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Biomedical subjects

Jürgen E Gschwend

Publications and source records attributed to Jürgen E Gschwend.

15 recordsLinked to original sources
PubMed2007

Pancreatic stellate cells are an important source of MMP-2 in human pancreatic cancer and accelerate tumor progression in a murine xenograft model and CAM assay.

The effect of the characteristic desmoplastic reaction of pancreatic cancer on tumor progression is largely unknown. We investigated whether pancreatic stellate cells, which are responsible for the desmoplastic reaction, support tumor progression. Immunohistology revealed that matrix metalloproteinase-2 (MMP-2), which is suggested to promote pancreatic cancer progression, is present in stellate cells adjacent to cancer cells. In vitro, stellate cells exhibited a much higher basal expression of MMP-2 compared with cancer cells. Panc1-, MiaPaCa2- and SW850-conditioned media stimulated MMP-2 release of stellate cells as detected by zymography. Cancer cells expressed and released basigin [BSG, extracellular matrix metalloproteinase inducer (EMMPRIN), CD147], a glycoprotein that is known to stimulate MMP-2 in mesenchymal cells, as detected by immunostaining, western blot and reverse transcription-polymerase chain reaction. Tumor cell-conditioned medium and BSG purified by affinity chromatography from supernatants of cancer cells, but not supernatants depleted from BSG, stimulated expression of MMP-1 and MMP-2 of stellate cells as demonstrated by western blot and zymography. Moreover, the interaction of stellate cells and cancer cells promoted the invasiveness of Panc-1 cells in the chorioallantoic membrane assay and increased the weight of tumors induced by all carcinoma cell lines in nude mice by 2.1-3.7-fold. Our findings support the assumption that the interaction of stellate cells and cancer cells promotes progression of pancreatic cancer.

Adenocarcinoma↗
PubMed2006

Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era.

PURPOSE: We studied the effect of radical cystectomy for transitional cell carcinoma of the bladder on survival and failure patterns when the 2 surgical standards cystectomy and neobladder were combined, when possible. MATERIALS AND METHODS: A consecutive series of patients undergoing radical cystectomy with pelvic lymph node dissection for transitional cell carcinoma of the bladder with curative intent was analyzed. Patients with neoadjuvant radiotherapy/chemotherapy were excluded. Pathological characteristics based on the 2002 TNM system, recurrence-free/overall survival and metastatic patterns were determined. RESULTS: A total of 788 patients with a mean age +/- SD of 65 +/- 10 years and a mean followup of 53.5 months who underwent surgery between 1986 and 2003 were analyzed. A neobladder was constructed in 75.4% of patients. Ten-year recurrence-free and overall survival rates were 59.1% and 44.9%, respectively. Positive lymph nodes were present in 143 patients (18%). The rate of recurrence-free survival at 5 years was 82.5% for pT2a pN0, 61.9% for pT2b and pT3a pN0, and 53.1% for pT3b pN0 disease. Local and distant failure rates were 4% and 9.5% for organ confined tumors, 15.9% and 19.2% for nonorgan confined tumors, and 20.4% and 45.1% in patients with positive lymph nodes, respectively. CONCLUSIONS: In patients with organ confined, lymph node negative transitional cell carcinoma excellent survival data can be achieved as long as the tumor is limited to the inner half of the detrusor. These data on a large group of patients support early aggressive surgical management for invasive bladder cancer. The results of this surgery only series may serve as a reference for other treatment modalities for bladder cancer.

Adult↗
PubMed2004

Inhibition of IkappaB kinase activity by acetyl-boswellic acids promotes apoptosis in androgen-independent PC-3 prostate cancer cells in vitro and in vivo.

