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  • 1
    Keywords: CELLS ; EXPRESSION ; GROWTH ; SURVIVAL ; tumor ; carcinoma ; human ; DRUG ; TUMORS ; LINES ; CELL-LINES ; ASSOCIATION ; MAGNETIC-RESONANCE ; MAGNETIC-RESONANCE-SPECTROSCOPY ; METABOLITES ; SPECTROSCOPY ; GLYCOPROTEIN ; ASSAY ; resistance ; CARCINOMA CELLS ; NMR-SPECTROSCOPY ; LINE ; CANCER-CELLS ; CARCINOMA-CELLS ; PHENOTYPE ; CALCIUM ; INTERFERON-ALPHA ; DRUG-RESISTANCE ; MULTIDRUG-RESISTANCE ; cell lines ; MRS ; K562 CELLS ; ANTAGONIST ; multidrug resistance ; GENE-PRODUCT ; renal cell carcinoma ; P-GLYCOPROTEIN ; NUCLEAR-MAGNETIC-RESONANCE ; LEVEL ; carcinoma cell ; ASSAYS ; PROFILES ; CELL-CARCINOMA ; human renal cell carcinoma ; RENAL-CELL-CARCINOMA ; INTACT-CELLS ; HUMAN TUMORS ; ALPHA-INTERFERON ; FREE MG2+ ; metabolomics ; P-31-NMR spectroscopy
    Abstract: KTCTL-26 and KTCTL-2 are renal cell carcinoma (RCC) lines with high and low expression of P-170 glycoprotein, respectively. Inherent differences between the two cell lines in terms of phosphate metabolites and growth characteristics in culture were examined for possible association with multidrug resistance (MDR). Differences in response to drug treatment were investigated for 40 h incubations with various doses of vinblastine (VBL) alone or as cotreatments with various concentrations of the calcium antagonist diltiazern (DIL) and/or interferon-alpha (IFN-alpha). Treatment effects were quantitated using the MTT survival assay and 31 p magnetic resonance spectroscopy (MRS) to determine phosphate metabolite profiles in intact cells. KTCTL-2 and KTCTL-26 cells exhibited significant inherent differences in phosphocholine, glycerophosphocholine, glycerophosphoethanolamine, and phosphocreatine levels. KTCTL-26 cells were more sensitive than KTCTL-2 to 0.011 mu M VBL alone (87% vs. 102% survival) or to 0.011 mu M VBL + 10 mu M DIL (55% vs. 80% survival). The latter treatment resulted in a significant decrease in the ratio of phosphocholine to glycerophosphocholine in KTCTL-26 cells but no significant changes in phosphate metabolites in KTCTL-2 cells. Metabolomic P-31 MRS detects different metabolite profiles for RCC cell lines with different MDR phenotypes and may be useful for noninvasive characterization of tumors in a clinical setting
    Type of Publication: Journal article published
    PubMed ID: 15977034
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  • 2
    ISSN: 1432-1076
    Keywords: Hyperoxaluria type I ; Liver transplantation ; Kidney transplantation ; Oxalate pool ; Paediatric patient
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 4.5-year-old boy received a combined liver and kidney transplant for correction of hyperoxaluria type 1. Both organs were from the same donor and functioned primarily. Three months after transplantation, urine oxalate excretion reached a maximum of 10500 μmol/24 h and remained above 2300 μmol/24 h for the next 2 months. Two months later, oxalate excretion decreased to about 565 μmol/24 h, indicating exhaustion of a large oxalate pool. Six months after transplantation plasma oxalate is near normal (4.9 μmol/l). With the exception of one episode of acute rejection of the renal transplant, both organs were tolerated well and continue to have a unimpaired function 9 months after transplantation. However, there is increased echogenity on renal ultrasound, indicating oxalate deposits in the grafted kidney. This case illustrates that successful combined transplantation of both liver and kidney can be performed in infants, resulting in cure of the metabolic defect. The prolonged or acute excretion of oxalate may lead to oxalate deposition in the grafted kidney without impaired graft function or early graft loss.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1433-0563
    Keywords: Schlüsselwörter Nierenzellkarzinom ; Hirnmetastasen ; Resektion ; Radiochirurgie ; Prognose ; Key words Renal cell cancer ; Brain metastasis ; Resection ; Radiosurgery ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Brain metastases develop as a late manifestation of renal cell cancer (RCC) and pose an increasing challenge to urologists as a result of the more frequent prolonged survival of patients with advanced RCC. Therapeutic options, including surgical resection and radiotherapy, were analyzed retrospectively to assess survival and to identify factors influencing prognosis in a group of 90 patients treated either by brain metastasectomy (n = 64) or radiotherapy (n = 26). The analysis confirmed that the overall median survival was a disappointing 461 days and the 1-year survival rate was 31 % for patients treated by surgical resection and 310 days and 15 % respectively for patients treated by radiotherapy. However, a subgroup of patients who benefitted significantly from aggressive treatment of metastases could be defined. The following favorable prognostic factors showed a trend toward improved survival: (1) metachronous appearance of brain metastases more than 1 year after nephrectomy (P 〈 0.0001), (2) good patient performance (Karnofsky 〉 70) (P 〈 0.0002), (3) patient's age under 50 years (P 〈 0.05), (4) solitary lesions (P 〈 0.05), (5) minimal or no neurological deficit (P 〈 0.05), and (6) the absence of/or minimal extracranial metastases (P 〈 0.05). No influence of lesion size and localization (infratentorial vs supratentorial) on survival was detected. Surgical treatment of recurrent brain tumors (n = 17) yielded an additional median survival advantage of 8 months as compared to untreated patients (n = 16). Our results suggest that, especially in patients with good prognostic criteria, a radical metastasectomy plus vigorous surgery of local recurrences and, if required, subsequent systemic immuno- or chemoimmunotherapy should be performed. In patients with poor prognosis, stereotactic radiosurgery is recommended for palliation and survival prolongation.
