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

In earlier studies of oncogene expression in ovarian and endometrial neoplasms, the authors reported that high tumor levels of fms-complementary transcripts correlate with high histologic grade and advanced clinical stage presentations. In this communication, they pursue these initial clinicopathologic investigations to demonstrate by in situ hybridization and immunohistochemistry that malignant epithelial cells of 14 of 14 invasive adenocarcinomas of the ovary express fms-complementary transcripts. By Northern blotting and by reverse transcription, followed by polymerase chain reaction amplification, the authors also were able to demonstrate fms transcript expression in several ovarian and endometrial carcinoma-derived cell lines. Because about half (6/14) of the invasive adenocarcinoma specimens were shown to coexpress fms and colony-stimulating factor 1, the authors propose that the expression of this lymphohematopoietic cytokine and its receptor by ovarian adenocarcinomas could contribute to their proliferative and invasive characteristics in vivo.
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PMID:Ovarian adenocarcinomas express fms-complementary transcripts and fms antigen, often with coexpression of CSF-1. 169 82

The cytokine interleukin-1 (IL-1) can inhibit growth of breast cancer cells in culture and promote cellular differentiation in synergism with other growth factors. A secreted IL-1 receptor antagonist (sIL-1ra) has been described and an intracellular version (icIL-1ra) has been cloned; both antagonists block IL-1-dependent responses. We compared mRNA expression of IL-1 and both receptor antagonists in normal and neoplastic endometrium. RNA was extracted from five benign endometrial and five endometrial cancer whole-tissue specimens, reverse transcribed into cDNA, then amplified by polymerase chain reaction using specific primers for IL-1 alpha, IL-1 beta, sIL-1ra, and icIL-1ra. IL-1 alpha and IL-1 beta were expressed in variable amounts in all tissues; there was no difference in expression between normal and cancer specimens. In contrast, high levels of icIL-1ra were expressed in four of five cancer specimens compared with none of five normal tissues (P = 0.02). There was no expression of sIL-1ra in cancer and normal tissues. These preliminary experiments suggest that IL-1 is ubiquitously expressed in endometrial tissues whereas endometrial cancer preferentially expresses icIL-1ra. IcIL-1ra may regulate IL-1-mediated events such as growth and differentiation in endometrial neoplasia.
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PMID:Expression of interleukin-1 and interleukin-1 receptor antagonists in endometrial cancer. 183 51

The human endometrial adenocarcinoma cells IK were found to be highly susceptible for TNF but rapidly developed a resistance to this cytokine. Inhibitors of RNA transcription or protein biosynthesis could not overcome this resistance. Moreover TNF resistance was not associated with increased resistance to hydrogen peroxide. The resistant phenotype remained stable and was not communicated to neighbouring cells in a paracrine manner. The TNF treatment did not induce a multidrug resistance on IK cells. Nude mice bearing xenotransplanted endometrial carcinoma cells did not benefit from TNF treatment.
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PMID:Rapid development of resistance to tumor necrosis factor alpha on Ishikawa human endometrial carcinoma cells. 239 31

Natural cell-mediated immunity against autologous tumor cells, autologous endometrial epithelium, and allogeneic epidermoid carcinoma cell line HeLa was tested in 8 patients with endometrial carcinoma and one patient with endometrial stromal sarcoma. The average cytotoxicity of unstimulated peripheral blood lymphocytes against autologous tumor and HeLa cells was weak but significant. Pretreatment of effector cells for 3-5 days with 300 U/ml recombinant interleukin-2 (rIL-2) resulted in increased cytotoxicity against malignant target cells in 7 out of 9 cases. The 2 patients' effector cells which were refractory to rIL-2 could be stimulated to appreciable lytic activity against the malignant target cells with a recently described cytokine which induces morphological differentiation of natural killer cells. Benign endometrial cells were weakly sensitive to rIL-2-activated lysis in 2 cases. The precursors of the rIL-2-activated killer cells were mostly CD16-positive and CD3-negative, and co-sedimented with endogenous natural killer cells in discontinuous density gradient centrifugations. These results indicate the rIL-2-activated killer cells have a capacity to distinguish between normal and malignant endometrial cells, and that the precursors of the lytic cells in this system belong to the same subpopulation of lymphocytes as endogenous natural killer cells. In addition, rIL-2 alone may not in all cases be sufficient for optimal generation of cytotoxicity against malignant cells.
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PMID:Interleukin-2-stimulated natural killer activity against malignant and benign endometrium. 349

