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K Günther

Publications and source records attributed to K Günther.

At least 19 recordsLinked to original sources
PubMed2005

RAS gene hot-spot mutations in canine neoplasias.

Point mutations in the cellular homologues HRAS, KRAS2, and NRAS of the viral Harvey and Kirsten rat sarcoma virus oncogenes are commonly involved in the onset of malignancies in humans and other species such as dog, mouse, and rat. Most often, three particular hot-spot codons are affected, with one amino acid exchange being sufficient for the induction of tumor growth. While RAS genes have been shown to play an important role in canine tumors such as non-small lung cell carcinomas, data about RAS mutations in canine fibrosarcomas as well as KRAS2 mutations in canine melanomas is sparse. To increase the number of tumors examined, we recently screened 13 canine fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot spots. The results were compared to the already existing data from other studies about these tumors in dogs.

Animals↗
PubMed2003

Angiogenesis and dendritic cell density are not correlated with metachronous distant metastasis in curatively operated rectal cancer.

BACKGROUND AND AIMS: Apart from surgery, treatment of rectal cancer increasingly involves the use of (neo-)adjuvant strategies. To optimize the selection process for these therapy regimens, especially in the field of cellular and molecular biology, new prognostic factors additional to the established TNM system are being investigated. PATIENTS AND METHODS: Two groups of patients ( n=2x85) with rectal carcinoma curatively treated by surgery alone were studied retrospectively (median follow-up 6.1 years). To exclude the effect of the surgeon only patients free of locally recurrent disease were selected. Patient groups were matched for age, gender, UICC stage, and year of operation (1982-1991) and differed only in subsequent metachronous distant metastatic spread, i.e., the criterion to be studied. The factors investigated in uni- and multivariate analysis were angiogenesis, density of dendritic cells, grading, venous invasion, and lymphatic invasion. RESULTS: Grading invariably proved to be the only significant prognostic factor. In univariate analysis the absence of venous invasion was also correlated significantly with increased disease-free survival. CONCLUSION: Angiogenesis and dendritic cell density are not prognostic factors for metachronous distant metastasis in rectal cancer and therefore cannot serve as selection parameters for adjuvant therapy.

Age Factors↗
PubMed2003

The dissipation, distribution and fate of a branched 14C-nonylphenol isomer in lake water/sediment systems.

A single tertiary isomer which is believed to be one of the major branched isomers of the isomeric nonylphenol was synthesized for use in investigations on its metabolism and estrogenicity in aquatic organisms. The physico-chemical properties of the isomer were determined to enable the prediction of its behaviour in aquatic environments. From laboratory investigations on its dissipation and distribution in lake water, which are reported in this paper, it was found that it had a half-life of dissipation of 38.1 days and 20.1 days in an open lake water and in an open lake water/ sediment system, respectively, and to be rapidly partitioned in to sediment giving a high concentration factor of 1.76 after 28 days with an initial dose concentration of 2.52 ppm. The main dissipation route was found to occur through volatilization and co-distillation. The isomer was, however, found to be resistant to biodegradation in both the lake water and sediment, showing only a slight 9% loss (after 56 days) and 4.2% loss (after 28 days), of the 14C-residues in lake water and lake water/sediment systems, respectively, by microbial activity. Transformation to other more polar metabolites possibly by hydroxylation was also found to be minimal in both lake water and sediment samples after 14 days by HPLC analysis. After 7 days, only 2.25 and 7.4% transformation to a more polar metabolite was detected in lake water and sediment samples, respectively.

Biodegradation, Environmental↗
PubMed2003

Patients with familial adenomatous polyposis experience better bowel function and quality of life after ileorectal anastomosis than after ileoanal pouch.

