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Biomedical subjects

K Christov

Publications and source records attributed to K Christov.

At least 19 recordsLinked to original sources
PubMed1991

Proliferation of normal breast epithelial cells as shown by in vivo labeling with bromodeoxyuridine.

The proliferative activity of normal acinar and ductal breast epithelial cells was studied by in vivo labeling with 5-bromodeoxyuridine (BrdUrd) in 26 cases with concurrent breast carcinoma. The BrdUrd-labeled cells were recognized in histologic sections of paraffin-embedded tissue, using an anti-BrdUrd antibody and an immunoperoxidase reaction. The percentage of BrdUrd-labeled cells showed great variability for both acinar (0% to 2.66%; mean, 0.70%; standard deviation [SD], 0.80%) and ductal cells (0% to 1.99%; mean, 0.51%; SD, 0.57%). The fraction of proliferating epithelial cells declined with the age of the patients and was significantly higher in premenopausal women (1.16% +/- 0.85% for acinar and 0.94% +/- 0.60% for ductal cells) as compared with the postmenopausal women (0.27% +/- 0.46% for acinar and 0.17% +/- 0.22% for ductal cells), P less than 0.01 for acinar and P less than 0.001 for ductal cells, respectively. In some patients, great variability in distribution of proliferating acinar and ductal cells among different lobules and ducts was observed. No difference was found in the number of proliferating acinar and ductal cells situated near or far from their corresponding tumors. No correlation was seen between cell proliferation of normal acinar or ductal cells and cell proliferation of the respective tumors.

Adult↗
PubMed1990

Cell kinetics of a rat thyroid transplantable tumour.

Changes in morphology and cell kinetics are described in a rat thyroid transplantable tumour (TTT) during the first few transplant generations. The growth of TTT in animals was possible only with an increased circulation level of the thyroid stimulating hormone (TSH). With serial transplantation subcutaneously in isologous animals, the morphology of TTT changed dramatically from that of a follicular tumour in the 3rd passage to become, by the 9th generation, a poorly differentiated tumour with a trabecular arrangement of cells. This change in tumour morphology was accompanied by an increase in the number of proliferating cells--mitotic index (MI), [3H]thymidine labelling index (LI), growth fraction (GF)--and cell loss factor (O) as well as a decrease in the cell cycle time (Tc) and potential population doubling time (TPD). TTT belongs to the class of tumours with a low proliferative activity and might be used in a variety of cell kinetic, radiobiological and chemotherapy studies.

Animals↗
PubMed1989

DNA aneuploidy and cell proliferation in breast tumors.

The cellular DNA content of 30 benign and 180 malignant breast tumors was analyzed by means of flow cytometry (FCM). All benign tumors exhibited a normal DNA content (diploid), whereas 65% of the malignant tumors showed an abnormal DNA content (aneuploid). The ploidy distribution of malignant tumors was bimodal with an increasing frequency near diploid DNA index (DI), and a second group had a DI ranging from triploid to tetraploid. In estimating the degree of malignancy eight independent histomorphologic and cytologic criteria were introduced. A good correlation was observed between DNA content abnormalities and the grade of differentiation of breast carcinomas. The percentage of S-phase cells of DNA aneuploid cell lines was significantly higher than in the diploid ones. The highly differentiated breast carcinomas (Grade 1) indicated lower S-phase values as compared to the undifferentiated (Grade 3) ones. S-phase values estimated by FCM were about two times higher than the 3H-thymidine labeling index (LI) obtained by an in vitro procedure. The data estimated in this study showed that DNA determinations as an adjunct to conventional histopathologic assessment may provide objective clinically relevant information with respect to the degree of malignancy and prognosis of patients with breast carcinoma.

Adult↗
PubMed1988

Flow cytometric analysis of DNA and cell proliferation in ovarian tumors.

DNA content in tumor cells from 50 patients with ovarian tumors was analysed by flow cytometry (FCM). Solid tissue samples were processed to obtain monodispersed cells. Staining for DNA analysis was achieved with ethidium bromide and mithramycin. Peripheral blood lymphocytes were used as reference diploid cell population. All benign ovarian tumors exhibited only diploid cells. DNA aneuploid cell lines were found 66.6% of serous carcinomas and in 80% of malignant granulosa cell tumors. The S-phase fraction of DNA diploid cells in benign ovarian tumors (S = 2.4 +/- 1.2%) was smaller than those of malignant tumors (S = 8.2 +/- 5.2%). DNA aneuploid cell populations in serous carcinomas display a higher S-phase fraction (S = 19.2 +/- 9.3%) than DNA diploid cells (S = 11.7 +/- 3.2%). No major differences were obtained between primary ovarian tumors and their metastases, as far as degree of aneuploidy and S-phase fraction are concerned. A high degree of correlation was established between the grade of differentiation of ovarian tumors and the DNA ploidy abnormalities.

