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)

Frozen sections of primary and metastatic human renal cell carcinoma (RCC) were analyzed for the expression of endogenous binding sites for carbohydrates. Fluorescent neoglycoproteins, carrying chemically linked carbohydrate residues on bovine serum albumin as a carrier protein, were applied to 44 primary tumor specimens. In the majority of specimens, accessible binding sites with specificity for maltose and N-acetylgalactosamine were detected. In specimens of normal kidney no specific binding of carbohydrate ligands was observed under these experimental conditions. Specimens of both the primary tumor and a metastasis were available in 10 cases. When the expression of specific binding sites of primary tumors and metastases was compared, the respective patterns were similar with no clear gain or loss of certain lectins in the metastases. We conclude that binding sites with specificity for maltose and N-acetylgalactosamine are present on human RCC and their corresponding metastases.
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PMID:Detection of endogenous receptors for carbohydrate ligands in primary and metastatic human renal cell carcinoma. 821 20

Normal and neoplastic cells interact with laminin via a variety of cell surface proteins. The specific binding sites on laminin for each particular cell surface laminin-binding protein have not yet been identified. In this study, the interaction between laminin and the high affinity metastasis-associated 67 kD laminin receptor (67 LR) was investigated by electron microscopy using the rotary shadowing technique. Laminin receptor that was purified from human colon carcinoma metastases appeared as a globular structure with a diameter of 5.2 +/- 0.8 nm. The 67 LR specifically bound to laminin on its long arm close to the intersection of the long and the short arms. There was no specific interaction of bovine serum albumin with laminin. Biochemical confirmation of the rotary shadowing experiments included slot blot solid phase assays in which [I125]-labeled 67 LR bound in a dose dependent manner to laminin as well as to the chymotrypsin resistant (C1) fragment of laminin that contains a short piece of the long arm. [I125]-labeled 67 LR did not bind to the pepsin resistant (P1) fragment of laminin that did not contain that segment on the long arm. This study therefore identifies the binding site on laminin for the 67 kD metastasis-associated laminin receptor as a region on the long arm of laminin close to the intersection of the four arms.
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PMID:Interaction between the 67 kilodalton metastasis-associated laminin receptor and laminin. 843 67

We have synthesized various formulations that have potential for active specific immunotherapy (ASI) of human cancers. Sialyl-Tn (STn) is a potentially important target structure for ASI because its expression on mucins is a strong, independent predictor of poor prognosis, suggesting that it may have functional significance in the metastatic process. In this first pilot study of synthetic sialyl-Tn hapten conjugated to keyhole limpet hemocyanin (STn-KLH), with Detox adjuvant, toxicity and humoral immunogenicity were assessed in 12 patients with metastatic breast cancer. Toxicity was minimal, restricted to local cutaneous reactions (apart from transient nausea and vomiting following single low-dose cyclophosphamide treatment). Using STn-conjugated human serum albumin in a solid-phase enzyme-linked immunosorbent assay, it was shown that all patients developed IgM and IgG specific for the synthetic STn hapten. Following immunization, most patients were shown to develop increased titres of complement-mediated cytotoxic antibodies, partially inhibited by synthetic STn hapten, but not by the related TF hapten. We also detected IgM and IgG antibodies reactive with natural STn determinants expressed on ovine submaxillary mucin, the STn specificity of this reactivity being confirmed by hapten inhibition. Evaluation of clinical efficacy in a small pilot study is difficult. Five patients are alive 12 or more months after entry, and another 4 patients are alive 6 or more months after entry into the study. All 3 patients with known widespread bulky disease progressed despite ASI, 2 having died from widespread cancer. Two patients had partial responses, each lasting 6 months. While several patients had disease stability for 3-10 months, 1 patient with pulmonary metastases remains stable 15 months after entry into the program.
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PMID:Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant. 843 84

We investigated the antitumor effect of 6-mercaptopurine (6-MP) and its analogs using the double grafted tumor technique. BALB/c mice were inoculated intradermally with MethA fibrosarcoma cells at the right inguinal region on day 0 (the primary tumor) and at the left on day 10 (the secondary tumor). Intraperitoneal or intra-lesional administration of 6-MP, 6-mercaptopurine riboside (6-MP-r) and 6-mercaptopurine riboside triacetate (6-MPRTA) from day 3 to 7 dose-dependently inhibited growth of the secondary tumor. Without the primary inoculation, 6-MP showed no effect on growth of the tumor inoculated on day 10, indicating that the antitumor effect of 6-MP could not be attributable to its direct antimetabolic or tumoricidal action only, and that the primary tumor inoculation is necessary for these compounds to inhibits growth of the challenging tumor. 6-MP did not inhibit the secondary MethA growth in the BALB/c (nu/nu) mouse. Both CD4+ and CD8+ T cells increased in the spleen of mice treated with 6-MP. Meanwhile, delayed-type hypersensitivity (DTH) reaction to the methylated bovine serum albumin (MBSA) antigen at the footpad was not augmented but inhibited by 6-MP-r and 6-MPRTA in both normal and tumor-bearing mice. Thus, the immunomodulatory activity of 6-MP could be observed in two opposite directions, augmentation of tumor immunity and inhibition of DTH to MBSA. This indicates that the immune mechanism and/or the type of effector cells induced in these two cell-mediated immune systems are different from each other.
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PMID:Augmentation of tumor immunity by 6-mercaptopurine (6-MP) and its analogs in the double grafted tumor system in mice. 859 65