OBJECTIVE: To evaluate the quality of life with emphasis on bowel function in patients undergoing either total colectomy with ileorectal anastomosis (IRA) or restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for familial adenomatous polyposis (FAP). PATIENTS AND METHODS: All 151 patients operated on in our department between 1971 and 2000 were analysed retrospectively. Since 42 patients had to undergo reoperations, a total of 194 bowel procedures were performed. The final operative breakdown was: 48 IRA, 62 IPAA, 33 total proctocolectomies and 8 other procedures. By the end of the period under consideration, 40 patients had died, 28 had been lost to follow-up, 83 patients were still alive and of these 76 were analysed. Continence function and quality of life with emphasis on overall bowel function (Wexner (WS)-, Jostarndt (JS)-, Oresland (OS)- and Pemberton (PS)-scores) were recorded in 59 patients (22 IRA and 37 IAP). RESULTS: Continence and bowel function were significantly better after IRA than after IPAA (mean scores: WS, 1.1 vs 5.4, P=0.001; JS, 32.5 vs 24.7, P=0.0001; OS, 2.9 vs 7.9, P=0.0001), as was quality of life (PS, 25.6 vs 19.6, P=0.001). The mean values for each single item of all 4 scores were consistently better after IRA. Neither gender, age nor type of pouch-anal anastomosis (stapled vs hand-sewn) had a significant influence on outcome. IPAA patients with uneventful follow-up (n = 27) had better mean values for all 4 scores (WS, 4.2 vs 7.3; JS, 26.1 vs 23.1; PS, 20.4 vs 17.7; OS, 6.6 vs 9.9) than those with postoperative complications (n = 10; 27%), but statistical significance was reached only in the OS (P = 0.026). No such difference was seen after IRA (14% complication rate). CONCLUSION: The significantly better continence after IRA resulting in superior patient comfort and quality of life must be balanced against the oncological disadvantage of this procedure. On the basis of large patient population studies, genotype-phenotype correlations with respect to the risk for rectal cancer may need to be taken into account. Postoperative complications may have a lasting negative effect on outcome after IPAA.

Adenomatous Polyposis Coli↗
PubMed2003

Rectal resection with low anastomosis: functional outcome.

OBJECTIVE: Function after anterior, low anterior and intersphincteric resection for rectal cancer was studied. METHOD: Of 139 patients 122 responded to a standardized questionnaire (Cleveland Clinic Continence Score) 108 +/- 46 weeks postoperatively and 70 underwent anorectal manometry at 26 +/- 15 weeks. RESULTS: The postoperative continence score was dependent on the procedure (anterior resection 4.1 +/- 4.6, low anterior resection 6.9 +/- 5.6, intersphincteric resection 11.5 +/- 5.2; P < 0.0001). It was poorer after radiochemotherapy (9.0 vs. 5.7; P = 0.030), but after colonic pouch reconstruction there was no significant difference between low anterior resection (5.6 vs. 7.3) and intersphincteric resection (10.0 vs. 12.5). Mean and maximal resting pressures were significantly reduced after intersphincteric resection (24 +/- 9 and 40 +/- 13 mmHg, respectively, P < 0.001) and further reduced by radiochemotherapy. Squeeze pressure was unaffected by the operative procedures and radiochemotherapy. Maximum tolerable volume and rectal compliance were reduced, after both low anterior and intersphincteric resection. Statistical correlation between continence score and maximal resting pressure (P = 0.014), mean resting pressure (P = 0.002), urge volume (P = 0.037), and neorectal compliance (P = 0.0018) reached significance. Satisfaction with the functional outcome was expressed by 71% of patients. CONCLUSION: After rectal resection the degree of impaired continence depended on the operative procedure and the form of reestablishment of intestinal continuity. Radiochemotherapy affected the outcome adversely. Despite reduced function, overall patient satisfaction was high.

Adenocarcinoma↗
PubMed2003

Neoadjuvant treatment with weekly high-dose 5-Fluorouracil as 24-hour infusion, folinic acid and oxaliplatin in patients with primary resectable liver metastases of colorectal cancer.

PURPOSE: To evaluate the efficacy and safety of neoadjuvant treatment comprising weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion, folinic acid (FA) and biweekly oxaliplatin (L-OHP), followed by metastatic resection in patients with primarily resectable liver metastases of colorectal cancer (CRC). PATIENTS AND METHODS: 20 patients with primarily resectable liver metastases of CRC were enrolled in a prospective phase II study. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m(2) L-OHP in the form of a 2-hour intravenous infusion and 500 mg/m(2) FA as a 1- to 2-hour intravenous infusion, followed by 2,600 mg/m(2 ) 5-FU administered as a 24-hour intravenous infusion once weekly. A single treatment cycle comprised one infusion per week during a period of 6 weeks followed by a 2-week rest. Two cycles were administered, with a third being added when the treatment was well tolerated. Thereafter, curative resection of the liver metastases was attempted, and the patients were followed up. RESULTS: After neoadjuvant therapy, 2 of the original 20 patients showed complete remission (CR; 10%) and 18 patients partial remission (PR; 90%). As the main symptom of toxicity, diarrhea (CTC toxicity grade 3-4) was observed in 6 patients (30%), followed by vomiting in 3 patients (15%). The curative resectability rate was 80% (16 of 20). In 9 of 18 patients (50%) undergoing surgical intervention, mild postoperative complications, mainly wound healing disturbances (n = 5), occurred. No postoperative mortality was observed. Over a median follow-up of 23 months (12-38) 6 of 16 curatively resected patients developed distant metastases and 1 patient a local pelvic recurrence. The 2-year disease-free survival rate was 52% and the 2-year cancer-related survival rate 80%. CONCLUSION: The neoadjuvant treatment with weekly high-dose 5-FU in the form of a 24-hour infusion combined with FA and L-OHP is very effective and well tolerated. Surgical morbidity does not appear to be increased by the neoadjuvant treatment.

