Expression analysis of delta-catenin and prostate-specific membrane antigen: Their potential as diagnostic markers for prostate cancer

The current approach to prostate cancer diagnosis has major limitations including the inability of prostate-specific antigen (PSA) assays to accurately differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the imprecision of transrectal ultrasound (TRUS) biopsy sampling. We have employed cDNA microarray screening to compare gene expression patterns in BPH and tumour samples to identify expression markers that may be useful in discriminating between these conditions. Screening of 3 individual cDNA arrays identified 8 genes with expression 3-fold greater in 6 tumour tissues than in 1 nontumour sample and I BPH sample. Real-time PCR was used to confirm the overexpression of these 8 genes and 12 genes selected from the literature against a panel of 17 tumours and I 1 BPH samples. Two genes, delta-catenin (delta-catenin; CTNND2) and prostate-specific membrane antigen (PSMA; FOLH1), were significantly overexpressed in prostate cancer compared to BPH. Prostate epithelial cells stained positively for S-catenin and PSMA in our prostate cancer tissues, whereas the majority of our BPH tissues were negative for both markers. Thus we have identified delta-catenin (not previously associated with prostatic adenocarcinoma) and confirmed the potential of PSMA as potential candidates for the diagnosis and management of prostate cancer. (C) 2002 Wiley-Liss. Inc.

Making decisions about treatment for localized prostate cancer

Objective To describe the decision-making processes used by men diagnosed with localized prostate cancer who were considering treatment. Patients and methods Men newly diagnosed with localized prostate cancer from outpatient urology clinics and urologist's private practices were approached before treatment. Their decision-making processes and information-seeking behaviour was assessed; demographic information was also obtained. Results Of 119 men approached, 108 (90%) were interviewed; 91% reported non-systematic decision processes, with deferral to the doctor, positive and negative recollections of others' cancer experiences, and the pre-existing belief that surgery is a better cancer treatment being most common. For systematic information processing the mean (SD, range) number of items considered was 4.19 (2.28, 0-11), with 57% of men considering four or fewer treatment/medical aspects of prostate cancer. Men most commonly considered cancer stage (59%), urinary incontinence (55%) and impotence (51%) after surgery, and low overall mortality (45%). Uncertainty about probabilities for cure was reported by 43% of men and fear of cancer spread by 37%. Men also described uncertainty about the probabilities of side-effects (27%), decisional uncertainty (25%) and anticipated decisional regret (18%). Overall, 73% of men sought information about prostate cancer from external sources, most commonly the Internet, followed by family and friends. Conclusions In general, men did not use information about medical treatments comprehensively or systematically when making treatment decisions, and their processing of medical information was biased by their previous beliefs about cancer and health. These findings have implications for the provision of informational and decisional support to men considering prostate cancer treatment.

Shoulder movement after breast cancer surgery: results of a randomised controlled study of postoperative physiotherapy

Breast screening programmes have facilitated more conservative approaches to the surgical and radiotherapy management of women diagnosed with breast cancer. This study investigated changes in shoulder movement after surgery for primary, operable breast cancer to determine the effect of elective physiotherapy intervention. Sixty-five women were randomly assigned to either the treatment (TG) or control group (CG) and assessments were completed preoperatively, at day 5 and at 1 month, 3, 6, 12 and 24 months postoperatively. The CG only received an exercise instruction booklet in comparison to the TG who received the Physiotherapy Management Care Plan (PMCP). Analyses of variance revealed that abduction returned to preoperative levels more quickly in the TG than in the CG. The TG women had 14degrees more abduction at 3 months and 7degrees at 24 months. Functional recovery at 1 month was greater in those randomised to the TG, with a dominant operated arm (OA) or receiving breast-conserving surgery. However, it was not possible to predict recovery over the 2 years postoperatively on the basis of an individual woman's recovery at 1 month postoperatively. The eventual recovery of abduction or flexion range of movement was not related to the dominance of the OA nor to the surgical procedure performed. The PMCP provided in the early postoperative period is effective in facilitating and maintaining the recovery of shoulder movement over the first 2 years after breast cancer surgery.

Physiotherapy after breast cancer surgery: results of a randomised controlled study to minimise lymphoedema

The development of secondary arm lymphoedema after the removal of axillary lymph nodes remains a potential problem for women with breast cancer. This study investigated the incidence of arm lymphoedema following axillary dissection to determine the effect of prospective monitoring and early physiotherapy intervention. Sixty-five women were randomly assigned to either the treatment (TG) or control group (CG) and assessments were made preoperatively, at day 5 and at 1, 3, 6, 12 and 24 months postoperatively. Three measurements were used for the detection of arm lymphoedema: arm circumferences (CIRC), arm volume (VOL) and multi-frequency bioimpedance (MFBIA). Clinically significant lymphoedema was confirmed by an increase of at least 200 ml from the preoperative difference between the two arms. Using this definition, the incidence of lymphoedema at 24 mo. was 21%, with a rate of 11% in the TG compared to 30% in the CG. The CIRC or MFBIA methods failed to detect lymphoedema in up to 50% of women who demonstrated an increase of at least 200 ml in the VOL of the operated arm compared to the unoperated arm. The physiotherapy intervention programme for the TG women included principles for lymphoedema risk minimisation and early management of this condition when it was identified. These strategies appear to reduce the development of secondary lymphoedema and alter its progression in comparison to the CG women. Monitoring of these women is continuing and will determine if these benefits are maintained over a longer period for women with early lymphoedema after breast cancer surgery.

