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Michael Stöckle

Publications and source records attributed to Michael Stöckle.

At least 19 recordsLinked to original sources
PubMed2006

Transitional cell carcinoma of the ureter: prognostic factors influencing progression and survival.

OBJECTIVES: We retrospectively evaluated prognostic factors for progression-free and disease-specific survival in a large cohort of patients with transitional cell carcinoma (TCC) of the ureter. METHODS: A single-centre series of 145 consecutive patients treated with partial resection of the ureter or nephroureterectomy between 1975 and 2004 was evaluated. Median follow-up was 96 mo. Routine preoperative laboratory parameters as well as clinical and tumour-specific data were assessed. Univariate and multivariate statistical analyses were performed. RESULTS: Five-year disease-specific survival ranged from 96.1% for stages pTa to 28.6% for pT4. Grade1 tumours were associated with 5-yr disease-specific survival rates of 100% compared with 84% for G2, and 51.9% for G3 tumours, respectively. Univariate analyses identified pT stage and grade, tumour diameter, cM and pN categories, weight loss, the presence of synchronous tumour in the renal pelvis as well as elevated levels for humoral factors such as serum alkaline phosphatase (AP), white blood cell (WBC) count, platelet count, gamma-glutamyl transferase, creatinin, and blood urea nitrogen as prognostic factors. In multivariate analyses, tumour grade and WBC counts were predictive for low progression-free survival rates, whilst simultaneous tumour in the renal pelvis, high AP levels, and WBC counts were correlated with worse disease-specific survival. CONCLUSIONS: Our retrospective analysis provides clinical factors to identify patients with TCC of the ureter at high risk for progression and death of disease. Interestingly, humoral factors such as elevated serum AP levels and high WBC counts were demonstrated to be of paramount prognostic significance besides tumour stage, grade and multifocality.

Adult↗
PubMed2006

Neutrophil granulocytes are required for effective Bacillus Calmette-Guérin immunotherapy of bladder cancer and orchestrate local immune responses.

The role of polymorphonuclear neutrophil granulocytes (PMN) in antitumoral immune responses displays a striking dichotomy. Under inflammatory conditions, PMN may promote tumor growth and progression. In contrast, especially in the context of therapeutic interventions, PMN can exert important antitumor functions. However, until now, the mechanisms of PMN-mediated activation of tumor immunity are poorly defined. Based on a murine model of Bacillus Calmette-Guérin (BCG) immunotherapy of bladder cancer, we provide evidence for a novel immunoregulatory role of this leukocyte subset. PMN immigrate into the bladder after intravesical BCG instillation and depletion of PMN from tumor-bearing mice completely abrogated antitumor efficacy of BCG. PMN stimulated with BCG in vitro as well as PMN isolated from the urine of BCG-treated patients were a major source of the chemokines interleukin-8, growth-related oncogene-alpha, macrophage inflammatory protein-1 alpha and of the inflammatory cytokine migration inhibitory factor. In vitro, BCG-stimulated PMN indirectly induced T-cell chemotaxis via the accessory function of activated monocytes. In vivo, depletion of PMN from BCG-treated mice significantly impaired CD4(+) T-cell trafficking to the bladder. These data show that PMN direct the migration of effector cells to the bladder and by this means are indispensable for effective tumor immunotherapy. Thus, our findings provide evidence for a novel early immunoregulatory role of these innate immune cells in local antitumor immunity.

Animals↗
PubMed2006

Excellent long-term cancer control with elective nephron-sparing surgery for selected renal cell carcinomas measuring more than 4 cm.

