Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum levels of interleukin 6 (IL-6) are correlated with the disease status and prognosis in cancer patients. IL-6 is also an important mediator of experimental cancer cachexia. We investigated the production of IL-6 and IL-6 receptors and expression of IL-6 mRNA by esophageal squamous carcinoma cells using immunohistochemical staining and in situ reverse transcription-PCR. We also measured levels of serum IL-6 using an ELISA in 50 patients with esophageal squamous cell carcinoma (ESCC) to determine the correlation between serum levels of IL-6 and clinicopathological factors IL-6 mRNA was expressed in the primary tumor. Esophageal squamous carcinoma cells produced both IL-6 and IL-6 receptor. IL-6 concentrations were significantly higher in the primary tumor than in the normal epithelium. The incidences of weight loss, tumor invasion to adjacent organs, and noncurative resection were significantly higher in ESCC patients with serum levels of IL-6 > or = 7 pg/ml (n = 13, group C) compared with patients with serum levels <7 pg/ml and > or = 3 pg/ml (n = 14, group B) and <3 pg/ml (n = 23, group A). Tumor size and C-reactive protein levels were significantly higher and albumin levels were significantly lower in group C. Results suggest that IL-6, which is produced by tumor cells, may be related to various disease parameters as well as to the nutritional status in patients with ESCC.
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PMID:Relationship between serum levels of interleukin 6, various disease parameters and malnutrition in patients with esophageal squamous cell carcinoma. 866 13

The ability of malignant cells to metastasize from a primary tumor and from secondary lesions is the most life-threatening aspect of cancer. Reported factors enabling this metastatic cascade to occur include reduced levels or an absence of cell-adhesion molecules, proteolytic enzymes, and angiogenic factors. The metastatic cell must also escape immune destruction. Defects in lymphocytes from renal-cell carcinoma patients with abnormalities in their proliferation, receptor structure, and signal transduction are present. The pathologic stage has been the most consistent single prognostic factor to influence survival. Other factors include the performance status, age, and histology grade and may include serum interleukin 6 (IL-6) levels and ploidy. Current and future therapeutic approaches that interfere with this metastatic cascade include applications of cytokines, antiadhesion-molecule strategies, and antisense nucleotides. An improvement in our understanding of the biology of metastases is essential before a significant increase in the cure rate can be realized.
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PMID:Biology of metastasis and its clinical implications: renal-cell cancer. 880 96

Angiogenesis has an important role in the progression of solid tumors. Therefore, we measured the blood levels (ELISA) of angiogenic factors [basic fibroblast growth factor (bFGF), hepatocyte growth factor/scatter factor, and vascular endothelial growth factor (VEGF)] and soluble adhesion molecules [E-selectin, intercellular adhesion molecule (ICAM-1), platelet endothelial cell adhesion molecule-1, and vascular cell adhesion molecule-1] in 76 consecutive patients with untreated renal cell carcinoma and 41 healthy controls to evaluate their prognostic value. The serum levels of bFGF, hepatocyte growth factor, and VEGF were significantly higher in patients with renal cancer than they were in healthy subjects. bFGF and VEGF values were significantly higher in patients with disseminated cancer (N+ and/or M+) than they were in those with undisseminated (M-N-) cancer: median = 27 pg/ml, range = 5-118, n = 15 versus median = 8 pg/ml, range = 1-149, n = 61 (P = 10(-4)) for bFGF; and median = 883 pg/ml, range = 200-2317, n = 15 versus median = 278 pg/ml, range = 0-1704, n = 61 (P = 0.006) for VEGF. The blood levels of ICAM-1 and vascular cell adhesion molecule-1 were significantly higher, and the levels of E-selectin and platelet endothelial cell adhesion molecule-1 were significantly lower in patients with renal cancer than they were in controls. Plasma ICAM-1 was higher in metastatic patients (M+) than they were in nonmetastatic (M-) patients: median = 687 ng/ml, range = 294-1091, n = 12 versus median = 408 ng/ml, range = 217-1375, n = 64 (P = 10(-4)). ICAM-1 and bFGF blood values were correlated with the size of the primary tumor. The interleukin 6 and tumor necrosis factor-alpha (TNF-alpha) values of these patients have been previously published and are included in the survival analysis. Univariate analysis showed that bFGF, ICAM-1, interleukin 6, and TNF-alpha, before treatment, were prognostic factors. In multivariate analysis for proportional hazard regression, only TNF-alpha was an independent prognostic indicator, with a normal plasma TNF-alpha being highly predictive for a good prognosis in patients with untreated renal cell carcinoma.
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PMID:Are angiogenic factors, cytokines, and soluble adhesion molecules prognostic factors in patients with renal cell carcinoma? 981 46

