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1.
With the use of time-lapse cinemicrography, we previously found that metaphase durations were significantly prolonged in SV40-transformed human fibroblasts when compared to untransformed controls. This was consistent with some earlier reports and suggested that prolonged metaphases could account for high metaphase/prophase ratios and possibly, in part, for increased mitotic indices seen in advanced tumours. However, there are inconsistencies in the literature and no comparable data available from malignant carcinomas. Presented in this paper are data from two cervical dysplasias, two cases of carcinoma in situ, nine malignant carcinomas and several other types of human cells. The results show that mean metaphase durations were prolonged in cells derived from most of the carcinomas but not from the other cell types. On the other hand, cytokinesis appears to progress more rapidly than normal in most of the tumour-derived cells. These and other findings indicate that the changes are a result of some metabolic alteration common to many but not all tumour cells. For reasons presented, we suggest as a working hypothesis that the alterations may be due to changes in calcium regulation, possibly resulting from alterations in mitochondrial metabolism.  相似文献   

2.
Early studies on the duration of mitotic stages and on metaphase-to-prophase ratios in a number of normal and neoplastic cells indicated that the process of mitosis becomes altered during the course of oncogenesis. However, the nature of these changes and their effects on each of the mitotic stages are still unclear. With the use of time lapse cinemicrography, we have compared the durations of mitotic stages of SV40/Wl-38 and SV40/Wl-26 cells to those of their normal counterparts and to other nontransformed human fibroblasts. We also examined the relative frequencies of the individual mitotic stages in fixed preparations of Wl-38 and SV40/Wl-38 cells. The data show that metaphase durations are increased in the transformed cells and as much as 3-4.7-fold in SV40/Wl-38 cells compared to Wl-38 and other nontransformed cells. Other stages are also prolonged though to lesser degrees. These findings suggest that increased metaphase/prophase ratios observed in many tumors are due to increases in duration of metaphase rather than to shorter prophases, and that increased mitotic indices commonly observed in malignant tumors and sometimes used as an index of growth rate are at least in part due to the prolongation of mitotic stages.  相似文献   

3.
Summary Blood-group-related antigens expressed in papillary carcinomas and other types of neoplasm of the human thyroid glands have been shown to be carried by poly-N-acetyllactosamines containing a linear domain susceptible to endo-β-galactosidase digestion. To make clear more precisely the backbone poly-N-acetyllactosamine structures, labelled lectins specific to different types of these structures and specific to core structures with β1-6GlcNAc branching of N- and O-linked glycoproteins were employed in conjunction with prior endo-β-galactosidase digestion on formalin-fixed, paraffin-embedded neoplasms of the human thyroid glands. In papillary carcinomas,Datura stramonium agglutinin (DSA) and succinyl wheat germ agglutinin (Suc-WGA) reacted most consistently and frequently with papillary carcinomas from all the individuals examined. Pokeweed mitogen (PWM) likewise stained the cells of papillary carcinomas from all the individuals examined, but in some individuals the number of lectin-reactive cells were very small.Lycoperscion esculentum aggultinin (LEA),Solanum tuberosum agglutinin (STA),Phaseolus vulgaris agglutinin L (PHA-L) andArtocarpus integrifolia agglutinin (jacalin) similarly bound to the cancer cells from most of the individuals, and in these cases the number of reactive cells was usually much more restricted than was the case with DSA or PWM. In adenoma and other types of carcinoma, such as follicular carcinomas, these lectins specific to poly-N-acetyllactosamine exhibited slight or no reactivity with the cells, whereas PHA-L and jacalin similarly bound to the cells of adenomas and carcinomas from most of the individuals examined. Prior digestion with endo-β-galactosidase completely eliminated or markedly reduced the reactivity with PWM and LEA in papillary carcinomas. Reactivity with DSA, Suc-WGA, STA, PHA-L and jacalin was slightly reduced or not at all affected by enzyme digestion. These results confirmed that poly-N-acetyllactosamine species found in papillary carcinomas are quite different from those in other types of thyroid neoplasm, suggesting that at least three different types of poly-N-acetyllactosamine, that is, linear unbranched short and long sequences and highly branched ones are produced in these cells.  相似文献   