OBJECTIVES: Elective nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) < 4 cm has been accepted as alternative to radical nephrectomy (RN). However, NSS for tumours > 4 cm is controversial. We present our experiences and long-term oncologic outcome of RCC > 4 cm treated with NSS in a retrospective single-institutional analysis of 69 patients. METHODS: Between 1975 and 2004, elective NSS was performed in 368 patients at our institution, including 69 patients with sporadic, nonmetastatic RCC > 4 cm. Overall and cancer-specific survivals were estimated using the Kaplan-Meier method. RESULTS: Complications were seen in nine patients (13.0%). After a mean follow-up of 6.2 yr (median, 5.8 yr) seven patients (10.1%) had died, none of them of tumour-related causes. Tumour recurrence was detected in four patients (5.8%). The 5-yr overall survival probability was 94.9%. The 10-yr and 15-yr overall survival rates were both 86.7%. Cancer-specific survival was 100% after 5, 10, and 15 yr. CONCLUSIONS: Selected patients with localized RCC even > 4 cm can be treated with elective NSS providing optimal long-term outcome. The surgeon's decision for organ-preserving surgery should depend on tumour localisation and technical feasibility rather than on tumour size.

Adult↗
PubMed2006

Antitumor activity of the antimicrobial peptide magainin II against bladder cancer cell lines.

OBJECTIVE: Magainin II belongs to a family of antimicrobial peptides and has been shown to exhibit antibiotic activity in a wide range of organisms. Recent studies have also reported a significant antitumor effect of magainin II against various cancer cell lines and tumor mice models. In this study, we evaluated the cytotoxic and antiproliferative potency of magainin II in bladder tumor cells and normal fibroblasts. METHODS: The antiproliferative and cytotoxic effect of magainin II was quantified by colorimetric WST-1-, bromodeoxyuridine (BrdU)-, and lactic dehydrogenase (LDH) assays in three bladder cancer cell lines (RT4, 647V, and 486P) and in the murine fibroblast cell line 3T3 as well as in a primary culture from human fibroblasts. The median inhibitory concentration (IC50) values were determined for each assay, representing the concentration at which cell viability was reduced by 50%. Scanning electron microscopy (SEM) was used to visualize the morphologic effects of magainin II on bladder tumor cells and fibroblasts. RESULTS: Magainin II inhibited cell proliferation of bladder cancer cells in a dose-dependent manner. The average IC50 of magainin II against all bladder cancer cell lines was 198.1 microM (range, 52.4-484.03 microM) for the WST-1 assay and 75.2 microM (range, 31.0-135.3 microM) for the BrdU assay. The normal murine and human fibroblast cell lines were not affected by magainin II and their IC50 could not be determined at the concentrations of magainin II tested. LDH release was increased in all bladder tumor cell lines in the presence of magainin II, whereas normal fibroblasts showed no cell lysis. SEM demonstrated lethal membrane perforation by peptide pore formation in bladder cancer cells, but not in fibroblasts. CONCLUSION: Magainin II peptide exerts cytotoxic and antiproliferative efficacy by pore formation in bladder cancer cells but has no effect on normal murine or human fibroblasts. Magainin II may offer a novel therapeutic strategy in the treatment of bladder cancer with potentially low cytotoxic effects on normal cells.

Antimicrobial Cationic Peptides↗
PubMed2006

Long-term survival under maintenance gemcitabine chemotherapy for metastatic transitional cell carcinoma.

We report a case of a 74-year-old patient who received 41 courses of maintenance therapy with gemcitabine over a length of 28 months for metastatic transitional cell carcinoma. One year earlier the patient had received three cycles of adjuvant cisplatin-based combination chemotherapy after nephro-ureterectomy for a locally advanced urothelial cancer of the right renal pelvis. This case demonstrates a paradigm shift in the palliative treatment of advanced urothelial cancer, with the implementation of more tolerable agents such as gemcitabine. Even elderly patients with impaired renal function may benefit in terms of tumor reduction and survival from systemic chemotherapy, which may be applied over a prolonged period of time.

Aged↗
PubMed2006

Complete long-term survival data from a trial of adjuvant chemotherapy vs control after radical cystectomy for locally advanced bladder cancer.