Signaling through NF-kappaB has been implicated in the malignant phenotype as well as the chemoresistance of various cancers. Here we show that the natural compounds acetyl-beta-boswellic acid and acetyl-11-keto-beta-boswellic acid (AKbetaBA) inhibit proliferation and elicit cell death in chemoresistant androgen-independent PC-3 prostate cancer cells in vitro and in vivo. Induction of apoptosis was demonstrated in cultured PC-3 cells by several parameters including mitochondrial cytochrome c release and DNA fragmentation. At the molecular level these compounds inhibit constitutively activated NF-kappaB signaling by intercepting the IkappaB kinase (IKK) activity; signaling through the interferon-stimulated response element remained unaffected, suggesting specificity for IKK inhibition. The impaired phosphorylation of p65 and the reduced nuclear translocation of NF-kappaB proteins were associated with down-regulation of the constitutively overexpressed and NF-kappaB-dependent antiapoptotic proteins Bcl-2 and Bcl-x(L). In addition, expression of cyclin D1, a crucial cell cycle regulator, was reduced as well. Down-regulation of IKK by antisense oligodeoxynucleotides confirmed the essential role of IKK inhibition for the proliferation of the PC-3 cells. Both compounds tested were active in vivo, yet AKbetaBA proved to be far superior. Indeed, topical application of water-soluble AKbetaBA-gamma-cyclodextrin on PC-3 tumors xenografted onto chick chorioallantoic membranes induced concentration-dependent inhibition of proliferation as well as apoptosis. Similarly, in nude mice carrying PC-3 tumors, systemic application of AKbetaBA-gamma-cyclodextrin inhibited tumor growth and triggered apoptosis in the absence of detectable systemic toxicity. Thus, AKbetaBA and related compounds acting on IKK might provide a novel approach for the treatment of chemoresistant human tumors such as androgen-independent human prostate cancers.

Androgens↗
PubMed2004

Pathological T0 prostate cancer without neoadjuvant therapy: clinical presentation and follow-up.

INTRODUCTION AND OBJECTIVES: Radical prostatectomy is a standard therapy for patients with prostate cancer diagnosed by prostatic needle biopsy, prostate cytology, transurethral resection of the prostate or prostatectomy. In a small group of patients no tumour can be found in the radical prostatectomy specimen. These cases are classified as stage pT0. The aim of this study was to evaluate the clinical presentation of this entity and their prognosis. MATERIAL AND METHODS: In a nation-wide database the clinical data of 3609 patients with prostate cancer were collected. 28 patients (0.8%) were staged as pT0 in the radical prostatectomy specimen. The data included age, prostate specific antigen (PSA), and pathological report at diagnosis, histology of the radical prostatectomy specimen and follow-up data. RESULTS: The diagnosis was made by TURP (transurethral resection of the prostate) in 15, prostatectomy in 2, needle biopsy in 11, and cytology in 2 patients. For patients who underwent TURP or prostatectomy the preoperative staging was T1a in 10 and T1b in 5 cases. 12 patients diagnosed by biopsy or cytology were classified T2a and one patient after biopsy as T2b. 9 patients had a GI- and 19 a GII-tumour, GIII-pattern was not represented. The mean age at diagnosis was 64.7 years (range 53-79 years). The PSA at the time of diagnosis was <4ng/ml in 8 cases; 4-10ng/ml in 16 cases and >10ng/ml in 4 patients. One patient presented with a micrometastasis in a single lymph node. Median follow-up was 62 months (19-150). All patients had undetectable PSA levels following surgery. No patient presented with clinical or biochemical progression. One patient died with no evidence of disease at 133 months after radical prostatectomy. CONCLUSIONS: None of the clinical parameters had a strong association with a pathologically proven T0 situation after radical prostatectomy in this setting. Interestingly no patient had a high-grade tumour. None of the patients classified as pT0 had a biochemical or clinical relapse during follow-up.

Adult↗
PubMed2004

Simultaneous expression of T-cell activating antigens in renal cell carcinoma: implications for specific immunotherapy.

