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Biomedical subjects

F W Rath

Publications and source records attributed to F W Rath.

At least 37 records · Page 2Linked to original sources
PubMed1998

Pattern of lymph node metastases in papillary thyroid carcinoma.

BACKGROUND: Incidence and pattern of lymph node metastasis (LNM) were evaluated in 35 patients who underwent primary surgery for papillary thyroid carcinoma. METHODS: Total thyroidectomy with systematic cervicocentral lymphadenectomy was performed routinely. Additionally, 22 patients underwent lymphadenectomy of the ipsilateral cervicolateral compartment. Sternotomy was performed in four patients. RESULTS: Primary tumour status was: pT1, n = 7; pT2, n = 12; pT3, n = 4; pT4, n = 12. Twenty-four patients had LNM in the ipsilateral cervicocentral compartment (pT1, n = 2; pT2, n = 8; pT3, n = 4; pT4, n = 10). Nineteen had LNM in the ipsilateral cervicolateral compartment (pT1, n = 4; pT2, n = 6; pT3, n = 2; pT4, n = 7). Contralateral cervicocentral LNM was restricted to patients with pT3 tumours (n = 2) or pT4 tumours (n = 3). No patient had LNM in the contralateral cervicolateral compartment. Only one patient (pT3 tumour) had mediastinal LNM. CONCLUSION: The cervicocentral compartment was most commonly involved with metastases, although the ipsilateral cervicolateral compartment was almost as often affected. In some patients ipsilateral cervicolateral LNM was present in the absence of cervicocentral LNM. Contralateral cervicolateral and upper mediastinal LNM, however, were rare. This study helps to plan radical surgery for papillary thyroid carcinoma.

Adolescent↗
PubMed1998

Detection of numerical chromosomal changes in 20 malignant fibrous histiocytomas by FISH.

We investigated 20 malignant fibrous histiocytomas (MFHs) with the help of specific centromeric probes for chromosomes 1, 3, 4, 6, 8, 9, 12, 16, 17 and 18. The results show a broad variation in the number of signals per nucleus. However, tumors can be assigned into four groups: i) with mostly disomic clones, ii) with a high percentage of polysomic clones, iii) with a considerable amount of monosomic and nullisomic clones and iv) with a tendency in both directions. A gain of spots per nucleus takes place in 75-100% of the investigated tumors - the highest incidence occurring with respect to chromosome 3. A loss of spots per nucleus occurred in 20-60% of the tumors - predominantly with respect to chromosome 1.

Aged↗
PubMed1998

Molecular characterization and liposomal transfection of a p53-mutated cell line established from a poorly differentiated leiomyosarcoma.

A human cell line LMS6-93 has been established from a leiomyosarcoma (LMS). Characteristics for ultrastructure, growth characteristics, cell cycle distribution, karyotype, protein expression detected by immunohistochemistry (IHC), p53 mutational status and liposomal transfection behaviour were studied and determined. The primary tumor was clearly positive for á-smooth muscle type actin and desmin in moderately differentiated areas and indicated a loss of myogenic differentiation in other regions and therefore was classified as a poorly differentiated LMS. The cell line LMS6-93 contains mainly polymorphic spindle shaped or polygonal tumor cells which possess the characteristics of primitive mesenchymal cells, based on their morphology and positive reaction with an antibody to vimentin. IHC staining for S100, synaptophysin A, NSE, neurofilament proteins and cytokeratins were negative. Cytogenetic analysis revealed in the cell line diploid karyotypes comparatively close to several structural and numerical aberrations for chromosomes 2, 5, 6, 9, 10, 12, 14, 17, 18, 20, 22, and Y. IHC positivity was found for the tumor suppressor protein Rb and the oncogene product MDM2. In a p53 mutational analysis a 1 bp insertional mutation in exon 6 (G insertion in codon 215) was detected and confirmed in the original primary tumor. The other p53 allele appears to be wild-type as indicated in Western hybridization. Using different cationic lipid formulations complexed with a reporter expression vector (GFP) successful transfection into LMS6-93 cells was observed. The highest transfection rates (20-30% GFP expression in the viable cell population) were obtained with lipofectin. These results suggest that LMS6-93 functions as a good in vitro model for transfection studies on an LMS cell line carrying a heterozygous p53-frameshift mutation.