OBJECTIVES: To report the long-term follow-up of patients with locally advanced bladder cancer treated with either adjuvant combined chemotherapy with methotrexate, vinblastine, doxorubicin/epirubicin, and cisplatin (MVAC/MVEC) or no additional treatment after radical cystectomy, to examine various survival endpoints and factors associated with long-term survival. PATIENTS AND METHODS: Between May 1987 and December 1990, 49 patients undergoing radical cystectomy for locally advanced bladder cancer were randomized to observation only or adjuvant systemic chemotherapy with three cycles of MVAC/MVEC (methotrexate 30 mg/m(2) on day 1, 15 and 22; vinblastine 3 mg/m(2) on day 2, 15 and 22; doxorubicin 30 mg/m(2) or epirubicin 45 mg/m(2) on day 2; and cisplatin 70 mg/m(2) on day 2 of a 28-day cycle). Data were obtained for progression-free, overall and tumour-specific survival. RESULTS: In all, 23 patients were randomized to the control arm and 26 to treatment with adjuvant chemotherapy. The trial intended to accrue 100 patients but was stopped after an interim analysis showed a marked difference in progression free-survival when these first 49 patients had been randomized. The intent-to-treat analysis, including hazard ratios (HR) with 95% confidence intervals and point estimates at 10 years for control vs adjuvant chemotherapy, was as follows: progression-free survival HR 2.84 (1.46-5.54; P= 0.002), 13.0% vs 43.7%; overall survival HR 1.75 (0.95-3.23; P= 0.069), 17.4% vs 26.9%; and tumour-specific survival HR 2.52 (1.28-4.99; P= 0.007), 17.4% vs 41.7%, respectively. CONCLUSIONS: The long-term results further support the use of adjuvant-combined chemotherapy with cisplatin-based regimens after radical cystectomy for locally advanced bladder cancer, as this significantly improves progression-free and tumour-specific survival.

Aged↗
PubMed2006

Genomic and expression analysis of the 3q25-q26 amplification unit reveals TLOC1/SEC62 as a probable target gene in prostate cancer.

Gain at chromosome 3q25-q26 has been reported to commonly occur in prostate cancer. To map the 3q25-q26 amplification unit and to identify the candidate genes of amplification, we did fluorescence in situ hybridization and quantitative real-time PCR for gene copy number and mRNA expression measurements in prostate cancer cell lines and prostate cancer samples from radical prostatectomy specimens. The minimal overlapping region of DNA copy number gains in the cell lines could be narrowed down to 700 kb at 3q26.2. Of all positional and functional candidates in this region, the gene TLOC1/SEC62 revealed the highest frequency (50%) of copy number gains in the prostate cancer samples and was found to be up-regulated at the mRNA level in all samples analyzed. TLOC1/Sec62 protein was also shown to be overexpressed by Western blot analysis. Intriguingly, the TLOC1/SEC62 gene copy number was increased in prostate tumors from patients who had a lower risk of and a longer time to progression following radical prostatectomy. These findings make TLOC1/SEC62 the best candidate within the 3q amplification unit in prostate cancer. TLOC1/Sec62 protein is a component of the endoplasmic reticulum protein translocation machinery, whose function during prostate carcinogenesis remains to be determined.

Cell Line, Tumor↗
PubMed2006

Phase II trial of adjuvant gemcitabine plus cisplatin-based chemotherapy in patients with locally advanced bladder cancer.