4.
Epithelial junctions and mucins play key roles in the gastrointestinal mucosal barrier, and their alterations are associated with numerous diseases, including carcinomas. The systematic expression of adhesion molecules and mucins in normal and malignant human gastrointestinal cells was investigated in this study. In normal human gastrointestinal cells, zonula occludens-1 (ZO-1), α-catenin, β-catenin, γ-catenin and desmoglein-2 (DSG2) were located in the cytoplasmic membranes, whereas symplekin stained in the nuclei. ZO-1, the three catenins, and DSG2 were observed in the gastric and colorectal carcinomas with reduced and heterogeneous expression and with abnormal distribution. Symplekin was detected in the nuclei of tumor cells in most tumors but not observed in some others. The immunohistochemical results for ZO-1 and symplekin on the tissues were consistent with the data for the cultured cells obtained by immunocytochemical staining and Western blot analysis. MUC1 was not stained in the normal gastrointestinal cells without periodate oxidation, but it was strongly labeled in the malignant gastrointestinal cells. MUC2 was detected in the normal and malignant gastrointestinal cells without the periodate treatment. These findings indicate that alterations in the expression of the epithelial junctions and mucins are associated with the malignant transformation of gastrointestinal cells. In addition, the gastrointestinal epithelial cells of rhesus macaques expressed these adhesion molecules and mucins, as did the human cells, suggesting that the rhesus monkey is a suitable experimental animal model for research on adhesion molecules and mucins.  相似文献   

5.
Simultaneous RNA and DNA estimations were carried out during the cell cycle of EMT6/M/CC cells growing in vitro following synchronization by mitotic selection. the determinations were performed with a flow cytofluorimeter on individual cells stained with acridine orange. It was found that the RNA content increased during G1 then remained virtually constant between early and mid S phase, but a second increase occurred during late S. the rate of uptake of tritiated uridine paralleled these changes in RNA levels, and it was also found that the rate of uptake in metaphase and anaphase was virtually zero, but a rapid increase occurred in telophase. the increase in DNA during S was approximately linear, and the intermitotic phase and cycle durations were very similar to previously reported results.  相似文献   

6.
Sedimentation studies of DNA from chromosomes extracted from human mitotic cells showed that highmolecular-weight DNA can be obtained if cell hypotonic treatments and prolonged metaphase blocks are avoided. Two types of large double-stranded DNA were observed. One of these (M r = 2.5×108) appeared as a size class with characteristics reminiscent of the chromosomal DNA subunit hypothesis. However, this DNA is the decay product of larger molecules, whose minimum molecular weight is 6×108.  相似文献   

7.
Summary The monoclonal antibody 5-D-4 recognizes heavily sulphated forms of keratan sulphate epitope. It reacted strongly with the cell surfaces of most thyroid papillary carcinomas from all the individuals examined, independently of the blood group of the patients. Cells of follicular variants of papillary carcinomas were also labelled by 5-D-4. In contrast, no labelling with this antibody was observed in other types of thyroid neoplasms, or in normal tissues. The reactivity of 5-D-4 with papillary carcinomas was markedly reduced or abolished by prior digestion with endo-β-galactosidase keratanase II, or N-glycosidase F. Although keratanase digestion had no effect on 5-D-4 labelling, it revealed the binding sites ofGriffonia simplicifolia agglutinin II (GSA-II), which recognizes terminalN-acetylglucosamine in a limited number of carcinoma cells from some individuals. Blood group ABH antigens, which are simultaneously expressed together with keratan sulphate epitope in cancer cells, were eliminated by digestion with endo-β-galactosidase and N-glycosidase F, but were resistant to keratanase and keratanase II treatment. These results indicate that keratan sulphate oligosaccharides are cancer-associated and are probably oncofoetal antigens, as are the blood group antigens in human thyroid glands. The results suggests that poly-N-acetyllactosamine, which is ubiquitously and consistently produced in papillary carcinomas, is modified in two different ways: sulphation on the 6-position of at least some units of either galactose, orN-acetylglucosamine or both, and decoration of non-reducing termini with the blood group antigens. Along with the endo-β-galactosidase-GSA-II labelling procedure, labelling with 5-D-4 may be a useful diagnostic means for distinguishing papillary carcinoma from other types of thyroid neoplasms.  相似文献   

