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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retroviral insertional activation of the expression of the Evi-1 is one of the most common events associated with transformation in murine myeloid leukemia. The murine Evi-1 gene encodes a 145 kDa nuclear, DNA binding protein that contains two domains containing seven and three sets of repeats of the zinc finger motif. During studies to determine the role of the Evi-1 gene in the transformation of human cells, we have found that the Evi-1 gene is uniquely expressed at low levels in HEC-1-A cells and at high levels in HEC-1-B cells, two related human endometrial carcinoma cell lines. cDNA clones were isolated and sequenced from the HEC-1-B cell line. The human gene is highly homologous to the murine gene and shows 91% and 94% homology in nucleotide or amino acid sequence respectively. In addition an alternatively spliced form of the gene was identified that encodes a protein with an internal deletion 315 amino acids including two of the zinc finger repeats. The possible basis for the unique expression of the Evi-1 gene by HEC-1 cells could not be determined by karyotype or Southern blot analysis.
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PMID:Unique expression of the human Evi-1 gene in an endometrial carcinoma cell line: sequence of cDNAs and structure of alternatively spliced transcripts. 211 46

The response of the human gynecological carcinoma cell-lines HEC-1-A (endometrial carcinoma) and OvCar-3 (ovarian carcinoma) to photodynamic therapy in vitro was examined. The porphyrin compound Photosan III (Ph III) was used for photosensitization of the cells after incubation times of 24 h (HEC-1-A) and 48 h (HEC-1-A and OvCar-3). The Ph III doses varied from 0-10 micrograms/ml medium. Irradiation was performed with laser light at 630 nm. Irradiation doses up to 20 J/cm2 were applied at an irradiance of 40-100 mW/cm2. Cell vitality of the untreated control groups and of the therapy group was determined 48 h after irradiation, using the trypan blue exclusion test. The experimental results show that treatment of OvCar-3 cells with 10 J/cm2 resulted in a decrease in vitality dependent on photosensitizer dose (0-5 micrograms/ml, 48 h incubation time) but independent of the irradiance (40-100 mW/cm2). Complete cell death was observed after application of irradiation doses in the range of 5-20 J/cm2 combined with drug concentrations of 10-2.5 micrograms/ml, at a fixed incubation time of 48 h. HEC-1-A cells did not survive photodynamic therapy with 10 J/cm2 after incubation with 5 micrograms/ml for 48 h. After a shorter incubation time of 24 h, 10 micrograms/ml Ph III was necessary for the same effect. There was a maximum decrease in cell vitality when measured 48 h after irradiation. This was not improved at 72 h.
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PMID:Response of human endometrium and ovarian carcinoma cell-lines to photodynamic therapy. 225 16

Previous studies from our laboratories demonstrated that cells from a human endometrial adenocarcinoma cell line (Ishikawa) responded to estradiol whereas cells from another endometrial cancer line (HEC-50) did not. In an attempt to identify factors responsible for the observed estrogen insensitivity we compared the characteristics of the estradiol receptor (ER) systems in Ishikawa and HEC-50 cells. Saturation analyses of cytosolic estrogen binders were performed over a 0.1-70 nM range of [3H]estradiol concentrations. Equilibrium dissociation constants and number of binding sites were determined by graphic analysis of Scatchard plots or computed by applying Fourier-derived affinity spectrum analysis (FASA) of the binding data. No significant differences were noted in the dissociation constants (Kd approx. 0.6 nM) or number of binding sites (approx. 6-10 fmol/mg protein) for the single binder that could be evaluated by the graphic method in cytosol from the two cell lines. However, 2 binders in Ishikawa cells (Kd approx. 0.2 and 6 nM) could be detected by the FASA method; the higher affinity binder in HEC-50 cells could not be clearly demonstrated. Structural differences in the specific estrogen binders which might distinguish HEC-50 from Ishikawa cells or normal endometrial tissue were investigated by using the anti-ER monoclonal antibody JS 34/32. Interaction of the antibody with [3H]estradiol binders of estrogen-responsive cells and tissue was evident from the formation of labeled complexes that were shown to sediment faster in glycerol density gradients and could be immunoprecipitated with Protein A attached to Sepharose beads. In contrast, the antibody did not recognize labeled specific binders in the HEC-50 cells. Furthermore, [3H]estradiol receptors in Ishikawa cells could be transformed into a species that exhibited increased hydrophilicity, evident from its binding to DNA-cellulose, whereas binders from HEC-50 could not. These results indicate that the lack of responsiveness of HEC-50 cells to estrogens might be due to structural or functional alterations in the ER protein resulting in a loss of its capability to undergo estrogen-directed conformational changes required for biological activity.
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PMID:Altered estrogen receptor system in estrogen-unresponsive human endometrial adenocarcinoma cells. 277 23

