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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two hemopoietic tumors induced in rats by Gross leukemia virus and dimethylbenz(a)anthracene, respectively, display distinctive and consistent patterns of metastases, the former in the thymus and lymph nodes, the latter in the liver and spleen. To investigate the role of circulatory anatomy in the localization of metastases, 51Cr-labeled cells were injected i.v., and their distribution was followed at various intervals. To explore the influence of immune mechanisms, Gross leukemia virus- and dimethylbenza(a)anthracene-induced leukemic cells as well as a line of antigenically modulated cells were administered to newborn, X-irradiated, and immunologically unresponsive recipients. The circulation of tumor cells through various organs was indiscriminate. The immune response of the host was operative in limiting the local and metastatic tumor growth but not in determining the site of secondary tumors. The conclusion of these experiments was that the selective organ distribution of tumor metastases was solely dependent on intrinsic cellular properties.
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PMID:Role of immune mechanisms in metastatic patterns of hemopoietic tumors in rats. 81 34

Malignant melanoma has been induced in the Weiser-Maple guinea pig by prolonged application of 7,12-dimethylbenz(a)anthracene. The tumor shows a biphasic growth pattern analogous to the radial and vertical growth phase of human cutaneous malignant melanoma. It evolves through a predictable series of cellular events classified as intraepidermal melanocytic hyperplasia, dermal melanocytosis, dermal melanocytoma, malignant melanoma without intralesional transformation, and, finally, malignant melanoma with intralesional transformation, which is characterized by the appearance of "new kinds of cells" and is associated with widespread metastases and massive lymph node involvement. Clinically, the lesions evolve from diffuse hyper-pigmentation to brown-black macules, to nodules of increasing size, to overt malignant melanoma associated with metastases, wasting, and death. Examples of intralesional transformation analogous to that in guinea pigs are found not only in human malignant melanomas, but in other human neoplastic systems, and such analogous cellular events are discussed in this paper.
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PMID:The developmental biology of induced malignant melanoma in guinea pigs and a comparison with other neoplastic systems. 82 48

The National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a phase II study of weekly oral menogaril as first-line therapy in 51 patients with incurable, metastatic or locally advanced breast cancer. While no prior chemotherapy for metastatic disease was permitted, prior adjuvant chemotherapy was allowed provided that no anthracycline or anthracene had been given. Forty-eight patients were evaluable for response. Two patients (4%) achieved complete remissions, 9 patients (19%) achieved partial remissions, 26 patients (54%) were stable and 11 patients (23%) failed. At the initial menogaril dose of 275 mg/m2 per week, 13 of 14 patients required a dose reduction and/or a treatment delay of one or more weeks. Therefore, the menogaril dose was reduced to 225 mg/m2 per week for the last 37 patients. At that those, 20 of 37 patients developed grade 3 or 4 granulocytopenia and 22 required dosage delays. At the initial starting dose, the average dose intensity actually delivered was 169 mg/m2 per week. At 225 mg/m2 the average dose intensity actually delivered was 197 mg/m2 per week. Toxic effects included mild to moderate nausea and vomiting, diarrhea, hair loss and occasional hyperpigmentation. In summary, menogaril is an anthracycline derivative that has modest activity when administered orally to minimally pretreated patients with breast cancer.
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PMID:Phase II study of oral menogaril as first line chemotherapy for advanced breast cancer: a National Cancer Institute of Canada Clinical Trials Group study. 153 20

Squamous cell carcinomas (SCC) of the mouse skin were produced by three different protocols of chemical carcinogenesis, i.e., complete carcinogenesis with 7,12-dimethylbenz(a)anthracene (DMBA) two-stage carcinogenesis with DMBA as initiator, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) as promoter and three stage carcinogenesis with DMBA, TPA and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as third-stage agent or progressor. Tumors were sequentially studied at weeks 38-52 of treatment. Although no significant differences in the rate of appearance of gamma-glutamyl transpeptidase (GGT) could be seen, a larger number of SCC produced by complete carcinogenesis protocols were GGT-negative. This coincided with the higher grade of malignancy of these tumors as evaluated by histopathology. In general terms high-grade tumors were seen more frequently in the complete carcinogenesis experiment than in the other two protocols. SCC produced by complete carcinogenesis also exhibited a markedly higher DNA index than the SCC from the other experimental groups. All three protocols were very effective in producing late metastasizing tumors, and no significant differences could be established in the incidence of spontaneous lung metastasis. This shows that, contrary to general knowledge, if adequately observed for more than 40 weeks, SCC of the murine skin is able to metastasize in the lung in approximately 30% of cases. Nevertheless, complete carcinogenesis-induced SCC were usually of higher histological grade, a proportion of these were GGT-negative and produced more multiple or diffuse metastases than the tumors induced by the multistage protocols.
Invasion Metastasis 1991
PMID:Metastatic potential of mouse skin carcinomas produced by different protocols of chemical carcinogenesis. 168 75

