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

Systemic administration of swainsonine, an indolizidine alkaloid, inhibits the experimental metastasis of B16-F10 murine melanoma cells. This activity can be attributed primarily to swainsonine-mediated enhancement of host natural killer cell activity. As one next step towards investigating the potential therapeutic utility of this drug, its efficacy in enhancing host survival in the same B16-F10 model system has been assessed. In studies employing intravenously injected tumor cells, pretreatment of mice with swainsonine-containing drinking water provided a reproducible protective effect for the host. This prolongation of survival was substantially enhanced when swainsonine was administered in combination with either of two other immunomodulators, polyinosinic: cytidylic acid (poly-IC) or interleukin-2. In studies in which combinations of these agents were administered after intravenous injection of tumor cells, or after subcutaneous implantation, a greatly reduced effect on host survival was observed. However, when used in combination with cyclophosphamide (to block the effects of suppressor T cells), swainsonine did increase mean survival time. The implications of these results for the use of swainsonine in treatment of metastatic or localized disease, together with its potential mechanism(s) of action, are discussed.
 ...
PMID:An assessment of the effects of swainsonine on survival of mice injected with B16-F10 melanoma cells. 210 78

Swainsonine, an inhibitor of alpha-mannosidases, has been shown to block experimental metastasis of B16F10 melanoma and MDAY-D2 lymphoid tumor cells in syngeneic mice. In this report we demonstrate that swainsonine also reduces the growth rate of human melanoma cells in vitro and in vivo. Graded doses of swainsonine were administered either orally or via implanted Alzet miniosmotic pumps to athymic nude mice bearing subcutaneously implanted human MeWo melanoma cells. Swainsonine at 10 micrograms/ml in the drinking water or 0.5 mg/kg/day administered by miniosmotic pump reduced the growth rate of the MeWo tumors by approximately 50% and inhibited the expression of complex-type oligosaccharides in tumors and host intestine by only 10-20%. Swainsonine doses of 4 mg/kg/day reduced expression of complex-type oligosaccharides by 85% in vivo but afforded no additional inhibitory effect. A glycosylation mutant of MeWo called 3S5 has a defect in the synthesis of complex-type asparagine-linked oligosaccharides resulting in incomplete processing similar to that observed in swainsonine-treated MeWo tumor cells. Swainsonine did not inhibit the proliferation of 3S5 cells in vitro nor the growth of 3S5 tumors in nude mice. The results suggest that expression of highly branched complex-type oligosaccharides commonly associated with the malignant phenotype may provide the tumor cells with a growth advantage.
 ...
PMID:Growth inhibition of human melanoma tumor xenografts in athymic nude mice by swainsonine. 210 89

In a controlled study, malignant murine P815 mastocytoma cells exposed in vitro to distilled and deionized water died as a result of progressive swelling, degranulation, and membrane rupture. A 90% mean cell death occurred when cells obtained directly from culture were exposed to deionized water for 2 minutes. Of 6 cryopreserved malignant murine cell lines, which included Cloudman S91 melanoma, CMT-93 rectum carcinoma, MMT-06052 mammary carcinoma, and S-180 Sarcoma, only P815 mastocytoma and YAC-1 lymphoma were significantly (P less than 0.05) affected by hypotonic shock; Cloudman S91 melanoma cells were the most resistant. Mastocytoma cells were selectively killed by hypotonic solution, and lymphoma cells were also killed by isotonic saline solution. Local mast cell tumor (MCT) recurrence and percentage survival were evaluated in 12 cats (21 MCT) and 54 dogs (85 MCT) subjected to surgery alone or local infiltration of deionized water as an adjunct to surgery. Of all 16 incompletely excised MCT in cats, there was no local recurrence following injection. Four mast cell tumors (2 cats) regressed after being injected in situ. In dogs with clinical stage-I MCT, local recurrence was detected in 50% (5/10), but with injection after incomplete excision, local MCT recurrence was significantly (P less than 0.05) less (6.6%, 1/15). Percentage recurrence was significantly (P less than 0.05) less and survival significantly greater when incompletely excised grade-II MCT were injected. Mean follow-up period after surgery in cats and dogs was 35 and 23.4 months, respectively.
 ...
PMID:Mast cell tumor destruction by deionized water. 211 68