8.
The duration of the cell cycle and its component phases in cell cultures of Haplopappus gracilis was estimated by means of pulse labelling with tritiated thymidine and subsequent autoradiographic techniques. The total duration of the mitotic cycle was found to be 22.0 hours. The average durations of the following component phases were: the synthetic period (S) 6.4 hours, the postsynthetic period (G2) 4.86 hours, prophase (P) 0.64 hours, metaphase (M) 0.40 hours, anaphase + early telophase (AT) 0.36 hours, the presynthetic period (G1) 9.34 hours. The results indicate that G1 and G2 are the phases, which are most prolonged in populations of cultivated cells when compared to the same phases in root lip cells from the same species.  相似文献   

9.
10.
Bimolane has been commonly used in China for the treatment of psoriasis and various types of cancer. Patients treated with bimolane have been reported to have an increased risk of developing therapy-related leukemias. Although bimolane has been identified as a human leukemia-inducing agent, little is known about its genotoxic effects, and a systematic study of the types of chromosomal alterations induced by this compound has not been performed. In this study, a combination of immunochemical, molecular and conventional cytogenetic techniques has been used to study the chromosomal alterations induced by bimolane in cultured human lymphocytes. Immunochemical staining with the CREST antibody indicated that bimolane induces micronuclei (MN) originating primarily from chromosome breakage. Interestingly fluorescence in situ hybridization (FISH) with differentially labeled chromosomes 1 and 9 centromeric probes indicated that bimolane also caused non-disjunction and polyploidy. Consistent with this, an expedited analysis of Giemsa-stained metaphase chromosomes in bimolane-treated lymphocytes revealed a high frequency of polyploidy/hyperdiploidy as well as dicentric chromosomes, and premature centromeric division (PCD). In addition, bimolane was also found to produce binucleated cells, possibly through an interference with normal functioning of intermediate filaments. As a follow-up to these studies, three different types of commercially available bimolane formulations obtained from different Chinese manufacturers were also evaluated. The effects seen with the formulated bimolane were similar to those seen with the synthesized compound. Our studies indicate that bimolane effectively induces a variety of cellular and chromosomal changes in cultured lymphocytes and that similar alterations occurring in bone marrow stem cells could contribute to the development of the secondary cancers seen in bimolane-treated patients.  相似文献   

11.
Stromelysin-3 (ST3; Basset, P., J.P. Bellocq, C. Wolf, I. Stoll, P. Hutin, J.M. Limacher, O.L. Podhajcer, M.P. Chenard, M.C. Rio, P. Chambon. 1990. Nature. 348:699–704) is a matrix metalloproteinase (MMP) expressed in mesenchymal cells located close to epithelial cells, during physiological and pathological tissue remodeling processes. In human carcinomas, high ST3 levels are associated with a poor clinical outcome, suggesting that ST3 plays a role during malignant processes. In this study we report the ST3 gene inactivation by homologous recombination. Although ST3 null mice (ST3−/−) were fertile and did not exhibit obvious alterations in appearance and behavior, the lack of ST3 altered malignant processes. Thus, the suppression of ST3 results in a decreased 7,12-dimethylbenzanthracene-induced tumorigenesis in ST3−/− mice. Moreover, ST3−/− fibroblasts have lost the capacity to promote implantation of MCF7 human malignant epithelial cells in nude mice (P < 0.008). Finally, we show that this ST3 paracrine function requires extracellular matrix (ECM)-associated growth factors. Altogether, these findings give evidence that ST3 promotes, in a paracrine manner, homing of malignant epithelial cells, a key process for both primary tumors and metastases. Therefore, ST3 represents an appropriate target for specific MMP inhibitor(s) in future therapeutical approaches directed against the stromal compartment of human carcinomas.  相似文献   

12.
Ultrastructural changes following increasing periods of water stress induced by means of polyethylene glycol 4000 (from 5 min to 18 h) were investigated in young epidermal cells of the primary roots ofZea mays. The sensitivity of the individual cell components to water stress was considered according to the time sequence in which their alterations appeared. Endoplasmic reticulum (ER) and mitochondria proved to be the most sensitive cell components, their structure changing after 5 min of water stress. By 8 h of stress, the condensation of nuclear chromatin in some cells was apparent, preceding polyribosome degradation but not all the other changes of the stressed cells. Similar types of structural alterations appeared slightly earlier in the more differentiated epidermal cells. The rapid changes in the structure of ER and mitochondria coincided with the rapid decrease of water potential of the root tips and the immediate cessation of the root growth.  相似文献   

