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

The purposes of this work are to: review the biological activities of Interleukin-2 (IL-2); evaluate the reported therapeutic benefits and toxicity of IL-2/lymphokine activated killer (LAK) cells; and project the role of IL-2/LAK cells in cancer therapy. Interleukin-2 is a glycoprotein lymphokine (mw 15,000) produced naturally by mitogen or antigen stimulated T-lymphocytes. The activities of IL-2 include: enhancement of IL-2 receptor positive T-lymphocytes and a variety of other in vitro and in vivo alterations of T cell function. The IL-2 gene has been cloned from the Jurkat leukemia cell line and expressed by recombinant biotechnology in an E. coli vector. In vitro incubation of IL-2 with selected T-lymphocytes results in the formation of lymphocyte activated killer (LAK) cells. Rosenberg and colleagues, in 1983, demonstrated that both exogenous IL-2 and LAK cells were needed in order to get maximum tumor regression in a murine model and later humans. Patients selected for IL-2/LAK cell therapy have clinical metastases or advanced unresectable cancers. Almost all patients treated demonstrate some toxic effects, including chills, fever, nausea, vomiting, diarrhea and hepatic dysfunction. Approximately 75 percent of the patients have profound hypotension and require intensive nursing care. A review of the literature indicates that tumor responsiveness will range from negligible (adenocarcinoma of the lung with metastases) to a 30+ percent response in renal cell carcinoma when complete and partial responders are totalled. Interleukin-2/LAK cell therapy has promise for some wide spread tumors for which no other therapy is available.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interleukin-2 and lymphokine activated killer cells: promises and cautions. 264 90

Carcinoembryonic antigen (CEA) is a glycoprotein that has been useful as a tumor marker to predict recurrence in gastrointestinal malignancies, but whose biological function has not been elucidated. With the recent evidence that CEA is a member of the immunoglobulin supergene family, CEA may be involved in intercellular recognition and binding. This review examines the role that CEA plays in the development of metastases by colorectal carcinoma.
Cancer Metastasis Rev 1989 Dec
PMID:Carcinoembryonic antigen: function in metastasis by human colorectal carcinoma. 269 74

A correlation between increased beta-1,6 branching of N-linked carbohydrates and the ability of a cell to metastasize or to form a tumor has been observed in several experimental models. Lec9 Chinese hamster ovary (CHO) mutants exhibit a drastic reduction in tumorigenicity in nude mice, and this phenotype directly correlates with their ability to attach an increased proportion of beta-1,6-branched carbohydrates to the G glycoprotein of vesicular stomatitis virus (J. Ripka, S. Shin, and P. Stanley, Mol. Cell. Biol. 6:1268-1275, 1986). In this paper we provide evidence that cellular carbohydrates from Lec9 cells also contain an increased proportion of beta-1,6-branched carbohydrates, although they do not possess significantly increased activity of the beta-1,6 branching enzyme (GlcNAc-transferase V). Biosynthetic labeling experiments show that a substantial degree of underglycosylation occurs in Lec9 cells and that this affects several classes of glycoproteins. Lec9 cells synthesize ca. 40-fold less Glc3Man9GlcNAc2-P-P-lipid and ca. 2-fold less Man5GlcNAc2-P-P-lipid than parental cells do. In addition, Lec9 cells possess ca. fivefold less protein-bound oligosaccharide intermediates, and one major species is resistant to release by endo-beta-N-acetylglucosaminidase H (endo H). Membranes of Lec9 cells exhibit normal mannosylphosphoryldolichol synthase, glucosylphosphoryldolichol synthase, and N-acetylglucosaminylphosphate transferase activities in the presence of exogenous dolichyl phosphate. However, in the absence of exogenous dolichyl phosphate, mannosylphosphoryldolichol synthase and glucosylphosphoryldolichol synthase activities are reduced in membranes of Lec9 cells, indicating that membranes of Lec9 cells are deficient in lipid phosphate. This was confirmed by analysis of lipids labeled by [3H]mevalonate, which showed that Lec9 cells have less lipid phosphate than parental CHO cells. Mechanisms by which a defect in the synthesis of dolichol-oligosaccharides might alter the degree of beta-1,6 branching in N-linked carbohydrates are discussed.
 ...
PMID:Control of carbohydrate processing: increased beta-1,6 branching in N-linked carbohydrates of Lec9 CHO mutants appears to arise from a defect in oligosaccharide-dolichol biosynthesis. 272 6