Aged↗
PubMed2003

Proteomic prediction of disease outcome in cancer : clinical framework and current status.

Better than gene sequencing or quantitative amplification, proteomics tools allow the study of tumor phenotype. Indeed, most current prognostic tests in cancer (carcinoembryonary antigen [CEA], prostate-specific antigen [PSA], CA 19-1, CA 125, alpha-fetoprotein [AFP], etc.) are based on the detection and quantification of single proteins in body fluids. However, a common characteristic of these tests is their relatively low predictive value, so that they are usually complemented with other procedures such as biopsy and/or endoscopy. Recently, improved analytical and bioinformatics tools have driven the attention on pattern recognition approaches rather then single-marker tests for prognostic forecasting. It is expected that predicting metastasization on the basis of tumoral protein patterns will soon be a reality. However, currently available technologies either limit the number of proteins that can be analyzed simultaneously or they are expensive, difficult, and time-consuming. Moreover, the tools adapted for expression proteomics might not be the same as those for prognostic studies that require investigation of protein function over time. We believe that clinical proteomics research designed within a precise clinical and pathology framework should be strongly supported, since many prognostic factors are determined not by the tumor itself, but by the patient, the treatment and the environment.

Animals↗
PubMed2002

[D3 versus D2 dissection in stomach carcinoma. A case-control study of postoperative morbidity, survival and early oncologic outcome].

INTRODUCTION: In western countries, the benefit of the Japanese extended D3 lymph node dissection in gastric cancer patients who have been operated on in curative intent has not been proven and higher rates of side effects are expected. The present matched-pair study retrospectively compared the new D3 method (1995-1999) with the historic D2 dissection (1982-1995). METHODS: Two 1:1 matched-pair populations were created: (1) regarding intra- and postoperative course, morbidity and mortality, 2 x 67 patients stratified to "age", "gender", "surgical procedure", "splenectomy" and "extended resections"; and (2) regarding early oncologic outcome, 2 x 32 patients additionally stratified to "UICC-stage" and "Laurén-classification". The D3 dissection was performed according to the Japanese method without routine pancreaticosplenectomy. RESULTS: D3 dissection harvested significantly (P = 0.004) more lymph nodes per patient: 56.4 vs. 46.8. Postoperative mortality was 3% (n = 2) in both groups, the overall complication rate of 30% (D3) vs. 25% (D2) was equivalent (P = 0.678) and the rate of surgical complications was identical (21%). Non-surgical complications of 21% after D3 dissection were not significantly elevated (vs. 10%; P = 0.143). Operative time [289 min (D3) vs. 218 min (D2); P = 0.0001] and postoperative stay [17.4 days (D3) vs. 14.5 days (D2); P = 0.003] were significantly longer after the extended procedure. The were no statistically significant differences between 2-year overall survival, locoregional-, distant- and overall recurrence-free survival. CONCLUSIONS: Compared to the D2 method, D3 dissection is feasible without disadvantages in the patients. However, D3 dissection cannot routinely be recommended because--possibly due to the short follow-up period and the small number of patients so far observed--an oncologic benefit could not be shown.

Adult↗
PubMed2001

Regioselective synthesis of a branched isomer of nonylphenol, 4-(3',6'-dimethyl-3'-heptyl)phenol, and determination of its important environmental properties.