13.
Lung cancer development involves multiple genetic abnormalities leading to malignant transformation of the bronchial epithelial cells, followed by invasion and metastasis. One of the most common changes is mutation of the p53 tumor suppressor gene. The frequency of p53 alterations in lung cancer is highest in small cell and squamous cell carcinomas. A genetic “signature” of the type of p53 mutations has been associated with carcinogens in cigarette smoke. The majority of clinical studies suggest that lung cancers with p53 alterations carry a worse prognosis, and may be relatively more resistant to chemotherapy and radiation. An understanding of the role of p53 in human lung cancer may lead to more rational targeted approaches for treating this disease. P53 gene replacement is currently under clinical investigation but clearly more effective means of gene deliver to the tumor cells are required. Novel approaches to lung cancer therapy are needed to improve the observed poor patient survival despite current therapies.  相似文献   

14.
To assess the effect of a single chromosomal translocation on the nuclear phenotype of human cells, seven diploid adenomas and five diploid carcinomas of the thyroid gland were studied using quantitative nuclear morphometry. Four adenomas and three carcinomas were cytogenetically normal, whereas three adenomas and two carcinomas had a unique chromosomal translocation. A densitometric parameter discriminated adenomas from carcinomas (skewness of the optical density histogram, SODH), and tumours with and without chromosomal translocation (standard deviation of the optical density, SDODH). These results demonstrate that single chromosomal structural rearrangements produce quantifiable alterations of nuclear organisation, but that other nuclear features which do not express an aneuploid DNA content or an abnormal karyotype differentially characterise benign and malignant conditions.  相似文献   

15.
A monoclonal antibody to the androgen receptor was applied to fine needle aspirates from patients with benign and malignant prostatic disease. The series includes six patients with benign hyperplasia and 24 patients with prostatic carcinomas. The androgen receptor was detected in most nuclei of both benign and malignant epithelial cells. The intensity of immunostaining varied. No obvious relation was observed between the intensity of the staining in benign versus malignant cells. In addition no clear differences were found in the proportion of androgen receptor positive cells in benign aspirates as compared with aspirates from well differentiated or moderately well differentiated prostatic carcinomas. The relative number of androgen receptor positive cells was highest in smears from poorly differentiated prostatic carcinomas.  相似文献   

16.
V. Baimai 《Chromosoma》1969,27(4):381-394
Drosophila birchii, a member of the melanogaster species group of the subgenus Sophophora, is common in the tropical rain forests of the Australia-New Guinea areas. Chromosome squashes are easily prepared from the larval ganglion cells and the sex chromosomes are readily recognizable. The species exhibits a remarkable karyotype variation. The metaphase plate figures, in general, show two pairs of V's, one pair of dots and one pair of sex chromosomes. Variations in metaphase chromosome morphology are found in the X (with four types), the Y (with three types) and chromosome IV (with two types). Chromosomal interchanges between X- and Y-chromosomes Type I are postulated to be involved in the differentiation of sex chromosome morphology while the modification of chromosome IV seems likely to be a result of the acquisition of extra heterochromatin. These chromosome types form seven distinct metaphase plate figures, all encountered in wild populations, thus giving D. birchii the most variable karyotype in the genus Drosophila.  相似文献   

17.
The matrix metalloproteinases (MMPs) are extracellular zinc-enzymes implicated in a number of physiological and pathological tissue remodeling processes, including cancer progression. For a long time they have been thought to be produced by malignant cells and to specifically contribute to tumor invasion, through their ability to degrade extracellular matrix components. However, studies performed over the last few years have demonstrated that extracellular proteinases implicated in the progression of human carcinomas, including most MMPs, are in fact predominantly expressed by stromal and not by cancer cells. Furthermore, membrane receptors, activators and/or binding sites for some of these proteinases are also predominantly found to be associated with stromal cells. These findings, together with the observation that MMPs can cleave some molecules implicated in controlling growth factor activities, suggest that the role of MMPs during cancer progression is not limited to facilitating malignant cell invasion alone but is also likely to participate in other aspects of the malignant phenotype. MMPs should in fact be regarded as pan-regulators of tissue neoformation characteristic of malignant tumors, which includes both epithelial cell expansion and stroma formation. In this context, synthetic MMP inhibitors which are presently designed should lead to the development of a new generation of anticancer agents which additional beneficial properties compared to the existing cytotoxic agents used in the treatment of human malignancies.  相似文献   