    Notes: Zusammenfassung Die Resektion bzw. Bestrahlung der Hirnmetastasen als Bestandteil eines interdisziplinären Therapiekonzepts bei disseminiert metastasiertem Nierenkarzinom hat angesichts der besseren Therapierbarkeit der systemischen Metastasen neuerdings an Bedeutung gewonnen. Um den eventuell daraus resultierenden Nutzen für die Patienten zu charakterisieren, wurden die klinischen Verläufe von 90 Patienten, die im Zeitraum vom 30. 06. 1977 bis zum 30. 06. 1993 wegen hirnmetastasiertem Nierenzellkarzinom entweder operiert (n = 64) oder bestrahlt (n = 26) wurden, retrospektiv analysiert und der Effekt möglicher prognostischer Faktoren auf das Überleben untersucht. Die Analyse bestätigte zwar grundsätzlich die ausgesprochen schlechte Prognose von Patienten mit Hirnmetastasen, wobei nach operativer Behandlung die Gesamteinjahresüberlebensrate 31 % und das mediane Überleben 461 Tage und nach Bestrahlung 15 % bzw. 310 Tage betrugen. Es konnte jedoch eine Gruppe von Patienten definiert werden, die in besonderer Weise von der Behandlung profitiert hatten. Die beste Langzeitprognose zeigten Kranke 1. im Alter von unter 50 Jahren, 2. in gutem Allgemeinzustand (Karnofsky über 70) (p 〈 0,0002), 3. mit Solitärmetastasen (p 〈 0,05) und 4. langem metastasenfreiem Intervall nach dem Auftreten des Primärtumors bis zur Hirnmetastasendiagnose von 〉 1 Jahr (p 〈 0,0001) sowie 5. keinen bzw. geringgradigen neurologischen Ausfällen und 6. keinen bzw. minimalen extrakraniellen Metastasen.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2277
    Keywords: Key words Preservation ; kidney ; rat ; Cryopreservation ; kidney ; rat ; Kidney ; (cryo)preservation ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Improving organ preservation techniques for transplantation is one of the most important goals of transplantation research. We have established a new, nonfreezing cryopreservation method to optimize the viability of rat kidneys for transplantation with up to 4 M dimethylsulphoxide (DMSO) in EuroCollins solution (EC) at −5°C to −15 °C. We have confirmed the occurrence of a tubular and glomerular defect pattern that mediates acute tubular necrosis (ATN) and that may be a cause of major histocompatibility complex (MHC) independent immunological components of chronic transplant rejection. The extent of this defect [transplant survival and function, 31P-NMR spectroscopy, histological defect index] in the nonfreezing cryopreserved groups (n = 22) is significantly (P = 0.017) lower than in the simple cold storage group (n = 12). Quality and localization of the lesions in kidney transplants can elucidate the context of organ preservation, progressive hyperfiltration defects, and the occurrence of graft failure without elevated frequency of acute rejection episodes. These results indicate that further efforts to provide higher pretransplant organ viability without using it to prolong cold storage intervals may provide better insight into MHC-independent factors of chronic transplant failure and may result in improved long-term transplant outcome.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2277
    Keywords: Pediatric renal transplantation ; Cyclosporin, low-dose, in children ; Growth, cyclosporin, in kidney transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fifty-one pediatric patients undergoing a first cadaveric kidney transplantation were followed for at least 2 years after grafting. They were divided into two groups: those treated with methylprednisolone plus azathioprine (AZA) and those treated with methylprednisolone plus low-dose cyclosporin A (CyA; median dose 109 mg/m2 per day ≙ 3.4 mg/kg per day after 1 year). The steroid dosage given was significantly lower in the second group. The 4-year graft survival rate was 68% for the AZA group and 78% for the CyA group. Renal function did not differ significantly in the two groups; after 1, 2, and 3 years, the median 24-h creatinine clearance was 79, 69, and 51 ml/min/1.73 m2, respectively, for the AZA group and 78, 63, and 68 ml/min/1.73 m2, respectively, for the CyA group. Linear growth was similar in the two groups. We conclude that in pediatric patients the results of low-dose CyA immunosuppression do not differ significantly from those obtained with AZA in terms of graft survival, renal function, or growth.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Der Onkologe 4 (1998), S. 229-236 
