Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor effect of biscoclaurine alkaloids, at a distant site was examined in the double grafted tumor system, in which mice received simultaneous intradermal inoculations of Meth-A in both right (10(6) cells) and left (2 x 10(5) cells) flanks and were then injected with 0.5 mg of CR in the right tumor on days 3, 4 and 5. CR inhibited the growth of not only the right but also the left, non-treated tumor. In order to examine the role of lymph nodes in the antitumor activity of CR, regional (axillary and inguinal) lymph nodes were resected. Since in resected mice the antitumor activity of CR against the left tumor was weakened, the regional lymph nodes have a very important role in the antitumor effect of intratumoral administration of CR at a distant site. Spleen cells prepared from CR treated mice were examined for Lyt-1, Lyt-2 and L3T4 phenotypes. The number of Lyt-1 positive lymphocytes increased in the spleen after intratumoral administration of CR. Isolated tumor cells obtained from the right tumor treated with CR and the left side tumor on day 6 were cultured for 24 h. The culture supernatants were harvested and tested for the presence of chemotactic activity for neutrophil or macrophage. Significant neutrophil chemotactic factor (NCF) activity was detected in the culture media from CR-treated right tumor tissue, and macrophage chemotactic factor (MCF) activity was detected in the culture media from left tumor tissue. CR-induced NCF was partially neutralized by treatment with anti-human IL-8 IgG, and might be murine IL-8 factor. These results suggest that intratumoral administration of CR first induces neutrophils in the right tumor, then Lyt-1 positive cells in the spleen, and subsequently induces cytotoxic macrophages in the left, non-treated tumor, thus bringing about the regression of distant tumors.
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PMID:[Antitumor Effector mechanism of plant alkaloid preparation, cepharanthin, by intratumoral administration]. 187 22

We have studied cytokine expression by the human bladder carcinoma cell line 5637 using a cDNA-PCR procedure. Transcripts for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-7, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, M-CSF, tumor-necrosis factor-alpha (TNF-alpha), and TNF-beta were constitutively present, whereas IL-3, IL-4, IL-5, and IL-9 mRNA sequences could not be detected. This expression pattern was not altered after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulation (4 and 8 h) of 5637 cells. Relative expression levels of cytokines were assessed by limiting dilution of the cDNA pool. This procedure proved to be a semiquantitative technique when compared to Northern blot analysis.
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PMID:Cytokine production by the bladder carcinoma cell line 5637: rapid analysis of mRNA expression levels using a cDNA-PCR procedure. 188 17

Gelatinases (type IV collagenases) produced by normal peripheral blood leukocytes were studied by the use of a substrate conversion assay. When monocytes were stimulated with IL-1 beta discrete amounts of a 85-kDa gelatinase were detected. This type of gelatinase comigrated with a phorbol ester-inducible metalloproteinase from human tumor cells. The levels of induction of the monocytic enzyme after stimulation with IL-1, double-stranded RNA, LPS, and mitogens paralleled those of the secondary cytokine IL-6. When peripheral blood neutrophils were stimulated with IL-8 or PMA significant amounts of a 91-kDa neutrophil gelatinase were released, whereas with IL-1 beta no effect was observed. Both neutrophil and monocyte gelatinases cross-reacted in immunoprecipitation experiments with tumor cell-derived gelatinases. Further evidence for structural similarity between the IL-1-inducible monocytic (85 kDa) and the IL-8-regulated neutrophilic (91 kDa) gelatinases was obtained after purification of the proteins to homogeneity: both gelatinases possessed an identical amino terminal amino acid sequence and appeared as truncated forms of gelatinase from tumor cells. Synovial fluids of arthritic joints contained extremely high concentrations of the 91-kDa gelatinase. The concentrations of this type of gelatinase were correlated with the titers of the marker cytokine IL-6. The controlled production and activity of leukocyte-derived gelatinase may play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. In the arthritis patient this enzyme might contribute to the pathogenesis of joint destruction and might constitute a useful marker of disease status.
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PMID:Cytokine-mediated regulation of human leukocyte gelatinases and role in arthritis. 193 76

