Detlef Ockert

Gene expression profiles of microdissected pancreatic ductal adenocarcinoma

In a search for new molecular markers of pancreatic ductal adenocarcinoma (PDAC), we compared the gene expression profiles of seven pancreatic carcinomas and one carcinoma of the papilla Vateri with those of duct cells from three non-neoplastic pancreatic tissues. In addition, the human pancreatic duct cell line and five PDAC cell lines (AsPC-1, BxPC-3, Capan-1, Capan-2, HPAF) were examined. RNA was extracted from microdissected tissue or cultured cell lines and analysed using a custom-made Affymetrix Chip containing 3023 genes, of which 1000 were known to be tumour associated. Hierarchical clustering revealed 81 differentially expressed genes. Of all the genes, 26 were downregulated in PDAC and 14 were upregulated in PDAC. In PDAC cell lines versus normal pancreatic duct cells, 21 genes were downregulated and 20 were upregulated. Of these 81 differentially expressed genes, 15 represented human genes previously implicated in the tumourigenesis of PDAC. From the genes that were so far not known to be associated with PDAC tumorigenesis, we selected ADAM9 for further validation because of its distinct overexpression in tumour tissue. Using immunohistochemistry, the over-expressed gene, ADAM9, was present in 70% of the PDACs analysed. In conclusion, using microarray technology we were able to identify a set of genes whose aberrant expression was associated with PDAC and may be used to target the disease.

Gene expression analysis of pancreatic cell lines reveals genes overexpressed in pancreatic cancer

Background: Pancreatic cancer is one of the leading causes of cancer-related death. Using DNA gene expression analysis based on a custom made Affymetrix cancer array, we investigated the expression pattern of both primary and established pancreatic carcinoma cell lines. Methods: We analyzed the gene expression of 5 established pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-1, Capan-2 and HPAF II) and 5 primary isolates, 1 of them derived from benign pancreatic duct cells. Results: Out of 1,540 genes which were expressed in at least 3 experiments, we found 122 genes upregulated and 18 downregulated in tumor cell lines compared to benign cells with a fold change >3. Several of the upregulated genes (like Prefoldin 5, ADAM9 and E-cadherin) have been associated with pancreatic cancer before. The other differentially regulated genes, however, play a so far unknown role in the course of human pancreatic carcinoma. By means of immunohistochemistry we could show that thymosin β-10 (TMSB10), upregulated in tumor cell lines, is expressed in human pancreatic carcinoma, but not in non-neoplastic pancreatic tissue, suggesting a role for TMSB10 in the carcinogenesis of pancreatic carcinoma. Conclusion: Using gene expression profiling of pancreatic cell lines we were able to identify genes differentially expressed in pancreatic adenocarcinoma, which might contribute to pancreatic cancer development.

Advances in cancer immunotherapy

Abstract Specific engagement of immune effector functions is a rapidly advancing field within experimental tumor therapy. A recent meeting**The 2nd International Dresden Symposium on Immunotherapy of Cancer was held at Dresden, Germany, on 12-13 June 1998. focused on the analysis of cellular and humoral immune responses against tumors and on clinical trials of antitumor vaccination and antibody therapy.

Systematic isolation of genes differentially expressed in normal and cancerous tissue of the pancreas.

Background: There is increasing knowledge about the genetic basis of pancreatic cancer (PaCa). Tumor suppressor genes (TSGs; e.g. p53 and DPC4) and oncogenes (e.g. K-ras) have been shown to be involved in the development of PaCa. However, the extent of chromosomal changes (gains and losses) implicates that many more genes may be involved in the multistep progression of PaCa. Identification of these genes is essential for understanding the molecular events in the development of PaCa. Methods: We assembled public and proprietary libraries of more than 4 million expressed sequence tags using newly developed software tools. Results: We identified a total of 249 genes with specific expression patterns in normal and cancerous tissue of the pancreas. Of these, 27 genes were found to be preferentially expressed in normal tissue of the pancreas, while 222 genes showed significant upregulation of expression in PaCa. Of the 249 genes, 232 (93.2%) were found to represent known human genes or putative human homologues of genes characterized previously in other species, while 17 (6.8%) represent putative new genes. Conclusion: These genes may represent a valuable source to identify novel TSGs and oncogenes involved in the carcinogenesis of PaCa.

