Peter Malone

The Androgen Receptor Is Significantly Associated with Vascular Endothelial Growth Factor and Hypoxia Sensing via Hypoxia-Inducible Factors HIF-1a, HIF-2a, and the Prolyl Hydroxylases in Human Prostate Cancer

Purpose: Hypoxia regulates key biological processes including angiogenesis via the transcription factor, hypoxia-inducible factor (HIF). In prostate cancer, angiogenesis is also influenced by androgens, and recent cell line studies suggest that this effect is partly mediated by HIF. The study aimed to assess whether a relationship exists in human prostate cancer between expression of the androgen receptor, HIFs, and the key angiogenesis factor, vascular endothelial growth factor (VEGF). Experimental Design: A tissue microarray comprised of 149 radical prostatectomy specimens was constructed. Semiquantitative immunohistochemical analysis was used to assess the expression of the androgen receptor, VEGF and HIF-1a and 2a, and their regulatory prolyl hydroxylase enzymes (PHD1, PHD2, and PHD3). Statistical analysis compared these factors with each other and with prostate-specific antigen relapse. Results: There was a significant correlation between HIF-1a and HIF-2a expression (P = 0.02), and with androgen receptor (P = 0.04 and P < 0.001, respectively) and VEGF expression (P = 0.05 and P < 0.001, respectively). VEGF was also significantly related to the androgen receptor (P = 0.05), whereas PHD2 was inversely related to HIF-2a expression. No significant association was shown between HIF-1a or HIF-2a and time to prostate-specific antigen recurrence (P = 0.20 and P = 0.94, respectively). Conclusions: These findings confirm the relationship between hypoxia and the androgen receptor in prostate cancer, and show for the first time, the role of HIF-2a in this disease process. They provide clinical evidence to support the recent cell line findings that androgens may regulate VEGF levels through the activation of HIF in androgen-sensitive tumors. Inhibition of both the HIF pathways may provide new therapeutic options in the management of this disease.

Prospective Study of Quantitation of Plasma DNA Levels in the Diagnosis of Malignant versus Benign Prostate Disease

Purpose: The aim of this study was to determine the potential of cell-free DNA levels as a diagnostic marker for prostate cancer, having first established the effect that blood sample processing has on this measurement. Experimental Design: A total of 152 blood samples were collected prospectively from patients before their prostate biopsy and 25 from men in two distinct control groups. Blood was processed to yield three components: one-spin plasma (n = 68), two-spin plasma (n = 152), and serum (n = 56) samples. Results: Having established the effect of sample preparation on the measured DNA level, the more reliable two-spin plasma sample was used to determine the relationship between DNA and the presence of prostate cancer. Those patients with cancer (n = 78) had a significantly higher level of DNA compared with the control groups (P < 0.0001 and P < 0.0001). However, DNA levels in patients with a benign biopsy (n = 74) were significantly higher than the 78 patients confirmed to have cancer (P = 0.02). Conclusions: We conclude that the sample type used in the quantitation of cell-free DNA has an effect on the level reported. Elevated levels are present in the two-spin plasma samples of patients with prostate cancer compared with healthy controls but are not of diagnostic value during the management of prostate cancer.

MALDI mass spectrometry in prostate cancer biomarker discovery

Matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry (MS) is a highly versatile and sensitive analytical technique, which is known for its soft ionisation of biomolecules such as peptides and proteins. Generally, MALDI MS analysis requires little sample preparation, and in some cases like MS profiling it can be automated through the use of robotic liquid-handling systems. For more than a decade now, MALDI MS has been extensively utilised in the search for biomarkers that could aid clinicians in diagnosis, prognosis, and treatment decision making. This review examines the various MALDI-based MS techniques like MS imaging, MS profiling and proteomics in-depth analysis where MALDI MS follows fractionation and separation methods such as gel electrophoresis, and how these have contributed to prostate cancer biomarker research. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.

