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Biomedical subjects

G Jakse

Publications and source records attributed to G Jakse.

At least 73 records · Page 4Linked to original sources
PubMed1998

The efficacy of 2',2'-difluorodeoxycytidine (gemcitabine) combined with interferon in human renal cell carcinoma cell lines.

The present in vitro study on three human renal cell carcinoma (RCC) cell lines (A-498, ACHN, SN12C) evaluated the efficacy of 2',2'-difluorodeoxycytidine (dFdC, gemcitabine), vinblastine (VBL), rhu-interferon-alpha (IFN-alpha) and rhu-interferon-gamma (IFN-gamma) alone or in combinations. The cytotoxicity was measured by using the sulphorhodamine B colorimetric cytotoxicity assay. Analyses were made from cells being continuously long-term (4 weeks) or short-term (4 h) with IFN-alpha or IFN-gamma with regard to the cytotoxicity of the chemotherapeutic agents. dFdC was more cytotoxic against ACHN and A-498 cells compared to VBL. Pre-treatment with IFN-alpha enhanced growth inhibition caused by dFdC (4/4 cell lines) and VBL (2/3 cell lines), and was more effective than IFN-gamma. Pre-exposure with IFN-alpha sensitized SN12C and ACHN cells for dFdC. A-498 cells achieved a decreased sensitivity to dFdC and VBL after pre-exposure to IFN-gamma. The resistance of newly established dFdC-resistant SN12C cells (23-times) decreased when pre-treated with IFN-alpha. The data demonstrate efficacy of dFdC in human RCC at concentrations below clinically achievable doses. dFdC was more effective compared to VBL. Combined therapy preferentially with IFN-alpha increased cytotoxicity of dFdC in vitro. In vivo studies in nude mice xenografts are under investigation to support these observations.

Antineoplastic Agents↗
PubMed1998

The efficacy of 2',2'-difluorodeoxycytidine (gemcitabine) and vinblastine combined with interferon in nude mice xenografts of human renal cell carcinoma.

Recent in vitro experiments indicated strong activity of 2',2'-difluorodeoxycytidine (dFdC, gemcitabine) in human renal cell carcinoma (RCC) cell lines and an increase of efficacy by combined application of interferon (IFN). In the present study, nude mice with xenografts from ACHN- or SN12C cells were treated by dFdC, dFdC plus IFN-alpha or vinblastine (VBL) plus IFN-alpha. ACHN-xenografts were significantly more inhibited by dFdC+/-IFN-alpha than by VBL+IFN-alpha. Complete remissions (CR) were only seen by dFdC. An additional treatment with IFN-alpha shortened the time to commencement of tumor remission and increased CR of ACHN- and SN12C-tumors (40%; 7%) compared to a treatment with dFdC alone (20%; 0). dFdC+IFN-alpha reduced the number of pulmonary metastases compared to untreated animals. Survival was significantly prolonged by dFdC+/-IFN-alpha in ACHN-mice and dFdC+IFN-alpha or VBL+IFN-alpha in SN12C mice. In conclusion, experimental data confirm dFdC as a superior drug against human RCC compared to VBL. Combined therapy with IFN-alpha increased the efficacy of dFdC in terms of tumor response in immunodeficient nude mice, thus clinical studies are strongly recommended in patients with metastatic renal cell carcinoma.

Animals↗
PubMed1998

Transforming growth factor-beta1 serum concentration in patients with prostatic cancer and benign prostatic hyperplasia.

OBJECTIVE: To assess serum levels of transforming growth factor-beta1 (TGF-beta1), normally markedly elevated in prostate cancer tissue, in patients with cancer of the prostate, and to correlate these levels with tumour stage and serum prostate specific antigen (PSA) levels. PATIENTS AND METHODS: Serum TFG-beta1 and PSA levels were determined in 32 patients with untreated prostate cancer. Patients were divided into: group 1, 14 patients with pT1-3pN0M0; group 2, four with T1-3pN+M0); and group 3, 14 with T1-4NxM+. Ten patients with histologically confirmed benign prostatic hyperplasia (BPH) served as controls. RESULTS: The median TGF-beta1 levels were no different between patients with cancer or BPH (30.7 ng/mL and 26.9 ng/mL, respectively; P > 0.05). Furthermore, there was no increase in TGF-beta1 concentrations with advancing tumour stage (group 1, 34.1 ng/mL; group 2, 33.0 ng/mL; group 3, 28.3 ng/mL; P > 0.05). There was no correlation with PSA levels (group 1, r= -0.42: group 2, r= -0.43; group 3, r= -0.23; BPH, r=0.38). CONCLUSION: TGF-beta1 levels did not discriminate between patients with BPH and prostate cancer, and there was no increase in TGF-beta1 levels with advancing tumour stage.

