P D Abel

Phenotypic and genotypic characterization of commonly used human prostatic cell lines

Objective To investigate and catalogue systematically the phenotypic and genotypic characteristics of the commonly used prostatic cell lines using immunocytochemistry and polymerase chain reaction (PCR) of hypervariable sequences within the genome to provide a ‘fingerprint’ characteristic of each cell line.

Molecular and cellular biology of prostate cancer

Prostate cancer is an enigmatic disease. Although prostatic-intraepithelial neoplasia appears as early as the third decade and as many as 80% of 80 year old men have epithelial cells in their prostate that fit the morphological criteria for cancer, only about 10% of men will ever have the clinical disease and less than 3% will die from it. There have been no significant proven interventions which have altered the natural history of the disease since hormone down regulation was introduced in the 1940s and new research has been poorly supported. There is however an urgent need to develop new criteria to distinguish those patients with localised disease who will benefit from intervention from those that do not require it or who will have occult extra prostatic metastases. Similarly, there is an urgent need to develop new treatment for those in whom the disease is extra-prostatic and therefore incurable by conventional treatments. This review covers the latest developments in epidemiology, cellular and molecular biology including new areas such as ion channels in the field of prostate cancer.

Development of the fertility adjustment scale

OBJECTIVE To develop a standardized measure of psychological adjustment to infertility. DESIGN A cross-sectional two-group comparison study. SETTING Two specialized fertility clinics in large teaching hospitals. PATIENT(S) Fifty men and 50 women undergoing evaluation and/or treatment of fertility problems. INTERVENTION(S) The Fertility Adjustment Scale was administered with the Hospital Anxiety and Depression Scale as a measure of concurrent validity. MAIN OUTCOME MEASURE(S) Scores on the Fertility Adjustment Scale and the Hospital Anxiety and Depression Scale. RESULT(S) Scores on the Fertility Adjustment Scale were distributed normally. Split-half and internal consistency were high. A significant correlation with measures of mood, anxiety, and distress provided evidence of concurrent validity. CONCLUSION(S) Preliminary results suggest that this measure will be a useful tool in assessing psychological reactions to fertility problems and outcomes of treatment.

Distress in sub-fertile men: A longitudinal study

Abstract This study aims to describe the experiences of sub-fertile men and to document change over time. Patients attending a specialist male sub-fertility clinic completed questionnaires at clinic attendance and at 6 weeks and 18 months following consultation. Data were collected on mood, blame, life satisfaction, sexuality and expectations of pregnancy. Results suggest that these men are highly anxious. They blame themselves for their fertility problems and often feel less of a man because of them. Their satisfaction with life is much less than they perceive it would be if they had a baby. Expectations of life satisfaction and blame are both implicated in contributing to distress. Measures of mood, life satisfaction and self-blame are unchanged at 6 weeks and 18 months.

Markers of the metastatic phenotype in prostate cancer

Metastatic malignant disease is the single most common cause of treatment failure and subsequent mortality of most human malignancies, including prostate cancer. Presently, cells expressing the metastatic phenotype cannot be identified within a primary tumor population. Hence, accurate assessment of the likely behavior of an individual primary malignancy cannot be made at the time of diagnosis. The studies now reported have been aimed at identifying some of the features that may be associated with the metastatic phenotype of prostatic cancer. Insight into those factors that may be involved in prostate cancer metastasis has been gained from a variety of experimental approaches as well as study of intact human prostate cancers.

Effect of fish oil on cancer cachexia and host liver metabolism in rats with prostate tumors

