Conjugated linoleic acids (CLAs) decrease prostate cancer cell proliferation: different molecular mechanisms for cis-9, trans-11 and trans-10, cis-12 isomers.

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.

Infectious mononucleosis.

Infectious mononucleosis in its classical presentation consists of the clinical triad of fever, pharyngitis, and cervical lymphadenopathy. The majority of cases are caused by primary infection with the Epstein-Barr virus (EBV). There is, however, a wide clinical spectrum of disease manifestations, including pulmonary, hematologic, and neurologic findings and a series of associated laboratory abnormalities, such as lymphocytosis, heterophile antibodies, and anti-EBV antibodies. The disease is typically self-limited and treated with supportive therapy only. Rarely, serious complications such as airway obstruction, severe thrombocytopenia, or severe hemolytic anemia can occur. Infectious mononucleosis does not cause congenital anomalies, and pregnant women are not at increased risk of serious complications resulting from the disorder.

Selective arterial embolization in the treatment of arterial priapism.

Arterial or 'high-flow' priapism is a rare complication of penile or perineal trauma. The case is reported of a patient with a more than 2-week history of priapism who was successfully treated by selective arterial embolization, with maintenance of potency.

Functional comparison of bovine, murine, and human beta2-microglobulin: interactions with murine MHC I molecules.

Fetal calf serum is a well known source of bovine beta2-microglobulin (beta2m) which can exchange with endogenous beta2m from, as well as promote peptide binding to, class I major histocompatibility (MHC I) molecules on cells cultured in vitro. Recombinant bovine beta2m was expressed and purified for direct functional comparison to human and murine beta2m for interactions with murine MHC I molecules H-2Kb, Db, Kd, Ld, and Dd. Bovine and human beta2m were equivalent in stabilizing MHC I heavy chains and facilitating peptide loading, suggesting similar affinities for murine MHC I heavy chains. The activity of murine beta2m was significantly weaker, consistent with previous work that demonstrated the lower affinity of murine human beta2m for murine heavy chains compared to human beta2m. Analysis of bovine beta2m in fetal calf serum revealed ten-fold higher concentrations than in adult bovine serum, levels shown to significantly affect MHC I stability and peptide loading. The ramifications for the study of MHC I molecules from cells in culture and the evolutionary implications of the higher affinity interactions of human and bovine beta2m are discussed.

Arachidonic acid metabolism in benign and malignant prostatic tissue in vitro: effects of fatty acids and cyclooxygenase inhibitors.

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.

Essential fatty acid distribution in the plasma and tissue phospholipids of patients with benign and malignant prostatic disease.

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.

Abnormalities of essential fatty acid distribution in the plasma phospholipids of patients with bladder cancer.

We have examined the composition of the essential fatty acids in the plasma phospholipid fractions of 98 patients with histologically proven bladder cancer. These patients were attending hospital for regular follow-up by check cystoscopy. Patients were divided into two groups, depending on the cystoscopic findings, of either active (tumour recurrence seen) or inactive (no evidence of tumour recurrence) disease. Compared with a normal population, the plasma levels of most of the fatty acids, including arachidonic acid, were significantly lower in the 98 cancer patients (P less than 0.001, t-test). We were unable, however, to demonstrate any significant differences (Mann-Whitney U-test) between the active and inactive disease groups. Plasma levels of the essential fatty acids are abnormal in patients with bladder cancer; they do not help, however, to distinguish those patients with active disease from those with inactive disease. This may arise because the deficit in essential fatty acids we have demonstrated is a predisposing factor for the development of bladder cancer rather than a metabolic consequence of the tumour. Further studies are needed to establish the possible clinical role of measurement of essential fatty acids in patients with bladder carcinoma.

Epidermal growth factor receptor, nuclear proliferation antigen and interleukin-2 receptor expression in prostatic cancer.

