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

E-selectin, an endothelial cell adhesion molecule, mediates the initial step of leucocyte adhesion to activated vascular endothelium. The soluble isoform of E-selectin promotes angiogenesis in rat cornea. In the present study, we investigated whether leucocyte adhesion and angiogenesis are also involved in tumour progression and metastasis of colorectal cancer. Therefore, we determined the level of circulating soluble E-selectin in serum samples of 38 patients with colorectal cancer; 20 patients with non-metastatic and 18 patients with metastatic disease. Median levels of soluble E-selectin were found to be significantly higher in metastatic tumour disease (88.7 ng/ml, range 25-203 ng/ml) than in healthy controls (34.9 ng/ml, range 15-59 ng/ml, P = 0.01), in patients with primary tumours or with local recurrences (39.5 ng/ml, range 22-100 ng/ml). Furthermore, there was no correlation with the serum level of C-reactive protein, fibrinogen or tumour necrosis factor alpha suggesting that the elevation of E-selectin is independent of inflammation in tumour patients. Therefore, we propose that elevated soluble E-selectin may reflect increased neovascularisation in metastatic tumour tissue.
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PMID:Elevated serum E-selectin in patients with liver metastases of colorectal cancer. 875 56

Pre-operative levels of the acute phase protein C-reactive protein (CRP), albumin (assessing nutritional status), the tumour marker CEA and three plasma protease inhibitors, i.e. C1-esterase inhibitor, alpha-2-macroglobulin and antithrombin III, were prospectively studied in 183 patients with various solid cancers. First, the predictive value of abnormal levels for operability at the primary operation was studied. Secondly, the predictive value of abnormal levels for cancer recurrence and metastases was evaluated during 2 years of follow-up. The results show that malignancy induces increased CRP and C1-esterase inhibitor levels and decreased albumin levels in serum. These changes, as well as raised alkaline phosphatase and lowered haemoglobin levels, also correlate to the 'overall' tumour burden. The most important conclusion is, that increased pre-operative CRP levels (CRP > or = 10 mg/l; sensitivity, 79%; specificity, 71%) and/or low albumin levels (albumin <37 g/l; sensitivity, 94%; specificity, 54%) are seen in inoperable cancer patients compared with patients having operable cancers. The second main important conclusion is, that high pre-operative C1-esterase inhibitor levels (C1-esterase inhibitor >152%; sensitivity, 45%; specificity, 90%), and in some patients a high alkaline phosphatase level, are seen in patients exhibiting early cancer recurrence (within 2 years post-operatively).
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PMID:Pre-operative plasma levels of C-reactive protein, albumin and various plasma protease inhibitors for the pre-operative assessment of operability and recurrence in cancer surgery. 900 49

We investigated the clinical relevance of doubling time (DT) of serum laboratory data obtained in routine clinical examination of patients with primary bone and soft tissue tumors, in comparison with major clinical and pathological parameters (age at presentation, sex, tumor size, location, clinical stage and histologic grade) by uni- and multivariate analyses. In 64 patients with primary bone and soft tissue tumors (primary bone tumors: 39, primary soft tissue tumors: 25) and 68 cancer patients, the pretreatment DT values of serum C-reactive protein (CRP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), calcium (Ca), phosphate (P) levels were measured, as well as the erythrocyte sedimentation rate (ESR: mm/60 min); these values were then compared with overall survival, local recurrence-free survival and metastasis-free survival. Only DT of CRP and ALP (CRP-DT, ALP-DT) were found to be correlated with disease outcome in patients with primary bone and soft tissue tumors. In cancer patients, only CRP-DT showed a relation with clinical stage and histologic grade, but the ALP-DT in patients with bone metastasis was significantly shorter than that in patients with metastases at other sites or in those with no metastasis. Among all tumor patients, those with bone metastasis showed the shortest ALP-DT compared with those with lung, liver and brain metastasis. Univariate analysis showed that shorter CRP-DT and ALP-DT are associated with poor overall survival, and the development of local recurrence and metastasis. These findings suggest that pretreatment CRP- and ALP-DT could be additional prognostic parameters for disease outcome in patients with primary malignant bone and soft tissue tumors. However, in multivariate analysis, only ALP-DT, but not CRP-DT, was an independent prognostic parameter for these disease outcomes.
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PMID:Prognostic value of the doubling time of serum C-reactive protein and alkaline phosphatase levels in primary bone and soft tissue tumors. 904 65

