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Biomedical subjects

A Roessner

Publications and source records attributed to A Roessner.

At least 145 records · Page 8Linked to original sources
PubMed1996

Mutation spectrum of p53 gene in highly malignant human osteosarcomas.

In this study, we analyzed the spectrum of p53 tumor suppressor gene mutations in 40 highly malignant osteosarcomas, one osteosarcoma metastasis, and one osteoblastoma with malignant transformation. Using predominantly formalin-fixed and paraffin-embedded material, we performed polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis of exons 4-8 and direct sequencing. Molecular genetic findings were correlated with immunohistochemical detection of p53 protein. A total of eight alterations (19%) were identified. Two splice mutations were detected in one case of a highly malignant osteosarcoma and its metastasis, and in one osteoblastoma with focal malignant transformation. Four of the mutations were missense mutations, one was of the silent type. These data correspond to the results found in the literature on bone and soft tissue tumors. Therefore, retrospective studies of p53 gene turn out to be quite appropriate for molecular biologic examinations.

Adolescent↗
PubMed1995

The urokinase plasminogen activator (u-PA) and its inhibitor (PAI-1) in embryo-fetal bone formation in the human: an immunohistochemical study.

The role of urokinase plasminogen activator and plasminogen activator inhibitor-1 in human embryo-fetal bone formation between the 9th and the 20th week of gestation has been studied immunohistochemically. While mature osteocytes of the secondary spongiosa and resting chondrocytes of the bone epiphyses were negative for both antigens in each developmental stage, metabolically active parts of the osseocartilaginous system showed a strong immunoreactivity. Until the end of the 10th week of gestation urokinase plasminogen activator and plasminogen activator inhibitor-1 could not be demonstrated in the shaft of the preexisting cartilaginous models of bones, which correlates with the morphological developmental stage of the embryos. Later, osteoblasts and chondrocytes in the areas of enchondral ossification, and the perivascular chondrocytes of the epiphyseal secondary ossification centres, showed similarly high concentrations of urokinase plasminogen activator and plasminogen activator inhibitor-1. Moreover, the individual ossification stages of the different bones in embryo-fetal development could be demonstrated immunohistochemically. While humeri and femora showed diaphyseal immunoreactivities at an early stage, positive reactions in the phalanges were found only much later. Thus, the enzymes of the fibrinolytic system studied are clearly involved in the desmal and enchondral ossification process in the osseocartilaginous compartment.

Bone and Bones↗
PubMed1995

Immunohistochemical analysis of nm23 protein expression in malignant bone tumors.

Expression levels of nm23 protein in 72 malignant bone tumors comprising 41 osteosarcomas, 22 chondrosarcomas, 6 Ewing's sarcomas, and 2 malignant fibrous histiocytomas were examined immunohistochemically, using anti-nm23 protein polyclonal antibody, and compared with 51 cases of benign bone tumors or tumor-like lesions. Malignant bone tumors showed significantly higher nm23 protein expression than benign bone tumors or tumor-like lesions (P < 0.0001). In chondrosarcoma, nm23 expression increased in high-grade tumors (grade I versus grade II and III: P = 0.0229). In the cases of osteosarcoma, however, grade IV osteosarcomas showed decreased expression of nm23 compared with grade III tumors (P = 0.0122). There was no significant relationship between nm23 expression and histological type. nm23 expression had no correlation with metastatic potential in osteosarcoma, although the therapy was not uniform in our cases. Furthermore, in 6 cases of osteosarcoma and 1 case of Ewing's sarcoma, there was no clear tendency for a decrease of nm23 in the metastatic sites compared with primary sites, as reported in breast cancer. These results showed that, in contrast to reports on breast cancer and experimental models, nm23 protein expression in human bone tumors may be associated with malignant potentiality, except in cases of osteosarcoma.

Adolescent↗
PubMed1995

Adamantinoma of long bones. A histopathological and immunohistochemical study of 23 cases.

The clinical and histological data of twenty-three cases of adamantinomas of the long bone collected by the Working Group on Bone Tumors at the DKFZ/FRG are reported including immunohistochemical observations in twenty-one of the cases. Females and males between 5 and 67 years (mean, 25.4 years) were affected equally (11/12). All adamantinomas were positive for cytokeratins often in coexpression with vimentin, at least focally. Although exhibiting varying histological patterns, no correlation between histology and clinical course was seen. However, sex and mode of initial therapy seem to influence an unfavorable clinical outcome. All three decreased patients were males receiving marginal or delayed surgery. This underlines the low-grade malignant character of adamantinoma. To assure the histological diagnosis pathologists should employ immunohistochemistry for demonstrating the sometimes sparse epithelial cell nests when radiology is suggestive for adamantinoma. Correct diagnosis should lead to resection with wide surgical margins.