A highly reproducible and technically straightforward technique for the isolation and long-term culture of normal human endometrial epithelial cells is described. The essential conditions for long-term culture are that the cells be seeded onto a gelatin matrix and that 'endothelial cell growth supplement' be present in the culture medium. Normal endometrial epithelial cells express cytokeratins and oestrogen receptors. They may be passaged five to six times without change in properties. Growth of normal endometrial epithelial cells was stimulated by 17-beta-oestradiol and epidermal growth factor. Expression of the mRNA coding for seven polypeptide angiogenic factors, by normal endometrial epithelial, stromal and three endometrial carcinoma lines, was examined. The endometrial epithelial and stromal cells express mRNA for the polypeptide angiogenic factors, basic fibroblast growth factor, vascular endothelial cell growth factor, transforming growth factor-beta 1 and pleiotrophin, as well as the cytokine midkine. Expression of the mRNA for both vascular endothelial growth factor and midkine by normal endometrial epithelial cells showed a 2-fold increase on treatment with a physiological dose of 17-beta-oestradiol (10(-10) M) while, in contrast, the mRNA of transforming growth factor-beta 1 decreased 4-fold on treatment with 17-beta-oestradiol (10(-10) M) and was abolished by exposure to progesterone (5 x 10(-9) M). Expression of the mRNAs for angiogenic polypeptides by the endometrial carcinoma lines was more restricted.
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PMID:The isolation and long-term culture of normal human endometrial epithelium and stroma. Expression of mRNAs for angiogenic polypeptides basally and on oestrogen and progesterone challenges. 753 45

The conversion of C19 steroids to estrogens occurs in a number of tissues, such as the ovary and placenta, and is catalyzed by aromatase P450 (P450arom; the product of the CYP19 gene). P450arom expression has also been detected in a number of uterine tumors, such as leiomyomas and endometrial cancer. On the other hand, P450arom expression was undetectable in normal endometrial and myometrial tissues. The present study was conducted to determine the presence or absence of aromatase expression in peritoneal endometriotic implants and in the eutopic endometrium of women with endometriosis. Endometriotic implants in pelvic peritoneum (n = 17; e.g. posterior culdesac, bladder, and anterior culdesac) and eutopic endometrial curettings (n = 11) of 14 patients with histologically documented pelvic endometriosis were obtained at the time of laparoscopy or laparotomy. Pelvic peritoneal biopsies distal to endometriotic implants as well as normal endometrial tissues (n = 7) from disease-free women were used as negative controls. We used competitive RT-PCR technology employing an internal standard to amplify P450arom transcripts in total ribonucleic acid (RNA) isolated from these tissues. P450arom transcripts were detected in all endometriotic implants and in all eutopic endometrial tissues from patients with endometriosis. P450arom messenger RNA species were not detectable in endometrial tissues from disease-free women or in endometriosis-free peritoneal tissues. The highest levels of transcripts were detected in an endometriotic implant that involved the full thickness of the anterior abdominal wall. The P450arom transcript level within the core of this endometriotic mass was 4-fold higher than that in the surrounding adipose tissue. It has been shown recently that aromatase expression in various human tissues is regulated by the use of tissue-specific promoters via alternative splicing. To analyze promoter usage, we amplified by RT-PCR the most likely promoter-specific untranslated 5'-termini of P450arom transcripts in 2 endometriotic implants. It appears that these endometriotic implants use both the adipose-type promoter I.4 and gonadal-type promoter II for aromatase expression. The use of promoter I.4 for aromatase expression in adipose tissue has been recently observed to be regulated by members of the interleukin-6 (IL-6) cytokine family. Based on these findings, we examined by RT-PCR, IL-6 and IL-11 messenger RNA expression in 5 endometriotic tissues and 1 eutopic endometrial sample from a patient with endometriosis. We detected IL-6 and IL-11 transcripts in all endometriotic tissues and in the eutopic endometrial tissue sample studied. Our findings indicate that both eutopic endometrial tissues and endometriotic implants from patients with endometriosis are biochemically different from normal endometrial tissues of disease-free women. The presence of aromatase expression in eutopic endometrial tissues from patients with endometriosis may be related to the capability of implantation of these tissues on peritoneal surfaces. Furthermore, the possibility of estrogen production in these implants may serve to promote their growth. Increased IL-6 and IL-11 expression in these tissues suggests that P450arom expression in endometriosis may be regulated in part by these cytokines.
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PMID:Aromatase expression in endometriosis. 855 Jul 48

