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

This study was designed to test the hypothesis that genotypic changes of tumor necrosis factor alpha (TNF-alpha) promoter region are associated with endometrial cancer. TNF-alpha gene encodes a cytokine involved in angiogenesis and oncogenesis of several cancers. Some uncommon alleles are reported to be associated with increased production of TNF-alpha and the onset of various cancers. Studies of such alleles are lacking in endometrial cancer. In this study, we examined the genetic changes at the polymorphic 3 loci of TNF-alpha promoter regions (-238, -308 and 488) in 41 Japanese patients with uterine endometrial carcinomas (UEC). Nine of 41 UEC samples (22%) had genotype changes from GA to A at -308 promoter region of the TNF-alpha gene. There were no genotype changes at -238 and 488 regions of TNF-alpha in UEC samples. The results of our study demonstrate for the first time that genotype changes from GA to A in UEC patients. We conclude that the genotype changes at -308 promoter region of TNF-alpha may play an essential role in the malignant transformation of endometrial cells.
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PMID:Frequent genotype changes at -308 of the human tumor necrosis factor-alpha promoter region in human uterine endometrial cancer. 1067 88

We describe a 65-year-old woman with a large surgically unresectable and chemoresistant liver metastasis of endometrial carcinoma who was treated by infusion with peripheral blood T cells stimulated with tumor lysate-pulsed autologous dendritic cells (DC). Extensive in vitro characterization of the DC-activated T cells included phenotypic analysis, cytotoxicity, and intracellular cytokine secretion. High cytotoxicity was observed against autologous tumor cells, but not against NK-sensitive K562 cells, autologous Con-A lymphoblasts, or autologous Epstein-Barr virus-transformed lymphoblastoid cells. Blocking studies demonstrated that lytic activity was HLA class I restricted. Two-color flow cytometric analysis revealed that a significant proportion of CD8+ T cells was also CD56+, and analysis of intracellular IFN-gamma and IL-4 expression suggested a type 1 cytokine bias. The patient was treated by three infusions of tumor-specific T cells at 3- to 4-week intervals, and in vivo distribution of the T cells was followed by (111)In oxine labeling and serial gamma camera imaging. Tumor localization and accumulation of labeled lymphocytes was consistently detected at serial time points following each injection. However, deep infiltration of the large tumor mass by activated T cells was minimal, as evaluated in 3 dimensions by single photon emission computerized tomography (SPECT) imaging. Transient serum increases of the tumor marker lactate dehydrogenase (LDH), were detectable after each injection. Similar posttreatment elevations were seen for serum uric acid and potassium. Clinically, stabilization of the large liver metastasis was obtained during treatment. Collectively, these results indicate that tumor-specific CD8+ cytotoxic T-cell responses can be generated in patients with endometrial cancer, and suggest that T-cell immunotherapy may be of therapeutic value in patients harboring metastatic disease.
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PMID:Development and therapeutic effect of adoptively transferred T cells primed by tumor lysate-pulsed autologous dendritic cells in a patient with metastatic endometrial cancer. 1072 62

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that stimulates the proliferation and differentiation of bone marrow progenitors. Moreover, the presence and activity of GM-CSF and its receptor (GM-CSF-r) has been documented on tissues and cell lines of a non-hemopoietic origin. In this paper we studied the expression and putative role of GM-CSF and GM-CSF-r in endometrial cancer. The modulation of GM-CSF-r alpha-chain upon progesterone treatment suggests a role for GM-CSF and its receptor in the pathogenesis and development of endometrial cancer.
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PMID:Hormonal modulation of GM-CSF receptor alpha-chain in in vitro models of endometrial cancer. 1094 2

The purpose of this study was to compare the cytotoxic capacity of peritoneal macrophages (PM) and peripheral blood monocytes (PBM) from patients with ovarian, endometrial, and cervical cancers after in vitro activation with gamma interferon (IFN-gamma) and lipopolysaccharide (LPS). Peritoneal macrophages were obtained from ascites or peritoneal washings and peripheral blood monocytes via peripheral venipuncture from 58 patients: 17 with ovarian, 19 with endometrial, and 10 with cervical cancers. PBM and PM from 12 patients with nonmalignant gynecologic conditions served as controls. Cytotoxicity was assessed by the ability of PBM and PM to lyze Cr51-labeled Chang hepatoma cells. Activated peripheral blood monocytes of ovarian and endometrial cancer patients and peritoneal macrophages from ovarian cancer patients were significantly more cytotoxic than those from nonactivated controls. Activated PBM and PM from cervical cancer and PM from endometrial cancer did not demonstrate increased cytotoxicity compared to nonactivated controls. There was no significant correlation of the cytotoxicity with grade, stage, differentiation or age of the cancers. These in vitro data would suggest that ovarian cancer and possibly endometrial cancer should receive further evaluation and consideration of cytokine-based and/or adoptive cellular immunotherapy.
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PMID:Tumor cytotoxicity of peritoneal macrophages and peripheral blood monocytes from patients with ovarian, endometrial, and cervical cancer. 1124 Aug 6

