Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The binding of 3H-R 1881 to cytosol prepared from benign and malignant prostatic neoplasms has been investigated. We have demonstrated that high affinity binding of 3H-R 1881 is present in cytosol preparations of benign prostatic hyperplasia, in specimens of prostatic cancer obtained from patients prior to hormonal therapy and in carcinoma of the prostate metastatic to lymph nodes. In addition, high affinity binding was present in all specimens of prostatic cancer from patients who had objective evidence of progressive metastatic disease after an initial response to hormonal therapy. Until greater numbers of patients have been studied the significance of these findings can only be speculative. Because the binding of 3H-R 1881 may measure androgen and progesterone receptors future investigations must include careful steroid specificity studies. Finally, because steroidal hormones exert their major influence within the nucleus of target tissues the measurement of nuclear receptor content may provide a more accurate means to predict the hormonal responsiveness of prostatic cancer.
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PMID:The binding of a potent synthetic androgen--methyltrienolone (R 1881)--to cytosol preparations of human prostatic cancer. 8 28

Androphilic protein in prostatic cancer was histochemically observed with dihydrotestosterone (DHT), R 1881, and mibolerone as ligands. Cancer cells were equally stained with fluorescent R 1881 and mibolerone, and this fluorescence seems to be made up of both the androgen receptor and progestin-binding protein. The staining with fluorescent DHT was weak. Sixty-two Stage D2 prostatic cancer patients were examined with histochemical androphilic protein, and they then received endocrine therapy. The presence of fluorescence of R 1881 was not correlated with grade, but a relationship between the presence of fluorescence and the response to endocrine therapy was noticed 6 months after the start of treatment. Moreover, fluorescence-positive patients showed better survival than fluorescence-negative patients. An examination with fluorescent DHT revealed a similar tendency to that of R 1881, but the frequency of positive fluorescence was lower, indicating that R 1881 is a suitable ligand in this type of study.
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PMID:Androphilic protein studied histochemically in stage D2 prostatic cancer. 244 48

The responses, in terms of cell proliferation and c-myc messenger RNA content, of human prostate cancer cells to androgen-receptor ligands were investigated. Experiments were performed with three types of cells (LNCaP, R2 and MOP) and three compounds (the androgen R 1881 and two anti-androgens: cyproterone acetate, CYPA, and RU 56187). MOP cells were established in the laboratory and the effects of RU 56187 had not been studied in culture. In terms of proliferation, LNCaP was stimulated by the three compounds, R2 was inhibited by R 1881 and RU 56187 but was stimulated by CYPA while MOP was inhibited by the three compounds. In the three types of cells, c-myc messenger RNAs were down regulated by R 1881 and RU 56187 but not by CYPA. The conclusions are: (1) the sets of responses of cell proliferation to three androgen-receptor ligands are cell specific; (2) the control of c-myc messenger RNA by R 1881 and RU 56187 may be related to the inhibition of cell proliferation by these compounds but not to their stimulatory effect on cell proliferation; (3) if prostate tumor cells would respond in vivo to androgens and antiandrogens like in culture, patients with prostate cancer could take benefits of reversible medical castration and sequential prescription of various antiandrogens.
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PMID:Control of the proliferation of prostate cancer cells by an androgen and two antiandrogens. Cell specific sets of responses. 974 20

Here are described the effects of androgens, and other molecules known to bind to androgen receptors (AR), on MOP cells established from the human prostate cancer cell line LNCaP. MOP cells contained AR: 100000 binding sites/cell, K(D) for 5alpha dihydrotestosterone (DHT) 0.5 nM, size 110 kDa. The AR gene has the same repetition polymorphism in exon 1 and the T876A mutation in exon 8 as LNCaP. The proliferation of MOP cells in culture was repressed by the synthetic androgen 17beta-hydroxy-17-methyl-estra-4,9,11-trien-3-one (R 1881), the antiandrogen cyproterone acetate (CYPA), estradiol (E2), progesterone and the synthetic progestin promegestone: 17,21 dimethyl-19 nor-4,9 pregnandiene-3,20 dione (R 5020). The number of cells recovered after 7 days decreased to approximately 40% of controls. ED(70)s ranged between 50 pM for R 1881 to 50 nM for E2 and CYPA. Treatment with R 1881 decreased [3H]thymidine incorporation into DNA and increased dramatically the doubling time. R 1881, CYPA and E2 blocked the cell cycle between G1 and S phases and they induced apototosis as demonstrated by the increase of blebs on the plasma membrane, nuclear fragmentation, TdT-mediated dUTP nick end-labeling (TUNEL)-positive cells and internucleosomal DNA breaks. In athymic nude mice, testosterone enanthate prevented the growth of MOP tumors and, when tumors did develop, brought about regression. However, the tumors did not regress completely and finally escaped treatment. In conclusion, a variant of the LNCaP cell line has been established. With these cells it was possible to confirm that androgens paradoxically repress the growth of some prostate cancer cells both in culture and in vivo. In addition it is demonstrated in culture but not in vivo, for the first time to the authors' knowledge, that a synthetic androgen is able to induce apoptosis of cells established from human prostate carcinoma.
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PMID:Inhibition of growth and induction of apoptosis by androgens of a variant of LNCaP cell line. 1107 Mar 52

The synthesis and preliminary evaluation of a doxorubicin-formaldehyde conjugate tethered to the nonsteroidal antiandrogen, cyanonilutamide (RU 56279), for the treatment of prostate cancer are reported. The relative ability of the targeting group to bind to the human androgen receptor was studied as a function of tether. The tether served to attach the antiandrogen to the doxorubicin-formaldehyde conjugate via an N-Mannich base of a salicylamide derivative. The salicylamide was selected to serve as a trigger release mechanism to separate the doxorubicin-formaldehyde conjugate from the targeting group after it has bound to the androgen receptor. The remaining part of the tether consisted of a linear group that spanned from the 5-position of the salicylamide to the 3'-position of cyanonilutamide. The structures explored for the linear region of the tether were derivatives of di(ethylene glycol), tri(ethylene glycol), N,N'-disubstituted-piperazine, and 2-butyne-1,4-diol. Relative binding affinity of the tethers bound to the targeting group for human androgen receptor were measured using a (3)H-Mibolerone competition assay and varied from 18% of nilutamide binding for the butynediol-based linear region to less than 1% for one of the piperazine derivatives. The complete targeted drug with the butynediol-based linear region has a relative binding affinity of 10%. This relative binding affinity is encouraging in light of the cocrystal structure of human androgen receptor ligand binding domain bound to the steroid Metribolone which predicts very limited space for a tether connecting the antiandrogen on the inside to the cytotoxin on the outside.
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PMID:Rational design and synthesis of androgen receptor-targeted nonsteroidal anti-androgen ligands for the tumor-specific delivery of a doxorubicin-formaldehyde conjugate. 1461 28