Pretreatment p53 immunoreactivity does not infer radioresistance in prostate cancer patients.

Purpose: To test, in a clinical context, the hypothesis that p53 aberrations, assessed by immunoreactivity, are related to radioresistance as suggested by several experimental studies.

Methods And Materials: Sixty patients with prostate cancer who underwent transurethral resection of the prostate or biopsy prior to definitive external beam therapy were retrospectively identified. The endpoint in the study was cancer specific survival.

Effects of endothelin-1 on the rat testicular vasculature.

Endothelin-1 (ET-1), a well-known vasoconstrictor substance, is present in the testis but its functional role is unknown. The present study was undertaken to elucidate whether ET-1 may influence testicular blood flow. ET-1 (0.

Bcl-2 immunoreactivity in prostate tumorigenesis in relation to prostatic intraepithelial neoplasia, grade, hormonal status, metastatic growth and survival.

The Bcl-2 protein prolongs cell survival by overriding apoptosis. To explore the role of Bcl-2 in prostate tumorigenesis, immunoreactivity for Bcl-2 was examined in untreated and androgen-deprived tumours and lymph node metastasis. Following the transurethral resection, 150 untreated patients were maintained under surveillance until death or for a minimum of 11 years, and castration was performed at symptomatic progression.

p53 immunoreactivity as prognostic marker for cancer-specific survival in prostate cancer.

Objectives: The objective of this study was to evaluate the role of p53 immunoreactivity as a prognostic marker in prostate cancer.

Methods: The nuclear accumulation of the aberrant p53 protein was determined by immunohisto-chemistry on surgical specimens and related to stage, grade and cancer-specific survival in 186 prostate cancer patients treated with transurethral resection and subsequent surveillance.

Results: There was a significant correlation between p53 staining and grade: 2% of the highly differentiated, 8% of intermediately, and 21% of the poorly differentiated tumors stained.

5-Hydroxytryptamine--a local regulator of testicular blood flow and vasomotion in rats.

The effects of 5-hydroxytryptamine (5-HT), 5-HT2 receptor antagonists (ritanserin and ketanserin), histamine and substance 48/80 on testicular blood flow and microcirculation were studied in adult rats. The substances were administered by topical application on the testicular surface and by intratesticular injections, and blood flow was measured by radioactive microspheres and with a laser Doppler flowmeter. Blood flow was decreased by 5-HT in a dose-dependent manner and vasomotion in the testis was inhibited, suggesting that it could be involved in the physiological regulation of the testicular vasculature.

Expression of multiple forms of brain cytochrome P450.

Multiple forms of cytochrome P450 (P450) in brain tissue have been demonstrated to be expressible in brain tissue using polymerase chain reaction (PCR) techniques, Northern blotting, hydroxylation activity assessment and cloning approaches. The antidepressant drug imipramine is metabolized by brain microsomes to multiple products by pathways inhibitable by quinidine, 7,8-benzoflavone, and ketoconazole, well-known inhibitors of P450-catalyzed reactions. Moreover, PCR studies revealed that a number of P450s are expressible in brain tissue and in glioma C6 cells.

Differentiation-stage specific expression of oncoprotein 18 in human and rat prostatic adenocarcinoma.

Oncoprotein 18 (Op18) is an intracellular phosphoprotein that has been shown to be overexpression in a number of human malignancies. In the present report we have studied the pattern of Op18 expression on normal, hyperplastic, and malignant prostatic tissue as well as in rat prostatic tumor lines. One of the objectives of the present work was to establish whether the level of Op18 expression can be used as a prognostic marker in human prostatic adenocarcinoma.

Castration plus oestrogen treatment induces but castration alone suppresses epithelial cell apoptosis in an androgen-sensitive rat prostatic adenocarcinoma.

The positive effect of castration in prostatic cancer patients is considered to be related to the induction of apoptosis in androgen-dependent tumour cells. However, castration apparently does not induce apoptosis in the highly differentiated, androgen-sensitive Dunning R3327PAP rat prostatic adenocarcinoma. To elucidate potential mechanisms of apoptotic induction in this tumour model, rats with subcutaneously implanted tumours were treated with vehicle (I), castration+vehicle (C) or castration + 50 micrograms of oestradiol benzoate per day s.