Adolescent↗
PubMed1995

New aspects of cell biology in osteosarcoma.

Among the solid tumors of childhood and adolescence, osteosarcoma (OS) represents the most prominent example of efficient aggressive chemotherapy with secondary surgical therapy. A specific subclassification of the tumor is indispensable and must include recent results of cell biology. The co-distribution of different collagen types I-VI reflects the diverse differentiation of osteosarcoma cells, supporting the concept of a pluripotent mesenchymal cell to be the stem cell of the tumor. In contrast, osteonectin (SPARC) may not be considered as a reliable marker for osteosarcoma. The experience of special proteins being secreted by osteosarcoma cells is rather limited. Detailed molecular biological studies are still lacking. A loss of alleles on chromosome 17, particularly in the defined region 17p 13, can be observed in more than 75% of all OS, suggesting the contribution of a tumor suppressor gene, p53, located in that region. It is a 53 kd nucleophosphoprotein binding the major transforming protein, the large T antigen of Simian Virus 40. Immunohistological results showed positive staining with the antibody Pab 240 in 13 of 18 cases. In one osteoblastic OS, a novel splice mutation resulting in a fusing of exon 5 directly to exon 7 was detected. RB1 gene is also of major importance for the tumorigenesis of OS. The multidrug resistance (mdr) is associated with a membrane-bound channel-forming transport protein, the P-glycoprotein. It is a conserved plasma membrane component of about 170 kd. Both the human isoforms mdr 1 and mdr 3 are localised in the long arm of chromosome 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Neoplasms↗
PubMed1995

Synchronous multifocal bone sarcomas--a case report and molecular pathologic investigation.

A case of a 54-year-old woman is described who developed synchronously two malignant bone tumors: a dedifferentiated chondrosarcoma in the olecranon and a malignant fibrous histiocytoma (MFH) in the lower tibia. The anaplastic part of the dedifferentiated chondrosarcoma revealed an MFH-like pattern. Myogenous differentiations were not observed in the anaplastic sarcoma cells. The MFH in the tibia showed a storiform-pleomorphic pattern. Single tumor cells showed positivity for M-actin and desmin pointing to myogenous differentiation. DNA-cytophotometry of the dedifferentiated chondrosarcoma showed an aneuploid stem cell line. The MFH in the tibia did not reveal aneuploid stem cells. Staining for p53 protein was negative in both tumors. SSCP analysis and sequencing of the p53 gene in both tumors revealed in the dedifferentiated chondrosarcoma a mutation in exon-8 with the transversion from G to T in codon 294 resulting in a substitution of a stop codon for GLU. The mutation was not observed in the MFH. From these immunohistologic, DNA-cytometric and molecular biologic investigations, we consider it probable that the tumor in the lower tibia is a second highly malignant bone tumor and not the metastasis of the dedifferentiated portion of the dedifferentiated chondrosarcoma in the olecranon.

Bone Neoplasms↗
PubMed1995

Extra-abdominal aggressive fibromatosis after treatment of a Morbus Hodgkin. A case report.

The proliferations of the connective tissue, which are summed up under the term fibromatoses, assume a special position with regard to their biologic behavior. While superficial fibromatoses are more likely to grow slowly, musculoaponeurotic fibromatoses (Desmoid tumor)--like malignant tumors--show a locally bound aggressive, rapid growth behavior. A metastazation, however, can never be proved. The research on etiology of fibromatoses has yielded only little knowledge. Besides genetic and hormonal factors, physical reasons are under discussion, too. The present study aims to add another description of a case report to the small number of case presentations on radiotherapy-associated fibromatosis. In 1977, a now 67-old-patient was irradiated because of a Morbus Hodgkin lymphoma in the left side of his neck. Prior to the radiation, the patient had undergone several surgeries. 17 years after the radiation, the patient developed an aggressive fibromatosis (prelaryngeal, right) in the formerly irradiated region. As the localization of the fibromatosis does not allow us to establish a connection to his numerous operations preceding the fibromatosis, a radiation-associated Desmoid tumor must be assumed. Immunohistologically, no estrogen receptors were detectable.

Actins↗
PubMed1995

Expression of growth factors and their receptors in human osteosarcomas. Immunohistochemical detection of epidermal growth factor, platelet-derived growth factor and their receptors: its correlation with proliferating activities and p53 expression.

