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

The ability of a neonatal testicular product to inhibit cancer cell line growth of Mullerian origin was tested in an "in vitro" system. Preliminary experiments indicated that increasing concentration of neonatal rat testicular homogenates showed increasing endometrial cancer (HEC-1) cell growth inhibition. Further investigation revealed that testes organ culture, similarly, inhibited HEC-1 cell growth. It is, therefore, concluded that neonatal rat testes elaborated a substance (or substances) which may be effective as an anti-tumor agent.
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PMID:In vitro inhibition of endometrial cancer growth by a neonatal rat testicular secretory product. 720 44

The alkaline phosphatase (ALPase) activity of a human endometrial cancer cell-line, established and designated as HEC-50-B in our laboratory, was investigated biochemically and histochemically in relation to its cell growth pattern and to the effects of the sex steroid hormones, oestradiol and progesterone. The ATPase activity increased sharply in the early stationary phase to reach an activity almost 2.5 times higher than that obtained in earlier stages of the culture. On administration of oestradiol to the culture medium, a sharp elevation of the ALPase activity was induced on an average of 2 days earlier (late logarithmic phase) than in the case of an ordinary culture (no hormone administration), without causing a notable change in cell growth pattern. It should be noticed, however, that progesterone at such a low concentration that had very little effect on cell growth in the culture could clearly prohibit the elevation of ALPase activity. This hormonal effect on the ALPase activity resembled that on the enzyme activity of the endometrium of adult women. The ALPase activity of both the cultured endometrial cancer cells and the endometrium was found to be a sensitive indicator of the effect of progesterone. It would be a useful tool for future study in elucidating the mechanism of hormonal control of the neoplasm.
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PMID:Effects of oestradiol and progesterone on the alkaline phosphatase activity of a human endometrial cancer cell-line. 735 60

The migration potential through a basement membrane in an endometrial cancer cell line, such as Ishikawa, HEC-1-A or HHUA cell, in terms of strength, was enhanced by estradiol, but not modified by progesterone, medroxyprogesterone acetate (MPA), danazol or tamoxifen alone, by which estradiol-enhanced migration potential was inhibited. The order of the level of estrogen receptor was Ishikawa > HEC-1-A > HHUA cells. Therefore, it is suggested that the invasiveness of endometrial cancer cells might be activated by estradiol via estrogen receptors, but inactivated by progesterone, MPA, danazol or tamoxifen as an antiestrogen action, and that endometrial cancer cells could become invasive in the estrogen-predominant milieu, and the antiestrogenic agents could protect it.
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PMID:Estrogen activates migration potential of endometrial cancer cells through basement membrane. 750 72

We investigated the synthesis and biological effects of platelet-activating factor (PAF) in the human endometrial cancer cell line HEC-1A. We found that HEC-1A cells actively synthesize and release PAF, as demonstrated by both [3H]acetate incorporation into PAF and gas chromatography-mass spectrometry studies. HEC-1A cells not only synthesize but also respond to PAF. Indeed, in fura-2-loaded cells, PAF stimulates [Ca2+]i increase with a median effective concentration of 5.6 nM. Furthermore, PAF induces a time-dependent expression increase of the nuclear protooncogene c-fos with a median effective concentration of 130 nM and stimulates DNA synthesis (median effective concentration, 700 nM). All of these effects are inhibited by the PAF receptor antagonist L659,989. Radioligand binding studies indicated the presence of two populations of PAF receptors with affinity constants in the nanomolar and micromolar range. Since the PAF antagonist per se inhibits DNA synthesis and cell proliferation, we suggest that PAF supports an autocrine growth circuit in HEC-1A cells. On the contrary, in the uterine leiomyosarcoma cell line SK-UT-1, which does not express specific binding sites for PAF, neither this phospholipid nor its receptor antagonist affect DNA synthesis. Our results provide evidence for the existence of an autocrine proliferative loop involving PAF in the endometrial cancer cell line HEC-1A.
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PMID:Platelet-activating factor mediates an autocrine proliferative loop in the endometrial adenocarcinoma cell line HEC-1A. 752 Mar 61

