Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With flow-cytometry we tested whether or not interferon can induce surface expression of HLA-ABC antigen on cell lines derived from various gynecologic cancers. The tumor cell lines used were Hela S3 derived from cervical cancer, OVK-18 derived from ovarian cancer, HHUA derived from endometrial cancer, SCH, JaR and BeWo derived from choriocarcinoma. 1000 IU/ml of interferon-gamma induced HLA-ABC antigen expression on Hela S3, OVK-18 and SCH but not on BeWo. HLA-ABC antigen was expressed on neither the surface of HHUA or JaR nor was its appearance induced by interferon. The clinical application of interferon may be effective in killing some tumors, taking advantage of the increased expression of HLA antigen.
 ...
PMID:Enhanced expression of HLA antigens on gynecologic cancer cells by interferon-gamma. 309 Jan 75

Methotrexate (MTX) was covalently bound to rabbit antibodies (IgG) against hCG and placental alkaline phosphatase (PLALP) by two different methods. By carbodiimide method, 16.9 mols of MTX could be coupled to one mol of IgG, but the antibody activity was completely lost. Whereas, 2.6-3.4 mols of MTX were bound to one mol of IgG and a quarter of original antibody activity was preserved by dextran bridge method. Choriocarcinoma cells BeWo and SCH were exposed to the IgG-MTX conjugates prepared by the latter method for 30 minutes, and the cell growth was investigated. To BeWo, which produces much hCG and less PLALP, anti hCG-IgG-MTX showed a considerable growth inhibition compared to the control groups (p less than 0.05). No effect was observed with anti PLALP-IgG-MTX, nonimmunized IgG-MTX, free MTX and anti hCG-IgG. In contrast, to SCH, which produces much PLALP and less hCG, anti PLALP-IgG-MTX exhibited considerable inhibition (p less than 0.05), whereas anti hCG-IgG-MTX showed no inhibition. Neither anti hCG-IgG-MTX nor anti PLALP-IgG-MTX showed any effect to the endometrial carcinoma cell HEC50B. We concluded that MTX bound to anti hCG-IgG and anti PLALP-IgG have specific growth inhibition effects to the choriocarcinoma cells in vitro, and suggested the possibility of specific immunochemotherapy of this disease.
 ...
PMID:[Specific effects of methotrexate bound to the antibodies against hCG and placental alkaline phosphatase to the cultured human choriocarcinoma cells]. 668 30

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.
 ...
PMID:Inhibitory effect of angiogenesis inhibitor TNP-470 on tumor growth and metastasis of human cell lines in vitro and in vivo. 768 19

Breast cancer is the most frequent cancer in women while it is the second cause of cancer death. Estrogens are well recognized to play the predominant role in breast cancer development and growth and much efforts have been devoted to the blockade of estrogen formation and action. The most widely used therapy of breast cancer which has shown benefits at all stages of the disease is the use of the antiestrogen Tamoxifen. This compound, however, possesses mixed agonist and antagonist activity and major efforts have been devoted to the development of compounds having pure antiestrogenic activity in the mammary gland and endometrium. Such a compound would avoid the problem of stimulation of the endometrium and the risk of endometrial carcinoma. We have thus synthesized an orally active non-steroidal antiestrogen, EM-652 (SCH 57068) and the prodrug EM-800 (SCH57050) which are the most potent of the known antiestrogens. EM-652 is the compound having the highest affinity for the estrogen receptor, including estradiol. It has higher affinity for the ER than ICI 182780, hydroxytamoxifen, raloxifene, droloxifene and hydroxytoremifene. EM-652 has the most potent inhibitory activity on both ER alpha and ER beta compared to any of the other antiestrogens tested. An important aspect of EM-652 is that it inhibits both the AF1 and AF2 functions of both ER alpha and ER beta while the inhibitory action of hydroxytamoxifen is limited to AF2, the ligand-dependent function of the estrogen receptors. AF1 activity is constitutive, ligand-independent and is responsible for mediation of the activity of growth factors and of the ras oncogene and MAP-kinase pathway. EM-652 inhibits Ras-induced transcriptional activity of ER alpha and ER beta and blocks SRC-1-stimulated activity of the two receptors. EM-652 was also found to block the recruitment of SRC-1 at AF1 of ER beta, this ligand-independent activation of AF1 being closely related to phosphorylation of the steroid receptors by protein kinase. Most importantly, the antiestrogen hydroxytamoxifen has no inhibitory effect on the SRC-1-induced ER beta activity while the pure antiestrogen EM-652 completely abolishes this effect, thus strengthening the need to use pure antiestrogens in breast cancer therapy in order to control all known aspects of ER-regulated gene expression. In fact, the absence of blockade of AF2 by hydroxytamoxifen could explain why the benefits of tamoxifen observed up to 5 years become negative at longer time intervals and why resistance develops to tamoxifen. EM-800, the prodrug of EM-652, has been shown to prevent the development of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat, a well-recognized model of human breast cancer. It is of interest that the addition of dehydroepiandrosterone, a precursor of androgens, to EM-800, led to complete inhibition of tumor development in this model. Not only the development, but also the growth of established DMBA-induced mammary carcinoma was inhibited by treatment with EM-800. An inhibitory effect was also observed when medroxyprogesterone was added to treatment with EM-800. Uterine size was reduced to castration levels in the groups of animals treated with EM-800. An almost complete disappearance of estrogen receptors was observed in the uterus, vaginum and tumors in nude mice treated with EM-800. EM-652 was the most potent antiestrogen to inhibit the growth of human breast cancer ZR-75-1, MCF-7 and T-47D cells in vitro when compared with ICI 182780, ICI 164384, hydroxytamoxifen, and droloxifene. Moreover, EM-652 and EM-800 have no stimulatory effect on the basal levels of cell proliferation in the absence of E2 while hydroxytamoxifen and droloxifene had a stimulatory effect on the basal growth of T-47D and ZR-75-1 cells. EM-652 was also the most potent inhibitor of the percentage of cycling cancer cells. (ABSTRACT TRUNCATED)
 ...
PMID:EM-652 (SCH 57068), a third generation SERM acting as pure antiestrogen in the mammary gland and endometrium. 1041 81