A method for the synthesis of a pure nonylphenol isomer, 4-(3',6'-dimethyl-3-heptyl)phenol, by Friedel-Crafts reaction between anisole and 3-bromo-3,6-dimethylheptane that gives a 47.3% overall yield is reported. The reactions were followed by GC-MS, and the chemical structures are in agreement with the NMR and IR spectra. The log K(ow) value for this compound, its water solubility, vapor pressure, and Henry's Law constant were also determined. These physicochemical properties were required for prediction of the compound's behavior in aquatic ecosystems.

Journal Article↗
PubMed2001

High-risk groups of patients with Stage II colon carcinoma.

BACKGROUND: It is unclear whether patients with Stage II colon carcinoma should be offered adjuvant chemotherapy. Therefore, the authors analyzed the risk factors of these patients to identify high-risk subgroups who may benefit from such treatment. METHODS: The data from 305 patients with Stage II colon carcinoma documented in the Erlangen Registry of Colorectal Carcinoma were analyzed to identify risk factors for distant metastasis and disease-related survival. The patients were divided into two subgroups: those in a low-risk group and those in a high-risk group. The data were then compared with those from 306 patients with Stage II colon carcinoma from the German Study Group for Colorectal Carcinoma (SGCRC). RESULTS: Emergency presentation, a primary tumor site in the left colon, pT3 tumors with a depth of invasion of > 15 mm beyond the outer border of the muscularis propria, and pT4 lesions were identified as the major risk factors for Stage II colon carcinoma. On dividing patients into subgroups according to these risk factors, it was found that patients in the high-risk group had a significantly higher risk of distant metastases and a significantly lower disease-related survival rate compared with patients in the low-risk group. On analyzing the SGCRC data, the authors also found a significantly higher rate of distant metastases in the high-risk group, but the disease-related survival rate differed only marginally. CONCLUSIONS: Among patients with Stage II colon carcinoma, it is possible to identify a high-risk group of patients who may be candidates for adjuvant chemotherapy. Stratification by the risk factors emergency presentation, tumor site, depth of tumor invasion, and surgical department should be employed in further clinical studies.

Adult↗
PubMed2001

Differences in genetic alterations between primary lobular and ductal breast cancers detected by comparative genomic hybridization.

Infiltrating ductal (DC) and lobular carcinoma (LC) of the breast represent the most frequently observed varieties of invasive breast cancer, characterized by differences in their histological and clinical properties. Although comparative genomic hybridization (CGH) of invasive breast carcinomas has revealed a complex and consistent pattern of DNA copy number changes, the data with regard to type specific aberrations are limited. A comprehensive study was therefore performed on 19 LCs and 29 DCs to ascertain type-specific differences of unbalanced DNA copy number changes by CGH. Statistical analysis revealed significantly higher frequencies for underrepresentation of chromosomes 16q (p<0.01), 22 (p<0.05), and 17q (p<0.05), and a lower frequency for overrepresentation of chromosome 8q (p<0.01) in LC. Similar frequencies of non-random chromosomal changes in LC and DC were obtained for gain of 1q (74%/59%) and loss of 19p (53%/52%), parts of 1p (42%/41%) and 11q (21%/24%). Less frequently, gains mainly involving parts of chromosomes 20q, 20p, 3q, and 5p and partial losses of chromosomes 17p and 13 were observed in both groups of tumours. Minimal regions of overlapping amplifications were mapped to 17q23 exclusively in DC (17%) and 11q13-q14 in both DC and LC (21% and 11%, respectively). High occurrences of DNA copy number decreases were detected at the distal part of chromosomes 1p, 19 and 22, but further analysis is required to confirm these imbalances. It is suggested that the observed differences are involved in the development of type-specific properties of DC and LC.

Adult↗
PubMed2001

A high-resolution reference map for cytoplasmic and membrane-associated proteins of Corynebacterium glutamicum.

We present a high-resolution reference map for soluble proteins obtained from Corynebacterium glutamicum cells grown in glucose minimal medium. The analysis window covers the pl range from 4-6 and the molecular mass range from 5-100 kDa. Using overlapping narrow immobilized pH gradients for isoelectric focusing, 970 protein spots were detected after second-dimensional separation on SDS-polyacrylamide gels and colloidal Coomassie-staining. By tryptic peptide mass fingerprinting 169 protein spots were identified, representing 152 different proteins including many enzymes involved in central metabolism (18), amino acid biosynthesis (24) and nucleotide biosynthesis (11). Thirty-five of the identified proteins have no known function. A comparison of the observed and the expected physicochemical properties of the identified proteins indicated that nine proteins were covalently modified, since variants with apparently identical molecular mass, but differing pl were detected. The N-termini of eight proteins were determined by post-source decay (PSD) analysis of selected peptides. In addition to the soluble proteins, a map of the membrane-bound proteins within the pl range 4-7 is presented, which contains 660 protein spots, 22 of which were identified, representing 13 different proteins.