The first use of granulocyte/macrophage-colony-stimulating-factor-transduced, lethally irradiated, autologous melanoma cells as a therapeutic vaccine in a patient, with rapidly progressive, widely disseminated malignant melanoma resulted in the generation of a novel antitumour immune response associated with partial, albeit temporary, clinical benefit. An initially negative reaction to non-transduced, autologous melanoma cells was converted to a delayed-type hypersensitivity (DTH) reaction of increasing magnitude following successive vaccinations. While intradermal vaccine sites showed prominent dendritic cell accrual, DTH sites revealed a striking influx of eosinophils in addition to activated/memory T lymphocytes and macrophages, recalling the histology of challenge tumour cell rejection in immune mice. Cytotoxic T lymphocytes (CTL) reactive with autologous melanoma cells were detectable at high frequency after vaccination, not only in limiting-dilution analysis, but also in bulk culture without added cytokines. Clonal analysis of CTL showed a conversion from a purely CD8+ response to a high proportion of CD4+ clones following vaccination. A prominent acute-phase response manifested by a five- to tenfold increase in C-reactive protein was observed, as was a systemic eosinophila. Vaccination resulted in the regression of axillary lymphatic metastases, stabilisation of pulmonary metastases, and a dramatic, reversible increase in cerebral oedema associated with multiple central nervous system metastases: however, lesions in the adrenal glands, pancreas and spleen proved refractory. The antitumour effects and immune response were not detectable 2 months following the last vaccination. Irradiation of the extensive cerebral metastases resulted in rapid deterioration and death of the patient.
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PMID:A case report: immune responses and clinical course of the first human use of granulocyte/macrophage-colony-stimulating-factor-transduced autologous melanoma cells for immunotherapy. 911 79

Patients with malignancies often present with signs of inflammatory reactions such as elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Since interleukin-6 (IL-6) is a possible regulator of these reactions and has been proposed as a predictor of prognosis, the aim of the study was to analyse its clinical significance in patients with renal cell carcinoma. Serum samples were collected from 196 patients before any treatment. IL-6 was analysed by an enzyme-linked immunoassay and compared with tumour grade, stage, acute-phase reactants and survival. Patients with renal cell carcinoma had significantly higher IL-6 levels (mean 28.1 +/- 63.4 ng/l; median 8.3 ng/l) compared with controls (mean 1.7 +/- 2.6 ng/l; median 0.5 ng/l; P < 0.001). Serum IL-6 levels in patients with distant metastases were significantly higher than for patients with tumours confined to the kidney (P = 0.02). This difference was more pronounced when serum IL-6 levels in patients with poorly differentiated tumours were compared with well-differentiated tumours (P < 0.001). A significant correlation between the acute-phase reactants CRP, ESR and IL-6 levels was found. Survival time was significantly shorter (P = 0.001) for patients with IL-6 levels above the median serum level compared with patients with lower levels. Similar significant prognostic results were obtained in the group of patients with metastatic disease, but not in group of patients with stage I-III. Serum levels of IL-6 correlated to tumour stage, grade and acute-phase reactants. Increased levels were related to the presence of metastases and adverse survival. Serum IL-6 proved univariate prognostic information but this prognostic significance was lost using a multivariate analysis.
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PMID:Serum interleukin-6 in relation to acute-phase reactants and survival in patients with renal cell carcinoma. 947 Aug 35