Aged↗
PubMed1998

Spontaneous retroperitoneal haemorrhage associated with renal disease.

Spontaneous retroperitoneal haemorrhage is an uncommon entity. It is even rarer when the underlying cause is associated with renal disease. In most cases the non-traumatic rupture of a kidney requires an emergency surgical intervention as the underlying disease only becomes clear intra-operatively. Most patients with a spontaneous kidney rupture have a renal tumour. Of these renal tumours, angiomyolipomas show a particular tendency to rupture. The cases are reported of five patients who presented with an acute onset of spontaneous retroperitoneal haemorrhage from different kidney disorders. The importance of considering the possibility of spontaneous kidney rupture in the evaluation of patients presenting with spontaneous retroperitoneal haemorrhage is stressed.

Adult↗
PubMed1998

FDG PET for detection and therapy control of metastatic germ cell tumor.

UNLABELLED: We investigated the use of PET and 2[18F]fluoro-2-deoxy-D-glucose (FDG) for detection and therapy control of metastatic germ cell cancer in comparison to CT. METHODS: Fifty-four PET studies were performed in addition to CT in 33 patients with histopathologically proven germ cell tumors (14 seminomas, 18 nonseminomas, 1 not classified). The scans were done either after initial diagnosis (Group 1; n = 12), within 2 wk after completion of chemotherapy (Group 2; n = 13) or 14-375 days after chemotherapy (Group 3; n = 29). PET and CT were validated either by histology (n = 19) or clinical follow-up for 182-1704 days (n = 35). Focal pathological uptake with PET was quantified using standardized uptake values (SUVs). RESULTS: PET was significantly more accurate than CT (0.86 versus 0.59; p < 0.025) for detection of residual viable tumor in Group 3. While sensitivities of PET and CT did not differ markedly, PET was significantly more specific than CT. No significant differences between PET and CT were found in Groups 1 and 2. PET scans after therapy resulted in false-negative findings in five of nine cases of Group 2 but only in two of nine cases of Group 3. False-positive PET findings occurred in three inflammatory processes. SUV of seminomas was significantly higher than in nonseminomas (p < 0.01). CONCLUSION: PET using FDG is superior to CT for assessment of residual tumor after chemotherapy of germ cell cancer and may thus have an increased effect on patient management in the future. PET must be performed at least 2 wk after completion of therapy. Further data are necessary to determine the role of FDG PET for initial staging of germ cell cancer.

Adult↗
PubMed1998

Biocompatibility, cell adhesion, and degradation of surface-modified biodegradable polymers designed for the upper urinary tract.

OBJECTIVES: The aim of this study was to develop a short bioresorbable ureteric stent and to characterize polymers and their surface modifications with respect to biocompatibility, degradation kinetics, cell adhesion properties, and incorporation of biologically active substances. Poly(D,L-lactide) PDLLA, poly(D,L-lactide-co-glycolide) PDLLA-co-GLY, and poly(D,L-lactide-co-trimethylenecarbonate) PDLLA-co-TMC were chosen as basic polymers. Surface modification was performed by plasma-induced graft polymerization and included grafting with hydroxyethylmethacrylate (HEMA), oligo(ethyleneoxide)-monomethacrylate (OEOMA), and acrylic acid (AAC). Biocompatibility of the polymers was assessed in vitro applying parameters of cell morphology, proliferative activity, and cell adhesion. All polymers were biocompatible and exerted no toxic effect on urothelial cell lines and on primary human urothelial cell cultures. A markedly reduced cell adhesion could be achieved in polymers grafted with HEMA, OEOMA, and AAC. Our results indicate that surface modification of bioresorbable polymers by grafting with HEMA, OEOMA, or AAC is an efficient approach to improve surface properties with respect to biocompatibility and cell adhesion properties.

Absorption↗
PubMed1997

Local expression of cytokines in rat bladder carcinoma tissue after intravesical treatment with Nocardia rubra cell wall skeleton and bacille-Calmette-Guerin.