BACKGROUND: Despite the general acceptance of gemcitabine/cisplatin in metastatic bladder cancer, its role and tolerability in the adjuvant setting, in which renal insufficiency is common, is unclear. PATIENTS AND METHODS: A total of 39 patients with locally advanced transitional cell carcinoma of the bladder (T2-T4, N0-N2) were treated with 4 cycles of gemcitabine/cisplatin/amifostine after radical cystectomy. All toxicities were evaluated by the National Cancer Institute Common Toxicity Criteria. Tumor samples were immunohistochemically stained for pRB, p53, and p16. RESULTS: Thirty-five patients (90%) completed 4 cycles of chemotherapy. Eleven patients (28%) experienced grade 4 hematologic toxicity, and 14 patients (36%) experienced grade 3 nonhematologic toxicity. The median increase in creatinine was 0.3 mg/dL. With a median follow-up of 22.8 months (range, 7-70 months), 13 patients (33%) had recurrent disease, 1 patient at 6 years after completion of therapy. Twelve patients (31%) died, including 11 (28%) with recurrent disease. Thirty-three tumor blocks were evaluated for pRB, p53, and p16 alterations. In an exploratory analysis, altered expression of p53, p16, and pRB was found in 15 (45%), 22 (67%), and 30 patients (91%), respectively. No association between altered p53 and disease-free or overall survival was detected, but altered p16 and pRB expression was associated with better outcome (P < or = 0.001). CONCLUSION: Gemcitabine/cisplatin with amifostine is tolerated in the adjuvant setting for patients with locally advanced bladder cancer. The favorable prognostic value of altered p16 and pRB raises the hypothesis of a relative beneficial effect of chemotherapy in this population but needs verification in other studies.

Adult↗
PubMed2005

Adjuvant cisplatin plus methotrexate versus methotrexate, vinblastine, epirubicin, and cisplatin in locally advanced bladder cancer: results of a randomized, multicenter, phase III trial (AUO-AB 05/95).

PURPOSE: Radical cystectomy as standard treatment of muscle-invasive urothelial carcinoma of the urinary bladder cures less than 50% of patients with locally advanced bladder cancer. We compared two adjuvant combination chemotherapies in patients with stage pT3a-4a and/or pathologic node-positive transitional-cell carcinoma of the bladder after radical cystectomy. PATIENTS AND METHODS: A total of 327 patients were randomly assigned to either adjuvant systemic chemotherapy with three cycles of cisplatin 70 mg/qm(2) on day 1 and methotrexate 40 mg/qm(2) on days 8 and 15 of a 21-day cycle (CM) or three cycles of methotrexate 30 mg/qm(2) on days 1, 15, and 22, vinblastine 3 mg/qm(2) on days 2, 15, and 22, epirubicin 45 mg/qm(2) on day 2, and cisplatin 70 mg/qm(2) on day 2 of a 28-day cycle (M-VEC). RESULTS: The hazard ratio for progression-free survival as the primary end point was 1.13 (90% CI, 0.86 to 1.48) for 163 CM patients compared with 164 M-VEC patients whose right-hand limit remained below the upper bound compatible with the noninferiority hypothesis (alpha = .0403). The 5-year progression-free, tumor-specific, and overall survival rates (point estimates +/- SE) for CM versus M-VEC were 46.3% +/- 4.6% v 48.8% +/- 4.5%, 52.0% +/- 4.6% v 52.3% +/- 4.8%, and 46.1% +/- 4.3% v 45.1% +/- 4.6%, respectively. WHO grade 3 and 4 leukopenia occurred in 7.0% of patients treated with CM and 22.2% of patients treated with M-VEC (P < .0001). CONCLUSION: CM cannot be considered inferior to M-VEC with regard to progression-free survival of patients with locally advanced bladder cancer after radical cystectomy. Moreover, patients receiving adjuvant CM combination therapy experienced significantly less grade 3 and 4 leukopenia than patients treated with M-VEC.

Adult↗
PubMed2004

Transrectal ultrasound guided biopsy of the prostate: random sextant versus biopsies of sono-morphologically suspicious lesions.