PURPOSE: The activation of antigen specific T cells by tumor associated antigens (TAA) might be a promising treatment strategy for patients with renal cell carcinoma (RCC). We analyzed TAA expression in patients with RCC as well as the prevalence of fitting HLA phenotypes and calculated the percent of patients eligible for peptide vaccination trials. MATERIALS AND METHODS: A total of 41 RCC samples from primary tumors were analyzed for TAA expression by reverse transcriptase-polymerase chain reaction. Genes of interest were MAGE-1, MAGE-3, G250 and PRAME since peptides derived from these genes have been shown to activate antigen specific cytotoxic T lymphocytes. Results were combined with data on the HLA gene and haplotype frequencies in the German population as an example of a white population. RESULTS: Tumor specific expression of at least 1 T-cell activating antigen was observed in all patients. Of the patients 80% expressed 2 or more TAAs simultaneously. HLA molecules suitable for presentation of the respective antigens were calculated to be expressed in 51% to 85% of white German patients. These results mirror with only minor variations most of the white populations in Europe and North America. CONCLUSIONS: We noted that T-cell activating tumor associated antigens are frequently expressed in patients with RCC. Based on HLA expression analysis in a white population at least 30% of patients with RCC are eligible for monovalent specific immunotherapy and 41% are eligible for polyvalent specific immunotherapy. These data are a rational basis for future prospective vaccination trials in patients with RCC.

Adult↗
PubMed2004

Cystectomy and orthotopic ileal neobladder: the impact on female sexuality.

PURPOSE: January 1986 and September 2003 cystectomy and formation of an ileal neobladder were performed in 86 female patients. In this retrospective study we focused on the impact of orthotopic reconstruction on female sexuality. MATERIALS AND METHODS: To assess female sexuality the standardized self-reporting instrument female sexual function index was mailed to 44 patients who were 70 years or younger at cystectomy with a recurrence-free followup of greater than 1 year, no pelvic irradiation and no concomitant diseases impairing sexual functions. The questionnaire analyzes 6 domains (desire, arousal, lubrication, orgasm, satisfaction and pain) with 19 items. It was returned by 29 patients (65.9%) with a median age of 65.0 years. The indication for cystectomy was benign disease in 8 cases and malignancy in 21. RESULTS: Factors influencing female sexuality were age younger than 60 years, benign disease, partnership at surgery and current partnership. Clean intermittent catheterization, urinary stress incontinence and hormonal therapy did not affect the results. The 11 of 17 patients who remained sexually active after cystectomy even had slight improvement in all female sexual function items. Six patients ceased to be sexually active postoperatively due to erectile dysfunction or partner death. One patient with interstitial cystitis became sexually active following cystectomy due to the loss of pelvic pain. Another 12 patients remained sexually inactive postoperatively. CONCLUSIONS: All aspects of female sexuality may remain unchanged following cystectomy and ileal neobladder formation as long as sexual activity is not ceased due to other reasons. Even fertility can be preserved when the internal genitalia do not have to be removed.

Aged↗
PubMed2003

Malignant non-urothelial neoplasms of the urinary bladder: a review.

OBJECTIVES: Non-urothelial bladder tumors frequently present a diagnostic and therapeutic challenge. We review the peer-reviewed literature to summarize the available evidence on the etiology, diagnosis and optimal management of malignant non-urothelial bladder tumors. METHODS: A comprehensive MEDLINE database search was performed. In addition, the proceedings of recent national and international urological and cancer society meetings were reviewed. RESULTS: Primary non-urothelial bladder tumors are rare in Europe and North America representing less than 5% of all bladder lesions combined. A large number of risk factors have been implicated in the etiology of non-schistosomiasis-related squamous cell carcinoma, yet their exact pathomechanism remains poorly defined. Squamous cell carcinoma, adenocarcinoma, small cell carcinoma, sarcoma and carcinosarcoma/sarcomatoid tumors share an unfavorable prognosis despite aggressive surgical management that relates both to an aggressive biological behaviour as well as to an often times advanced stage at the time of diagnosis. Inflammatory pseudotumors are benign tumors of uncertain histogenesis that may mimic sarcomas. Paraganglioma, primary melanoma and lymphoma represent additional, exceedingly rare bladder tumors. CONCLUSIONS: The systematic investigation of most non-urothelial bladder tumors is limited by the rarity of these lesions. A concerted effort of multiple institutions linked together in a national or international tumor registry will be necessary to advance our understanding of these tumors, evaluate treatment strategies and optimize patient outcome in the future.

Adenocarcinoma↗
PubMed2003

Bladder substitution.

