These results suggest that further studies of the effect of newer generation bisphosphonates on BPFS in men with metastatic prostate cancer are warranted.

The aims of this study were to examine the anti-proliferative effects of different concentrations of a commercial preparation of conjugated linoleic acids (CLA) mixture of isomers [cis-9, trans-11 CLA (c9,t11 CLA): trans-10, cis-12 CLA (50:50)] and their constituent isomers on PC-3, a human prostatic carcinoma cell line, and to study their effects on gene expression (mRNA and protein levels) of different enzymes and oncoproteins involved in oncogenesis and progression of prostate cancer. This includes pathways for arachidonic acid metabolism [cyclooxygenase 1 (COX-1), 2 (COX-2) and 5-lipoxygenase (5-LOX)], apoptosis (bcl-2) and cell cycle control (p21(WAF/Cip1)). Our results indicate a significant decrease in PC-3 proliferation elicited by CLA, although with high variability between isomers. The trans-10, cis-12 CLA was the most effective isomer (55% inhibition). This isomer was also able to decrease bcl-2 gene expression and to increase p21(WAF1/Cip1) mRNA levels (60% increase at highest concentration). In contrast, cis-9, trans-11 had no effect on these proteins but had a clear effect on 5-LOX expression and to a lesser degree on COX-2 protein level isomers. In conclusion, the anti-proliferative effects on PC-3 of CLA mixture and their constituent isomers are not equivalent, due to the different pathways involved for individual isomers. Trans-10, cis-12 seems to work preferentially through modulation of apoptosis and cell cycle control, while c9,t11 CLA isomer affects arachidonic acid metabolism.

Concentrations of fatty acids (FA) in prostatic tissue of patients with either benign or malignant prostatic disease have previously been shown to be significantly different. In particular, there was a significant reduction in arachidonic acid (AA, C20:4n-6) and docosapentaenoic acid (DPA, C22:5n-6) concentrations in malignant prostatic tissue (PCa) phospholipids (PL). It was suggested that the decreased AA concentration in PCa may be due to its increased metabolism via the cyclooxygenase (CO) and/or lipoxygenase (LO) pathways to produce eicosanoids such as prostaglandins (PGs) and/or leukotrienes (LTs) rather than an impairment in desaturase activity in situ. The eicosanoid production in benign prostatic tissue (BPH) and PCa was determined using [3H]AA. The only eicosanoid produced in significant amounts by either tissue was PGE2 and PCa converted radiolabelled AA to PGE2 at an almost 10-fold higher rate than BPH. PGE2 production from [3H]AA by PCa was investigated in the presence of oleic acid (OA, C18:1n-9), eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosatetraynoic acid (ETYA) and ketoprofen (KPN) respectively. OA was found to be the most effective inhibitor of PGE2 production by PCa compared with DHA, EPA, ETYA and KPN, while DGLA was the least effective. Diacylglycerol (DAG) formation from labelled AA by PCa was about 4-fold greater than in BPH. Such high levels of DAG may be a means of promoting tumorigenesis through activation of protein kinase C as found with phorbol esters which can be regarded as DAG analogues.

There is increasing evidence that essential fatty acids (EFA) may have a role to play in the aetiology of some types of cancer although their precise mode of action is unknown. Differences in the metabolism of EFA between patients with benign or malignant prostatic disease may help to elucidate their role in the latter. We have, therefore, measured the concentration of the essential fatty acids, and their metabolites, in the phospholipid fractions of both plasma and tissue, in patients with either benign or malignant prostatic disease. Comparison of the median concentration of fatty acids in each group (n = 10) revealed significant differences between them. The phospholipid component of total lipid was greater in malignant (P less than 0.04, unpaired t-test) than in benign tissue. The concentrations of linoleic acid (LA) and di-homo gamma linolenic acid (DGLA) in plasma and tissue were not different between the two groups of patients, but a significant reduction in arachidonic acid (ARA) (P less than 0.002, Mann-Whitney U-test) and docosapentaenoic acid (DPA) (P = 0.009) concentrations was observed in malignant tissue as compared to benign. Patients with malignant prostatic disease also had a significantly higher concentration of oleic acid in phospholipids from both plasma and prostatic tissue. The stearic to oleic acid ratio was similar in plasma but was significantly reduced in malignant tissue (P = 0.006). We suggest that the decreased arachidonic acid concentration in malignant tissue may be due to its increased metabolism, via the lipoxygenase and cyclooxygenase pathways to produce higher concentrations of eicosanoids, rather than an impairment in desaturase activity in situ.

Blood transfusion in the perioperative period has been reported to have a detrimental effect on survival in many types of cancer. Other studies have failed to confirm this. We have examined retrospectively the records of 246 patients with prostatic carcinoma who underwent transurethral resection of the prostate (TURP) in Aberdeen Royal Infirmary between 1977 and 1982. Bilateral orchiectomy (BLO) was performed in 193 patients. Of these patients, 71 of 246 (29 per cent) received perioperative blood transfusion. After controlling for differences due to a number of variables, transfusion of non-autologous blood was shown to be associated with a significant negative effect on survival. Perioperative transfusion of non-autologous blood should be avoided in patients with malignancy, unless there are clear overriding clinical indications. Prospective trials are needed urgently.