Carcinomas of the rat prostate induced by a single injection of N-methyl-N-nitrosourea, 7,12-dimethylbenz(a)anthracene, and 3,2'-dimethyl-4-aminobiphenyl, after sequential treatment with cyproterone acetate and testosterone propionate, were evaluated as potential animal models for prostatic cancer. All ten carcinomas examined were located in the dorsolateral prostate region and did not involve the distal parts of the seminal vesicles and coagulating glands. The incidence of urinary obstruction leading to the animals' death was 6 of 10 rats, and metastases in the lung, abdominal lymph nodes, and/or liver also occurred in 6 of 10 rats. The tumors were invasive adenocarcinomas, showing frequent perineural invasion and a variable degree of differentiation. There were ultrastructural similarities with human prostatic carcinomas, such as intracellular lumina. Plasma acid phosphatase was increased. Enzyme histochemical analysis revealed similarities with the Dunning R3327H and -HI prostatic carcinomas but was not helpful in determining the site of origin of the tumors. The gross and microscopic appearance of the tumors and the observation of preneoplastic lesions exclusively located in the dorsolateral prostate suggest this lobe as site of origin of the carcinomas. Preneoplastic lesions (n = 9) included atypical hyperplasias (n = 5) and lesions with all histological characteristics of carcinoma except for local invasion and metastases, which were classified as carcinoma in situ (n = 4). Although androgen sensitivity could not be assessed, the observed characteristics of the tumors [their long latency time (46-80 weeks), the presence of preneoplastic lesions, and the short duration of the treatment, leaving the animals intact] all indicate that the present approach is a valid animal model for the study of prostatic carcinogenesis.
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PMID:Characterization of adenocarcinomas of the dorsolateral prostate induced in Wistar rats by N-methyl-N-nitrosourea, 7,12-dimethylbenz(a)anthracene, and 3,2'-dimethyl-4-aminobiphenyl, following sequential treatment with cyproterone acetate and testosterone propionate. 210 61

To study the relationship between metastatic ability and activated ras expression, a cloned, low metastatic, dimethylbenz(a)anthracene-induced rat mammary cancer cell line (RMC1) was transfected with the v-H-ras oncogene. Cloned transfectants were characterized as high, medium, or low expressors of the v-H-ras gene, on the basis of Southern, Northern, and Western blot analysis. Following s.c. inoculation in syngeneic rats, all transfectants produced tumors; however, the in vivo growth rate of cloned transfectants which expressed any level of v-H-ras oncogene was significantly higher (approximately 5-fold) than that observed in the untransfected RMC1 cells. Control (neo only) transfectants exhibited no change in growth rate and had a low metastatic ability comparable to that of the parental untransfected cells. Certain cloned v-H-ras expressing transfectants were highly metastatic to the lungs and lymph nodes. These highly metastatic H-ras transfectants differed widely however, in their level of H-ras expression. The lung colonization potential following i.v. inoculation was increased in all transfectants which expressed any level of v-H-ras gene. These studies suggest that while v-H-ras transfection can result in the development of metastatic ability in rat mammary cancer cells, there is no simple dose-response relationship between the level of v-H-ras expression in cloned rat mammary cancer cell transfectants and the development of experimental or spontaneous metastases.
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PMID:Relationship between metastatic ability and H-ras oncogene expression in rat mammary cancer cells transfected with the v-H-ras oncogene. 210 38

Transplantation of five liver tumors induced with the chemicals diethylnitrosamine (DEN) and 7,12-dimethylbenz[a]anthracene (DMBA) in small live-bearing fish of the genus Poeciliopsis is reported. Five permanent strains representing three distinct tumor types were established in isogenic hosts. Histological characterization of hepatocellular carcinoma, hemangiopericytic sarcoma, and cholangiocarcinoma and the development of the neoplasms in host fish is presented. Transplantability of the experimental liver tumors provides evidence of their malignant nature. Metastasis of the hepatocellular carcinoma occurred from tumor implants in the dorsal musculature or peritoneal cavity and from the hemangiopericytic sarcoma implanted in the intraperitoneal cavity.
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PMID:Transplantable chemically-induced liver tumors in the viviparous fish Poeciliopsis. 298 24