The aim of this study was to investigate whether tumor-induced cachexia and aberrations in host liver metabolism, induced by the MAT-LyLu variant of the Dunning prostate tumor, could be prevented by ω3 fatty acids from fish oil. On day 0, adult Copenhagen-Fisher rats fed normal chowad libitum were inoculated with 106 MAT-LyLu cells (n=14) or saline (n=9). On day 7, when tumors were palpable, four tumor-bearing (TB) and four nontumorbearing (NTB) rats were put on isocaloric diets with 50% of total energy as fish oil. The introduction of fish oil-enriched diets caused a reduction in energy intake to less than half of the energy intake by animals fed normal diets during days 7–14 (difference by dietary group: NTB,P<0.001; TB,P<0.001). During days 14–21, energy intake in fish oil-fed animals returned to approximately 75% of energy intake by animals fed normal diets (difference by dietary group: NTB,P<0.003; TB,P=0.001). Carcass weight of animals on day 21, when the study was terminated, was significantly related to initial weight (P=0.05) and mean food intake during the study (P=0.01). When data were adjusted for these variables using analysis of covariance, with NTB animals on normal diets being the reference group, significant loss of carcass weight was observed in TB animals on normal diets only (mean ±SEM 58±10 g loss,P<0.001), but not in TB animals on fish oil diets (8±18 g loss,P=0.67). This positive effect of fish oil diets on carcass weight in TB animals was statistically significant (50±19 g,P<0.02), implicating that the fish oil enriched diet inhibited tumor-induced weight loss by more than 85%. No effect of fish oil diets on tumor growth was detected. In all TB animals, regardless of diet, hepatic [Pi]/adenosine triphosphate] ratios measured by31P magnetic resonance spectroscopy (MRS)in vivo andin vitro were elevated, and absolute concentrations of phosphocholine, glycerophosphocho-line, glycerophosphoethanolamine and glucose-6-phosphate as determined by31P MRSin vitro were reduced. Ultrastructural studies of liver tissue revealed increased numbers of mitochondria and increased amounts of endoplasmic reticulum in the host liver of TB animals, without differences between dietary group. In conclusion, fish oil supplementation partially inhibited MAT-LyLu tumor-induced cachexia, but did not prevent the majority of31P MRS-detectable alterations in host liver metabolism.

Androgen-Independent Prostate Cancer: Potential Role of Androgen and ErbB Receptor Signal Transduction Crosstalk

In prostate cancer (PC), increasing evidence suggests that androgen receptor (AR) signalling is functional under conditions of maximal androgen blockade. PC cells survive and proliferate in the altered hormonal environment possibly by interactions between growth factor-activated pathways and AR signalling. The present review article summarizes the current evidence of this crosstalk and focuses on the interactions among the ErbB receptor network, its downstream pathways, and the AR. The potential role of this crosstalk in the development of androgen independence and in relation to antiandrogen therapy is discussed. Such interactions provide insight into possible complementary or additional strategies in the management of PC.

Correlation between androgen receptor expression and FGF8 mRNA levels in patients with prostate cancer and benign prostatic hypertrophy.

AIM: To investigate the correlation between androgen receptor expression and fibroblast growth factor 8 (FGF8) mRNA levels. METHODS: 39 human prostate cancers and 14 benign prostatic hypertrophy specimens were examined immunohistochemically for androgen receptor expression and by in situ hybridisation and reverse transcription polymerase chain reaction for FGF8 expression. RESULTS: In 39 tumours there was a statistically significant negative correlation between tumour grade and FGF8 expression and a positive correlation between FGF8 and androgen receptor expression. All 14 benign hypertrophy specimens expressed moderate to high levels of FGF8 and androgen receptor. CONCLUSIONS: Loss of FGF8 may be a factor involved in the development of prostatic cancer.

Second messenger up‐regulation of androgen receptor gene transcription is absent in androgen insensitive human prostatic carcinoma cell lines, PC‐3 and DU‐145

A theoretical pathway of transcriptional regulation of the androgen receptor (AR) gene is via a cAMP response element (CRE) present in its promoter region (−508 to −501). After 20 h of stimulation with 8‐bromo‐cAMP, AR mRNA was upregulated in LNCaP but not in either PC‐3 or DU‐145 cell lines. We have demonstrated that the level of CRE binding protein (CREB) was the same in all cell lines and that the putative AR‐CRE forms specific and competable protein interactions with CREB. The ability to regulate AR gene transcription via the second messenger pathway is lost in the PC‐3 and DU‐145 cell lines. This may be an important primary mechanism of androgen insensitivity in prostate cancer.

Psychological Distress before and Immediately after Attendance at a Male Sub-Fertility Clinic

Where treatment options are limited, the role of clinical consultation in providing information and support becomes more important. This study examines the immediate impact of medical consultation on male sub-fertility clinic attenders anxiety, depression, self-blame, information appraisal and perceptions of future fertility. Data were collected pre- and immediately post-consultation. Clinical information and consultation details were recorded. Results showed that anxiety levels were high before consultation. Following consultation anxiety and self-blame were both reduced while depression increased. Despite information about poor prognosis being given during consultation, participants remained overly optimistic about their chances of achieving a pregnancy. It appears that the consultation has a distinct psychological impact and possible mechanisms underlying this are discussed.