PURPOSE OF REVIEW: Radical cystectomy and urinary diversion is the accepted standard of care for invasive bladder cancer, with orthotopic neobladders as the preferred method of bladder substitution in male and female patients. Last year's studies and reports on this subject are summarized and reviewed. RECENT FINDINGS: Today, most patients considered candidates for radical cystectomy, independent of sex, are potential candidates for orthotopic bladder substitution. It has been shown that orthotopic bladder replacement is well tolerated and feasible even in selected patients with locally advanced tumors with or without positive nodes. The complication rates for orthotopic bladder substitutes are similar to, or lower than, the morbidity rates after conduit formation or continent cutaneous diversion. It has been shown that an afferent tubular segment without any antireflux flap-valve-type implantation techniques protects the upper urinary tract adequately for more than a decade. The true impact of the chosen type of urinary diversion on distress symptoms, quality of life and patients' well-being among survivors of bladder cancer remains controversial and requires further clinical investigation. SUMMARY: The excellent functional outcome and voiding pattern with orthotopic bladder substitution, even in the long-term, argues in favor of this technique as the preferred method for lower urinary tract reconstruction following radical cystectomy for invasive bladder cancer.

Carcinoma, Transitional Cell↗
PubMed2003

T2a transitional cell carcinoma of the bladder: long-term experience with intravesical immunoprophylaxis with bacillus Calmette-Guerin.

PURPOSE: In this prospective study we evaluate the effect of combined transurethral resection of early muscle invasive bladder cancer and immunotherapy with bacillus Calmette-Guerin (BCG) in patients unfit for radical cystectomy or refusing more aggressive therapies. MATERIALS AND METHODS: A total of 22 patients with a mean age 73.6 years were included in the study. Inclusion criteria were histologically proven muscle invasive transitional cell carcinoma of the bladder with a tumor-free second resection and negative staging examinations in patients unfit for radical cystectomy or refusing more aggressive therapies. All patients received 6 weekly instillations of 120 mg. BCG starting 14 to 21 days after the last transurethral resection of the tumor. Followup at 3 months included cystoscopy, urinary cytology, ultrasound of the abdomen and chest x-ray. Every 6 months computerized tomography of the abdomen and bone scans were performed. RESULTS: The overall 5-year survival rate was 69.1%, while the disease specific 5-year survival rate was 94%. One muscle invasive recurrence was noted at 69 months, which was again treated with the same regimen but ultimately led to radical cystectomy 21 months later. One patient died of progressive recurrence in the upper urinary tract. The 5-year recurrence-free survival rate was 46.5%. The only severe complication was BCG pneumonitis. CONCLUSIONS: The data show encouraging results for transurethral resection of bladder tumor with intravesical BCG therapy in select patients with T2a bladder cancer who are not candidates for radical cystectomy.

Administration, Intravesical↗
PubMed2003

Outcome in patients with seminal vesicle invasion after radical cystectomy.

PURPOSE: We evaluated the impact of seminal vesicle invasion by transitional cell carcinoma of the bladder in a large cystectomy series. MATERIALS AND METHODS: Between January 1985 and February 2002, 1,125 cystectomies were performed at our 2 institutions. In 68 male patients there was pathologically proved tumor extension to the perivesical fat, prostatic stroma and/or seminal vesicles, including group 1: 38 to the prostatic stroma alone, group 2-12 to the seminal vesicles alone, and group 3-18 to the seminal vesicles and prostatic stroma. Complete followup was available for all patients. Overall disease specific and progression-free survival rates were calculated using the Kaplan-Maier-Method. Survival rates were compared using the log rank test. RESULTS: The overall 5-year survival rate for all 68 patients was 23.1%. The 5-year disease specific survival rates were 41.1%, 0% and 0%, and the 5-year progression-free survival rates were 32.1%, 0% and 0% for groups 1 to 3, respectively. Survival was significantly decreased in patients with seminal vesicle infiltration with or without prostatic stromal infiltration compared with prostatic involvement alone. This difference was independent of lymph node status in groups 1 versus 2 and 3. CONCLUSIONS: Seminal vesicle invasion by bladder carcinoma has a significant impact on disease specific and progression-free survival compared with prostatic stromal involvement alone.

