PubMed Health⌕ Search

Biomedical subjects

S Pomer

Publications and source records attributed to S Pomer.

At least 19 recordsLinked to original sources
PubMed2005

Investigation of multidrug resistance in cultured human renal cell carcinoma cells by 31P-NMR spectroscopy and treatment survival assays.

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 diltiazem (DIL) and/or interferon-alpha (IFN-alpha). Treatment effects were quantitated using the MTT survival assay and 31P 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 mircroM VBL alone (87% vs. 102% survival) or to 0.011 microM BL + 10 microM 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 31P 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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

PURPOSE: We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine. RESULTS: Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P =.0248). Both arm A (median overall survival, 25 months; P =.0440) and arm B (median overall survival, 27 months; P =.0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-alpha-2a-based therapies were moderately or well tolerated. CONCLUSION: Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.

Adult↗
PubMed2004

[Urodynamic findings in patients with infantile cerebral palsy].

OBJECTIVE: Aim of study was to evaluate the urodynamic findings in patients with infantile cerebral palsy. MATERIAL AND METHODS: In 29 patients (aged 3-53), a videourodynamic investigation was performed after evaluation of urological anamnesis, clinical assessment and sonographic determination of residual urine. The patients were divided into group 1 (23 symptomatic patients aged 5 years and older with recurrent urinary tract infection, pollakiuria or urinary incontinence) and group 2 (6 asymptomatic patients). RESULTS: In group 1, 21/23 patients (91%) had reduced compliance (0.6 - 16.4 ml/cmH(2)O) and 16/23 patients (70%) increased leak point pressure (> 40 cmH(2)O). In all 23 patients, detrusor instability and detrusor sphincter dyssynergia (during voiding) was found. Fluoroscopy showed bladder trabeculation or diverticula in 14 patients (61%) and 2nd-3rd degree vesicoureterorenal reflux in 2 patients (9%). In group 2, 2/6 patients (33%) had reduced compliance (0.7 and 5.8 ml/cmH(2)O) and 4/6 (67%) increased leak point pressure (> 40 cmH(2)O). In 5/6 patients (83%), detrusor instability and detrusor sphincter dyssynergia was seen. Fluoroscopy showed bladder trabeculation in 3 patients (50%), whereas no reflux was observed. Only one of the 29 patients (3 %) showed no pathological videourodynamic or anamnestic findings. CONCLUSIONS: We conclude that videourodynamic assessment should be performed in all patients with infantile cerebral palsy. The decision should not be based on clinical symptoms such as pollakiuria, recurrent urinary tract infection or urinary incontinence.

Adolescent↗
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↗
PubMed2000

VHL alterations in human clear cell renal cell carcinoma: association with advanced tumor stage and a novel hot spot mutation.

To elucidate the role of somatic alterations for renal cancer etiology and prognosis, we analyzed 227 sporadic renal epithelial tumors for mutations and hypermethylations in the von Hippel-Lindau tumor suppressor gene VHL. Tumors were classified according to the recommendations of the Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Somatic VHL mutations were identified by PCR, single-strand conformation polymorphism analysis, and sequencing, and hypermethylations were identified by restriction enzyme digestion and Southern blotting. Frequencies of VHL alterations were established, and an association with tumor type or tumor type and tumor stage was evaluated. VHL mutations and hypermethylations were identified in 45% of clear cell renal cell carcinomas (CCRCCs) and occasionally (3 of 28) in papillary (chromophilic) renal cell carcinomas (RCCs). Lack of VHL mutations and hypermethylations in chromophobe RCCs and oncocytomas was statistically significant (P = 0.0001 and P = 0.0004, respectively). RCCs carrying VHL alterations showed, in nine cases (12%), mutations at a hot spot involving a thymine repeat (ATT.TTT) in exon 2. Tumor staging was critical to the VHL mutation/hypermethylation detection rate in CCRCCs shown by separate evaluation of patients from medical centers in Munich, Heidelberg, and Mainz. The spectrum of pT1, pT2, and pT3 CCRCCs and the VHL mutation/hypermethylation detection rate varied among these three groups. Altogether, VHL alterations were significantly associated with pT3 CCRCCs (P = 0.009). This is the first evidence of frequent somatic VHL mutations at a particular site within exon 2 and an association of VHL mutations/hypermethylations with a standard prognostic factor.

Adenoma, Oxyphilic↗
PubMed2000

[Preoperative staging of renal cell carcinoma with caval thrombus: is staging in MRI justified? Prospective histopathological correlated study].

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.

