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

Gelatin encapsulated nitrogen microbubbles were effective ultrasonic contrast agents in in vitro phantom and in vivo rabbit V2 carcinoma studies. Intra-arterial injection of 80-micrometer gelatin encapsulated nitrogen microbubbles appeared to improve tumor visualization by rim enhancement, which persisted for several minutes.
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PMID:Gelatin encapsulated nitrogen microbubbles as ultrasonic contrast agents. 739 50

Basement membrane forms widespread barriers to tumor invasion. It has been shown that tumor-secreted, basement membrane-degrading enzymes, namely metalloproteinases (MMPs) play an important role in tumor invasion and metastasis. In this study, we determined the enzymatic activity, content, and mRNA of both the 72 kDa (MMP-2) and 92 kDa (MMP-9) MMPs in primary cultures of human giant-cell tumor of bone (GCT) in vitro and in tissue extracts (in vivo). Gelatin zymography showed the presence of lytic bands at M(r) 121,000, 92,000, and 72,000, and these enzymatic activities were inhibited by EDTA, an inhibitor of MMPs. Western blots with antibodies specific for MMP-2 and MMP-9 confirmed the presence of MMP-2 and MMP-9 both in vitro and in vivo, but GCT cells at late passage showed only MMP-2. Northern blots using labeled cDNA probes specific for these molecules revealed the presence of 3.1 kb transcript for MMP-2 and a 2.9 kb transcript for MMP-9. Using specific antibodies to 72 kDa and 92 kDa type IV collagenases, we studied their cellular distribution by immunohistochemical means. Stronger immunoreactivity was found for 92 kDa type IV collagenase than 72 kDa type IV collagenase in the giant cells. It appears, therefore, that MMP-9 may play an important role in the malignant behavior of GCTs and suggests a potential therapeutic role for protease inhibitors in attempting to minimize the invasive behavior of GCTs.
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PMID:Expression of 72 kDa and 92 kDa type IV collagenases from human giant-cell tumor of bone. 758

Previous primary and secondary co-transfections of genomic DNA from a metastatic human small cell lung cancer cell line into NIH/3T3 cells resulted in a murine fibrosarcoma cell line (Tx93B) that produced frequent spontaneous lung metastases in subcutaneously injected tumor-bearing nude mice. In order to transfer the acquired metastatic behavior to additional cell lines that could then be tested in syngeneic immunocompetent animals, DNA from Tx93B cells was transfected without additional neo gene into Balb/c embryo fibroblasts, which led to the isolation of a tertiary transfectant cell line (D3) of low spontaneous metastatic potential in normal Balb/c mice. Subsequent cell lines established serially from lung metastases in mice injected with D3, and metastatic descendants of D3 (all selected for the original neo marker in G-418), resulted in three generations of metastatically variant cell lines capable of causing pulmonary metastases in 11.1%, 54.6%, and 89.5%, respectively, of subcutaneously injected animals, and in 100% of normal mice injected intraperitoneally. There was no apparent ras-family oncogene participation in the metastatic behavior of either of the two DNA donor cell lines or in the metastatically variant tertiary transfectants. Gelatin zymography indicated that the secretion of gelatinolytic enzymes in vitro by the variant cell lines was inversely proportional to their metastatic capability. Human Alu repeat gene sequences detected in the metastatic variants suggested that co-transfected metastasis-associated genes present in the original human DNA donor cell may have contributed to acquisition of the metastatic phenotype by the tertiary transfectant cell lines. The increase in metastatic potential observed in successive generations of the D3-derived tumor cell lines, further suggested that selection for cells having increased metastatic capability had occurred during passage in vivo accounting for the phenotypic change. Because of their common origin and progressively metastatic nature these cell lines may prove useful in the identification of metastasis-associated genes accessible through the use of differential expression cloning strategies.
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PMID:Acquisition and enhanced expression of the metastatic phenotype following transfections of genomic mouse tumor DNA containing human SCLC gene sequences. 775 Feb 8

Radiolabeled substrate degradation assays and gelatin zymography are routinely employed to assay 72 kDa gelatinase A (MMP-2) and 92 kDa gelatinase B (MMP-9) in biological fluids. Enzyme-linked immunosorbent assays (ELISA) have recently been developed for the quantitation of these matrix metalloproteinases (MMP). In this study, we have compared ELISA to standard substrate degradation assays for measurement of MMP-2 and MMP-9 in human plasma and tumor-conditioned media. Gelatin Sepharose chromatography and gel filtration chromatography were employed as partial purification procedures for MMP-2 and MMP-9. The ELISA data for MMP-2 and MMP-9 are linear on a log:log regression curve over a wide range of MMP concentrations and are specific for the designated gelatinase, with no overlap detected with related metalloproteinases. The minimum detectable concentrations of MMP-2 and MMP-9 were approximately 0.5 ng/ml and 0.2 ng/ml, respectively, in the ELISA as compared to 4 ng/ml and 3 ng/ml, respectively, in gelatin zymography. The [3H]gelatin degradation assay required a combination of > 50 ng/ml of MMP-2 and MMP-9 for detection. Although gelatin zymography was less sensitive than ELISA (primarily due to the smaller sample volume employed) and was more difficult to quantitate, this procedure offers the important advantage of being able to distinguish between latent and activated gelatinases.
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PMID:Comparison of techniques for measurement of gelatinases/type IV collagenases: enzyme-linked immunoassays versus substrate degradation assays. 828 15

