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)

Biological studies on [Fe(L)2](NO3).0.5H2O (1), [Fe(L)2][PF6] (2), [Co(L)2](NCS) (3), [Ni(HL)2]Cl2.3H2O (4) and Cu(L)(NO3) (5), where HL=C7H8N4S, pyridine-2-carbaldehyde thiosemicarbazone, have been carried out. The crystal structure of compound 3 has been solved. It consists of discrete monomeric cationic entities containing cobalt(III) ions in a distorted octahedral environment. The metal ion is bonded to one sulfur and two nitrogen atoms of each thiosemicarbazone molecule. The thiocyanate molecules act as counterions. The copper(II) and iron(III) complexes react with reduced glutathione and 2-mercaptoethanol. The reaction of compound 1 with the above thiols causes the reduction of the metal ion and bis(thiosemicarbazonato)iron(II) species are obtained. The redox activity, and in particular the reaction with cell thiols, seems to be related to the cytotoxicity of these complexes against Friend erithroleukemia cells and melanoma B16F10 cells.
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PMID:Biological activity of complexes derived from pyridine-2-carbaldehyde thiosemicarbazone. Structure of. 1137 90

When the natural logarithm of the surviving fraction is plotted against the dose of radiation, curves with shoulders at relatively high survival levels are obtained after gamma-rays. The curves were practically linear in case of HMV-I and HA-1 cells irradiated by charged particle beams. These cells were derived from human malignant melanoma and Chinese hamster cells, respectively. The amount of DNA single strand breaks (ssb) by gamma-rays or nitrogen-ions (LET=530KeV/micrometers) in HMV-I cells increases linearly with increment in dose, when the ssb is detected using the alkaline elution technique. There is no close relationship between the dose-response curve of the ssb and the dose-survival curves after gamma-rays or N-ions. The amount of DNA double strand breaks (dsb) by gamma-rays increases quadratically with increment of dose, in both HMV-I cells and HA-1 cells, when the dsb is detected using the neutral elution technique. The survival fraction for HA-1 cells is slightly higher than that for HMV-I cells, at the same dose, and the amount of dsb for HA-1 cells is considerably greater than that for HMV-I cells. These results suggest that the radiosensitivities to gamma-rays in different cell lines do not correspond to the number of DNA strand breaks. The amount of both non-repairable ssb and dsb also increases quadratically with increment of dose for gamma-rays and almost linearly with increment of dose for N-ions and alpha-particles (LET=36keV/micrometers for HA-1 cells and LET=77keV/micrometers for HMV-I cells). The dose-response curves for non-repairable dsb in case of these radiations seemed to mirror image the dose-survival curves for these radiations, in both cell lines. The number of non-repairable DNA strand breaks in the two cell lines, at the same level of survival was much the same. These results show the close relationship between the induction of non-repairable DNA strand breaks and cell killing.
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PMID:DNA-lesion and cell death by alpha-particles and nitrogen ions. 1153 17

During 1999 marine antitumor pharmacology research involved researchers in Austria, Australia, England, France, Germany, Greece, Holland, Italy, Japan, Spain, Taiwan and the United States. Thirty six papers were published in peer-reviewed journals describing the antitumor and cytotoxic properties of 30 marine natural products belonging to four structural types, namely polyketides, terpenes, nitrogen-containing compounds and polysaccharides. The organisms yielding these bioactive marine compounds comprised a diverse group of marine animals, algae, fungi and bacteria. A variety of antitumor pharmacological studies were conducted with 17 marine natural products with established mechanisms of action in a number of experimental and clinical models. Didemnin B, a tunicate-derived depsipeptide with potent antitumor effects, completed a Phase II anticancer clinical trial which resulted indeterminate in respect to activity against human melanoma due to anaphylactoid reactions. In vitro cytotoxicity data with murine and human cell lines were reported for 14 novel marine chemicals with as yet undetermined mechanisms of action. This 1999 literature overview thus highlights the fact that the multinational effort aimed at the discovery of novel marine antitumor agents remained at the same level of research activity as during 1998.
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PMID:Marine pharmacology in 1999: antitumor and cytotoxic compounds. 1172 12

Melanoma exhibits heterogeneous growth patterns and widely varying sensitivities to multiple treatment modalities. This variability may reflect intrinsic genetic differences in factors giving rise to altered metabolism. Glucose is the primary energy source of tumours, including melanoma, and glucose transporter isoform 1 (Glut-1) and hexokinase are key rate-limiting factors in glucose metabolism. The levels of Glut-1 and total hexokinase activity were measured in 31 melanoma biopsies to determine the extent of tumour-to-tumour variability in these parameters. Relative Glut-1 levels were determined by Western immunoblot analysis using human anti-Glut-1 rabbit polyclonal antibody, and hexokinase activity was measured in the same samples by an enzymatic assay monitoring the reduction in the oxidized form of nicotinamide adenine dinucleotide phosphate (NADP+) (in nmol NADP+ reduced/min per mg protein). All melanomas were from patients who had received no therapy prior to surgery. Immediately after excision, tumour biopsies were disaggregated to single cells by collagenase and DNase and frozen in liquid nitrogen. Thirty human melanomas exhibited a 22-fold variation in levels of Glut-1 and 29 exhibited a nine-fold variation in total cellular hexokinase activity. Glut-1 levels and hexokinase activity were not correlated with one another. The broad range in Glut-1 levels and hexokinase activity observed between melanomas suggests that these glycolytic rate-limiting parameters that influence the rate of glucose metabolism may contribute to the variability in melanoma response to treatment modalities.
Melanoma Res 2002 Feb
PMID:Variability in glucose transporter-1 levels and hexokinase activity in human melanoma. 1182 56

