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Biomedical subjects

A Roessner

Publications and source records attributed to A Roessner.

At least 109 records · Page 6Linked to original sources
PubMed1998

Alterations of the p16/MTS1-tumor suppressor gene in gastric cancer.

Deletions, mutations and the functional inactivation of tumor suppressor gene p16 are involved in the genesis of different neoplasias. Little is known about the role of p16 gene alterations in the genesis of gastric carcinomas. This study aimed to detect genetic alterations of the p16 gene in gastric carcinomas. We analyzed p16 gene mutations and the frequency of loss of heterozygosity (LOH) at the p16 locus in 43 gastric carcinomas. PCR-SSCP analysis of exons 1 and 2 revealed only one gene mutation in a carcinoma of the diffuse type. Besides carcinomas of the diffuse, intestinal and the mixed type, we also investigated a small-cell primary gastric carcinoma, which was the only one to show a deletion in the p16 gene. LOH analysis was performed using two polymorphic markers located near the p16 gene (D9S171, D9S162) and a sequence-tagged-site marker (c5.1). Allelic loss was noted in two carcinomas of the diffuse type and in one carcinoma of the intestinal type. Allelic instabilities were found in one tumor of the intestinal type and diffuse type each. Although only five of 43 (11.6%) gastric carcinomas had p16 alterations, tumors of the diffuse type tend to show a higher number of genetic alterations near the p16 locus.

Adenocarcinoma↗
PubMed1998

Clinicopathologic implications of MDM2, p53 and K-ras gene alterations in osteosarcomas: MDM2 amplification and p53 mutations found in progressive tumors.

It is widely recognized that various oncogenes and tumor suppressor genes contribute to tumorigenesis and progression of osteosarcomas. However, whether genetic alternations enable us to predict the prognosis of patients with osteosarcomas is unclear. Southern blotting and polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analyses were performed to search for MDM2, ras family and p53 gene alterations in 17 patients with high-grade osteosarcomas. Amplification of the MDM2 gene was found in three tumors, two of which were obtained from a regional lymph node metastasis and the other from a locally advanced lesion. Point mutations of the p53 gene were found in exons 4 and 5 in two tumors each. One of the four tumors with p53 mutations was obtained from a lymph node metastasis, one from a recurrent tumor and another from the primary tumor of a patient who developed lung metastases. Coexistence of MDM2 amplification with point mutation of the p53 gene was observed in two tumors. A point mutation of the K-ras oncogene was detected at codon 13 in two tumors. MDM2 amplification and p53 mutation may reflect tumor progression, although no correlation between alteration and response to chemotherapy or patient survival was demonstrated.

Adolescent↗
PubMed1998

Genetic instability in osteoblastic tumors of the skeletal system.

At the histological level, the differential diagnosis of osteoblastic bone tumors is characterized by several problems that cannot be solved by conventional histological methods including immunohistology. Differentiating aneurysmal bone cyst from telangiectatic osteosarcoma or giant cell tumor from giant cell-containing highly malignant osteosarcoma are only two examples reflecting the complexity of this field. To develop a new approach to these diagnostic problems, we analyzed the genetic instability in a large number of bone-forming tumor-like lesions as well as in benign and malignant osteoblastic tumors. Our research concentrated on genetic alterations in cell cycle regulator genes: mutations in the p53 gene and ras gene, loss of heterozygosity at the p53, p16 and Rb-locus, and amplification of the mdm2-gene and the c-myc-gene. In addition to cell cycle regulators, the telomerase activity has also been analyzed. The results show that the number of genetic alterations increases with the malignancy of the tumors. The highest number of genetic alterations could thus be found in conventional intraosseous osteosarcoma. In tumor-like lesions, genetic alterations have rarely been observed. The results of this study show that analyzing the genetic instability probably contributes to an improvement in the differential diagnosis of osteoblastic tumors.

Bone Neoplasms↗
PubMed1998

Overexpression of platelet-derived growth factor (PDGF) B chain and type beta PDGF receptor in human chronic pancreatitis.

