Unexpected tumor response, radiation myelitis and increased in vitro-radio-sensitivity of lymphocytes in a patient with non-small lung cancer.
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Carcinoma, Non-Small-Cell Lung↗
Biomedical subjects
E Gebhart
Publications and source records attributed to E Gebhart.
Multiple chromosomal changes and karyotypic evolution in a patient with myelofibrosis.
Several subclones were identified in unstimulated peripheral blood cells from a patient with chronic myeloproliferative disease, which was classified as myelofibrosis by morphologic terms. These subclones were characterized by an unusual number of different karyotype anomalies. Some of the more complex chromosomal rearrangements could be clearly defined by fluorescence in situ hybridization. Chromosome arms involved in clonal aberrations were 1q, 3p, 6p, 7q, 11q, 13q, 15q, 17q, 18p, and 20q. Reconstruction of karyotype evolution was attempted by karyotypic analysis of 100 metaphase spreads each in two separate investigations.
Aged↗
Trisomy 7 in short-term cultures of colorectal adenocarcinomas.
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Adenocarcinoma↗
Cytogenetic, oncogenetic, and histopathologic characteristics of colorectal carcinomas with 17p abnormalities.
From a total of 65 colorectal adenocarcinomas studied by cytogenetic methods, 33 were selected for the present study; in addition to other karyotypic anomalies, these 33 showed a loss of the short arm of chromosome 17. This loss was either the result of a deletion or rearrangement, or caused by the loss of a whole chromosome 17. The 17p- tumors were characterized by a high grade of karyotypic abnormality including a high incidence of cases with double minutes. A gain of chromosomes 2, 7, 19, and 20, and the loss of chromosome 18 and the Y-chromosome were the most frequent numerical anomalies associated with 17p-, as were structural changes of chromosomes 1 and 5. The most impressive difference in the pattern of proto-oncogene over-expression between the 17p- tumors and those without this anomaly was the significantly increased frequency of cases with c-erbB over-expression. Some significant, but also loose, associations were found between cytogenetic/oncogenetic and histopathologic or clinical features of these tumors. The patterns of genetic changes in cells of colorectal carcinomas may thus reflect the potential of the future development, rather than the present clinical features, of the respective tumor. Therefore, the character of the change seems to be more prognostic than diagnostic.
Adenocarcinoma↗
Anticlastogenicity in cultured mammalian cells.
Basic and applied research on anticlastogenicity has not only revealed valuable evidence on the mechanisms governing the induction of chromosomal aberrations by environmental mutagens, but also contributed effective ideas on a practical employment of this knowledge for the protection of individuals at risk. Considering the basic role played by chromosomal anomalies in oncogenesis, additional weight must be attributed to studies on anticlastogenicity. The employment of human cells in this kind of study dates back to 1969/70, while classical mammalian cell systems were used only later on. Various modes of application of both clastogens and anticlastogens (AC) were examined, but simultaneous addition to the cultures of both reagents was the most favored way. A wide spectrum of cytogenetic endpoints can be studied, but differences can be demonstrated with regard to efficacy of inhibitors on different types of cytogenetic changes, e.g., open breaks vs. rearrangements, but also vs. SCEs. Depending on their mode of influence on this spectrum, ACs can be arranged in various categories which are of practical importance, for instance, with regard to their oncogenic potential. A wide variety of factors was shown to influence AC action, e.g., time and mode of application of the test substances, physiologic and metabolic features of the cell types studied, type and mechanism of the clastogen used, etc. The addition of S9 mix can drastically change the patterns of efficacy of the ACs. The combined application of two or more ACs, as far as investigated, apparently neither potentiates nor even merely adds their effects.
Animals↗
Changes in the proliferation of human lymphocytes induced by several cytostatics and revealed by the premature chromosome condensation technique.
