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Biomedical subjects

M Stöckle

Publications and source records attributed to M Stöckle.

At least 19 recordsLinked to original sources
PubMed2006

An improved in vitro model to characterize invasive growing cancer cells simultaneously by function and genetic aberrations.

Invasion into the surrounding tissue and bone metastasis is a common feature of advanced prostate cancer. Chromosomal and other genetic or epigenetic abnormalities were aligned to this behaviour mostly by using permanent cell lines, paraffin embedded tissue or primary tumour samples. Both attempts fail to reflect either the original situation or functional information in the patient's tissue. Thus, we developed an improved in vitro assay to follow invasion of prostate cancer cells derived from fresh samples of radical prostatectomy specimens. Fresh tumour samples were applied onto Matrigeltrade mark-coated invasion chambers using a cocultivation model. Invasive growing cells were harvested from the bottom of the membrane or from the underlying gel and further characterized using comparative genomic hybridization. Prostate cancer cells have the capability to invasively grow through the barrier of a Matrigeltrade mark and could easily be sampled in a pad of Matrigeltrade mark. Comparative genomic hybridization revealed characteristic chromosomal aberrations of the invasive growing cells. Noteworthy is their ability to spheroid formation, which allows for further cell propagation by standard cell culture methods. Thus, our improved invasion model is a tool for the sampling of invasive growing cancer cells from fresh human tumour material allowing for functional as well as genetic studies.

Cell Line, Tumor↗
PubMed2006

[Expression of antimicrobial peptide MUC7 in kidneys with pyelonephritis].

BACKGROUND: Mucins are glycoproteins secreted by epithelial cells of various organ systems exerting multiple functions. MG2 as the protein transcript of the MUC7 gene has first been described as secreted by serous salivary glands in the oral cavity. We sought to explore changes of MUC7 expression in the kidney stimulated by bacterial infection of the upper urinary tract. METHODS: We investigated the gene expression of MUC7 by reverse transcriptase-polymerase chain reaction in voided urine specimens from 15 patients with acute pyelonephritis compared to 15 healthy volunteers. Furthermore, the gene and protein expression of MUC7 was studied in 15 renal tissue samples with chronic bacterial pyelonephritis versus 10 normal human kidney samples taken from tumor-bearing organs. RESULTS: MUC7 gene expression was detected in 5 of 15 voided urine samples of patients with pyelonephritis and in 2 samples from 15 healthy volunteers (Fisher's exact test p=0.39). MUC7 gene expression was detected in 7 of 15 tissue samples of kidneys with chronic pyelonephritis and in none of 10 normal renal tissue samples from tumor bearing organs (p=0.02). Immunohistochemical staining with the monoclonal antibody PANH3 revealed protein expression in 6 of the 15 tissue samples with chronic pyelonephritis, but not in normal tissue samples. CONCLUSION: Upregulated MUC7 expression in the urinary tract particularly in renal tubular epithelium can occur under inflammatory conditions. This indicates a putative role of MUC7 as an antimicrobial host defense molecule within the urogenital tract.

Adult↗
PubMed2006

Outcome of renal tumors in young adults.

PURPOSE: Sporadic RCC is rare in young adults. We retrospectively reviewed the outcomes of patients 20 to 40 years old at our institution. MATERIALS AND METHODS: Between 1975 and 2004, 2,710 patients were treated surgically for renal masses at our institution. We found 120 patients (4.4%) 20 to 40 years old. We analyzed the clinical presentation, pathological characteristics and outcome of these patients, and compared it to patients older than 40 years. RESULTS: The mean age of 120 young adults was 34.1 years (range 20.4 to 39.8). Symptomatic presentation was documented in 49.5% of patients. RCC was found in 87 (72.5%) young adults. Young patients generally had a higher rate of organ confined tumors than patients older than 40 years (73.6% vs 59.3%, p <0.05). Histopathological characteristics, tumor size, lymph node metastases and distant metastatic disease did not differ significantly in young and older patients. Women were significantly more likely to have benign lesions (41% vs 20%, p <0.05). Mean followup for 120 patients was 80.6 months and 15 of 87 patients with RCC (17.2%) died of tumor related causes (mean followup 27.5 months). The 10-year cancer specific survival rate was 78% in young adults and 68% in older patients (p = 0.22). Multivariate Cox regression analysis revealed lymph node metastases and tumor differentiation grade as independent prognostic parameters in young patients. CONCLUSIONS: Young patients are more likely to have symptomatic tumors at presentation. Nevertheless, they have more favorable pathological features and a definite trend to superior disease specific survival following surgical treatment. Organ sparing surgery should be considered in young women since benign lesions are frequent found in this population.