Castration therapy rapidly induces apoptosis in a minority and decreases cell proliferation in a majority of human prostatic tumors.

Major differences in the long-term clinical response to castration therapy of prostatic carcinoma suggests intertumoral differences in cellular response and defines a need for identification of patients with an eventually positive outcome as well as those in need of additional treatment. Using morphometry, monoclonal antibodies against Bcl-2, c-myc, Ki-67, and p53 proteins, and an in situ method to visualize apoptotic cells, we examined the short-term response of prostatic tumors to castration in core biopsies from 18 prostatic cancer patients taken the day before and 7 days after castration. At the histological level, 3 tumors seemed practically unaffected by castration.

Tobacco smoke disrupts testicular microcirculation in the rat.

Anaesthetized adult rats were exposed repeatedly to cigarette smoke for 2 s interspersed with exposure to fresh air for either 10, 15 or 30 s using a smoking apparatus. The acute effects of this treatment on testicular microcirculation were studied using laser Doppler flowmetry. Peripheral tissue O2 saturation was measured continuously in the foot during the experiment.

Effect of testicular temperature on vasomotion and blood flow.

Vasomotion (spontaneous rhythmic variations in blood flow) has been demonstrated in the parenchyma of the testes of anaesthetized rats, using a laser-Doppler flow probe. As the temperature of the testis was increased, mean blood flow showed no change, but the frequency of vasomotion increased and its amplitude decreased, until vasomotion disappeared between 36 degrees C and 42 degrees C. As the testis was then cooled, vasomotion reappeared, and increased in amplitude and decreased in frequency as the temperature fell.

DNA fragmentation induced by the antimitotic drug estramustine in malignant rat glioma but not in normal brain--suggesting an apoptotic cell death.

Estramustine, a combination of 17 beta-oestradiol and nor-nitrogen mustard, has been shown to be metabolised and to induce specific antiproliferative effects in malignant glioma, including arrest of glioma cells in the G2/M phase of the cell cycle, damage to cell membranes and DNA and induction of free oxygen radicals. To evaluate further the effects of estramustine, an in vivo rat glioma model using inbred BD-IX rats and the BT4C cell line was set up. In order to detect cells with fragmented DNA, tumour and brain specimens were, following fixation for histological examination, processed for in situ end labelling (ISEL) with biotin-labelled nucleotides.

Localization and quantity of hyaluronan in urogenital organs of male and female rats.

The histochemical distribution of hyaluronan was analysed in various urogenital organs of male and female (non-pregnant and pregnant) rats by use of a hyaluronan-binding protein and avidin biotin/peroxidase staining. Microwave-aided fixation was used to preserve the extracellular location of hyaluronan. The concentrations of hyaluronan in the different tissues were measured with a highly sensitive radio-assay.

Effects of estrogens and progestogens on the membrane permeability and growth of human prostatic carcinoma cells (PC-3) in vitro.

The effects of estrogens and progestogens in the management of prostatic adenocarcinoma are generally believed to be related to their suppressive effect on the hypothalamic-pituitary-testicular axis, but other mechanisms have also been suggested. The present study was designed to investigate if an androgen-insensitive human prostatic cancer cell line (PC-3) is sensitive to estrogens or progestogens and to elucidate possible mechanisms of action. Both estrogens and progestogens in high doses (10(-5) M) suppressed tumor cell growth.

Epidermal growth factor receptor content in rat prostatic adenocarcinoma: effects of endocrine treatment.

Epidermal growth factor receptor (EGF-R) was studied in Dunning prostatic cancer models using competitive binding assays and solution hybridization assay. EGF-R-binding capacity and mRNA were demonstrated in a hormone-sensitive R3327 prostatic tumor from both control and castrated animals while no such activity was found in the hormone-independent AT-1 tumors. Castration induced no quantitative changes in the EGF-R.