The sine qua non of malignancy is the ability of tumor cells to migrate and invade surrounding tissue. There are many substances that have been described that enhance cell motility and hyaluronic acid is prominent among these. Hyaluronic acid is a high molecular weight alternating disaccharide polymer found in abundance in extracellular matrices whenever rapid cell proliferation or tissue regeneration and repair occur. It creates a permissive environment for cell motility during embryogenesis, and high levels of hyaluronic acid also correlate with increased tumor cell invasion and aggressiveness. Little is known about the regulation of hyaluronic acid production, either in normal tissue or in malignancy. In this study, we characterize a hyaluronic acid-stimulating activity in fetal calf serum and describe a similar activity in the sera of breast cancer patients. The stimulating activity was measured by placing aliquots of test substance on fibrosarcoma cells. These indicator cells, which synthesize copious quantities of hyaluronic acid, respond to stimulation in a time- and dose-dependent fashion. The fetal calf serum hyaluronic acid-stimulating activity is maximum early in gestation and then falls rapidly to essentially no activity at term. This activity was partially purified from 120-day fetal calf serum by concanavalin A-Sepharose affinity and ion exchange chromatography and is accounted for by a glycoprotein with a molecular weight of 150,000 on gel filtration under native conditions. The sera of breast cancer patients with measurable burden of disease also contained hyaluronic acid-stimulating activity, which was not present in normal serum donors or in breast cancer patients without evidence of disease. The production of this stimulating activity may contribute to the development of the malignant phenotype by inducing hyaluronic acid-rich microenvironments that are permissive to tumor cell invasion and metastases.
 ...
PMID:Hyaluronic acid-stimulating activity in sera from the bovine fetus and from breast cancer patients. 273 Nov 71

Urinary-tumor-associated antigen (U-TAA) is a glycoprotein present in the urine of melanoma patients. Previous studies have addressed the role of U-TAA in immunoprognosis. The present investigation was undertaken to determine whether the administration of whole melanoma cell vaccine (MCV) could induce the formation of anti-(U-TAA) antibodies in melanoma patients. The subjects of this study were stage II and III melanoma patients receiving MCV alone or in conjunction with cyclophosphamide. Anti-(U-TAA) IgM and IgG antibody levels were determined by enzyme immunoassay in sequential serum samples from 15 stage II and III melanoma patients receiving MCV. U-TAA purified from the urine of a melanoma patient was used as a target in this assay. The mean anti-(U-TAA) IgM titer prior to vaccination was similar to that of a non-vaccinated melanoma control group (1:1138 +/- 214, n = 15 vs 1:1334 +/- 254, n = 7; P = 0.375) but prevaccination IgG levels were generally higher than in the control group (1:3984 +/- 602 vs 1:2595 +/- 423; 0.1 greater than P greater than 0.05). While only 6 of the 15 patients demonstrated a rise in levels of IgG antibodies (mean 1:2964 +/- 1047 pre-MCV to 1:9958 +/- 2677 post MCV, P less than 0.01), 11 of the 15 patients demonstrated a greater than twofold rise in their anti-(U-TAA) IgM titers following vaccination (1:1051 +/- 259 pre-MCV to 1:2518 +/- 576 post-MCV; P less than 0.005). In addition, patients with visceral metastases consistently elicited anti-(U-TAA) responses equivalent to those with more limited disease. Concomitant administration of cyclophosphamide did not affect the response rates of peak antibody levels. The possibility that these antibody responses were actually against histocompatibility locus antigens (HLA) (contaminating our U-TAA preparation) was ruled out because the target antigen (U-TAA) was devoid of HLA, and because the induction of anti-(U-TAA) antibodies did not correlate with the induction of anti-HLA antibodies. These results demonstrate augmentation of anti-(U-TAA) IgM and IgG antibodies by immunization with the MCV.
 ...
PMID:Induction of antibodies to a tumor-associated antigen by immunization with a whole melanoma cell vaccine. 275 92

Cathepsin B activity, including that of a plasma membrane-associated cathepsin B, has been linked to tumor malignancy. As cathepsin B at the tumor cell surface has been hypothesized to play a role in the focal degradation of basement membrane during the metastatic cascade, we have examined the ability of human tumor cathepsin B to degrade laminin, an adhesive glycoprotein found exclusively in the basement membrane. We report that at pH 6.5 and 7.0 tumor cathepsin B degraded by specific, limited proteolysis both subunits of native laminin. The disappearance of both subunits and the appearance of lower Mr protein bands could be observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Accumulation of degradation products was also observed using gel filtration chromatography and a fluorescamine assay. The proteolysis of laminin by tumor cathepsin B could be inhibited by an active site titrant for cysteine proteinases or stefin B, an endogenous low-Mr cysteine proteinase inhibitor.
Clin Exp Metastasis
PMID:Degradation of laminin by human tumor cathepsin B. 278 14