Our purpose was to determine the maximum tolerated dose and toxicity associated with soluble Chinese hamster ovary [s(CHO)] recombinant human interleukin (IL) 1 receptor (IL-1R; Immunex, Seattle, WA) administration in humans and to determine the effective biological dose and/or maximum tolerated dose of the s(CHO) IL-1R in combination with high-dose IL-2 as determined by reduction in IL-2 toxicity and modulation of its biological effects. Twenty-seven patients with metastatic cancer were treated with escalating doses of s(CHO) IL-1R at 1, 1, 5, 10, 20, 40, and 55 mg/m2 i.v. on days -6 (except cohort 2), 1, and 15 and IL-2 at doses of 300,000 IU/kg (cohort 1) and 600,000 IU/kg (cohorts 2-7) i.v. every 8 h on days 1-5 and 15-19. No toxicity directly attributable to s(CHO) IL-1R was observed. The median number of IL-2 doses was 23. Hypotension and neurotoxicity were the major dose-limiting toxicities for the IL-2/s(CHO) IL-1R combination. Of the 24 patients treated with full-dose IL-2, there were six responses, three complete and three partial (response rate, 25%). Three patients developed thyroid dysfunction, and all 3 responding melanoma patients exhibited vitiligo. The t1/2 of s(CHO) IL-1R alone was 24-30 h and was not significantly altered by coadministration with IL-2. Whole-blood functional assays indicated that sufficient s(CHO) IL-1R was present in the circulation at top dose levels to inhibit the in vitro effects of IL-1beta on IL-8 induction; however, no effect on IL-2-induced IL-8 induction, or on the IL-1beta- or IL-2-induced tumor necrosis factor production, was observed. Suppression of IL-2-mediated tumor necrosis factor alpha and IL-6 induction in vivo during the first 24 h after IL-2 administration was observed, and the neutrophil chemotactic defect normally seen with IL-2 was not observed. IL-1R antagonist induction far exceeded that seen previously with IL-2 alone. No inhibition of either serum C-reactive protein induction or enhanced urinary nitrate excretion and no consistent effect on IL-2-related changes in peripheral blood mononuclear cell phenotype or endothelial adhesion molecule expression were seen. The coadministration of s(CHO) IL-1R produced no apparent reduction in IL-2 clinical toxicity manifested by either the ability to administer more IL-2 than anticipated or a reduction in the toxicity associated with a given amount of IL-2. Therefore, no effective biological dose could be identified for the s(CHO) IL-1R.
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PMID:A two-part phase I trial of high-dose interleukin 2 in combination with soluble (Chinese hamster ovary) interleukin 1 receptor. 960 78

Our purpose was to determine the effective biological dose and/or maximum tolerated dose of recombinant human tumor necrosis factor receptor:IgG chimera (rhuTNFR:Fc; Immunex, Seattle, WA) in combination with interleukin 2 (IL-2) with regard to reduction in IL-2 toxicity and modulation of biological effects of high-dose IL-2 administration. Twenty-four patients with metastatic cancer were treated with escalating doses of rhuTNFR:Fc at 1, 1, 5, 10, and 20 mg/m2 i.v. on days 1 and 15 (dose levels 1-5) or 10, 20, and 30 mg/m2 days 1 and 15 plus 50% dose on days 3, 5, 17, and 19 (dose levels 6-8) prior to IL-2 at doses of 300,000 IU/kg (dose level 1) and 600,000 IU/kg (dose levels 2-8) i.v. every 8 h on days 1-5 and 15-19. The t1/2 of rhuTNFR in patients receiving IL-2 was 72 h. The median number of IL-2 doses was 24, and central nervous system, skin, and cardiac arrhythmias were the major dose-limiting toxicities. TNF bioactivity was inhibited, and the polymorphonuclear leukocyte chemotactic defect normally seen with IL-2 was not observed. Increases in C-reactive protein, IL-6, IL-8, and IL-1 receptor antagonist levels were partially suppressed relative to historical controls, whereas peripheral blood mononuclear cell phenotypes, urinary nitrate, endothelial adhesion molecule expression in skin biopsies, and cellular infiltrates in tumor biopsies were consistent with findings in patients treated with IL-2 alone. Four patients developed thyroid dysfunction. There were five responses: two complete responses (both melanoma) and three partial responses (response rate, 21%). rhuTNFR:Fc may modulate the toxicity and some of the biological effects of IL-2 while preserving antitumor activity. Dose level 6 (10 mg/m2 on days 1 and 15, and 5 mg/m2 on days 3, 5, 17, and 19) has been chosen for a randomized, double-blind, placebo-controlled trial of IL-2 with and without rhuTNFR:Fc.
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PMID:Phase I trial of interleukin 2 in combination with the soluble tumor necrosis factor receptor p75 IgG chimera. 981 6