The role of cell-free DNA size distribution in the management of prostate cancer

Cell-free DNA has been shown to have diagnostic potential in a number of malignant diseases. Recently, the integrity or size distribution of these fragments has also been identified as having possible diagnostic value. The current study explores the role of this novel parameter in the clinical diagnosis of prostate cancer. Plasma samples, collected prospectively from men undergoing investigation for prostate cancer, were used to obtain a cell-free DNA sample. Real-time PCR was used to quantify the level of cell-free DNA (ng/ml) and its size distribution (delta CD in each case. Sixty-one samples were collected from patients with prostate cancer and 62 from those with benign histology. Analysis failed to reveal a statistically significant relationship between either the level of cell-free DNA (p = 0.82) or its size distribution (p = 0.91) and the presence of cancer. These results demonstrate that cell-free DNA is unlikely to be of diagnostic value in the clinical management of this disease.

Expression of BNIP3 correlates with hypoxia-inducible factor (HIF)-1α, HIF-2α and the androgen receptor in prostate cancer and is regulated directly by hypoxia but not androgens in cell lines†

BNIP3 is a hypoxia‐induced protein involved in cell death and survival but its role in human tumors is unclear. This study investigated the role of BNIP3 in prostate cancer.

A seven-year follow-up of men following a benign prostate biopsy.

OBJECTIVES To determine the incidence and clinical relevance of newly diagnosed cases of prostate cancer in a group of men who had an elevated PSA and benign prostate biopsy 7 years previously. PATIENTS AND METHOD Patients under the age of 80 years with an elevated PSA who had had a benign prostate biopsy in the 12 months between March 1, 1994 and February 28, 1995 were studied. One hundred and sixty four patients with a mean age of 66.8 years (range 47-79 years) were identified. The mean PSA for this group was 10.3ng/ml (range 4.1-81ng/ml). One hundred and fifty nine of the 164 (97%) hospital records were available for review and all but 21 (12.8%) of the General Practitioners were contacted. RESULTS Eighteen (11%) of the original 164 patients were subsequently diagnosed with prostate cancer, 2 died from their disease. CONCLUSIONS In a population where the follow-up of patients with a benign biopsy was arranged on clinical grounds alone, 11% of the study group were diagnosed with prostate cancer during a seven-year follow-up. Although some of these cancers appear to be slow growing, most of those diagnosed in the initial follow-up period were deemed to be clinically significant and a small proportion progressed rapidly to metastases. All patients who have an elevated PSA, but benign biopsy, should undergo a period of PSA monitoring until it is clear that their PSA is not rising. We propose an initial intensive monitoring period to avoid missing those with clinically aggressive disease.

The results of real time brachytherapy for the management of low and intermediate risk prostate cancer in patients with prostate volumes up to 100 ml

Study Type – Therapy (case series)

Harold Horace Hopkins: a short biography.

Harold Horace Hopkins (Fig. 1) was born in 1918 in Leicester, UK. His father was a baker and he was the last of six children. Despite the hardships of the 1920s, he was encouraged to study by his mother, a socialist who had a deep-rooted respect for education. He obtained one of only two scholarships to Gateway, a local grammar school at the age of 11. His natural ability to master languages made his previous headmaster persuade him to drop the sciences. However, the new head recognized his remarkable mathematical ability and facilitated his return to the study of science. At the age of 18, he won a scholarship to University College, Leicester and he graduated in physics and mathematics three years later (Fig. 2).

Urethrocutaneous fistula: preserve the tract and turn it inside out: the PATIO repair

To describe a novel technique for repairing penile urethrocutaneous (UC) fistula, by dissecting out the fistula tract, but instead of excising it, to preserve it and turn it inside out (PATIO); this creates a flap valve inside the urethral lumen that prevents the ingress of urine allowing the fistula to heal.

Actinomycosis Associated with Pilonidal Sinus of the Penis

We report a case of actinomycosis associated with a penile pilonidal sinus. This association does not appear to have been described previously. We recommend the submission of biopsies of unusual lumps in the genital region (fresh biopsies for bacteriological examination and fixed biopsies for histomorphological assessment).