UMLS:C0598934 - FACTA Search

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Query: UMLS:C0598934 (tumor growth)
58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of Tamoxifen (TAM) on tumor growth was investigated experimentally using ovarian dysgerminoma serially transplanted into nude mice. The mice were divided into two groups according to estrogen receptor (ER) content of initially transplanted tumor; groups TAM-A and -B indicated ER rich and ER poor tumor, respectively. Their own control (CNT) was included in each group. After TAM treatment, the tumor size of TAM-A and -B groups was 150 fold and 350 fold that of initial tumor respectively, while that of group CNT was over 500 fold, suggesting that a strong anti-tumor effect of TAM was exerted especially on ER rich tumor. Histological changes following tamoxifen treatment such as a decline in the size of tumor cells and nuclei as well, and a decrease in the mitotic index were observed only in the TAM-A group. The concentration of ER and progesterone receptor (PR) in the cytosol of these tumors were measured. The ER levels in the initial tumor tissue of TAM-A and -B were 14.7 and 3.3 fmol/mg protein, respectively. The significant increase in PR content in TAM-A following TAM administration obviously indicated a so-called TAM-dependent PR induction effect. These results indicated that ovarian cancer containing ER, even though it originated from germ cells, would be responsible for antiestrogen therapy.
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PMID:Experimental endocrinotherapy with tamoxifen of human ovarian dysgerminoma transplanted into nude mice. 342 92

A two-component estrogen (E2)-binding system has been characterized in the E2-independent MTW-9B rat mammary tumor by Scatchard analysis, sucrose gradient analysis, and isoelectric focusing. One cytosol receptor protein (type I) conforms to the classical estrogen receptor with a high affinity (Kd = 0.45 nM) for E2 and limited binding capacity [maximum binding (Bmax) = 53 fmol/mg protein]. The second component (type II) demonstrates a high number of sites (Bmax = 164 fmol/mg protein) and low E2-binding affinity (Kd = 22.3 nM). The type I and type II E2-binding components were shown to sediment on sucrose gradients at 9.6S and 4.5S, respectively, and to focus at isoelectric points of 6.6 and 8.0, respectively. The addition of 0.4 M KCl to the homogenization buffer converted the high affinity receptor species to a form that cosedimented and cofocused with the low affinity E2-binding protein. When tumors were grown in intact male rats, the ratio of the type II to the type I protein, as assessed by sucrose gradient analysis, increased 4.5-fold relative to that in tumors from intact females. Concomitantly, the Kd values of the type I and type II proteins were increased 9- and 2-fold, respectively, and the Bmax of the type I protein was decreased. No changes in the ratios of the E2-binding proteins were observed in tumors grown in ovariectomized female or castrated male rats; however, the Kd for both proteins was increased in tumors from the latter group. Relative to that in intact females, tumor growth was retarded in intact male rats, but was unaffected by ovariectomy or castration. These studies demonstrate that the presence of the low affinity E2-binding protein does not necessarily predict E2 responsiveness. While the role of the type II cytosolic protein has not yet been established, it is possible that it could act as a reservoir for E2, which is required to activate specific biochemical functions such as progesterone receptor synthesis. Alternatively, it could be a nonactivated, perhaps norphosphorylated, form of the E2 receptor which binds E2 with only a very low affinity.
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PMID:Characterization and hormonal regulation of estrogen binding proteins in the MTW-9B transplantable rat mammary tumor. 365 28