In the present study, we analyzed the expression of a multifunctional cytokine, interleukin-8 (IL-8), in metastatic endometrial carcinoma cells. Our data demonstrate that human serous papillary endometrial adenocarcinoma (SPEC) and human endometrial adenocarcinoma (HEC) cells expressed steady-state IL-8-specific mRNA transcript and secreted IL-8 protein. The levels of IL-8 mRNA in SPEC-2 cells established from stage IV serous papillary adenocarcinoma were three-fold higher as compared to endometrial adenocarcinoma cells, HEC-1 A, established from stage IA endometrial cancer. Further, we observed higher levels of IL-8 mRNA and protein expression in the metastatic variants of SPEC-2 and HEC-1A cells as compared to the parent cell lines, demonstrating that IL-8 expression was associated with metastatic potential. Further, the treatment of endometrial carcinoma cells with inflammatory cytokines, IL-1beta and tumor necrosis factor-alpha (TNF-alpha), demonstrated that IL-1beta and TNF-alpha induced IL-8 expression in endometrial cancer cells. IL-1beta was a more potent inducer of IL-8 expression than TNF-alpha in our studies. These data demonstrate that constitutive and induced IL-8 expression in endometrial carcinoma cells might be an important regulatory mechanism of tumor growth and metastasis.
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PMID:Expression of interleukin-8 in human metastatic endometrial carcinoma cells and its regulation by inflammatory cytokines. 1128 34

Uterine serous papillary carcinoma is a highly aggressive variant of endometrial cancer histologically similar to high grade ovarian cancer. Unlike ovarian cancer, however, it is a chemoresistant disease from onset, with responses to combined cisplatinum-based chemotherapy in the order of 20% and an extremely poor prognosis. In this study, we demonstrate that tumour lysate-pulsed autologous dendritic cells can elicit a specific CD8(+) cytotoxic T lymphocyte response against autologous tumour target cells in three patients with uterine serous papillary cancer. CTL from patients 1 and 2 expressed strong cytolytic activity against autologous tumour cells, did not lyse autologous lymphoblasts or autologous EBV-transformed cell lines, and were variably cytotoxic against the NK-sensitive cell line K-562. Patient 3 CD8(+) T cells expressed a modest but reproducible cytotoxicity against autologous tumour cells only at the time of the first priming. Further priming attempts with PBL collected from patient 3 after tumour progression in the lumboaortic lymph nodes were unsuccessful. Cytotoxicity against autologous tumour cells could be significantly inhibited by anti-HLA class I (W6/32) and anti-LFA-1 MAbs. Highly cytotoxic CD8(+) T cells from patients 1 and 2 showed a heterogeneous CD56 expression while CD56 was not expressed by non-cytotoxic CD8(+) T cells from patient 3. Using two colour flow cytometric analysis of intracellular cytokine expression at the single cell level, a striking dominance of IFN-gamma expressors was detectable in CTL populations of patients 1 and 2 while in patient 3 a dominant population of CD8(+) T cells expressing IL-4 and IL-10 was consistently detected. Taken together, these data demonstrate that tumour lysate-pulsed DC can be an effective tool in inducing uterine serous papillary cancer-specific CD8(+) CTL able to kill autologous tumour cells in vitro. However, high levels of tumour specific tolerance in some patients may impose a significant barrier to therapeutic vaccination. These results may have important implications for the treatment in the adjuvant setting of uterine serous papillary cancer patients with active or adoptive immunotherapy.
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PMID:Induction of tumour-specific CD8(+) cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer. 1185 27

Granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]) is a powerful cytokine that is able to stimulate the generation of dendritic cells. Adjuvant treatment with continuous low-dose GM-CSF has been shown to prolong survival of stage III/IV melanoma patients. Data on continuous low-dose GM-CSF therapy in tumors other than prostate cancer are still lacking. This pilot trial was initiated in order to evaluate the efficacy and tolerability of continuous low-dose GM-CSF as salvage in various chemotherapy-refractory carcinomas. A total of 19 patients who had failed a median of 4 prior chemotherapies were included. Their malignancies included metastatic breast cancer, recurrent ovarian carcinoma, metastatic endometrial carcinoma, and recurrent squamous cell cancer of the cervix uteri. Continuous low-dose GM-CSF was delivered subcutaneously at a daily starting dose of 125 microg. GM-CSF was increased at 25-microg increments until a maximum of 250 microg was reached or when mild leukocytosis (10-20 g/L) was achieved, providing that the relative eosinophil count did not exceed 15%. Therapy was continued until progression or refusal by the patient. Toxicity was generally mild. Only one patient was withdrawn due to grade 3 fatigue. In three additional patients, temporary dose reduction was necessary because of grade 1 injection site reactions, which recovered spontaneously. Mild to moderate leukocytosis was obvious in 10 patients. Systemic hypersensitivity-like reactions did not occur and no patient required hospitalization for other life-threatening side effects. The objective response rate was 37%: 1 complete and 6 partial responses, 4 disease stabilizations, 8 progression of disease. Median response duration was 6 months. Notably, 6 of 7 responders but only 1 of 8 patients with disease progression developed leukocytosis during therapy. Therefore, we conclude that continuous low-dose GM-CSF has substantial activity in heavily pretreated patients with either metastatic breast cancer or female genital tract cancer. Achievement of mild leukocytosis seems to be a predictor of response.
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PMID:Continuous low-dose GM-CSF as salvage therapy in refractory recurrent breast or female genital tract carcinoma. 1593 97

