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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant neoplasms of endocrine tissues represent almost half of the cancers diagnosed clinically in the United States, and many of these respond to hormonal therapies. Estrogen-induced testicular Leydig cell tumors in the mouse would seem to represent a realistic model for the laboratory investigation of this significant group of cancers. Data accumulated over the past few years clearly show that the Leydig cell is a target tissue for estrogens. Administering large doses of estrogen results in a reduction of enzymes converting progesterone to testosterone and induces a transient, but quantitatively very significant, synthesis of DNA in the Leydig cells of tumor-susceptible strains of mice. Neither of these actions of estrogen is mediated via the hypophysis. It has been demonstrated that the Leydig cells have specific protein receptors in their cytoplasm that bind estrogens and transport them to the nucleus where they are also bound. The genetic composition of the Leydig cells themselves is extremely important for the development of tumors. An adequately functioning pituitary gland is also essential for tumor formation. Confining the testes to the abdomen results in enzyme changes similar to those produced by estrogen administration and significantly augments the development of Leydig cell tumors. Once tumors form they frequently are dependent for their continued growth on estrogenic stimulation and/or on a functioning hypothysis. Regressed tumors may remain dormant for many months only to resume progressive growth when placed in and adequate hormone environment.
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PMID:Estrogen-induced Leydig cell tumor in the mouse: a model system for the study of carcinogenesis and hormone dependency. 1 51

Cells of sarcoma 180 and of Ehrlich's carcinoma were maintained by serial transplantation in male and female Swiss mice. Either estrogen, progesterone, or testosterone were injected im at doses of 1 mg/mouse. Ascitic fluid was aspirated at intervals of 1, 3, 6, 24, and 48 hours following hormone injections. Enzyme activities were analyzed by subjective grading according to the intensity of staining reaction. Estrogen produced enhancement of alkaline phosphatase activity in both types of cells in both sexes of mice. Progesterone produced increased alkaline phosphatase activity in both types of cells from female hosts but an inhibitory effect in male hosts' cells. Testosterone produced no change in enzyme activity in tumor cells of female hosts but in male hosts it inhibited enzyme activity of sarcoma 180 cells and activated activity in carcinoma cells. The effect of all 3 hormones on acid phosphatase activity was activation. With adenosine triphosphatase, estrogen stimulated the activity in both types of tumor in both sexes. Progesterone stimulated cells from male hosts with little or no effect on cells from female hosts. This enzyme was resistant to testosterone. Succinate dehydrogenase activity under similar conditions was different. Estrogen reduced this activity and progesterone produced some inhibition of activity. Testosterone inhibited the sarcoma cells but had no effect on carcinoma cells of either sex. Others have shown that sex hormones affect the enzyme activities beyond the target tissues, particularly in the liver, kidney, and pancreas. Different responses of the enzymes seemed to depend on the endogenous hormonal status of the mice.
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PMID:Enzymatic responses of transplanted tumour cells towards estrogen, progesterone and testosterone. 13 8

The metabolism of dehydroepiandrosterone and testosterone by human mammary tumor was investigated. Estrogen synthesis from dehydroepiandrosterone was observed in 9 of 10 estrogen-receptor-negative tumors and only in 2 of 8 receptor-positive tumors (p less than 0.025). Conversion of testosterone to estrogens was observed in 7 of 8 receptor-negative and 2 of 7 receptor-positive tumors. Tumors which are capable of transforming dehydroepiandrosterone to estrogens were also able to aromatize testosterone suggesting that the presence of the aromatase enzyme is inherent to certain tumor cells. No estrogen formation was detected by the mitochondrial-microsomal fraction of normal breast cells while fractions from both fat cell and tumor cell showed estrogen synthesis. Estrogen formation by tumor cell fraction ranged from 5 to 190 times that observed for fat cells. The physiological significance of these results in the neoplastic tissue and its relationship to hormone dependence are discussed.
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PMID:Aromatization of androgens by human breast cancer. 15 71