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Die bedeutendste konventionelle Untersuchung zur Früherkennung eines Nierenzellkarzinoms, die dem Kliniker heutzutage zur Verfügung steht, ist die Sonographie der Nieren. Sämtliche bislang bekannt gewordene Serumtumormarker sind in Frühstadien dieses Leidens ohne diagnostischen Nutzen. Durch die Fortschritte der molekularen Diagnostik zeichnen sich jedoch auch beim Nierenzellkarzinom genetisch orientierte Strategien ab, die in Zukunft möglicherweise präzise biologische Marker zur Diagnostik dieses Tumors in die klinische Routine einbringen werden. Vielversprechend sind sowohl neue Markersysteme zur Diagnostik als auch Ansätze zur Prognosebeurteilung beim Nierenzellkarzinom.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1433-0563
    Keywords: Schlüsselwörter Staging • MRT • CT • Nierenzellkarzinom • Kavathrombus ; Key words Staging • MRI • CT • Renal • Kidney • Cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary To evaluate whether MRI is usefull in staging renal cell carcinomas with caval thrombus the accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in staging renal tumors with caval thrombus were preoperatively examined. Tumor staging by CT and MR imaging were correlated with histopathological tumor stadium. In MRI 4 out of 7 thrombi were correctly diagnosed with high accuracy, in CT none. In advanced renal carcinoma MRI with Gadolinium was superior to CT imaging, especially in diagnosing tumor thrombus. Consequently the extent of tumor thrombus may be assessed by MRI which therefore may replace conventional cavography.
    Notes: Zusammenfassung Ziel dieser Untersuchung war die Evaluation der optimalen und effektiven Diagnostik beim präoperativen Staging von Nierenzellkarzinomen mit Kavazapfen. Ist der Einsatz der MRT gerechtfertigt? Es wurden 7 Nierenzellkarzinome der Tumorstadien T3b und T3c präoperativ in der CT und MRT untersucht und das Staging mit dem histopathologischen Ergebnis korreliert. In der MRT wurden 4 von 7 Kavazapfen in ihrer Ausdehnung korrekt und sicher beurteilt, in der CT keiner korrekt und sicher. Die MRT mit Gadolinium ist der CT im Staging von Nierenzellkarzinomen der hohen Tumorstadien überlegen und kann hier die Kavographie ersetzen. Die MRT ist in den Fällen, in denen sonographisch ein hohes Tumorstadium mit Kavazapfen vermutet wird, als präoperative Diagnostik gerechtfertigt.
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  • 8
    ISSN: 1433-0563
    Keywords: Schlüsselwörter Xenotransplantation ; Komplement ; Löslicher Komplementrezeptor Typ 1 (sCR1) ; Key words Xenotransplantation ; Complement ; Soluble complement receptor type 1 (sCR1)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In this study a modified experimental kidney xenograft model was developed, which reproduced, in a reliable way, the course of hyperacute rejection. In this model guinea-pig kidneys were transplanted to rats using end-to-side anastomoses with recipient aorta and vena cava, respectively, and ureter drainage for diuresis monitoring. The aim of this study was to investigate the protective effects of complement modulation by soluble complement receptor 1 (sCR1) on the xenografts. Twenty-four xenotransplantations were performed and recipients randomized for treatment either by 3 ml saline or 50 mg/kg sCR1 as a 3-ml bolus. It was found that sCR1 was highly efficient in delaying hyperacute rejection from 10.5 ± 2.1 min in the control group to at least 2 h in the therapy group and in prolongation of graft function. The complement activity was significantly reduced in the sCR1-treated rats, even at the time of rejection, as a result of complement modulation in this group of xenograft recipients. Xenografts from saline-treated animals showed necroses, interstitial haemorrhages and platelet aggregates occluding the vessels as soon as 10 min after the reperfusion started. No such changes could be seen even after 120 min in the xenografted kidneys of sCR1-treated rats. Also C3 deposits in the glomeruli and interstitium were markedly reduced.