Phenolic melanin precursors can be utilized for the development of anti-melanoma agents. The sulphur homologue of tyrosine, 4-S-cysteinylphenol (CP) and its decarboxylation product, 4-S-cysteaminylphenol (CAP) were shown to be substrates of melanoma tyrosinase, forming melanin-like pigment. Both, but in particular the 4-S-CAP, exhibited a significant in vivo depigmenting effect. Here, we report on the in vivo anti-melanoma effect of 4-S-CP, and 4-S-CAP and its N-acetyl derivative. In a previous in vitro study, it was shown that 4-S-CP and 4-S-CAP required a catalytic amount of dopa for optimal mammalian tyrosinase activity. To enhance the potential anti-melanoma effect of these two compounds. L-dopa and a decarboxylase inhibitor (carbidopa) were given concomitantly. We found that 4-S-CAP showed a significant growth inhibition of B16 melanoma inoculated s.c. into C57BL/6J mice. The anti-melanoma effect was increased significantly by combination of L-dopa and carbidopa. In addition, we tested the in vivo anti-melanoma effect of an N-acetyl derivative of 4-S-CAP (N-Ac-4-S-CAP). We found that N-Ac-4-S-CAP was the tyrosinase substrate and potent inhibitor of melanoma growth. N-acetyl 4-S-CAP showed a marked increase in water solubility. We suggest that N-Ac-4-S-CAP may prove to be a valuable model for the development of anti-melanoma agent using a metabolic pathway of melanin synthesis.
 ...
PMID:The in vivo antimelanoma effect of 4-S-cysteaminylphenol and its n-acetyl derivative. 212 52

The etiology of the paramagnetic relaxation enhancement seen in malignant melanoma on proton magnetic resonance (MR) images has been the subject of many recent investigations and has been ascribed to iron from associated hemorrhage or chelated metal ions, rather than directly due to melanin. The purpose of this study was to correlate proton relaxation times on MR images in malignant melanomas with histopathologic features (i.e., degree of pigmentation, iron deposition, and necrosis), water content, and electron paramagnetic resonance (EPR) spectra to elucidate the etiology of the relaxation behavior demonstrated by these neoplasms. Cultured cells derived from human malignant melanoma metastases were implanted subcutaneously into nude mice. Twelve separate lesions were evaluated in 10 mice. Magnetic resonance imaging was performed in vivo at 1.9 T using spin echo and inversion recovery acquisitions for the purposes of calculating T1, T2, and proton density [N(H)]. Histopathologic examination was performed on specimens resected immediately after imaging, using hematoxylin/eosin, Prussian blue, and Fontana stains to assess tumor necrosis, and iron and melanin content. Dry/wet weight ratios and EPR spectra were also obtained on resected specimens. Our results indicate that T1 shortening correlates with increasing melanin content and not with increasing iron deposition, EPR-active metallic cations, necrosis, or water content. In fact, a presumably unrelated statistical correlation was found between increased iron and T1 prolongation. The T2 relaxation times did not correlate with the presence of any single factor other than proton density. Although the unique relaxation behavior of nonhemorrhagic malignant melanoma in vivo cannot be traced to a single cause, our data suggest that, contrary to previous investigations, it is strongly influenced by the presence of melanin rather than iron or other naturally occurring paramagnetic ions.
 ...
PMID:Human malignant melanomas with varying degrees of melanin content in nude mice: MR imaging, histopathology, and electron paramagnetic resonance. 216 37

Physics studies related to radiation source, spectroscopy, beam quality, dosimetry, and biomedical applications using the Kyoto University Reactor Heavy Water Facility are described. Also, described are a Nickel Mirror Neutron Guide Tube and a Super Mirror Neutron Guide Tube that are used both for the measurement of boron concentration in phantom and living tissue and for precise measurements of neutron flux in phantom in the presence of both light and heavy water. Discussed are: (1) spectrum measurements using the time of flight technique, (2) the elimination of gamma rays and fast neutrons from a thermal neutron irradiation field, (3) neutron collimation without producing secondary gamma rays, (4) precise neutron flux measurements, dose estimation, and the measurement of boron concentration in tumor and its periphery using guide tubes, (5) the dose estimation of boron-10 for the first melanoma patient, and (6) special-purpose biological irradiation equipment. Other related subjects are also described.
 ...
PMID:Biomedical irradiation system for boron neutron capture therapy at the Kyoto University Reactor. 217 58

