Biomedical subjects

Susanne Winkler

Publications and source records attributed to Susanne Winkler.

8 recordsLinked to original sources

PubMed2006

Polysomy 13 in a canine prostate carcinoma underlining its significance in the development of prostate cancer.

The dog is a well-accepted model for prostate cancer in man because of the striking similarities between both species with respect to the clinical course of the disease as well as to its similar histopathology. Cytogenetic investigations of human prostate cancers has revealed the frequent occurrence of trisomies 7, 8, and 17. In this report, we present a case of prostate carcinoma in a dog characterized by polysomy 13 as the sole cytogenetic abnormality. Along with the known homology between canine chromosome 13 and human chromosome 8 these findings suggest that a homologous area on both chromosomes plays a crucial role in subsets of prostate cancer in both species.

Aneuploidy↗

PubMed2005

Cloning and characterization of the canine receptor for advanced glycation end products.

Metastasis is one of the major problems when dealing with malignant neoplasias. Accordingly, the finding of molecular targets, which can be addressed to reduce tumour metastasising, will have significant impact on the development of new therapeutic approaches. Recently, the receptor for advanced glycation end products (RAGE)-high mobility group B1 (HMGB1) protein complex has been shown to have significant influence on invasiveness, growth and motility of tumour cells, which are essential characteristics required for metastatic behaviour. A set of in vitro and in vivo approaches showed that blocking of this complex resulted in drastic suppression of tumour cell growth. Due to the similarities of human and canine cancer the dog has joined the common rodent animal model for therapeutic and preclinical studies. However, complete characterisation of the protein complex is a precondition to a therapeutic approach based on the blocking of the RAGE-HMGB1 complex to spontaneously occurring tumours in dogs. We recently characterised the canine HMGB1 gene and protein completely. Here we present the complete characterisation of the canine RAGE gene including its 1384 bp mRNA, the 1215 bp protein coding sequence, the 2835 bp genomic structure, chromosomal localisation, gene expression pattern, and its 404 amino acid protein. Furthermore we compared the CDS of six different canine breeds and screened them for single nucleotide polymorphisms.

Amino Acid Sequence↗

PubMed2004

The canine HMGA1.

Due to the emerging advantages of numerous canine diseases as a genetic model for their human orthologs, the dog could join the mouse as the species of choice to unravel genetic mechanisms, e.g. of cancer predisposition, development and progression. However, precondition for such studies is the characterisation of the corresponding canine genes. Human and murine HMGA1 non-histone proteins participate in a wide variety of cellular processes including regulation of inducible gene transcription, integration of retroviruses into chromosomes, and the induction of neoplastic transformation and promotion of metastatic progression of cancer cells. Chromosomal aberrations affecting the human HMGA1 gene at 6p21 were described in several tumours like pulmonary chondroid hamartomas, uterine leiomyomas, follicular thyroid adenomas and others. Over-expression of the proteins of HMGA1 is characteristic for various malignant tumours suggesting a relation between high titer of the protein and the neoplastic phenotype. In this study, we characterised the molecular structure of the canine HMGA1 cDNA, its splice variants and predicted proteins HMGA1a and HMGA1b. Furthermore, we compared the coding sequence(s) (CDS) of both splice variants for 12 different breeds, screened them for single nucleotide polymorphisms (SNPs) and characterised a basic expression pattern.

Alternative Splicing↗

PubMed2003

Do patients with a higher body mass index have a greater risk of advanced-stage renal cell carcinoma?

OBJECTIVES: To evaluate whether patients with a higher body mass index (BMI) are at elevated risk of an advanced tumor stage for renal cell carcinoma at diagnosis. A high BMI has recently been proved to be associated with advanced tumor stages for some malignant diseases. METHODS: From January 1994 to December 2000, 693 operations for renal cell carcinoma were performed in 683 patients at our institution. Ten patients underwent surgery twice for bilateral tumors. Of the 683 patients, 417 were men and 266 women. The mean age at surgery was 62.2 years, and the mean tumor diameter was 5.2 cm. Seventy-eight percent of the patients were asymptomatic at tumor diagnosis. The following parameters were evaluated with regard to a possible correlation to tumor stage and/or tumor diameter: BMI, presence of symptoms, age, sex, hemoglobin, lactate dehydrogenase, erythrocyte sedimentation rate, serum cholesterol, and triglycerides. For statistical analysis, the Spearman rank correlation test was used. RESULTS: The mean BMI was 26.8 +/- 4.4 (range 16.9 to 44.3). Statistical analysis showed a significant positive correlation between advanced T stage and the presence of symptoms (P <0.0001), erythrocyte sedimentation rate (P <0.0001), lactate dehydrogenase (P = 0.0015), and age (P = 0.046), and an inverse correlation with hemoglobin (P <0.0001) and serum cholesterol (P <0.0001). For all other investigated parameters, including BMI, no significant correlation could be proved. CONCLUSIONS: Our data indicate that obese patients are not at greater risk of advanced tumor stages of renal cell carcinoma at the time of diagnosis compared with a population of normal weight.

