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)

We examined the immunotherapeutic ability of activated B cells which bound to anti-CD3 monoclonal antibody (mAb) to enhance antitumor T cell immunity in vivo. A flow cytometric analysis revealed that LPS (lipopolysaccharide)-activated B cells (LPS blasts) expressed Fc receptor (FcR) which can bind to anti-CD3 mAb. LPS blasts were also stained with CTLA-4Ig, which can bind to costimulation molecules with high affinity, which suggested that LPS blasts expressed costimulation molecules on their surface. In an in vitro assay, T cells remarkably proliferated in the presence of LPS blasts and soluble anti-CD3 mAb, whereas this proliferation was blocked by the addition of CTLA-4Ig. In a model of metastasis established by the intravenous inoculation of melanoma cells, the in vivo administration of LPS blasts incubated with anti-CD3 mAb and followed by treatment with polyethylene glycol, to reinforce the binding, induced a low but significant antitumor activity against melanoma. The antitumor activity induced by the in vivo administration of LPS blasts which bound to anti-CD3 mAb was also detected in the spontaneously established model of metastasis. These results therefore suggest that the in vivo administration of activated B cells which bound to anti-CD3 mAb was able to enhance the antitumor T cell response against metastatic melanoma.
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PMID:The antitumor activity induced by the in vivo administration of activated B cells bound to anti-CD3 monoclonal antibody. 786 78

The antimetastatic activities of synthetic peptides corresponding to fragments of the adhesion-related molecules, such as fibronectin and laminin, were examined. We prepared three peptides derived from the type III connecting segment domain (IIICS) of fibronectin: Glu-Ile-Leu-Asp-Val (EILDV), Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (EILDVPST), Arg-Glu-Asp-Val (REDV), and a laminin-related peptide, Tyr-Ile-Gly-Ser-Arg (YIGSR). Each peptide inhibited the experimental tumor metastasis of B16-BL6 melanoma, while EILDV had the strongest effect. The peptides conjugated with poly(ethylene glycol) (PEG) were more effective than the unmodified peptides in molar ratio terms. A mixture composed of PEG hybrids with EILDV, REDV and YIGSR significantly inhibited tumor metastasis.
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PMID:Antimetastatic effects of synthetic peptides containing the core sequence of the type III connecting segment domain (IIICS) of fibronectin. 794 46

Fusion of mouse melanoma cells grown in monolayers has been directly monitored by fluorescence resonance energy transfer between fluorescein and rhodamine probes attached to octadecanoic acid. Various poly(ethylene glycol)s (PEG), either alone or in combination with amphipathic molecules, have been used as fusogens. Fusion starts at a maximum rate as soon as PEG is removed from the medium and reaches a plateau after 20-30 min. Both the initial rate and extent of fusion have been recorded for each experiment. The extent of fusion shows in general a positive correlation with the initial rate, although PEGs with different molar masses appear to induce fusion at different rates, but to a similar extent. A good correlation has been found between the extent of fusion, as measured by fluorescence, and the 'fusion index' computed from cell and nucleus counting; a calibration curve is provided for the interconversion of both parameters. Optimum fusion values are obtained with 50% (w/v) PEG 1500. The effect of pre-treatments with surfactants (Triton X-100, sodium dodecylsulphate) on PEG-induced fusion has also been tested. Sodium dodecylsulphate, but not Triton, enhances considerably both the rate and extent of cell fusion. The in situ generation of the amphipathic molecule diacylglycerol, through the catalytic activity of a phospholipase C, also enhances significantly the fusion parameters. These results are in good agreement with previous studies based on syncytia counting.
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PMID:Real-time measurements of chemically-induced membrane fusion in cell monolayers, using a resonance energy transfer method. 829 22

Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis, tumor cell proliferation, and metastatic potential. Inhibition of calcium influx and calcium-dependent events is a potential common mechanism underlying these effects of CAI. The cytostatic and antiangiogenic properties of CAI led to its development for clinical investigation. In a Phase I clinical trial open to patients with refractory solid tumors, 49 patients received p.o. administered CAI daily or every other day. Two oral formulations, PEG-400 CAI solution and a gelatin capsule containing CAI in PEG-400, were tested. All administered dosages of CAI yielded plasma concentration at or above the range demonstrated to be effective in inhibiting signaling and cancer progression in vitro and in preclinical models (1 microgram/ml, 2.3 microM). Toxicity of p.o. administered CAI most commonly consisted of dose-related grade 1-2 nausea, vomiting, and occasional anorexia. CAI administration at bedtime ameliorated gastrointestinal complaints in many patients; others required addition of simple antiemetic regimens, usually consisting of metoclopropamide or prochlorperazine. Gastrointestinal complaints were the cause for compliance-limiting toxicity at 175 mg/m2/day of the liquid formulation and 125 mg/m2/day of the gelatin capsule formation. Reversible and rare sensory axonal neuropathy (grade 3, 1 patient) and neutropenia (grade 4, 1 patient) were dose-limiting toxicities observed at the 330 mg/m2 every-other-day liquid CAI dose level. No evidence of cumulative end organ damage or central nervous system injury was observed. Disease stabilization and improvement in performance status was observed. Disease stabilization and improvement in performance status was observed in 49% of evaluable patients who had disease progression before CAI. Disease stabilization and associated improvement in performance status was seen in patients with renal cell carcinoma (7 months), pancreaticobiliary carcinomas (3, 5, and 5 months), melanoma (7 months), ovarian cancer (7 months), and non-small cell lung cancer (3 months). The recommended Phase II doses from this trial are 150 mg/m2/day in the liquid formation and 100 mg/m2/day in the gelatin capsule formation.
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PMID:Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers. 856 73