Blotting, Western↗
PubMed1998

[Liposomal DNA transfection of human sarcoma cells with p53 alterations].

An vital assay allows to optimize liposomal transfection for human tumor cells via FACS. Various cationic lipids were tested to analyse the reporter gene expression (green fluorescent protein, GFP) in different soft tissue sarcoma (STS) cells with known genetic alterations. Furthermore, the cellular uptake of fluorescence-labeled oligodeoxynucleotides (ODN's) was determined. The results obtained with two self-established sarcoma cell lines (LMS6-93, US8-93) were compared with ATCC sarcoma cell lines (Saos-2, A-204, RD) and fibroblast cells. We found maximal 37% cells expressing GFP 24 h post-transfection. All mesenchymal (tumor) cells but not fibroblast cells could be transfected in a cell-specific and lipid-dependent manner. In kinetic studies highest transfection rates were determined between 24 and 48 h, whereas the GFP expression is downregulated after 72 h. Furthermore, we found transfectability is p53 mutation-independent and a relative low toxicity of the new lipids (Lipotaxi and Clonfectin) in comparison to other lipids (Lipofectin, Lipofectamine). By a cell sorting system sarcoma cell lines expressing the reporter gene could be enriched up to 84% of the living cell population. Labeled ODN's were taken up more efficiently (> 90%) when they were mixed with lipids before, but ODN's alone were incorporated into sarcoma cells only in a low percentage (< 10%) and concentration. STS cell cultures showed also a relative high ODN uptake compared with cell lines. We propose the liposomal transfection strategy as an efficient method which can be applied to adherent-growing tumor cells. The method allows simultaneously to study transfection rates, apoptosis and cell cycle alterations in vitro. Furthermore, in future, extension on ex vivo and in vivo transgene expression (xenotransplanted sarcomas) will be evaluated.

Gene Expression Regulation, Neoplastic↗
PubMed1998

[Frequency, distribution and prognostic relevance of p53 mutations in soft tissue sarcomas].

Soft tissue sarcomas although rarely occurring (about 1% of malignant tumors), are because of their histo-morphological diversity and often similar appearance to tumor-like lesions difficult to characterize and estimate in their tumor biological behaviour. Analysis of molecular characteristics as alterations in tumor-suppressor and oncogenes may allow insight in STS genesis. We have chosen the in carcinomas well, but in STS not comprehensively investigated tumor-suppressor gene p53 for mutational analysis. In 16 out of 146 STS patients we could identify p53-mutations. In a multivariate Cox-regression analysis prognosis was correlated with the p53-mutation type. However, only patients with non-frameshift mutations possessed a poorer prognosis (RR = 2.42; p = 0.014) in comparison to patients without mutations, but frameshift-mutations didn't seem to affect prognosis negatively. Compiling our results and those of the literature an overall frequency of 16.3% of p53-mutations in STS, with various frequencies in different entities is detectable. STS specific hotspots are not recognizable. Rather mutational hotspots in codons 175, 245, 248 and 273 well known from studies in carcinomas are also apparent in STS. Summarizing, we want to state that the occurrence of p53-mutations (non-frameshift mutations) is of prognostic importance in STS. Combination of histo-pathological, clinical and molecular characteristics may allow to distinguish in future different groups of patients for an individual treatment.

Codon↗
PubMed1998

[p53 overexpression as independent prognostic marker in soft tissue sarcomas is antibody dependent].