This study aimed to investigate local immunotherapy with Nocardia rubra cell wall skeleton (N-CWS) and bacille-Calmette-Guerin (BCG) in chemically induced rat bladder carcinoma. After being fed with 0.025% N-butyl-N-(4-hydroxybutyl) nitrosamine for 26 weeks, female Wistar rats were treated once a week by intravesical instillation of 100 microg N-CWS or 5 x 10(6) Colony-Forming Units (CFU) BCG. Tissue specimens were obtained 4 h after the ninth instillation and analyzed by reverse transcription polymerase chain reaction (RT-PCR) for mRNA expression of rat cytokines. The analysis showed high expression of interleukin (IL)-1 alpha, tumor necrosis factor (TNF)-alpha, IL-2, and interferon (IFN)-tau in BCG (7/7, 7/7, 7/7, 5/7) and N-CWS (9/9, 9/9, 8/9, 8/9) treated tumors in comparison to low expression in controls (3/9, 0/9, 3/9, 3/9). Interestingly, intravesical instillation of N-CWS tended to be less effective at preventing local invasion of the tumors. It is speculated that this difference may result from a more strongly induced expression of T-helper cell-derived lymphokines (IL-2, IFN-tau) by BCG.

Actins↗
PubMed1997

Detection of circulating prostatic cells during radical prostatectomy.

The detection of micrometastasis of prostate cancer could help to decide more appropriate therapeutic strategies in an individual patient. We have developed a flow cytometric method for detecting cytokeratin-positive cells in the peripheral blood before, during and after radical prostatectomy in patients with prostatic carcinoma. By means of this technique we were able to detect a higher number of cytokeratin-positive cells in the intraoperative blood sample than in the pre- and postoperative blood sample in 15 patients with prostate cancer (P < 0.05). Our results show an increase in the number of cytokeratin-positive cells with increasing tumor stage and grade, as well a good correlation of prostate-specific antigen (PSA) value with the number of cytokeratin-positive cells (r > 0.6). Our results underline the importance of no-touch techniques at prostatectomy to minimize release of tumor cells into the circulation during surgery. In the light of our results we consider that the indication for cell savers during radical prostatectomy should be reevaluated. The possibility of detecting single metastatic cells in peripheral blood will enable better individual patient management, and open up new modalities for diagnosing early prostate cancer and enhancing patient monitoring in relapse and tumor progression.

Aged↗
PubMed1997

[Improved discrimination between prostatic carcinoma and benign prostatic hyperplasia by determination of free prostate-specific antigen percentage].

We investigated whether the free-to-total prostate-specific antigen (PSA) ration (f-PSA/t-PSA ratio; i.e. percentage of free PSA) represents a better discriminator for the detection of cancer of the prostate (CaP). In a retrospective analysis, the percentage of free PSA was determined in the sera of 35 patients with histologically proven benign prostatic hyperplasia (BPH) and 35 patients with clinically localized CaP. Patients with urolithiasis (n = 33) served as a control group. Serum levels of free PSA and total PSA were determined employing a chemiluminescent enzyme immunoassay. Patients with CaP demonstrated a lower percentage of free PSA (median: 8.7) than patients with BPH (median: 20.0; P < 0.001). Determination of the percentage of free PSA enhances the differentiation between BPH and CaP and may reduce the number of unnecessary biopsies in patients with an elevated PSA. Confirmation of our preliminary results is required.

Aged↗
PubMed1997

Development of a biodegradable ureteric stent: surface modification and in vitro assessment.

The aim of the present study was to develop a short bioresorbable ureteric stent and to characterize the chosen polymers with respect to surface modification, biocompatibility, and loading of a biologically active compound. As materials for the stent, poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) were chosen. Degradation experiments were carried out and analytical data were obtained by contact angle measurement, X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy in the attenuated reflection mode (FTIR-ATR). Gas loading technology was used to incorporate biologically active compounds, and biocompatibility of the polymers was assessed by in vitro cellular assays, applying measures such as cell morphology, proliferative activity, and membrane integrity. Our results indicate that surface modification of bioresorbable polymers is a suitable and efficient approach to improve the surface properties. Incorporation of biologically active compounds was possible without loss of activity, and in vitro assessment of cellular responses demonstrated the biocompatibility of the chosen polymers and modifications.

Absorption↗
PubMed1997

Cystoplasty in pigs: a suitable model for the functional and morphological examination of urinary diversion.

Although in the last years surgery for urinary diversion became routine in clinical practise, various problems have to be solved. Therefore, a safe, universal animal model is necessary. An ileal pouch anastomosed to the subtotally resected urinary bladder was formed in 6 domestic pigs. Ureters remained untouched and the reservoir was not drained by any tubes. Animals were followed up for 3 months, every 3-4 weeks blood was drawn for electrolytes, renal and hepatic function and blood gas analysis. The animals were sacrificed after 3 months and a thorough pathohistological examination of the reservoir was performed. No intraoperative or operation-related postoperative complications were seen. Laboratory parameters were stable and no micturition problems appeared. Upper urinary tract was normal. The animal model presented is safe with regard to inflammatory or metabolic side effects and to disturbances of supravesical urinary tract. Therefore, this model is suitable to serve for short- as well as long-term studies of various forms of urinary diversions.