Platelet-derived growth factors (PDGF) are mitogenic polypeptides that are involved in cellular proliferation and tissue repair. The expression of PDGFs and type beta PDGF receptor was examined in the normal human pancreas and in chronic pancreatitis, a fibrotic disease associated with fibroblastic proliferation, atrophy, and acinar cell dedifferentiation. In the normal human pancreas, PDGF A chain mRNA levels were relatively abundant, whereas PDGF B chain mRNA levels were not detected, and type beta PDGF receptor mRNA transcripts were present at low levels. In the normal pancreas, PDGF immunoreactivity was present in islet cells, whereas type beta PDGF receptor immunoreactivity was present in acinar cells. In chronic pancreatitis, PDGF A chain mRNA transcripts were also abundant, and 11 of 19 samples exhibited the PDGF B chain mRNA transcript. In addition, there was a significant increase in the mRNA levels of type beta PDGF receptor in the pancreatitis samples by comparison with the normal pancreas (P < 0.001). In chronic pancreatitis tissues, PDGF and type beta PDGF receptor immunoreactivity were present in acinar, ductal, islet, and endothelial cells, fibroblasts, and leukocytes. The concomitant overexpression of PDGFs and of the type beta PDGF receptor points to the existence of autocrine and paracrine PDGF-dependent loops in human chronic pancreatitis.

Blotting, Northern↗
PubMed1998

Performance of a rapid whole blood test for Helicobacter pylori in primary care: a German multicenter study.

BACKGROUND: Serological rapid whole-blood tests for the detection of H. pylori are presently being promoted for use in primary care. We conducted a multi-center study to investigate the diagnostic accuracy of the Boehringer Mannheim Helicobacter pylori test (BM test), which is identical with the Cortecs Helisal test. PATIENTS AND METHODS: A previous diagnosis of H. pylori, a history of peptic ulcer diseases, or proton-pump inhibitor, bismuth or antibiotic use during the preceding month were exclusion criteria. The BM test was performed prior to endoscopy by 7 primary care physicians, 5 practicing gastroenterologists, or a single physician in the university hospital outpatient service. During endoscopy, antral and corpus biopsies were obtained for histology and rapid urease testing (RUT). H. pylori positivity was defined by histology and/or RUT as reference methods. H. pylori IgG-ELISA was performed additionally. RESULTS: Of the 203 patients included, 151 were H. pylori-positive by reference methods (74.4%). The overall accuracy of the BM test was 77.3%. Eight BM tests were indeterminate, and in the other 195 patients the test performed as follows: sensitivity 80.3%, specificity 81.3%, positive predictive value 92.9%, negative predictive value 57.4%. Using IgG-ELISA as reference, the BM test performance was similar. It also did not differ substantially among the three groups of physicians involved. CONCLUSIONS: We found the performance of the BM test to be insufficiently accurate, as both over- and underdiagnosis of H. pylori infection were not infrequent. This test needs to be improved before its use in primary care can be recommended.

Adolescent↗
PubMed1998

Differing patterns of Helicobacter pylori gastritis in patients with duodenal, prepyloric, and gastric ulcer disease.

BACKGROUND: We investigated the risk relationship between histotopographic patterns of Helicobacter pylori gastritis and peptic ulcer site. METHODS: Three hundred and eighty-three infected patients were classified as having duodenal ulcer (n = 79), prepyloric ulcer (n = 39), gastric (angular) ulcer (n = 28), and no ulcer (n = 237). Antral and corpus biopsy specimens were taken. Sydney system-based scores for bacterial density and activity and degree of gastritis were added to antral and corpus sum scores (SS) (range, 0-9). These were used to categorize the phenotype of gastritis. In addition, the presence or absence of mucosal atrophy was taken into account. The relative risk for ulcer association with these conditions was calculated. RESULTS: High-grade antral (SS > 5) associated with mild to moderate corpus (SS > 5) gastritis increased duodenal (RR = 4.9; confidence interval (CI), 2.8-8.5) and prepyloric ulcer risk (RR = 2.99; CI, 1.4-6.2). High-grade gastritis in the antrum (SS > 5) and corpus (SS > 5) increased gastric ulcer risk (RR = 3.7; CI, 1.6-8.3). Antral atrophy and/or intestinal metaplasia is associated with an increased gastric ulcer risk (RR = 3.3; CI, 1.4-7.8). CONCLUSION: The pattern of H. pylori gastritis may define a risk for peptic ulcer at various sites, but additional factors, not reflected in histology, also contribute to this risk.

Atrophy↗
PubMed1998

Analysis of K-ras gene mutations in rare pancreatic and ampullary tumours.