Surgical Therapy of Intrapancreatic Metastasis from Renal Cell Carcinoma

Background: Pancreatic metastases from renal cell carcinoma (RCC) are clinically rare but highly resectable. The aim of this article is to identify patients who profit from pancreatic resection of RCC despite the invasiveness of the surgery. Methods: Between January 1996 and December 2007, data from 744 patients were collected in a prospective pancreatic surgery database, and patients with metastasis into the pancreas from RCC were identified. Results: Resective surgery was performed in 14 patients with metastasis to the pancreas from RCC. Most patients were clinically asymptomatic. The median interval between primary treatment of RCC and occurrence of pancreatic metastasis was 94 months (range 32–158). The morbidity rate was 42.8%. Patients with a metastasis size <2.5 cm had a much better survival after resection (100 months) than those with a metastasis size >2.5 cm (44 months). Moreover, the number of metastases predicts the survival after resection. Conclusions: In patients with pancreatic metastases from RCC who have only limited disease, complete resection of all lesions can be successfully performed with a low rate of complications. Thus, patients with a history of RCC should be monitored for more than 10 years after nephrectomy to detect recurrence.

Gastrointestinal stromal tumor presenting as a scrotal mass

We describe a huge abdominal gastrointestinal stromal tumor (GIST) extending through the right inguinal canal. The reported case illustrates that the scrotum might be a place of initial presentation of a GIST growing along preformed anatomical structures. Urologists should be aware of this condition that might be mistaken for a primarily testicular malignancy.

D-PCa-2: A novel transcript highly overexpressed in human prostate and prostate cancer

Identification of genes selectively expressed in tumors or individual tissues is a crucial prerequisite for molecular diagnosis and treatment of cancer by addressing molecular targets. By screening an expression database, we identified the novel gene D‐PCa‐2 (Dresden prostate carcinoma 2), which is highly overexpressed in normal prostate tissue and prostate carcinoma (PCa). The corresponding transcript contained an open reading frame of 453 nucleotides encoding a putative protein of 150 amino acids. A large part of exon 8 of the D‐PCa‐2 gene shows strong similarity to the high‐mobility‐group nucleosomal binding protein 2 (HMGN2) cDNA. The highly specific transcription of the D‐PCa‐2 gene in normal and malignant prostate tissues and in a few additional tumors was demonstrated by using multiple tissue dot blot, cancer profiling dot blot and real‐time PCR analyses. Examination of 18 pairs of tumorous and nontumorous prostate tissues from PCa patients by quantitative RT‐PCR revealed D‐PCa‐2 transcripts in all specimens. The potential usefulness of D‐PCa‐2 as a sensitive marker for metastatic prostate carcinoma cells in lymph nodes was demonstrated by the detection of one LNCaP cell in 1 × 105 normal lymph node cells using real‐time RT‐PCR. Examination of 22 lymph nodes from PCa patients either containing metastatic prostate cancer cells or diagnosed as cancer‐free was in full concordance with histopathologic diagnoses. These results validate D‐PCa‐2 as a transcript with high tissue specificity and with a potential application in the diagnosis of PCa.

Cancer immunotherapy: novel strategies and clinical experiences

Abstract The 4th International Dresden Symposium on Immunotherapy of Cancer was held in Dresden, Germany from 21–22 June 2002.

Biotherapy of cancer: Perspectives of immunotherapy and gene therapy

Prospects for a new biologically based strategy of cancer treatment are being discussed. While physically and chemically based therapies, such as radio- and chemotherapy, are not directed against cancer tissue only and have a suppressive effect on the immune system, immunotherapy and gene therapy, which are discussed here, try to be more selective and to stimulate rather than suppress antitumor immune mechanisms. On the basis of personal experience with these new technologies, good future prospects are predicted for the application of cancer vaccines and immune T lymphocytes for active specific immunization (ASI) and adoptive immunotherapy (ADI) respectively. While ASI strategies aim at micrometastases being affected by activated host immune T cells, and might find a place for postoperative adjuvant treatment in high-risk cancer patients, cellular therapies such as ADI do not require an intact host immune system and could therefore also find application in advanced stages of disease. In spite of the exciting new perspectives of immuno- and gene therapy for the cancer patient, this therapy is not yet a defined discipline and requires years of further research.

Liposarcoma of the diaphragm: CT and sonographic appearances

Malignant tumors arising from the diaphragm are exceedingly rare. We describe the first case, to our knowledge, of a primary diaphragmatic liposarcoma and demonstrate computed tomographic and sonographic findings.