Kaposi sarcoma-associated herpesvirus (KSHV), or human herpervirus 8 (HHV-8), is a gamma-herpesvirus that infects human lymphocytes and is associated with primary effusion lymphoma (PEL). Currently, the role of viral infection in the transformation of PEL cells is unknown. One possibility is that KSHV, like the lymphotropic viruses Epstein-Barr virus (EBV) and human T-cell leukemia virus I (HTLV-I), activates the transcription factor NF-kappaB to promote survival and proliferation of infected lymphocytes. To examine this possibility, we assessed NF-kappaB activity in KSHV-infected PEL cell lines and primary tumor specimens by electrophoretic mobility shift assay (EMSA). We observed that NF-kappaB is constitutively activated in all KSHV-infected lymphomas, and consists of 2 predominant complexes, p65/p50 heterodimers and p50/p50 homodimers. Inhibition experiments demonstrated that Bay 11-7082, an irreversible inhibitor of IkappaBalpha phosphorylation, completely and specifically abrogated the NF-kappaB/DNA binding in PEL cells. PEL cells treated with Bay 11 demonstrated down-regulation of the NF-kappaB inducible cytokine interleukin 6 (IL-6), and apoptosis. These results suggest that NF-kappaB activity is necessary for survival of KSHV-infected lymphoma cells, and that pharmacologic inhibition of NF-kappaB may be an effective treatment for PEL.
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PMID:Inhibition of NF-kappaB induces apoptosis of KSHV-infected primary effusion lymphoma cells. 1100 8

Cancer progression and metastasis involves interactions between tumor cells and the tumor microenvironment (TME). We reported that mice deficient for cytosolic phospholipase A(2) (cPLA(2)-KO) are protected against the development of lung tumors. The goal of this study was to examine the role of cPLA(2) in the TME. Mouse lung cancer cells (CMT167 and Lewis lung carcinoma cells) injected directly into lungs of syngeneic mice formed a primary tumor, and then metastasized to other lobes of the lung and to the mediastinal lymph nodes. Identical cells injected into cPLA(2)-KO mice showed a dramatic decrease in the numbers of secondary metastatic tumors. This was associated with decreased macrophage staining surrounding the tumor. Wild-type mice transplanted with cPLA(2)-KO bone marrow had a marked survival advantage after inoculation with tumor cells compared with mice receiving wild-type (WT) bone marrow. In vitro, coculturing CMT167 cells with bone marrow-derived macrophages from WT mice increased production of interleukin 6 (IL-6) by cancer cells. This increase was blocked in cocultures using cPLA(2)-KO macrophages. Correspondingly, IL-6 staining was decreased in tumors grown in cPLA(2)-KO mice. These data suggest that stromal cPLA(2) plays a critical role in tumor progression by altering tumor-macrophage interactions and cytokine production.
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PMID:Depletion of cytosolic phospholipase A2 in bone marrow-derived macrophages protects against lung cancer progression and metastasis. 1920 32

To examine whether tissue levels of interleukin 6 (IL-6) are associated with the clinicopathologic status in human breast cancer, immunoreactive IL-6 concentration was measured in tumor extracts of 75 breast cancer patients. IL-6 was detectable in 69 of 75 tumor extracts by enzyme-linked immunosorbent assay, the concentration ranging from 10 to 10.690 pg/mg protein. When breast cancer specimens were categorized into four groups in terms of clinical stage of disease at diagnosis, IL-6 concentration (mean +/- SE) in tissue extracts was significantly higher in stage IV patients (2859 +/- 840 pg/mg protein) than in stage I-III patients (344 +/- 117, 350 +/- 150 and 564 +/- 230 pg/mg protein, respectively). Correlation analyses between IL-6 concentration and clinicopathologic factors showed that tissue levels of IL-6 were significantly higher in patients with distant metastasis compared with those without. Furthermore, IL-6 concentration was significantly higher in tumors of more than 5.0 cm in size as compared to less than 5.0 cm. However, no significant association was found between IL-6 concentration and age, histological type, histological grade, lymph node involvement, or hormone receptor status. These results suggest that primary tumor levels of IL-6 are closely associated with clinical stage in human breast cancer.
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PMID:Primary tumor levels of interleukin-6 in relation to tumor burden in human breast-cancer. 2160 12