Overexpression of fibroblast growth factors (FGFs) has been implicated in prostate carcinogenesis. FGFs function via their high-affinity interactions with receptor tyrosine kinases, FGFR1 -4. Expression of FGFR1 and FGFR2 in prostate cancer (CaP) was not found to be associated with clinical parameters. In this report, we further investigated for abnormal FGFR expression in prostate cancer and explore their significance as a potential target for therapy. The expression levels of FGFR3 and FGFR4 in CaP were examined and corroborated to clinical parameters. FGFR3 immunoreactivity in benign prostatic hyperplasia (BPH) and CaP (n ¼ 26 and 57, respectively) had similar intensity and pattern. Overall, FGFR4 expression was significantly upregulated in CaP when compared to BPH. A significant positive correlation between FGFR4 expression and Gleason score was noted: Gleason score 7 -10 tumours compared to BPH (Po0.0001, Fisher's exact test), Gleason score 4 -6 tumours compared to BPH (Po0.0004), and Gleason 7 -10 compared to Gleason 4 -6 tumours (Po0.005). FGFR4 overexpression was associated with an unfavourable outcome with decreased disease-specific survival (Po0.04, log rank test). FGF-induced signalling is targeted using soluble FGF receptor (sFGFR), potent inhibitor of FGFR function. We have previously shown that sFGFR expression via a replication-deficient adenoviral vector (AdlllcRl) suppresses in vitro FGF-induced signalling and function in human CaP DU145 cells. We tested the significance of inhibiting FGF function along with conventional therapeutic modalities in CaP, and confirmed synergistic effects on in vitro cell growth (proliferation and colony formation) by combining sFGFR expression and treatment with either Paclitaxel (Taxol s ) or g-irradiation. In summary, our data support the model of FGF system as valid target for therapy in CaP. Prostate cancer is the commonest cancer in men and the second commonest cause of cancer-related death in men, and its incidence is increasing (Woolf, 1995;Boyle et al, 1996). Prostate cancer is an enigmatic disease. It is histologically present in 80% of men over the age of 80 years, but will only clinically manifest itself in about 10%. Increasing use of serum measurement of prostate-specific antigen is facilitating early diagnosis of prostate cancer. There are currently limited prognostic markers that may allow patients found to have early prostate cancer to be stratified into different management plans. Hence, new methods of predicting disease progression are urgently needed.Abnormal expression of peptide growth factors and their highaffinity receptor tyrosine kinases are important in the development and progression of prostate cancer. These mitogens enhance tumour proliferation and invasion while inhibiting apoptosis. Several peptide growth factors have been implicated in prostate cancer development and progression, including insulin-like growth factors, epidermal growth factor and members of the fibroblast growth factors (Byrne et al, 1996;Tennant et al, 1996;Dorkin et...
We present a case of cutaneous metastases from a primary bladder transitional cell carcinoma (TCC), with a prolonged survival of 23 years. Cutaneous metastases from primary bladder TCC are uncommon and, like all metastases, have a poor prognosis. The common modality of treatment of cutaneous metastases from a primary bladder cancer is wide local excision of the metastases followed by combination chemotherapy. Here, we present a case of a solitary cutaneous metastasis from a primary bladder TCC, which was treated with wide local excision and single agent chemotherapy. Twentythree years on, the patient remains disease and recurrence free.
temperatures throughout the procedure were recorded accurately and analysed. RESULTSThe IceRods were better able to freeze tissue, reaching lower temperatures than conventional cryoneedles. The IceRods were also capable of forming ice-balls with a maximum diameter of > 6 cm after freezing at full power for 10 min. The TMS probes depicted real-time temperature gradients over either four or eight points in a linear array, enabling more thorough monitoring of the temperature changes during a treatment cycle. In the clinical setting, in all 20 patients, therapeutic freezing of <− 40 ° C was achieved in both the cycles. Temperatures of ≈ − 40 ° C were attained in the area just outside the prostate, as measured by the TMS probes, but with variation along the longitudinal axis. The rectal and external urinary sphincter temperatures did not fall below 0 ° C at any of the points along the eight-point temperature probe, but there was variation in temperature along the prostate. CONCLUSIONIceRods and the TMS probes are clinically useful, requiring fewer cryoneedles and with more efficient temperature monitoring; this would be expected to reduce morbidity and increase safety without compromising an adequate oncological outcome. The IceRods were useful in larger prostates of > 3.5 cm long, which obviated the need for a 'pull-back' technique. The TMS probes showed convincingly the variation in temperatures along one line, suggesting that single-point temperature monitoring might not accurately depict the lowest temperatures reached during treatment, which is particularly important in the rectum. This is a significant development in cryosurgery and would make the procedure safer, reproducible and allow interested clinicians to learn the technique safely and more quickly.
Prostate cancer treatment has undergone vast development over the last few decades, but the most notable changes have included nerve-sparing open radical prostatectomy, laparoscopic radical prostatectomy, including robot-assisted and, more recently, cryotherapy and high-intensity focused ultrasound (HIFU). While radical surgery is the current gold standard, the less invasive therapeutic options of cryotherapy and HIFU are regarded as largely experimental by governing bodies. In the case of cryotherapy, a wealth of experience has been accumulated demonstrating its efficacy. Initially used as a salvage treatment for radiation-failed prostate cancer, cryotherapy has been widely used as a primary treatment for localized and locally advanced prostate cancer. More recently, there has been interest expressed in the concept of focal therapy in prostate cancer. This has been evaluated as a primary treatment for prostate cancer, but little information is available regarding the potential use as a salvage treatment. In this article, we evaluate the potential for focal treatment in the salvage setting.
A replication deficient adenoviral vector system reproducibly expresses sFGFR in prostate cells. Suppression of in vitro growth in DU145 cells by sFGFR provides the basis of a novel therapeutic approach.
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