The phenotype of a "Cdc2 kinase target site-deficient" mutant of oncoprotein 18 reveals a role of this protein in cell cycle control.

Oncoprotein 18 (Op18) is a cytosolic protein that is expressed in all proliferating cells. This phosphoprotein is up-regulated in a variety of human neoplasm, and phosphorylation of its two Cdc2 kinase target sites, Ser-25 and Ser-38, fluctuates dramatically during the cell cycle. We have investigated the potential role of the Cdc2 kinase-mediated phosphorylation of these two sites by expressing a "Cdc2 kinase target site-deficient" mutant of Op18 (Op18-S25,38A), and analyzed the phenotype on the level of cell cycle regulation.

Localization of hormone-sensitive lipase to rat Sertoli cells and its expression in developing and degenerating testes.

Using in situ hybridization, hormone-sensitive lipase was found to be expressed in a stage-dependent manner in Sertoli cells of rat testis. No expression was found in Leydig cells but expression in spermatids could not be excluded. These results suggest a role for hormone-sensitive lipase in the metabolism of lipid droplets in Sertoli cells, in contrast to its previously proposed function in steroid biosynthesis.

A new method for the relative quantification of rCBF examined by 99Tcm-HMPAO SPECT.

A new method for the analysis of regional cerebral blood flow (rCBF) studies, the 'Min-Max' method, was compared with the conventional method, the 'Average' method. Regional CBF was examined by single photon emission computed tomography (SPECT) using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO). The two methods were used to quantify the rCBF in a population of patients with various dementia disorders, and in healthy controls.

Quantitative SPECT cisternography in normal pressure hydrocephalus.

Twenty-one patients with normal pressure hydrocephalus (NPH), 8 patients with various brain diseases with an element of hydrocephalus, and 7 patients with miscellaneous dementia disorders were investigated with quantitative radionuclide cisternography (RC) using single photon emission computerized tomography (SPECT). The total intracranial counts as well as the counts in the lateral and third ventricles were measured. All 15 NPH patients accessible for postoperative examination were improved after shunt surgery.

Prostatic tumor regrowth after initially successful castration therapy may be related to a decreased apoptotic cell death rate.

Castration of rats transplanted with the androgen-sensitive Dunning R3327-PAP prostatic tumor results initially in a reduction of tumor growth, but after some time, some of the tumors start to grow again. The relapsed, androgen-insensitive PAP tumor shows a dedifferentiated morphology. In the present study, we examined whether this androgen-independent tumor regrowth was due to an increased cell proliferation rate or to a reduction of the number of tumor cells dying by apoptosis.

Estrogen treatment postpones the castration-induced dedifferentiation of Dunning R3327-PAP prostatic adenocarcinoma.

Male Copenhagen x Fisher F1 rats, transplanted with the androgen-sensitive Dunning R3327 PAP rat prostatic adenocarcinoma, were castrated when tumor volumes were approximately 1300 mm3. The rats were thereafter followed with measurements of tumor volume. Castration stopped tumor growth, but some of the tumors started to regrow after 7-36 weeks.

Castration induces apoptosis in the ventral prostate but not in an androgen-sensitive prostatic adenocarcinoma in the rat.

Apoptosis in the androgen-sensitive Dunning R3327 PAP prostatic adenocarcinoma was studied during the post castration period of 14 days and compared with the ventral prostate. The mRNA expression of testosterone repressed prostatic message-2 and tissue-type plasminogen activator in the Dunning tumor and in the ventral prostate was analyzed by Northern blot experiments and immunohistochemical procedures. The degree of endonuclease-degraded genomic DNA was examined by gel electrophoresis.

The influence of respiration induced motion of the kidneys on the accuracy of radiotherapy treatment planning, a magnetic resonance imaging study.

An MRI study has been performed to determine the respiration induced motion of the kidneys. Under normal respiration conditions displacements of the left and right kidney varied from 2 to 24 mm and 4 to 35 mm, respectively. Under forced respiration conditions displacements were larger and ranged from 10 to 66 mm for the left kidney and 10 to 86 mm for the right kidney.