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F W Rath

Publications and source records attributed to F W Rath.

97 records · Page 6Linked to original sources
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Presarcomatous lesions of experimentally induced sarcomas in rats: morphologic, histochemical, and immunohistochemical features.

Morphological studies have been performed mainly on manifest sarcomas, leading to divergent views of its histogenesis. However, histogenesis requires understanding of the tumor precursor cells and cannot be resolved by static morphologic studies. Defining presarcomatous lesions is made more difficult because they do not possess a basement membrane that serves as biologic and nosologic boundary like in epithelial cancers. The present study, therefore, investigated the early phases of experimentally induced rat sarcoma, which closely resembles human malignant fibrous histiocytoma (MFH). Histological, enzyme- and immunohistochemical methods were used to define the sequential events involved in tumorigenesis. A benzo[a]pyrene-oil mixture was injected intramuscularly into the thighs of rats, producing MFH 120 days later. Groups of animals were sacrificed every 10 days. The injections produced soft tissue lesions characterized by three distinct phases that overlapped or existed simultaneously in one animal: an initial acute inflammatory reaction characterized by an infiltration of lymphocytes, monocytes and macrophages, a second mesenchymal fibromatous phase characterized by the predominance of spindle-shaped, focally atypical fibroblast-like cells and collagen, and a third premalignant neovascularization phase characterized by dominant capillary proliferations. Overt MFH developed 120 days after injection and consisted of spindle-shaped fibroblast- and histiocyte-like cells containing atypical mitoses and arranged in a storiform pattern. Control animals injected with olive oil revealed acute inflammatory reactions after 30 days and no signs of chronic inflammation or malignancy after 60 and 120 days. We concluded that these experimentally-induced rat sarcomas develop in a triphasic pattern that resembles non-healing granulation tissue, with neovascularization preceding the occurrence of overt MFH.

Animals↗
PubMedDate not supplied

A multifactorial prognostic model for adult soft tissue sarcoma considering clinical, histopathological and molecular data.

Soft tissue sarcomas (STS) are malignant mesenchymal lesions with a high degree of prognostic variability. Different prognostic markers such as grading, staging, tumour type and localisation are known. The establishment of these markers was based on the evaluation at results of extensive cohorts of patients. Therefore, only the established markers provide us with information about probabilities in relation to other qualities. Considering as many different markers as possible in one prognostic statement should increase the value of the resultant information. Therefore, we developed a model involving known prognostic markers to formulate an individual prognostic index. In a retrospective analysis, different prognostic factors of 198 adult STS patients with histological tumour free resection margins were evaluated using a multifactorial analysis. On the basis of a Cox-Regression-Model with proportional hazards, the prognostic factors (tumour type, staging, localisation and type of surgical resection) were selected using previous knowledge and a statistical step backward selection procedure adjusting the immunohistochemical status of p53/Mdm2 expression. On the basis of the baseline survival function of our cohort (S0 (t)), the cumulative probability of survival for two S (2) and five S (5) years was estimated. As a result of our analysis the equations S (2) = (e-00393)P and S (5) = (e-00869)P can be used to estimate the individual two and five-year probability of survival in our cohort. Here p is the result of the amount of the estimated regression-coefficients of the exact variables of the respective individual patient. This model makes it possible to include all the evaluated prognostic factors which, in turn, increases the accuracy of the prognostic information for individual patients underlining the proportional hazards assumption.

Abdominal Neoplasms↗
PubMedDate not supplied

Glycohistochemical monitoring of chemically induced sarcomas at different stages of tumorigenesis.