Human cells contain several homologs of the bacterial mutL gene required for mismatch repair, including a gene on chromosome 7 designated hPMS2. We have identified an endometrial carcinoma cell line, HEC-1-A, that has a C-->T mutation in hPMS2 that generates a nonsense codon and yields a protein truncated at the C terminus. No wild-type gene or gene product was detected. The missing amino acids in hPMS2 are highly conserved among PMS homologs, suggesting that they may be critical for function. In support of this, extracts of HEC-1-A cells are defective in repairing a variety of mismatched substrates. Moreover, di-, tri-, and tetranucleotide repeated sequences are highly unstable in single cell clones of HEC-1-A cells, and HEC-1-A cells are resistant to killing by N-methyl-N'-nitro-N-nitrosoguanidine. The results provide strong experimental support for the involvement of the hPMS2 gene product in mismatch repair in human cells and support the concept that a defective hPMS2 gene may lead to predisposition to certain forms of cancer.
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PMID:A hPMS2 mutant cell line is defective in strand-specific mismatch repair. 762 32

A series of drug combination sequence studies was conducted in vitro using HEC-1A human endometrial carcinoma cells or 8226 myeloma cells. Four drugs were evaluated for schedule-dependent and sequence-dependent inhibition of human tumor colony formation in soft agar. Six different two-drug combinations were analyzed using the median dose effect method, and three different three-drug combinations were examined using the cumulative surviving fraction method. The results show that the specific sequence and method of drug exposure significantly influenced the production of antagonistic, additive, or synergistic cytotoxicity patterns. Drug combinations that were consistently synergistic included bleomycin or mitomycin C and cisplatin in 8226 cells, and etoposide plus bleomycin in human endometrial cancer (HEC-1A) cells. Most other two-drug combinations of bleomycin, etoposide, cisplatin, and mitomycin C were antagonistic in vitro, irrespective of the sequence of exposure. Among the three-drug combinations tested, consistent synergism was noted with cisplatin, etoposide, and bleomycin when either of the latter two agents was tested as a continuous exposure in vitro. Within individual two- and three-drug combinations, it was possible to observe synergism, additivity, or antagonism based on the particular exposure sequence tested. These results suggest that antitumor agent cytotoxicity in vitro can be radically influenced by the sequence of drug administration, a feature commonly overlooked in many clinical combination drug regimens.
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PMID:The effect of anticancer drug sequence in experimental combination chemotherapy. 767 39

Antitumor activity of angiogenesis inhibitor TNP-470 was evaluated in eight human cultured cell lines derived from choriocarcinoma: SCH, NUC-1, and GCH-1(m); ovarian cancer; TYK and Nakajima; and uterine endometrial cancer: HEC-6, HEC-50, and HEC-1-A. After 7-day culture with TNP-470, in medium at the concentration of 10(1) to 10(-2) micrograms/ml, the inhibition of growth was observed in all of the eight cell lines. The 50% inhibitory concentration of choriocarcinona cell lines was at an extremely low level compared to that of epithelial ovarian cancer and uterine endometrial cancer. In addition, the antitumor effect of this compound was studied in in vivo experiments using nude mice with tumors of GCH-1(m), NUC-1, or Nakajima cells. When the size of the transplanted tumor reached 100-200 mm3 in volume, 3, 10, or 30 mg/kg of TNP-470 was injected s.c. every other day. The inhibitory effect of TNP-470 was obtained by the administration of 10 and 30 mg/kg in GCH-1(m) and NUC-1 cells, respectively, while in Nakajima cells no significant effect was observed. In nude mice treated with 30 mg/kg of TNP-470, lung metastasis of GCH-1(m) cells was strongly inhibited both in the number and in the size of tumor nodules, indicating that the capillary growth in the originally developed tumor was also significantly reduced. These results suggest that the clinical setting using TNP-470 may be one of the promising treatments for the metastasis of tumor cells.
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PMID:Inhibitory effect of angiogenesis inhibitor TNP-470 on tumor growth and metastasis of human cell lines in vitro and in vivo. 768 19

The present study was undertaken to determine whether endometrial cancer cell line HEC-1-A differ from nontransformed cells, in that the cAMP and protein kinase C pathways may enhance IGF-I effects in mitogenesis by acting at the G1 phase of the cell cycle instead of G0. Immunofluorescence staining of HEC-1-A cells using the proliferating cell nuclear antigen (PCNA) monoclonal antibody and flow cytometric analysis determined that HEC-1-A cells do not enter the G0 phase of the cell cycle when incubated in a serum-free medium. Approximately 51% of the cells were in G1, 12% were in S and 37% in G2 phase of the cell cycle prior to treatment. Forskolin and phorbol-12-myristate 13-acetate (PMA) were used to stimulate cAMP production and protein kinase C activity, respectively. IGF-I, forskolin and PMA each increased (P < 0.01) [3H]-thymidine incorporation in a dose and time dependent manner. The interaction of forskolin and PMA with IGF-I was then determined. Cells preincubated with forskolin or PMA followed by incubation with IFG-I incorporated significantly more (P < 0.01) [3H]-thymidine into DNA than controls or any treatment alone. It is concluded that forskolin and, to a lesser extent, PMA exert their effect at the G1 phase of the cycle to enhance IGF-I effects in cell proliferation.
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PMID:cAMP and PMA enhance the effects of IGF-I in the proliferation of endometrial adenocarcinoma cell line HEC-1-A by acting at the G1 phase of the cell cycle. 773 22

