Nutrition and risk of prostate cancer.
Explore the source record for details and available documents.
Antioxidants↗
Biomedical subjects
R Ackermann
Publications and source records attributed to R Ackermann.
Up-regulation of cyclin-dependent kinase 4/cyclin D2 expression but down-regulation of cyclin-dependent kinase 2/cyclin E in testicular germ cell tumors.
Testicular germ cell tumors (GCT) characteristically display two chromosome 12 abnormalities: the isochromosome i(12p) and concomitant deletions of the long arm. Some genes important in the control of the G(1)-S cell cycle checkpoint G(1)-S, i.e., cyclin-dependent kinases 2 and 4, cyclin D2 are located on this chromosomal region. Therefore, testicular GCTs were analyzed as to the expression of CDK2, CDK4, CDK6, and the expression of their catalytic partners cyclins D1, D2 and E by semiquantitative reverse transcription-PCR. Cyclin D2, located on 12p, was overexpressed in 69% (31 of 45) of the tumors by a mean factor of 8, including all histological subtypes. In addition, the cyclin D2 partner CDK4 was increased in 41% (21 of 51) of all tumors by a factor of 6, most strongly in embryonal carcinomas. Sixty-four percent of the seminomas and 23% of the non-seminomas had decreased expression of CDK6 by a mean factor of 5 (P = 0.009). Statistical analysis using configural frequency analysis and regression analysis revealed that cyclin D2 and CDK4 expression were strongly correlated (r(2) = 0.682; P = 0.000052), whereas expression of CDK6 did not correlate with either of them (r(2) = 0.382; P = 0.00085). CDK2 and its catalytic partner cyclin E were down-regulated in 40% (19 of 47) and 42% (19 of 45) of the tumors, respectively, by a factor of 7 each. Western blots and immunohistochemical experiments confirmed cyclin D2 and CDK4 overrepresentation and reduced expression of cyclin E and CDK2 tumors in the few tumors under protein study. Despite its localization on 12q13, a hot spot for loss of heterozygosity in testicular GCTs (>40%), Southern blotting revealed no gross DNA alteration of the CDK2 gene. Because up-regulation of the cyclin D2/CDK4 complex and down-regulation of cyclin E/CDK2 complex were found in seminomas as well as in non-seminomas and in all tumor stages, these findings seem to be early events during tumorigenesis of testicular GCTS: Together with previous findings that retinoblastoma mRNA and protein expression is strongly decreased in these tumors, these data suggest an unusual deregulated G(1)-S checkpoint as a decisive event for germ cell tumors.
CDC2-CDC28 Kinases↗
[Prognostic factors in urothelial carcinoma].
Intense efforts are being made to identify prognostic markers in superficial and muscle invasive bladder cancer in order to get more detailed information on the biological properties of urothelial cancer. Tumor associated antigens, angiogenetic factors and their inhibitors, cell adhesion molecules, cell cycle regulating genes and proteins, oncogenes and tumor suppressor genes are subjects of clinical investigations. This article provides a contemporary review of prognostic factors in bladder cancer and their possible clinical implication. A better characterization of urothelial cancer can be anticipated from new technologies allowing analysis of multiple genes or gene products in an automated one-step procedure.
Biomarkers, Tumor↗
Whole-body kinetics and dosimetry of cis-4-[(18)F]fluoro-L-proline.
The whole-body distribution of 4-cis[(18)F]fluoro-L-proline (cis-FPro) was studied in six patients with urological tumors by PET. Based on the IMEDOSE and MIRDOSE procedures radiation absorbed doses were estimated from whole-body PET scans acquired at 1 and 3-5 h after i.v. injection of 400 MBq cis-FPro. Cis-FPro showed high retention in the renal cortex and a slight uptake in liver and pancreas. Urinary excretion ranged from 12 to 19% at 5 h p.i. Highest absorbed doses were found for the urinary bladder wall and the kidneys (44.1/44.0 microGy/mbq). The effective dose according to ICRP 60 was 15.1 microSv/mbq for adults. This leads to an effective dose of 6.0 mSv in a PET study using 400 MBq cis-FPro.
Adult↗
Simultaneous diagnosis of a metanephric adenoma and a clear cell carcinoma of the contralateral kidney.
Metanephric adenoma of the kidney is a rare, newly recognized entity of a unique benign renal tumor. Clinically, pain, hematuria and palpable mass are the most common presenting signs. Females predominate by well over 2:1. A higher incidence of polycythemia is often found in these patients. Only a few cases of this type of adenoma have been reported in the literature. We report on a 78-year-old female patient with a metanephric adenoma of the left kidney, which showed typical clinical, radiologic, microscopic and immunohistochemical findings. A clear cell carcinoma of the contralateral kidney was also discovered and treated.
