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A NOVEL APPROACH TO INVESTIGATE INFLUENCE OF WEATHER CONDITIONS ON URETEROCOLIC ONSET: AN ITALIAN STUDY
65 A NEW IMMUNOTHERAPEUTIC APPROACH FOR ADVANCED RENAL CELL CANCER WITH TUMOR LYSATE PULSED INTERLEUKIN-12 SECRETING AUTOLOGOUS DENDRITIC CELLS Wimpissinger F.1 , Felzmann T.2 , Huegel H.2 , Funovics P.2 , Stackl W.1 1 Rudolfstiftung Hospital, Urology and Lbi for ESWL and Endourology, Vienna, Austria; 2 Children’s Cancer Research Institute – CCRI, St. Anna Children’s Hospital, Vienna, Austria INTRODUCTION & OBJECTIVES: We have conducted a clinical phase I trial to evaluate feasibility and safety of dendritic cell-based immunotherapy in patients with advanced renal cell carcinoma (RCC). As opposed to previous cancer vaccination studies, dendritic cells were specifically enabled to secrete interleukin 12 (IL-12). MATERIAL & METHODS: Patients with advanced RCC (n = 11) received six weekly intranodal vaccinations with autologous monocyte-derived dendritic cells (mDCs). MDCs were loaded with autologous tumor cell lysate and were specifically stimulated to secrete IL-12 to polarize type-1 T-helper lymphocytes (Th1) and to directly present tumor antigens to cytotoxic T lymphocytes (CTL). RESULTS: There was no significant treatment-related toxicity and no clinical evidence of autoimmunity. Vaccination was very well tolerated. Five patients had stable disease for at least five months, while four patients had progressive disease. Two patients with early clinically significant disease progression had to be excluded before completion of the treatment. In addition, we could detect enhanced anti-tumor immunity in vitro comparing immune response before versus after cancer vaccination. CONCLUSIONS: Tumor vaccination therapy with IL-12 secreting mDCs is well tolerated and has potential clinical – and clear immunological – effects in patients with advanced RCC.
66 A NOVEL APPROACH TO INVESTIGATE INFLUENCE OF WEATHER CONDITIONS ON URETEROCOLIC ONSET: AN ITALIAN STUDY Dal Moro F.1 , Abate A.2 , Arandjelovic G.1 , Tosato F.3 , Mancini M.1 , Artibani W.1 1 University of Padova Medical School, Urology, Padova, Italy; 2 University of California, Electrical Engineering and Computer Sciences Department, Berkeley, USA; 3 University of Padova Medical School, Emergency Department, Padova, Italy INTRODUCTION & OBJECTIVES: The aim of this study is to investigate the seasonal variations of ureterocolic incidence by a novel methodological approach. MATERIAL & METHODS: 1163 patients with acute ureterocolic, admitted to the Emergency Department of our hospital during the year 2003 were gathered. District climatic data (temperature and humidity) were obtained from 15 meteorological ground stations. Eigen decomposition and signal reconstruction of thermometric and hygrometric patterns were performed to recognize any cyclic variation. Average temperatures and humidity values were calculated over time sets of 15-30-45-60 days to point out the best period on which the average parameters had to be computed to evaluate the influence of the climatic exposition nearby each ureterocolic. RESULTS: 1163 patients with ureterocolic were evaluated: 733 males (63%) and 430 females (37%). There was a significant difference about male and female age distribution (p < 0.0001), with an earlier peak of incidence for women. Ureterocolics were grouped every 30 days, as Eigen found it to be an interval with homogeneous climatic features. With an average timeset of 15 days nearby each ureterocolic, a positive correlation coefficient with temperature (r = +0.75 with CI 0.31−0.93, p < 0.005) and a cubic relationship at the regression analysis (R = 82.4%, p = 0.015) were found. We observed a negative correlation between humidity and ureterocolics (rho = −0.70 with CI −0.92 to −0.21, p < 0.01), with an inverse relation as regression model (R = 57.9%, p < 0.05). CONCLUSIONS: This study has demonstrated an association between the occurrence of ureterocolic and the exposition to climatic features such as hot and dry weather nearby the colic event.
