Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A low-molecular-weight cytotoxic protein has been purified from Pyrularia pubera Michx. (Santalaceae). By comparison with the behavior of proteins of known molecular weight during Sephadex G-75 gel filtration and denaturing electrophoresis, a molecular weight of somewhat less than 6000 is indicated. Purification involves ammonium sulfate fractionation followed by either gel filtration on Sephadex G-75 or separation on a carboxymethyl cellulose CM52 column. At concentrations of 0.04 mg/ml the protein causes visible disruption of cultured mouse B16 melanoma cells. The complete amino acid sequence has been determined. The toxin contains 47 amino acids arranged as follows:Lys-Ser-Cys-Cys-Arg-Asn-Thr-Trp-Ala-Arg-Asn-C ys-Tyr-Asn-Val-Cys-Arg-Leu-Pro-Gly-Thr-Ile-Ser-Arg-Glu-Ile-Cys-Ala-Lys- Lys-Cys-Asp-Cys-Lys-Ile-Ile-Ser-Gly-Thr-Thr-Cys-Pro-Ser-Asp-Tyr-Pro-Ly s-OH. The protein is clearly a thionin, as shown by its close resemblance to the thionins from wheat and barley, to the viscotoxins from mistletoes, and to crambin.
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PMID:A toxic thionin from Pyrularia pubera: purification, properties, and amino acid sequence. 398 14

The intraperitoneal (i.p.) injection of tuftsin, Thr-Lys-Pro-Arg, into C57BL/6 mice that were injected with B16/5B melanoma cells, resulted in a considerable suppression and elimination of solid tumor growth. While 100% of control animals exhibited tumor growth, 38% of the treated animals failed to show tumor formation for the duration of the experiment, 60-80 days. The octapeptide, tuftsinyltuftsin, was effective at 3 ng per mouse as was a dose of 2 and 20 micrograms per mouse. In each case there was a significant number of mice free of tumors. The octapeptide was also quite effective against L1210 cells resulting in the survival of 35-40% of the treated animals. The lethal effect of increased superoxide, O X 2, production by tuftsin treatment may explain the antineoplastic effect of the tetrapeptide. This may result not only from higher concentrations of O X 2 but also from the potentially lethal effects of H2O2 and OH X radical, both of which are products of O X 2 metabolism.
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PMID:The antineoplastic effects of tuftsin and tuftsinyltuftsin on B16/5B melanoma and L1210 cells. 632 37

A mouse MAb3 50H.19 raised against the human melanoma cell line MEL-T binds to carcinoma cell lines, carcinoma biopsy material, and certain epithelia of normal tissues. It immunoprecipitates two components from carcinoma cell lines, a major component of 22 kd which is O-glycosylated and a minor one of 24 kd which is additionally N-glycosylated. The immunocomplexed 50H.19 antigen exhibits protein kinase activity with substrate-specificity for casein and phosvitin, but not for histones. It phosphorylates on serine and threonine, but not tyrosine residues. Enzyme activity is cyclic AMP-independent.
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PMID:Human tumor cell membrane glycoprotein associated with protein kinase activity. 651 Nov 25

An acid-stable transforming growth factor (TGF) that interacts with epidermal growth factor (EGF) receptors and is structurally related to EGF was isolated from serum-free culture fluids of Snyder-Theilen feline sarcoma virus-transformed rat embryo (FeSV-Fre) cells. Purification of this EGF-like TGF (eTGF) was achieved by molecular filtration chromatography and successive reverse-phase high pressure liquid chromatography steps on octadecyl support eluted with acetonitrile and 1-propanol gradients, respectively. Rat eTGF consists of a 7.4-kD single polypeptide chain that co-migrates with biological activity in dodecyl sulfate-polyacrylamide electrophoresis gels. Like preparations of a related TGF from human melanoma cells (Marquardt, H., and Todaro, G.J. (1982) J. Biol. Chem. 257, 5220-5225), but unlike EGF from rat, human, or mouse, rat eTGF has phenylalanine and lacks methionine. However, the sequence of the first 30 amino acid residues in rat eTGF is H2N-Val-Val-Ser-His-Phe-Asn-Lys-Cys-Pro-Asp-Ser-His-Thr-Gln-Tyr-Cys-Phe-His-Gly - Thr-(x)-Arg-Phe-Leu-Val-Gln-Glu-Glu-(Lys)-(Lys)-, which is significantly (20% and 28%) homologous to the NH2-terminal region of mouse EGF and human EGF, respectively. In addition to eTGF, molecular filtration chromatography of acid-soluble extracts from medium conditioned by FeSV-Fre cells resolved a 14-kD transforming factor(s) apparently devoid of intrinsic mitogenic activity but able to elicit a strong anchorage-independent growth response in the presence of eTGF or EGF. These results show that: 1) a 7.4-kDa TGF structurally and functionally related to EGF has been isolated from FeSV-Fre cells and 2) the full anchorage-independent growth-promoting activity of medium conditioned by FeSV-Fre cells is due to the coordinate action of at least two types of factors, the 7.4-kDa eTGF and a second 14-kDa transforming factor(s).
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PMID:Epidermal growth factor-like transforming growth factor. I. Isolation, chemical characterization, and potentiation by other transforming factors from feline sarcoma virus-transformed rat cells. 660 68