Most changes in p53 result in a protein with prolonged half life. This permits immunohistochemical detection. P53-overexpression seems to have prognostical relevance in soft tissue sarcomas (STS). The goal of this study was to compare the prognostic relevance of five different p53 antibodies in immunohistochemistry of primary STS using a Cox regression model with adjustment to staging, localization, tumor type, and surgical therapy. We investigated 198 primary STS of six different tumor types for p53-overexpression using the antibodies DO-1, DO-7, Pab1801, Pab240, and CM-1. The rate of positivity (cut of point 10% positive tumor cells) was between 36.2% and 62.6% dependent on the applied antibody. Prognostic significance could be determined only for the N-terminal binding monoclonal antibodies (DO-1, p = 0.0014; DO-7, p = 0.005; Pab1801, p = 0.02) with the highest level for combination of DO-7 and Pab1801 positivity (RR = 2.57, p = 0.0098). Pab240 (epitope amino acids 213-217) and CM-1 (polyclonal) showed no prognostic relevance in the multivariate analysis. We therefore suggest that for immunohistochemical evaluation of p53-overexpression in STS a pannel of two N-terminal antibodies should be used at least.

Antibodies, Monoclonal↗
PubMed1997

Prognostic value of immunohistochemistry for p53 in primary soft-tissue sarcomas: a multivariate analysis of five antibodies.

Most changes of tumor suppressor p53 and its pathway involve a protein with prolonged half-life that permits immunohistochemical detection. The goal of this study was to compare the prognostic relevance of five different p53 antibodies in primary soft-tissue sarcomas (STS) with known p53 mutation status, using a multivariate Cox regression model (adjusted to tumor grading, staging, localization, tumor type, and therapy). A group of 198 primary STS of six types were investigated for p53 overexpression, using p53 antibodies DO-1, DO-7, Pab1801, Pab240, and CM-1. A positive marker frequency between 36.2% and 62.6% was detected. Out of 65 patients whose primary tumor reacted positively to all five antibodies, 52 (80%) died within the study period. Only the N-terminal-binding monoclonal antibodies DO-1, DO-7 and Pab1801 showed a multivariate correlation with survival (P = 0.0014, 0.0048 and 0.02). CM-1 and Pab240 had a univariate, but not a multivariate correlation, with a confounding effect of grading. The prognostic relevance for the five p53 antibodies was: DO-1 > Pab1801 > DO-7 > CM-1 > Pab240. This is the first study that investigates multivariately the prognostic relevance of p53 immunostaining in STS. If monoclonal antibodies with an epitope in the N-terminal region of the p53 protein (DO-1, Pab1801, DO-7) are applied, p53 immunohistochemistry provides an independent prognostic marker in STS.

Antibodies, Monoclonal↗
PubMed1997

Immunohistochemical and clinical evaluation of cathepsin expression in soft tissue sarcomas.

Lysosomal proteases are known to enhance the spread of epithelial tumour cells, but little is known of the possible role of proteases in the growth of soft tissue sarcomas (STS). We investigated the expression of cathepsins D, B, S, H, L and procathepsin L in frozen sections of 34 STS from 34 patients by immunohistochemistry (IHC). Cathepsins D, B and H were relatively highly expressed in STS (77-91%). The expression rate of cathepsins S and L and of procathepsin L was lower (40-66%). Cathepsin S and L expression showed a moderate (P = 0.078 and P = 0.019) and procathepsin L a strong (P = 0.00001) correlation with the survival rate of STS patients. Cathepsin S expression is also correlated with the local recurrence rate (P < 0.01). Lysosomal proteases may play a role in STS progression, and cathepsin expression may also have significance as a prognostic factor in STS.

Adult↗
PubMed1997

Prognostic relevance of C-terminal Mdm2 detection is enhanced by p53 positivity in soft tissue sarcomas.

