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Biomedical subjects

Peter Alken

Publications and source records attributed to Peter Alken.

64 records · Page 4Linked to original sources

Sacral anterior root stimulation and posterior rhizotomy in spastic neuropathic bladder.

The combination of sacral anterior root stimulation (SARS) and posterior rhizotomy is a successful procedure for the restoration of bladder function after supraconal spinal cord injury. Today, complete posterior rhizotomy has become part of the standard therapy. Conventional SARS leads to simultaneous activation of both the detrusor muscle and the external urethral sphincter. We evaluated the possibilities of different neurostimulation techniques to overcome stimulation-induced detrusor-sphincter-dyssynergia and to achieve physiological voiding. Selective detrusor activation improves current sacral neurostimulation of the bladder, including the "poststimulus voiding" principle. Selec-tive neurostimulation is possible in the following techniques: anodal block, high-frequency block, depolarizing prepulses, sinusoidal pulses and cryoblock. The anodal block technique and cryotechnique are excellent methods for selective bladder activation to avoid detrusor-sphinc-ter-dyssynergia and thus improve stimulation-induced voiding. Our experience has shown that future modern selective bladder neurostimulation systems will be based on either the anodal block technique or the cryotechnique.

Journal Article↗

Cytotoxicity of cisplatin in bladder cancer is significantly enhanced by application of bcl-2 antisense oligonucleotides.

BACKGROUND: The aim of our study was to examine the effects of the combined application of cisplatin and bcl-2 antisense oligonucleotide on human bladder cancer cell lines to determine the possible synergistic effects in cytotoxicity and to estimate its potential value for subsequent in vivo trials. MATERIALS AND METHODS: Human bladder cancer cell lines (UM-UC 3, RT 112, T24/83 and HT 1197) were treated with bcl-2 antisense oligonucleotide, cisplatin, or a combination of both and incubated for 48 h under standard conditions. Cell survival was determined using a Neubauer haemocytometer or standard MTT assay. BCL-2 expression was verified using western blotting. RESULTS: The combined treatment resulted in significant lower cell survival rates compared to individual treatment. Additionally, there was a decrease in cell survival rate with an increase in cisplatin concentration in combined treatment that was not observed in cisplatin mono treatment. CONCLUSIONS: For the combined treatment with oligonucleotides and cisplatin a synergistic effect can be strongly suggested. Therefore, further investigations and in vivo trials have to be done to determine the possible benefits for clinical applications.

Antineoplastic Agents↗

Diverticular carcinoma of the urinary bladder: diagnosis and treatment problems. A case report.

OBJECTIVES: To report a case of a primary carcinoma arising in a vesical diverticulum. CLINICAL PRESENTATION AND INTERVENTION: A 59-year-old male patient presented with painless macrohematuria. A primary carcinoma arising in a vesical diverticulum was detected with cystoscopy and confirmed with rectal endosonography and computer tomography. and radical cystoprostatovesiculectomy with ileal conduit was performed. Chemotherapy with cisplatin and methotrexate followed. The patient died of an acute cardiac event in the 4th postoperative month. CONCLUSION: This report illustrates that in a case of a closed opening of a bladder diverticulum, rectal endosonography and computer tomography do provide additional support for making a diagnosis of a hidden tumor in the diverticulum.

Antineoplastic Combined Chemotherapy Protocols↗

Intrinsic presence of poly (ADP-ribose) is significantly increased in malignant prostate compared to benign prostate cell lines.

Poly(ADP-ribosyl)ation plays important roles in cellular DNA repair mechanisms as well as in cellular proliferation and genomic stability. Four carcinoma cell lines, LNCaP, PC-3, C4-2 and MatLu, and one prostate epithelial cell line, PNT1A, were tested using the H10 antibody to poly(ADP-ribose) by Western blotting and FACS analysis for basal and activated (10 mM H2O2) PARP activity. In both analyses, higher levels of basal polymer were present in the LNCaP cell line than in the prostate epithelial cell line or the MatLu cell an line. LNCaP cells demonstrated greater than 90% positive analyzed cells in FACS analysis both before and after treatment with H2O2. PNT1A epithelial cells demonstrated evidence of polymer presence only after treatment with H2O2. Microsatellite instability due to increased oxidative damage in tumor cells has been proposed as a means for accumulation of genetic changes. As oxidative stress can stimulate poly(ADP-ribose) reactions, an increased presence of the polymer may indicate a high level of oxidative damage occurring in the tumor cells, contributing to higher levels of genetic instability towards progression.

