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Biomedical subjects

R Nenutil

Publications and source records attributed to R Nenutil.

14 recordsLinked to original sources
PubMed2001

Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence.

The two prohibitin proteins, Phb1p and Phb2p(BAP37), have been ascribed various functions, including cell cycle regulation, apoptosis, assembly of mitochondrial respiratory chain enzymes, and aging. We show that the mammalian prohibitins are present in the inner mitochondrial membrane and are always bound to each other, with no free protein detectable. They are coexpressed during development and in adult mammalian tissues, and expression levels are indicative of a role in mitochondrial metabolism, but are not compatible with roles in the regulation of cellular proliferation or apoptosis. High level expression of the proteins is consistently seen in primary human tumors, while cellular senescence of human and chick fibroblasts is accompanied by heterogeneous decreases in both proteins. The two proteins are induced by metabolic stress caused by an imbalance in the synthesis of mitochondrial- and nuclear-encoded mitochondrial proteins, but do not respond to oxidative stress, heat shock, or other cellular stresses. The gene promoter sequences contain binding sites for the Myc oncoprotein and overexpression of Myc induces expression of the prohibitins. The data support conserved roles for the prohibitins in regulating mitochondrial respiratory activity and in aging.

Animals↗
PubMed1998

Differences in p53 and Bcl-2 expression in relation to cell proliferation during the development of human embryos.

AIMS: To study the patterns of p53 and Bcl-2 expression in relation to cell proliferation during human embryogenesis in order to help elucidate their potential roles in the regulation of cell proliferation and apoptosis during morphogenesis. METHODS: Immunohistochemistry for p53, Bcl-2, and proliferating cell nuclear cell antigen (PCNA) proteins was performed, using a variety of monoclonal antibodies, on paraffin was embedded sections of tissues from 68 human embryos and fetuses of between 4 and 30 weeks gestation. RESULTS: Positive relations between sites of proliferative activity (as detected by PCNA expression) and p53 expression were found in the kidney, early developmental stages of intestine and lungs, liver, pancreas, heart, and in embryonic osteoblasts. On the other hand, positive relations between proliferative activity and Bcl-2 expression were found in the gonads, adrenal glands, in the cells of the dental lamina, hair follicles, syncytiotrophoblast, chondrocytes, and more advanced stages of intestinal development. In tissues of the central nervous system, p53 and Bcl-2 were co-expressed at the same sites but there was an inverse relation between p53/Bcl-2 expression and proliferative activity. CONCLUSIONS: These data suggest that p53 and Bcl-2 have tissue specific and stage specific functions during embryogenesis.

Cell Division↗
PubMed1997

DNA flow cytometry: a predictor of a high-risk group in cervical cancer.

We studied the relationship between the 5-year disease-free interval or the occurrence of distant metastases, and the flow cytometric nuclear DNA content in a group of 55 patients treated by radiation for squamous cell carcinoma of the uterine cervix, stages Ib-IIIb (FIGO). The diploid DNA content was associated with a better prognosis and a lower incidence of distant metastases, while aneuploid tumors tended to be prognostically unfavorable and had distant metastases more often. We consider the flow cytometric nuclear DNA content a prospective prognostic parameter in squamous cell carcinoma of the uterine cervix treated by radiotherapy.

Aneuploidy↗
PubMed1997

The intermediate filaments and prognostically oriented morphological classification in ductal breast carcinoma.

The expression of cytokeratins 7, 8, 14, 18, 19 and vimentin was examined in 100 cases of ductal invasive breast carcinomas. While the predominantly diffuse immunohistological positivity of simple epithelia cytokeratins 7 (in 93), 8 (in 100), 18 (in 100) and 19 (in 97) cases represents a constant feature of these tumors, cytokeratin 14 was detected in only 36 cases which were mostly of low grade and in a focal pattern. Vimentin positivity was found in 53 intermediate and high grade tumors and, again the pattern was also rarely diffuse. The ductal carcinomas can be grouped into four classes according to vimentin and cytokeratin 14 immunoreactivity. This grouping correlates well with tumor grade and with simple histological classification of ductal breast carcinoma, consisting of the low, intermediate and high malignancy categories, as proposed here. The types ofductal carcinomas can be sorted into prognostically different subgroups, according to ICD-O morphologic terminology and commonly adopted results of morphologic and prognostic studies.

