Human endometrial carcinoma

When studied in a model of human endometrial carcinoma, such as EnCa 101 tumors in athymic mice, ICI 164384 not only showed no stimulatory activity on tumor progression but also blocked the tamoxifen-stimulated growth of the tumor (Gottardis et al. 1990). 

Gottardis MM, Ricchio ME, Satyaswaroop PG, Jordan VC (1990) Effect of steroidal and nonsteroidal antiestrogens on the growth of a tamoxifen-stimulated human endometrial carcinoma (EnCalOl) in athymic mice. Cancer Res 50 3189-3192... 

Yu Z, Shah DM. 2007. Curcumin down-regulates Ets-1 and Bcl-2 expression in human endometrial carcinoma HEC-l-A cells. Gynecol Oncol 106 541-548. 

The consequence of the partial agonistic activity of tamoxifen is that complete blockade of the action of estrogens cannot be achieved with tamoxifen (Wakeling, 1993) or the other compounds demonstrated to exert stimulatory effects, reversible with EM-652 on the proliferation of human breast cancer cells and alkaline phosphatase in human endometrial carcinoma cells. It is thus reasonable to expect that the availability of a pure antiestrogen, in addition to avoiding the risk of inducing endometrial carcinoma, should provide significant benefits over tamoxifen in the treatment of breast cancer. 

Varriale, L., Coppola, E., Quarto, M., Veneziani, B. M., and Palumbo, G. 2002, Molecular aspects of photodynamic therapy low energy pre-sensitization of hypericin-loaded human endometrial carcinoma cells enhances photo-tolerance, alters gene expression and affects the cell cycle. FEBS Letters, 512,287-290. 

Bonatz, G., Liittges, J., Hedderich, J., Inform, D., Jonat, W., Rudolph, P., and Parwaressch, R. 1999. Prognostic significance of a novel proliferation marker, Anti-Repp 86, for endometrial carcinoma A multivariate study. Human Pathol. 30 949-956. 

Hammerhead ribozymes that cleave the hTR RNA template have been shown to inhibit telomerase activity in human (66) and endometrial carcinomas (67,68) and in human melanoma cell extracts (69). Also, telomerase activity was down-regulated in vitro in endometrial carcinoma and human melanoma cells (68,69) however, no telomere shortening was observed in the human melanoma cells (69), and this approach to inhibition of telomerase activity has not been further investigated. 

Yokoyama Y. 2001. Hammerhead ri-bozymes to modulate telomerase activity of endometrial carcinoma cells. Human Cell 14 223-31... 

Specific forms of immunoreactivity of Purkinje cells have been discovered in human paraneoplastic conditions. Subacute cortical cerebellar degeneration in man may be associated with several types of carcinoma (see Vecht et al., 1991 for review). It has been most frequently observed in association with ovarian or endometrial carcinoma, but it also occurs as a rare sequal of small-celled bronchial carcinoma. It is generally characterized by a diffuse or patchy loss of Purkinje cells granule cells also can be affected (Brain et al., 1951 McDonald, 1961 Brain and Wilkinson, 1965 Schmid and Riede, 1974 Steven et al., 1982). 

Iwamori M, Sakayori M, Nozawa S, Yamamoto T, Yago M, Noguchi M, Nagai Y. Monoclonal antibody-defined antigen of human uterine endometrial carcinomas is Leb. J Biochem (Tokyo) 1989 105 718-722. 

Strick R, Ackermann S, Langbein M, Swiatek J, Schubert SW, HashemoUiossieini S, Koscheck T, Fasching PA, Schild RL, Beckmann MW, Strissel PL. Proliferation and cell-cell fusion of endometrial carcinoma are induced by the human endogenous retroviral sync)nin-l and regulated by TGF-beta. J Mol Med. 2007 85 23-38. 

The folate receptor a-isoform is another attractive target for tumor diagnosis and therapy, because it is physiologically expressed in only limited regions of the body and is overexpressed by a number of human tumors and, notably, by aU ovarian and endometrial carcinomas (164,165). For imaging purposes, several folate conjugates have been labeled with galUum isotopes... 

Usnic acid, the most extensively studied lichen metabolite since its first isolation in 1844, exhibited an antiproliferative effect on human leukemia cells (K562) and endometrial carcinoma (HEC-50) cells (Cardarelli et al. 1997 Ingolfsdottir 2002 Kristmundsdottir et al. 2002). Therefore, the usnic acid is one of the most interesting lichen metabolites for the study of their antitumor effects. The cytotoxicity, the in vitro antitumor effects, and the mechanism of action of usnic acid need to be investigated in greater detail in order to reach clinical trials and to allow further applications (Table 5.1). 

Miproxifene (TAT-59) is a prodrug of 4-hydroxy-tamoxifen that has been developed for tamoxifen-resistant carcinoma, but relatively little information has been published on this drug. Compared with tamoxifen, miproxifene inhibits estradiol-stimulated proliferation of MCF-7 cells at a threefold lower dose than that of tamoxifen, and of dimethyl-benzanthracene (DMBA)-induced rat mammary tumors at a dose tenfold lower than tamoxifen (Toko et al. 1990). In any event, in preclinical castrated rat models, it shows an endometrial stimulation activity that is similar to that of tamoxifen, which means it has limited potential use in the prevention or treatment of osteoporosis or cardiovascular disease (Shibata et al. 2000). Similarly, considering the preclinical findings of endometrial stimulation reported on GW5638 (Willson et al. 1997), it is likely that this new SERM belonging to the triphenylethylene family will be limited in clinical use to the treatment of advanced tamoxifen-resistant breast cancer once its efficacy is demonstrated in human clinical trials. 

Cancer. There is inconclusive evidence that 1,1-dichloroethane may be carcinogenic in humans. A significant positive dose-related trend was observed for the incidence of hemangiosarcomas and mammary adenocarcinomas in female rats, hepatocellular carcinoma in male mice, and endometrial stromal polyps in female mice. However, only the incidence of endometrial stromal polyps in female mice was significantly increased over the corresponding control animals. Limitations in this study (e.g., poor survival in both treated and control animals) preclude the consideration of these results as conclusive evidence of carcinogenicity (NC11977). 

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