Aged↗
PubMed1999

Interferon alpha2b differentially affects proliferation of two human renal cell carcinoma cell lines differing in the P-glycoprotein-associated multidrug-resistant phenotype.

PURPOSE: Interferon alpha (IFNalpha) has been used in the immunotherapy of renal cell carcinoma (RCC), but the various mechanisms of its antiproliferative effects are poorly understood. Recent evidence suggests that IFNalpha is involved in the up-regulation of multidrug resistance (MDR) gene expression, and that the MDR gene product, P-glycoprotein (Pgp). facilitates the transport of several cytokines, some of which have been implicated in mediating tumor antiproliferative effects. We hypothesized that IFNalpha-induced antiproliferative activity may require Pgp-mediated transport, and that susceptibility to IFNalpha may thus correlate with Pgp expression. METHODS: Pgp expression by the human RCC cell lines KTCTL-2 and KTCTL-26 was characterized by immunofluorescence staining, using the Pgp-specific primary antibodies C219 and JSB1. KTCTL-2 and KTCTL-26 cell lines were subsequently treated with IFNalpha2b, and growth kinetics of treated and control cell cultures were determined daily by cell counting. RESULTS: KTCTL-2 expresses Pgp at low levels, whereas KTCTL-26 is a highly expressing cell line. IFNalpha2b treatment abrogated cell proliferation in KTCTL-26, whereas proliferation of KTCTL-2 was only partially inhibited. CONCLUSIONS: We have identified two RCC cell lines that differ in the MDR phenotype and exhibit different responses to the antiproliferative activity of IFNalpha2b. These preliminary findings raise the possibility that susceptibility to the antiproliferative effects of IFNalpha2b may correlate with Pgp expression, and further studies are warranted.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Nonfreezing cryopreservation--a possible means of improving long-term transplant function?

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 degrees C to -15 degrees 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.

Animals↗
PubMed1998

[The staging of renal-cell carcinomas in MRT and CT--a prospective histologically controlled study].

PURPOSE: To evaluate the accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in staging renal carcinoma. MATERIAL AND METHODS: 33 renal carcinomas were preoperatively examined for tumour staging by CT and MR imaging and correlated with histopathological staging. CT imaging was performed at first as a non-contrast scan. Finally incremental images (10 mm) after intravenous contrast injection were obtained. In MR imaging we performed a transversal T1-weighted GE sequence (112/5) with and without GDTPA, a transversal fat-suppressed double-echo sequence (3900/22/90), a coronal T1-weighted GE sequence with and without GDTPA and a coronal T2-weighted TSE sequence (2800/128). In addition, dynamic T1-weighted GE imaging after GDTPA injection as well as TOF angiography in coronal direction were performed. Finally CT and MRI findings were correlated with surgical and histopathological staging results. RESULTS: CT and MRI staging was correct in 27 and 28 of 33 tumours. Sensitivity and specificity for tumour stage T3b to T4 was for MRI and CT 88.9% and 95.8%. With MRI 4 out of 7 thrombi were correctly diagnosed with high accuracy, but via CT none. CONCLUSION: In early stage renal carcinoma CT and MR imaging yielded similar staging accuracies. In advanced renal carcinoma MRI was superior to CT imaging, especially in diagnosing tumour thrombus. Consequently the extent of tumour thrombus may be assessed by MRI which may therefore replace conventional cavography.

Adult↗
PubMed1998

[Significance of the complement system for xenotransplantation: strategies for therapeutic intervention].

Hyperacute graft rejection triggered by the activation of the recipient's complement system represents the major obstacle to successful xenotransplantation. After the binding of preformed antibodies to vascular glycoproteins complement-induced activation and injury of endothelial cells with subsequent thrombosis leads to rapid destruction of foreign tissues. Inhibition of complement activation is therefore considered as a prerequisite for xenograft survival. Recent animal and cell culture experiments suggest that support of the physiological regulation of the complement system appears to be most promising. Besides the application of soluble complement inhibitors (e.g. soluble complement receptor 1, sCR1; C1 inhibitor) the genetic transfer of human membrane-bound complement regulatory proteins (e.g. DAF, CD59) offers new chances to protect the xenograft against the cytolytic complement attack. Results from the authors' experiments shall be included in a short overview to the issue.

Animals↗
PubMed1997

[Brain metastases in renal cell carcinoma. Results of treatment and prognosis].

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 and 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.

Adult↗
PubMed1997

Surgical treatment of invasive penile cancer--the Heidelberg experience from 1968 to 1994.