Leydig cell tumors formed in BALB/c mice were found to be able to be transplanted subcutaneously in the same strain. One of the sublines, called T 22137, showed growth inhibition in response to estrogenization of host mice. The other subline (T 124958-O), which was originally classified as an estrogen-independent line, was observed to contain the low-affinity estradiol binding component in the cytosol fraction. At a later stage of transplantation, however, the growth of this subline was modestly but significantly enhanced by estrogenic stimuli. This alteration was accompanied by appearance of an estrogen receptor-like molecule which was associated with chromatin even in the absence of estrogen stimuli. In the presence of estrogen selection pressure, a new tumor line, designated as T 124958-R, was established, which showed marked estrogen-dependent growth. T 124958-R was found to contain the cytosolic estrogen receptor. The additional difference was that the annulate lamellae were identified only in T 124958-R, but not in T 124958, by electron microscopic studies. The estrogen dependency of T 124958-R was further substantiated by demonstration of an estrogen secretory protein as well as the estrogen-enhanced formation of 5 alpha-steroids. T 22137 showed growth inhibition in tamoxifen-treated mice. The growth of T 124958-R was enhanced by the administration of tamoxifen to mice. This tamoxifen-induced tumor growth was further stimulated by the simultaneous administration of estrogen. These observations would suggest that mouse Leydig cell tumor systems provide us with a valuable model to investigate the influence of estrogen as well as antiestrogen on malignant cells.
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PMID:Biological and biochemical characterization of estrogen-dependent mouse Leydig cell tumors. 369 89

Diethylstilbestrol (DES), diethylstilbestrol monophosphate (DES-MP) and diethylstilbestrol diphosphate (DES-DP) were tested for their estrogen receptor affinity, estrogenic potency and mammary tumor-inhibiting activity in vitro and in vivo. DES had a much higher receptor binding affinity than its mono- or diphosphate. All three compounds inhibited the growth of the hormone-dependent MCF-7 and hormone-independent MDA-MB 231 breast cancer line only at relatively high concentrations. The estrogenic potency in the immature mouse uterine weight test decreased in the order DES greater than DES-MP much greater than DES-DP. The hormone-dependent MXT mammary tumor of the mouse was inhibited by all three compounds at a dosage of 1.0 mg/kg per week. At a dose of 0.01 mg/kg, DES, DES-MP, and DES-DP stimulated the tumor growth. Thus, for the first time, a biphasic effect on tumor growth was demonstrated in intact mature animals. As the effects of all three compounds were similar in this assay, a cleavage of the phosphate groups is likely. A decrease in estrogenic potency concomitant with a retained antitumor effect of DES-MP and DES-DP compared to DES was not demonstrable in the mature mouse using the MXT assay, only in the uterotrophic test in the immature mouse.
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PMID:Studies on the mammary tumor-inhibiting effects of diethylstilbestrol and its mono- and diphosphate. 375 57

1,1,2-Triphenylbut-1-enes substituted with 3- or 4-acetoxy (OAc) groups on one, two, or three phenyl rings were tested for their estrogen receptor affinities, their estrogenic and antiestrogenic properties in the immature mouse, and their effect on the growth of the hormone-dependent MXT mammary tumor of the mouse. The 4-OAc-substituted compounds had a stronger uterotrophic potency than their 3-OAc-substituted analogs. A certain correlation between estrogenic properties and receptor affinities was demonstrable. Compounds with 3-OAc groups generally had antiestrogenic properties. By varying the aromatic substitution it was possible to obtain compounds ranging from strong estrogens to potent antiestrogens with almost no agonistic activity. The 4-OAc-substituted triphenylbut-1-enes had a better antitumor effect than the compounds with 3-OAc moieties. Thus, the tumor inhibiting activity correlates more with the estrogenic than with the antiestrogenic properties. The strong antiestrogens among these compounds did not show any significant antitumor effect. Further studies are necessary to solve the problem why strong antiestrogens do not, in contrast to ovariectomy, inhibit tumor growth.
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PMID:Acetoxy substituted 1,1,2-triphenylbut-1-enes: estrogenic, antiestrogenic and mammary tumor inhibiting activity. 377 20