The expression of both epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), and of their receptors (EGFR and PDGFR) was immunohistochemically examined in 37 cases of osteosarcoma. Furthermore, immunostaining for p53 protein and Ki-67 antigen by MIB-1 was carried out and compared with the above results. EGFR (81%) expressed more often than EGF (51%) and the expression of EGF and EGFR, and PDGF and PDGFR were recognized in 49% and 38%, respectively. In eleven cases (30%), the expression of both growth factors and their receptors was combined. Anaplastic osteosarcoma showed higher MIB-1 index than osteoblastic and fibroblastic subtypes (P < 0.05). High grade osteosarcomas (G3 and G4) revealed higher MIB-1 index compared with low grade tumors (G1 and G2). PDGF positive tumors (MIB-1 index: 20.0) showed significantly higher proliferation compared with PDGF negative tumors (MIB-1 index: 6.5) (P < 0.01). Five out of 37 cases (13.5%) showed positive immunoreaction for p53. There was no correlation of p53 status with MIB-1 index and the expression of growth factors or their receptors. Our results suggest that PDGF expression may be an important mediator of cell proliferation control, via an autocrine mechanism, in human osteosarcoma.

Antibodies, Monoclonal↗
PubMed1994

Rapid detection of loss of heterozygosity of chromosome 17p by polymerase chain reaction-based variable number of tandem repeat analysis and detection of single-strand conformation polymorphism of intragenic p53 polymorphisms.

Intragenic restriction site polymorphisms in amino acid residue 72 in exon 4 and a Mspl polymorphism in intron 6 of the p53 tumour suppressor gene can both serve as polymorphic markers. Probe YNZ22 (D17S5) is a highly polymorphic, variable number of tandem repeat (VNTR) marker which maps to chromosome 17p13.1 where the p53 gene is located. Locus specific amplification by polymerase chain reaction (PCR) technique and subsequent non-isotopic single-strand conformation polymorphism analysis of the PCR fragments was used for the detection of loss heterozygosity (LOH) of 17p including the p53 gene locus. In combination with a PCR-based method for the analysis of the VNTR locus D17S5 using unique sequences flanking the polymorphic region of YNZ22 we investigated tumour DNA and corresponding constitutional DNA from 69 patients, including 39 patients with gastric cancer, 21 patients with osteosarcomas and 9 patients with Ewing's sarcomas. Using all three methods, 49/69 (71%) patients were informative for LOH, which revealed allelic loss in 5/39 (12.8%) gastric cancers, 1/9 (11.1%) Ewing's sarcoma, and 4/20 (20%) osteosarcomas.

Base Sequence↗
PubMed1994

Expression of matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) induced by tumour necrosis factor alpha correlates with metastatic ability in a human osteosarcoma cell line.

We have examined the correlation between matrix metalloproteinase (MMP) expression and metastatic properties of a low metastatic osteosarcoma cell line, osteosarcoma takase (OST), under stimulation by tumour necrosis factor alpha (TNF alpha). In vivo, OST cells exhibited significantly increased colonization in the lungs of nude mice in a dose-dependent manner when they were treated by TNF alpha prior to injection. In vitro, TNF alpha enhanced tumour cell invasion through the reconstituted basement membrane in a transwell chamber up to 2.5-fold. Gelatin zymography and sandwich enzyme immunoassays demonstrated marked production of MMP-9 [92-kDa gelatinase/type IV collagenase (gelatinase B)] but not MMP-2 [72-kDa gelatinase/type IV collagenase (gelatinase A)], MMP-3 (stromelysin-1) or MMP-7 (matrilysin). Motility of the tumour cells and adhesion to cultured endothelial cells were slightly increased by the TNF alpha treatment up to 1.6-fold and 1.4-fold, respectively, while the growth rate was decreased. These results suggest that upregulation of MMP-9 together with enhanced motility and endothelial adhesion contribute to the increased metastatic ability of OST cells induced by TNF alpha treatment.

Collagenases↗
PubMed1994

Ultrastructural localization of the S-100-like proteins MRP8 and MRP14 in monocytes is calcium-dependent.

MRP8 and MRP14 are members of the S-100 family of Ca(2+)-binding proteins and are expressed by granulocytes and monocytes. Members of this family have been described to be involved in membrane and cytoskeleton interactions; we therefore studied the subcellular distribution of MRP8/MRP14 in cultured human monocytes at the ultrastructural level. Monospecific rabbit antisera against MRP8 and MRP14 and a monoclonal antibody (moAb 27E10), which exclusively recognizes the MRP8/MRP14 heterodimer but not the monomers, were used in both immunoperoxidase/preembedding- and immunogold/cryotechniques. Comparing non-stimulated monocytes with Ca2+ ionophore A23187-treated cells, we could demonstrate that MRP8 and MRP14 associate with membrane and cytoskeletal structures in a Ca(2+)-dependent manner. Employing moAb 27E10, MRP8/MRP14 complexes were shown to be translocated to these cellular components. In addition, immunogold double-labelling experiments revealed a clear co-localization of MRP8/MRP14 complexes with the type III intermediate filament vimentin. Analysis of immunogold-labelled cryosections of renal allografts after acute vascular rejection demonstrated that a subpopulation of infiltrating macrophages showed a similar association of MRP8/MRP14 to the cytoskeleton in situ; this finding emphasizes the in vivo relevance of our observations. We conclude that Ca(2+)-dependent translocation of MRP8/MRP14 occurs to distinct subcellular components suggesting a role of these proteins for the modulation of cytoskeletal and membrane interactions.