Peroxisome proliferator-activated receptor alpha in the human breast cancer cell lines MCF-7 and MDA-MB-231

Peroxisome proliferator-activated receptor (PPAR) alpha is a ligand-activated transcription factor that has been linked with rodent hepatocarcinogenesis. It has been suggested that PPARalpha mRNA expression levels are an important determinant of rodent hepatic tumorigenicity. Previous work in rat mammary gland epithelial cells showed significantly increased PPARalpha mRNA expression in carcinomas, suggesting the possible role of this isoform in rodent mammary gland carcinogenesis. In this study we sought to determine whether PPARalpha is expressed and dynamically regulated in human breast cancer MCF-7 and MDA-MB-231 cells. Having established the presence of PPARalpha in both cell types, we then examined the consequence of PPARa activation, by its ligands Wy-14,643 and clofibrate, on proliferation. With real-time reverse transcriptase-polymerase chain reaction, we showed that PPARalpha mRNA was dynamically regulated in MDA-MB-231 cells and that PPARalpha activation significantly increased proliferation of the cell line. In contrast, PPARalpha expression in MCF-7 cells did not change with proliferation during culture and was present at significantly lower levels than in MDA-MB-231 cells. However, PPARalpha ligand activation still significantly increased the proliferation of MCF-7 cells. The promotion of proliferation in breast cancer cell lines following PPARalpha activation was in stark contrast to the effects of PPARgamma-activating ligands that decrease proliferation in human breast cancer cells. our results established the presence of PPARalpha in human breast cancer cell lines and showed for the first time that activation of PPARalpha in human breast cancer cells promoted proliferation. Hence, this pathway may be significant in mammary gland tumorigenesis. (C) 2002 Wiley-Liss, Inc.

Second primary oesophageal cancer following radiation for breast cancer

The management of 12 women who presented with a second primary oesophageal cancer following radiotherapy for breast cancer was reviewed. It was concluded that nine cases fitted the classical description of a radiation-induced malignancy. Most cases were successfully managed with combined modality therapy in spite of their previous radiotherapy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58 515 women with breast cancer and 95 067 women without the disease

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P

Estimation of total body water from bioelectrical impedance analysis in patients with pancreatic cancer - agreement between three methods of prediction

Introduction Bioelectrical impedance analysis (BIA) is a useful field measure to estimate total body water (TBW). No prediction formulae have been developed or validated against a reference method in patients with pancreatic cancer. The aim of this study was to assess the agreement between three prediction equations for the estimation of TBW in cachectic patients with pancreatic cancer. Methods Resistance was measured at frequencies of 50 and 200 kHz in 18 outpatients (10 males and eight females, age 70.2 +/- 11.8 years) with pancreatic cancer from two tertiary Australian hospitals. Three published prediction formulae were used to calculate TBW - TBWs developed in surgical patients, TBWca-uw and TBWca-nw developed in underweight and normal weight patients with end-stage cancer. Results There was no significant difference in the TBW estimated by the three prediction equations - TBWs 32.9 +/- 8.3 L, TBWca-nw 36.3 +/- 7.4 L, TBWca-uw 34.6 +/- 7.6 L. At a population level, there is agreement between prediction of TBW in patients with pancreatic cancer estimated from the three equations. The best combination of low bias and narrow limits of agreement was observed when TBW was estimated from the equation developed in the underweight cancer patients relative to the normal weight cancer patients. When no established BIA prediction equation exists, practitioners should utilize an equation developed in a population with similar critical characteristics such as diagnosis, weight loss, body mass index and/or age. Conclusions Further research is required to determine the accuracy of the BIA prediction technique against a reference method in patients with pancreatic cancer.

Monitoring and isolation of blood dendritic cells from apheresis products in healthy individuals: a platform for cancer immunotherapy

The fundamental role of dendritic cells (DC in initiating and directing the primary immune response is well established. Furthermore, it is now accepted that DC may be useful in new vaccination strategies for preventing certain malignant and infectious diseases. As blood DC (BDC physiology differs from that of the DC homologues generated in vitro from monocyte precursors, it is becoming more relevant to consider BDC for therapeutic interventions. Until recently, protocols for the isolation of BDC were laborious and inefficient; therefore, their use for investigative cancer immunotherapy is not widespread. In this study, we carefully documented BDC counts, yields and subsets during apheresis (Cobe Spectra), the initial and essential procedure in creating a BDC isolation platform for cancer immunotherapy. We established that an automated software package (Version 6,0 AutoPBPC) provides an operator-independent reliable source of motionuclear cells (MNC for BDC preparation. Further, we observed that BDC might be recovered in high yields, often greater than 100% relative to the number of circulating BDC predicted by blood volume. An average of 66 million (range, 17-179) BDC per 10-1 procedure were obtained, largely satisfying the needs for immunization. Higher yields were possible on total processed blood volumes of 151. BDC were not activated by the isolation procedure and, more importantly, both BDC subsets (CD11c(+)CD123(low) and CD11c(-)CD123(high)) were equally represented. Finally, we established that the apheresis product could be used for antibody-based BDC immunoselection and demonstrated that fully functional BDC can be obtained by this procedure. (C) 2002 Published by Elsevier Science B.V.