Alkaline phosphatase activity in human endometrial cancer cells of the estrogen-responsive Ishikawa line was markedly stimulated (3-20-fold in 4 days) by estrogens, 5 alpha-dihydrotestosterone, and dehydroepiandrosterone but not by testosterone, medroxyprogesterone acetate, glucocorticoids, several peptide hormones, prostaglandins, or growth factors. Maximum responses to estradiol were obtained at concentrations between 10(-9) and 10(-7) M; at 10(-8) M estradiol, the highest activity was reached 48-72 h after addition of the hormone. A linear relationship between enzyme activity at 48 h and the length of exposure to the hormone was observed. Dibutyryl cyclic guanosine 3':5'-monophosphate, but not dibutyryl cyclic adenosine 3':5'-monophosphate enhanced alkaline phosphatase activity and acted synergistically with estradiol. trans-4-Monohydroxytamoxifen completely antagonized the stimulatory effect of estradiol and had no agonistic activity. Dihydrotestosterone and dehydroepiandrosterone appear to exert their effects, at least in part, by interacting with estrogen receptors, since the simultaneous presence in the medium of monohydroxytamoxifen abolished their influence on alkaline phosphatase activity. The specific antiandrogen monohydroxyflutamide partially antagonized the effect of these hormones, suggesting that their action involved androgenic mechanisms as well. Exposure to elevated temperature and to specific inhibitors identified alkaline phosphatase of Ishikawa cells as a placental-type isoenzyme, thus contrasting with the nonplacental type found in glandular epithelial cells of normal endometrium and in another human endometrial cancer cell line, HEC-50. This study extends our previous observations of estrogen responsiveness in the Ishikawa cell line. In addition to the previously reported stimulatory effects on growth and progesterone receptor levels, we are now describing the stimulation by estrogens and C19 steroids of an enzyme, alkaline phosphatase, which can be used as a convenient end point to examine mechanisms of hormonal action.
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PMID:Effects of steroid hormones and antisteroids on alkaline phosphatase activity in human endometrial cancer cells (Ishikawa line). 293 30

The effects of estradiol on DNA polymerase alpha activity were investigated in an estrogen-responsive human endometrial cancer cell line (Ishikawa) derived from a well differentiated endometrial adenocarcinoma. These cells are known to respond to estradiol by increasing progesterone receptor levels, alkaline phosphatase activity, and cell density. Four- to 5-fold increases in DNA polymerase alpha activity occurred when estradiol was added to cultures of Ishikawa cells in medium containing charcoal-treated fetal bovine serum. Maximal stimulation was achieved at 18 h during incubations with 10(-8) M estradiol, but significant effects also were found with 10(-9) and 10(-6) M. These effects were almost completely counteracted by a 100-fold excess of 4-hydroxytamoxifen. At 10(-6) M, the antiestrogen had no influence on the basal levels of DNA polymerase alpha. Medroxyprogesterone acetate (10(-6) M) was ineffective as either an enhancer of enzymatic activity or an antiestrogen when tested in combination with 10(-8) M estradiol, even in the presence of appreciable levels of specific progesterone binders. The responsiveness of the Ishikawa cells to estrogen contrasts with the lack of effects of estradiol on DNA polymerase alpha activity in another human endometrial adenocarcinoma cell line (HEC-50).
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PMID:Effects of estradiol on deoxyribonucleic acid polymerase alpha activity in the Ishikawa human endometrial adenocarcinoma cell line. 294 47

