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1.
Scand J Urol Nephrol ; 43(2): 104-8, 2009.
Article in English | MEDLINE | ID: mdl-18979375

ABSTRACT

OBJECTIVE: Antiprostasome antibodies (APAs) have been identified in serum of patients with prostate cancer and have been proposed as a new marker for metastatic disease. This study reassesses the role of APAs as a prognostic indicator for prostate cancer. MATERIAL AND METHODS: Serum samples from healthy controls (n=7) and patients with prostate cancer (n=22) were assayed for APAs using an enzyme-linked immunosorbent assay. RESULTS: APAs in varying amounts were present in healthy individuals as well as in men with prostate cancer. Higher levels were inversely and significantly associated with prostate-specific antigen (PSA). No significant relationships were noted between APA levels and other parameters such as age, time since diagnosis, metastatic status, Gleason histological score and hormonal treatment. CONCLUSIONS: The presence of serum APA is unlikely to be a strong prognostic indictor for prostate cancer on an individual basis as false positives will occur. However, such immune reactions which may be associated with PSA in cancer patients are in any case of interest in both the biology of prostate cancer and male fertility. The source of prostasomal antigen may be of critical importance to the outcome of the assay. However, immune reactions to prostasomes may be of considerable interest and warrant continued investigation.


Subject(s)
Antibodies, Neoplasm/blood , Autoantibodies/blood , Prostatic Neoplasms/immunology , Secretory Vesicles/immunology , Adult , Female , Humans , Male , Prognosis
2.
Semin Thromb Hemost ; 33(1): 3-12, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17253184

ABSTRACT

Human semen spontaneously coagulates and subsequently liquefies following ejaculation. The exact reasons for this phenomenon are not entirely understood. Research has resulted in the discovery of several seminal proteins that are already known from another major domain of human physiology (i.e., blood coagulation and fibrinolysis). Some believe that regulation of seminal coagulation and fibrinolytic liquefaction may bear analogies to the well-described pathways operational in blood. We here attempt to summarize the subject, revisiting earlier findings and covering the more recent and extensive data on hemostatically functional seminal proteins, including the findings of our own group. Evidence for the existence of each key hemostatic factor in semen is presented along with any correlation with indices of male fertility. Several probably possess alternative functions including anti-inflammatory action, aiding sperm capacitation and classic hemostasis following intercourse-induced bleeding. Established mechanisms such as the high molecular weight seminal vesicle system are also considered as potentially interacting with conventional hemostatic pathways to regulate seminal coagulation and liquefaction. Although our grasp of this subject continues to evolve, there still remain many unanswered questions. A more complete understanding may one day prove useful in designing technologies for improved diagnostics in male infertility and potentially aiding assisted human reproductive therapies.


Subject(s)
Blood Coagulation Factors/metabolism , Fertility/physiology , Fibrinolysis/physiology , Hemostatics/metabolism , Semen/metabolism , Seminal Plasma Proteins/metabolism , Humans , Infertility, Male/diagnosis , Infertility, Male/metabolism , Infertility, Male/therapy , Male
3.
Semin Thromb Hemost ; 33(1): 75-9, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17253193

ABSTRACT

Prostasomes are membrane-bound secretory vesicles produced by prostatic epithelial cells. They are known to carry many proteins, including tissue factor, and have membranes unusually rich in cholesterol and sphingomyelin. Prostasomes have well-documented effects on fertility, promoting sperm motility, stabilizing the acrosome reaction, and facilitating immunosuppression. This article reviews the evidence of the effects of prostasomes on in vitro angiogenesis assays, and the mechanism by which these effects occur. Seminal prostasomes seem to inhibit angiogenesis, whereas the equivalent particles released by malignant prostate cells promote angiogenesis. In both cases, the effects seem preserved after heat treatment to denature the protein content, suggesting an important role for lipid transfer, in particular, transfer of sphingomyelin.


Subject(s)
Epithelial Cells/metabolism , Neovascularization, Pathologic/metabolism , Prostate/metabolism , Prostatic Neoplasms/metabolism , Secretory Vesicles/metabolism , Thromboplastin/metabolism , Acrosome Reaction , Biological Transport , Cholesterol/metabolism , Humans , Male , Sperm Motility , Spermatozoa , Sphingomyelins/metabolism
4.
BJU Int ; 98(4): 845-8, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16978282

ABSTRACT

OBJECTIVE: To determine the effect of nephroureterectomy (NU) on the glomerular filtration rate (GFR), and to determine whether the estimated GFR after NU is influenced by age and other factors associated with renal impairment. PATIENTS AND METHODS: We retrospectively identified 131 patients who had had a NU at either of two UK institutions. Their serum creatinine levels were recorded before and after NU, along with comorbidity data, and from this their GFR before and after NU was estimated using the Modification of Diet in Renal Disease Study Group equation. RESULTS: At a median follow-up of 5 years there was an 18% deterioration in estimated GFR in the 131 patients. The percentage deterioration in estimated GFR was greater in those aged >or= 70 years than in those aged <70 years (20% vs 15% deterioration). Those with more risk factors for renal impairment had a greater percentage deterioration in estimated GFR than those with no such risk factors. CONCLUSIONS: This study shows that NU has a profound effect on future estimated GFR, an effect that is further compounded in those with risk factors for renal impairment. This study therefore provides both the patient and the urologist with an idea of potential future renal function after NU and contributes greatly to preoperative counselling.


Subject(s)
Carcinoma, Transitional Cell/surgery , Glomerular Filtration Rate/physiology , Nephrectomy/adverse effects , Ureter/surgery , Urologic Neoplasms/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Creatinine/blood , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies
5.
BJU Int ; 98(4): 907-11, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16978292

ABSTRACT

OBJECTIVES: To investigate whether cellular exosomes liberated by prostatic cell lines in culture might be acting as the transport vehicles for the dietary antioxidant lycopene, known to be sequestered in the prostate gland and to reduce the risk of developing benign prostatic hyperplasia (BPH) and prostate cancer; its subsequent secretion into seminal plasma also confers protection to spermatozoa against oxidative free-radical damage. MATERIALS AND METHODS: Using benign and malignant human prostatic cell culture models, we assessed the role that their exosomes (the putative in vitro analogues of prostasomes) might have in the transport of lycopene. RESULTS: Cells exposed to lycopene in vitro accumulated the molecule and secrete lycopene-enriched exosomes. This continued after the lycopene exposure was stopped. Extraction of lycopene from the exosomes, followed by high-performance liquid chromatography, confirmed nanogram quantities of lycopene per milligram of exosomal protein. Packaging into exosomes for export resulted in reduced degradation of this labile antioxidant, and therefore maximized the effectiveness of delivery to the sites of action. CONCLUSION: These results support the likelihood that these organelles act as the transport vehicles for this important lipophilic agent known to have a role in the chemoprevention of various urological pathologies such as BPH, prostate cancer and male infertility.


Subject(s)
Anticarcinogenic Agents/pharmacology , Antioxidants/pharmacology , Carotenoids/pharmacology , Prostatic Hyperplasia/prevention & control , Prostatic Neoplasms/prevention & control , Transport Vesicles/metabolism , Anticarcinogenic Agents/therapeutic use , Antioxidants/therapeutic use , Carotenoids/therapeutic use , Cell Line, Tumor , Chemoprevention , Humans , Lycopene , Male , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/pathology
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