Adenocarcinoma, Clear Cell↗
Uptake of cis-4-[18F]fluoro-L-proline in urologic tumors.
UNLABELLED: Tumor uptake of the amino acid cis-4-[18F]fluoro-L-proline (cis-FPro) was studied with PET in eight patients with urologic tumors. METHODS: Three patients had primary renal cell carcinomas (RCCs), one had a local recurrence of RCC, one had squamous RCC, one had an adrenal hemangioma, one had inguinal metastases of penile squamous carcinoma, and one had suspected metastatic disease from prostate cancer. PET scans of the trunk were acquired at 1 and 3-5 h after intravenous injection of 400 MBq cis-FPro and compared with 18F-FDG PET scans and CT. RESULTS: None of the tumors or metastases showed significant uptake of cis-FPro. FDG uptake was seen in one of the three primary RCCs, in the local recurrence of RCC, in the squamous RCC, and in the metastases of penile cancer. CONCLUSION: Cis-FPro appears not to be a promising PET tracer in oncology.
Adult↗
Collagens serve as an extracellular store of bioactive interleukin 2.
The binding of certain growth factors and cytokines to components of the extracellular matrix can regulate their local availability and modulate their biological activities. We show that interleukin 2 (IL-2), an important stimulator of T cell growth, preferentially binds to collagen types I, III, and VI and to a lesser degree to collagen types II, IV, and V, immobilized on polystyrene or nitrocellulose. These interactions are inhibited by denatured, single collagen chains or a subset of their cyanogen bromide peptides in a dose-dependent manner. Cross-inhibition experiments and ligand blotting of collagen-derived peptides point to a limited set of collagenous consensus sequences mediating the binding of IL-2. This interaction is saturable, with dissociation constants of approximately 10(-)(8) m, and estimated molar ratios of 4-6 molecules of IL-2 bound to one molecule of triple helical collagen. Furthermore, collagen-bound IL-2 stimulates proliferation of mouse lymphocytes. We conclude that its specific binding to the abundant interstitial collagens leads to a spatial pattern of bioavailable IL-2 which is dictated by the local organization of the collagenous extracellular matrix. This interaction may contribute to the particular phenotype of stromal lymphocytes and could be exploited for devising collagenous peptide analogues that modulate IL-2 bioactivity.
Animals↗
Novel mutations of the von hippel-lindau tumor-suppressor gene and rare DNA hypermethylation in renal-cell carcinoma cell lines of the clear-cell type.
Renal-cell carcinoma (RCC) is the most common neoplasm of the kidney, accounting for about 3% of all adult malignancies. Histopathologically, 80% of all cases can be classified as clear-cell RCC. Of these, approximately 55% to 70% are associated with mutations in the von Hippel-Lindau (VHL) tumor-suppressor gene. Here, new mutations of the VHL gene were defined by the use of temperature gradient gel electrophoresis and subsequent sequencing. In addition, DNA hypermethylation, an alternative mechanism of VHL gene silencing, was evaluated by methylation-specific PCR. Twenty-six clear-cell, 3 chromophilic, and 2 chromophobic RCC cell lines were analyzed. Among the clear-cell RCC cell lines tested, 12 (47%) contained 13 mutations overall: 8 (62%) in exon 1, 3 (23%) in exon 2, and 2 (15%) in exon 3. Ten of these mutations have thus far not been described. All single base pair changes were transversions. Six mutations led to alteration of a single amino acid. Seven mutations generated a frameshift or a stop codon. One cell line contained a complex duplication of 36 bp. All cell lines with mutations showed loss of heterozygosity in the VHL gene. No mutations could be detected in the chromophilic or chromophobic RCC samples. Significant hypermethylation was not observed in any of the cell lines. These data provide further evidence that distinct mutations in the VHL gene are a characteristic feature of clear-cell RCC. In contrast, hypermethylation of the gene is probably a rare event. The high frequency of transversion mutations suggests a role for exogenous carcinogens in the etiology of clear-cell RCCs.
Adenocarcinoma, Clear Cell↗
Glutathione transferase isozyme genotypes in patients with prostate and bladder carcinoma.