The aims of this study were to assess whether 99Tcm-phytate can detect metastatic skeletal lesions, and to compare it with 99Tcm-methylene diphosphonate (99Tcm-MDP) and 99Tcm-labelled human serum albumin nanocolloids (99Tcm-NC). Twenty-four patients with multiple bony metastases, investigated by 99Tcm-MDP whole-body scintigraphy, underwent 99Tcm-phytate bone marrow imaging. A separate bone marrow scintigram with 99Tcm-NC was performed in 20 of the patients. All of the metastatic lesions detected on the 99Tcm-phytate scintigrams exhibited photon-abundant foci only. Most of the 99Tcm-phytate scintigrams detected fewer metastatic lesions than the corresponding bone scintigrams. Visual comparison of the 99Tcm-NC images showed that 13 of 20 99Tcm-NC images were superior to the 99Tcm-phytate images in the detection of metastatic involvement of the skeleton. Thus 99Tcm-phytate should not be used as a bone marrow imaging agent for the detection of skeletal metastases.
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PMID:Clinical evaluation of the bone marrow imaging agent 99Tcm-phytate in the detection of bone metastases. 900 98

Adhesion of metastatic cancer cells at secondary sites is known to be regulated by several families of adhesion proteins, including selectins and integrins. Colon carcinoma cells have been shown to tether to and roll on both stimulated endothelial cells and purified E-selectin. We have demonstrated that HT-29 human colon carcinoma cells adhere specifically to an E-selectin-IgG chimera. Upon adhesion to E-selectin, the amount of tyrosine phosphorylation of several proteins in HT-29 cell lysates increases compared with cells in bovine serum albumin-coated wells on phosphotyrosine Western blots; this increase is statistically significant. This effect is specific for adhesion to E-selectin, since addition of an E-selectin blocking monoclonal antibody (MAb), E3, to the wells causes a statistically significant decrease in tyrosine phosphorylation relative to E-selectin alone on phosphotyrosine Western blots. One protein that is affected this way has been identified as c-src. Kinase assays show a dose-dependent and statistically significant decrease in c-src activity upon adhesion to E-selectin, which correlates with an increase in phosphorylation of Tyr 527, the negative regulatory tyrosine. CnBr digestion of 32P-labeled c-src shows an increase in phosphorylation of tyrosine 527 after adhesion to E-selectin. Our results may identify a signaling pathway involving the E-selectin ligand on HT-29 cells and c-src.
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PMID:Adhesion of HT-29 colon carcinoma cells to E-selectin results in increased tyrosine phosphorylation and decreased activity of c-src. 917 21

We investigated the possible causative role of interleukin 6 (IL-6) in the paraneoplastic inflammatory syndrome and in paraneoplastic cholestasis (Stauffer syndrome) associated with renal-cell carcinoma in a series of 119 patients with metastases. IL-6 levels were found significantly higher in patients with paraneoplastic fever and weight loss. Patients with detectable serum IL-6 (n = 90, 76%) had significantly higher serum CRP, haptoglobin, and serum alkaline-phosphatase and gammaglutamyl-transferase levels. Platelets, polymorphonuclear neutrophil (PMN) and monocyte counts were also significantly higher in patients with detectable serum IL-6; in contrast, hemoglobin levels were significantly lower in patients with serum IL-6 over 80 pg/ml. Three of these patients were included in a phase-II trial of an anti-IL-6 monoclonal antibody given daily during 21 days. Reductions of CRP, haptoglobin and serum alkalin phosphatases were observed in all 3 patients during anti-IL-6 administration, with a subsequent increase up to or above pre-treatment levels after the end of anti-IL-6. Decrease of platelets, PMN and monocyte counts were also observed in the 3 patients during anti-IL-6 administration, with a normalization of cell counts in a patient with increased platelets, PMN and monocyte counts. Hemoglobin concentration, serum albumin concentration and lymphocyte counts remained stable in the 3 patients during and after anti-IL-6 administration. Serum IL-6, as evaluated by IRMA, decreased in the 3 patients during anti-IL-6 administration, but increased above pre-treatment levels after the end of anti-IL-6 administration. These results demonstrate that IL-6 is involved in the physiopathology of paraneoplastic syndromes observed in patients with metastatic renal-cell carcinoma, in particular CRP and haptoglobin increase, paraneoplastic cholestasis, also paraneoplastic thrombocytosis, neutrophilia and monocytosis.
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PMID:Role of interleukin-6 in the paraneoplastic inflammatory syndrome associated with renal-cell carcinoma. 924 85