Chemical conjugation of a recombinant human interleukin-1 alpha (IL-1) with gelatin was conducted using a water-soluble carbodiimide in an attempt to augment the indirect effect of IL-1 on in vivo tumor cell growth in mice. Chromatographic studies of the IL-1-gelatin conjugate demonstrated that the apparent molecular weight of IL-1 was increased by the gelatin conjugation and about 60% of IL-1 activity was retained in the prepared conjugate. Intraperitoneal (i.p.) injection of the conjugate significantly suppressed the intraperitoneal growth of a subline of Meth A fibrosarcoma cells (RR1 cells), compared with the effect of free IL-1 at the same dose, although the cells per se were resistant not only to free IL-1 but also to gelatin-conjugated IL-1. Simple mixing of gelatin with free IL-1 did not augment the in vivo antitumor effect as compared with that of free IL-1. Gelatin conjugation improved the in vivo stability of IL-1. Prolonged retention of IL-1 activity in the peritoneal cavity as well as the circulation of mice was observed after i.p. injection of the IL-1-gelatin conjugate in comparison with free IL-1 injection, irrespective of the presence of tumor cells. Gelatin conjugation was effective in augmenting the in vivo antitumor effects of IL-1 to activate host cells, e.g. macrophages (M phi). The i.p. injection of the conjugate enhanced M phi infiltration into the peritoneal cavity of tumor-bearing mice and peritoneal M phi were strongly activated to inhibit the in vitro growth of RR1 cells. Thus, gelatin conjugation was effective in augmenting the indirect effect of IL-1 via host cells, leading to a high suppressive effect on in vivo growth of tumor cells.
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PMID:Potentiation of in vivo antitumor effects of recombinant interleukin-1 alpha by gelatin conjugation. 834 Feb 57

Human giant cell tumor (GCT) consists of multinucleated giant cells and mononuclear stromal cells, and is characterized by frequent vascular invasion without distant metastases. To study the role of matrix metalloproteinases (MMPs) in the vascular invasion, we examined production of MMP-1 (tissue collagenase), -2 (gelatinase A), -3 (stromelysin-1), -9 (gelatinase B), and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in GCT. MMP-9 was highly and predominantly expressed in giant cells by both immunohistochemistry and in situ hybridization. Expression of other MMPs was also observed in some cases but was inconstant. Sandwich enzyme immunoassays demonstrated that MMP-9 is the predominant MMP secreted by GCT. There was a definite imbalance between the amounts of MMP-9 and those of TIMPs in the culture media of GCT, leading to detectable gelatinolytic activity in an assay using 14C-gelatin. Gelatin zymography demonstrated the main activity at about 90 kd, which was identified as the zymogen of MMP-9 by immunoblotting. Immunohistochemistry for type IV collagen and laminin, major basement membrane components, showed that disappearance of the proteins is closely associated with MMP-9-positive giant cells. These results indicate the production of MMP-9 by multinucleated giant cells and suggest that the metalloproteinase may contribute to proteolysis associated with vascular invasion and local bone resorption in human GCT.
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PMID:Matrix metalloproteinase 9 (gelatinase B) is expressed in multinucleated giant cells of human giant cell tumor of bone and is associated with vascular invasion. 857 23

We established and characterized high- (LuM1) and low-lung-metastatic (NM11) cell lines derived from murine colon adenocarcinoma 26 tumor line. LuM1 cell line was established as a clonal cell line from a cultured cell mixture derived from a lung-metastatic nodule after 7 sequential subcutaneous transplantations of lung-metastatic tumors in the abdominal wall of BALB/c mice. NM11 cell line was established from a cultured cell mixture derived from a subcutaneous transplant of murine colon adenocarcinoma 26 tumor cells. LuM1 cells showed marked spontaneous lung metastases, but NM11 cells rarely did. High invasive potential of LuM1 cells was revealed by in vitro invasion assay using Matrigel reconstituted membranes. Rapid retraction was observed in monolayers of human umbilical vein endothelial cells and bovine aortic endothelial cells when LuM1 cells were added on the monolayers. Gelatin zymography and immunochemical examinations with monoclonal antibodies against gelatinase B (Mr 95,000 type IV collagenase) showed secretion of large amounts of the gelatinase by LuM1 cells.
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PMID:Establishment and characterization of high- and low-lung-metastatic cell lines derived from murine colon adenocarcinoma 26 tumor line. 860 53