67
EFFECTS OF FGF-8B OVEREXPRESSION ON PHENOTYPE AND GENE EXPRESSION IN MOUSE REPRODUCTIVE GLANDS Elo T.1 , Valve E.2 , Tarkkonen K.2 , Sepp¨anen J.2 , Poutanen M.3 , H¨ark¨onen P.4 1 University of Turku, Department of Anatomy, Institute of Biomedicine, Turku, Finland; 2 University of Turku, Institute of Biomedicine, Department of Anatomy, Turku, Finland; 3 University of Turku, Institute of Biomedicine, Department of Physiology, Turku, Finland; 4 Lund University, Umas, Wallenberg Laboratory, Department of Laboratory Medicine, Malm¨o, Sweden
INTRODUCTION & OBJECTIVES: FGF-8 (fibroblast growth factor 8) is a mitogenic growth factor that has important roles in embryonic development whereas in adult tissues its expression is mainly restricted to germ cells. Expression of FGF-8 has been found to be elevated in breast, ovarian and prostate cancer as well as in premalignant PIN (prostatic intraepithelial neoplasia)lesions. In order to study the effects of FGF-8 in vivo, we have generated a transgenic mouse strain overexpressing FGF-8b in an androgen dependent manner in prostate and some other reproductive tract tissues. MATERIAL & METHODS: The transgene construct used consisted of human FGF-8b cDNA linked to rat probasin promoter (ARR2 PB), which directs the transgene expression primarily to prostatic epithelium. Expression of FGF-8 in mouse tissues were studied by RT-PCR, Western blotting and immunohistochemical stainings. Histological changes were evaluated from H&E stained tissue sections. Expression of FGF-8b and its possible target genes were studied by quantitative-RT-PCR method. Search for diffentially expressed genes in ventral prostate and epididymis is also being done by microarray analysis. RESULTS: Western blotting and immunohistochemical studies demonstrated that the level of FGF-8b transgene expression is highest in ventral prostate of transgenic mice. In addition, expression of transgene was found in other lobes of prostate, seminal vesicles, ductus deferens and epididymis. Marked macroscopic abnormalities including increased size of prostate, epididymis and seminal vesicles were observed in transgenic mice. Histological samples showed hypertrophy of prostatic glands and epididymal ducts as well as stromal expansion in both organs. Signs of inflammation and PIN-like lesions were also found. In addition, many of transgenic male mice were infertile. According to quantitative RT-PCR results, the expression level of FGF-8b in different FGF8b-transgenic mouse sublines varies remarkably and seems to correlate with the severity of phenotypical abnormalities. Expression studies searching for possible target genes of FGF-8b in mouse prostate and epididymis are ongoing. CONCLUSIONS: In conclusion, over-expression of FGF-8b linked to probasin promoter induces marked changes in the morphology of the prostate, seminal vesicle and epididymis of transgenic mice. The molecular mechanisms leading to these effects may help understanding the role and importance of FGF-8 in prostatic tumorigenesis.
68
QUANTITATIVE RT-PCR ANALYSIS OF CA9 GENE IN CONVENTIONAL RENAL CELL CARCINOMA (RCC): A USEFUL TOOL FOR PREDICTION OF EARLY METASTASIS AFTER NEPHRECTOMY Li G.1 , Feng G.2 , Gentil-Perret A.3 , Genin C.2 , Tostain J. 1 ´ ´ CHU of Saint-Etienne, Dept of Urology, Saint-Etienne, France; 2 CHU of Saint´ ´ ´ Etienne, Clinical Immunology Lab, Saint-Etienne, France; 3 CHU of Saint-Etienne, ´ Dept of Pathology, Saint-Etienne, France
INTRODUCTION & OBJECTIVES: 30–40% RCC patients will metastasize after nephrectomy. CA9 may have diagnostic and prognostic value for RCC. The present study is to test if quantitative RT-PCR of CA9 can provide useful information on the prediction of early metastasis after nephrectomy. MATERIAL & METHODS: A total of 63 patients with conventional RCC entered into this study. There were 42 men and 21 women. Their mean age was 63 years (35–86). The mean follow-up was 45 months (36–60). There were 24 pT1, 3 pT2, 24 pT3a, 10 pT3b and 2 pT3c. The grade was: 8 G1, 30 G2, 20 G3 and 5 G4. 10 tumors were N+ or/and M+ at diagnosis. 9 M0N0 patients were found to have a metastasis during the follow-up. Quantitative RT-PCR of CA9 gene expression was performed. The metastasis-free survival curve was established according to the Kaplan-Meier method with comparison by the Log-Rank test. RESULTS: CA9 gene expression was significantly higher in the low stage (pT1-pT2 N0M0) or low grade (G1–2 N0M0) than in the high stage (pT3 N0M0) or high grade (G3–4 N0M0) (p = 0.018, p = 0.003, respectively). At diagnosis, the average of CA9 gene expression was significantly low (p = 0.00012) in metastatic tumors (N+ or/and M+) than in non-metastatic tumors (N0M0). For the follow-up of M0N0 patients, the metastasis-free survival rate was significantly higher (p = 0.033) in the high CA9 group than in low CA9 group, but no significant difference in regard with the stage or grade (p = 0.115, p = 0.065, respectively). When the stage or grade was combined with CA9, the metastasis-free survival rates were significant (p = 0.004, p = 0.003, respectively). Finally, when the stage, grade and CA9 were combined, there was a significant difference (p = 0.001) in metastasis-free survival rates (T1T2+G1G2+high expression of CA9 versus T3+G3G4+low expression of CA9). CONCLUSIONS: Our study confirms that the expression level of CA9 gene in clear cell RCC is related to the metastasis. Quantitative RT-PCR may be a new tool to predict early metastasis after the nephrectomy and to guide the post-operative follow-up and treatment. Support: la ligue nationale contre le cancer du comit´e de la Loire.