Genotype distributions for GSTP1, GSTM1, and GSTT1 were determined in 91 patients with prostatic carcinoma and 135 patients with bladder carcinoma and compared with those in 127 abdominal surgery patients without malignancies. None of the genotypes differed significantly with respect to age or sex among controls or cancer patients. In the group of prostatic carcinoma patients, GSTT1 null allele homozygotes were more prevalent (25% in carcinoma patients vs. 13% in controls, Fisher P =0.02, chi2 P=0.02, OR=2.31, CI = 1.17-4.59) and the combined M1-/T1 -null genotype was also more frequent (9% vs. 3%, chi2 P=0.02, Fisher P = 0.03). Homozygosity for the GSTM1 null allele was more frequent among bladder carcinoma patients (59% in bladder carcinoma patients vs 45% in controls, Fisher P=0.03, chi2 P=0.02, OR=1.76, CI=1.08-2.88). In contrast to a previous report, no significant increase in the frequency of the GSTP1b allele was found in the tumor patients. Except for the combined GSTM1-/ T1-null genotype in prostatic carcinoma, none of the combined genotypes showed a significant association with either of the cancers. These findings suggest that specific single polymorphic GST genes, that is GSTM1 in the case of bladder cancer and GSTT1 in the case of prostatic carcinoma, are most relevant for the development of these urological malignancies among the general population in Central Europe.
Aged↗
Garlic: effects on cardiovascular risks and disease, protective effects against cancer, and clinical adverse effects.
Explore the source record for details and available documents.
Administration, Oral↗
High frequency of alterations in DNA methylation in adenocarcinoma of the prostate.
BACKGROUND: Alterations of DNA methylation have been reported in many human cancers. In prostatic carcinoma, hypermethylation of the GST P gene promoter and an overall decrease in methylcytosine content have been reported. The aim of the present study was to investigate the frequency and extent of these alterations in relation to tumor stage and grade, in order to explore their clinical relevance and to determine their relationship to each other. METHODS: DNA from 32 histologically verified adenocarcinomas of the prostate was analyzed for GST P hypermethylation by a semiquantitative PCR method and for overall DNA methylation by quantitative Southern blot analysis or LM-PCR of LINE-1 repetitive sequence methylation. RESULTS: GST P hypermethylation was detected in 24/32 (75%) specimens, and LINE-1 hypomethylation in 17/32 (53%). Both alterations tended to increase in frequency and extent with tumor stage. All but 1 of 8 carcinomas with lymph node involvement were positive for GST P hypermethylation. Six of these as compared to 2 out of 24 showed strong hypomethylation (P = 0.005). Hypermethylation and hypomethylation did not show a quantitative correlation, but all except two samples with weak LINE-1 hypomethylation also displayed GST P hypermethylation. CONCLUSIONS: GST P hypermethylation is an extremely frequent change in prostatic carcinoma which most probably precedes genome-wide hypomethylation. It appears useful for sensitive detection of prostatic carcinoma, whereas pronounced LINE-1 hypomethylation may be associated with progressive tumors.
Adenocarcinoma↗
Establishment of experimental conditions for the rapid detection of mutations in the von Hippel-Lindau gene by parallel temperature gradient gel electrophoresis.
Renal cell carcinoma (RCC) is the most common adult kidney neoplasm and is present in approximately 3% of all adult malignancies. Mutations of the von Hippel-Lindau (VHL) gene had been found in 55-70% of sporadic RCC and appear to be a critical event in the pathogenesis of clear-cell RCC. Several screening procedures for the detection of mutations in the VHL gene such as single-strand conformation polymorphism analysis, Southern blot and polymerase chain reaction (PCR)-employing methods had been used. Recently, the perpendicular temperature gradient gel electrophoresis (TGGE) was successfully applied to detect genetic alterations in the VHL gene. Here, the experimental conditions for parallel TGGE were established. The results on eleven samples with mutations in different exons demonstrate that parallel TGGE can be used as a simple and rapid method to detect mutations in the VHL gene. Several samples can be run at the same time, making parallel TGGE ideal for the screening of a large number of samples.
Adult↗
[Reconstructive surgery of the efferent urinary tract in pelvic exenteration of gynecological tumors].
In locally advanced or recurrent tumors of the female genital tract anterior or total exenteration may be mandatory in case of tumor invasion into the lower urinary tract or if a second course of radiation therapy is not feasible. The management of resection and reconstruction of the affected lower urinary tract has to be well integrated into the gynecological therapeutic concept. In 11/32 patients the reconstruction of the partially resected lower urinary tract was feasible with preservation of a functionally intact urinary bladder. Urinary diversion following pelvic exenteration was achieved in 13/17 patients with a continent urinary reservoir and in 4/17 patients with an ileal conduit. Operative reinterventions were needed only in patients with continent urinary diversion in 5 cases. All these patients had a past history of primary radiation therapy of their gynecological tumor. In the remaining other 11 patients with a history of primary radiation therapy no complications occurred. 9 of 32 patients survived the operative procedure 40.8 (25-57) month with no evidence of recurrent tumor. Continent urinary diversion represents an excellent therapeutic option for replacement of function lost due to exenterative pelvic surgery. Stringent selection of patients is mandatory to consider the presented therapeutic concept a reasonable tool in the management of the described clinical situations.
