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

A case of recurrent retroperitoneal desmoid tumor successfully treated with tamoxifen (Nolvadex tablets, ICI Pharma, Division of ICI Americas, Wilmington, DE) is reported. The patient presented late in her second pregnancy with a large retroperitoneal pelvic desmoid tumor that was treated with surgical excision and megestrol acetate. When the tumor recurred 12 months later, it was again treated with surgery, this time followed by radiation therapy. The desmoid tumor quickly recurred. The patient was then treated with tamoxifen, resulting in a complete tumor regression that has remained stable for 27 months. Tamoxifen should be considered as first-line therapy in recurrent desmoid tumors.
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PMID:A recurrent pelvic desmoid tumor successfully treated with tamoxifen. 199 11

Certain substances when given orally to rats have effects on the neuroendocrine cells of the fundic stomach. Such compounds also have effects on acid or its secretion, which is to a greater or lesser extent suppressed, with a consequent rise in serum gastrin, followed by an increase in the number of histamine-secreting ECL cells. These changes are seen with the histamine H2 receptor antagonists loxtidine, SKF 93479, ICI 162,846 and ranitidine; with the hypolipidaemic agents clofibrate, ciprofibrate and benzofibrate; with sodium bicarbonate and pentagastrin; and with omeprazole, a potent inhibitor of the parietal cell proton pump mechanism. Changes in the pH of the rat stomach stimulate the neuroendocrine G cells of the pylorus to secrete gastrin, which acts on the ECL cells of the fundus causing the production of histamine, which in turn stimulates the parietal cell. This sequence leads to an excess of circulating gastrin, which is detectable within 5 days. Subsequently increases in the number of ECL cells occur, the hyperplasia being related to hypergastrinaemia and the degree of acid suppression. The hyperplastic response is rapid, being so obvious with loxtidine at 39 days that there is good reason to suppose it could well be detected earlier. Using omeprazole, hyperplasia was found at 28 days after oral doses of 140 mg/kg/day. In order to get an equivalent degree of acid suppression with ranitidine it was necessary to deliver 420 mg/kg/day by subcutaneous infusion using an osmotic minipump, when hyperplasia occurred. Interestingly, only omeprazole produced a hyperplastic response of G cells. Such results reflect the covalent binding of omeprazole to the proton pump as opposed to the competitive binding of ranitidine to the histamine H2 receptor site. In addition to ECL cell hyperplasia there is ample evidence from lifetime studies in rats and mice that neoplasia may result. Neuroendocrine carcinomas (carcinoids) of the rat fundic stomach have been observed with loxtidine, omeprazole, SKF 93479 and ICI 162,846. They are seen late in the 2-year rat studies and are most unlikely to have arisen purely as an extension of the hyperplastic response. It is possible that the prolonged disturbance of gastric homoestasis resulting from achlorhydria result in the production of a carcinogen or carcinogens, in which event it is not too surprising, in view of the neuroendocrine hyperplasia, that the tumours seen are neuroendocrine carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuroendocrine cell hyperplasia and neuroendocrine carcinoma of the rodent fundic stomach. 204 87

Tamoxifen is the endocrine treatment of choice for breast cancer. In several laboratory models in vivo tamoxifen is a tumoristatic agent. When MCF-7 breast cancer cells are inoculated into athymic mice, palpable tumors do not grow unless the animals are treated with estrogen, and tamoxifen inhibits estrogen-stimulated growth. If tamoxifen is stopped, tumors regrow. These results suggest that adjuvant tamoxifen therapy should involve long treatment periods (even lifetime) to prevent tumor recurrence. Unfortunately resistance to therapy and patient relapse inevitably occur, and such disease recurrence involving tamoxifen resistance is difficult to treat successfully. A laboratory model of endocrine therapy failure has been developed. When athymic mice with MCF-7 tumors are treated for 6-8 months with tamoxifen, several tumors grew and continued to grow in tamoxifen-treated mice. These estrogen receptor-positive tumors grow with either tamoxifen or estradiol. Tamoxifen-stimulated tumor growth has been observed in human endometrial tumors implanted into athymic animals. Growth of these tamoxifen-stimulated tumors can be inhibited with the pure antiestrogen ICI 164,384 upon withdrawal of tamoxifen. These data are discussed in terms of treatment strategies for tamoxifen-failed patients.
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PMID:Sensitivity and insensitivity of breast cancer to tamoxifen. 228 88