Estrogen-dependent renal adenocarcinoma and normal proximal tubules of the hamster kidney exhibit junctional differences. Although both cell types possess gap junctions, the neoplastic cells have in addition a cytoplasmic configuration of gap-junctional membrane (annular nexuses) not found in the kidneys of untreated or estrogenized hamsters or in the nontumorous kidney adjacent to the adenocarcinoma. The presence of these unique structures in the renal tumor and its abdominal metastases was demonstrated by electron microscopy with the use of lanthanum impregnation. A possible correlation between these structures and the estrogen sensitivity of the kidney neoplasm is made.
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PMID:Junctional specialization in estrogen-induced renal adenocarcinomas of the golden hamster. 16 65

Estrogen and prolactin receptor concentrations were measured in 24 carcinogen-induced rat mammary tumors and correlated with the tumor response to host ovariectomy or hypophysectomy. It was found that essentially all of the tumors contained some specific estrogen receptor, and all but three contained prolactin receptor. The values for each receptor comprised a continuum from very low to relatively high concentrations, suggesting that previous considerations of hormone dependence on the basis of presence or absence of hormone receptors may be oversimplified. The concentration of each receptor tended to be lower in the hormone-independent than in the hormone-dependent tumors, but there were a number of hormone-independent tumors with higher receptor levels than some of the hormone-dependent tumors had. A better correlation of tumor response to endocrine ablation resulted from a combination of the 2 receptor levels than from either receptor concentration alone. These results suggest that there is a complex relationship between mammary tumor response to endocrine ablatin and levels of estrogen and prolactin receptors and that some tumors may be dependent upon 1 or both of these hormones for growth.
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PMID:Estrogen and prolactin receptor concentrations in rat mammary tumors and response to endocrine ablation. 17 95

Estrogen-binding parameters of cytoplasmic and nuclear receptors in an established rat endometrial cell line and tumor were investigated. The equilibrium dissociation constants (Kd) and the Rate constants for the receptor-estradiol interaction in these cells and tumors were similar to those of the cytosol receptor in the rat uterus. A mean Kd of 3 X 10 less than -10 greater than M with a rate of association (ka) of 3 X 10 less than 5 greater than M second and a rate of dissociation (kd) of 1.5 X 10 less than -5 greater than/second were obtained for nuclear and cytosol receptors for both tumors and cells. For uterine cytosol a Kd of 8 x 10 less than -10 greater than M, ka of 2.8 X 10 less than 5 greater than /M/ second and kd of 1 X 10 less than -5 greater than/second were obtained. No differences were seen in equilibrium and kinetic parameters for estradiol-17beta binding between the nuclear and cytosol receptors of tumors and cells but an apparent difference in the relative affinities ofnuclear and cytosol receptors for estrone was detected. These results suggest that the binding site in nuclear receptors may have been modified. Implications of this observation are being considered with regard to receptor translocation and the mechamism of action of sex hormones.
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PMID:Estrogen-binding parameters of cytoplasmic and nuclear receptors in an established rat endometrial cell line and tumor. 17 77

Regulation of the lactogen specific binding sites of rat liver was studied in several different high lactogen states. The specific binding of [125I]iodo-hGH was determined as a measure of these sites. Hypophysectomy of pregnant rats produced a much smaller decrease in hepatic binding of [125I]iodo-hGH than was seen in nonpregnant females. Three different prolactin secreting tumors (MtT/F4, MtT/F45, MtT/W5) produced greatly elevated levels of both rPRL and hepatic binding of [125I]iodo-hGH in both male and female rats. The increased binding reflected an increase in the concentration of lactogen specific membrane binding sites. There was no change in the apparent affinity of binding. Hypophysectomy of tumor-bearing rats was not followed by a decrease in the concentration of hepatic sites. Pituitary transplants beneath the kidney capsules of hypophysectomized (hypox) rats produced elevated rPRL levels and increased [125I]iod-GH specific binding to hepatic membranes. The elevation of serum rPRL preceded the increase in hepatic binding. There was a direct correlation between rPRL levels attained by 8 days after implantation and the level of hepatic binding. Estrogen treatment did not alter this correlation. Hormonal replacement with prolactin in combination with various hormones failed to induce the lactogen specific hepatic sites in estrogen treated hypox males, and did not prevent the marked decrease in hepatic binding observed in females following hypophysectomy. It is suggested that chronic elevation of prolactin plays a role in inducing lactogen specific binding sites in rat liver. Estrogen's inductive action seems to be largely effected at the pituitary level.
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PMID:Regulation of lactogen specific binding sites in rat liver: studies on the role of lactogens and estrogen. 18 50

