PSA and PSMA during objective clinical response to CAB is associated with long progression-free survival in stage D2 disease.

Androgen Antagonists↗