OBJECTIVE: Mutation of the K-ras oncogene is a frequent event in pancreatic ductal carcinogenesis and it is believed to occur at an early stage in the development of pancreatic cancer. However, little is known of the role of K-ras mutations in rare pancreatic epithelial neoplasms, endocrine tumours or other non-epithelial tumours of the pancreas. Furthermore, limited data are available regarding the role of K-ras mutations in the pathogenesis of ampullary tumours. DESIGN AND METHODS: Using single-strand conformation polymorphism (SSCP) and direct sequencing of polymerase chain reaction (PCR)-amplified fragments, we analysed codons 12 and 13 for the presence of oncogenic mutations of the K-ras oncogene. Tissues were obtained from patients undergoing tumour resection for various rare pancreatic or ampullary neoplasms (number of cases in brackets): ampullary adenoma (1), neuro-endocrine tumour (3), malignant fibrous histiocytoma of the pancreas (1), pancreatic cystadenocarcinoma (1), serous cystadenoma (1), and primary and metastatic adenocarcinoma of the ampulla (5) and pancreas (3). RESULTS: K-ras gene mutations at codon 12 were detected in both pancreatic adenocarcinomas and in the metastatic lesion, whereas two ampullary cancers harboured a point mutation at codon 13: GGC-->GGG and GGC-->GGT. None of the other tumours exhibited a K-ras gene mutation at codons 12 or 13. CONCLUSION: Pancreatic tumours other than ductal adenocarcinoma of the pancreas do not harbour mutations of the K-ras oncogene. In addition, ampullary adenocarcinomas may present with codon 13 mutations; however, these mutations were not associated with amino acid substitution. Therefore, K-ras gene mutations seem to be a specific genetic alteration contributing to the pathogenesis of pancreatic ductal adenocarcinoma.

Adenocarcinoma↗
PubMed1998

Intestinal metaplasia at the gastro-oesophageal junction: Helicobacter pylori gastritis or gastro-oesophageal reflux disease?

BACKGROUND: Intestinal metaplasia, whether in the cardia or the distal oesophagus, has been uniformly defined as specialised columnar epithelium, suggesting a relation with Barrett's oesophagus. It is, however, not clear whether the risk factors associated with intestinal metaplasia are identical at both sites. AIMS: To investigate biopsy specimens obtained below the squamocolumnar junction (SCJ) in relation to endoscopic aspect, gastric histology, and clinical presentation. PATIENTS AND METHODS: In 423 patients investigated the endoscopic aspect of the SCJ was classified as unremarkable (group I, n = 315) or suggestive of Barrett's oesophagus (group II, n = 108). Standardised biopsy specimens from the antrum, corpus, and directly below the SCJ were investigated. RESULTS: Intestinal metaplasia was detected at the SCJ in 13.4% of group I patients, where it was significantly associated with gastric intestinal metaplasia (odds ratio (OR) 6.96; confidence interval (CI) 2.48 to 19.54) and H pylori (OR 7.85; CI 2.82 to 21.85), and in 34.3% of group II patients where it was significantly associated with reflux symptoms (OR 19.98; CI 6.12 to 65.19), erosive oesophagitis (OR 12.16; CI 3.86 to 38.24), and male sex (OR 6.25, CI 2.16 to 18.14), but not with H pylori or gastric intestinal metaplasia. CONCLUSION: This study suggests that the pathogenesis of intestinal metaplasia at the SCJ is not uniform: at an endoscopically unremarkable SCJ it is a sequela of H pylori gastritis, but coexisting with endoscopic features of Barrett's oesophagus it is associated with male sex and gastro-oesophageal reflux disease.

Barrett Esophagus↗
PubMed1998

Expression of mdm2 and p53 in epithelial neoplasms of the colorectum.

AIMS: To evaluate the respective roles of mdm2 (murine double minute 2) and p53 in the development of colorectal carcinoma. METHODS: Formalin fixed, paraffin wax embedded tissues from 72 sporadic adenomas and 55 carcinomas were investigated by means of immunohistochemistry for mdm2 and p53. RESULTS: mdm2 was expressed weakly in 17 of 72 (23.6%) adenomas and in 14 of 55 (25.4%) carcinomas. p53 was expressed in 19 of 72 (26.4%) adenomas and in 23 of 55 (41.8%) carcinomas. Four adenomas and five carcinomas showed positive staining for both proteins. Overexpression of p53 in adenomas was associated with moderate and severe dysplasia but not with tumour size. No associations were found between the expression of mdm2 and either the degree of dysplasia or tumour size. In carcinomas, neither the expression of p53 nor mdm2 correlated with Dukes's stage, metastasis, or differentiation. No associations were found between the expression of p53 and mdm2 in either adenomas or carcinomas. CONCLUSIONS: Although mdm2 has been reported to be an oncogene, it does not appear to play a major role in the development of colorectal carcinoma.

Adenocarcinoma↗
PubMed1998

P21 protein expression and ras-oncogene mutations in gastric carcinoma: correlation with clinical data.