This study was conducted to determine the mechanisms for the enhanced inhibitory effect of cell-adhesive peptides conjugated to polyethylene glycol (PEG) on tumor metastasis. Tyr-Ile-Gly-Ser-Arg (YIGSR), a laminin-derived peptide, conjugated with amino-PEG (YIGSR-aPEG) inhibited lung metastasis of B16-BL6 melanoma cells more effectively than unconjugated YIGSR peptide. [125I]-YIGSR-aPEG and native [125I]-YIGSR showed similar biphasic elimination and profiles after intravenous injection into C57BL/6 mice. Both [125I]-YIGSR and [125I]-YIGSR-aPEG expressed similar plasma half-lives and organ distributions. The radioactivity of both compounds was transported rapidly from the blood to the kidneys, and immediately excreted into the urine. [125I]-YIGSR was almost completely degraded in the urine, but [125I]-YIGSR-aPEG was not. In an in vitro stability assay, [125I]-YIGSR was degraded immediately upon incubation with mouse serum, whereas [125I]-YIGSR-aPEG was not degraded after 180 min incubation in mouse serum. These findings indicate that the enhanced inhibitory effect of YIGSR-aPEG on lung metastasis might be due to its increased stability in the blood.
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PMID:Synthetic cell-adhesive laminin peptide YIGSR conjugated with polyethylene glycol has improved antimetastatic activity due to a longer half-life in blood. 862 Dec 71

Water-soluble paclitaxel may cause less side effects and be less costly to administer in comparison to a taxol formulation using a cremophor EL/alcohol vehicle. In this study, polyethylene glycol (PEG; MW 5000) was conjugated to the 2' position of paclitaxel through a spacer succinyl group. PEG-paclitaxel as a non-ionic paclitaxel prodrug was highly water soluble (> 20 mg equiv. paclitaxel/ml). The release of paclitaxel from phosphate-buffered solution was pH dependent. The half-life of PEG-paclitaxel was 7.6, 54 and 311 min at pH 9.0, 7.4 and 6.0, respectively. PEG-paclitaxel inhibited the growth of B16 melanoma cells to an extent similar to that of paclitaxel. In MCA-4 mammary tumor-bearing mice, a single dose of PEG-paclitaxel (40 mg equiv. paclitaxel/kg body weight) significantly delayed tumor growth. The average number of days for the tumor to reach 12 from 8 mm in diameter increased from 6.5 days for control animals to 8.5 days for PEG-paclitaxel-treated animals and 9.4 days for paclitaxel-treated animals. These studies demonstrated that PEG may be used as an effective solubilizing carrier for paclitaxel.
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PMID:Synthesis and evaluation of water-soluble polyethylene glycol-paclitaxel conjugate as a paclitaxel prodrug. 891 32

We previously reported that the optimally PEGylated tumor necrosis factor-alpha (MPEG-TNF-alpha), in which 56% of the TNF-alpha-lysine amino groups were coupled with polyethylene glycol (PEG), had about 100-fold greater anti-tumor effect than native TNF-alpha. Here, we assessed the usefulness of MPEG-TNF-alpha as a systemic anti-tumor therapeutic drug, using B16-BL6 melanoma and colon-26 adenocarcinoma, which have been reported to be resistant to TNF-alpha in vivo, as compared with Meth-A fibrosarcoma. MPEG-TNF-alpha markedly inhibited the growth of both tumors without causing any TNF-alpha-mediated side-effects, whereas native TNF-alpha had no anti-tumor effects and caused adverse side-effects. In addition, MPEG-TNF-alpha drastically inhibited the metastatic colony formation of B16-BL6 melanoma. MPEG-TNF-alpha may, thus, be a potential systemic anti-tumor therapeutic agent.
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PMID:In vivo anti-tumor efficacy of polyethylene glycol-modified tumor necrosis factor-alpha against tumor necrosis factor-resistant tumors. 895 67