Mice were injected in the hind limb with a mouse mammary adenocarcinoma cell line, EMT6, and tumor growth at the primary site as well as the incidence of lung metastases were measured. Groups of animals were treated with the acute-phase reactant C-reactive protein, (native-CRP), or a conformationally modified form of CRP (mCRP) made by dissociating CRP subunits under chelating, denaturing conditions. Each form of CRP was injected (intravenously) through the tail vein, encapsulated in large unilamellar lipid vesicles made by an extrusion technique (LUVETs). mCRP was also injected without the LUVET carrier. Mice not treated, or treated with LUVETs alone, exhibited both progressive tumor growth at the primary site and a high incidence of metastatic lung tumors quantified at necropsy. Treatment with native-CRP encapsulated in LUVETs had little or no effect on either tumor growth or metastases. Treatment with mCRP, however, alone or encapsulated in LUVETs, effectively slowed or stopped the progression of tumor growth, and in some mice, showed a decrease in tumor size. After cessation of mCRP injections, tumor growth resumed at a rate comparable to that measured in untreated animals. Fifty to 85% of mice treated with mCRP or mCRP in LUVETs developed necrotic lesions at the primary tumor site within 24-48 h following the initial injection of protein. Furthermore, at necropsy, only 6% of mice treated with mCRP in LUVETs and 40% of mice treated with mCRP alone showed evidence of lung metastases compared to 67-80% of animals in no-treatment, native-CRP in LUVETs and in LUVET control group animals. These results show that the prototypic acute-phase reactant, CRP, has therapeutic anticancer and antimetastatic activity only when the native pentameric subunit structure is dissociated to form the mCRP conformer.
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PMID:Inhibition of mouse mammary adenocarcinoma (EMT6) growth and metastases in mice by a modified form of C-reactive protein. 1005 Jan 6

The aim of this study was to determine the value and limitations of 18F-fluorodeoxyglucose (FDG)-position-emission tomography (PET) for differentiating benign and malignant pancreatic disease and for staging malignant disease. One hundred fifty-nine patients with 89 malignant and 70 benign pancreatic lesions all received PET, computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) before pancreatic surgery. The original reports were compared for all patients (group I; N = 159), for a subgroup that neither had fasting plasma glucose levels > or =130 mg/dL or known elevated levels of C-reactive protein ([CRP], group II; n = 123), and for the remaining patients (group III; n = 36). For group I, accuracy values (areas under receiver operating characteristic [ROC] curves) for differentiation of benign/malignant masses were 0.86 (PET), 0.93 (ERCP), 0.82 (CT), and 0.95 for ERCP + PET (N = 159). For group II, ROC areas increased to 0.92 (PET), 0.94 (p < 0.05; n = 123) (ERCP), 0.82 (CT), 0.97 (p < 0.05; n = 123) (ERCP + PET). The results for group III were 0.71 (PET), 0.81 (CT), and 0.93 (ERCP); (n = 36). With 54 patients of group II that either had contradictory or indeterminate/technically unsuccessful CT/ERCP, PET was correct in 43 patients (84%). Sensitivity/specificity for lymph node staging was 49%/63%, respectively. For patients with hepatic metastasis, PET was 70% sensitive and 95% specific, missing some metastasis that were <1 cm. PET detected peritoneal metastasis in 25% of patients, missing poorly localized microscopic spread. For selected patients who have indeterminate pancreatic masses but no hyperglycemia or serologic evidence of active inflammation, FDG-PET is an independent functional assay that significantly adds to the diagnostic accuracy of ERCP and CT in the differentiation of benign and malignant pancreatic disease. PET can reliably detect hepatic, peritoneal, and other distant metastases that are > or =1 cm.
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PMID:Values and limitations of 18F-fluorodeoxyglucose-positron-emission tomography with preoperative evaluation of patients with pancreatic masses. 1070 24

Of 67 patients with recurrent breast cancer accompanied by liver metastases admitted to our facility between January 1990 and August 1993, 8(12%) were found to have tumor-associated fever. We examined the characteristics of these patents. These patients had fever (over 38 degrees C) for more than one week. Their leukocyte counts did not exceed 10000/mm(3), and C-reactive protein (CRP) was below 5 mg/dl in 6 patients. ALL 8 patients had extensive liver metastases. Six patients had massive metastatic lesions, while the remaining 2 had diffuse metastases. Following systemic chemotherapy, 3 patients showed a reduction in tumor size and remission of fever; they remain alive at 14, 16 and 19 months after treatment. Of the remaining 5 patients who did not respond to systemic chemotherapy, 4 died within 6 months. The results of this study suggest that unexplained fever in patients with recurrent breast cancer is closely related to liver metastases.
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PMID:Tumor-associated Fever in Recurrent Breast Cancer with Liver Metastases. 1109 23


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