Adult↗
[Lymph node metastases in urologic tumors--a therapeutic dilemma].
Explore the source record for details and available documents.
Female↗
Venous incompetence in erectile dysfunction: evaluation with color-coded duplex sonography and cavernosometry/-graphy.
The purpose of this study was to assess the accuracy of multi-parameter measurements with color-coded duplex sonography (CCDS) for the diagnosis of venous leakage in patients with erectile dysfunction. Sixty patients with repeated unsatisfactory reactions after intracavernous injection of vasoactive substances underwent CCDS. Following intracavernous injection of prostaglandin E1, peak systolic velocity (PSV), enddiastolic velocity (EDV), time averaged velocity (TAV), resistance index (RI), and pulsatility index (PI) were measured in the cavernous arteries over 30 min (one measurement per minute). The results were compared with independent measurements based on dynamic pharmaco-cavernosometry/cavernosography (DPCC). Dynamic pharmaco-cavernosometry/cavernosography revealed venous leakage in 33 patients. Of 48 patients with normal PSV ( > 25 cm/s), 25 had veno-occlusive dysfunction and the remainder presented normal venous function. No statistically significant differences between these groups were found in EDV, RI, and PI measurements. In contrast, differences in TAV were significant between patients with (mean 9.4 +/- 4.6 cm/s) and without venous leakage (mean 5.5 +/- 2.2 cm/s; p = 0.001). Analysis of relative frequencies revealed a broad overlap of EDV, TAV, RI, and PI measurements between both groups. Sensitivities and specificities determined from receiver-operating-characteristic curves were > 80 % and > 50% for a TAV threshold of 5 cm/s, and an RI threshold of 1.0. Measurements of EDV, TAV, RI, and PI in patients with repeated unsatisfactory reactions on intracavernous prostaglandin injection are poor predictors of venous leakage and should not replace DPCC in the investigation of vasculogenic impotence.
Adult↗
Primary treatment of ureteral stones by new multiline lithotripter.
BACKGROUND AND OBJECTIVES: During the last 15 years, a second and a third generation of lithotripters have been developed. We present the results achieved by primary extracorporeal shockwave lithotripsy (SWL) of ureteral calculi treated with the new Multiline Lithotripter (Siemens). PATIENTS AND METHODS: From April 1996 until February 1997, 50 men and 17 women ages 19 to 82 (mean 50.9) years, underwent SWL as a primary treatment of ureteral stones at the Department of Urology, University of Düsseldorf. Data were analyzed retrospectively. More than half (60%) of the 67 patients had left ureteral stones. The most frequent site was proximal (46%) followed by distal (37%). The mean stone diameter was 9 mm. A total of 118 treatments were performed. RESULTS: The success rates of SWL monotherapy for upper, mid, and lower ureteral calculi were 71%, 82%, and 72%, respectively. Although in 62% of the cases, complete, and in 33% partial, stone disintegration was achieved, auxiliary procedures (ureteral stenting, nephrostomy, and ureteroscopy) were necessary in 43% of the patients. Renal hematoma occurred in two patients, who were treated for upper ureteral calculi. Two thirds of the patients were discharged from the hospital free of stones. CONCLUSIONS: Primary SWL treatment of ureteral stones with the new Multiline showed good results in about 84% of cases, although 43% of patients required auxiliary procedures. The occurrence of renal hematoma after the treatment of upper ureteral stones is an unexpected complication and makes reduction of the applied energy necessary if the kidney lies within the field of shockwave application.
Adult↗
Staging of pelvic lymph nodes in neoplasms of the bladder and prostate by positron emission tomography with 2-[(18)F]-2-deoxy-D-glucose.
OBJECTIVES: The aim of this study was to evaluate whether pelvic lymph node metastases in patients with neoplasms of the bladder or prostate can be detected applying positron emission tomography with 2-[(18)F]-2-deoxy-D-glucose (FDG-PET). METHODS: Eight patients with bladder cancer and 17 patients with prostate cancer were examined with FDG-PET before pelvic lymph node dissection. Results of PET were then compared to histology of pelvic lymph nodes obtained at surgery. RESULTS: Lymph node metastases were detected by histopathological examination in 3 patients with bladder cancer and in 6 patients with prostate cancer. At the sites with histologically proven metastases, increased FDG uptake suspicious of metastatic disease was found in 2/3 and 4/6 patients, respectively. The smallest detected metastasis was a micrometastasis with a diameter of 0.9 cm. In 3 additional patients who all had histopathologically proven micrometastases ( </=0.5 cm), FDG uptake was within the normal range. No false-positive results were obtained. CONCLUSIONS: These results suggest that FDG-PET may be a valuable diagnostic tool in the staging of pelvic lymph nodes in bladder and prostate cancer.
Aged↗