Tamoxifen (TAM), a nonsteroidal antiestrogen, is used in the adjuvant treatment of breast cancer. Previous studies, however, have indicated that some human breast and endometrial tumors are stimulated to grow with TAM in the athymic mouse. One such TAM-stimulated tumor is the EnCa101 human endometrial adenocarcinoma. Our aim was to evaluate the ability of different doses of TAM or other nonsteroidal antiestrogens to stimulate the growth of EnCa101 tumors in athymic mice. Additionally we have evaluated less estrogenic antiestrogens (two steroidal antiestrogens, RU 39,411 and ICI 164,384, and two nonsteroidal antiestrogens, keoxifene and MER-25) for their ability to inhibit TAM-stimulated growth. All experiments were done in ovariectomized athymic mice transplanted in the axillary mammary fat with 1-mm3 pieces of EnCa101 tumor. Sustained release preparations (0.5-2.0-cm Silastic capsule or 5-mg TAM cholesterol pellet) of TAM caused similar tumor growth. The growth rate was not altered by an additional daily i.p. injection of 1 mg TAM in 0.1 ml peanut oil. A 3-mg TAM daily dose was toxic. Four weeks of treatment (100-micrograms s.c. injections, every other day) with nonsteroidal antiestrogens, trioxifene mesylate, enclomiphene, or nafoxidine stimulated tumor growth. However, keoxifene stimulated this tumor to a lesser degree than TAM and partially inhibited TAM-stimulated growth. ICI 164,384 showed no stimulatory activity (1-mg s.c. injections every other day) alone compared to controls but inhibited TAM-stimulated (0.25-cm Silastic capsule) growth. In a parallel experiment, RU 39,411 (1-mg s.c. injections every other day) stimulated EnCa101 to grow. In contrast when RU 39,411 was administered in a sustained release preparation (2.0-cm Silastic capsule) there was no stimulatory growth compared to controls. Additionally RU 39,411 inhibited TAM-stimulated growth, but the low-potency antiestrogen, MER-25, was less effective in this regard. These data suggest that less "estrogenic" antiestrogens can inhibit TAM-stimulated tumor growth in vivo. Thus these compounds or derivatives may prove useful as a second-line endocrine therapy should TAM-stimulated tumor growth occur in the clinic.
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PMID:Effect of steroidal and nonsteroidal antiestrogens on the growth of a tamoxifen-stimulated human endometrial carcinoma (EnCa101) in athymic mice. 233 15

A human endometrial tumor (Ishikawa) cell line in culture responded to estradiol stimulation, as measured by growth and alkaline phosphatase activity. These effects were similar whether the medium was enriched with serum or was serum-free. Estradiol increased placental alkaline phosphatase activity 2-3-fold over control in these Ishikawa cells. The mechanism for this increase appeared to be at the level of transcription, at least in part, since there was an increase in the concentration of placental alkaline phosphatase mRNA. The administration of tamoxifen or 4-hydroxytamoxifen was unable to antagonize the estradiol-stimulated alkaline phosphatase enzyme activity or mRNA expression. The administration of tamoxifen alone had no effect on alkaline phosphatase enzyme activity, but tamoxifen did stimulate the steady state concentration of alkaline phosphatase mRNA. In contrast, a new antiestrogen, ICI 164,384, was able to antagonize both of these estradiol-stimulated effects.
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PMID:Estrogen regulation of placental alkaline phosphatase gene expression in a human endometrial adenocarcinoma cell line. 233 23

In order to determine if the correlated expression of transformation and tumorigenicity is affected by the agents used to induce transformants or by the immune status of the host used to test the tumorigenicity of transformants, we derived a series of cloned cell lines from foci of transformed cells induced by treatment of the contact-inhibited mouse cell line B/C-N7.ICI with the DNA demethylating agent 5-azacytidine (5-AZC) or the DNA demethylating and mutating agent benzo(a)pyrene dihydrodiol epoxide (BPDE). The transformed cell lines were injected into syngeneic nude and normal mice to determine their tumorigenicity. The results of this analysis showed that 93% of the transformants induced by 5-AZC treatment grew as tumors when injected into nude mice. Of those lines capable of growing as tumors in nude mice, 86% were also tumorigenic when injected into normal mice. In contrast, only 64% of BPDE-induced transformants grew as tumors in nude mice, and of those, only 44% were also tumorigenic in normal mice. The existence of non-contact-inhibited transformants that are tumorigenic only in nude mice indicates that host anti-tumor immune surveillance mechanisms are operative in normal mice. Further, the difference in both the percentage of transformed cell lines that are tumorigenic and the percentage of tumorigenic transformants that are susceptible to immune surveillance when transformants are induced by BPDE as compared to 5-AZC indicates that the transforming agent can affect both the correlation between the expression of transformation and tumorigenicity, and the interaction between the immune system and tumorigenic transformants.
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PMID:Anti-tumor surveillance of non-contact-inhibited transformed cell lines. 245 24

In a 28-year-old patient with a large uterine leiomyoma, complete tumor regression was achieved by the LHRH agonist Zoladex (ICI 118.630) when administered three times. During the follow-up period of three months, new myoma growth did not occur. On the basis of this case study, it is necessary to discuss a new therapy concept for the differentiated treatment of uterine leiomyomata in young women with a desire for pregnancy.
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PMID:[New possibilities for differentiated therapy of leiomyoma of the uterus using the GnRH agonist zoladex]. 252 4