Transrectal ultrasound (TRUS) guided multiple systematic random biopsies are presently the method of choice for determining the presence or absence of prostate cancer. TRUS image information is only used to guide the biopsy needle into the prostate, but not to localize and target cancerous lesions. Our aim in this study was to evaluated the possible predictive value of tumor suspicious endosonographic lesions of the prostate for prostate biopsies. We prospectively compared six systematic biopsies with lesion guided biopsies in a consecutive series of 217 patients. All patients had a prostate specific antigen (PSA) level of >4 ng/ml without a history of prostate disease. In a subgroup of 145 men with sonomorphologic lesions suggestive for prostate cancer (hypoechoic areas or asymmetries predominantly in the peripheral zone), lesion-guided biopsies were taken in addition to the systematic biopsies. We evaluated the number of tumors which were diagnosed or missed by both of the biopsy strategies. Of the 217 evaluated patients, 64 (29%) had histology confirmed cancer. Four patients with negative sextant biopsies had a positive TRUS guided biopsy. Out of 145 patients with a normal TRUS, three were cancer positive by sextant biopsy. A total of 1,387 individual biopsy cores were evaluated. Of the 1,304 systematic biopsy cores, 182 (14%) were positive and 1,122 (86%) negative. Of the 329 TRUS lesion guided biopsy cores 139 (42%) were positive and 190 (58%) negative. Patients with tumor suggestive TRUS lesions have a considerably higher risk of being diagnosed with prostate cancer compared to patients without such lesions. Both systematic sextant and TRUS lesion guided biopsies missed detectable prostate cancer in a minority of patients. Taking the endosonographic morphology of the prostate gland into consideration for biopsy strategies may improve the quality of the biopsy and avoid unnecessary invasive procedures in selected cases.

Biopsy↗
PubMed2004

Wilms' tumor in adults: results of the Society of Pediatric Oncology (SIOP) 93-01/Society for Pediatric Oncology and Hematology (GPOH) Study.

PURPOSE: In the Society of Pediatric Oncology (SIOP) 93-01 study, 30 patients older than 16 years were found to have Wilms' tumor. They were treated according to the pediatric protocol and were analyzed for clinical presentation, stage distribution, and prognosis. PATIENTS AND METHODS: Patient age ranged from 16 to 62 years (median, 25.4 years). Tumor stages were defined according to SIOP, and treatment was risk-adapted according to SIOP 93-01/Society for Pediatric Oncology and Hematology (GPOH) protocol. The patients were evaluated with regard to response, toxicity, and prognosis. Specimens of all tumors were centrally reviewed. RESULTS: Ten patients (33%) had metastatic disease at the time of diagnosis (liver, four patients; lung, three patients; liver and lung, three patients). The local stage distribution showed a predominance of higher stages (stage I, eight patients; stage IIN-, three patients; stage IIN+, four patients; stage III, 15 patients). Histologic studies revealed intermediate-risk in 23 of 30 tumors; two tumors were classified as high-risk; and three tumors were clear-cell sarcomas. Two of 30 patients showed a nephroblastoma and a renal cell carcinoma simultaneously in the same kidney. A complete remission was achieved in 24 patients; four patients relapsed after complete remission; and three of them reached a second remission with further treatment. Event-free survival was 57%, with an overall survival of 83% (median observation time, 4 years). CONCLUSION: Adults can be cured in a high percentage by a multimodal treatment according to pediatric protocols. Toxicity is higher than in children, but acceptable in view of the high remission rate.

Adolescent↗
PubMed2004

The superior prognostic value of humoral factors compared with molecular proliferation markers in renal cell carcinoma.