The protein-bound polysaccharide extracted from a fungus, PSK, has been used as a biological response modifier in the treatment of cancer patients in Japan for over ten years. Although the antitumor mechanism of PSK is not fully understood, host-mediated antitumor activity has been claimed to play a significant role. The administration of PSK to tumor-bearing rodents inhibited tumor growth and modulated immune responses. To clarify the potential immunomodulating activities of PSK, we examined the direct effect of PSK on cytokine gene expression and production in human peripheral blood mononuclear cells (PBMC) in vitro. As determined by Northern blotting, PSK was a potent inducer of gene expression for IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor (TNF-alpha) and monocyte chemotactic and activating factor (MCAF), but not for IL-2 and lymphotoxin (LT). Expression of mRNA occurred at 1-3 hr in a dose dependent manner using from 5-400 micrograms/ml of PSK. Furthermore, these cytokines were also produced in response to PSK as detected by ELISA, RIA or bioassays. We speculate that these cytokines may mediate immunoenhancing actions of PSK in vivo.
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PMID:Induction of gene expression and production of immunomodulating cytokines by PSK in human peripheral blood mononuclear cells. 209 Aug 74

The antitumor effect of PSK, a Coriolus preparation, at a distant site was analyzed with the use of a double grafted tumor system in which male BALB/c mice received simultaneous intradermal inoculations of Meth-A tumor in the right (10(6) cells) and the left (2 x 10(5) cells) flanks and were then injected with PSK in the right tumor on the third day thereafter. The antitumor effect of intratumoral administration of PSK in the right tumor on days 3, 4 and 5 was compared with the effect of surgical resection of the right tumor on day 5. Three out of 8 mice given PSK intratumorally became tumor-free whereas no mouse tumor-free in the left flank was found among the surgically resected mice. As regards sinecomitant immunity, tumor inoculation into the right flank followed by intra-tumoral administration of PSK on days 3 and 5 and surgical excision of the primary tumor on day 6 resulted in complete rejection of a tumor challenge in the left flank on day 21. The combination of presurgical intratumoral injections of PSK (more than 2 times) and postoperative oral administration of PSK appeared to be most effective in eradicating secondary tumors. Isolated TILs (tumor-infiltrating lymphocytes), obtained from the right tumor (treated with PSK) and the left tumor on day 10 in the double grafted tumor system were cultured in RPMI1640 with 10% fetal calf serum for 24 h. The culture supernatants were harvested and tested for the presence of chemotactic activity for neutrophils or macrophages. Significant neutrophil chemotactic factor (NCF) and macrophage chemotactic factor (MCF) activities were detected in the culture media from PSK-treated TILs that had been cultured for 24 h. Neither significant neutrophil nor macrophage chemotactic activity was detected in the media from untreated TILs. NCF and MCF activities were also detected in the culture supernatant from PSK-treated tumor tissue on day 6. PSK-induced NCF in the murine tumor was neutralized by treatment with anti-human IL-8 IgG, and might be murine IL-8-like factor. Therefore, neutrophil and macrophage infiltrations of tumors following intratumoral injections of PSK are probably mediated by inductions of IL-8-like factor and MCF.
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PMID:Antitumor effect of PSK at a distant site: inductions of interleukin-8-like factor and macrophage chemotactic factor in murine tumor. 212

A monocyte chemotactic and activating factor (MCAF) has been purified from TNF-stimulated 8387 human fibrosarcoma cell line-conditioned media. The purified MCAF showed microheterogeneity yielding two bands on SDS-PAGE analysis. Fibrosarcoma-derived MCAF specifically competed with THP-1 (a human monocytic cell line)-derived 125I-labeled MCAF in binding to human PBMC, whereas a similar basic heparin-binding leukocyte chemoattractant, IL-8, did not. The purified MCAF stimulated superoxide anion and N-acetyl beta-D glucosaminidase-releasing activity in human monocytes, as well as monocyte cytostatic augmenting activity against tumor cells and chemotactic activity for monocytes. When injected subcutaneously into Lewis rat ears, the purified human MCAF also induced considerable in vivo local monocyte infiltration beginning at 3 h and becoming maximal at 18 h. In conclusion, the data presented in this paper indicate that MCAF is a potent activator of monocytes as well as a monocyte recruitment factor that acts through receptors that are specific for this novel molecule. This novel cytokine might have an important role in tumor growth control due to its ability to attract and activate monocytes.
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PMID:Properties of monocyte chemotactic and activating factor (MCAF) purified from a human fibrosarcoma cell line. 216 98