The in vitro invasive ability, the expression of cell adhesion molecule E-cadherin, activity of matrix metalloproteinase (MMP) and K-ras point mutation were investigated in eight human endometrial carcinoma cell lines. 1) In vitro invasive abilities of endometrial carcinoma cell lines depend on the degree of cell differentiation and the origin of cell lines. A poorly-differentiated carcinoma cell line (NUE-1) and a cell line derived from metastatic lymph node (SNG-M) were more invasive than moderately-(HEC-1A, HEC-1BE) and well-differentiated (HEC-6, Ishikawa) cell lines. 2) Immunohistochemically, less or non-invasive cell lines expressed E-cadherin strongly, whereas a highly invasive cell line (NUE-1) expressed E-cadherin weakly. 3) When cultured on Matrigel-coated dishes, the tumor cells derived from moderately- and well-differentiated carcinoma aggregated with each other and did not invade Matrigel in the invasion assay. The aggregated cells expressed E-cadherin more strongly when cultured on Matrigel. 4) 72-kD gelatinase (MMP-2) was secreted in serum-free conditioned medium of all cell lines. In an invasive cell line (NUE-1,SNG-M), the activity of MMP-2 was stronger than in other cell lines. And the activity of 92-kDa gelatinase (MMP-9) was detected in most invasive cell line (NUE-1). 5) Point mutation of K-ras codon 12 was detected in four of eight (50%) cell lines by the PCR-RFLP method. The changes in the DNA sequence were identified, but K-ras point mutation was not correlated with in vitro invasiveness of the tumor cells.
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PMID:[The factors involved in invasive ability of endometrial carcinoma cells]. 804 Jun 23

Established monolayer cell lines derived from human endometrial carcinoma (Ishikawa and HEC-50) were sensitive to the cytotoxic activity of peripheral blood lymphocytes (PBLs). The percentages of hormone-responsive Ishikawa cells lysed by the cytotoxic activity of lymphocytes were 45.7 +/- 4.3 (mean +/- SE), 31.5 +/- 4.1, and 20.1 +/- 1.6, at effector/target (E/T) ratios of 50:1, 25:1, and 12:1, respectively. Values of 44.7 +/- 5.4%, 29.4 +/- 4.6%, and 20 +/- 4.9% were obtained when non-hormone-responsive HEC-50 cells were used as targets at the same E/T ratio. The percentages of epithelial and stromal cells, isolated from human endometrial cancer, lysed by the cytotoxic activity of lymphocytes were 40 +/- 5.4 and 25.2 +/- 3.8, respectively, at an E/T ratio of 25:1. The addition of interferon-beta (IFN-beta) to the culture increased tumor target cell sensitivity to the lytic activity of untreated PBL. The increase produced by 10 IU/ml of IFN-beta ranged between 0.60- and 0.89-fold (P < 0.01 Student's t test, two-tailed, unpaired) in Ishikawa cells and between 0.37- and 0.72-fold P < 0.05) in HEC-50 cells. Higher concentrations of IFN-beta (100 and 1000 IU/ml) were less effective in increasing the sensitivity of the target cells. There was no significant increase in the cytotoxic activity of lymphocytes treated with IFN-beta whereas cytotoxic activity toward untreated tumor target cells increased when lymphocytes were treated with IFN-alpha. The effects of IFN-beta were also evaluated using epithelial and stromal cells derived from human endometrial cancer. It was found that IFN-beta at low concentrations (10 IU/ml) significantly increased the sensitivity of both epithelial and stromal cells, by 48 and 73%, respectively. Our data indicate that Ishikawa, HEC-50, epithelial, and stromal cells may provide a useful experimental model for studying the effects of immunomodulant agents such as IFN-beta in hormone-related tumors. IFN-beta increases endometrial target cell sensitivity, rather than the lytic activity of lymphocytes.
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PMID:Interferon-beta increases the sensitivity of endometrial cancer cells to cell-mediated cytotoxicity. 806 35


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