Immunological therapy of BALB/c nude mice (nu/nu) implanted with human breast tumors, estrogen receptor negative MX-1 and estrogen receptor-positive MCF-7, was carried out with four monoclonal antibodies (MoAbs) raised against human milk fat globule membrane glycoproteins also present on normal breast epithelial cells. MoAbs injected singly or as a partial mixture arrested growth of the tumors but to a lesser extent than a mixture ("cocktail") of all four MoAbs. Two model systems were developed in order to examine the capabilities of the four MoAbs to arrest human mammary tumor growth. In the first model the ability of these MoAbs to arrest tumor growth during a 6- to 8-week period was tested by injection of the MoAbs immediately before and after implantation (passive immunization) and thereafter every other day. In the second model the effect of these MoAbs on established and growing tumors was tested. Using the cocktail in the passive immunization protocol, human mammary tumor growth in nu/nu mice was arrested either completely or averaging to one-tenth the size of the controls for those mice in which the tumors had taken. Other human carcinomas, colon and lung, under the same protocol, were not affected. Injection of cocktail every 2 days into nu/nu mice with established and growing human breast tumors (both estrogen receptor positive and negative) produced arrests of tumor growth of 44.1, 45.2, 49.8% of their controls after 7 to 8 days of treatment. Previously, it has been established that human mammary tumors are heterogeneous in expression of the human milk fat globule antigens recognized by our antibodies to the extent that some cells may have large amounts and others no detectable amount of a particular antigen. Those MX-1 tumors treated for a prolonged time with the cocktail of MoAbs that survived and continued to grow could be the result of the preferential multiplication of those cells in the heterogeneous population which had low or no antigen content. The breast tumors that did grow in the nu/nu mice after 8 weeks of injection of the cocktail revealed by immunoperoxidase staining a 90% reduction in the antigen content as recognized by these MoAbs when compared with untreated tumors. These results attest to the effectiveness of unconjugated anti-human milk fat globule MoAbs to arrest human breast tumor growth in nu/nu mice, and they also suggest that to best arrest tumor growth the use of a mixture of MoAbs should be considered.
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PMID:Experimental immunotherapy of human breast carcinomas implanted in nude mice with a mixture of monoclonal antibodies against human milk fat globule components. 379 Dec 39

Tumors of 89 women, aged 75 or above, that were operated on for primary mammary carcinoma were analyzed with regard to histologic type and differentiation, estrogen receptor (ER) content, and nuclear DNA distribution pattern. The majority of the tumors were invasive ductal carcinomas but a relatively high frequency of papillary and colloid carcinomas was also found. The cancers were predominantly ER-positive (87%) and diploid (70%), indicating a favorable response to anti-estrogens and slow tumor growth. Despite these characteristics, the prognosis of elderly women with mammary carcinoma is no better than that of other age groups, as shown in previous studies. Nonsurgical treatment is often preferable in very old patients. Analysis of DNA profile can provide additional information and prognostic guidance when selecting patients for endocrine therapy.
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PMID:Assessment of malignancy potential in mammary carcinoma in elderly patients. 382 95

The thymidine labeling index (TLI) was measured in 757 primary, invasive breast carcinomas in women by an in vitro method that achieved intense labeling of S-phase cells. The frequency distribution of the TLI was positively skewed but could be normalized by taking logarithms. The mode was 2%; median, 5.2%; geometric mean, 4.5%; mean 7.1%. The TLI was significantly related to a number of pathological features. Carcinomas of large size, with inflammatory or otherwise locally aggressive, undifferentiated histologic and nuclear characteristics, necrosis, inflammatory cellular response, and circumscribed tumor border showed strong tendencies to have high TLIs. The TLI was not significantly related to race, axillary lymph nodal status, or invasion of lymphatics and blood vessels. Breast carcinomas replicated cells at high rates ("rapid growth") more often in young women than in aged women. Lack of either estrogen receptor (ER) or progesterone receptor (PgR) was associated with high TLI. Although the inverse relationship between TLI and PgR was more or less linear, and the relationship between TLI and ER was not, differences in TLI between PgR-negative and PgR-positive patients were no greater than between ER-negative and ER-positive tumors. The degree of inflammatory infiltrate was strongly related to both proliferative rate and evidence of cell-death, indicative of a secondary phenomenon rather than a role in regulation of tumor growth. The proliferative rate of breast carcinoma appears to be an important determinant of morphologic patterns. Although it modulates the pace of progress of the disease, it is at most a weak determinant of metastasis.
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PMID:Breast carcinoma cell kinetics, morphology, stage, and host characteristics. A thymidine labeling study. 394 41