Adiponectin, a pleiotropic cytokine, exerts its effects via the specific receptors AdipoR1 and AdipoR2. Whereas circulating adiponectin concentrations decrease in women with endometriosis and endometrial cancer, possible effects of adiponectin and the presence of the receptors in the endometrium have not been determined. In this study, we examined the expression of adiponectin receptors AdipoR1 and AdipoR2 in the human endometrium and assessed effects of adiponectin in endometrial cells. Expression of AdipoR1 and AdipoR2 in endometrial tissues was evaluated by real-time quantitative PCR, in situ hybridization, and Western blotting. The effects of adiponectin on phosphorylation of AMP-activated protein kinase, a regulator of energy homeostasis, in cultured endometrial stromal cells (ESCs) and epithelial cells (EECs) were studied by Western blotting. The effects of adiponectin on IL-1beta-induced secretion of IL-6, IL-8, and monocyte chemoattractant protein 1 from cultured ESCs were determined using specific ELISAs. The expression of AdipoR1 and AdipoR2 was detected in the endometrium. The expression of both genes was increased in the midluteal phase, the period of embryo implantation. In situ hybridization revealed that both AdipoR1 and AdipoR2 appeared to be equally expressed in the epithelial cells and in the stromal cells. Adiponectin increased phosphorylation of AMP-activated protein kinase in ESCs and EECs. Adiponectin decreased IL-1beta-induced secretion of IL-6, IL-8, and monocyte chemoattractant protein 1 from ESCs. These findings suggest that adiponectin exerts energy-homeostatic and antiinflammatory effects in the endometrium, and these effects might be relevant to pathological and physiological endometrium-related events such as implantation and endometriosis.
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PMID:Expression of adiponectin receptors and its possible implication in the human endometrium. 1660 Nov 38

Exposure to unopposed estrogen is a potent risk factor for developing human endometrial cancer. However, little is known about the transcriptional changes elicited by estrogens in endometrial carcinogenesis, in part, because of genetic and environmental heterogeneity of human tumors. We have begun to chart the expression signatures of endometrial tumors promoted with the synthetic estrogen, diethylstilbestrol (DES), in inbred mice. As expected, laser-capture-microdissected endometrial cancers from DES-treated mice displayed a large number of transcriptional changes when compared to uninvolved endometrial epithelium. Genes differentially expressed in carcinomas included cell adhesion and extracellular matrix genes (Decorin as 1 example), developmental genes (Hoxa11), and cytokine signaling genes (Socs3). The DES-promoted carcinomas appeared to fall into 2 distinct transcriptional classes, and expression of the tumor suppressor Pten was among the top discriminators between the 2 cancer groups. Pten was down regulated in the majority of the DES-promoted carcinomas, which is analogous to the frequent loss of PTEN expression in human endometrial tumors. Although preliminary, these observations suggest that the cancers that arise in the DES model bear similarities to human endometrial cancers and provide insights into transcriptional alterations that accompany estrogen-driven endometrial carcinogenesis.
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PMID:Transcriptional profiling endometrial carcinomas microdissected from DES-treated mice identifies changes in gene expression associated with estrogenic tumor promotion. 1680 99

Interleukin-6 (IL-6) is proinflammatory cytokine that produces multifunctional effects. It is also involved in the regulation of immune reactions, hematopoiesis and inflammatory state. Interleukin-6 has been shown to be associated with tumor progression including inhibition of cancer cells apoptosis and stimulation of angiogenesis. Anti-IL-6 therapy is a new strategy in the inflammatory autoimmune diseases and cancer. Clinical studies have shown elevated serum IL-6 concentrations in patients with endometrial cancer, non-small cell lung carcinoma, colorectal cancer, renal cell carcinoma, breast and ovarian cancer. Serum IL-6 levels correlate with tumor stage, and survival of patients. In this article we have focused on a role of IL-6 as a prognostic factor in several malignancies such as colorectal cancer, breast cancer, gastric cancer and pancreatic cancer.
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PMID:[Clinical significance of interleukin-6 (IL-6) as a prognostic factor of cancer disease]. 1803 Aug 75


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