Adult↗
PubMed2002

Carbon-11 acetate positron emission tomography can detect local recurrence of prostate cancer.

We investigated the potential of [(11)C]acetate positron emission tomography (PET) to detect local recurrence in prostate cancer (PCA) in patients with increasing PSA following complete prostatectomy. A total of 31 patients were studied and compared with the results of transrectal ultrasound (TRUS) combined with biopsy and clinical follow-up. Whole-body PET scan was performed 5 min after injection of 0.8 GBq [(11)C]acetate and completed within 1 h. Focally increased tracer uptake below the urinary bladder or in an abdominal lymph node region was considered as relapse. TRUS followed by biopsy verified recurrence in 18 patients and ruled it out in 13 patients. PET demonstrated local recurrence in 15 out of the aforementioned 18 patients. PET also demonstrated distant lymph node involvement and bone metastases in five patients each. No focal [(11)C]acetate uptake was demonstrated in the prostate bed in patients with negative biopsy. These patients had no evidence of disease during 6 months of follow-up. In the subgroup of patients with PSA <2.0 ng/ml ( n=8), five patients had positive PET findings, with four of them verified by biopsy. It is concluded that [(11)C]acetate PET is a promising new tool for the diagnosis of PCA recurrence and can influence patient management.

Acetates↗
PubMed2002

Disease specific survival as endpoint of outcome for bladder cancer patients following radical cystectomy.

OBJECTIVE: To directly compare disease specific and overall survival as endpoints in the outcome analysis of a large number of cystectomy patients and to define predictors for survival. MATERIALS AND METHODS: We retrospectively analyzed the records of 686 patients who underwent bilateral pelvic lymph node dissection (PLND) and radical cystectomy from 1980 to 1990 at Memorial Sloan-Kettering Cancer Center. RESULTS: Disease specific survival characterized a clearly more favorable patient outcome than overall survival in the entire patient population as well as patients with organ confined (OC) and non-organ-confined disease (NOC): 10-year disease specific and overall survival rates for patients with OC disease ( or=P3b) were 72.9% versus 49.1%, 61.7% versus 40.8% and 33.3% versus 22.8%, respectively. In node positive (N+) patients 10-year disease specific and overall survival rates were 27.7% and 20.9%, respectively. In a multivariate analysis organ confinement and nodal status were the strongest independent predictors of disease specific survival in all patient categories. However, stratification according to organ confinement and nodal status revealed additional prognostic parameters. CONCLUSION: Organ-confined bladder cancer translates into high disease specific survival rates following radical cystectomy. Outcome is best characterized by disease-specific survival versus overall survival, which underestimates the impact of treatment in patients with favorable tumor and nodal stage. Subgroup analysis of patients with organ confinement and nodal status identified additional prognostic variables within the more favorable patient categories not apparent in the entire population. The poor prognosis of patients with NOC and/or N+ tumors emphasized the importance of future randomized trials in which such stratification variables may be of value.

Aged↗
PubMed2002

An innovative mobile lithotripter for extracorporeal shock wave lithotripsy and therapy.

INTRODUCTION: To assess the performance of a new mobile device for extracorporeal shock wave lithotripsy (ESWL) and therapy (ESWT). MATERIALS AND METHODS: 278 patients underwent 399 treatment for stone disease. 28 patients received 64 treatments for orthopaedic issues such as pseudarthrosis or enthesiopathies resistant to conservative treatment. RESULTS: During ESWL, minor pain symptoms were well resolved with analgesics intravenously. 45% of patients were stone-free and 50% had irrelevant fragments at the time of discharge. 66% of patients underwent a single treatment. Auxiliary measures after ESWL were necessary in 5%. After ESWT, pain symptoms of all patients were reduced on average to 5.2 points on a numerical rating scale from 1 to 10. Patients with bony nonunions produced callus if the bone scan before ESWT showed activity. No complication related to either form of treatment was observed. CONCLUSIONS: This innovative mobile lithotripter fulfils all expectations a user can have in an upt-to-date equipment: good disintegration, low side effects, easy handling, fast installation, dual imaging and suitability for ESWL and ESWT.

Adolescent↗