Ras oncogenes coding for P21 protein are frequently involved in the carcinogenesis of various human tumours. For gastric carcinomas, the role of these oncogenes has not yet been fully understood. Forty-five primary gastric carcinomas were investigated for point mutations in the hot spot regions codon 12 and 13 of exon 1 and codon 61 of exon 2 of H-, K- and N-ras gene. PCR-SSCP technique followed by direct sequencing was used. The expression of P21 protein was analysed immunohistochemically. The results were correlated to clinicopathologic data. There were no point mutations in the genes of the ras family. The incidence of P21 protein expression was 66.7% (30 of 45 cases). This expression was more common in carcinomas of the intestinal type than in carcinomas of the diffuse type. There was no correlation with tumour size, metastasis, localisation of the tumour in the stomach, histologic type, grade of malignancy, gender, or clinical outcome of the disease. Overexpression of ras oncoproteins without point mutation seems to occur frequently in gastric carcinoma, particularly in tumours of the intestinal type. There is no prognostic impact. P21 protein expression cannot be used in a predictive staging system.

Adenocarcinoma↗
PubMed1998

Gene alterations at the CDKN2A (p16/MTS1) locus in soft tissue tumors.

The CDKN2A gene (p16/MTS1) is a tumor suppressor that is frequently deleted, mutated, or inactivated by transcriptional silencing in certain tumor types and many tumor cell lines. We analyzed CDKN2A gene mutations and the frequency of loss of heterozygosity (LOH) at the CDKN2A locus in 135 soft tissue sarcomas. PCR-SSCP analysis of exons 1 and 2 of CDKN2A gene revealed only one missense mutation in codon 15 in a rhabdomyosarcoma. LOH-analysis was performed with two polymorphic markers in the surrounding regions of the CDKN2A gene (D9S171, D9S162) and the sequence-tagged-site marker c5.1. An allelic loss was found in 7/135 cases (5.1%) and was a characteristic of poorly differentiated sarcomas. We observed a high frequency of microsatellite instability expressed as allelic imbalances (25%). Presumably, alterations of the CDKN2A gene do not contribute to the oncogenesis in the majority of soft tissue tumors.

Alleles↗
PubMed1998

[Genetic instability in osteoblastic tumors of the skeletal system].

In the histological differential diagnosis of osteoblastic bone tumors, several problems could not have been solved by conventional histological methods including immunohistology. Some well-known examples are the differential diagnosis between aneurysmal bone cyst and telangiectatic osteosarcoma and giant cell tumor versus giant cell-containing highly malignant osteosarcoma. As a new approach to these diagnostic problems, we analyzed the genetic instability in a larger number of bone-forming tumor-like lesions, benign and malignant osteoblastic tumors. Analysis focused on genetic alterations in cell cycle regulator genes: Mutations in the p53 gene and ras gene, loss of heterozygosity at the p53, p16 and Rb-locus, and amplification of the mdm2 gene and the c-myc-gene. In addition to cell cycle regulators, the telomerase activity has also been analyzed. The results show that the number of genetic alterations increases with the malignancy of the tumors. The highest number of genetic alterations could thus be found in conventional intraosseous osteosarcoma. In tumor-like lesions, genetic alterations have rarely been observed. The results of this study show that the analysis of genetic instability will probably contribute to an improved differential diagnosis of osteoblastic tumors.

Bone Neoplasms↗
PubMed1998

[Antisense inhibition of urokinase in a human osteosarcoma cell line].

In the multistep process of tumor metastasis, different cellular functions are known to be influenced by the urokinase plasminogen activator (u-PA). In different types of malignancies, u-PA has been shown to correlate strongly with a malignant tumor cell phenotype. Besides its proteolytic activity, the enzyme is effective by signal transduction mechanisms. To elucidate u-PA functions in osteosarcoma, in the present study, the osteosarcoma cell line MNNG/HOS was transfected with an antisense (as) expression vector encoding the 3' end of u-PA-cDNA. Several stably transfected cell clones were characterized and compared with the parental cell line. The antisense transfection resulted in: (1) stable incorporation of the vector construct into cellular genome, as demonstrated in Southern blot; (2) decreased u-PA expression in Northern blot; (3) 50% reduced u-PA protein expression in both cell homogenate and cell culture medium; (4) unchanged cellular proliferation and u-PAR (urokinase plasminogen activator receptor) expression. In comparing functional analysis, as-clones showed (I) significant reduced in vitro invasion and motility (chemotaxis with collagen I); (II) significantly reduced adhesion activity to both vitronectin and collagen I matrices but unchanged adhesion on matrigel; (III) reduced in vivo metastasis in chick embryos after i.v.-application. All together, this data show that malignancy of the osteosarcoma cell line MNNG/HOS is positively influenced by urokinase in terms of migration and selective adhesion. Both effects were observed besides the previously described enzyme functions in tumor cell invasion and basement membrane degradation.