Immunohistochemical methods have been used to study the relationship between epidermal growth factor receptor (EGF-R), T-lymphocyte infiltrate, interleukin-2 receptor (IL-2R) expression and the degree of cellular proliferation using the monoclonal antibody Ki-67. EGF-R was detected in only 2 out of the 19 malignant biopsies, but was present in the benign elements of all twelve of the heterogeneous biopsies examined. The level of immune response, as indicated by the percentage of T cells expressing the IL-2R, did not correlate with the expression of the nuclear proliferation antigen determined by Ki-67 monoclonal antibody staining intensity. This study fails to show a statistically significant correlation between the expression of EGF-R or nuclear proliferation antigen and the degree of the cell mediated immune response to the tumour.

Blood transfusion and survival following surgery for prostatic carcinoma.

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.

Androgen receptors--a method to measure functional behaviour in human prostatic cancer.

Androgen receptors were measured in soluble and nuclear fractions of tissues obtained from 25 patients. A method using mibolerone, a synthetic androgen, as a ligand is described. This method, which includes the presence of excess ORG 2058 to eliminate interaction with progesterone receptors, gives a reliable determination of androgen receptor content and has been used to predict response to hormonal treatment. However, the results suggest that the presence of functional receptor is not, in itself, a sufficient index of hormonal dependence of the tumour.

Urothelial tumours of the upper urinary tract.

We present a retrospective 10 year analysis of 76 patients with urothelial tumours of the upper urinary tract. Patients older than 65 years, and female patients, presented with more advanced stages and had a worse prognosis. The grade and stage of the tumour has the greatest impact on survival. No conclusions can be drawn on the efficacy of various types of surgery, but simple nephrectomy gave a 5-year survival of 68%, with a stump recurrence rate of 15%. We observed that patients with urothelial tumours had 4 fold increased chance of developing gastrointestinal cancer.

The cost of bilateral orchiectomy as a treatment for prostatic carcinoma.

Advanced prostatic carcinoma may be treated by a variety of methods of hormonal manipulation which affect the production of the male hormones. This can be achieved by surgical means, usually bilateral orchiectomy, or medically, by a number of drugs. One advantage of surgical over medical castration is that it is a once-only procedure. Another factor, which could be considered a major advantage, is the low cost of the surgical procedure. This report outlines the costs involved in treating prostatic carcinoma by surgical castration and compares them with the costs of some forms of medical treatment.

Ketoconazole as primary treatment of prostatic cancer.

Ketoconazole 400 mg 8-hourly was used as primary hormonal treatment in 12 patients with advanced prostatic carcinoma. Four patients were withdrawn because of side effects and 1 died. The 7 patients who tolerated the drug had a reduction in testosterone and adrenal androgens. Six patients were fully evaluable. There was one partial response with complete remission of symptoms. Two patients enjoyed a subjective response and 3 showed no response. Ketoconazole had an effective biochemical action but the side effects seen in this study severely limit its usefulness. Ketoconazole has now been withdrawn as a treatment for prostatic cancer. However, less toxic derivatives might prove a useful addition to the drugs available to treat this condition.

Short-term cephradine prophylaxis in elective transurethral prostatectomy.

A prospective randomized trial was conducted to assess the value of short-term antibiotic prophylaxis in elective transurethral resection of the prostate. Two hundred patients were randomized to receive 1.5g cephradine intramuscularly preoperatively and 1g cephradine orally before removal of the urethral catheter or to receive no antibiotic prophylaxis. Fifty-eight patients were excluded because of occult neoplasm or protocol violation. There was no difference in time to removal of catheter, incidence of pyrexial episodes, length of hospital stay or minor complication rate between the two groups. We conclude that a short-term antibiotic regime is of no value in the elective patient with sterile urine.

Blood transfusion and survival following nephrectomy for carcinoma of kidney.

Blood transfusion has been reported adversely to affect survival following surgery for a number of malignancies. We have examined retrospectively the records of 126 patients undergoing nephrectomy for renal carcinoma and established that 80 (63%) were transfused. Comparison of the two groups of patients, after controlling for differences in age, sex, tumour stage and haemoglobin level, showed that the transfused patients did not necessarily have poorer survival. In this study, peri-operative transfusion did not appear to have an adverse effect on long-term survival following surgery for renal cancer.