Attempts by early workers to induce liver tumours by the local implantation of carcinogens had by and large not been successful, so that the liver came to be viewed as being "resistant" to tumourigenesis by this means. A review of these early studies showed not only that fibrosarcomas could be easily induced by the local application of 3-methylcholanthrene (3-M.C.), but that there were also reasons why the apparently low susceptibility of the liver to the localised induction of hepatocellular tumours should not be accepted as established dogma. In an attempt to re-investigate this problem pellets made of cholesterol (CHOL), anthracene (ANT), alpha-naphthylisothiocyanate (ANIT), 3-M.C. or 4-dimethylaminoazobenzene (DAB) were implanted into the livers of male litter-mate weanling rats. The evolution of the response was studied by histological examination of the implantation site at varying intervals. In each instance the liver responded with the formation of a firm, complete connective tissue capsule which, however, did not prevent the gradual degradation of the implants. No tumours or other significant changes were observed with the control implants of CHOL or ANT. ANIT, known to damage biliary ducts, elicited what appeared to be an intense serous exudation which was separated from the adjacent parenchyma by a shell-like deposition of calcium in the connective tissue capsule. No significant biliary changes were observed, however, and no tumours were produced. Attention should be drawn to this reproducible, regularly occurring, in vivo model of extra-osseous calcification. The 3-M.C. induced a high incidence of large solitary bosselated tumours associated with the carcinogenic pellet which was found embedded in the tumour mass. The architectural arrangement and bizarre cytological appearance of the tumours led to the currently widely used diagnosis of malignant fibrous histiocytoma (M.F.H.) rather than the fibrosarcoma or rhabdomyosarcoma of the early workers. Some tumours produced large numbers of implantation metastases in the peritoneal cavity, but no distant metastases were observed in this series. Of particular interest is the fact that it was not possible to determine the site of origin of these tumours despite histological sampling at intervals of the site of implantation of the pellets. In contrast to these pleomorphic, clearly mesenchymal tumours reliably produced by 3-M.C., the implantation of pellets of DAB produced fewer tumours which were classified as large, singly occurring hepatocellular carcinomas (H.C.C.).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Localized hepatocarcinogenesis: the response of the liver and kidney to implanted carcinogens. 311 99

To study the biological characteristics of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats, 20 Sprague Dawley female rats received a single oral dose of 5 mg of this carcinogen. During the 35-week observation time 78 primary tumors were removed. While in most cases the primary tumor could be removed completely, 7 out of 20 animals eventually had to be sacrificed for inoperable local recurrence of the primary tumor. Notwithstanding, the long period of time given for tumor metastases to develop (mean time between tumor removal and termination was 18.5 weeks), tumor spread either to lungs or regional lymph nodes could not be established. This relatively benign behavior of the tumor was in contrast with the morphological characteristics of the tumor, which uniformly showed the features of adenocarcinomas. The difference in biological behavior between DMBA-induced mammary tumors in rats and malignant mammary tumors in humans suggests that as a model this system is of limited value for investigations of mechanisms of malignant behavior of human tumors.
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PMID:Is the 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor model suitable as a preclinical model to study mammary tumor malignancy? 312 16

Mammary tumors induced in female Sprague-Dawley rats by feeding 7,12-dimethylbenz(a)anthracene (DMBA; 20 mg/100 g body weight) were classified according to histological criteria of tissue differentiation, cellular atypia, and evidence of invasion. The 549 tumors could be placed in three categories, nodular hyperplasia, nodular hyperplasia with atypia, and carcinoma, and combinations of all three. Although tumors classified histologically as carcinomas did not metastasize, upon transplantation to the kidney capsule, a tumor classified as a carcinoma grew for eight generations and metastasized. Tumor heterogeneity was a common finding in DMBA-initiated tumors. Carcinomas were an early lesion. As the length of time between DMBA treatment and sacrifice increased, more tumors with areas of carcinoma were found. Therefore, DMBA-initiated tumors progressed to carcinomas either soon after initiation or later by development within nodular hyperplasias. In 4 separate groups of animals (74 adrenalectomized rats and 90 intact rats), postinitiation adrenalectomy increased the numbers of carcinomas compared to intact animals. This effect was consistently seen in the cervical and thoracic mammary glands. We propose that the mechanism for enhancement of progression to greater malignancy by adrenalectomy may be inhibition of differentiation of initiated cells in the absence of glucocorticoids.
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PMID:Adrenal regulation of mammary tumorigenesis in female Sprague-Dawley rats: histopathology of mammary tumors. 313 21


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