Adult↗
PubMed2005

Elective nephron sparing surgery should become standard treatment for small unilateral renal cell carcinoma: Long-term survival data of 216 patients.

OBJECTIVES: Our experiences with elective nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) in a consecutive series of 216 patients are presented. Clinicopathological features and long-term oncological outcome is compared to patients treated with radical nephrectomy (RN). METHODS: Between 1975 and 2002, NSS was performed in 488 patients; 311 of these patients had elective indications. Renal cell carcinoma was found in 241/311 patients (77.5%). Long-term follow up data could be obtained in 216/311 patients. Cancer-specific survival was estimated using the Kaplan-Meier method. Cox's regression analysis and log-rank tests were used to evaluate independent predictive values of different clinicopathological features. Survival data of the 216 patients after NSS surgery were compared to 369 patients with small RCC treated with RN. RESULTS: After a mean follow up of 66 months (median 64 months) 29 (13.4%) of 216 patients treated with NSS had died, 4 of them (1.8%) tumour-related. Tumour recurrence was detected in 12 patients (5.6%). 204 patients (94.4%) were free of tumour at last follow-up. Cancer specific survival rates at 5 and 10 years for patients treated with NSS (RN) were 97.8% (95.5%) and 95.8% (84.4%). CONCLUSIONS: Elective NSS surgery provides optimal long-term outcome in patients with small localized RCC. Compared to RN, renal parenchyma is preserved without any disadvantage in survival rates. Consequently elective NSS should be accepted as gold standard for small renal tumours.

Adult↗
PubMed2005

[Therapy for systemic urothelial cancer recurrence].

Detailed data on treating systemic recurrences of urothelial cancer after radical cystectomy and/or radical upper tract surgery are sparse. This review describes the data available from two large clinical phase III trials, one on systemic chemotherapy for metastatic/inoperable urothelial cancer and the other on adjuvant systemic chemotherapy after radical cystectomy for locally advanced bladder cancer. In addition, an overview of contemporary series on metastasectomy for urothelial cancer with palliative as well as curative intent is presented. The impact of therapeutic options for the treatment of systemic urothelial cancer recurrences such as radiotherapy, surgery or systemic first and second line therapy represented by conventional chemotherapy and contemporary target therapy are discussed.

Antineoplastic Agents↗
PubMed2005

Current TNM classification of renal cell carcinoma evaluated: revising stage T3a.

PURPOSE: : Recent studies of rare cases of pT3a renal cell carcinoma extending directly into the adrenal gland showed worse survival than in other pT3a cases and recategorization as stage pT4 was suggested. We assessed the prognostic validity of a stage pT3a diagnosis based on perirenal fat infiltration. MATERIALS AND METHODS: : The records of 1,794 patients with renal cell carcinoma who underwent surgical resection between 1975 and 2000 at our institution were analyzed retrospectively. Focusing on pT3a tumors, as defined by perirenal fat infiltration, numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods with cancer specific survival as the primary end point. RESULTS: : We identified 237 of 1,794 patients with perirenal fat infiltration, classified as having pT3a disease. In patients with pT3a tumors tumor size was a significant parameter predicting survival. The most significant cutoff value for tumor size in pT3a disease was 7 cm. Patients with distant metastasis had a worse prognosis independent of T classification. Therefore, to assess the prognostic value of the current T classification in regard to T3a tumors we excluded patients with tumor stage cM+ for further subgroup analysis. Survival comparison of pT1 pNall, cM0 (744 of 1,794 cases) and pT3a pNall, cM0 7 cm or less (100 of 237) as well as pT2 pNall, cM0 (265 of 1,794) and pT3a pNall, cM0 greater than 7 cm (93 of 237) yielded similar results. After splitting pT3a into a modified T1/T2 classification a significant difference in 5-year survival analysis for a modified T1/T2 stage was found (pT1 plus pT3a less than 7 cm 90% vs pT2 plus pT3a greater than 7 cm 73%, p <0.001). Subsequently multivariate analysis in all 1,794 patients showed that modified T stage was an independent significant predictor of cancer specific survival. CONCLUSIONS: : We suggest revising the current pT3a classification based on perirenal fat infiltration but rendering a modified pT1/pT2 classification, which resolves pT3a cases without the loss of prognostic validity. Perirenal fat infiltration should not be used to assign T category. Tumors directly infiltrating the adrenal gland should be reclassified as T4.