Adenocarcinoma↗

Expression of different vascular endothelial markers in prostate cancer and BPH tissue: an immunohistochemical and clinical evaluation.

BACKGROUND: The microvessel density (MVD) is often used as a quantitative parameter for angiogenesis. The aim of this study was to evaluate the three most commonly used endothelial markers of microvessels, CD31, CD34 and vWF, in benign and malignant prostatic tissue. MATERIALS AND METHODS: Fifteen benign hyperplastic prostate and 54 prostate cancer specimens were immunohistochemically stained for CD31/CD34/vWF. The MVD obtained by each marker was quantified by a vessel count in standardized grids within the area of maximum angiogenesis. The data on MVD was interrelated and compared to tumor staging, grading and clinical follow-up. RESULTS: A significant correlation of the CD31/CD34/vWF-MVD data was observed in BPH tissue, but not in PCa. In PCa, the most sensitive marker for newly derived blood vessels was CD34. While CD34-MVD demonstrated a significant association with tumorgrading and PSA follow-up, CD31- or vWF-MVD did not. CONCLUSION: CD34 is a suitable marker for the immunohistochemical visualization of microvessels in benign and malignant prostate tissue.

Aged↗

Acoustic energy: a new transfection method for cancer of the prostate, cancer of the bladder and benign kidney cells.

BACKGROUND: Clinical use of gene therapy is limited by the poor efficacy and accuracy of intracellular DNA delivery. Known concepts of DNA transfection have not yet become clinical routine in the treatment of human disorders. We therefore focused on new transfection methods using different forms of acoustic energy as potentially safe and topographically applicable methods for gene delivery in the field of urology. MATERIALS AND METHODS: Three different cell lines (prostatic and urothelial cancer, benign kidney) were transfected by different forms of acoustic energy. The effect of several parameters of electromagnetic shock wave treatment (number and frequency of impulses, energy flow density and plasmid concentration) as well as focused ultrasound on the transfection rate was assessed in a standardized experimental setup. The transfection rate was measured through reporter genes (pEGFP) by FACScan. Transfection by lipofectamine and electroporation served as positive controls. RESULTS: All cell lines were transfectable by acoustic energy. Maximum transfection rate was achieved using focused ultrasound (49.5o%; 200 W, 500 ms, 200 microg/ml DNA). 31.3% of kidney cells were transfected by electromagnetic shock waves (1500 impulses, 200 microg/ml DNA, 0.5 mJ/mm2 energy density, 2 Hz). Plasmid strand breaks were identified as a limiting factor of the transfection rate. CONCLUSION: Transfection by acoustic energy, especially focused ultrasound, can be achieved at a high level in different cell lines. The possible topical application to urological organs and the low level of side-effects make acoustic energy a promising new gene therapy treatment option in urology.

Acoustics↗

Urolithiasis in children.

In general, the criteria for the treatment of urolithiasis in children are the same as those for adults. Today, extracorporeal shock wave lithotripsy (ESWL) is the method of choice in the treatment of most pediatric urinary stones. Stone-free rates between 67% and 93% at short-term follow-up, and 57% to 92% at long-term follow-up, have proven the efficacy of ESWL treatment in children. Nevertheless, the demand for auxiliary measures still remains. In order to achieve the most beneficial success rates under low complications, it is advisable to perform this type of ESWL in centers that claim the experience necessary for ESWL and endourological measures in children.

Journal Article↗

Identification of metastasis-associated genes in prostate cancer by genetic profiling of human prostate cancer cell lines.