We examined production and tissue localization of matrix metalloproteinase (MMP)-1 (tissue collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-9 (gelatinase B), tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in human breast carcinomas. In more than half of the cases, MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 were immunolocalized in carcinoma cells and MMP-2 was on the carcinoma cell membranes as well, whereas MMP-3 was positively stained in less than 15% of the cases. MMP-1 staining in carcinoma cells was significantly higher in scirrhous carcinoma than in other types of carcinoma. MMP-9 expression was remarkably higher in the carcinoma cases with lymphnode metastasis than in the non-metastatic cases. MMP-3 was mainly expressed in T-lymphocytes infiltrated in the tumor stroma. Stromal fibroblasts were positive for all these MMPs except for MMP-3. The TIMP-1 levels released into the culture media by carcinoma tissues were significantly lower than those by fibroadenoma tissues, although there were no significant differences in the levels of MMP-1, MMP-2, MMP-9 and TIMP-2. Gelatin zymographical analyses showed that the activation rate of the zymogen of MMP-2 (proMMP-2) is significantly higher in the more advanced carcinoma group with lymphnode metastasis than in the metastasis-negative and fibroadenoma groups. These data indicate that MMP-1, MMP-2 and MMP-9 are highly expressed in human breast carcinoma tissue and suggest that activation of proMMP-2 may be an indicator of lymphnode metastasis of the breast carcinoma.
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PMID:Production of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human breast carcinomas. 876 24

Three stable carcinoma cell lines, designated PLS10, PLS20 and PLS30, have been established from 3,2'-dimethyl-4aminobiphenyl plus testosterone-induced carcinomas in the dorsolateral prostate of male F344 rats. The cells are keratin-positive and grow as typical epithelial monolayers in culture. When injected into intact male nude mice, PLS10 and PLS30 cells form well-differentiated adenocarcinomas with abundant connective tissue stroma, while PLS20 cells give rise to poorly differentiated adenocarcinomas. Growth of all PLS cell lines in nude mice is not affected by castration and the cells are immunohistochemically negative for androgen receptors. Tumor growth rates in nude mice were found to be PLS20 > PLS10 > PLS30, with significant in vitro stimulation by insulin/transferrin, but not epidermal growth factor, dexamethasone or basic fibroblast growth factor. Spontaneous lung metastases were observed in all cases. However, skeletal invasion including bone is essentially observed only with the PLS20 tumors. Gelatin zymography showed predominant secretion of the active form of gelatinase B (Mr 92,000 type IV collagenase) by all the cell lines. Karyotype analysis revealed PLS10, PLS30 and PLS20 to be diploid, hyperdiploid and hypertetraploid, respectively. The results demonstrate that the three PLS cell lines are androgen-independent and metastatic in common, but have different histology, growth potential and invasiveness. They may therefore be useful models for understanding progression and metastasis of human prostatic carcinomas.
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PMID:Establishment and characterization of three androgen-independent, metastatic carcinoma cell lines from 3,2'-dimethyl-4-aminobiphenyl-induced prostatic tumors in F344 rats. 904 56

The regulation of tumor growth by cytokine-induced alterations in host effector cell recruitment and activation is intimately associated with leukocyte adhesion and angiogenic modulation. In the present study, we have developed a novel tumor model to investigate this complex series of events in response to cytokine administration. Gelatin sponges containing recombinant human basic fibroblast growth factor (rhFGFb) and B16F10 melanoma cells were implanted onto the serosal surface of the left lateral hepatic lobe in syngeneic C57BL/6 mice. The tumor model was characterized by progressive tumor growth initially localized within the sponge and the subsequent development of peritoneal carcinomatosis. Microscopic examination of the sponge matrix revealed well developed tumor-associated vascular structures and areas of endothelial cell activation as evidenced by leukocyte margination. Treatment of mice 3 days after sponge implantation with a therapeutic regimen consisting of pulse recombinant human interleukin-2 (rhIL-2) combined with recombinant murine interleukin-12 (rmIL-12) resulted in a marked hepatic mononuclear infiltrate and inhibition of tumor growth. In contrast to the control group, sponges from mice treated with rhIL-2/rmIL-12 demonstrated an overall lack of cellularity and vascular structure. The regimen of rhIL-2 in combination with rmIL-12 was equally effective against gelatin sponge implants of rhFGFb/B16F10 melanoma in SCID mice treated with anti-asialo-GM1 in the absence of a mononuclear infiltration, suggesting that T, B, and/or NK cells were not the principal mediators of the anti-tumor response in this tumor model. The absence of vascularity within the sponge after treatment suggests that a potential mechanism of rhIL-2/rmIL-12 anti-tumor activity is the inhibition of neovascular growth associated with the establishment of tumor lesions. This potential mechanism could be dissociated from the known activities of these two cytokines to induce the recruitment and activation of host effector cells. Moreover, this model provides a unique opportunity to study the cellular and molecular mechanism(s) underlying both tumor angiogenesis and leukocyte recruitment to metastatic lesions.
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PMID:Regulation of local host-mediated anti-tumor mechanisms by cytokines: direct and indirect effects on leukocyte recruitment and angiogenesis. 913 9


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