Microheterogeneity of connective tissue activation peptide III (CTAP-III) was revealed by preparative and analytical isoelectric focusing. Proteolytic activities in human platelet preparations resulted in four cleavage products of platelet-derived CTAP-III. Three isoforms (CTAP-III des 1-13, des 1-14, and des 1-15/NAP-2) stimulate [14C]glycosaminoglycan synthesis; two isoforms also promote [3H]DNA synthesis in human fibroblast cultures. Elastase (from porcine pancreas) cleavage of human platelet-derived CTAP-III and rCTAP-III-Leu-21 to the des 1-15 isoforms was associated with either preservation of specific anabolic biologic activity or an actual increase in specific activity. Nonenzymatic glycosylation of lysyl residues and deamination of the NH2-terminal asparagine of platelet-derived CTAP-III were commonly present, but did not correlate with the biologic activities that were measured. Protein sequence homology shows CTAP-III and its isoforms to be members of a family of proteins (including NAP-1/II-8, MGSA, and platelet factor-4) known to be associated with growth, wound repair, inflammation, and neoplasia. The consequences of proteolytic processing reported here for CTAP-III may be characteristic of the other proteins in this group.
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PMID:Connective tissue activation. XXXIV: Effects of proteolytic processing on the biologic activities of CTAP-III. 221 61

Cytokines are (glyco)proteins that are synthesized and secreted by various cells, which bind to specific receptors on target cells and which regulate activation, proliferation, and differentiation of immune as well as non-immune cells. Keratinocytes upon injury release interleukin (IL)-1, IL-6, IL-8, colony-stimulating factors, and tumor-necrosis factor, as well as growth and suppressor factors. There is also strong evidence for a network of interacting cytokines, which has been only partially characterized so far, maintaining a proper balance. However, excessive or insufficient production of these mediators may contribute to certain disease states, particularly those with infectious and autoimmune genesis. Therefore the understanding of cytokine interactions may be helpful in elucidating the pathomechanisms of such diseases. Moreover, certain cytokines, as well as their analogues and antagonists, may prove to be of therapeutic value.
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PMID:Evidence for an epidermal cytokine network. 225 24

Adherence of monocytes to endothelial cells or extracellular matrices is likely to play a critical role in triggering monocyte activation in extravascular sites of infection, chronic inflammatory disorders, tissue damage and neoplastic growth. We have constructed a cDNA library from monocytes adhered for 30 min on plastic and have screened it by differential hybridization for mRNA rapidly induced by adherence. Two of the cDNA isolated have been identified as IL-1 beta and superoxide dismutase. Sequence data from three other adherence specific clones demonstrates the presence of ATTTA mRNA instability sequences in their 3' untranslated regions signifying inflammation-associated genes. The deduced amino acid sequences indicate the presence of open reading frames with sequence homologies to a family of host defense cytokines, one of them being identified as IL-8. Of the 14 clones initially identified, 4 have been analyzed for induction of mRNA expression. Although 3 of the 4 clones were equally induced by PMA and LPS under nonadherent conditions, all 4 cDNA showed distinct patterns of induction with adherence to extracellular matrix components or endothelial cells. The deduced amino acid sequence homologies indicate that we have isolated cDNA that code for three unique gene products. These cDNA belong to a gene family of early host defense cytokines involved in inflammation and cell growth, but which are differentially regulated by adherence to different surfaces.
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PMID:Monocyte adherence results in selective induction of novel genes sharing homology with mediators of inflammation and tissue repair. 234 26

In a study of the structural basis for leukocyte specificity of chemoattractants, we determined the complete amino acid sequence of human glioma-derived monocyte chemotactic factor (GDCF-2), a peptide that attracts human monocytes but not neutrophils. The choice of a tumor cell product for analysis was dictated by its relative abundance and an amino acid composition indistinguishable from that of lymphocyte-derived chemotactic factor (LDCF), the agonist thought to account for monocyte accumulation in cellular immune reactions. By a combination of Edman degradation and mass spectrometry, it was established that GDCF-2 comprises 76 amino acid residues, commencing at the N terminus with pyroglutamic acid. The peptide contains four half-cystines, at positions 11, 12, 36, and 52, which create a pair of loops, clustered at the disulfide bridges. The relative positions of the half-cystines are almost identical to those of monocyte-derived neutrophil chemotactic factor (MDNCF), a peptide of similar mass but with only 24% sequence identity to GDCF. Thus, GDCF and MDNCF have a similar gross secondary structure because of the loops formed by the clustered disulfides, and their different leukocyte specificities are most likely determined by the large differences in primary sequence.
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PMID:Complete amino acid sequence of a human monocyte chemoattractant, a putative mediator of cellular immune reactions. 264 85


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