OBJECTIVES: Prostate cancer (PCa) is a heterogeneous tumour entity with known interindividual differences in biological behaviour regarding tumour aggressiveness and metastatic potentiaL To date, the prediction of the metastatic status of patients with PCa has not been possible. To identify the molecular causes behind these differences, the gene expression profiles of two cell lines (LNCaP and LNCaP C4-2) with different metastatic potentials were examined using DNA microarray technology. MATERIALS AND METHODS: LNCaP and LNCaP C4-2 cells were cultured under standard conditions. RNA was isolated using Trizol extraction. After processing the total RNA according to the manufacturer's instructions, we performed Affymetrix GeneChip analysis with HG-U133A chips. Data analysis was performed using NetAffx, dChip, GenMAPP and OMIM software. RESULTS: After statistical evaluation of the raw data, we obtained a set of 158 differently expressed probe sets in the LNCaP and LNCaP C4-2 cells. The search for genes associated with proliferation, cell metabolism, growth factors, metastatic potential and tumour progression in this list revealed a number of 42 differently expressed probe sets. The comparison of this list of probe sets with the literature resulted in a list of 14 differently expressed genes which could well contribute to the metastatic potential and progression of PCa. Of these 14 genes only 6 (Cip1, IGF-1, NK4, CXCL 12, ILGF2R, RHOE) have already been associated with PCa, whereas the other 8 genes (FSTL-1, SOCS-2, Midkine, Thrombospondin 1, Secretory leukocyte protease inhibitor, Desmoglein 2, MLT 1, PTPRF) had not been previously related to PCa. CONCLUSION: DNA microarray technology offers the possibility of screening a large number of genes with regard to alterations in the expression level or mutations. In this study, we identified 14 genes that are most probably associated with the higher metastatic potential of LNCaP C4-2 cells as compared to LNCaP cells. Eight of these 14 genes are potential new molecular markers for assessing the metastatic potential of PCa, or may serve as therapeutical targets.

Apoptosis↗

Prostate cancer therapy: standard management, new options and experimental approaches.

The management of prostate cancer is one of the core tasks for urologists today. This review focuses on therapeutic options for the curative and palliative treatment of prostate cancer. Within the area of urological competence, radical prostatectomy remains the standard procedure for the curative treatment of localised prostate cancer. Recently, interest in minimally-invasive procedures such as brachytherapy, focused ultrasound and cryotherapy has increased considerably. Established palliative treatment strategies include hormonal treatment schemes as the gold standard. Chemotherapeutic regimes are used for the hormone refractory disease. In addition to both the standard and new urological therapeutic options, promising experimental systemic strategies for the generalised disease are presented in this review.

Brachytherapy↗

[The influence of "differentiated trandurethral resection" in the recurrence and progression of superficial bladder cancer].

OBJECTIVES: Experimental data show the relationship between the area of injured urothelium and recurrence rates in superficial bladder cancer. Tumor cell adherence is increased by the exposure to the extracellular matrix (ECM). Transurethral resection uncovers the ECM and might lead to recurrent tumors. The question if recurrences are increased by enlarged urothelium resection areas is difficult to answer because there will be no prospective studies available. We investigated if deeper and larger urothelial injuries, which are caused by differentiated resections lead to higher recurrence and progression rates than regular resections of bladder tumors. METHODS: 163 patients with superficial bladder cancer were retrospectively evaluated. Sixty-six received a differentiated resection and 97 a regular one. We analyzed the recurrence and progression rates over a minimum of 48 months as well as tumor persistence in the second resection. RESULTS: Patients with differentiated resections of bladder tumors were found to have no higher incidence of tumor recurrence and progression but showed a significantly higher percentage of tumor free second resections. CONCLUSIONS: As a model of enlarged urothelial lesions the differentiated resection technique for superficial bladder cancer has no negative influence on recurrence or progression rates. It seems unlikely that the extracellular matrix uncovered by resection is the main reason for the high recurrence rates. The significantly lower incidence of tumor persistence in the second resection favors the differentiated resection technique in the transurethral treatment.

Adult↗