Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The progression of papillomas to squamous cell carcinomas (malignant conversion) was studied in the skin of SENCAR and Charles River CD-1 mice, using a three-stage treatment protocol. After initiation with 7,12-dimethylbenz(a)anthracene (DMBA) (stage 1) and limited promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) (stage II), papilloma-bearing mice were treated (stage III) with either tumor initiators, such as urethane, N-methyl-N'nitro-N-nitrosoguanidine (MNNG) or 4-nitroquinoline-n-oxide (R-NQO), the promoter TPA, or solvent (acetone). Similar final carcinoma yields were found in the mice treated in stage III with TPA or acetone, although carcinomas developed earlier in the TPA-treated mice. In contrast, treatment with tumor initiators in stage III increased both the rate of appearance and the final yield of carcinomas. Similar results were obtained in both SENCAR and CD-1 mice. A papilloma stage appears to be necessary for carcinoma development since elimination of TPA treatment in stage II greatly reduced the incidence of both papillomas and carcinomas in both stocks of mice. The heterogeneity of papillomas with regard to progression to carcinomas is demonstrated by the low rate of conversion of TPA-dependent papillomas and the high rate of conversion of persistent papillomas in CD-1 mice. The carcinomas that develop using the three-stage regimen vary in metastatic potential. In CD-1 mice, the frequency of metastases to lymph nodes were similar in groups treated in stage III with MNNG, urethane, 4-NQO, TPA, or acetone, but treatment with urethane substantially increased metastases to the lung.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Malignant conversion and metastasis of mouse skin tumors: a comparison of SENCAR and CD-1 mice. 378 Jun 34

This study describes the effects of medroxyprogesterone acetate on tumor growth and metastases in transplanted uterine adenocarcinoma cells of the rat. High-and-low-tumorigenic cloned cells of Sprague-Dawley rat uterine adenocarcinoma originally induced by 7,12-dimethylbenz (alpha) anthracene in vivo were used. Both were derived from the same parent culture. They were cultured for more than 2 years and both retained almost the same transplantability. Survival rate of cell colonies in vitro was reduced in both lines after progesterone treatment of more than 8 mcg per ml. This reduction was dose dependent. About 1 million cells suspended in .2 ml culture medium were injected sc into the interscapular region of isologous newborn rats. At 5 weeks these rats were given .5 mg medroxyprogesterone acetate twice a week for 2 weeks. At 7 weeks they were killed. High-tumorigenic cells produced growing tumors in all newborn rats. About a third of these rats died of metastases during the 7-week observation period. Tumors produced by low-tumorigenic cells grew slowly and occasionally regressed without metastases to the lung. Tumors in female rats were larger than those in males. Enhancement of tumor growth and metastases by this progesterone compound was observed in rats inoculated with low-tumorigenic cells as compared to controls. The enhancement was not significant in tumors produced by high-tumorigenic cells. The progesterone may act immunosuppressively in vivo, or make alterations in environmental conditions of the tumors.
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PMID:Enhancement of tumor growth and metastases by medroxyprogesterone acetate in transplanted uterine adenocarcinoma cells of the rat. 481 Sep 70

The spontaneous production of elongated derivatives by cuboidal rat mammary epithelial cells was examined with the use of a series of single-cell clones grown in tissue culture. Four representative cell lines derived from a 7,12-dimethylbenz[a]anthracene-induced mammary tumor in an inbred WF rat were examined for morphologic stability, chromosome number, presence of immunoreactive fibronectin, laminin, prekeratin, and milk fat globule membrane (MFGM) antigens, ultrastructural characteristics, and tumorigenicity in syngeneic hosts. Conversion of cuboidal to elongated cells occurred by way of apparent morphologic intermediates, examples of which were isolated and cloned. Levels of immunoreactive fibronectin and laminin were greater in the elongated than the cuboidal clones, whereas the converse was true of prekeratin. MFGM antigens were present to a variable extent in all 4 clones. When grown on 0.3% collagen gels, cells of Rama 37 CL-A3 and Rama 37CS-A2 cuboidal clones exhibited surface microvilli and desmosomes. A minority of elongated cells contained microfilamental structures and pinocytotic vesicles similar to those seen in myoepithelial cells; the remainder lacked distinguishing ultrastructural features. After injection into syngeneic recipients, Rama 37 CL-A3 cuboidal line gave rise to glandular tumors consisting of cuboidal cells arranged in acinar structures, Rama 37 E5 elongated line induced spindle cell tumors, and Rama 37 CS-A2 and Rama 37 E8 lines induced tumors containing nests of mixed spindle and cuboidal cells. The majority of these tumors failed to metastasize.
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PMID:Phenotypic instability of rat mammary tumor epithelial cells. 641 41