Cell Cycle↗
PubMed1988

Histological grading, DNA content, cell proliferation and survival of patients with astroglial tumors.

Light microscopy, image cytometry (ICM), and flow cytometry (FCM) were used to study the degree of differentiation, DNA content, and S-phase of astrocytomas and glioblastoma multiforme in 102 patients. The postoperative real survival time (RST) was also studied. Using ICM, 62 astrocytomas were investigated. Grade I astrocytomas were composed of DNA-diploid cell lines, while grade III and glioblastoma multiforme consisted predominantly of DNA-aneuploid lines. Moderately differentiated astrocytomas were divided as follows: 14 DNA-diploid and 18 DNA-aneuploid. Forty astrocytomas were studied by FCM. Using the DNA index (DI) value, cases with abnormal DNA cell lines were established in all astrocytomas, with their number increasing in grades II and III astrocytomas. FCM indicated the same subdivision of moderately differentiated astrocytomas: 12 with DNA-diploid and 12 with DNA-aneuploid stem lines. Patients with DNA-diploid cell lines in the astrocytomas and low S-fraction survived longer than patients with abnormal DNA cell populations and higher S-fraction. The results from this study indicate that, together with the degree of differentiation of astroglial tumors, the appearance of cell lines with abnormal DNA value and higher S-fractions also have prognostic value.

Adolescent↗
PubMed1987

[DNA in koilocytotic dysplasia of the cervix uteri, cytophotometric studies].

In koilocytotic dysplasia of the uterine cervix the DNA content in squamous cells was quantitated by cytophotometry in histological preparations stained according to Feulgen. Three patterns of DNA distribution in the squamous cells were found. In type one (21.4%) the cells had DNA content in the diploid and paradiploid zone of the histogram. In type two (35.7%) cells with triploid and tetraploid DNA values were found, but with a conspicuous modal class of cells. In type three no modal class cells were found (42.9%). The quantitative DNA changes in squamous cells show that some of the HPV induced alterations may be regarded as precancerous.

Adult↗
PubMed1986

Flow cytometric DNA measurements in human thyroid tumors.

By means of flow cytometry (FCM), DNA distribution pattern and the fraction of cells in the various phases of the cell cycle were studied in 52 samples of normal thyroid tissues, follicular adenomas, follicular carcinomas, medullary carcinoma and fibrosarcomas. In the normal thyroid tissues and follicular adenomas DNA diploid cell populations only were found. Among 20 follicular carcinomas in 13 cases (65%) together with the DNA diploid cells, DNA aneuploid cell lines were also observed. S-phase fraction in follicular adenomas is higher than in the normal thyroid tissues and lower than those in thyroid carcinomas. The percentage of S-phase cells in DNA aneuploid populations is significantly higher (S = 19 +/- 9.3%) than in the diploid cell lines (S = 3.7 +/- 2.6%). DNA aneuploid cell populations were predominantly observed in carcinomas with a high degree of morphological anaplasia.

Adenocarcinoma↗
PubMed1986

Flow cytometry in brain tumors. I. Ploidy abnormalities.

Flow cytometry (FCM) was introduced for estimation of DNA content in 75 brain tumors. Among these astrocytomas (38 cases) and meningiomas (16 cases) predominated. Astrocytomas were histologically subdivided into 3 groups of malignancy grade. Aneuploid cell populations were found in 1 out of 4 cases of astrocytoma grade I, in 11 out of 20 astrocytomas grade II and in 10 out of 14 astrocytomas grade III of malignancy. DNA index (DI) in most aneuploid astrocytomas is in the range between 1 and 2. More than one cell population with aneuploid value of DNA was found in 36% of all aneuploid tumors.

Aneuploidy↗
PubMed1985

Cell population kinetics and DNA content during thyroid carcinogenesis.

