UMLS:C0025202 - FACTA Search

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Query: UMLS:C0025202 (melanoma)
69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tripeptide tyroservatide (tyrosyl-seryl-valine, pTyr-Ser-Val-NH2) has been shown to have antitumor effects on experimental hepatocarcinoma. This study aimed to observe the effects of tyroservatide on other five human carcinomas: A549 (nonsmall cell lung carcinoma), BGC-823 (gastric cancer), MCF-7 (breast cancer), K562 (leukemia), A375 (melanoma) and two murine cancers: Lewis lung cancer and B16 (melanoma) in vivo. In vivo nude mice bearing xenografts of five different human tumors or C57BL/6 mice bearing xenografts of two different murine tumors were given daily intraperitoneal injections of tyroservatide or saline as controls, after tumor implantation. The inhibition of xenografts was determined by calculating the tumor volume and measuring tumor weight. Tyroservatide could significantly inhibit the growth of human lung carcinoma A549, human leukemia K562 and human melanoma A375 in nude mice (P<0.05). In addition, tyroservatide significantly inhibited the subcutaneous tumor growth of Lewis lung carcinoma and B16 melanoma (P<0.05). Tyroservatide, however, could not significantly suppress xenografts of BGC-823 and MCF-7 in nude mice (P>0.05). The results obtained indicate that tyroservatide exhibits different effects on different tumors, which will provide clinical applications guidance of tyroservatide as an anticancer drug.
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PMID:Inhibition of five xenografted human cancers and two murine cancers by the tripeptide tyroservatide. 1735 99

Parallel solution-phase chemistry has yielded a series of secondary amide analogues of the fungal natural product 3-chloro-4-hydroxyphenylacetamide. 3-Chloro-4-hydroxyphenylacetic acid was coupled to a variety of primary amines using 1-ethyl-3-(3'-dimethylamino- propyl)-carbodiimide hydrochloride. The desired products were obtained in good yield and high purity following rapid silica purification. All analogues were spectroscopically characterised using NMR, UV, IR and MS data. One compound displayed moderate cytotoxicity against the human melanoma and prostate cell lines, MM96L and DU145.
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PMID:Synthesis and spectroscopic characterisation of a combinatorial library based on the fungal natural product 3-chloro-4-hydroxyphenylacetamide. 1737 64

T-lymphokine-activated killer cell-originated protein kinase (TOPK) is overexpressed in highly proliferating tumors such as leukemias and myelomas, and seems to play a key role in tumorigenesis or metastasis. However, the precise role and regulatory mechanism explaining the effects of TOPK on tumor cells still remain elusive. Here, we reported that TOPK regulates UVB-induced c-Jun-NH2-kinase 1 (JNK1) activity, and is essential for H-Ras-induced activator protein-1 activity and cell transformation. We showed that TOPK associated with and phosphorylated JNK1 following UVB irradiation in vitro or in vivo. Moreover, UVB-induced JNK1 activity was greatly augmented in mouse epidermal JB6 Cl41 cells that stably expressed TOPK cDNA. On the other hand, JNK1 activity was markedly attenuated by stable expression of small interfering RNA against TOPK in malignant melanoma RPMI 7951 cells. Interestingly, TOPK interacted with JNK-interacting protein 1 and caused an elevation of JNK-interacting protein 1 scaffolding activity, thereby enhancing JNK1 activity. Furthermore, JNK1 was required for TOPK-mediated activator protein-1 transcriptional activity and transformed foci induced by UVB or H-Ras. Taken together, these findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras. These studies might also provide a novel molecular mechanism for the role of TOPK in UVB-mediated skin carcinogenesis.
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PMID:T-lymphokine-activated killer cell-originated protein kinase functions as a positive regulator of c-Jun-NH2-kinase 1 signaling and H-Ras-induced cell transformation. 1754 98