The growth inhibitory effects of medroxyprogesterone acetate (MPA) and tamoxifen (TAM) were tested on three long-established endometrial carcinoma cell lines (HEC-1, KLE, and RL95-2) and on UM-EC-1, a new endometrial carcinoma cell line established in our laboratory. MPA and TAM were used in growth experiments either alone, simultaneously, or sequentially. The MCF-7 breast cancer cell line was used as a control. None of the endometrial carcinoma cell lines showed significant sensitivity to 0.1-10 microM MPA. In contrast, 10 days exposure to 5 microM TAM induced 83 and 70% growth inhibition in HEC-1 and KLE cultures, whereas the growth of UM-EC-1 was inhibited by 99.7% and RL95-2 cultures by 100%. TAM-induced growth inhibition was reversible since all cell lines resumed logarithmic growth when TAM was removed from the culture medium. Addition of 17 beta-estradiol (E2) to the culture medium did not accelerate recovery, and reversal of TAM-induced growth inhibition was not seen when TAM and E2 were added simultaneously. This is consistent with our finding that, except for MCF-7, these cell lines did not show detectable estrogen receptor (ER) activity in assays performed at the time of these experiments. When treated sequentially with TAM and MPA, all cell lines resumed logarithmic growth when medium containing TAM was replaced with medium containing MPA. Simultaneous exposure to 5 microM MPA and 5 microM TAM resulted in a slight additive growth inhibitory effects only in KLE cultures. Our results show that MPA does not have growth inhibitory effects in these endometrial carcinoma cell cultures, whereas TAM exerts a potent inhibitory effect that is not reversed by estrogen and may thus be mediated through a mechanism different from blockade of ER. In vitro results with the UM-EC-1 cell line correlated with the clinical response of the cell line donor. Her disease progressed during postoperative MPA therapy, but subsequently she responded to TAM therapy.
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PMID:In vitro growth regulation of endometrial carcinoma cells by tamoxifen and medroxyprogesterone acetate. 296 31

The in vitro antiproliferative activity of human recombinant interferon-gamma (IFN-gamma) was tested against human tumor cells in vitro in combination with doxorubicin, cisplatin, or vinblastine. Using a human tumor clonogenic assay (HTCA), IFN-gamma alone showed dose-dependent inhibition of colony growth in six or seven human tumor cell lines as well as in each of nine fresh ovarian tumor specimens. The combination of IFN-gamma and either doxorubicin or cisplatin showed additive antiproliferative effects against all the cell lines with the exception of an IFN-gamma-resistant endometrial cancer cell line (HEC-1A). In combination with vinblastine, IFN-gamma rarely had an additive effect. Inclusion of macrophages from malignant effusions in the HTCA potentiated the antiproliferative effect of IFN-gamma alone as well as the combination of IFN-gamma and doxorubicin; however, the efficacy of the two agents was never more than additive. The results show that combinations of IFN-gamma with doxorubicin or cisplatin are additive and warrant further investigation. The antitumor effect of IFN-gamma alone or in combination with cytotoxic drugs may be significantly enhanced by tumor-associated macrophages.
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PMID:Interferon-gamma and cytotoxic agents studied in combination using a soft agarose human tumor clonogenic assay. 310 48

