587 The response to sublethal heat treatment of prostatic tumour cells and of prostatic tumour infiltrating T-cells

585 THE EFFECT OF ISOFLAVONE PROFILES AND ANTI-OXIDATION DISEASES OF THE PROSTATE

INTAKE

ON SERUM BIOCHEMICAL SYSTEM IN PATIENTS WITH

Lirn K.P.I. McClmton

Hong S.J.l, Lee M.J.Z, Kim J.S?, Yoon S.“, Lee J.M.’ ‘Yonsei University ‘Yonsei University,

College

of Medicine,

Foods

& Nutritions,

University,

Science

Animal

INTRODUCTION to evaluate

short term effects

elderly

men with prostatic

application

of isoflavone

MATERIAL excluding

specific

of Urology,

Seoul, South Korea,

& Biotechnology,

& OBJECTIVES:

such as scmm prostate

Department

Kyungsangpook-Do,

supplementation

antigen (PSA), lipid profile

diseases

in prostatic

and to establish

Seoul, South Korea,

3Kyungpook

National

South Korea

The present preclinical

of isoflavone

study was undertaken on biochemical

and anti-oxidation

a basis for further

profiles

system in

research

on the

diseases.

& METHODS:

Sixteen benign prostatic hyperplasia (BPH) patients drugs that might influence semm biochemical profiles and 10 cancer (PC) patients were recruited. They were administered 15Omg

those taking

lnetastatic prostate isoflavone per day for 2 months and pre- and post-treatment serum PSA, SMA, CBC, and lipid profile were measured. In PC cases anti-oxidation system was analyzed by lneasuring serum total antioxidant status (TAS) and by cornet assay.

RESULTS: Comparing pre- and post-treatment with isoflavone, total serum cholesterol level significantly decreased in both BPH and PC patients (p=O.O34 and p=O.O32, respectively). Among CBC profile, WBC count significantly increased in BPH (p=O.O09), while the increase was not statistically significant in PC (p=O.475). Serum PSA decreased in both BPH and PC, but without statistical significance. Serum haemogiobin, platelets count, RBC count, alkaline phosphatase, BUN/creatinine, serum GOT and GPT were not influenced by isoflavone intake. In PC patients there was an increase in TAS, but it did not reach statistical significance (p=O.O92). However. all 5 PC patients with pre-treatment TAS of less than 1.29nmol/l had their TAS increased after treatment. Results of comet assay showed insignificant change in tail lnoment (p=O.225), but significant decrease in tail length (p=O.O43). CONCLUSIONS: showed a decrease in DNA

Oral administration of isoflavone 150mg per day for 2 months in serum total cholesterol level, an increase in TAS and a decrease

damage of blood lymphocytes.

However,

it failed to decrease

serum PSA level

significantly. Long-term changes in serum PSA, prostate volume and histology, and intraprostatic biochemical profiles should be monitored in the future to assess the effects of isoflavone on the prostate.

587 THE RESPONSE TO SUBLETHAL HEAT TUMOUR CELLS AND OF PROSTATIC T-CELLS

TREATMENT TUMOUR

Kramer G., Steiner G., Groebl Marberger M.

K., Newman

University

of Vienna,

Department

M., Hrachowitr

of Urology,

586 ALTERATIONS IN PROTEIN EXPRESSION IN RESPONSE TO INCREASED APOPTOSIS FOLLOWING FATTY ACID SUPPLEMENTATION TO DOCETAXEL TREATMENT IN PROSTATE CANCER CELLS

OF PROSTATIC INFILTRATING

‘University

Royal

of Aberdeen,

Infirmary.

University,

S2, Heys S.‘, Wahle K.j, Schofield A.’

Vienna,

Austria

INTRODUCTION & OBJECTIVES: To investigate the possibilities offered by high focused ultrasound (HIFU) in the field of tumour vaccination, we analyzed how prostatic cancer (Cap) cells react towards heat treatment and whether increased access to CaP cells by the immune system would be the result.