The synthesis of symmetrically 2,2'-disubstituted butestrols [meso-2,3-bis(4-hydroxyphenyl)butanes] and of 6,6'-disubstituted metabutestrols [meso-2,3-bis(3-hydroxyphenyl)butanes] are described [2,2'-substituents: H (1), OH (2), F (3), Cl (4), Br (5), CH3 (6), and C2H5 (7); 6,6'-substituents: H (8), OH (9), Cl (10), and CH3 (11)]. Compounds 1-11 were obtained by reductive coupling of the corresponding 1-phenylethanols with TiCl3/LiAlH4 and separation of the meso diastereomers. The binding affinity of the test compounds to the calf uterine estrogen receptor was measured relative to that of [3H]estradiol by a competitive binding assay. With the exception of 9, all other compounds showed remarkably high relative binding affinity (RBA) values between 1.0 and 29% that of estradiol. Compounds 3 and 6 (RBA values: 15 and 29), as well as 10 and 11 (1.7 and 5.2), exceeded those of the corresponding unsubstituted compounds 1 and 8 (12 and 1.0). The compounds exhibited strong (3, 4, 6, and 7), moderate (1, 2, and 10), weak (11), or no (8) estrogenic activity in the uterine weight test of the immature mouse. Compounds 1, 2, 8, 10, and 11 showed antiestrogenic activity inhibiting the estrone-stimulated uterine growth (25-35% inhibition). Compound 11 led to a significant inhibition of the tumor growth when tested on the 9,10-dimethyl-1,2-benzanthracene induced, hormone-dependent mammary carcinoma of the Sprague-Dawley rat.
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PMID:Ring-substituted 1,2-dialkylated 1,2-bis(hydroxyphenyl)ethanes. 3. Synthesis, estrogen receptor binding affinity, and evaluation of antiestrogenic and mammary tumor inhibiting activity of 2,2'-disubstituted butestrols and 6,6'-disubstituted metabutestrols. 633 Mar 56

In the C3H mouse mammary adenocarcinoma, estradiol cannot induce the progesterone receptor, and the tumor growth rate is not decreased by ovariectomy. To find an explanation for this estrogen resistance, we have compared the estrogen receptor (ER) from this tumor to the ER of uterus and of the mammary tumors induced in rats by dimethylbenz(a)anthracene. Since the ER concentration of the C3H tumor is low (congruent to 20 fmol/mg protein), we have used iodoestradiol of high specific activity to label the receptor. Several criteria of ER activation were studied. The dissociation rates of estradiol with or without sodium molybdate were similar in all tissues. In metrizamide isopycnic gradients, ER from rat uterus and C3H tumor had a similar density, both in the presence or absence of DNA. The binding of ER to DNA-cellulose was analyzed by incubating to equilibrium a constant amount of ER with a variable amount of DNA, the cellulose concentration being kept constant. The saturation data were plotted according to the method of Scatchard. The apparent affinity for DNA of the cytosol ER was similar for the rat dimethylbenz(a)anthracene tumors and the uterus (Kd congruent to 10 microM) but was significantly higher for the C3H tumor ER (Kd congruent to 2.3 microM). Neither the substitution of estradiol by iodoestradiol, nor the difference in cytosol protein and ER concentrations, nor the nonspecific steroid binding to DNA-cellulose could explain this result. This difference was confirmed when using DNA-agarose or soluble DNA in sucrose gradients. Finally, the salt concentrations necessary to elute ER from DNA-cellulose columns were 0.20 and 0.28 M for uterine and C3H tumor ER, respectively. To conclude, the C3H tumor has a low content of ER which appears to have a higher affinity for DNA than the ER of estrogen-responsive tissue. We suggest that the reason for the inefficiency of ER in the C3H tumor may be related to its increased affinity for nonspecific DNA sites.
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PMID:Increased DNA binding of the estrogen receptor in an estrogen-resistant mammary cancer. 640 33

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