Hyaluronidase, a matrix-degrading enzyme, was assayed in extracts from breast primary tumors and regional metastases using a pool of human sera as a standard. Optimal activities of tumor extracts and serum were found for concentrations of 0.15-0.20 M NaCl in pH 3.8-4.0 buffer. In evaluating contamination by serum due to vascular proliferation, we expressed our results as the ratio of the entire activity (mU/l extract) on serum albumin content of tumors (g/l). Median (interquartile range) activities were 9.02 (6.04-14.34) for primary tumors and 37.36 (24.06-99.63) mU/g albumin for metastases. The difference was significant. Zymographic analysis showed that 3 bands of activity were detected which corresponded to 68, 53 and 49 kDa for tumoral hyaluronidase. The same pattern was observed for cellular extracts of breast cancer cell line CAL51, demonstrating that hyaluronidase detected in tumor extracts had mainly a cellular origin. Our results suggest that hyaluronidase may be involved in the metastatic process.
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PMID:Increased hyaluronidase levels in breast tumor metastases. 935 77

The records of 116 patients from a single center (1970-1993) with newly diagnosed Ewing's sarcoma or primitive neuroectodermal tumor were reviewed retrospectively. The aim of this study was to ascertain the impact of pretreatment variables on disease-free survival. Median age was 14 years (range 1-34). Twenty patients presented with metastatic disease. Treatment consisted of systemic multiagent chemotherapy plus local irradiation (39%), wide resection (22%), or both (35%). Median potential follow-up was 10.7 years (range 2-26). Three patients developed second malignancies (1 breast carcinoma, 2 acute myeloid leukemias). Median time to relapse was 24 months (range 3-143). The actuarial disease-free survival was 37.4% at 5 years, 33.3% at 10 years and 27.8% at 15 years. Neoadjuvant chemotherapy and a therapy-induced tumor necrosis > or = 90% were associated with a better outcome. Patients undergoing surgical resection had a superior disease-free survival than those treated without surgery (45 vs. 18% at 10 years, p = 0.0009). Multiple regression analysis showed that raised serum lactate dehydrogenase levels (p < 0.001), hypoalbuminemia (p = 0.001) and distant metastases at diagnosis (p = 0.03) were independent adverse prognostic factors. In conclusion, one third of patients with Ewing's sarcoma become long-term survivors with combined modality treatment. Late relapses and second neoplasms are of concern. Prognostic factors should be considered in the selection of therapy, and the value of serum albumin warrants confirmatory studies.
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PMID:Long-term follow-up and prognostic factors in Ewing's sarcoma. A multivariate analysis of 116 patients from a single institution. 942 71

We investigated the antitumor effect of vitamin A(VA) using the double grafted tumor technique to examine whether VA administered into a primary tumor (intralesionally or i.l.) accelerates antitumor immune reactions so that growth of the secondary tumor may be more effectively inhibited than by other systemic administration routes. In the double grafted tumor system, where BALB/c mice were inoculated with MethA fibrosarcoma cells into the right inguinal region (1 x 10[6] cells) on day 0 and later into the left (3 x 10[6] cells) on day 10, the injection of VA at a dose of 1000 IU/mouse i.l., s.c., i.p., and i.v. on days 3 through 7 inhibited the growth of the secondary tumor to the same extent, while VA at the i.l. dose of 100 IU/mouse into the primary tumor inhibited more effectively than by any other administration route. VA did not inhibit the secondary MethA growth in BALB/c (nu/nu) mice. The spleen cells taken from VA-treated tumor-bearing mice prevented the growth of MethA tumors in naive BALB/c mice when given as a mixture with the MethA inoculum (the Winn assay). The delayed-type hypersensitivity (DTH) response to methylated bovine serum albumin (MBSA) antigen was augmented when VA (1000 IU) was injected at the site of the antigen injection. These results suggest that the direct interaction of VA with the tumor cells may be necessary for the tumor immunity-potentiating effect of VA, and that T-lymphocyte-mediated tumor immunity is involved in the anti-tumor effect of VA. The antitumor mechanism of VA seems to involve retinoid receptors, because the benzoic acid derivative Am80, which has been reported to exert retinoidal activity by binding to specific retinoid receptors, also showed activity.
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PMID:Augmentation of tumor immunity in mice by intralesional injection of vitamin A. 958 69


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