BACKGROUND: The American Joint Committee on Cancer and the Union Internationale Contre le Cancer have acknowledged routine laboratory parameters, such as serum calcium, alkaline phosphatase, hemoglobin, and the erythrocyte sedimentation rate (ESR), as predictors of survival in patients with renal cell carcinoma. The predictive value of these parameters compared with proliferation markers, such as Ki-67, proliferating cell nuclear antigen (PCNA), topoisomerase II-alpha, and p100, has not been determined. METHODS: Forty-eight consecutive patients who underwent nephrectomy for nonmetastatic renal cell carcinoma between 1990 and 1994 were observed up to 120 months postoperatively. Ten of 48 patients developed tumor progression 6-69 months after surgery. Routine preoperative laboratory parameters as well as tumor-specific data were assessed. Findings were compared with tumor proliferation indices, which were obtained by immunohistochemical staining for nuclear antigens Ki-67, PCNA, topoisomerase II-alpha, and p100 in paraffin embedded tumor tissue. RESULTS: Univariate and multivariate statistical analyses demonstrated superiority of routine laboratory values compared with tumor proliferation indices in predicting progression-free survival and disease-specific death. The best predictor after tumor size and symptomatic presentation was ESR (P < 0.0001), with ESR values > 70 mm at 2 hours indicating a significantly poorer prognosis. Only the proliferation marker Ki-67 reached univariate significance at a threshold of 7%. CONCLUSIONS: Routine laboratory parameters, such as alkaline phosphatase, lactate dehydrogenase, thrombocyte count, and especially ESR, provided superior long-term prognostic information for patients with nonmetastatic renal cell carcinoma compared with the molecular tumor proliferation markers Ki-67, PCNA, topoisomerase II-alpha, and p100.

Adult↗
PubMed2004

Detection of occult tumor cells in lymph nodes from bladder cancer patients by MUC7 nested RT-PCR.

OBJECTIVE: Systemic progression is the prevalent form of bladder tumor recurrence after radical cystectomy. The detection of occult bladder tumor cells in histopathologically normal lymph nodes could be of prognostic value. We examined the possibility that mucin 7 (MUC7) RNA might reflect the presence of occult tumor cells in lymph nodes from bladder cancer patients. We used the polymerase chain reaction (RT-PCR), a highly sensitive assay, to monitor MUC7 RNA. METHODS: We collected 240 pelvic lymph nodes from 25 bladder cancer patients undergoing radical cystectomy. We also obtained 20 lymph nodes from patients with prostate cancer and interstitial cystitis to use as negative controls. Each lymph node was divided in two parts to provide tissue for both histopathological and PCR analysis. RESULTS: 166/240 lymph nodes from bladder cancer patients were usable for MUC7 RT-PCR. By conventional histopathology, six of these nodes contained metastases. MUC7 RT-PCR analysis was positive for five of the six histologically proven lymph node metastases. Histopathological reevaluation of the sixth node revealed tumor in an adjacent vein, not in the lymph node, itself. In contrast, 46/160 (29%) histologically classified normal lymph nodes (pN0) from 17 bladder cancer patients were positive for MUC7. All 20 lymph nodes from control patients were MUC7-negative. CONCLUSION: MUC7 RT-PCR is a specific and sensitive method for the detection of occult tumor cells in lymph nodes from bladder cancer patients. Long-term observation will be necessary to evaluate the clinical value of MUC7 as a prognostic indicator of lymph node metastasis and disease progression.

Aged↗
PubMed2004

Prenatal diagnosis of congenital mesoblastic nephroma associated with renal hypertension in a premature child.

In the present article, we report, for the first time, a prenatal diagnosis of a congenital mesoblastic nephroma in combination with a post-partum hyperreninemia with hypertension. A newborn was delivered at 35 weeks gestation who had an intrauterine diagnosis of a renal mass as early as 32 weeks gestational age by ultrasound examination. Tumor nephrectomy was performed on day 11 after delivery when an increase in hypertension was observed in the newborn.

Adult↗
PubMed2004

The measurement of complexed prostate-specific antigen has a better performance than total prostate-specific antigen.