Carcinoma, Renal Cell↗
PubMed2004

Proteasome inhibitors and their combination with antiandrogens: effects on apoptosis, cellular proliferation and viability of prostatic adenocarcinoma cell cultures.

The 26S proteasome is a ubiquitin-dependent proteolytic system that has been implicated in the regulation of cell cycle progression and apoptosis. We investigated the effects of the proteasome inhibitors MG115 and PSI alone or in combination with different concentrations of the antiandrogen hydroxyflutamide on the cellular proliferation, apoptosis and viability of 10 prostatic adenocarcinoma cell cultures. Treatment with both proteasome inhibitors resulted in apoptosis induction, whereas the combinations with hydroxyflutamide generally did not, with the exception of MG115 combined with 10(-7) M hydroxyflutamide. MG115 caused a significant decrease in cellular proliferation, as did the combinations of both proteasome inhibitors with hydroxyflutamide, whereas hydroxyflutamide alone was only effective at a concentration of 10(-5) M. Cellular viability was significantly reduced when both proteasome inhibitors were combined with 10(-5) M hydroxyflutamide. Although the results varied among different cell lines, we conclude that proteasome inhibitors are able to induce apoptosis and reduce cellular proliferation. They might prove effective as antineoplastic substances in prostatic adenocarcinoma alone or in combination with antiandrogens.

Adenocarcinoma↗
PubMed2004

[Proteasome inhibitors: induction of apoptosis as new therapeutic option in prostate cancer].

New perspectives in prostate cancer genesis and putative clinical management have emerged in recent years . Apoptosis plays a major role in this environment. Proteasome inhibitors block the action of a multicatalytic proteinase complex involved in the degradation of intracellular proteins, particularly with regard to cell cycle regulation and apoptosis. Numerous in vitro studies have demonstrated the ability of these compounds to induce apoptosis and enhance the activity of conventional tumoricidal agents in many cancer cell types, including prostate cancer cells. They point out the use of these potent inhibitors as a new potential molecular approach to the therapeutic management of prostate cancer. Furthermore, the action of proteasome inhibitors has been tested in animal models and in patients with hormone refractory prostate cancer, resulting in both PSA and tumor volume decrease. PS-341 (bortezomib, Velcade) is the first proteasome inhibitor with clinical application in cancer therapy that has been used in clinical trials to date. This report reviews the current status of those papers that have tried to analyze the connection between the proteasome pathway and apoptosis. We present our results of proteasome inhibition in individual prostate cancer cell lines. Proteasomal inhibition may offer a new therapeutic access in "molecular targeting" of prostate cancer.

Animals↗
PubMed2004

Adrenal metastases in 1635 patients with renal cell carcinoma: outcome and indication for adrenalectomy.

PURPOSE: Routine removal of the ipsilateral adrenal gland in patients with renal cell carcinoma who undergo nephrectomy has been a matter of dispute. In a retrospective study we screened for subgroups of patients with renal cell carcinoma from a large single center patient population who may have benefited from ipsilateral adrenalectomy. MATERIALS AND METHODS: Radical nephrectomy was performed in 1635 patients at a single institution between 1980 and 2000. A total of 1010 patients underwent radical nephrectomy plus ipsilateral adrenalectomy, whereas in 625 no simultaneous adrenalectomy was performed. Numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods for their predictive value in regard to cancer specific survival. RESULTS: Metastases in the adrenal gland were found in 5.5% of patients (56 of 1010) undergoing nephrectomy with adrenalectomy. Of 30 patients with adrenal metastasis and preoperative computerized tomography/magnetic resonance imaging 23 were found to have histological evidence of cancer, approaching a false-negative rate of 23.3%. All patients with false-negative computerized tomography/magnetic resonance imaging had a primary tumor of greater than 4 cm. Patients with adrenal metastases predominately had pT3 or greater tumor stage (82%). Cancer specific survival rates (75% vs 73% for adrenalectomy vs no adrenalectomy) and postoperative complications rates (7% vs 8%) did not differ significantly between the 2 groups. The prognosis in patients with a solitary adrenal metastasis (18 of 56) was more favorable than in patients with additional metastatic sites (38 of 56). CONCLUSIONS: Adrenal metastases from primary renal cell carcinoma were found significantly more often in patients with advanced tumor stages. Ipsilateral adrenalectomy should be recommended for all resectable renal cell carcinoma with a primary tumor of greater than 4 cm or with nonorgan confined tumor stages (T3 or greater) since a false-negative rate of about 20% can be expected with current imaging techniques.