Malignant soft tissue tumors still represent a source of uncertainty and controversy concerning histogenetic origin and histological behavior. Considering this, chemically induced sarcomas furnish an attractive model for the elucidation of cellular alterations during tumorigenesis. This approach allows us to closely follow cyto- and histological changes within coherent stages of tumor development. The specimen under scrutiny comprised 35 rat tissue samples from day 10 up to day 200 after benzo[a]pyrene injection. Additionally, for comparison and validation two human malignant fibrous histiocytomas (MFH) were investigated. The essential biological significance of protein-carbohydrate interactions warranted the histochemical application of synthetic tools (neo-glycoproteins-NGP) and lectins in order to reveal phenotypical dynamics in this aspect throughout the process of tumor development. Namely, 6 plant lectins (carbohydrate-binding proteins with defined saccharide specificity), 7 custom-made synthetic NGP (as the corresponding ligands visualizing endogenous lectins) and additionally three antibodies were employed. Characteristic cell populations were histochemically demonstrated in four stages of tumor development: exudation (n = 5), mesenchymal proliferation (n = 7), atypical granulation tissue (n = 7) and sarcoma (n = 16). Changes of glycohistochemical binding patterns were in close phenotypic relation to cellular activity, differentiation, local distribution as well as malignant transformation and tumor progression. At present, the new glycobiological features of the malignant phenotype substantiate the assumption that not only glycosylation but also the receptor display is altered upon carcinogenesis. In conclusion, this chronological longitudinal study takes advantage of the combination of a coherent model of tumorigenesis with innovative histochemical tools whose ligands are supposed to act as mediators of cell-cell- and cell-matrix interactions. It clearly demonstrates the suitability of the glycohistochemical method for comparative approaches. The systematic analysis of glycohistochemical determinants will improve our understanding of the early tumor biological processes with potential implications for therapeutic interventions.

Animals↗
PubMedDate not supplied

A permanent cell line of the crayfish Orconectes limosus as a potential model in comparative oncology.

A cell line, designated OLGA-PH-J/92, was established from neuronal tissue of the crayfish Orconectes limosus. To date the cell line has been subcultured more than 150 times. From the original cell line two 'daughter' cell lines and one cloned cell line were isolated. Best growth was obtained when the cells were incubated in Eagle's Minimum Essential Medium supplemented with 6% fetal bovine serum at a temperature of 27 degrees C. Under these conditions the population doubling time lasted between 23 and 25 hours. The shape of the cells is dendritic, but can change to spherical when conditions are less optimal. The cell lines showed features of transformation, such as anchorage independence, loss of contact inhibition, and low serum requirement. The number of chromosomes found in the cell lines ranged from 11 to 136, while in the donor species numbered between 98 and 106. It will be of interest to study if the O. limosus cell lines grow malignantly in vivo. OLGA-PH-J/92 and the derivative cell lines should also be suitable for studying viral infections in crustaceans.

Animals↗
PubMedDate not supplied

The p53 gene in soft tissue sarcomas: prognostic value of DNA sequencing versus immunohistochemistry.

BACKGROUND: The aim of this study was to compare sequencing and immunohistochemistry (IHC) for their ability to detect p53 mutations and to assess their prognostic value in soft tissue sarcomas (STS). MATERIAL AND METHODS: 146 STS samples were investigated by single strand DNA conformation polymorphism (SSCP)-sequencing for p53 mutations. Additionally, IHC with five p53 antibodies (CM-1, Pab1801, Pab240, DO1, DO-7) was performed. RESULTS: In 65 to 131 tumor samples (44.5% to 90.4%) elevated levels of p53 protein were recorded by IHC, depending on the antibody applied. Sixteen out of 146 STS tumor samples (11%) had p53 gene mutations. 13 cases (81.2%) of the 16 tumors with p53 mutations could be detected by DO-1. However, of the 93 DO-1 positive tumors 79 were negative by SSCP-sequencing analysis. Using multivariate regression analysis (Cox proportional hazards model) both p53 mutations (non-frameshift mutations) and IHC detection of p53 protein overexpression were prognostic predictors for poor survival. CONCLUSIONS: This study suggests that IHC is valuable for assessing p53 mutations in STS, but sequencing provides additional important information on the molecular characteristics of the alterations.

DNA, Neoplasm↗