Breast Neoplasms↗
PubMed1996

A constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies.

We report a constitutional point mutation of codon 278 in exon 8 of the TP53 gene that has not yet been described as a germ-line mutation. A 52-year-old female developed multiple primary malignancies (liposarcoma, breast cancer, malignant histiocytoma, occult adenocarcinoma). The mutation found in her tumour and peripheral blood lymphocyte DNA is a cytosine to thymine transition at the second position of codon 278 resulting in an amino acid exchange from proline to leucine in the DNA-binding domain. Evaluation of the patient's family revealed that both of her sons were affected by the same mutation. Although the patient's mother had died already, we were able to demonstrate by polymorphic microsatellite analysis that the defective allele originated from the maternal side. As four brothers and one sister had inherited the same allele, which however was wild type, we were able to show that the mutation must have occurred in the germ cells of the patient's mother and that it may therefore be called de novo. This explains the lack of a high cancer incidence in the family history. All tumours tested showed positive immunohistochemical staining for p53. Loss of heterozygosity was found in five of seven tumours, one showing chromosome 17 monosomy.

Alleles↗
PubMed1995

Absence of p53 autoantibodies in a significant proportion of breast cancer patients.

We analysed antibodies specific for human p53 in sera from primary breast cancer patients using three different immunoassays and we related these results to the p53 level in tumour tissue detected by immunohistochemistry. Only 44% (11/25) of apparently enzyme-linked immunosorbent assay (ELISA)-positive sera were from patients with a high level of p53 protein in more than 50% of their tumour cells. Surprisingly, 36% (9/25) of the sera originated from patients with no detectable p53 protein at all. Immunoprecipitation data suggested that the reason for this discrepancy is that at least some of the antibodies detected as positive in the ELISA in these sera from patients with clinical stage I and stage II breast cancers may be induced by immunogens other than p53 protein. Many of these reactions give apparently positive signals in a variety of p53 assays, and very stringent analysis is required to avoid possible misinterpretation of these responses as a p53-specific B-cell response in human cancer patients.

Autoantibodies↗
PubMed1995

p53 protein overexpression associates with growth patterns rather than with metastasizing in operable breast cancer.

We have analyzed p53 protein expression in 121 primary breast cancer biopsies by immunohistochemistry using the monoclonal antibody DO-1 and polyclonal serum CM-1. p53 protein overexpression has correlated in our study with mitotic activity (p=0.001), nuclear atypia (p=0.002), less favorable histological type of tumor and in a lesser extent with tumor size. The inverse, but highly significant, correlation (p=0.007) has been observed with lymph node involvement. There was also a trend for higher p53 positivity among DNA aneuploid tumors as compared with DNA diploid cases, but this was not significant. Our study suggests that p53, at least in some patients, may not be directly involved in the process of metastatic progression in breast cancer. Preliminary data would suggest that the detection of p53 protein overexpression could be a useful additional prognostic parameter in breast cancer.

Aged↗
PubMed1994

[Cytokeratin expression in spinocellular carcinoma of the uterine cervix].

Expression of cytokeratins 7, 8, 10, 14, 18 and 19 was studied in 48 cases of advanced (stage II and III) squamous cell carcinomas of the uterine cervix. Despite of the degree of differentiation, the expression of simple epithelia cytokeratins 8 (72.9%) and 19 (97.9%) was high. A subset of eight (16.6%) predominantly poorly differentiated tumours had the expression restricted to simple epithelia pattern (cytokeratin 7 and/or 8 and 18 and/or 19). In twenty cases (41.7%) the cytokeratin 14 was added to this pattern, representing an intermediate differentiation level, while the other twenty tumours, usually exhibiting more pronounced squamous differentiation had the most complete cytokeratin pattern including class 10. This grouping was of no prognostic significance but might represent a valuable tool in the classification of cervical squamous cell carcinoma.