Adrenal Gland Neoplasms↗
PubMed2003

[Molecular diagnostics of prostate cancer].

Although a number of studies have identified molecular markers for prostate cancer, their clinical utility remains mainly unclear. Markers, which allow improved determination of the biological aggressiveness of individual prostate cancers, may help to optimize therapeutic management of this heterogeneous tumor type. Here, a subset of molecular markers, which are intensively discussed in the literature or which are supposed to gain clinical utility in the future, are described in more detail. For a better survey, the markers are divided into (a) susceptibility markers, (b) malignancy markers, and (c) aggressiveness markers. The number of markers described as well as the inconsistency across studies in assessing their clinical utility reflect the heterogeneity of prostate cancer also on a genetic level so that it is unlikely that a single marker will gain clinical relevance. Future research must include systematic analysis of the clinical utility of not only single markers but rather of marker profiles in appropriate studies.

Genetic Markers↗
PubMed2003

[Gemcitabine/cisplatin vs. MVAC. 5 year survival outcome of the phase III study of chemotherapy of advanced urothelial carcinoma in Germany].

Of 405 patients with stage IV transitional cell carcinoma from an international multicenter phase III trial, 70 were randomized in Germany to receive either gemcitabine/cisplatin or standard MVAC systemic chemotherapy for locally advanced or metastatic urothelial cancer. Overall survival as the primary endpoint of the study was similar in both arms (median survival GC 15.4 months vs MVAC 16.1 months), as were tumor-specific survival and time to progressive disease. In the intent-to-treat analysis, the 5-year overall survival rate was 10% for patients randomized to GC and 18% randomized to MVAC. Tumor overall response rates (GC 54%, MVAC 53%) were similar. The toxic death rate was 0% in the GC arm and 3% (one patient) in the MVAC arm. Significantly more GC than MVAC patients experienced grade 3/4 anemia (GC 52%, MVAC 20%) with significantly more red blood cell transfusions in the GC arm.Significantly more GC than MVAC patients had grade 3/4 thrombocytopenia (GC 54%, MVAC 17%) without grade 3/4 hemorrhage or hematuria in either arm. More MVAC patients experienced grade 3/4 neutropenia (GC 56%, MVAC 61%, p=1.000), neutropenic or leukopenic fever (GC 0%, MVAC 10%, p=0.237), mucositis (GC 0%, MVAC 7%, p=0.495), and alopecia (GC 6%, MVAC 36%, p=0.004). GC represents a reasonable alternative for the palliative treatment of patients with locally advanced and metastatic transitional cell carcinoma. Sustained long-term survival was only found for patients with locally advanced cancer, lymphatic metastases, or solitary distant metastasis but not for visceral metastatic disease.

Adult↗
PubMed2003

Mucin 7 and cytokeratin 20 as new diagnostic urinary markers for bladder tumor.