Premature chromosome condensation was induced by cell fusion in stimulated human lymphocytes treated with different cytostatics. Changes in the proportion of the cell-cycle stages were investigated after 72 h of culture. Although it has been reported that some agents which induce severe DNA damage accumulate cells in G2, our results have shown some differences in the modes of action of the different tested chemicals. These variations could be due to several factors like mechanisms of action of the drugs, sensitivity of lymphocyte subpopulations to the cytostatics, inter- and intra-individual variability in the response of donors.
Cell Cycle↗
[Ocular manifestations in a patient with Cockayne syndrome and simultaneous reduced DNA repair].
A 14 year old white boy presented with the typical clinical findings of Cockayne syndrome. Photodermatosis was known since the third week of life. He had disproportionate short stature with a short trunk, long limbs and flexion contractures of the large joints. He also was cachectic and prematurely aged. He had a typical facies. The hearing was slightly impaired. The prominent ocular findings were corneal opacifications, salt and pepper like retinal pigment epithelial changes and optic atrophy. On fibroblast culture the DNA repair activity is usually normal in patients with Cockayne syndrome. The DNA repair activity in our patient however was markedly reduced to 25% of normal. On lymphocyte culture a significantly increased 4-nitroquinoline-1-oxide sensitivity (cytotoxicity and increased break-rate) was found. These findings indicate that the boy has a specific variant of Cockayne syndrome with simultaneously reduced DNA-repair activity.
Adolescent↗
[Chromosome mutagenicity of a 193 nm Excimer laser].
Considering the fundamental role somatic mutations play in carcinogenesis, inducing mutations by any form of therapy should be avoided as far as possible. The mutagenicity of UV irradiation in the wavelength range of 248 to 310 nm is well established. The data on shorter wavelengths, e.g. 193 nm, however, are so far not clear-cut. Therefore, the potential chromosome-damaging effect of a 193 nm excimer laser was examined in the present study. Cultures of primary human fibroblasts and the Chinese hamster cell line CHO were the object of examinations. The in situ preparation technique used allowed detection of a locally limited clastogenic (chromosome damaging) effect in the neighborhood of the irradiated area. A slight increase in the frequency of chromosome aberrations could be observed in the area close to the laser-exposed field, which was attributed to the fluorescence generated by the laser under the given experimental conditions. Quantitative comparison with the data obtained from experiments with 254 nm irradiation from a UV lamp or exposure to 248 nm excimer laser-pulse irradiation, however, made the former activity appear somewhat insignificant. If one considers the practical aspects of the new laser surgery, the chromosome-damaging effect of the 193 nm pulse laser seems to be negligible.
Animals↗
The activity of bleomycin and modifiers of its clastogenic effect on the interphase chromatin of Indian muntjak fibroblasts.
Premature chromosome condensation was induced in Indian muntjak fibroblasts after exposure of the cells to bleomycin. Further experiments were devoted to the interaction of anticlastogens and a repair inhibitor, streptovitacin A. Chromosomal aberrations due to bleomycin treatment were S-phase-independently visible in the G1 and G2 phase of the cell cycle. For premature chromosome condensation experiments, a 100-fold lower concentration of the mutagen produced a similar extent of chromosome damage as in metaphase studies. Additional exposure to the anticlastogens beta-aminoethylisothiouronium or N-acetylcysteine revealed differences between corresponding interphase and metaphase effects and between different exposure conditions. Streptovitacin A, known as an inhibitor of protein synthesis, acted like an anticlastogen in the G2 phase of the cell cycle. Our studies show that the premature chromosome condensation technique offers various qualitative insights into primary processes of mutagenicity and antimutagenicity, but requires further improvement and careful choice of the cell system for study.
Acetylcysteine↗
[Chromosome diagnosis in leukemia].
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Chromosome Aberrations↗
Clastogen-induced fragility may differentiate pancytopenia of congenital dyskeratosis from Fanconi anaemia.