Animals↗
PubMed1997

C-reactive protein as a marker for tissue damage in patients undergoing ESWL with or without retrograde stone manipulation.

In this study we attempt to evaluate the advantages and disadvantages of extracorporeal shock wave lithotripsy (ESWL) in situ versus retrograde stone manipulation before ESWL (ESWL+push back) in patients with proximal ureteral stones with regard to tissue damage and inflammatory processes. Several studies have revealed that C-reactive protein (CRP) is a useful marker for tissue damage and inflammation. Thirty patients following primary ESWL in situ, with residual calculi, were randomized to retreatment with ESWL in situ or ESWL+push back. Four of 15 patients in the ESWL+push back group demonstrated an increase in CRP levels after treatment compared with no significant increase in 15 patients in the ESWL in situ group. We conclude that ESWL+push back did not cause significantly higher CRP values than ESWL in situ. ESWL+push back may cause irritation, inflammation, and slight tissue damage in some cases; however, these effects are probably minor and would not contraindicate its use. The implications of this study are that serum CRP levels may be utilized to monitor tissue injury in patients undergoing auxiliary procedures.

Biomarkers↗
PubMed1997

Prostate-specific antigen immunoreactivity in spinal fluid.

OBJECTIVES: Prostate-specific antigen (PSA) is no longer believed to be tissue specific for prostate epithelial cells as it has been documented in various human tissues. The physiological role of PSA in this context is currently unknown. Furthermore the distribution of PSA throughout the human body remains to be established. We therefore investigated PSA immunoreactivity in human spinal fluid (SF). METHODS: The PSA concentration was measured in the SF and sera of 34 men and 6 women. The SF was obtained prior to spinal anesthesia and was kept frozen at -20 degrees C until analysis. RESULTS: PSA was detected in the SF of male patients. Median SF PSA was 0.03 ng/ml in the 34 men, whereas SF PSA was below the detection limit in the 6 women. In men we could establish a positive correlation between SF PSA and serum PSA with a correlation coefficient of r = 0.85 (p < 0.001). CONCLUSION: These results confirm recent literature reports indicating that PSA is detectable in various human tissues and fluids.

Adult↗
PubMed1997

Direct invasion of the renal vein by metastatic testicular cancer.

We report a case of metastatic seminoma with direct invasion of the left renal vein. A tumor thrombus was found in the renal vein while the vena cava thrombosis proved to be a noncancerous blood clot developing as an extension of the tumor thrombus. Primary chemotherapy could not be completed because of thrombotic growth requiring surgical intervention. Although surgical specimens were free of viable tumor and two cycles of adjuvant chemotherapy were applied, the tumor relapsed in the area of renal vein invasion.

Adult↗
PubMed1997

Evaluation of possible tissue damage in patients undergoing extracorporeal shock wave lithotripsy employing C-reactive protein.

Extracorporeal shock wave lithotripsy (ESWL) has become the most common treatment for stones in the upper urinary tract. Tissue injury related to ESWL has been documented. C-reactive protein (CRP) is the classical acute-phase protein most recognized as an early marker in diseases characterized by inflammation and tissue injury. Possible tissue trauma by ESWL was evaluated by serial CRP determinations in 150 patients with kidney stones, whose follow-up was uneventful. The mean CRP-concentration prior to ESWL was 6.34 mg/l. The majority of patients did not show any further elevation of CRP-levels. Mean CRP-levels were 7.62 mg/l on the first, 6.12 mg/l on the third and 5.09 mg/l on the fifth day after ESWL. No correlation was observed between the number of shock waves and CRP levels. Judged by CRP-determinations tissue damage induced by ESWL can be considered to be minimal as no marked CRP-elevations could be observed in patients with an uneventful follow-up after ESWL.

Acute-Phase Reaction↗
PubMed1997

Adenocarcinoma of the urachus: 3 case reports and a review of the literature.

Urachal carcinoma of the bladder is a very rare tumor which has to be differentiated from primary adenocarcinoma of the urinary bladder. The treatment of choice is extended partial cystectomy with inclusion of the umbilicus and the peritoneum. Symptoms occur late and the diagnosis has to be made by preoperative transurethral biopsy. We herein report on 3 cases of urachal adenocarcinoma of the urinary bladder and reviewed the literature.

Adenocarcinoma, Mucinous↗