Bone Neoplasms↗
PubMed1998

[Telomere lengths and telomerase activity in liposarcomas].

We measured telomerase activity in 36 malignant and seven benign lipomatous neoplasias from 34 patients to assess the role of telomerase in the development of liposarcoma. The sensitive PCR-based telomerase assay (telomeric repeat amplification protocol-TRAP) was applied. We correlated telomerase activity with the shortening or elongation of telomeric repeat fragment length (TRF), measured by using hybridization with a telomere specific oligonucleotide probe. Telomerase activity was demonstrated in 69% of malignant tumors. This information may be helpful in distinguishing benign tumors from malignant neoplasias. Telomerase expression, however, seems to be characteristic of poorly differentiated liposarcomas. Telomerase activity was not correlated with age at the time of diagnosis or with sex. We observed that telomerase expressing tumors had higher proliferation indices than neoplasias lacking telomerase. Telomerase activity was observed in all eight recurrences, suggesting a close association of telomerase with the biologic behavior of liposarcomas. Therefore, we assume that telomerase plays a key role in the establishment and progression of lipomatous tumors.

Humans↗
PubMed1998

Immunocytochemical detection of somatostatin receptors sst1, sst2A, sst2B, and sst3 in paraffin-embedded breast cancer tissue using subtype-specific antibodies.

The long-acting somatostatin analogue octreotide (SMS 201-995) inhibits growth of certain breast cancer cell lines in vivo and in vitro. Because the antiproliferative action of octreotide depends on at least the presence of somatostatin receptors, it is crucial to determine the pattern of somatostatin receptor protein expression on the tumor cells. In the present study, we have raised polyclonal antibodies to somatostatin receptor subtypes (ssts) sst1, sst2A, sst2B, and sst3 using peptides corresponding to their COOH-terminal sequences. These antisera were used for immunocytochemical staining of paraffin sections of 33 primary breast cancers. Somatostatin receptor-like immunoreactivity (Li) was predominantly localized to the plasma membrane of the tumor cells. In the vast majority of positively stained tumors, somatostatin receptor-Li was uniformly present on nearly all tumor cells. Both the level and the pattern of expression of ssts varied greatly between individual carcinomas. sst2A-Li and/or sst2B-Li was detectable in 28 tumors (85%); among these, 14 tumors (42%) showed particularly high levels of sst2-Li. sst1-Li was found in 17 (52%) cases and sst3-Li in 16 (48%) cases. The expression of ssts was independent of patient age, menopausal status, diagnosis, histological grade, and levels of estrogen and progesterone receptors. The immunocytochemical determination of somatostatin receptor status allows direct detection of receptor protein on the tumor cells and, hence, may provide more precise information than reverse transcription-PCR for predicting response to octreotide therapy in breast cancer.

Adult↗
PubMed1997

Expression of plasminogen activators and plasminogen activator inhibitor 1 in dedifferentiated chondrosarcoma.

BACKGROUND: The plasminogen activator system plays an important role in different malignant tumors. These enzymes participate in the destruction of intercellular matrices and basement membranes and/or can modulate the growth potency of tumor cells and may even promote metastases. In this study, the expression of three glycoproteins that play a role in the plasminogen activator system as activators of proteolysis-urokinase type plasminogen activator (u-PA), tissue type plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) were studied in various components of dedifferentiated chondrosarcomas of bone. METHODS: The expression of u-PA, t-PA, and PAI-1 was investigated in 10 dedifferentiated chondrosarcomas and 14 conventional chondrosarcomas. The plasminogen activator/inhibitor glycoproteins were visualized immunohistochemically on paraffin sections and the levels of expression were assessed semiquantitatively. RESULTS: In dedifferentiated chondrosarcoma, high grade dedifferentiated components displayed strong, diffuse coexpression of u-PA, t-PA, and PAI-1. For all glycoproteins studied, the immunoreactivity was significantly increased compared with the reactions in the low grade cartilaginous component of the same tumor and conventional chondrosarcoma. In the latter, u-PA, t-PA, and PAI-1 expression was found to be enhanced at invasive foci and in regions of endochondral ossification. CONCLUSIONS: The current study documents the overexpression of u-PA, t-PA, and PAI-1 in dedifferentiated chondrosarcoma and suggests involvement of the plasminogen activator system in the biology of these tumors.

Bone Neoplasms↗