Carcinoma, Squamous Cell↗
PubMed1992

[DNA flow cytometry: perspective prognostic parameters in carcinoma of the uterine cervix].

We studied the relation between the 5-year disease free interval and the flow cytometric DNA content in a group of 55 patients treated by radiation for squamous cell carcinoma of the uterine cervix, stages Ib-IIIb (FIGO). The diploid DNA content was associated with a better prognosis, while prognostically unfavourable tumours tended to be aneuploid. The relation was statistically significant in the whole group (p = 0.016), in stage II disease (p = 0.003) and in the subgroup formed by the combination of stages I and II (p = 0.000). In stage III we did not prove the relation. Analysis of the survival function revealed also a better prognosis of diploid tumours (p = 0.041) in the whole group. The division into clearly diploid and non-diploid tumours seems to be more suitable for evaluation (p = 0.012). The difference between the prognostically favourable and unfavourable groups is expressed more clearly. We consider the flow cytometric DNA content a perspective prognostic parameter in squamous cell carcinoma of the uterine cervix. Its significance is apparent especially in patients treated by radiotherapy, because the size of the tumour cannot be assessed reliably in these cases.

Carcinoma, Squamous Cell↗
PubMed1991

Histological grading and DNA content as predictors of distant metastases in squamous cell carcinoma of the uterine cervix.

Squamous cell carcinoma of the uterine cervix with distant metastases can be treated by adjuvant chemotherapy. The at-risk patients are those with histologically proven metastases, the presence of tumour in paracervical tissue and parametrium, evidence of vascular invasion, a great depth of invasion, or poor tumour differentiation. Our studies lead us to believe that differentiation and DNA content are also important criteria.

Aneuploidy↗
PubMed1990

A panel of monoclonal antibodies to keratin no. 7: characterization and value in tumor diagnosis.

Reactivity patterns of seven mouse monoclonal antibodies to human keratin 7 were compared using immunoblotting and immunohistochemistry on cultured cells and normal human and animal tissues. Differences in keratin specificities as determined by two-dimensional immunoblots and interspecies cross-reactivity data on 8 mammalian species suggest that at least six nonidentical epitopes of the keratin 7 molecule are recognized by this panel of reagents. Immunohistochemical examination of a panel of various human neoplasms with monoclonal antibodies monospecific for keratins 7, 18 and 19 revealed potential value of keratin subtyping in differential diagnosis of tumors in general and in subclassification of carcinomas in particular.

Animals↗
PubMed1989

Monoclonal antibodies recognizing different epitopes of cytokeratin No.18.

A comparative study of six mouse monoclonal antibodies against human 45 kDa keratin polypeptide (keratin No. 18) was undertaken using three experimental approaches: immunohistochemistry on normal human tissues, examination of interspecies cross-reactivity and identification of the target polypeptides in 1-D and 2-D immunoblots. The data suggest that at least five different antigenic sites of keratin 18 are recognized by this panel of reagents. The C-04 epitope is keratin 18-specific and widely conserved among mammalian species, while the antibodies DA7 and DC10 also react specifically with the 45 kDa keratin but stain simple epithelia of human origin only. Two antibodies, C-11 and C-66, decorate simple as well as stratified epithelia in human and in all seven animal species tested, but their respective target epitopes are shared by different groups of keratin polypeptides, which indicates their non-identity. In contrast to keratin specificity of the five above mentioned antibodies, the C-08 antibody cross-reacts with a 70 kDa nuclear lamina protein found in human and bovine tissues. The results of the present study provide the necessary basis for future applications of these antibodies in both routine immunodiagnostic work and as probes to study the biology of epithelial cells in general and the significance of keratin intermediate filaments in particular.

Animals↗