OBJECTIVES: This study was performed to establish oncological guidelines for the surgical treatment of invasive penile cancer. MATERIALS AND METHODS: The medical records of 51 patients with invasive penile cancer seen between 1968 and 1994 were reviewed in respect to treatment and long-term outcome. RESULTS: For stage T1 tumors treated with organ-preserving procedures the local recurrence rats was 56%, whereas no patient experienced a local recurrence after partial amputation. For stage T2 tumors, local recurrence rate was 100% (organ preservation) versus 20% (amputative procedures). There was no significant difference related to regional recurrence between surveillance, inguinal radiation and lymphadenectomy for stage N0 tumors. For N+ stages, survival was related to the extent of inguinal metastasis after dissection (5-year survival rate for N1: 71 vs. 33% for N2/3). CONCLUSIONS: Organ-preserving procedures include a high risk of local and regional recurrence. Adjuvant regional lymphadenectomy seems beneficial only in patients with solitary metastasis.

Adult↗
PubMed1996

Concomitant overexpression of the EGFR and erbB-2 genes in renal cell carcinoma (RCC) is correlated with dedifferentiation and metastasis.

Gene amplification or structural alteration of different erbB genes exerts a transforming effect in a variety of human neoplasms. Overexpression of the EGF receptor is associated with tumor initiation and progression of renal cell carcinoma (RCC). However, the role of erbB-2 in these processes remains unknown. We investigated 34 renal cell carcinomas for gene amplification and expression of the EGFR and erbB-2 genes at the mRNA and protein level and their relationship to pathological and clinical parameters. No amplification of both genes has been observed. However, high expression of the EGF receptor protein and p185erbB2 was frequent in RCC and statistically significantly related to higher tumor grades. We could demonstrate a close correlation of p185erbB2 overexpression with high EGF receptor levels. Co-overexpression of both receptor types was significantly associated with metastatic disease. Our results suggest a synergistic involvement of both EGF receptor and p185erbB2 in the progression of RCC.

Blotting, Southern↗
PubMed1996

[Effect of complement modulation with the soluble complement receptor sCR1 on survival and function of kidney xenotransplant. An experimental study with a new guinea pig to rate transplant model].

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.

Animals↗
PubMed1996

Aetiology, diagnosis and management of spontaneous perirenal haematomas.

This study focuses on the diagnostic and therapeutic challenge posed by spontaneous perirenal haematomas (SPHs). The medical records of 18 patients with SPHs seen in the past 8 years were reviewed with respect to aetiology, diagnosis and therapeutic management. SPH was secondary to angiomyolipoma (n = 4), polycystic kidneys (n =4), panarteritis nodosa (n = 3), renal cell carcinomas (RCCs, n = 2), glomerulonephritis, pyelonephritis, Morbus Wegener and cortical adenoma (one each). One case remained unclear. With appropriate imaging techniques (computed tomography and angiography) the underlying disorder was detected in 72%; in 4 cases the diagnosis was revealed by exploration and biopsy. Surgery was necessary in 16 patients. The cause of bleeding can be revealed by appropriate imaging in most cases. When imaging procedures fail to reveal the cause of SPH, exploration and biopsy are mandatory to exclude RCC. If the cause of SPH remains unclear even after exploration, patient monitoring by CT is justified.

Adenoma↗
PubMed1996

[Effect of HLA compatibility on the transplanted kidney in relation to recipient age].

Donor-recipient histocompatibility, as evaluated by the HLA matching results, plays an important role in the outcome of renal transplants, although much controversy surrounds the benefit of kidney allocation based on HLA typing. In this report HLA matching and survival data on 1,342 transplants performed at the University of California at San Francisco between 1984 and 1992 and treated uniformly by quadruple immunosuppression were analyzed in relation to the recipient's age. With respect to the influence of the increasing number of mismatches from 0 to 6, the analysis revealed decreasing 3-year graft survival rates as follows: 85.4%; 87.3%; 71.3%; 78.2%; 75.8%; 70.9% and 67.5%. Whereas the impact of cold ischemia time and histocompatibility was equally important during the 3-year postoperative period, the essential positive influence of good HLA matching on the long-term graft survival was demonstrated. The children aged between 5 and 18 years were identified as a high-risk group by the analysis, HLA-A incompatibility being attributed to poor graft survival in this age group. With respect to the effect of HLA-A histoincompatibility, the data provide evidence that HLA-A matching results seem to play an important role in graft survival in children, whereas transplants well matched in terms of HLA-B did well in adult recipients. No age difference in the impact of HLA-DR could be detected. In conclusion, HLA matching is still essential. It seems that there are differences in the impact of HLA loci in relation to the recipient's age.

Adolescent↗