Antigens, Differentiation↗
PubMed1994

Immunohistochemical localization of PDGF B, PDGF beta receptors and IGF I receptors during atherogenesis.

Growth factors and their receptors may be involved in initiation and progression of atherosclerotic intima changes. In this study, sections of human arteries in different stages of atherosclerosis were investigated for cellular expression of PDGF B, PDGF beta receptors and IGF I receptors. The applied immunohistochemical approach detected IGF I receptor synthesis in endothelial cells of atherosclerotic vessels. A possible role in atherogenesis may be seen in the control of IGF I transfer into subendothelial tissues. PDGF B chain production was observed in endothelial cells and macrophages in all stages of lesion development. The corresponding receptor for PDGF B (PDGF beta receptor) was expressed by transformed smooth muscle cells within the thickened intima from the stage of macrophage infiltration onwards. These results support the thesis that locally produced PDGF acts as a mitogen on smooth muscle cells and may promote proliferation during atherogenesis.

Animals↗
PubMed1994

Plasminogen activators and their inhibitor in osteosarcomas and other bone tumors.

The concentrations of the plasminogen activators u-PA and t-PA as well as the inhibitor PAI-1 were studied immunohistochemically in 35 osteosarcoma specimens compared to 15 Ewing's sarcomas and various other bone lesions. The immunoreactivities of plasminogen activators in osteosarcoma specimens were significantly higher than PAI-1. Biochemically in cell cultures and immunohistochemically in the pathological specimens of the osteosarcomas u-PA was the dominant antigen, all factors showing a generally strong reactivity. Here a relation to the malignancy and invasivity of the tumors could be seen, which was comparable to the results in other tumors. This correlation, however, could not be detected in Ewing's sarcomas. On the whole low immunoreactivity of all enzymes, and of u-PA in particular, could be seen. In comparison in some benign lesions (fibrous dysplasias, aneurysmal bone cysts) the immunohistochemical reactions were distinctly stronger. Dominant antigens did not exist in Ewing's sarcomas. In all mesenchymal tumors studied the immunohistochemical localisation and concentration of the antigens showed a definite correlation with their histological differentiation. Chondroblastic differentiations in different tumors (chondrosarcomas, enchondromas, chondroblastic osteosarcomas) or chondroid parts were always negative for both activators and the inhibitor, especially in their central parts. Here, the biological malignancy was not decisive for the result.

Bone Neoplasms↗
PubMed1994

[Determination of the growth rate of tumor-like space-occupying lesions of the bones. A study of 1154 lesions of the long tubular bones].

In 1088 primary and secondary bone tumors and tumorlike lesions and in 66 inflammatory lesions, the growth rate was graded according to the Lodwick classification. Grade IA and grade IB were correlated with benign lesions in 99.8% and 91.3% of cases, respectively. In contrast, grade III and grade II were associated with malignant tumors in 100% and 89.6%, respectively. With increasing age, the proportion of malignant tumors among those graded as IB or II increased significantly. Tumors classed as grade IC were benign in 57.5% and malignant in 42.5% of cases. The growth rates of the individual tumor entities were analyzed.

Adolescent↗
PubMed1993

Development of hypertension in neuroblastoma during therapy: a case report.

A case of stage 4 neuroblastoma that developed excessive hypertension on day 120 of chemotherapy is presented. The tumor initially had responded well to chemotherapy; however, while the tumor mass decreased, plasma and urine catecholamines and the blood pressure increased. The plasma concentrations of noradrenaline, adrenaline, and dopamine increased to 26.4, 1.8, and 36.2 micrograms/l, respectively. The profile of catecholamine metabolites changed: on day 150 of therapy, noradrenaline, adrenaline, and dopamine levels were increased, whereas HVA and VMA levels were decreased when compared to day 1 of therapy. The only residual neuroblastoma tissue visible on MIBG scintigraphy on day 150 of treatment was a metastasis in the left tibia which was irradiated with 24 Gy. The adrenaline concentration in the left femoral vein was twice as high compared to the right femoral vein. A treatment, possibly radiation-associated tumor cell alteration resulting in a different catecholamine production, is discussed.

Abdominal Neoplasms↗