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

The purpose of these studies was to determine whether the biological and metastatic behaviors of tumor cells isolated from fresh surgical specimens of human colon carcinomas are influenced by the isolation method and the organ site of implantation and growth in nude mice. Three surgical specimens were obtained from three different patients. Two tumors were primary human colorectal carcinomas (HCC) classified as Dukes' B2 (KM12) and Dukes' D stages (KM20), and the third was from a liver metastasis (KM23). The tumors were enzymatically dissociated, and viable cells were implanted into the subcutis or spleen of different nude mice or were established in culture. Tumors developed in both sites of implantation, but hepatic metastases were found only in those nude mice that received splenic implantations of HCC cells. Cells from Dukes' D stage tumors produced more hepatic disease than cells from the Dukes' B tumor. Cells of the parental KM12C (culture) were injected into the spleen or cecum of nude mice to produce experimental and spontaneous hepatic metastases, respectively. HCC lesions were harvested from livers of nude mice and established as individual cell lines in culture. This procedure yielded cell lines KM12SM (spontaneous metastasis) and KM12L1 (experimental metastasis). The selection cycle for cells implanted into the spleen was repeated three more times to produce the cell line designated KM12L4. Cells of the parental KM12C and the three selected variants were injected into nude mice by different routes: i.v., s.c. into the cecum, and into the spleen. Subsequent to implantation into the spleen, all cell lines were shown to be tumorigenic. Cells from the selected KM12L4 and KM12SM lines produced a significantly higher number of experimental liver metastases than the parental cells. Moreover, subsequent to the injection into the cecum, cells of the once-selected KM12SM (for spontaneous metastasis) produced a higher incidence of spontaneous liver metastasis than all other lines. The human origin of all the lines was confirmed by isoenzyme and karyotype analyses. The two highly metastatic lines (KM12L4 and KM12SM) were tetraploid and produced elevated levels of type IV collagenolytic activity. Collectively, the results demonstrate that the orthotopic implantation of HCC cells into the appropriate organ environment can be used for efficient isolation and for study of metastatic subpopulations of cells from human colon carcinoma.
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PMID:Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice. 284 63

The metastatic behavior of the HT-29 human colorectal carcinoma cell line was studied following injection into nude mice by different routes. After intrasplenic injection, experimental metastases formed in the livers of most mice. Variant lines were established in culture from the liver lesions and from tumors growing at the site of injection, the spleen. Cells of the HT-29 LMM line exhibited slightly enhanced ability to form liver metastases compared with cells of the non-selected parent line. When injected i.v., the HT-29 cells produced only a few small experimental metastases in the lungs, but in most of the mice macroscopic tumors were found in various lymph nodes and the interscapular fat. Analyses of the distribution of IdUrd-labeled cells did not reveal a preferential localization of the HT-29 cells in sites where metastases subsequently formed. This suggested that the growth of the human colon carcinoma cells in those sites might be the result of a stimulatory interaction between the tumor and host cells as opposed to growth in sites such as the lungs, where numerous cells arrested after i.v. injection but only a few, small metastases were seen 60 days later.
Clin Exp Metastasis
PMID:Organ distribution of experimental metastases of a human colorectal carcinoma injected in nude mice. 290 28

The therapeutic potential of rHuIFN-alpha A/D, a hybrid human IFN molecule with equal activity on murine cells, was studied in experimental and spontaneous metastatic models of a murine colon carcinoma COLON 26. rHuIFN-alpha A/D inhibited experimental pulmonary metastases of COLON 26 and prolonged the survival of BALB/c mice. Dose scheduling, survival and tumour-cell clearance studies showed that the first 5 days were critical in the inhibition of pulmonary metastases. However, it is unlikely that lung NK cells were involved in the anti-metastatic effect of rHuIFN-alpha A/D because inhibition of pulmonary metastases and a decrease in radio-labelled tumour-cell survival was seen in BALB/c mice depleted selectively of their NK cells by prior treatment with rabbit antiasialoGMI serum. Although rHuIFN-alpha A/D stimulated NK-cell activity in BALB/c mice, it was ineffective in abrogating the NK suppressant action of rabbit anti-asialoGMI serum on murine lung NK cells. Thus, IFN may mediate its early antimetastatic effect via a mechanism independent of NK-cell stimulation. IFN also inhibited the development of lung metastases from s.c. COLON 26 tumors in normal, NK-depleted and T-cell-deficient mice.
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PMID:Action of recombinant alpha interferon against experimental and spontaneous metastases in a murine model. 291 Aug 26