    Notes: Zusammenfassung In der vorliegenden Arbeit wurde ein modifiziertes tierexperimentelles Modell der Nierenxenotransplantation entwickelt, im Rahmen dessen der Verlauf einer hyperakuten Abstoßungsreaktion hochgradig reproduzierbar ist. In diesem Modell wurden Meerschweinchennieren als Spenderorgane auf Wistarratten als Empfängertiere verpflanzt, wobei End-zu-Seit-Gefäßanastomosen mit Spenderaorta, bzw. V. cava und Harnleiterdrainage mittels Schienung zur Diureseüberwachung zum Einsatz kamen. Ziel der vorliegenden Untersuchung war es die protektive Wirkung der Komplementmodulation mit Hilfe des löslichen Komplementrezeptors Typ 1 (sCR1) auf die Nierenxenotransplantate zu analysieren. Insgesamt wurden 24 Xenotransplantationen vorgenommen und randomisiert mit 3 ml 0,9 % NaCl (Kontrollgruppe), bzw. 50 mg/kg sCR1 als 3-ml-Bolus (Behandlungsgruppe) therapiert. Der lösliche Komplementrezeptor Typ 1 (sCR1) war wirksam in bezug auf die Verlängerung der Transplantatüberlebenszeit (von 10,5 ± 2,1 min in der Kontrollgruppe auf mindestens 2 h in der Behandlungsgruppe) und seine Funktion. Serologisch konnte eine deutliche Reduktion der Komplementaktivität in der sCR1-Gruppe festgestellt werden, die auf eine modulatorische Wirkung des sCR1 zurückzuführen ist. Bereits 10 min nach Reperfusionsbeginn zeigten sich histologisch in der Kontrollgruppe massenhaft Thrombozytenaggregate, Fibrinablagerungen in den Kapillaren und interstitielle Infiltrate. Die mit sCR1 behandelten Nierentransplantate wiesen dagegen nach 120 min eine deutlich reduzierte intravasale Thrombenbildung und geringere interstitielle Infiltration auf. Die immunhistologische Studie ließ eine gleichermaßen verminderte Ablagerung von C3 in den Glomeruli und im Interstitium in der Therapiegruppe erkennen.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1433-8726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary On a genetic level, renal-cell carcinoma has been characterized by an abnormality on the short arm of chromosome 3 (3p), which suggests the inactivation of a tumor suppressor gene. One tumor suppressor gene at 3p, the von Hippel-Lindau disease gene, is implicated in tumor development of a whole spectrum of hereditary neoplasms, including renal-cell carcinoma. It is not clear whether the same tumor suppressor gene accounts for all, i.e., hereditary and sporadic, renal-cell carcinomas. Analysis of 28 patients with sporadic renal-cell carcinomas for loss of heterozygosity was performed at chromosomal regions that contain known tumor suppressor genes so as to assess their potential involvement during renal tumorigenesis. We focused on chromosome 3p because it contains the von Hippel-Lindau (VHL) disease gene, on 5q because it harbors tumor suppressor genes involved in colorectal carcinoma, and on 17p because it includes a tumor suppressor gene involved in breast, colon, and lung carcinoma. Loss of alleles at 3p affected 96% of the evaluable patients, with frequencies being highest in the VHL region in 3p25-26 and at loci in 3p21. These data confirm the importance of a 3p defect early during tumorigenesis; however, the question as to the existence of a second renal-cell carcinoma gene remains unresolved. Changes at 5q were 53% and those at 17p were 35%, suggesting that these loci may not contribute to the initiation of the disease but rather may represent accumulating genetic defects associated with progression and malignancy.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0584
    Keywords: HCV ; HNANB ; PTH ; Blood transfusion ; Kidney transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The hepatitis C-virus (HCV) is the main etiologic agent of posttransfusion hepatitis (PTH). Most patients depending on hemodialysis need transfusion of blood before kidney transplantation. Of 272 patients after kidney transplantation, 27 (10%) were found to be anti-HCV-ELISA-positive (HCV-Antibody-ELISA, Ortho Diagnostics). The antibodies could be neutralized by HCV C-100-3 antigen. Eight of 22 patients (36%) who had more than one kidney transplantation were classified anti-HCV positive [30% (8/27) of all anti-HCV positive patients]. The number of transfused blood units ranged from 0 to 99 BU. Receiving more than one kidney graft or the transfusion of more than 5 units of blood increased the risk for HCV infection 3.5 or 4.1 times, respectively, compared with one transplantation or less than 5 units of blood. No significant interactions were seen between these two variables. Of the anti-HCV positive patients, 48% were anti-HBc negative as well as HBs-antigen negative, 52% were anti-HBc positive.
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