We have synthesized a stable and clinically relevant nanodevice (cRGD-BT-ND; ND for short) that exhibits superior binding to the biologic target alphavbeta3 integrins, when either compared to the same free cRGD peptide or to the biotinylated nanodevice without covalently attached peptides (BT-ND). Selective targeting of alphavbeta3 integrins was achieved by coupling cyclic cRGD peptides to the nanodevice (ND) surface, while biotin groups (BT) were used for amplified detection of bound cRGD-BT-ND by anti-biotin antibody or avidin linked to horseradish peroxidase after binding. The synthesis involved the following steps: the amino-terminated ethylenediamine core generation 5 poly(amidoamine) (PAMAM_E5.NH2) dendrimer was first partially acetylated and then biotinylated, and residual primary amine termini were converted to succinamic acid groups (SAH), some of which finally were conjugated with cRGD peptide residues through the amino group of the lysine side chain. The starting material and all derivatives were extensively characterized by polyacrylamide gel electrophoresis (PAGE), size exclusion chromatography (SEC), potentiometric acid-base titration, MALDI-TOF, and NMR. Cytotoxicity of all dendrimer derivatives was examined in B16F10 melanoma cell cultures using the XTT colorimetric assay for cellular viability. Binding of nanodevices to the biological target was determined using plates coated with human alphavbeta3 integrin and alphavbeta3 receptor expressing human dermal microvascular endothelial cells (HDMECs). The PAMAM_E5.(NHAc)72(NHBT)8(NHSAH)35(NHSA-cR GD)4 nanodevice is nontoxic within physiologic concentration ranges and specifically binds to the alphavbeta3 integrins, apparently much stronger than the cyclic cRGD peptide itself.
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PMID:Synthesis and characterization of PAMAM dendrimer-based multifunctional nanodevices for targeting alphavbeta3 integrins. 1756 76

Early detection of primary melanoma tumors is essential because there is no effective treatment for metastatic melanoma. Several linear and cyclic radiolabeled alpha-melanocyte stimulating hormone (alpha-MSH) analogs have been proposed to target the melanocortin type 1 receptor (MC1R) overexpressed in melanoma. The compact structure of a rhenium-cyclized alpha-MSH analog (Re-CCMSH) significantly enhanced its in vivo tumor uptake and retention. Melanotan II (MT-II), a cyclic lactam analog of alpha-MSH (Ac-Nle-cyclo[Asp-His-DPhe-Arg-Trp-Lys]-NH2]), is a very potent and stable agonist peptide largely used in the characterization of melanocortin receptors. Taking advantage of the superior biological features associated with the MT-II cyclic peptide, we assessed the effect of lactam-based cyclization on the tumor-seeking properties of alpha-MSH analogs by comparing the pharmacokinetics profile of the 99mTc-labeled cyclic peptide betaAla-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 with that of the linear analog betaAla-Nle-Asp-His-DPhe-Arg-Trp-Lys-NH2 in melanoma-bearing mice. We have synthesized and coupled the linear and cyclic peptides to a bifunctional chelator containing a pyrazolyl-diamine backbone (pz) through the amino group of betaAla, and the resulting pz-peptide conjugates were reacted with the fac-[99mTc(CO)3]+ moiety. The 99mTc(CO)3-labeled conjugates were obtained in high yield, high specific activity, and high radiochemical purity. The cyclic 99mTc(CO)3-labeled conjugate presents a remarkable internalization (87.1% of receptor-bound tracer and 50.5% of total applied activity, after 6 h at 37 degrees C) and cellular retention (only 24.7% released from the cells after 5 h) in murine melanoma B16F1 cells. A significant tumor uptake and retention was obtained in melanoma-bearing C57BL6 mice for the cyclic radioconjugate [9.26 +/- 0.83 and 11.31 +/- 1.83% ID/g at 1 and 4 h after injection, respectively]. The linear 99mTc(CO)3-pz-peptide presented lower values for both cellular internalization and tumor uptake. Receptor blocking studies with the potent (Nle4,DPhe7)-alphaMSH agonist demonstrated the specificity of the radioconjugates to MC1R (74.8 and 44.5% reduction of tumor uptake at 4 h after injection for cyclic and linear radioconjugates, respectively).
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PMID:Melanoma targeting with alpha-melanocyte stimulating hormone analogs labeled with fac-[99mTc(CO)3]+: effect of cyclization on tumor-seeking properties. 1818 29

