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A Segaloff

Publications and source records attributed to A Segaloff.

At least 19 recordsLinked to original sources
PubMed1990

Structure of 3-hydroxy-1-methyl-1,3,5(10)-estratriene-11,17-dione.

C19H22O3, Mr = 298.39, orthorhombic, P2(1)2(1)2(1), a = 11.332 (6), b = 14.596 (7), c = 9.567 (4) A, V = 1582.6 (5) A3, Z = 4, D chi = 1.252 Mg m-3, lambda(Mo K alpha) = 0.71073 A, mu = 0.0778 mm-1, F(000) = 640, T = 273 K, R = 0.067 for 1762 unique observed reflections where F greater than 2 sigma (F). The structure was studied to observe the effect of 1-methyl and 11-keto substitution. The 3-hydroxyl is hydrogen bonded to O11 at 2.76 A. The B ring is in a 7 alpha, 8 beta half-chair conformation. The molecule twists about the C(9)--C(10) bond to relieve the steric interaction between the 1-methyl and 11-keto groups. The C1--C10--C9--C11 torsion angle is 55 vs 33.5 degrees, the average of 38 estradiol analogue structures.

Estrone↗
PubMed1985

An evaluation of the effect of vincristine added to cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone in advanced breast cancer.

A multi-institutional randomized clinical trial was carried out to evaluate the effect of vincristine (V) added to cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) for the treatment of metastatic breast cancer. There were 427 patients entered into the study and randomly assigned to one of the two treatments, i.e. the five drug therapy CMFPV or the four drug therapy CMFP. The differences in patient survival and tumor response between the two treatment groups were not statistically significant. The data were also analyzed using multivariate procedures to determine those factors ascertained at entry into the study which were predictors of survival or predictors of response to therapy. The one factor that predicted both response and survival was performance status. An additional important predictor of survival was sites of metastatic involvement. Other significant predictors of response were menopausal age, BUN, and hematocrit.

Adult↗
PubMed1984

Structure-activity relationships of estrogens: effects of esterification of the 11 beta-hydroxyl group.

Fourteen esters (formate, acetate, propionate, butyrate, hexanoate, heptanoate, and benzoate) located at C-11 of 11 beta-hydroxyesterone and 11 beta-hydroxyestradiol-17 beta were synthesized and evaluated for uterotropic and gonadotropin release inhibition in rats, as well as their ability to displace (3H) estradiol-17 beta from the rat uterine cytosolic estrogen receptor. The most potent uterotropic agent was 11 beta-formoxyestrone which was 1,625 or 2,500 times as active as 11 beta-hydroxyesterone in the uterotropic or gonadotropin release inhibition assay, respectively. 11 beta-Formoxyestrone was 7.5 times as uterotropic as estradiol-17 beta and equal to estradiol-17 beta in inhibiting gonadotropin release. However, the most potent inhibitor of gonadotropin release was 11 beta-acetoxy-estradiol-17 beta which had 133% of the activity of estradiol-17 beta, although it had only 38% of the activity of estradiol-17 beta in the uterotropic assay. Esters larger than the acetoxy group showed sharply decreased activities in either assay. Despite the high estrogenic potency of the 11-formates or 11-acetates, they were rather weak (6% to 35% as active as estradiol-17 beta) in displacing (3H) estradiol-17 beta from the rat uterine cytosolic estrogen receptor.

Animals↗
PubMed1983

Structure-activity relationships of estrogens. Effects of 14-dehydrogenation and axial methyl groups at C-7, C-9 and C-11.

Thirty compounds were evaluated in the rat for uterotropic effects, inhibition of gonadotropin release, and competitive displacement of (3H) estradiol-17 beta from uterine cytosolic preparations. 7 alpha-Methylestradiol-17 beta was 150% as active as estradiol-17 beta as an uterotropic agent. Estradiol-17 beta was the most active inhibitor of gonadotropin release. 11 beta-Methylestradiol-17 beta had 124% of the activity of estradiol-17 beta in displacing (3H) estradiol-17 beta from the "estrogen receptor." The 9 alpha-methyl group considerably decreased the potency of estrogens in any of the three assays. The 14-dehydro modification was advantageous only in the estradiol-17 beta 3-methyl ether series. Uterotropic activities and inhibition of gonadotropin release did not parallel. The best compound for inhibiting gonadotropin release, as compared to uterotropic activity, was estrone. The "estrogen receptor" assay data correlated fairly well with uterotropic assay data, but only for compounds having free 3-hydroxyl groups; even so, some exceptions were noted.

Animals↗
PubMed1983

Structure-activity relationships of 9 beta-estrogens.

The 9 beta isomers of estradiol-17 beta, estradiol-17 a estrone and 17-ethinylestradiol-17 beta were synthesized and compared with their 9a-counterparts in the rat uterine cytosol estrogen receptor, uterotropic, and gonadotropin release inhibition assays. Except for 17-ethinyl-9 beta-estradiol-17 beta which was as active as its 9a isomer in the uterotropic assay, none of the 9 beta estrogens exhibited any biological activity which was equal to or greater than their 9a counterparts. For examples, 9 beta-estradiol-17 beta was 1/10 as active as estradiol-17 beta, and 9 beta-estrone was 1/4 as active as estrone in the uterotropic assay.

Animals↗
PubMed1981

Structure-activity relationships of four 11-hydroxyestrones isomeric at the C-9 and C-11 positions.