One hundred thirty-four pre- and perimenopausal patients presenting with metastatic breast cancer (median age, 42 years; range, 25 to 55) were treated with goserelin (Zoladex [ICI 118 630]; ICI Pharma, Plankstadt, Germany) a long-acting gonadotrophin-releasing hormone (GnRH)-analogue depot formulation, injected subcutaneously every 4 weeks, as a first-line therapy. One hundred eighteen patients were evaluable for response. Serum concentrations of estradiol, luteinizing hormones (LH), and follicle-stimulating hormones were significantly suppressed by Zoladex. Mean serum estradiol values fell into the range of castrated or postmenopausal women within 2 to 3 weeks of therapy. This suppression was maintained for the duration of therapy. Overall objective response was: 12 (10.2%) complete remission; 41 (34.7%) partial remission; 33 (28.0%) no change; and 32 (27.1%) progression. In responders, the median time to response was 4 months (range, 2 to 11 months), median duration of response was 8 + months (range 2 to 24 months), and median time to progression was 11 + months (range, 5 to 30 months). Objective responses were seen for different sites of metastases: loco-regional (62.5%), bone (46.7%), visceral (45.0%), and multiple (35.1%). Tumor remission was more common in patients in which the primary tumor was estrogen receptor (ER)-positive (49.3%) or ER-unknown (44.0%), but appreciable response rates were also observed in ER-poor patients (33.3%). Zoladex depot was well tolerated both locally and systemically. It produced effective castration and the objective response rates and duration of remission are at least comparable to those seen following oophorectomy; however, the side effects are less. The use of depot Zoladex avoids the psychological trauma and operative morbidity of the irreversible operative castration.
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PMID:Goserelin, a depot gonadotrophin-releasing hormone agonist in the treatment of premenopausal patients with metastatic breast cancer. German Zoladex Trial Group. 252 63

Estrogen is known to stimulate the proliferation and basement membrane invasiveness of the MCF-7 human breast cancer cell line. We have compared the new steroidal antiestrogen ICI 164,384, the triphenylethylene 4-hydroxytamoxifen (OHT), and the benzothiophene LY 117018, for their effects on the proliferation and invasiveness of the MCF-7 cell line and its antiestrogen-resistant variant LY-2. While all three antiestrogens blocked the proliferative effects of 17 beta-estradiol on MCF-7 cells, OHT and LY 117018, but not ICI 164,384 stimulated their proliferation in the absence of estrogen. The proliferative effects of OHT and LY 117018 were blocked by ICI 164,384. Basement membrane invasiveness of MCF-7 cells was stimulated by 17 beta-estradiol and OHT, but not LY 117018 or ICI 164,384. Both ICI 164,384 and LY 117018 were able to block the invasiveness induced by either 17 beta-estradiol or OHT. The LY-2 antiestrogen-resistant variant of the MCF-7 cell line showed increased basal proliferation, and responded only slightly to estrogen. ICI 164,384, but not OHT or LY 117018 antagonized the effects of 17 beta-estradiol, but did not reduce proliferation below control levels. The LY-2 line was not resistant to the antiestrogenic effects of LY 117018 or ICI 164,384 on invasiveness, and was stimulated by LY 117018 for this parameter. Thus, ICI 164,384 is a pure antiestrogen for MCF-7 cell proliferation and invasiveness, and may offer clinical advantage over nonsteroidal antiestrogens which can stimulate these activities in tumor models in vitro.
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PMID:ICI 164,384, a pure antagonist of estrogen-stimulated MCF-7 cell proliferation and invasiveness. 258 35

This investigation examines the tamoxifen (TAM)-dependent growth in vivo of an MCF-7 tumor variant, MCF-7TAM, previously reported in this journal (M. M. Gottardis and V. C. Jordan, Cancer Res., 48: 5183-5187, 1988). Ovariectomized athymic mice were implanted with 1-mm3 pieces of MCF-7TAM and were treated with Silastic capsules of varying sizes containing TAM to demonstrate dose-dependent growth over a 10-wk experiment. TAM was necessary to maintain tumor growth. Animals whose capsules were removed at 6 wk showed complete tumor stasis after 20 wk of observation. Removal of TAM after 11 wk caused the rate of tumor growth to decrease compared with TAM-treated animals. Tumor areas were significantly different (P less than 0.03) at Wk 20. The growth of TAM-stimulated tumor, MCF-7TAM, was inhibited by the novel steroidal antiestrogens, ICI 164,384 and RU 39,411. TAM-stimulated growth (0.5-cm Silastic capsule) was maintained at control levels by 8 wk of treatment with ICI 164,384 (1 mg s.c. every other day). ICI 164,384 alone had no stimulatory activity. At the same dose, RU 39,411 inhibited TAM-stimulated growth of MCF-7TAM, although not to control levels. RU 39,411 was slightly stimulatory when administered alone. The growth of MCF-7TAM was stimulated by either TAM or 17 beta-estradiol. The antiestrogen, RU 39,411, effectively inhibited estradiol-stimulated tumor growth. Overall, these studies confirm and extend the previous observation on TAM-stimulated growth of breast cancer cells in vivo and demonstrate the possibility of developing novel antiestrogens to prevent this form of drug resistance should it occur in the clinic.
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PMID:Inhibition of tamoxifen-stimulated growth of an MCF-7 tumor variant in athymic mice by novel steroidal antiestrogens. 274 3


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