The NO donor trans-[Ru(NO)(NH(3))(4)(py)](BF(4))(3).H(2)O (py=pyridine) was loaded into poly-lactic-co-glycolic acid (PLGA) microparticles using the double emulsification technique. Scanning electron microscopy (SEM) and dynamic light scattering revealed that the particles are spherical in shape, have a diameter of 1600nm, and have low tendency to aggregate. The entrapment efficiency was 25%. SEM analysis of the melanoma cell B16-F10 in the presence of the microparticles containing the complex trans-[Ru(NO)(NH(3))(4)(py)](BF(4))(3).H(2)O (pyMP) showed that the microparticles were adhered to the cell surface after 2h of incubation. The complex with concentrations lower than 1x10(-4)M did not show toxicity in B16-F10 murine cells. The complex in solution is toxic at higher concentrations (>1x10(-3)M), with cell death attributed to NO release following the reduction of the complex. pyMP is not cytotoxic due to the lower bioavailability and availability of the entrapped complex to the medium and its reducing agents. However, pyMP is phototoxic upon light irradiation. The phototoxicity strongly suggests that cell death is due to NO release from trans-[Ru(NO)(NH(3))(4)(py)](3+). This work shows that pyMP can serve as a model for a drug delivery system carrying the NO donor trans-[Ru(NO)(NH(3))(4)(py)](BF(4))(3).H(2)O, which can release NO locally at the tumor cell by irradiation with light only.
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PMID:trans-[Ru(NO)(NH3)4(py)](BF4)3.H2O encapsulated in PLGA microparticles for delivery of nitric oxide to B16-F10 cells: Cytotoxicity and phototoxicity. 1821 22

The BRAFV600E mutation is common in human melanoma. This mutation enhances IkappaB kinase (IKK)/nuclear factor-kappaB (NF-kappaB) and extracellular signal-regulated kinase/activator protein signaling cascades. In this study, we evaluated the efficacy of targeting either B-Raf or IKKbeta in combination with the DNA alkylating agent temozolomide for treatment of advanced metastatic melanoma. Xenografts of Hs294T human metastatic melanoma cells exhibiting the BRAFV600E mutation were treated with inhibitors of IKKbeta (BMS-345541), B-Raf (BAY 54-9085), and/or temozolomide. Drug response was mechanistically analyzed in vitro and in vivo. In this study, we determined that the antitumor activity of all three drugs depends on inhibition of NF-kappaB. BMS-345541 inhibits IKKbeta-mediated phosphorylation of IkappaBalpha and thus blocks the nuclear localization of NF-kappaB, whereas BAY 54-9085 inhibits activation of NF-kappaB through a mechanism that does not involve stabilization of IkappaBalpha. Moreover, BMS-345541, but not BAY 54-9085, activates the death pathways of p53 and c-Jun-NH2-kinase, contributing to the killing of melanoma cells. Temozolomide inhibits both NF-kappaB and extracellular signal-regulated kinase activity, conferring effective in vivo antitumor activity. Thus, temozolomide, but not BAY 54-9085, has a synergistic in vivo antitumor effect with BMS-345541. We conclude that the efficacy of antimelanoma therapy depends on inhibition of expression of antiapoptotic genes transcriptionally regulated by NF-kappaB. In contrast, drug targeting of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway alone in melanoma cells is ineffective for melanoma therapy in cases where NF-kappaB is not also targeted.
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PMID:Molecular determinants of melanoma malignancy: selecting targets for improved efficacy of chemotherapy. 1927 65