We examined the clinical value of immunohistochemical (IHC) Mdm2 detection by an N-terminal (IF2) and a C-terminal (19E3) binding monoclonal antibody (Ab) in soft tissue sarcomas (STSs) with regard to the p53 status. Therefore, we investigated a cohort of 198 patients with STSs of six entities with known p53 IHC by using a multivariate Cox regression model to determine the prognostic value of Mdm2 staining. Only positivity with the 19E3 Ab correlated multivariately significantly with survival (RR = 2.32, p = 0.0035). We stratified the C-terminal Mdm2 staining (19E3) according to p53 IHC (DO-1) and found patients could be divided into three groups with an increasing risk: (a) patients with Mdm2 (19E3)-negative as well as p53 (DO-1)-negative tumors, (b) patients with tumors that were either Mdm2 (19E3) or p53 (DO-1) positive, and (c) patients with tumors that were Mdm2 (19E3) as well as p53 (DO-1) positive. Positive staining for both Mdm2 and p53 meant a very poor prognosis with a relative risk of 4.63 (p = 0.00001). This points to the possibility that--in addition to the p53-dependent pathway--Mdm2 could have an effect through a p53-independent pathway. Thus, our results indicate that C-terminal Mdm2 staining (19E3) constitutes an independent prognostic marker in STS.

Adolescent↗
PubMed1997

Detection of p53 autoantibodies in sera of gastric cancer patients and their prognostic relevance.

BACKGROUND: Changes in the p53 gene product can be immunogenic and enable the formation of p53 serum antibodies (p53ab), detectable in patients with different cancer types. So far, there have been no reports describing the detectability of p53ab in gastric cancer patients. METHODS: We investigated the presence of p53ab and their clinical relevance in a cohort of 74 gastric cancer patients, using an enzyme-linked immunosorbent assay system. RESULTS: In our investigation 20.3% of all patients (15 of 74) and 46.9% of the patients with immunohistochemically (IHC) p53-positive tumors (15 of 32) showed detectable p53ab in serum. All p53ab-positive patients had IHC p53-positive tumors. We have found a significant correlation of p53ab with a higher tumor stage (P = 0.002) and also with a poor prognosis of survival (P = 0.04). CONCLUSION: We have shown that in gastric cancer patients p53ab are also detectable and that p53ab positivity is a predictor of an unfavorable prognosis.

Adult↗
PubMed1996

Frequent occurrence of p53 mutations in rhabdomyosarcoma and leiomyosarcoma, but not in fibrosarcoma and malignant neural tumors.

We have analyzed soft-tissue sarcomas (STS) molecularly for mutations in the tumor-suppressor gene p53 and immunohisto-chemically for expression of p53 and mdm2 proteins. In this study, tumor samples from 3 groups of soft-tissue sarcomas, i.e., fibrosarcomas, myogenic sarcomas and malignant neural tumors (MNT), were investigated. The methods applied encompass immunohistochemistry on 198 tumor samples using p53 antibodies (DO-1 and DO-7) and an mdm2 antibody (IF-2). Out of these, 100 samples were subjected to non-radioactive PCR-SSCP-sequencing analysis. Immunohistochemical detection rate for p53 (range of 57% to 67%) and for mdm2 proteins (range of 19 to 44%) was similar in all 3 groups. In higher tumor grades, an increased rate of immunopositivity was found for p53 but not for mdm2. Investigation of p53 mutational status revealed 6 mutations in myogenic sarcomas but none in malignant neural tumors or fibrosarcomas, suggesting different roles of p53 in the 3 STS groups. Interestingly, a G-->A transition in codon 245 (a CpG site) was found in 3 myogenic sarcomas. Our results and those of others suggest p53 codon 245 as a mutational hotspot in sarcomas, as recognized in carcinomas.

Base Sequence↗
PubMed1995

Molecular and immunohistochemical p53 status in liposarcoma and malignant fibrous histiocytoma: identification of seven new mutations for soft tissue sarcomas.