Although the hematoporphyrin derivative (Hpd) is one of the most studied photosensitisers for photodynamic therapy (PDT), it is far from ideal. Therefore, many laboratories have been investigating a new group of sensitisers, the phthalocyanines. Particularly, in our laboratory we decided to study the aluminum disulfonated phthalocyanines (AlS2PC). They are chemically stable, readily soluble in water and have a strong absorption in the red part of the spectrum at 675 nm. Mice bearing the MS-2 fibrosarcoma treated with 5 mg/kg of AlS2PC survived indefinitely also using a low laser power of 100 mW/cm2 X 10' of exposure time, in contrast to experiments carried out with Hpd where the optical therapeutic laser power was 400 mW/cm2 X 10' and the dose of Hpd was 25 mg/kg. Furthermore, treatment of mice bearing the highly metastatic tumor, B16 melanoma, with 5 mg/kg of AlS2PC and laser light (100 mW/cm2 X 10'), significantly prolonged the survival time in respect to mice treated with 25 mg/kg of Hpd and laser light (400 mW/cm2 X 10').
 ...
PMID:Comparative study of the therapeutic effect of photoactivated hematoporphyrin derivative and aluminum disulfonated phthalocyanines on tumor bearing mice. 220 71

Dihydroambazone (DHA) is a water-soluble derivative of the experimental anticancer drug ambazone. In vitro, a combination of DHA and human recombinant tumor necrosis factor alpha (TNF) exerted a strong synergism of cytotoxicity against both mouse melanoma B16K cells and the TNF-sensitive mouse fibroblast line L-M (S). Furthermore, in a colony-forming assay with B16K cells a combination of TNF and DHA inhibited colony-formation much more severely than either drug alone. An increased antiproliferative efficiency was also confirmed in vivo against established subcutaneous melanoma B16 tumors of C57BL/6 mice.
 ...
PMID:Synergistic cytotoxic effect of human recombinant tumor necrosis factor alpha combined with dihydroambazone. 222 40

Rhodamine 123 has been shown to be an efficient photosensitizer for the argon laser treatment of a human squamous carcinoma and a melanoma cell line in vitro. Rhodamine 123 laser phototherapy also eradicates these human squamous cell carcinomas when grown as subcutaneous tumor transplants in athymic mice. This study extends these observations by testing a panel of 19 human tumor cell lines of various histologic origins for in vitro sensitivity to rhodamine 123 and the argon laser. Rhodamine 123 with an absorption maxima of 502 nm in water was found to undergo a redshift to 516 nm after uptake by the mitochondria of human tumor cells. Rhodamine 123-sensitized brain tumor cells were inhibited by over 80% after 15 seconds and by 98% after 60 seconds of laser exposure (514.5 nm, 4 W, Tmax = 39 degrees C), as measured by reduced [3H]thymidine incorporation into cellular DNA. Laser or rhodamine 123 alone did not significantly inhibit (greater than 20%) tumor cell [3H]thymidine uptake. Sensitization with 20 micrograms rhodamine 123 for 1 hour before 45 seconds of laser illumination decreased cell [3H]thymidine uptake by 40% to 99% in four melanoma lines, five carcinomas, five leukemias, and four of five other human tumor lines. Two melanomas, two leukemias, and a lymphoma cell line also exhibited a 70% to 80% reduction in [3H]thymidine uptake after sensitization in vitro with 1 microgram/mL rhodamine 123 and laser illumination. Rhodamine 123-sensitized tumor cells were inhibited even more strongly by fractional dose laser irradiation at nonthermal temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tumors of diverse histology are sensitive to rhodamine 123 laser phototherapy in vitro. 224 Apr 15

New platinum(II) complexes, bis(bilato)-1,2-cyclohexanediammineplatinum(II) which were lipophilic and water-miscible, were tested for antitumor activity against lung nodules from intravenously injected B16-F10 melanoma cells in C57BL/6 mice by intravenous administration of the complexes in water suspension form. Among them, DACHP(litho)2 and DACHP(urso)2 had high antitumor activity but others had no activity. The antitumor activity of DACHP(urso)2 was increased significantly by injecting it three times; T/C was over 280% with 100-day survivors of 3 of 6 mice tested. Large amounts of total platinum were found in lung and liver tissues by atomic absorption spectroscopy after single intravenous injection of DACHP(urso)2 suspension in ICR mice.
 ...
PMID:Effect of bis(bilato)-1,2-cyclohexanediammineplatinum(II) complexes on lung metastasis of B16-F10 melanoma cells in mice. 226 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>