Previous studies using metabolic labeling of fresh colonic mucosa and colorectal carcinoma with [35S]sulfate followed by biochemical analysis demonstrated that the amount of a sulfated high-molecular-weight glycoprotein expressed in primary colorectal carcinoma was lower than that in normal mucosa, and that the amount further decreased in liver metastases. This suggested that this sulfated molecule represented a sulfomucin previously defined by histochemical reactivity with a cationic dye. We have extracted and partially purified this high-molecular-weight sulfated glycoprotein from normal human colonic mucosa. We immunized mice with the partially purified sulfomucin and generated hybridomas. One cloned hybridoma, designated as 91.9H, produced a monoclonal antibody strongly reactive with a component which migrated at an identical position as the metabolically [35S]sulfate-labeled high-molecular-weight glycoprotein after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The reactive molecules appeared to have a polydisperse nature with a molecular weight ranging between 400,000 and 900,000. The [35S]sulfate-labeled high-molecular-weight glycoprotein was bound to Staphylococcus Protein A-agarose coated with this monoclonal antibody but did not bind to unconjugated Protein A-agarose. The immunoprecipitated substance also migrated at an apparent molecular weight range of 400,000 to 900,000. The reactivity of monoclonal antibody 91.9H with the extracts of normal mucosa, colorectal primary carcinoma, and metastasis was compared by dot blot assay on a nitrocellulose membrane. This antibody was more reactive with the extracts of mucosa adjacent to carcinoma tissues than with the carcinoma extracts. Primary tumors showed higher reactivity than metastases in most of the cases. These results strongly suggest that this antibody is specific to colonic sulfomucins or at least to mucins closely related to colonic mucins previously identified by metabolic labeling with [35S]sulfate.
 ...
PMID:Monoclonal antibody against human colonic sulfomucin: immunochemical detection of its binding sites in colonic mucosa, colorectal primary carcinoma, and metastases. 291 59

The nature of the inhibitory activity of sera of patients with metastatic cancer on in vitro immunoassays remains unclear. Serum glycoprotein levels in cancer patients show a reasonable correlation with the clinical status, especially with progressive metastatic disease. Glycoproteins like acute phase reactants have been connected with immunosuppressive activity in cancer patients' sera. In this study, we examined the influence of glycoprotein fractions of normal and cancer sera, separated by Con A immunoadsorption, on the mixed lymphocyte culture as a reference system for suppressive activity. Glycoprotein rich fractions with the utmost recovery of the acute phase reactants inhibited the mixed lymphocyte culture in a dose-dependent manner. This effect was more pronounced in patients sera as compared to control sera. But there is evidence of additional blocking activity in the glycoprotein poor serum fraction, indicating blocking factors still to be identified.
 ...
PMID:Glycoprotein-adsorption from cancer sera--influence on a mixed lymphocyte culture. 293 52

Variability of tumor-associated antigens among and within human tumor cell groups presents a potential problem in the development and optimization of immunodiagnostic and therapeutic procedures for cancer. We determined the degree of expression of a tumor-associated antigen in the primary and metastatic lesions of 23 patients with infiltrating ductal carcinoma; this was accomplished using monoclonal antibody B72.3, an IgG1 generated against membrane-enriched fractions of human metastatic breast carcinomas and reactive with a 220,000-400,000 d glycoprotein complex, termed TAG-72, and the avidin-biotin complex immunoperoxidase method on fixed tissue sections. Sixteen of the 23 breast carcinomas (70%) demonstrated MAb B72.3 reactivity (range 5% to 100% of tumor cells staining). Reactivity of lymph node metastases was present in 14 of 21 patients (67%). MAb reactivity in metastases to distant sites, including bone, adrenals, liver, skin and effusions, was present in 10 of 18 patients (56%). In one patient, neither the primary carcinoma nor the metastasis to the lymph node demonstrated reactivity. There was a statistically significant positive correlation between MAb B72.3 reactivity in both primary and lymph node metastases (Kendall's Correlation Coefficient = 0.60, p = 0.0006) and between lymph node and distant metastases (Kendall's Correlation Coefficient = 0.48, p = 0.02) of the same patient. No correlation existed between antibody reactivity seen in the primary and that found in the distant lesions of that patient. These studies thus demonstrate that monoclonal antibody B72.3 can detect expression of a tumor-associated antigen in both primary and metastatic infiltrating ductal carcinoma lesions, and may prove valuable in the understanding of tumor biology of metastases and as a means for diagnosing occult disease.
 ...
PMID:Tumor-associated antigen TAG-72: correlation of expression in primary and metastatic breast carcinoma lesions. 299 65

Tumor invasion and metastases is the major cause of treatment failure for cancer patients. There is a great need to develop new clinical methods to predict the clinical aggressiveness of a patient's tumor and to identify and eradicate clinically silent micrometastases. Such new methods may be derived from basic research into the biochemical mechanisms of invasion and metastases. We have isolated proteins involved in tumor cell attachment, invasion, and locomotion. The 'laminin receptor' is a tumor cell surface protein which specifically binds laminin, a glycoprotein of basement membranes. The laminin receptor may play a role in tumor cell attachment. 'Type IV collagenase' is a metalloproteinase which cleaves type IV basement membrane collagen but not interstitial collagens. The 'autocrine motility factor' is a secreted protein which binds to the cell surface and profoundly stimulates cell locomotion. All of these proteins appear to be augmented in actively metastatic tumor cells, at least in the models studied. They may provide strategies for diagnosis and therapy of metastases.
 ...
PMID:Biochemical mechanisms of tumor invasion and metastases. 304 Mar 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>