A male infant is reported with congenital dyskeratosis and pancytopenia Zinsser-Engman-Cole. The bone marrow pathology showed similarities to Fanconi anaemia. Ophthalmological complications were vitreous haemorrhage, haemorrhagic cataracta complicata and glaucoma. Spontaneous and diepoxybutane-induced chromosomal fragility was within the range of normal cells but was elevated through induction with 4-nitroquinoline-oxide. These findings are contrasted with those of Fanconi anaemia.
Anemia, Aplastic↗
Spontaneous and induced chromosomal instability in Werner syndrome.
In extension of a previous study, spontaneous and clastogen-induced chromosome damage was analyzed in cultures of peripheral blood lymphocytes from six further patients with Werner syndrome (WS) and six healthy controls. In addition, sister chromatid exchange (SCE) was estimated in four of these cases. Lymphocytes of patients with various other diseases were used for another series of control experiments. Diepoxybutane (DEB), 4-nitroquinoline-1-oxide (NQO), and bleomycin (BLM) were the standard clastogens throughout the study. While the spontaneous frequency of chromosomal breakage was significantly higher in lymphocytes from all the patients than in the control cells, the basis SCE rate was unaffected in WS cells. Sensitivity of WS cells to the chromosome-damaging action of BLM did not differ from that of control cells, and their sensitivity to DEB was slightly greater than that of control lymphocytes. However, NQO induced a more distinct increase of both break and interchange aberrations in the WS cells than in control cells or cells from patients with other diseases. This effect was not found for the SCE rate. Our data demonstrate the exceptional cytogenetic features of this syndrome: Although the spontaneous and the DEB- and NQO-induced chromosomal breakage rate would suggest that WS is like a classic chromosomal instability syndromes, the lack of sensitivity of WS cells to bleomycin and their stable SCE frequency compared with that of control cells clearly delimitate this syndrome from other entities.
4-Nitroquinoline-1-oxide↗
Induction by chemical clastogens of aberrations in prematurely condensed interphase chromatin of Chinese hamster ovary cells.
The clastogenic activities of diepoxybutane and bleomycin were comparatively studied on prematurely condensed interphase chromatin and metaphase chromosomes of Chinese hamster ovary cells. The yield of chromosomal aberrations was distinctly higher in G2-premature chromosome condensation as compared to metaphase. Most notably, the clastogenic activity of bleomycin was visible in premature chromosome condensation after application of much lower final concentrations than necessary for induction of chromosome aberrations in metaphase. In addition, the different mechanisms of action of both clastogens were reflected by the aberration yield in G1 and G2 immediately after exposure. While bleomycin induced aberrations throughout all stages of interphase, diepoxybutane did not induce aberrations in G1 or G2. Though certainly not a routine system for genotoxicity testing, premature chromosome condensation analyses provide a powerful opportunity to demonstrate relationships between DNA damage and repair, and the production of chromosomal changes at the site of their formation.
Animals↗
Ophthalmic surgical complications in Werner's syndrome: report on 18 eyes of nine patients.
In ten of 18 eyes from nine patients with Werner's syndrome cataract surgery was complicated by wound dehiscence and its consequences: peripheral anterior synechiae (4X), secondary epiretinal gliosis (4X), cystoid macular edema (3X) in the framework of Hruby-Irvine-Gass syndrome, unplanned filtering bleb (2X), and postoperative anterior ischemic optic neuropathy (1X). Additionally, corneal endothelial decompensation occurred in eight eyes. In view of the fibroblasts' reduced growth potential, we suggest small surgical incisions, extracapsular cataract surgery using phacoemulsification, intraocular irrigation solutions protecting corneal endothelium, nonabsorbable single knot sutures not removed before 1 year after surgery, and no local or systemic use of cortisone.
Adult↗
Microcell-mediated chromosome transfer from human tumor cells to human recipient cells evidenced by premature condensation of the transferred chromosomes.