The aim of this study was to compare the diagnostic utility of complexed prostate-specific antigen (cPSA) with total PSA (tPSA) in screening for prostate cancer. Serum concentrations of tPSA and cPSA were measured in 4479 adult men during the prostate cancer screening program in the Saarland region (Germany). The percentage of men with c/tPSA ratio above the cut-off value of 0.75 increased with increasing tPSA intervals: tPSA 0-0.9 microg/l, 4.4%; 1.0-1.9 microg/l, 24.3%; 2.0-2.9 microg/l, 43.9%; 3.0-3.9 microg/l, 50.4%; and 4.0-20 microg/l, 60.2%. The commonly accepted tPSA cut-off value of 3.9 microg/l matched to the 93rd percentile of the overall population (corresponding cPSA value, 2.9 microg/l). A total of 202 men out of 313 with increased cPSA had increased c/tPSA ratio (cut-off > or = 0.75) vs. 186 out of 312 men with increased tPSA. Thus, an additional 16 men at high risk for prostate cancer were selected only if cPSA was utilised as a first line parameter. Our data show that, compared to tPSA, cPSA measurement will always detect more high-risk patients, independent of the cut-off levels utilised for cPSA, tPSA and c/tPSA ratio. cPSA is more effective than tPSA in selecting subjects with an elevated c/tPSA ratio who are at high risk of prostate cancer. Thus, cPSA might be seen as the superior first-line parameter in screening for prostate cancer. Using lower cut-off values for tPSA or cPSA than the commonly accepted values seems reasonable for screening purposes.

Adult↗
PubMed2003

Is there standard chemotherapy for metastatic bladder cancer? Quality of life and medical resources utilization based on largest to date randomized trial.

A large multinational phase III trial performed during the late 1990s compared two systemic chemotherapy regimens gemcitabine plus cisplatin and methotrexate, vinblastine, doxorubicin, cisplatin (M-VAC) in more than 400 patients with advanced or metastatic urothelial cancer. This trial has been discussed to landmark the beginning of a new era following M-VAC polychemotherapy which has dominated treatment of advanced urothelial cancer throughout the previous decade. Despite the fact that gemcitabine/cisplatin combination therapy did not surpass M-VAC therapy in regard to patient survival as initially intended, this combination demonstrated a more favourable toxicity profile with improved tolerability and superior cost effectiveness, rendering this combination an attractive alternative to M-VAC. This review on the largest to date phase III trial for advanced or metastatic urothelial cancer will focus on issues of quality of life including indicators such as performance status and changes in body weight. Furthermore, data on medical resources utilization as accounted during systemic polychemotherapy and related toxic events will be reconsidered, particularly under the impression of decreasing health care resources worldwide.

Antineoplastic Agents↗
PubMed2002

Expression of human beta-defensins 1 and 2 in kidneys with chronic bacterial infection.

BACKGROUND: Constitutive expression and localization of antimicrobial human beta-defensin-1 (HBD-1) in human kidneys as a potential mechanism of antimicrobial defense has been previously reported. Inducible expression of human beta-defensin-2 (HBD-2) has been described in various epithelial organs but not for the urogenital tract. METHODS: We investigated the gene- and protein expression of HBD-1 and HBD-2 by reverse transcriptase-polymerase chain reaction, and immunohistochemistry in 15 normal human kidney samples and 15 renal tissues with chronic bacterial infection. Additionally, cell culture experiments were performed to study HBD gene expression by real-time RT-PCR in response to inflammatory cytokines TNFalpha and IL-1beta as well as lipopolysaccharide from Gram-negative bacteria. RESULTS: Constitutive HBD-1 gene- and protein expression was detected in normal renal tissue and kidneys with chronic infection. As a novel finding, inducible HBD-2 gene- and protein expression was demonstrated in tubulus epithelia with chronic infection but not in normal renal tissue. In pyelonephritic kidneys HBD-1 and HBD-2 expression showed a similar pattern of localization in distal tubules, loops of Henle and in collecting ducts of the kidney. Furthermore, real-time RT-PCR of kidney derived cell lines stimulated with inflammatory agents TNF-alpha, IL-1beta and LPS revealed a strong increase in relative HBD-2 transcription level and also a slight increase in relative HBD-1 transcription level. CONCLUSIONS: Upregulated HBD-2 expression in renal tubulus epithelium indicates a role of a wider range of human defensins for antimicrobial host defense in the urogenital tract than previously recognized.

Adolescent↗