The synthesis of 11 alpha-hydroxyestrone, 11 alpha-hydroxy-9 beta-estrone, and 11 beta-hydroxy-9 beta-estrone are presented. The reduction of 11-keto-9 beta-estrone 17-ethyleneketal by sodium in ethanol or sodium borohydride resulted in 11-hydroxy-9 beta-estrones. The 11-hydroxyl group configurations were opposite to expectations: sodium in boiling ethanol afforded the axial 11 beta-hydroxy-9 beta-estrone, while sodium borohydride in boiling tetrahydrofuran gave the equatorial 11 alpha-hydroxy-9 beta-estrone. In immature rat uterotropic bioassays using subcutaneous injections, 11 alpha-hydroxyestrone was 2 times as active as 11 alpha-hydroxy-9 beta-estrone, and 11 beta-hydroxyestrone was 10 times as active as 11 beta-hydroxy-9 beta-estrone.

Animals↗
PubMed1980

Current practices of estrogen receptor determination.

Questionnaires completed by 133 oncology investigators provided information about the use of estrogen receptor determination in breast cancer. All investigators reported measuring estrogen receptor levels in all primary breast cancers and often in metastatic cancers as well. Nearly half of these determinations are done in the institutions' own laboratories, and the rest elsewhere. Most commonly used in the dextran-coated charcoal procedure. Investigators generally classify assay results simply as positive or negative, using arbitrary levels for the decision. In one third of the institutions, this determination is used as the sole criterion for the use of hormonal therapy. A sharp difference of opinion exists regarding whether premenopausal cancer patients should castrated even if breast tumor receptor levels are negative.

Breast Neoplasms↗
PubMed1980

Identification of breast cancer patients with high risk of early recurrence after radical mastectomy: III. Steroid hormones measured in urine.

The relationship of the levels of selected urinary steroid metabolites to breast cancer recurrence after radical mastectomy was studied. An analysis of variance of the steroid measurements suggested that the measurements standardized to per gram of creatinine were the appropriate measure to use in exploring these relationships. No significant associations were found for premenopausal patients; however, for postmenopausal patients, low levels of total 17-ketosteroids were associated with a reduced two-year recurrence-free rate whereas low and high levels of OHA and high levels of total estrogens were associated a relatively low high two-year recurrence-free rate. Because of the large number of significance tests performed and the lack of consistent patterns, it is questionable whether the observed associations are of any importance. Including these steroid quantities in a multivariate regression model along with previously determined clinical prognostic factors indicated that the steroid determinations were the least important variables and did not make a significant contribution to the fit of the model.

17-Ketosteroids↗
PubMed1980

Steroid structure and function VII. remarkable estrogenicity of 3-hydroxy-9 beta-estra-1,3,5(10)-triene-11,17-dione.

Remarkably high estrogenic activity was observed for 3-hydroxy-9 beta-estra-1,3,5(10)-triene-11,17-dione despite its unusual bent conformation. The 9 alpha epimer of this compound has markedly less activity despite the fact that its overall shape is nearly identical to that of estrone. The potency of these compounds in enhancing uterine weight in Fischer rats and reducing ovarian weight in parabiosed rats was compared with that of estrone, and the structures were unambiguously identified by X-ray crystallographic study. The results underscore the importance of the phenolic ring A to estrogenic activity, and suggest a tolerance of the putative estrogenic receptor to flexibility in overall molecular shape.

Animals↗
PubMed1979

The in vivo metabolism of 7 beta, 17-dimethyltestosterone-6,7-3H.

7 beta, 17-Dimethyltestosterone (17 beta-hydroxy-7 beta, 17-dimethyl-4-androsten-3-one) (I) was given to three subjects in oral doses of 400 mg per day for ten days. The initial dose contained the steroid tritiated in the 6 and 7 positions. Plasma levels and urinary excretion patterns were followed in all three subjects. Isolations were done on the urine, plasma, and stools of one patient. From the urine 7 beta, 17-dimethyl- 5 alpha-androstane-3 beta,17 beta-diol (VI) was isolated from the nonhydrolyzed fractions. Unchanged (I), 7 beta,17-dimethyl-5 beta-androstane-3 alpha,17 beta-diol (III) and 7 beta, 17-dimethyl-5 beta-androstane-3 beta,17 beta-diol (IV) were isolated from the nonhydrolyzed and enzyme-hydrolyzed fractions. 7 beta,17-dimethyl-5 alpha-androstane-3 alpha,17 beta-diol (V) was isolated from the enzymatic fractions. From the stools were isolated unchanged (I), (III), (IV), (V), and (VI). Unchanged (I) and its 5 alpha-dihydro derivative (17 beta-hydroxy-7 beta,17-dimethyl-5 alpha-androstan-3-one) (II) were identified in the plasma. The total recovery of radioactivity in the one patient on whom the isolations were done was 57%; 40% from the urine and 17% from the stools.

Adult↗
PubMed1979

The pros and cons of estrogen therapy.

Hormone deficiency is the most obvious indication for its use, but estrogen therapy is sometimes beneficial in other conditions. Since rather serious complications are now being associated with such therapy, however, a decision to use estrogen calls for caution in determining the dose and the duration of administration.

Adenoma↗
PubMed1978

Relaxin.

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Amino Acid Sequence↗