Eur Urol Suppl 2006;5:803
66 A NOVEL APPROACH TO INVESTIGATE INFLUENCE OF WEATHER CONDITIONS ON URETEROCOLIC ONSET: AN ITALIAN STUDY Dal Moro F.1 , Abate A.2 , Arandjelovic G.1 , Tosato F.3 , Mancini M.1 , Artibani W.1 1 University of Padova Medical School, Urology, Padova, Italy; 2 University of California, Electrical Engineering and Computer Sciences Department, Berkeley, USA; 3 University of Padova Medical School, Emergency Department, Padova, Italy INTRODUCTION & OBJECTIVES: The aim of this study is to investigate the seasonal variations of ureterocolic incidence by a novel methodological approach. MATERIAL & METHODS: 1163 patients with acute ureterocolic, admitted to the Emergency Department of our hospital during the year 2003 were gathered. District climatic data (temperature and humidity) were obtained from 15 meteorological ground stations. Eigen decomposition and signal reconstruction of thermometric and hygrometric patterns were performed to recognize any cyclic variation. Average temperatures and humidity values were calculated over time sets of 15-30-45-60 days to point out the best period on which the average parameters had to be computed to evaluate the influence of the climatic exposition nearby each ureterocolic. RESULTS: 1163 patients with ureterocolic were evaluated: 733 males (63%) and 430 females (37%). There was a significant difference about male and female age distribution (p < 0.0001), with an earlier peak of incidence for women. Ureterocolics were grouped every 30 days, as Eigen found it to be an interval with homogeneous climatic features. With an average timeset of 15 days nearby each ureterocolic, a positive correlation coefficient with temperature (r = +0.75 with CI 0.31−0.93, p < 0.005) and a cubic relationship at the regression analysis (R = 82.4%, p = 0.015) were found. We observed a negative correlation between humidity and ureterocolics (rho = −0.70 with CI −0.92 to −0.21, p < 0.01), with an inverse relation as regression model (R = 57.9%, p < 0.05). CONCLUSIONS: This study has demonstrated an association between the occurrence of ureterocolic and the exposition to climatic features such as hot and dry weather nearby the colic event.
67
EFFECTS OF FGF-8B OVEREXPRESSION ON PHENOTYPE AND GENE EXPRESSION IN MOUSE REPRODUCTIVE GLANDS Elo T.1 , Valve E.2 , Tarkkonen K.2 , Sepp¨anen J.2 , Poutanen M.3 , H¨ark¨onen P.4 1 University of Turku, Department of Anatomy, Institute of Biomedicine, Turku, Finland; 2 University of Turku, Institute of Biomedicine, Department of Anatomy, Turku, Finland; 3 University of Turku, Institute of Biomedicine, Department of Physiology, Turku, Finland; 4 Lund University, Umas, Wallenberg Laboratory, Department of Laboratory Medicine, Malm¨o, Sweden
INTRODUCTION & OBJECTIVES: FGF-8 (fibroblast growth factor 8) is a mitogenic growth factor that has important roles in embryonic development whereas in adult tissues its expression is mainly restricted to germ cells. Expression of FGF-8 has been found to be elevated in breast, ovarian and prostate cancer as well as in premalignant PIN (prostatic intraepithelial neoplasia)lesions. In order to study the effects of FGF-8 in vivo, we have generated a transgenic mouse strain overexpressing FGF-8b in an androgen dependent manner in prostate and some other reproductive tract tissues. MATERIAL & METHODS: The transgene construct used consisted of human FGF-8b cDNA linked to rat probasin promoter (ARR2 PB), which directs the transgene expression primarily to prostatic epithelium. Expression of FGF-8 in mouse tissues were studied by RT-PCR, Western blotting and immunohistochemical stainings. Histological changes were evaluated from H&E stained tissue sections. Expression of FGF-8b and its possible target genes were studied by quantitative-RT-PCR method. Search for diffentially expressed genes in ventral prostate and epididymis is also being done by microarray analysis. RESULTS: Western blotting and immunohistochemical studies demonstrated that the level of FGF-8b transgene expression is highest in ventral prostate of transgenic mice. In addition, expression of transgene was found in other lobes of prostate, seminal vesicles, ductus deferens and epididymis. Marked macroscopic abnormalities including increased size of prostate, epididymis and seminal vesicles were observed in transgenic mice. Histological samples showed hypertrophy of prostatic glands and epididymal ducts as well as stromal expansion in both organs. Signs of inflammation and PIN-like lesions were also found. In addition, many of transgenic male mice were infertile. According to quantitative RT-PCR results, the expression level of FGF-8b in different FGF8b-transgenic mouse sublines varies remarkably and seems to correlate with the severity of phenotypical abnormalities. Expression studies searching for possible target genes of FGF-8b in mouse prostate and epididymis are ongoing. CONCLUSIONS: In conclusion, over-expression of FGF-8b linked to probasin promoter induces marked changes in the morphology of the prostate, seminal vesicle and epididymis of transgenic mice. The molecular mechanisms leading to these effects may help understanding the role and importance of FGF-8 in prostatic tumorigenesis.
68
QUANTITATIVE RT-PCR ANALYSIS OF CA9 GENE IN CONVENTIONAL RENAL CELL CARCINOMA (RCC): A USEFUL TOOL FOR PREDICTION OF EARLY METASTASIS AFTER NEPHRECTOMY Li G.1 , Feng G.2 , Gentil-Perret A.3 , Genin C.2 , Tostain J. 1 ´ ´ CHU of Saint-Etienne, Dept of Urology, Saint-Etienne, France; 2 CHU of Saint´ ´ ´ Etienne, Clinical Immunology Lab, Saint-Etienne, France; 3 CHU of Saint-Etienne, ´ Dept of Pathology, Saint-Etienne, France
INTRODUCTION & OBJECTIVES: 30–40% RCC patients will metastasize after nephrectomy. CA9 may have diagnostic and prognostic value for RCC. The present study is to test if quantitative RT-PCR of CA9 can provide useful information on the prediction of early metastasis after nephrectomy. MATERIAL & METHODS: A total of 63 patients with conventional RCC entered into this study. There were 42 men and 21 women. Their mean age was 63 years (35–86). The mean follow-up was 45 months (36–60). There were 24 pT1, 3 pT2, 24 pT3a, 10 pT3b and 2 pT3c. The grade was: 8 G1, 30 G2, 20 G3 and 5 G4. 10 tumors were N+ or/and M+ at diagnosis. 9 M0N0 patients were found to have a metastasis during the follow-up. Quantitative RT-PCR of CA9 gene expression was performed. The metastasis-free survival curve was established according to the Kaplan-Meier method with comparison by the Log-Rank test. RESULTS: CA9 gene expression was significantly higher in the low stage (pT1-pT2 N0M0) or low grade (G1–2 N0M0) than in the high stage (pT3 N0M0) or high grade (G3–4 N0M0) (p = 0.018, p = 0.003, respectively). At diagnosis, the average of CA9 gene expression was significantly low (p = 0.00012) in metastatic tumors (N+ or/and M+) than in non-metastatic tumors (N0M0). For the follow-up of M0N0 patients, the metastasis-free survival rate was significantly higher (p = 0.033) in the high CA9 group than in low CA9 group, but no significant difference in regard with the stage or grade (p = 0.115, p = 0.065, respectively). When the stage or grade was combined with CA9, the metastasis-free survival rates were significant (p = 0.004, p = 0.003, respectively). Finally, when the stage, grade and CA9 were combined, there was a significant difference (p = 0.001) in metastasis-free survival rates (T1T2+G1G2+high expression of CA9 versus T3+G3G4+low expression of CA9). CONCLUSIONS: Our study confirms that the expression level of CA9 gene in clear cell RCC is related to the metastasis. Quantitative RT-PCR may be a new tool to predict early metastasis after the nephrectomy and to guide the post-operative follow-up and treatment. Support: la ligue nationale contre le cancer du comit´e de la Loire.
Eur Urol Suppl 2006;5:803