Tuftsin, a physiological tetrapeptide derived from the Fc region of leukophilic IgG possesses a variety of immunopotentiating properties including the ability to act as an immunotherapeutic agent against the experimental tumors, L1210 leukemia and Cloudman S-91 melanoma. Although the mechanism of action of tuftsin in vivo is not known, several types of leukocytes have been shown to become cytotoxic effector cells following activation with tuftsin. These cells presently include macrophages, natural killer cells, and granulocytes. The possibility that tuftsin can also activate other types of effector cells have not been ruled out. We feel this small peptide has a high potential (largely unrecognized) as an antitumor immunopotentiating agent. It is naturally occurring in man and appears to be relatively non-toxic. Its exact sequence (Thr-lys-Pro-Arg) is known and it can be chemically synthesized. Methods are also available to monitor the levels of tuftsin in body fluids. These properties along with its ability to control infectious disease make this agent one of the more promising immunopotentiators.
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PMID:Antitumor effect of tuftsin. 689 73

Interleukin-8 (IL-8) is a potent inflammatory mediator that belongs to the family of C-X-C chemokines. IL-8 promotes the activation and the extravasation of circulating neutrophils to the site of inflammation. Two IL-8 receptor isotypes (type A and B) are identified in human and rabbit neutrophils. IL-8 receptors belongs to the superfamily of G-protein-coupled receptors. Both receptor subtypes A and B bind with high affinity to human IL-8, but they exhibit distinct binding affinity to two functional and structurally related IL-8 peptides, melanoma growth-stimulating activity peptide (MGSA) and neutrophil-activating peptide-2 (NAP-2). Human IL-8 receptor A binds with low affinity to MGSA or NAP-2. In contrast, human IL-8 receptor B binds MGSA with high affinity, and NAP-2 with lesser affinity. Using receptor subtype chimeras, we determined that the N-terminal domain of the receptor confers ligand binding specificity (LaRosa, G. J., Thomas, K. M., Kaufmann, M. E., Mark, R., White, M., Taylor, L., Gray, G., Witt, D., and Navarro, J. (1992) J. Biol. Chem. 267, 25402-25406). In this work, we characterized by molecular cloning and expression a mouse receptor structurally homologous to the IL-8 receptor. We isolated a clone by screening a mouse genomic library with a rabbit IL-8 receptor A cDNA fragment as a probe. The mouse clone exhibited an open reading frame encoding a 359-amino acid protein. Hydropathy plot analysis of the amino acid sequence reveals seven transmembrane domains characteristic of G-protein-coupled receptors. The N terminus and the second extracellular loop contain one and two putative N-glycosylation sites, respectively. The intracellular C-terminal tail contains Ser and Thr residues as potential phosphorylation sites. Northern blot analysis showed that the mouse receptor gene is expressed in mouse neutrophils. The mouse receptor shows 65, 74, 66, and 70% amino acid identity to the rabbit IL-8 receptor subtypes A and B and human IL-8 receptor subtypes A and B, respectively. However, neither mouse neutrophils nor CHO cells expressing the mouse receptor bind human IL-8 in the nanomolar range. To identify the domain(s) conferring high affinity binding to IL-8, we constructed rabbit/mouse receptor chimeras.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The N terminus of interleukin-8 (IL-8) receptor confers high affinity binding to human IL-8. 751 26

Plasminogen (PG), urokinase-type plasminogen activator (u-PA) and tissue-type PA (t-PA) are the main molecules involved in fibrinolysis and in many other physiological and pathological processes. In the present study we report that human t-PA, purified from human melanoma cells, and PG, purified from human plasma, both contain P-Tyr residues, as revealed by immunoblotting analyses with monoclonal anti-P-Tyr antibodies. In addition HPLC amino acid analysis of acid-hydrolyzed t-PA, PG and u-PA, shows that: (i) P-Ser and P-Tyr residues are present in t-PA; (ii) P-Thr and P-Tyr are present in PG; (iii) P-Ser, P-Thr and P-Tyr are present in u-PA. The utilization of monoclonal anti-P-Ser and anti-P-Thr antibodies in immunoblotting experiments has confirmed these data which indicate that phosphorylation is a common feature of PAs and of PG.
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PMID:Phosphorylation of human plasminogen activators and plasminogen. 753 24