Daily sc injections of 8 mg N6, O2'-dibutyryl 3',5'-cyclic AMP (DBcAMP) beginning 1 day after tumor implantation significantly increased the growth rate of R32230AC rat mammary adenocarcinomas, which nearly doubled in in situ volume by day 40 compared to similarly implanted tumors in saline-injected controls. Weights of excised tumors, intact, drained, and dried all increased approximately 80%, which suggested that the increase in tumor size was not due to accumulation of secreted fluid or tissue water. Injections of 17beta-estradiol valerate (0.1 mg/wk) from day 1 or of DBcAMP from day 22 resulted in insignificant changes in growth--28% and 35% increases in tumor volume and a 5% decrease and an 18% increase, respectively, in drained wet weight. Electron microscopic examination revealed that estrogen and DBcAMP caused differentiation of the tumor cells into two different states: Estrogen-treated tumors resembled lactating mammary glands; they contained large lipid droplets, organized rough endoplasmic reticulum, and vesicles containing electron dense granules resembling protein. DBcAMP-treated tumor cells were marked by a proliferation of the Golgi complex and numerous vesicles containing fine granular material.
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PMID:Enhancement of R3230AC rat mammary tumor growth and cellular differentiation by dibutyryl cyclic adenosine monophosphate. 19 Apr 20

The activity of estrogen 16alpha-hydroxylase was measured for nine Morris hepatomas of different growth rates and host livers. Activity was measured in the microsomal fraction of the cell (100,000 X g). In the spectrum of hepatomas studied, 16alpha-hydroxylase activity was significantly decreased in parallel with the increase in hepatoma growth rate. The decrease in enzymic activity ranged from 16 to 19% for the slow-growing tumors (Hepatomas 44, 28A, and 9633), 2 to 9% for the intermediate-growing tumors (Hepatomas 38B, 7795, and 5123A), and 0% for the fast-growing tumors (Hepatomas 7288C, 7777, and 42A). Estrogen 16alpha-hydroxylase activity of the liver of tumor-bearing rats differed from that of liver of healthy animals. There was a decrease in enzymic activity ranging from 66% to 90% of normal control rats. The activity level of the host liver did not correlate with tumor growth rate. Stimulation of 16alpha-hydroxylase with phenobarbital showed a 4-fold increase in activity in normal liver and only a 2- to 3-fold increase in host livers. The slow- and intermediate-growing hepatomas showed a 1.2-to 1.4-fold increase in enzyme activity, and no activity or stimulation in the fast-growing hepatomas was observed.
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PMID:Metabolism of estrogens in hepatomas of different growth rates. 19 Nov 75

The effect of prolactin in supporting the growth of 7, 12-dimethylbenz(a)anthracene-induced mammary tumor in adult female Sprague-Dawley rats was investigated when estrogen receptors were blocked by the nonsteroidal antiestrogen, Tamoxifen, ICI 46,474. Following an oophorectomy-induced remission, perphenazine, which stimulates endogenous prolactin release, was able to restore tumor growth whether or not Tamoxifen was added. A second course of perphenazine treatment, instituted after the tumors were allowed to shrink, was again effective in stimulating tumor growth. After a regression in tumor size induced by oophorectomy and daily administration of Tamoxifen, perphenazine was able to restore original tumor size despite continued treatment with Tamoxifen. In intact rats, after regression was obtained by daily administration of Tamoxifen and the prolactin inhibitor, lergotrile mesylate, perphenazine induced tumor growth when the latter was discontinued, even though Tamoxifen was continued for 50 days. Estrogen receptors measured at the time of maximum stimulation by perphenazine were undetectable. On the other hand, estradiol did not stimulate tumor growth when serum prolactin was depressed to undetectable levels by lergotrile. These results indicate that prolactin supports the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor and that estrogen receptors are not required under these conditions.
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PMID:Predominant role of prolactin in stimulating the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor. 19 Nov 82


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