The proliferation kinetics and DNA content of thyroid follicular cells in rats were studied by autoradiography and cytophotometry. Continuous treatment of animals with methylthiouracil (MTU) results in hyperplasia followed by tumour growth in the thyroid gland. The mitotic index (MI) increases from 0.006 +/- 0.002% in controls to 0.13 +/- 0.06% in hyperplasia and to 0.09 +/- 0.03% in malignant cells. The same is true for the labelling index (LI) which rises from 0.08 +/- 0.003% in controls to 1.4 +/- 1.1% in hyperplasia and to 1.0 +/- 0.6% in follicular adenomas. The S-phase duration (TS) is shortened from 8.0 +/- 1.2 hr in controls to 6.0 +/- 1.4 hr in animals treated for 9 months with MTU and prolonged to 15.4 +/- 2.1 hr in papillary carcinomas. In all MTU-treated animals a decrease in the value of the potential population doubling time (TPD) and thyroid weight doubling time (TD) was observed. The cell loss factor (phi) decreases in animals treated for 3 months with MTU and increases during the stage of tumour growth in the gland (animals treated 12-15 months with MTU). DNA measurements in the nuclei of hyperplastic and neoplastic thyroid tissues reveal cells with values exceeding that in control animals. However, no difference was found in the DNA content between thyroid adenomas and carcinomas, nor between thyroid hyperplasia and neoplasia.

Adenoma↗
PubMed1985

Flow cytometry of radiation-induced tumors in rats.

Hundred sixty female Wistar rats were total-body irradiated with 4 Gy gamma rays. Mammary gland tumors started to occur 8 months after irradiation, beside that also tumors of different sites appeared. By flow cytometry (FCM) 30 tumors were examined: mammary gland--22, skin--4, adrenal gland--2, liver--1, thymus--1. Eight tumors were characterized as malignant and 22 as benign. All benign and 6 malignant tumors were composed of diploid cells only. In 2 carcinomas together with diploid cells aneuploid cell lines were also found. DNA index (DI) of aneuploid cells in both carcinomas (1 mammary gland and 1 adrenal gland) indicated values of 1.66 and 1.68, respectively. Most cells of the benign and the malignant tumors occupied G1/0 (79-94%) phase of the cycle. The fraction of S (4.1-14.3%) and G2M (0.5-7.7%) cells was relatively small that suggests a low proliferative activity of radiation-induced tumors.

Animals↗
PubMed1984

Increased proteolysis in chromatin of terminally differentiated and quiescent cells.

Endogenous proteolysis in chromatin of terminally differentiated, quiescent, and actively proliferating cells was studied by measuring the released acid-soluble radioactivity of [3H]tryptophan-prelabelled nuclear proteins, and by following the specific quantitative and qualitative changes in electrophoregrams of chromosomal proteins. The experiments suggest that the chromatin of differentiated mouse kidney and liver cells, as well as chromatin from Friend cells induced to commit terminal differentiation, exhibit increased proteolysis in comparison with that of chromatin isolated from actively proliferating cells. Enhanced proteolysis was found also for the slowly renewing and quiescent cells from adult mice. The control experiments designated to discriminate between the two possible alternatives explaining the difference--increased activity of the proteolytic enzymes associated with chromatin, or increased susceptibility of the chromosomal proteins to proteases--supported the latter alternative.

Animals↗
PubMed1984

DNA content in reactive hyperplasia, precancerosis, and carcinomas of the oral cavity. A cytophotometric study.

Cytophotometry has been used to study DNA content in oral epithelial cells of Feulgen-stained specimens from a total of 43 patients: 3 with erythema exudativum multiforme (EEM), 5 with pemphigus, 3 with stomatitis aphtosa, 5 with lichen ruber planus, 8 with leukoplakia, and 19 with carcinomas. In contrast to reactive hyperplasia (EEM, pemphigus, stomatitis aphthosa) leukoplakia has histograms closest to those of carcinoma, with a high percentage of cells in the polyploid regions. This emphasizes the significance of cytophotometry for diagnosis of preneoplastic and neoplastic lesions of the oral cavity.

DNA↗
PubMed1982

Effect of irradiation on the proliferation kinetics of thyroid follicular cells in infant rats.

Changes in the 3H-thymidine labeling index (LI), cell cycle time (TC) and growth fraction (GF) of the thyroid follicular cells were studied in 10 days old rats irradiated in the neck region with a single dose of 3 Gy X-rays. During the first 2 days after irradiation the number of proliferating follicular cells sharply increased, followed between the 2nd and 6th days by a phase of sharp decrease. Later, between the 10th and 16th days again an increase in the LI was observed. During the cell proliferation phase, the cell cycle was shortened from 79 hours in the control animals to 30.9 hours in irradiated animals. The GF was decreased from 40% in the former to 25% in the latter. S-phase duration (TS) was 1.6 hours longer in irradiated animals than in controls. The shortening of the cell cycle of irradiated animals is predominantly a result of diminishing G1-phase duration.

Animals↗