BACKGROUND: p53 mutations are the most frequently observed tumor-related genetic changes. Mutational analysis concerns mostly carcinomas and is not comprehensive for soft tissue sarcomas. Among soft tissue sarcomas, malignant fibrous histiocytoma (MFH) and liposarcoma represent the most frequent tumor types. Most of the few identified mutations for soft tissue sarcomas are localized in the core domain of p53. A correlation between p53 positive immunoreactivity, missense mutations, and a poor prognosis is generally assumed. However, the character of p53 mutations and their functional importance for the clinical process is still unknown. METHODS: Sixty-two soft tissue sarcoma samples were investigated for the presence of p53 mutations and for p53 immunoreactivity. Exons 4-9 of the p53 gene were amplified from genomic DNA with the polymerase chain reaction. A prescreen for mutations was performed by nonradioactive single strand conformation polymorphism analysis; striking cases were sequenced directly. For an evaluation of the immunohistochemical status, five p53 antibodies were used. RESULTS: In 10 tumor samples 7 new p53 mutations and one polymorphism were identified. Mutations were detected for five liposarcomas (four patients) and four MFHs (three patients). Of the seven mutations, three were missense point mutations, three were deletions, and one was a complex conversion. All mutations but one were localized in the core domain of p53. Of 62 tumor samples, 56% (14 of 32 liposarcomas and 21 of 30 MFHs) were positive for p53 immunostaining. CONCLUSIONS: The mutations identified in the core domain affect codons that are structurally or functionally involved in DNA binding. A relation between p53 positive immunoreactivity and a poor prognosis, but not with an exclusively high tumor grade, is evident. p53 mutations in soft tissue sarcomas have a similar spectrum to those in carcinomas.

Histiocytoma, Benign Fibrous↗
PubMed1993

Cytogenetic analysis of a benzpyrene induced osteosarcoma in the rat (Rattus norvegicus).

A cytogenetic comparison of primary and transplant tumor cell-lines, both originating from a benzpyrene induced osteosarcoma, with normal rat cell-lines (Rattus norvegicus) is presented here. In all tumor cell-lines tested, the number of chromosomes was increased by one or two. Using Giemsa-banding, structural chromosomal changes, i.e. a Robertsonian translocation t(4;4)(q10;q10) and an interstitial deletion del(6)(q11q16) could be recorded. Furthermore, staining of nucleolus organizer regions (NORs) revealed a shift in NOR activity from chromosome number 11 to 12 and a decrease in NOR activity at chromosome number 3.

Aneuploidy↗
PubMed1992

[A rare complication of shunt therapy. Metastasis of brain tumors by cerebrospinal fluid drainage].

Shunting of cerebrospinal fluid to extracranial spaces has been a common and effective procedure for symptomatic therapy of hydrocephalus since the fifties. In 1954 the first spreading of tumor cells via a ventriculo-pleural shunt was reported. We are presenting a case of a 10 month old girl with a medulloblastoma of the lower brain stem with spreading of the intracranial tumor through a ventriculoperitoneal shunt. Further 43 cases of the world literature with shunt-associated metastasizing of brain tumors are analysed. The extraneural spreading of tumor cells through shunt tubes must be considered as a possible complication of the shunting procedure.

Cerebellar Neoplasms↗
PubMed1991

The influence of zinc administration on the development of experimental lung metastases after an injection of tumour cells into the tail vein of rats.

Rats having received drinking water enriched with zinc (zinc acetate, 22.8 mmol/l) developed significantly more pulmonal metastases after an i.v. injection of 5 x 10(5) cultivated cells of a benzpyrene-induced sarcoma than receiving normal drinking water. Zinc ions seem to promote the emigration, implantation and outgrowth of circulating tumour cells.

Animals↗
PubMed1991

[Leprosy: dimorphous variant].

A dimorphous variant of leprosy in a male from Cuba, 33 years of age, is reported in this paper. The case was characterised by granulomatous epithelioid cell reaction and histiocytic reaction with so-called Virchow cells, as established by lymph node biopsy. The histopathological findings are described, and their relations to immunity are discussed.

Adult↗