Aberdeen.

United

Kingdom,

United Kingdom,

‘Aberdeen

‘RobeIt

Gordon

INTRODUCTION & OBJECTIVES: Prostate cancer is the second commonest cancer in men in the UK with a 5.year survival rate of 68.5%. Docetaxel has attracted interest for use in advanced hornlone insensitive prostate cancer. Initial studies have shown response rates of up to 46%, which mean more than half of patients, still fail to respond. One novel approach has been the use of fatty acids to potent&e other chemotherapeutic agents. Fatty acids can potentiate taxane cytotoxicity against in &TO breast cancer cell lines. The aim of our study was to investigate the effect of fatty acids on docetaxel-induced apoptosis in prostate cancer cells. MATERIAL & METHODS: Prostate cancer cell lines LNCaP (hormone sensitive) and PC3 (hormone insensitive) were shidied. The cells were treated with docetaxel and fatty acids. Fatty acids used were conjugated iinoleic acid (CLA cis-9. trans-1 I and CLA trans.IO, cis-12 isomers), linoleic acid (LA). eicosapentaenoic (EPA)and docosahexaenoic acid (DHA). Cell viability was quantified with MTT assay and the effects expressed as IC,, (concentration of drug required to inhibit 50% cell growth). The nature of the interaction was then analysed using the isobologram method. Apoptosis was measured morphologically with DAPI staining, and expressed as an apoptotic index (AI). Finally, western analysis was used to assess how alterations in expression of key apoptotic-regulatov proteins (~53, ~21, bax, and bcl-2) correlated with the changes seen. RESULTS: IC,, for docetaxel was reduced in both cell lines following addition of fatty acids. Significant effects were seen with CLA cis-9, trans.1 I and DHA in LNCaP cells; and with LA and DHA in PC3 cells. Isobologram analysis demonstrated that all enhancements were synwgistic in nature. DAPI staining showed that CLA cis-9, trans.11 and DHA supplementation to docetaxel increased AI to 48.7% f 5.6 and 52.1% + 6.4 in LNCaP cells, compared to 30.9% + 4.6 in treatments with docetaxel alone. Similarly, AI was increased in PC3 cells following addition of LA (42.8% i 6.1) and DHA (50.9% -t 6.4) to docetaxel treatment, compared with docetaxel alone (21.0% i 2.8). The expression of ~53, ~21, bcl-2 and bax was reduced in LNCaP cells receiving the combined treatment when compared to docetaxel treatment alone. No significant changes in PC3 protein expression was noted in either treatment regime. CONCLUSIONS: This study demonstrated that fatty acids can modulate the anti-tumour effect of docetaxel in prostate cancer cells. Variations in key apoptotic-regulatory proteins suggested that more than one molecular mechanism was responsible for this action. Nevertheless, these results have important implications for the use of dietary nutrients in improving the effectiveness of do&axe1 in prostate cancer treatment.

P33

UROTHELlALTUMOURS:MANAGEMENTOFlNFlLTRATlVEANDADVANCEDTUMOURSI Friday, 26 March, 15.45-17.15, HallG/ Blue level

SELF-ASSESSED THERAPY FOR

S.,

of Surgery. Aberdeen.

of Urology,

School of Life Sciences, Aberdeen, Umted Kingdom

WELL BLADDER

Henninesohn L.‘, Steven Onekv E.O, Stemeck G.6

M.; Madersbacher

Depafiment

Department

BEING IN CANCER

K.2, WlJkstrBm

499 PATIENTS H.‘.

Pedersen

AFTER

J.‘,

Ahlstrand

588

RADICAL C.‘,

Aus

G.‘,

‘Centre for Surgical Sciences, Karolinska Institute, Department of Urology, Stockholm, Sweden, 2Herlev Umversity Hospital. Department of Urology, Copenhagen, Denmark, 3iirebro Universiry Hospital. Department of Urology. iirebro, Sweden, ‘LinkGping University Hospital, Hospital, Department of Urology, Linkeping, Sweden, ?Sahlgrenska University Department of Urology, Gothenburg, Sweden, “Karolinska Institute, Clinical Cancer Epidemiology, Stockholm, Sweden