Micronucleation was induced by vincristine, colcemid, and colcemid in combination with cytochalasin B in cells of a human metastatic breast carcinoma cell line (MDA MB 231). Cells treated with the latter combination were enucleated subsequently by centrifugation in the presence of cytochalasin B. The resulting "microcell" fraction was fused with mitotic human primary fibroblasts or mitotic HeLa cells using polyethyleneglycol (PEG). The success of the microcell-mediated chromosome transfer thus could be demonstrated as premature condensation in the mitotic recipient of the transferred micronuclei. This technique of cytogenetic analysis allowed a fast and simple control of the influence of different conditions on micronucleation and fusion of micronuclei with recipient cells. It could be shown that microcell-mediated chromosome transfer from human tumor cells into human normal, as well as human tumor, recipient cells is practicable if the techniques figured out by the present study are employed.
Breast Neoplasms↗
Premature chromosome condensation--studies on human metastatic carcinoma cells.
Utilizing the phenomenon of premature chromosome condensation (PCC) studies were carried out on interphase chromatin of metastatic cells from 52 cancerous effusions obtained from 45 patients presenting with various solid carcinomas. A highly individual pattern of distribution of the various interphase stages was detected, reflecting the heterogeneity of human solid tumors in an advanced stage. Nevertheless a variety of clinical, biologic, and technical factors were examined for their possible influence on these PCC patterns. The duration in culture was one of the influencing factors, as were the time lapse between the first diagnosis and the sampling of the respective effusion, or the nature of cytostatic therapy. Cytogenetic equivalents of gene amplification, as represented by "double minutes", could be found in the prematurely interphase chromatin of 35 of the 52 effusions. G1-PCC proved to be most reliable with regard to screening of double minutes. In addition, an adequate quality of Giemsa banding was achieved in PCC of 21 out of 24 effusions yielding a sufficient number of well-spread PCC. In six of these 21 cases PCC was superior to metaphase analysis in obtaining karyotypes, while the same was true for 14 of the 52 effusions screened for double minutes. Thus the PCC technique was shown to be an indispensable additional source of cytogenetic information in cells of human solid tumors.
Adult↗
Cytogenetic studies on human breast carcinomas.
Cytogenetic studies were performed on cell material obtained from surgical specimens of 50 human breast carcinomas and from 61 cancerous effusions of 46 patients. Classical cytogenetic analyses of numerical chromosome changes and marker chromosomes revealed the non-random involvement of chromosomes #X and #22 as monosomics, of chromosomes #3, #7, and #19 as trisomics, and chromosome #1 (particularly p 13 to q 12) in marker formation. Karyotypic evolution was followed in vitro and in vivo and showed a highly individualistic pattern of stability and variability. In addition, a systematic screening for the presence of cytogenetic equivalents of gene amplification (double minutes 'DM', homogeneously staining regions 'HSR') was carried out. A high incidence of DM-positive cases was detected in primary tumors (48%) as well as in metastatic cells from effusions (40%), with the frequency of DM-containing metaphases ranging from 1 to 100% in the positive cases. This finding supports the assumption of the fundamental biological importance of gene amplification in human solid tumors. Furthermore, chromosome breakage and micronuclei were observed in breast carcinoma cells as an apparent consequence of therapy-independent mutability.
Breast Neoplasms↗
Double minutes in prematurely condensed chromatin of human tumor cells.
Comparative studies on the occurrence of double minutes (DMs) were performed on metaphases and prematurely condensed interphases (G1, G2) of cells from 28 cancerous effusions of 24 carcinoma patients. In 21 of these effusions, agreement between metaphase and prematurely condensed chromatin (PCC) data was obtained concerning occurrence or nonoccurrence of DMs (10 DM positive, 11 DM negative). In two cases, DMs were observed in metaphases only, whereas in five cases, they were found in interphases only. In normal cells, no DMs could be found, neither in metaphase nor in PCC. No causal correlation of the occurrence of DMs and cytostatic therapy was found. The data suggest that cytogenetic screening of prematurely condensed interphase cells from human tumors or cancerous effusions provides a valuable method for estimating the incidence of gene amplification in malignant cells, particularly in those with poor mitotic yield.
Adult↗