Bisphosphonates (BPs), bone targeted drugs that disrupt osteoclast function, are routinely used to treat complications of bone metastasis. Studies in preclinical models of cancer have shown that BPs reduce skeletal tumor burden and increase survival. Similarly, we observed in the present study that administration of the Nitrogen-containing BP (N-BP), zoledronic acid (ZA) to osteolytic tumor-bearing Tax+ mice beginning at 6 months of age led to resolution of radiographic skeletal lesions. N-BPs inhibit farnesyl diphosphate (FPP) synthase, thereby inhibiting protein prenylation and causing cellular toxicity. We found that ZA decreased Tax+ tumor and B16 melanoma viability and caused the accumulation of unprenylated Rap1a proteins in vitro. However, it is presently unclear whether N-BPs exert anti-tumor effects in bone independent of inhibition of osteoclast (OC) function in vivo. Therefore, we evaluated the impact of treatment with ZA on B16 melanoma bone tumor burden in irradiated mice transplanted with splenic cells from src(-/-) mice, which have non-functioning OCs. OC-defective mice treated with ZA demonstrated a significant 88% decrease in tumor growth in bone compared to vehicle-treated OC-defective mice. These data support an osteoclast-independent role for N-BP therapy in bone metastasis.
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PMID:The bisphosphonate zoledronic acid decreases tumor growth in bone in mice with defective osteoclasts. 1944 20

The polyamines spermine, spermidine and putrescine are ubiquitous cell components. These molecules are substrates of a class of enzymes that includes monoamine oxidases, diamine oxidases, polyamine oxidases and copper-containing amine oxidases. Amine oxidases are important because they contribute to regulate levels of mono- and polyamines. In tumors, polyamines and amine oxidases are increased as compared to normal tissues. Cytotoxicity induced by bovine serum amine oxidase (BSAO) and spermine is attributed to H(2)O(2) and aldehydes produced by the reaction. This study demonstrated that multidrug-resistant (MDR) cancer cells (colon adenocarcinoma and melanoma) are significantly more sensitive than the corresponding wild-type (WT) ones to H(2)O(2) and aldehydes, the products of BSAO-catalyzed oxidation of spermine. Transmission electron microscopy (TEM) observations showed major ultrastructural alterations of the mitochondria. These were more pronounced in MDR than in WT cells. Increasing the incubation temperature from 37 to 42 degrees Celsius enhances cytotoxicity in cells exposed to spermine metabolites. The combination BSAO/spermine prevents tumor growth, particularly well if the enzyme has been conjugated to a biocompatible hydrogel polymers. Since both wild-type and MDR cancer cells after pre-treatment with MDL 72527, a lysosomotropic compound, are sensitized to subsequent exposure to BSAO/spermine, it is conceivable that combined treatment with a lysosomotropic compound and BSAO/spermine would be effective against tumor cells. It is of interest to search for such novel compounds, which might be promising for application in a therapeutic setting.
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PMID:Potential anticancer application of polyamine oxidation products formed by amine oxidase: a new therapeutic approach. 2001 14

The angiotensin (Ang) IV analog norleual [Nle-Tyr-Leu-psi-(CH2-NH2)(3-4)-His-Pro-Phe] exhibits structural homology with the hinge (linker) region of hepatocyte growth factor (HGF) and is hypothesized to act as a hinge region mimic. Norleual competitively inhibited the binding of HGF to its receptor c-Met in mouse liver membranes, with an IC(50) value of 3 pM. Predictably, norleual was able to inhibit HGF-dependent signaling, proliferation, migration, and invasion in multiple cell types at concentrations in the picomolar range. Ex vivo studies demonstrated that norleual exhibited potent antiangiogenic activity, an attribute that would be predicted for a HGF/c-Met antagonist. Furthermore, norleual suppressed pulmonary colonization by B16-F10 murine melanoma cells, which are characterized by an overactive HGF/c-Met system. Together, these data suggest that AngIV analogs exert at least some of their biological activity through interference with the HGF/c-Met system and may have utility as therapeutic agents in disorders that are dependent on an intact HGF/c-Met system. Finally, the ability of norleual to induce marked biological responses in human embryonic kidney cells, which do not express insulin-responsive aminopeptidase (IRAP), coupled with the observed effects of norleual on the HGF/c-Met system, casts doubt on the physiological significance of AngIV-dependent inhibition of IRAP. [Corrected]
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PMID:The angiotensin IV analog Nle-Tyr-Leu-psi-(CH2-NH2)3-4-His-Pro-Phe (norleual) can act as a hepatocyte growth factor/c-Met inhibitor. 2008 56

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