INTRODUCTION & OBJECTIVES: Radical cystectomy and orthotopic reconstmction of the urinary tract 1s generally believed to result in a better quality of life than after comment or incontinent cutaneous diversion and following irradiation for bladder cancer. To assess this issue the well being and the frequency and intensity of a number of symptoms were assessed by a validated questionnaire.

MATERIAL & METHODS: Heat/stress response of CaP cells in situ and of CaP cell lines was analyzed by immunohistochemistry, Western blotting and Atlas array. A heat-induced change in immune recognition was analyzed functionally using T-helper (Th) 1 and Th2-cytokine release with TIL as responder and autologous CaP cells either heated or untreated as stimulator cells.

MATERIAL & METHODS: Patients treated for bladder cancer between the ages of 40 and 85 years were included. The study Included a consecutive series of treated (surgery or radiotherapy) patients in Stockholm, 8rebro, JBnkBping. LmkBping and Copenhagen. The sense of well being and a number of different symptoms (frequency and intensity) were assessed by a validated questionnaire. Possible confounding and effect-modifying factors were assessed by epidemiological methods. Age-matched Swedish and Danish control groups were included.

RESULTS: Transcription of 68 out of 500 genes was upregulated by sublethal heat in LNCaP and PC3 cells. Significantly upregulated stress protein expression [Heat shock protein (HSP)72,-73,Glucose regulated protein(GRP)75,-781 was seen at the border zone of HIFU treatment. Remarkably, even untreated benign prostatic hyperplasia (BPH) specimens revealed relative over expression of HSP72,-73 and GRP75,-78. Heated CaP cells increased Thl cytokine (interleukin2, interferon-y, tumour necrosis factor-cc) release but decreased Th2 cytokine (interleukin-4,-5,-10) release of TIL.

RESULTS: A total of 499 of 576 (87%) consecutive patients treated for invawe bladder cancer were included. Total 417 patients had undergone radical cystectomy of which 218 had a conduit, 8X continent cutaneous diversion and III an orthotopic neobladder; 48 had undergone radical radiotherapy. 34 patients were excluded due to recurrence. Seventy-three percent of the control individuals (4221581) answered the questionnaire. The neobladder group reported the highest mean score, 5.84, versus 5.69 (p=O.32) for the control group. The mean score for the conduit group was 5.39, and for the reservoir group 5.27 against only 4.98 for the irradiated patients. The last three differed statistically significantly from the controls, p=O.OZ, 0.01 and 0.001 respectively. By grouping/dichotomizing the well-being scale Into low (l-2), moderate (3-4-5) or high (6-7). 67% of patients with an orthotopic neobladder reported a high well-being compared to 55% of the conduit, 47% of the reservoir, 46% of the Irradiated patients and 62% of the controls. The relatwe risks of a low/moderate well being were 1.4 (1.0.1.9), 1.6 (1.2-2.3) and 1.6 (1.1-2.4) for the conduit, reservoir and irradiated groups. respectively, compared to patients wth an orthotopic neobladder.

CONCLUSIONS: HIFU treatment may alter the presentation of prostate tissue and tumour antigens and this presentation is most likely stimulatory. HSP 72/73 over expression in untreated BPH may suggest a mechanism by which BPH can incite inflammation.

CONCLUSIONS: Radical cystectomy including orthotopic reconstruction provides a better sense of well bemg in bladder cancer survivors than either continent or incontinent cutaneous diversion. Quality of hfe following radiotherapy was inferior to that achieved by cystectomy. European

Urology

Supplements

3 (2004)

No. 2, pp. 149