PURPOSE: We determine the sensitivity and specificity of cytokeratin 20 (CK-20) and mucin 7 (MUC7) gene expression in voided urine samples taken from patients with bladder tumor and from control groups to investigate putative, noninvasive urinary markers for bladder tumor detection and monitoring. MATERIALS AND METHODS: Voided urine samples were collected from 50 patients with histologically proven bladder neoplasms (pTaN0M0G1-3 in 19 and pTisN0M0G3-pT4pN1M1G3 in 31), 20 patients with urolithiasis, 20 patients with urinary tract infection, 20 patients with other urological neoplasms and 20 healthy volunteers. Total RNA was extracted from exfoliated cells collected from 200 ml. voided urine. All RNA samples were investigated by a specific CK-20 and MUC7 nested reverse transcriptase polymerase chain reaction. RESULTS: The overall sensitivity of CK-20 gene expression in voided urine samples for the detection of bladder neoplasms was 78%. In contrast, voided urine samples from control patients and healthy volunteers showed a high rate of false-positive CK-20 detection resulting in a low specificity of 36%. The overall sensitivity of the MUC7 test for all bladder tumor cases was 66%. The sensitivity for papillary urothelial neoplasms (pTaN0M0G1-3) was 42% whereas analysis of the carcinoma in situ and invasive bladder cancer group (pTisN0M0G3-pT4pN1M1G3) yielded a sensitivity of 81%. The overall specificity of the MUC7 nested reverse transcriptase polymerase chain reaction method in the control groups was 80%. CONCLUSIONS: A high positive CK-20 detection rate was found not only in voided urine samples from patients with bladder tumor, but also in urine specimens from control groups. Therefore, CK-20 is not a reliable urinary tumor marker for bladder neoplasms. In contrast to CK-20, analysis of MUC7 demonstrated a high sensitivity and high specificity for carcinoma in situ and invasive bladder cancer, thus fulfilling the criteria of a urinary tumor marker.

Adult↗
PubMed2003

[Spectral analysis of the ECG R-R interval permits early detection of vagal responses to neurosurgical stimuli].

OBJECTIVE: To assess the efficacy of ECG spectral analysis, compared with heart rate (HR) monitoring in the detection of vagal response to surgical stimuli. METHODS: Twenty Asa II-III patients (age: 65 +/- 13 years) scheduled for surgery of cerebellopontine angle or implantation of sacral root stimulator were examined. Target controlled infusion of propofol (2-4 microg x ml(-1)) and remifentanil (4 ng x ml(-1)) was guided by the bispectral index (Bis). Arterial pressure via a radial catheter, pulse oximetry and end tidal CO2 were continuously monitored. Spectral analysis was achieved by connecting a computer to the cardiorespiratory monitor. Online power spectrum densities were calculated from the ECG R-R interval by software based on the fast Fourier transform (LabView, National Instruments, USA). Low frequency (LF: 0.04-0.15Hz) and high frequency (HF: 0.15-0.4Hz) were associated with sympathetic and parasympathetic activities respectively. We defined vagal reaction as a decrease in FC or an increase in HF >10% of the prestimuli value. HF and FC were compared according to the detection delay (by a Student t test with p < 0.05 considered significant) and a concordance test with a kappa coefficient (kappa): -1 = total discordance to 1 = total concordance. RESULTS: Twelve vagal reactions (observed in 8 patients) were detected within 5.5 +/- 1.3 s (HF) and 12.4 +/- 1.6 (FC); p < 0.001. Concordance between the 2 parameters was 95% (kappa =0.9). CONCLUSION: The ECG spectral analysis is a non-invasive technique, which permits the detection of intra-operative vagal reactions earlier than conventional monitoring of HR.

Aged↗
PubMed2003

[Systemic chemotherapy for transitional cell carcinoma of the urothelium].

Moderate activity of systemic chemotherapy for advanced urothelial cancer has been reported for more than 30 years. Only with the advent of potent combination therapy in the mid eighties of the past century clinically significant response rates as well as prolonged survival has been documented. This review summarizes seven Phase-III trials of systemic chemotherapy for advanced urothelial carcinoma as well as results from adjuvant and neoadjuvant Phase-III trials for muscle-invasive bladder cancer including the most recent reports.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Gemcitabine in advanced bladder cancer].

MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) has been the standard treatment for patients with advanced urothelial cancer for more than 15 years. Combination chemotherapy including gemcitabine/cisplatin showed similar tumor response and survival rates with a more tolerable toxicity profile in a recent multinational phase III study when compared to MVAC. Effectiveness of gemcitabine as a single agent or in combination with other cytotoxic agents had been investigated before in several phase II studies treating patients with advanced urothelial cancers. The tumor response rate for single agent gemcitabine in advanced urothelial cancers is between 11% and 28%. Tumor response rates rise to 50% when combining gemcitabine with cisplatin, and median survival times between 12 and 15 months can be expected. Triplet therapy schedules including gemcitabine may yield response rates in up to 80% of patients, particularly when used sequentially with other regimens. Further improvement of tolerability during systemic gemcitabine/cisplatin combination therapy without compromising effectiveness was recently demonstrated by a German phase II study when the 4-week schedule was reduced to a 3-week schedule with gemcitabine given on days 1 and 8.

Antimetabolites, Antineoplastic↗