Effects of combination treatment with human recombinant alpha-2b interferon (IFN-alpha 2b) and gamma interferon (IFN-gamma) and sequencing of the combination on colony formation of human tumor cells were studied in a human tumor clonogenic assay (HTCA) with or without ascites-associated macrophages (AAM). Five different human tumor cell lines were studied. Three of the five cell lines (ovarian cancer cell line BG-1, cervical cancer cell line ME-180, and melanoma cell line SK-MEL 28) were sensitive to both IFNs. Cervical cancer cell line CaSki was sensitive to IFN-alpha 2b but resistant to IFN-gamma. Endometrial cancer cell line HEC-1A was resistant to both IFNs. Synergistic interaction was observed in BG-1 and SK-MEL 28 with a combination of the IFNs. ME-180 did not exhibit a positive interaction, in spite of its sensitivity to each IFN. CaSki and HEC-1A also did not exhibit a positive combined interaction at clinically achievable concentrations. One sequential combination method (method 1: IFN-alpha 2b----IFN gamma with a 24-h interval) resulted in a similar antitumor effect as the simultaneous combination. A reversed sequential method (method 2: IFN-gamma----IFN-alpha 2b with a 24-h interval) was less effective in three of the five cell lines. In BG-1, AAM enclosed in the lower layer markedly enhanced the antitumor effect of combined IFNs as well as each IFN alone. The antitumor effect with method 1 was significantly greater than that achieved with simultaneous combination or combination according to method 2 in the presence of AAM (P less than 0.01). These results suggest that (1) a synergistic antitumor effect of IFN-alpha 2b and IFN gamma is demonstrable in selected types of tumors, depending upon the sensitivity of each tumor cell line to both IFNs; (2) optimal scheduling for the direct antitumor effect of combined IFNs seems to be long-term exposure of cells to the IFN, the cells being treated with both IFNs either simultaneously or sequentially (IFN-alpha 2b preceding IFN-gamma); and (3) AAM potentiate the antitumor effect of IFNs either alone or in combination. Finally, IFN-alpha 2b may have some priming effects for the indirect effect of IFN gamma mediated through AAM in certain tumor cells.
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PMID:Effects of scheduling and ascites-associated macrophages on combined antiproliferative activity of alpha-2b interferon and gamma-interferon in a clonogenic assay. 313 42

By statistical study on 135 patients with endometrial carcinoma, it is clarified that the most effective prognostic factor of the cancer is the histological grading. Well differentiated type is best prognostic and possesses hormone receptors. Application of cell culture is one of the most suitable choices in the study of hormone and human endometrial carcinoma. Present paper is to show usefulness of in vitro study by taking example of the above theme. 1) Binding ability of endometrial carcinoma cells to estrogen: Being explained by Gurpide et al. by using HEC-1 cells, the ability is under control of cGMP and cAMP ratio. 2) Responses to estrogen: DNA polymerase alfa of Ishikawa cells which possesses both estrogen and progesterone receptors (ER, PR) is stimulated first showing peak at 18 hours and alkaline phosphatase (ALP) is at 72 hours by E(2)10(-8)M, which is antagonized by OH-tamoxifen. PR level is also enhanced at its maximum after 3 day E2 treatment, and is analyzed by immunocytochemistry with PR mono-clonal antibody as well as biochemical assay. Gorski and Greene's theory that steroid receptor is localized in nuclei is confirmed in endometrial carcinoma. Growth of Ishikawa cells is apparently enhanced in the aspects of shortened cell cycle and unlimited saturation density. 3) Responses to progestogen: Nucleic acid syntheses of HEC-1 are immediately suppressed by progesterone (P) 2.5 microg or more. Electron microscopic findings show appearances of Golgi apparatus and lysosomal granules. Growth suppression is observed in the cell lines regardless of PR positivity. ALP activity of PR-negative HEC-50 cells
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PMID:[Cell culture--its application in the study of hormone and endometrial carcinoma and feed-back to clinical medicine]. 315 Aug 47

Despite the fact that adenocarcinoma of the endometrium is currently the most common gynecologic malignancy in the United States, few chromosomal studies have been done to date characterizing this disease. HEC-1A, a cell line used by many laboratories as a reference cell line for endometrial carcinoma, has never been subjected to definitive karyotyping. For this reason, with the use of improved banding techniques, this has now been accomplished, and several consistent abnormalities have been identified. There was a marker chromosome formed from an insertion of 2q21, probably representing an insertion of the lacking chromosome 14. In addition, there was a translocation to the telomeric region of 1p; and trisomies of 3, 7, and 17. Many of these abnormalities are known to consistently be associated with other primary malignancies. In addition, the chromosomes in which trisomy is noted carry genes associated with epidermal growth factor and estrogen receptors, which also bear marked homology to known oncogenes. It would appear that further detailed studies of various grades and stages of endometrial carcinoma, as well as histologic types and "precursor lesions," may lead to an understanding of those chromosomal changes associated with disease initiation and progression.
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PMID:Cytogenetics of an endometrial adenocarcinoma cell line and its implications. 341 Mar 49


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