18.
In situ denaturation of metaphase chromosomes with alkali results in a shift from green to yellow, orange, brown and red fluorescence with acridine orange, indicating increasing denaturation of chromosomal DNA. The kinetics and characteristics of denaturation are described. Mouse and Microtus agrestis chromosomes denature uniformly but human cells show sequential denaturation. With increasing concentrations of alkali, the secondary constrictions in chromosomes 1, 9 and 16 are the first, and the distal half of the Y chromosome the last, to become denatured. — Reassociation of chromosomal DNA occurs within seconds after the start of incubation in salt solution. Areas containing repetitious DNA, e.g. mouse centromeres, fluoresce much more strongly than other regions with acridine orange after prolonged reassociation. Since human and Microtus centromeric regions behave similarly, it is proposed that they, too, contain repetitious DNA. — Reassociation treatment leads to enhancement of bright quinacrine mustard fluorescence in regions already bright before treatment. Furthermore, regions containing repetitious DNA, e.g. the secondary constrictions in human chromosomes 1, 9 and 16, whose fluorescence is dull before treatment, turn bright after reassociation. — The methods of fluorescence analysis of mammalian chromosomes with acridine orange and quinacrine mustard permit the localization and study of different classes of chromosomal DNA.  相似文献   

19.
Arf6 and its effector AMAP1 are overexpressed in malignant breast cancer cells, and are involved in their invasion and metastasis. We recently revealed that GEP100, a guanine nucleotide exchanging factor, is responsible for the activation of Arf6 which induces invasion and metastasis. GEP100 associated directly with ligand-activated epidermal growth factor receptor (EGFR) to be activated. Disruption of E-cadherin-mediated cell-cell adhesion is one of the major steps involved in acquisition of invasive phenotypes of most carcinomas. The EGFR-GEP100-Arf6 pathway not only activated matrix invasion activity but also perturbed E-cadherin function. GEP100 was found to be expressed in more than 80% of invasive ductal carcinomas. However, 60% of ductal carcinomas in situ were also positive for GEP100, in which GEP100 was preferentially coexpressed with EGFR in their malignant cases. Microenvionments have been highly implicated in the development of tumor malignancy. Our results reveal an aspect of the precise molecular mechanism of cancer invasion and metastasis, in which full invasiveness is not acquired just by alterations of cancer cells themselves, but their microenvironments may also play pivotal roles.  相似文献   

20.
Chrysotile is one of the six types of asbestos, and it is the only one that can still be commercialized in many countries. Exposure to other types of asbestos has been associated with serious diseases, such as lung carcinomas and pleural mesotheliomas. The association of chrysotile exposure with disease is controversial. However, in vitro studies show the mutagenic potential of chrysotile, which can induce DNA and cell damage. The present work aimed to analyze alterations in lung small cell carcinoma cultures after 48 h of chrysotile exposure, followed by 2, 4 and 8 days of recovery in fiber-free culture medium. Some alterations, such as aneuploid cell formation, increased number of cells in G2/M phase and cells in multipolar mitosis were observed even after 8 days of recovery. The presence of chrysotile fibers in the cell cultures was detected and cell morphology was observed by laser scanning confocal microscopy. After 4 and 8 days of recovery, only a few chrysotile fragments were present in some cells, and the cellular morphology was similar to that of control cells. Cells transfected with the GFP-tagged α-tubulin plasmid were treated with chrysotile for 24 or 48 h and cells in multipolar mitosis were observed by time-lapse microscopy. Fates of these cells were established: retention in metaphase, cell death, progression through M phase generating more than two daughter cells or cell fusion during telophase or cytokinesis. Some of them were related to the formation of aneuploid cells and cells with abnormal number of centrosomes.  相似文献   

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