Phytohemagglutinin-stimulated regional lymph node cells obtained from gynecological cancer patients exerted a significant antiproliferative activity against an endometrial cancer cell line, RL95-2 on a human tumor clonogenic assay, and released a high amount of tumor necrosis factor alpha (TNF alpha), and interferons. The activity was thought to be partly due to released TNF alpha, because RL95-2 was highly sensitive to recombinant TNF alpha. However, anti-TNF alpha failed to inhibit the activity, which indicated the probability of some as yet unclarified participation of cytokines. Therefore, the regional lymph nodes might be used as sites of endogenous cytokine therapy in endometrial cancer patients.
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PMID:An attempt to generate an antitumor effect in the regional lymph nodes against endometrial cancer cells by inducing antitumor cytokines. 864 Jul 46

Oestrogen deficiency is by far the major factor contributing to the high rate of osteoporotic fractures in women. The anti-osteoporotic effect of estrogen may be explained by its property to regulate cytokine secretion and thus balance bone remodeling. In oestrogen deficiency, increased resorption and remodeling will occur leading to osteoporosis. It has been extensively shown that oestrogen replacement therapy (ERT) prevents postmenopausal bone loss and reduces fracture risk by half, provided that an appropriate dose is used. In order to optimize osteoporosis prevention, ERT should be started a early as possible in menopause and be maintained as long as possible. ERT may also be effective in elderly osteoporotic patients in preventing bone loss and, reducing fracture risk. The acceptance of ERT, however, at an older age has not been thoroughly evaluated. A reduction of cardiovascular disease and of climateric symptoms are among other benefits of ERT. So far, only few postmenopausal women are treated with ERT. ERT without progestins has been repeatedly found associated with an increased risk of developing endometrial cancer, but the cyclic addition of progestins protects from endometrial hyperplasia and carcinoma. Combined oestrogen-progestin therapy is as efficient as estrogen therapy alone, but not more so. Since progestins may oppose some of the beneficial effects of estrogens, the lowest dose with the least metabolic impact should be prescribed. Women who have had a hysterectomy, should probably be treated by estrogen replacement therapy only. Meta-analyses concerning breast cancer associated with ERT found a very moderately increased risk (RR = 1.06). Therefore ERT prescription should be discussed openly with women considering all risks and benefits. In women who have suffered from breast cancer, a bone sparing effect of tamoxifen has been shown.
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PMID:Osteoporosis prevention and treatment with sex hormone replacement therapy. 884 55

Estrogen biosynthesis in adipose tissue increases with age and obesity, and has been implicated in the development of endometrial cancer and breast cancer. In normal human adipose tissue, expression of the CYP19 gene which encodes aromatase P450, the enzyme responsible for estrogen biosynthesis, is regulated by a distal promoter, namely promoter I.4. Stimulation of expression in adipose stromal cells by members of the type 1 cytokine family, i.e. interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF) and oncostatin M (OSM), is mediated via a Jak-STAT3 signaling pathway and a GAS element upstream of promoter I.4. In contrast, aromatase expression in breast adipose tissue proximal to tumor is increased three- to four-fold to the utilization of another promoter, namely promoter II, proximal to the translation initiation site. In the present report, we show that prostaglandin (PG) E2 is the most potent factor which stimulates aromatase expression via cyclic AMP and promoter II. PGE2 acts via EP1 and EP2 receptor subtypes to stimulate both the PKC and PKA pathways. The combined stimulation of both of these pathways results in the maximal expression of promoter II-specific CYP19 transcripts. Because PGE2 is a major secretory product both of breast tumor epithelial cells and fibroblasts, as well as of macrophages infiltrating the tumor site, then this could be the mechanism whereby estrogen biosynthesis is stimulated in breast sites adjacent to a tumor, leading in turn to increased growth and development of the tumor itself.
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PMID:Transcriptional regulation of CYP19 gene (aromatase) expression in adipose stromal cells in primary culture. 936 91

We present a 66-year-old woman who developed eruptive keloids in association with endometrial carcinoma in the absence of trauma, surgery, inflammation, or other known preludes to keloid formation. Keloid formation and endometrial carcinoma are both associated with similar cytokine abnormalities and as such, we hypothesize that this is a previously unreported paraneoplastic phenomenon.
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PMID:Eruptive paraneoplastic keloids. 1054 78


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