Adolescent↗

PubMed2003

Impact of tumor-associated symptoms on the prognosis of patients with renal cell carcinoma: a single-center experience of 683 patients.

OBJECTIVES: To evaluate the impact of cancer-associated symptoms present at the diagnosis of renal cell carcinoma (RCC) on the prognosis of patients. Increasing numbers of RCC are currently detected incidentally by routine ultrasonography. METHODS: From January 1994 to December 2000, 693 operations for RCC in 683 consecutive patients have been performed at our institution. Overall, tumor-specific, and progression-free survival were investigated using the Kaplan-Meier method. For multivariate analysis regarding tumor-specific survival, the Cox regression model, including risk ratios, was used. A receiver operating characteristics curve regarding the sensitivity and specificity for the association between tumor size and symptoms was used. RESULTS: Of the 683 patients, 417 patients were male and 266 female. The mean patient age was 62 years (range 16 to 88). Of the 683 patients, 141 (20.8%) presented with symptoms suspicious for cancer. The 5-year overall, progression-free, and cancer-specific survival rates were 82%, 79%, and 86%, respectively, for asymptomatic patients compared with 60%, 55%, and 65%, respectively, for patients with symptoms at diagnosis (P <0.0001, log-rank test). The cutoff value of 5 cm for the tumor diameter to result in symptoms was chosen on the receiver operating characteristic curve. Multivariate analysis found tumor grade (P = 0.001), tumor stage (P = 0.001), presence of symptoms (P = 0.013), and tumor diameter (P = 0.005) to be independent prognostic parameters for cancer-specific survival. CONCLUSIONS: Tumors larger than 5 cm were significantly more likely to cause symptoms compared with smaller tumors in our series. In multivariate analysis, patients presenting with symptoms suspicious for cancer at the diagnosis of RCC had a 1.8-fold greater risk of dying of cancer compared with patients without symptoms.

Adolescent↗

PubMedDate not supplied

Expression pattern of the HMGB1 gene in sarcomas of the dog.

BACKGROUND: The human high mobility group protein B1 (HMGB1) has attracted considerable interest among oncologists because it sensitises cancer cells to the anticancer drug cisplatin by shielding cisplatin-DNA adducts from nucleotide excision repair. MATERIALS AND METHODS: Since cisplatin is the cornerstone of adjuvant systemic therapy for osteosarcomas, in both humans and dogs, the expression pattern of the HMGB1 gene in seven canine sarcomas was investigated by Northern blot analysis and semi-quantitative RT-PCR. RESULTS: A strong intertumoural variation of HMGB1 expression was detected by Northern blot analysis and confirmed by the semi-quantitative RT-PCR established herein. CONCLUSION: The observed variations of HMGB1 expression in canine sarcomas emphasises the role of HMGB1 as a potential marker of clinical interest as its expression level may predict the clinical outcome of therapies based on cisplatin. The semi-quantitative RT-PCR established allows a quick and convenient determination of the HMGB1 expression level as necessary for clinical applications.

Animals↗

PubMedDate not supplied

Absence of ras-gene hot-spot mutations in canine fibrosarcomas and melanomas.

Point mutations within ras proto-oncogenes, particularly within the mutational hot-spot codons 12, 13 and 61, are frequently detected in human malignancies and in different types of experimentally-induced tumours in animals. So far little is known about ras mutations in naturally occurring canine fibrosarcomas or K-ras mutations in canine melanomas. To elucidate whether ras mutations exist in these naturally occurring tumours in dogs, in the present study we screened 13 canine fibrosarcomas, 2 feline fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot-spots, making this the first study to investigate a large number of canine fibrosarcomas. None of the samples showed a K- or N-ras hot spot mutation. Thus, our data strongly suggest that ras mutations at the hot-spot loci are very rare and do not play a major role in the pathogenesis of the spontaneously occurring canine tumours investigated.

Animals↗

PubMedDate not supplied

Cytogenetic investigations in four canine lymphomas.

Four cases of canine lymphoma are presented, including histological examination and cytogenetic investigation. The first case showed a derivative chromosome 13, the second case showed a clonal trisomy 8 and the third case showed a complex karyotype with a clonal trisomy 13 and additional clonal trisomies of the chromosomes 20, 30 and 37, as well as a non-clonal tetrasomy 9. Case four showed a single trisomy 2. Comparing these results with human hematopoietic malignancies, there are notable similarities between both species.

Animals↗