N-Methyl-N-nitrosourea (MNU) given iv to rats 50-55 days old induced mammary tumors in 70% of F344/N and 91% W/ICRF inbred females with mean latency periods of 149 and 93 days, respectively. Reduction of the MNU dose did not affect tumor incidence in W/ICRF rats. Of the mammary tumors, 98% were classified histologically as adenocarcinomas, which grew progressively. Primary tumors of nonmammary origin were detected at low incidence. Upon histologic examination, no evidence was found for metastases of either the mammary or other primary tumors. No evidence for tumor-induced hypercalcemia was found. Oophorectomy at the time of MNU administration prevented tumor development; oophorectomy when at least 1 tumor/animal was palpable caused growth delay or regression. All MNU-induced and 7,12-dimethylbenz[a]anthracene-induced mammary tumors tested contained cytoplasmic estrogen receptor (ER) at similar concentrations and were indistinguishable histologically. MNU-induced tumors in F344 rats were transplantable and retained ER through three transplantations.
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PMID:N-methyl-N-nitrosourea-induced rat mammary tumors. Hormone responsiveness but lack of spontaneous metastasis. 677 42

A histopathological study is reported of the autopsy finding in two strains of rats treated with N-methyl-N-nitrosourea (MNU). The induced mammary tumours were histologically indistinguishable from those produced by dimethylbenz(a)anthracene (DMBA). A number of other primary tumours were found and there was no evidence of metastases.
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PMID:N-nitrosomethylurea-induced rat mammary tumours as models of human breast cancer. 678 Jun 89

Several transplantable 7,12-dimethylbenz[a]anthracene-induced SC chicken fibrosarcoma (CHCT-NYU) lines were studied for their ability to grow in internal organs after iv injection (artificial metastases) into 1- to 3-week-old chickens. Some tumor lines were recently derived, whereas others were studied after many serial subcutaneous transplantations. STriking similarities as well as differences were found between tumor lines' ability to grow in various organs. Artificial metastases were seen primarily in the stomach, pancreas, lungs, heart, and muscle, and occasionally also in the kidneys and in the liver. Agammaglobulinemic recipients showed more extensive organ involvement than normal recipients of the same age. Whole-body gamma-irradation also enhanced the incidence of artificial metastases, particularly in lungs. Antibody from the serum of a primary tumor-bearing host reduced the growth of the corresponding tumor in many organs. The metastatic pattern of line CHCT-NYU4 was a relatively stable property, since there was little difference in the internal localization of these tumor cells studied before and after 15 serial subcutaneous transplants. However, intravenous transplantation of tumor cells from line CHCT-NYU4 taken from the liver, lungs, and pancreas of a single recipient established sublines with changes in organ specificity. After a few such serial transplants of liver-derived tumor, a line was derived that grew virtually in the liver alone. A subline with preference for growth in lungs was also obtained, but its ability to grow in the pancreas persisted. A pancreas-derived tumor line also grew in the liver and lungs. Subcutaneous transplants of tissue fragments of the lung-derived tumor line caused the appearance of spontaneous metastases in lungs. The incidence of spontaneous metastases with the lung-derived line was much greater than that with the liver-derived line or with the original CHCT-NYU4 line.
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PMID:Derivation of transplantable 7,12-dimethylbenz[a]anthracene-induced chicken fibrosarcoma lines: differences in metastasizing properties and organ specificity. 681 7

Dose-response relationships for the induction of mammary tumors by a single i.v. injection of N-methyl-N-nitrosourea (MNU) were studied. At 50 days of age, groups of 20 virgin female Sprague-Dawley rats received single doses of 50, 45, 40, 35, 30, 25, 20, 15, or 10 mg MNU per kg body weight; a group of 10 control rats received 0.85% NaCl solution only. Animals were observed for the appearance of mammary tumors over their life span or until 600 days after carcinogen administration. Both malignant and benign mammary tumors appeared in all groups; however, malignant tumors appeared earlier and at a faster rate than did benign tumors. Incidence of cancer and number of cancers per animal increased with increasing MNU dose; the latent period for cancer increased with decreasing dose. The number of benign tumors induced as a percentage of total tumors increased with decreasing dose, ranging from approximately 10% in groups receiving more than 30 mg MNU per kg to 58% in the group receiving 10 mg/kg. Foci of metastatic mammary carcinoma were found in lungs of animals in several MNU dose groups. Data from the present study indicate that a single i.v. administration of MNU induces mammary cancer in a dose-related fashion, with little toxicity and a short latent period; induced cancers metastasize to distant sites. The single-dose MNU model thus appears to be superior to both the 7,12-dimethylbenz(a)anthracene and multiple-dose MNU models, particularly for use in studies of modification of mammary carcinogenesis.
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PMID:Lifetime dose-response relationships for mammary tumor induction by a single administration of N-methyl-N-nitrosourea. 721 38