Computed tomography (CT) of three patients with Krukenberg tumor was reviewed retrospectively. CT showed large, lobulated, multicystic masses with soft-tissue components, indistinguishable from primary ovarian carcinoma. Indeed, CT and sonography of all three patients were initially interpreted as primary ovarian carcinoma. The ovary is a frequent site of metastases, particularly from colon carcinoma. These can be quite large, yet diagnosis is seldom made preoperatively. Much has been written about metastatic ovarian tumor, but this is the first report in the radiologic literature about their CT features. The authors emphasize the importance of recognizing the ovary as a frequent site of metastases and the proper approach to this problem. In patients with a history of colon or gastric carcinoma, the mixed cystic and solid ovarian mass on CT should be regarded as metastatic tumor until proven otherwise. A careful search for gastrointestinal tract signs or symptoms should be done in any patient with a pelvic tumor. When CT is done for evaluation of ovarian tumor, the stomach and colon should be carefully evaluated, and the ovaries routinely examined in the preoperative CT staging of gastric or colon carcinoma.
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PMID:Computed tomography of Krukenberg tumors. 299 52

The cytoskeletons of various human neuroendocrine (NE) tumors were analyzed immunohistochemically using antibodies against intermediate-filament (IF) proteins as well as by two-dimensional gel electrophoresis of proteins from microdissected tissue samples. All of the tumors studied were found to contain cytokeratin filaments and are therefore referred to as 'NE tumors of the epithelial type'. In addition, neurofilaments were found in most cutaneous and some pulmonary NE tumors, as well as in medullary carcinomas of the thyroid and in pancreatic islet cell tumors. The neurofilament staining was frequently concentrated in cytoplasmic IF aggregates. Gel-electrophoretic analyses showed that all NE tumors examined synthesize 'simple epithelium-type' cytokeratin polypeptides, cytokeratins nos. 8 and 18 being the most prominent ones, whereas cytokeratin no. 19 was found in variable and usually minor amounts. A new cytoskeletal protein, designated IT protein, with a relative molecular weight of 46,000 and an isoelectric pH value of approximately 6.1 (in 9.5 M urea) was detected in all 9 cases of cutaneous NE tumors ('Merkel-cell carcinomas'), including 2 lymph-node metastases, but was not found in any of the 17 cases of pulmonary NE tumors. In addition, 2 medullary carcinomas of the thyroid, 2 islet cell tumors of the pancreas, and 1 intestinal carcinoid tumor also seemed to lack this protein. A protein indistinguishable from IT protein by electrophoresis and tryptic peptide mapping was found in cytoskeletal preparations of mucosal cells of human intestine and in cultured human colon carcinoma cells of line HT-29. A possible relationship between IT protein and the type-I subfamily of cytokeratin polypeptides is discussed. Our study shows that the co-expression of cytokeratin filaments and neurofilaments may provide a criterion which is useful for the recognition of some NE tumors but which does not distinguish between NE tumors of different types and origins. In contrast, IT protein seems to be present specifically in cutaneous NE tumors, but absent in pulmonary NE tumors. The implications of these findings for the elucidation of the histogenesis of cutaneous NE tumors and for the histopathological differential diagnosis of NE tumors of cutaneous and pulmonary origin are discussed.
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PMID:Cytoskeletal differences between human neuroendocrine tumors: a cytoskeletal protein of molecular weight 46,000 distinguishes cutaneous from pulmonary neuroendocrine neoplasms. 300 49

Messenger RNA levels of the c-fos, c-myc, c-Ha-ras and c-Ki-ras genes were studied in 39 tissue samples obtained from 17 patients undergoing surgery for colon carcinoma and other colon diseases. DNA extracted from the same samples was studied by Southern analysis. The tissues were tumors and grossly normal mucosa from each case and in some instances benign polyps and metastases. Our results indicate: (1) that 50% of cases studied show an increase in expression of at least one of the oncogenes studied; (2) that over-expression is not random, some cases over-expressing several of the genes studied; (3) that the expression pattern of the oncogenes studied varies between primary tumor and metastases; (4) that amplification is a rare event, being limited to one instance in which c-myc was amplified in a metastasis; (5) that cases which exhibit high levels of mRNA in one or more genes studied correlate with biologically aggressive tumors; and (6) that "non-expressors" are at higher risk for local recurrence based on correlations with mucin histochemistry.
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PMID:Prognostic implications of expression of the cellular genes myc, fos, Ha-ras and Ki-ras in colon carcinoma. 304 May 97