Using an in situ kinase assay we have identified kinases that are elevated in some multidrug resistant cells. Kinases were detected by measurement of 32P incorporation in proteins that were renatured after being subjected to SDS-polyacrylamide gel electrophoresis and transferred to polyvinylidene difluoride membranes [Ferrell and Martin: J Biol Chem 264:20723-20729, 1989; Mol Cell Biol 10:3020-3026, 1990]. Kinases at 79, 84, and 92 kDa showed increased activity in the multidrug resistant human KB-V1 cells as compared to the sensitive parental KB-3-1 cells. The KB-V1 multidrug resistant cell line exhibited a 170 kDa membrane associated kinase activity that was not present in the parental drug sensitive line. The 170 kDa kinase activity was not affected by Ca++, phosphatidylserine, or cAMP, but was diminished after incubation in the presence of the kinase inhibitors staurosporine, K252a and KT5720. The 170 kDa kinase activity phosphorylated mainly threonine, with no evidence of tyrosine phosphorylation, and was not identical to either the multidrug resistance associated P-glycoprotein or the EGF receptor. Other multidrug resistant cell lines also showed elevated 170 kDa kinase activity, such as the human breast cancer MCF-7/Adr(R) and murine melanoma B16/Adr(R) cells, but the activity was not present in murine leukemia P-388 sensitive or multidrug resistant cells.
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PMID:Identification of a 170 kDa membrane kinase with increased activity in KB-V1 multidrug resistant cells. 769 26

A 29-kDa monomeric dispase-digestive fragment of human plasma fibronectin has been purified by heparin affinity chromatography. The NH2-terminal sequence was determined as Ala1687-Val-Thr-Thr-Ile-Pro-Ala-Pro. By mass spectrometry the molecular weight was determined to be 30,241.9 with standard deviation of 3.9 amu. Therefore, we defined the C-terminal sequence of the 29-kDa fragment as Arg1957-Lys-Lys-Thr-Gly-Gln-Glu. This indicates that the fragment is composed of 277 amino acids. 125I-fibronectin and the 125I-labeled 29-kDa fragment bound to HL-60 (human acute promyelocytic leukemia) cells in a time-dependent, saturable, and reversible manner. Approximately 120 min was required to reach maximal binding. There were no differences in quantity or rate of binding of labeled fibronectin and 29-kDa fragment at temperatures of 4 degrees, 22 degrees, and 37 degrees C. The number of binding sites per HL-60 cell of fibronectin and the 29-kDa fragment were 140,000 with a Kd of 133 nM and 108,000 with a Kd of 250 nM, respectively. The binding of fibronectin to HL-60 cells was completely inhibited by this fragment, and by the peptides of RGDS and CS1 with IC50s of 3.6, 840, and 670 microM, respectively. Native fibronectin inhibited the direct binding of the 29-kDa fragment to HL-60 cells; however, RGDS peptide, peptide CS1, or two melanoma cell adhesion-promoting domain peptides in this 29-kDa fragment (peptide I; Tyr1906-Val1924, peptide II; Asp1946-Thr1960) did not block this binding. Neither heparitinase nor chondroitinase treatment of cells had any effect on these bindings. These results indicate that the C-terminal cell- and heparin-binding domain of fibronectin mediates HL-60 cell binding by direct interaction independently of RGD, CS1, and melanoma cell adhesion domains in this fragment.
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PMID:Binding site in human plasma fibronectin to HL-60 cells localizes in the C-terminal heparin-binding region independently of RGD and CS1. 769 49

The two major glycoforms of full-length human thrombomodulin (TM), one with (TM(CS+)) and one without (TM(CS-)) chondroitin sulfate (CS) were analyzed on Western blots of primary and transformed cells and in cells expressing recombinant TM. TM on the surface of Chinese hamster ovary and COS-7 cells is solely TM(CS-). Primary arterial endothelial cells (HAEC and HPAEC) express a greater fraction of TM with CS attached than venous cells (HUVEC). Human lung carcinoma cells (A549) express more TM(CS+) than primary cells and recombinant TM on human melanoma cells (CHL-1) occurs in two very high molecular weight forms of TM(CS+). We explored this variation in TM(CS+) with soluble recombinant TM in several cell lines and analyzed the ambiguous CS addition site in human TM by site-directed mutagenesis. Mutation of Ser474 to Ala blocks CS addition in Chinese hamster ovary and COS-7 cells but not CHL-1 cells which add CS to Ser472 and Ser474. Structure of the O-link domain affects partitioning into TM(CS+) since substituting with the decorin CS addition sequence, substituting all Ser and Thr except Ser474 with Ala, and deleting around the potential beta-turn all increase the ratio of TM(CS+) to TM(CS-). A combination of the decorin substitution and deletion of the remaining O-link domain yields the most TM(CS+).
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PMID:Modulation of glycosaminoglycan addition in naturally expressed and recombinant human thrombomodulin. 792 88


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