A human tumor cloning system has been utilized to culture 431 patients' breast cancer specimens. Overall, 288 or 67% of the specimens formed colonies in soft agar. Of the primary lesions 188/260 (72%) formed colonies and 100/171 (58%) of the metastatic lesions formed colonies. The median number of colonies per 500,000 nucleated cells plated was 47 for the primary lesions and 30 for the metastatic lesions. Growth from a variety of metastatic sites ranged from 22% for intradermal lesions to 77% for solid visceral metastases. Methods to increase the number of colonies from a specimen are reported including increasing the number of nucleated cells plated and making a variety of changes in the growth media. None of these methods has had a major impact on colony growth. The antitumor activity of standard anticancer agents such as adriamycin and medroxyprogesterone in the assay is presented. In addition, in vitro results with two new anthracene derivatives demonstrate good antitumor activity for the derivatives. The cloning assay represents a new model for both the basic and clinical studies of human breast cancer.
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PMID:Potential and problems with growth of breast cancer in a human tumor cloning system. 734 71

Several epidemiological studies have indicated that residential or occupational exposure to 50 or 60 Hz magnetic fields (MF) may increase the risk of breast cancer, possibly by suppression of pineal production of the oncostatic hormone melatonin. In view of the methodological problems of epidemiological studies on MF exposure and cancer risk, laboratory studies are needed to determine whether 50/60 Hz exposure can initiate, promote or copromote mammary cancer. In the present study, 216 female Sprague-Dawley rats were divided into four groups. Two of the groups (with 99 animals each) received oral applications of 7,12-dimethylbenz[a]anthracene (DMBA) and were either sham-exposed or exposed in a 50 Hz, 100 muT MF for 24 h/day 7 days/week for a period of 91 days. The other two groups (nine animals each) were either sham-exposed or MF-exposed without DMBA treatment. The exposure chambers and all other environmental factors were identical for MF-exposed and sham-exposed animals. At the end of the 3 month period of MF exposure, all rats were used for histopathological diagnosis of lesions. At the time of necropsy, significantly more MF-exposed DMBA-treated rats exhibited macroscopically visible mammary tumours than DMBA-treated controls. Furthermore, the size of mammary tumours was significantly larger in MF-exposed rats. Histopathological examination of the mammary gland showed that the number of neoplastic and non-neoplastic lesions did not significantly differ between groups, indicating that MF exposure had not altered the incidence of mammary lesions but had only accelerated tumour growth, consistent with a co-promoting effect. In the MF-exposed group, significantly more rats exhibited malignant mammary tumours than in controls, indicating that MF exposure had affected the progression of DMBA-induced lesions. The number of metastases of mammary tumours or of primary lesions in other organs in response to DMBA was not affected by MF exposure. In rats without DMBA application, no non-neoplastic or neoplastic lesions were determined. The data demonstrate that long-term exposure of DMBA-treated female rats promotes the growth and progression of mammary tumours, while tumour incidence is not affected, at least under the experimental conditions of the present study. The data thus add to the accumulating evidence that MF exposure exerts tumour co-promoting effects.
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PMID:A histopathological study on alterations in DMBA-induced mammary carcinogenesis in rats with 50 Hz, 100 muT magnetic field exposure. 783 96

Evidence suggests that the plasminogen activators (PAs), in particular urokinase-type PA (uPA), play a pivotal role in tumor invasion and metastasis. We studied the contribution of the PAs to the malignant phenotype through the chemical induction of melanocytic neoplasms in uPA-deficient mice. Primary tumors were induced and promoted concurrently in 35 uPA-/- deficient and 35 uPA+/+ wild-type mice using a single application of 7,12-dimethylbenz(a)anthracene followed by repetitive applications of croton oil. Animals were sacrificed at 60-day intervals for 1 year. At necropsy, the four largest pigmented lesions in each animal were excised, characterized histologically, and evaluated microscopically for evidence of invasion. The regional lymph nodes, lungs, and solid abdominal visceral organs were sectioned and examined microscopically for evidence of metastatic disease. Cellular blue nevi were induced in 100% of uPA-/- and uPA+/+ promoted animals. Although a reduction in the radial and vertical progression of these lesions was noted in the uPA-deficient mice compared with the wild-type group, more than 95% of cellular blue nevi induced in both groups of animals invaded the underlying tissues. These lesions did not metastasize to the regional lymph nodes. Malignant melanoma arose in 5 of 35 (14.3%) of promoted wild-type mice. These tumors were locally aggressive, produced tissue-type PA, but were not metastatic to the regional nodes, lungs, or abdominal viscera. These results indicate that the invasive capability of melanocytic lesions may depend more on tissue-type PA than uPA activity. No melanomas were induced in the uPA-/- mice. The resistance of the uPA -/- strain to melanoma induction suggests that uPA contributes to malignant progression. We propose that the absence of uPA negatively affects tumorigenesis by decreasing the liberation and availability of growth factors such as basic fibroblast growth factor.
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PMID:Induction of primary cutaneous melanocytic neoplasms in urokinase-type plasminogen activator (uPA)-deficient and wild-type mice: cellular blue nevi invade but do not progress to malignant melanoma in uPA-deficient animals. 875 32


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