Twenty-six adults, ages 27 to 60, with refractory metastatic solid tumors were treated with high-dose cyclophosphamide (Cy) + carmustine (BCNU) at one of three escalating dose schedules followed by autologous bone marrow transplantation (ABMT). Toxicity was severe and dose-related, with the maximum tolerated dose for the combination determined to be Cy 160 mg/kg and BCNU 900 mg/m2. Median time to WBC recovery (greater than or equal to 1,000/microL) was 13 days post-ABMT (range, nine to 22 days) and to a platelet count of greater than or equal to 50,000/microL, 22 days (range, 13 to 83 days). Sixteen of 20 evaluable patients (80%) responded to therapy with at least 50% reduction in measurable tumor, and three patients achieved complete remission (CR). Responders included eight of nine evaluable patients with breast carcinoma, two of five with melanoma, two of two with sarcoma, and four of four with colon carcinoma. Response durations were short (median, 4 months), even for complete responders, and relapses generally occurred at sites of previous metastases. In order for this approach to have a more significant impact on overall survival, it may need to be applied earlier in the natural history of the malignancy.
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PMID:High-dose combination alkylating agent therapy with autologous bone marrow rescue for refractory solid tumors. 304 66

A mouse monoclonal antibody (BLMRL-HMFG-Mc5) prepared against a defined cell surface antigen of human mammary epithelial cells, non-penetrating glycoprotein (NPGP), was used in imaging and distribution studies in athymic nude mice grafted with human breast tumors. For in vivo tissue distribution studies, 125I-labeled monoclonal antibody was injected into nude mice carrying simulated metastases of human tumors (breast and colon carcinomas). After 22-24 hr the amount of radioactivity per gram of tissue was 3-4 times higher in the breast tumor than in liver, brain, lung, muscle, or spleen. In contrast, colon carcinoma tissue, grafted and treated likewise, did not show higher accumulation of radioactivity relative to other tissues. At 4 days, the incorporation in breast tumors remained almost as high, while the circulating radioactive tracer and the incorporation in tissues other than breast had fallen significantly. In tumor imaging studies, breast tumor masses as small as 4 mm in diameter were clearly localized on a whole body scan using 131I-labeled BLMRL-HMFG-Mc5 antibodies with a High-Purity germanium gamma camera. Normalization of 131I-distribution to that of 99mTc-pertechnetate increased the specificity of this imaging methodology. The quantitative density of 131I-label was 2-3 fold higher over the breast tumor than over comparable areas of the mouse. No positive localization images were obtained for similar implants of colon and lung carcinomas or melanomas after injections of 131I-labeled BLMRL-HMFG-Mc5. Localization of human breast tumors in this model can be achieved with 131I-labeled anti-breast epithelial monoclonal antibodies.
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PMID:Localization of human breast tumors grafted in nude mice with a monoclonal antibody directed against a defined cell surface antigen of human mammary epithelial cells. 307 29

Abnormal accumulation of Tc-99m MDP in two metastatic lesions of the liver was observed in a patient with resected colon carcinoma. Single-photon emission computed tomography (SPECT) revealed characteristic marginal accumulation of Tc-99m MDP in both of those metastatic lesions. X-ray CT showed the corresponding marginal calcification in one of the metastases, but no apparent calcification was observed in the other lesion. Two months later, however, the latter also became calcified on x-ray CT. These findings suggest that the accumulation of Tc-99m MDP in the present case is strongly related to the calcium deposition and that Tc-99m MDP may accumulate in a calcified metastatic lesion before the calcification appears on x-ray CT.
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PMID:Accumulation of Tc-99m methylene diphosphonate in calcified metastatic lesions of the liver from colonic carcinoma. Comparison with calcification on X-ray computed tomogram. 315 10

To identify sequences associated with a metastatic phenotype, DNA fragments isolated from 2 separate human colon carcinoma metastases were transfected into a mouse bladder carcinoma cell line together with the neoR gene as selectable marker. It was found that bulk populations of neomycin resistant cells carrying these human sequences caused more metastases in syngeneic mice than did control cells transfected with calf thymus DNA. Cells isolated from metastases retained the highly metastatic phenotype when transferred to secondary hosts.
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PMID:Selective enhancement of metastatic capacity in mouse bladder carcinoma cells after transfection with DNA from liver metastases of human colon carcinoma. 316 81


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