Bacterial Proteins↗
PubMed2001

Mutation screening at the RNA level of the STK11/LKB1 gene in Peutz-Jeghers syndrome reveals complex splicing abnormalities and a novel mRNA isoform (STK11 c.597(insertion mark)598insIVS4).

This study was intended to evaluate a diagnostic reverse transcriptase polymerase chain reaction based protein-truncation test for the identification of germline mutations in the serine/threonine protein kinase 11 (STK11, also designated LKB1) gene in Peutz-Jeghers syndrome (PJS). Our data exemplify that the inactivation of STK11 can be due to unusual disturbances in splicing regulation which result in truncations of the protein. However, nonsense mediated mRNA decay must be blocked with puromycin to detect shortened STK11 gene products contained in the leucocytic mRNA pool of PJS patients. Interestingly, two mutations escaped from detection by exon sequencing techniques with usual flanking PCR primers, since alterations were located right in the middle of intronic sequences. We describe a compound heterozygous PJS patient who carried two different mutations in intron 1 on separate alleles. Each of the two mutations was transmitted individually to one of his two children. In the course of our RNA based analyses we detected high level expression of a novel STK11/LKB1 mRNA variant retaining intron 4 (STK11 c.597(insertion mark)598insIVS4) in various tissues. This mRNA isoform was initiated from an alternative transcription regulatory region as revealed by primer extension analyses even in cell lines with complete methylation of the normal promoter. As a consequence of novel mutational mechanisms identified we discuss the impact of RNA based strategies for the detection of germinal STK11 mutations in PJS.

AMP-Activated Protein Kinase Kinases↗
PubMed2001

[Angiogenesis and density of dendritic cells do not correlate with metachronous distant metastases after curative surgery of rectal carcinoma].

INTRODUCTION: Besides surgery, treatment of rectal cancer increasingly comprises (neo-)adjuvant strategies. To optimise the selection process for these therapy regimens especially in the field of cellular and molecular biology, new prognostic factors besides the established TNM system are being investigated. METHODS: Retrospectively, two groups of patients (n = 2 x 85) with rectal carcinoma curatively treated by surgery alone were studied (median follow-up: 6.1 years). The patients were selected to be free of local disease, in order to exclude surgical influence. Patient groups were matched for age, gender, UICC stage and year of operation (1982-1991) and differed only in subsequent metachronous distant metastatic spread, the criterion to be studied. The factors to be investigated in uni- and multivariate analysis were angiogenesis, density of dendritic cells, grading, venous and lymphatic invasion. RESULTS: Grading always proved to be the only significant prognostic factor (P < 0.0001). In univariate analysis, absent venous invasion also correlated significantly with increased disease-free survival (P = 0.0170). CONCLUSIONS: Angiogenesis and density of dendritic cells in rectal cancer are not prognostic factors for metachronous distant metastasis and, therefore, cannot serve as selection parameters for adjuvant therapy.

Analysis of Variance↗
PubMed2001

Endocrine-disrupting nonylphenols--ultra-trace analysis and time-dependent trend in mussels from the German bight.

A very sensitive and efficient analytical procedure is presented for the determination of 4-nonylphenols (NP) in blue mussels by use of off-line coupling of high-performance liquid chromatography (HPLC) and gas chromatography with mass spectrometric detection (GC-MS). Combined steam distillation and solvent extraction were used to extract the analytes from the mussel samples. Before quantification by GC-MS the raw extracts were purified by normal-phase HPLC. 4-n-Nonylphenol was used as internal standard. The detection limit was 15 ng NP absolute, calculated from the blank value. The method was applied to the determination of NP in blue mussel samples from the German North Sea sampled over a period of 10 years. Collection, homogenization, and storage of the mussels were performed according to the Standard Operating Procedures of the German Environmental Specimen Bank since 1985. The total NP concentrations in the mussels decreased significantly from 1985 (4 microgram kg (-1)) to 1995 (1.1 microgram kg (-1)).

Animals↗