John Davies

Publications of John Davies

• Prognostic value of initial prostate-specific antigen levels after salvage cryoablation for prostate cancer.

  Authors: Mohamed Ismail, Ash Sood, John Davies

  BJU international. 03/2011; 107(6):1010; author reply 1010.

• Immunoregulatory effects of freeze injured whole tumour cells on human dendritic cells using an in vitro cryotherapy model.

  Authors: Mohamed Ismail, Richard Morgan, Kevin Harrington, John Davies, Hardev Pandha

  Cryobiology. 12/2010; 61(3):268-74.

  Tumour cryotherapy has been described as both immunostimulatory and immunoinhibitory in previous studies. However, previous studies have not accurately reproduced the precise conditions of currentTumour cryotherapy has been described as both immunostimulatory and immunoinhibitory in previous studies. However, previous studies have not accurately reproduced the precise conditions of current clinical cryotherapy. The objective of this study is to assess the immunological effects of cryotreated whole tumour cells on dendritic cells (DC) maturation and function using an in vitro model. Prostate cancer cells were cooled using Endocare cryo-system to mimic temperatures achieved during clinical cryotherapy. Human DC were prepared from cluster of differentiation (CD) 14 monocytes and matured with lipopolysaccharide (LPS). Cryotreated cancer cells were added to DC on day 3. On day 7, DC were harvested and phenotyped. Cytokine gene expression was assessed using real time quantitative polymerase chain reaction (RT-PCR). Functional activity of DC was assessed in allogenic mixed lymphocyte reaction (MLR) and the molecular changes using gene microarray technology. There was statistically significant upregulation of costimulatory molecules and maturation markers (CD86, CD83, CD80 and CL II) in DC loaded with cryotreated whole tumour cells compared to both control DC and DC matured with LPS (P < 0.001). There was a significant increase in stimulatory cytokines gene expression (IL-2, IL-12, IL-15, IL-18 and IFN-γ). However, IL-10 and TGF-β expression reduced significantly. The effect of different freezing temperature was equal. cDNA microarray analysis showed upregulation of interleukin 1 (IL-1) and cycline dependent kinase inhibitor 1A (CDKN1A (p21) and downregulation of Caspase 8 and BCL2. Overall, our findings suggest that the effect of cryotherapy is generally stimulatory to DC which may enhance anti-tumour effects. Therefore, the combination of cryotherapy and DC vaccine may represent a novel method to increase the efficacy of cryotherapy especially at the peripheral zones of the prostate where cells are exposed to sub-lethal temperature.

• Enhancing prostate cancer cryotherapy using tumour necrosis factor related apoptosis-inducing ligand (TRAIL) sensitisation in an in vitro cryotherapy model.

  Authors: Mohamed Ismail, Richard Morgan, Kevin Harrington, John Davies, Hardev Pandha

  Cryobiology. 08/2009;

  Cryotherapy is a minimally invasive treatment for prostate cancer. Complete ablation of cancer tissue some times fails and results in disease recurrence. In this study we investigate the effect ofCryotherapy is a minimally invasive treatment for prostate cancer. Complete ablation of cancer tissue some times fails and results in disease recurrence. In this study we investigate the effect of TRAIL as a sensitising agent to enhance the effects of cryotherapy on prostate cancer cells.Prostate cancer cells were cooled using Endocare cryo-system to mimic temperatures achieved during clinical cryotherapy. The effects of TRAIL, cryotherapy or combination of both treatment on DU-145 and PC-3 were evaluated. Viability and mode of cell death was assessed following treatment.Cryotherapy did not result in complete cell death at temperature -40 degrees C. Cells died by both necrosis and apoptosis. Cells which survived freeze-thaw cycle became more sensitive to a second freezing injury. TRAIL resulted in minimal cell death. Concomitant treatment of the tumour cells with TRAIL and cryotherapy resulted in complete loss of viability at -10 and -20 degrees C. Cell death was mainly due to marked increase in necrosis. Our finding demonstrates that combined treatment of TRAIL and cryotherapy represent a novel approach to increase the sensitivity to cryotherapy. This combined approach may be feasible for locally advanced prostate cancer.

• Salvage cryotherapy for recurrent prostate cancer after radiation failure: a prospective case series of the first 100 patients.

  Authors: Mohamed Ismail, Shwan Ahmed, Christof Kastner, John Davies

  BJU international. 10/2007; 100(4):760-4.

  OBJECTIVE: To report the short- to intermediate-term experience of using salvage targeted cryoablation of the prostate (TCAP) for the recurrence of localized prostate cancer after radiotherapy.OBJECTIVE: To report the short- to intermediate-term experience of using salvage targeted cryoablation of the prostate (TCAP) for the recurrence of localized prostate cancer after radiotherapy. PATIENTS AND METHODS: Between May 2000 and November 2005, 100 patients had salvage TCAP for recurrent prostate cancer after radiotherapy; the mean follow-up was 33.5 months. All patients had biopsy-confirmed recurrent prostate cancer. Biochemical recurrence-free survival (BRFS) was defined using a prostate specific antigen (PSA) level of <0.5 ng/mL and by applying the American Society for Therapeutic Radiology and Oncology (ASTRO) definition for biochemical failure. Patients were stratified into three risk groups, i.e. high-risk (68 men), intermediate-risk (20) and low-risk (12). RESULTS: There were no operative or cancer-related deaths; the 5-year actuarial BRFS was 73%, 45% and 11% for the low-, intermediate- and high-risk groups, respectively. Complications included incontinence (13%), erectile dysfunction (86%), lower urinary tract symptoms (16%), prolonged perineal pain (4%), urinary retention (2%), and recto-urethral fistula (1%). CONCLUSION: Salvage TCAP is a safe and effective treatment for localized prostate cancer recurrence after radiotherapy.

• History of cryosurgery.

  Authors: Lanja Ahmed, Shwan Ahmed, John Davies

  Journal of endourology / Endourological Society. 08/2006; 20(7):471-4.

• Emerging minimally invasive techniques for treating localized prostate cancer.

  Authors: Shwan Ahmed, Bronagh Lindsey, John Davies

  BJU international. 01/2006; 96(9):1230-4.

• Managing the complications of prostate cryosurgery.

  Authors: Shwan Ahmed, John Davies

  BJU international. 04/2005; 95(4):480-1.