Generalized lymphadenopathy due to metastases of keratinizing squamous cell carcinoma developed in a 68-year-old woman who was a carrier of human T-cell leukemia Type I (HTLV-I). On her 74th hospital day, she died of massive metastases of the superficial and deep-seated lymph nodes, thyroid, lungs, pleura, liver, spleen, pancreas, kidneys, and retroperitoneum. At autopsy, the primary tumor was found in the uterine cervix. The depth of stromal invasion was approximately 4.0 mm. Such an extensive dissemination usually does not occur in cervical cancer with this type of early stromal invasion. It is conceivable that the chronic HTLV-I infection compromised the immunosurveillance against cancer and accelerated progression of the disease in this patient.
The binding of steroidal alkylating agents to specific tissue component is necessary for the selective distribution of these compounds to their target tissues. The in vivo interaction of Estracyt or NSC-112259 with oestrogen receptors may play an important role in their action mechanism.Both Estracyt and NSC-112259 which were administrated in vivo, gradually reduced the binding of [3H] oestradiol to cytoplasmic oestrogen receptor in rabbit uteri. From this, it was suggested that a negligible amount of oestradiol was released from these compounds and that the oestradiol moiety was useful as a carrier for the nitrogen mustard moiety. And it appeared that the synthesis of a new receptor protein was inhibited by the nitrogen mustard moiety, thereby causing a decrease in the cytoplasmic oestrogen receptor level.Estracyt and oestradiol mustard (NSC-112259), a single and double nitrogen mustard ester of oestradiol-17/3 (Fig. 1), have been used for the treatment of prostatic and mammary tumours. The selective distribution of these compounds in tumours and the reduction of toxicity have been reported (Wall et al. 1969;Carroll et al. 1972;Szendröi et al. 1973;Müntzing et al. 1974).From the report by Kirdani et al. (1975) that Estracyt affects the uptake of labelled oestradiol-17/3 (Oe2) or oestriol in the rat or dog prostate, it is prob¬ able that the binding of nitrogen mustard ester of Oeo to specific Oeo receptors may be necessary for the selective distribution of these compounds in target tissues. Moreover, the interaction between these compounds and the oestrogen
A new assay method was developed to determine the quantity of oestrogen cytoplasmic receptors which are capable of associating with acceptor sites on chromatin. The quantity of oestrogen receptor complexes associated with chromatin is of paramount importance in the mechanism of action of oestrogen. This method is based on the specific binding properties of oestrogen to the receptor and on the binding of the complex to chromatin. Cytosol was pre-incubated with [3H] oestradiol-17β ([3H]Oe2) to form a complex, and further incubated with a constant amount of chromatin. After this the quantity of [3H]Oe2 cytosol receptor complexes specifically associated with the chromatin was determined. The binding activity of the chromatin to the [3H]Oe2 receptor complex was stable for at least six months in 0.15 m NaCl at −20°C. This method enables us to determine the quantity of the biologically active oestrogen receptors more specifically than with other methods.
Biological actions of progesterone are correlated with the ability of the progesterone receptor(PR) to bind to nuclear acceptor sites. Measurement of not only the presence of PR in a tissue but also the amount of that receptor which is able to bind to nuclear acceptor sites is important in predicting tissue response to progesterone. Activation of PR is required for effective binding to chromatin. Since the dextrancoated charcoal assay does not distinguish between an activated and a non-activated receptor, a rapid, relatively simple assay is needed which can account for an activated form of PR. Therefore, ATP-Sepharose column chromatography was tested to identify an activated form of PR. PR in crude uterine cytosol from estrogen-primed immature rabbits was labeled with 3H-progesterone at 0 degree C. The labeled PR was then incubated at 4 degrees C with uterine chromatin from ovariectomized mature rabbits. The freshly prepared PR had little capacity to bind to the chromatin. After activation manipulation at low temperature, low ionic strength and neutral pH, this PR was able to bind to chromatin approximately fourfold more than that activated by heating at 25 degrees C. The affinity of the activated and the non-activated PR for ATP was evaluated on ATP-Sepharose column chromatography. The activated PR was selectively adsorbed onto columns of ATP-Sepharose, and the binding ability of the activated PR to ATP paralleled that of the rabbit uterine chromatin. These results suggest that ATP-Sepharose column chromatography could be useful to identify an activated PR as a substitute for chromatin binding assay.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.