Peptides (H-Glu-Ile-Leu-Asp-Val-NH2, H-Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr-NH2, H-Arg-Glu-Asp-Val-NH2) and their poly(ethylene glycol) (PEG) hybrids related to the core sequence of the type III connecting segment domain of fibronectin A chain were prepared by the solution method or the solid phase method. Their inhibitory effects on the adhesion and migration of B16-BL6 melanoma cells to fibronectin were assessed in vitro, and their therapeutic potency against tumor metastasis were also examined. Anti-adhesive and anti-migrative effects of the synthetic fibronectin-related peptids were superior to those of their PEG hybrids, so we found that the in vitro bioactivity of peptides decreased by PEGylation. In the in vivo assay, we found that the synthetic peptides containing Glu-Ile-Leu-Asp-Val and Arg-Glu-Asp-Val sequences exhibited an inhibitory effect on the experimental metastasis of B16-BL6 melanoma. Of the synthetic peptides, H-Glu-Ile-Leu-Asp-Val-NH2 exhibited the most potent inhibitory effect. Hybrid formation of Arg-Glu-Asp-Val with poly(ethylene glycol) resulted in potentiation of the inhibitory effect of the parent peptides. A mixture composed of PEG hybrids of Glu-Ile-Leu-Asp-Val, Arg-Glu-Asp-Val and Tyr-Ile-Gly-Ser-Arg dramatically inhibited tumor metastasis.
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PMID:Amino acids and peptides. XXIX. Synthesis and antimetastatic effects of peptides and peptide-poly(ethylene glycol) hybrids related to the core sequence of the type III connecting segment domain of fibronectin. 899 42

An analogue of human melanin-concentrating hormone (MCH) suitable for radioiodination was designed in which Tyr13 and Val19 of the natural peptide were replaced by phenylalanyl and tyrosyl residues: [Phe13, Tyr19]-MCH. The peptide was synthesized by the continuous-flow solid-phase methodology using Fmoc-strategy and polyhipe PA 500 and PEG-PS resins. The linear MCH peptides with either acetamidomethyl-protected or free cysteinyl residues were purified to homogeneity and cyclized by iodine oxidation, yielding the final product with the correct molecular weight of 2434.61. Radioiodination of the C-terminal tyrosine was carried out enzymatically using solid-phase bound glucose oxidase/lactoperoxidase, followed by purification on a reversed-phase mini-column and by high-pressure liquid chromatography. The resulting [125I]-[Phe13, Tyr19]-MCH tracer was the first radiolabelled MCH peptide suitable for radioreceptor assay: saturation binding analysis using mouse G4F-7 melanoma cells demonstrated the presence of 1090 MCH receptors per cell. The dissociation constant (KD) was 1.18 x 10(-10) M, indicating high-affinity MCH receptors on these cells. MCH receptors were also found in other cell lines such as mouse B16-F1 and G4F and human RE melanoma cells as well as in PC12 and COS-7 cells. Competition binding analyses with a number of other peptides such as alpha-MSH, neuropeptide Y, substance P and pituitary adenylate cyclase activating peptide, demonstrated that the binding to the MCH receptor is specific. Atrial natriuretic factor was found to be a weak competitor of MCH, indicating topological similarities between MCH and ANF when interacting with MCH receptors.
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PMID:Synthesis and iodination of human (phenylalanine 13, tyrosine 19) melanin-concentrating hormone for radioreceptor assay. 922 84

Dendritic cells (DCs) are the most effective APCs and are being studied as natural adjuvants or Ag delivery vehicles to elicit T cell-mediated antitumor immunity. This study examined whether inoculation of DCs fused with poorly immunogenic tumor cells elicited tumor-reactive T cells for adoptive immunotherapy. DCs derived from bone marrow of C57BL/6 (B6) mice were fused with syngeneic B16 melanoma or RMA-S lymphoma cells by polyethylene glycol. The B16/DC and RMA-S/DC fusion hybrids expressed MHC class I, class II Ags, costimulatory molecules, as well as DC-specific and tumor-derived surface markers. The tumor/DC hybrids were capable of processing and presenting tumor-derived Ags, and immunization of B6 mice with irradiated B16/DC or RMA-S/DC vaccine elicited tumor-specific CTL activities. Vaccination of B6 mice with irradiated B16/DC fusion preparations induced partial host protective immunity against B16 tumor challenge. Reduced tumor incidence and prolonged survival time were observed. Adoptive transfer of T cells derived from B16/DC vaccine-primed lymph nodes into B16 tumor-bearing mice greatly reduced the number of established pulmonary metastases with or without in vivo administration of IL-2. Moreover, adoptive transfer of RMA-S/DC vaccine-primed, cultured lymph node T cells eradicated disseminated FBL-3 tumor. The results demonstrate that tumor/DC fusion products are effective cellular vaccines for eliciting T cell-mediated antitumor immunity.
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PMID:Eliciting T cell immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines. 982 May 28


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