A library with 63 paclitaxel analogues modified at the C10 position of paclitaxel has been prepared using parallel solution phase synthesis. Most of the C10 analogues were slightly less active than paclitaxel in the tubulin assembly assay and had reduced potency in the B16 melanoma and MCF-7 cell line cytotoxicity assays. These modifications at C10, however, did not lead to the total loss of activity, indicating that the C10 moiety of paclitaxel may not be directly involved in the drug-microtubule interactions, but could influence its binding affinity to P-glycoprotein. Approximately 50% of the analogues demonstrated better activity against the drug resistant cell line MCF7-ADR. However, the increase in activity was 10-fold at most. This result demonstrates that the cytotoxicity against this drug resistant cancer cell line is sensitive to structural changes at the C10 position of paclitaxel. It was also found that the presence of a nitrogen atom in the C10 substituent might play a role in the interaction of analogues with microtubules.
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PMID:A systematic SAR study of C10 modified paclitaxel analogues using a combinatorial approach. 1186 Mar 38

The novel derivatives of thieno[3',2':4,5]thieno[2,3-c]quinolones 6a, 6b, 7, 10a and 10b were synthesized in multistep synthesis starting from thiophene-3-carboxaldehyde and malonic acid reacting in aldol condensation or from 3-bromothiophenes or methyl 4-bromothiophene-2-carboxylate reacting in Heck reaction. They resulted in corresponding substituted thienylacrylic acids 3a-c, which were cyclized into thieno[2,3-c]thiophene-2-carbonyl chlorides 4a-c and converted into thieno[2,3-c]thiophene-2-carboxamides 5a-d. Prepared carboxamides were photochemically dehydrohalogenated into corresponding substituted thieno[3',2':4,5]thieno[2,3-c]quinolones 6a-d. Compound 7 was prepared from 6d by alkylation with N-[3-(dimethylamino)propyl]chloride hydrochloride in the presence of NaH. Compounds 10a and 10b were prepared from 6c in the multistep synthesis over acid 8 and acid chloride 9. Compounds 6a, 6b, 7, 10a and 10b were found to exert cytostatic activities against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), colon carcinoma (CaCo-2), melanoma (HBL), and human fibroblast cell lines (WI-38). The compound 6b, which bears the 3-dimethylaminopropyl substituent on quinolone nitrogen and methoxycarbonyl substituent on position 9, exhibited marked antitumor activity. On the contrary, compound 7, which also bears the 3-dimethylaminopropyl substituent on the quinolone nitrogen but anilido substituent on position 9, exhibited less antitumor activity than the others.
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PMID:Synthesis, photochemical synthesis and antitumor evaluation of novel derivatives of thieno[3',2':4,5]thieno[2,3-c]quinolones. 1203 23

Pamidronate belongs to the class of nitrogen-containing bisphosphonates that are potent inhibitors of bone resorption frequently used for the treatment of osteoporosis and cancer-induced osteolysis. The inhibition of osteoclasts' growth has been suggested as the main mechanism of the inhibitory effect of pamidronate on bone metastases. Recent findings indicated that bisphosphonates also have a direct apoptotic effect on other types of tumour cells. Nitrogen-containing bisphosphonates were shown to inhibit farnesyl diphosphate synthase, thus blocking the synthesis of higher isoprenoids. By this mechanism they inactivate monomeric G-proteins of the Ras and Rho families for which prenylation is a functional requirement. On the background of the known key role of G-proteins in tumorigenesis, we investigated a possible beneficial use of pamidronate in the treatment of malignant melanoma. Our results indicate that pamidronate inhibits the cell growth and induces apoptosis in human melanoma cells in vitro. Susceptibility to pamidronate did not correlate to CD95 ligand sensitivity or p53 mutational status. Furthermore it is interesting to note that overexpression of bcl-2 did not abolish pamidronate-induced apoptosis. These data suggests that pamidronate has a direct anti-tumour effect on malignant melanoma cells, independently of the Bax/Bcl-2 level.
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PMID:The bisphosphonate pamidronate induces apoptosis in human melanoma cells in vitro. 1217 10

The root of Panax ginseng C. A. Meyer is one of the most popular natural tonics in oriental countries. In this study, we have isolated polysaccharide fraction of Panax ginseng (ginsan) and examined its effect on the function of murine peritoneal macrophages. When macrophages were treated with ginsan, cytotoxic activity against B16 melanoma cells was significantly induced. In addition, the levels of cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6 and Interferon-gamma (IFN-gamma) were increased and the production of reactive oxygen/nitrogen components such as nitric oxide (NO) and hydrogen peroxide (H2O2) was enhanced. Moreover, phagocytic activity was induced in ginsan-treated macrophages compared to the control. The expression of CD14 and 1-Ab on murine peritoneal macrophages was increased by the treatment with ginsan, while the expression of CD11b was decreased. Taken together, these results suggest that ginsan has an immunopotentiating effects on macrophages and these abilities could be used clinically for the treatment of diseases such as cancer.
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PMID:Immunostimulating effects of acidic polysaccharides extract of Panax ginseng on macrophage function. 1237 41

We investigated the need for continuous immunosuppression to maintain experimental tumours derived from human uveal melanoma cells implanted in the choroid of pigmented rabbits. Two groups of pigmented rabbits immunosuppressed with cyclosporin A (CsA) were implanted with human uveal melanoma cells in the suprachoroidal space. After 5 weeks, CsA was discontinued in group 2. Animals were treated with prophylactic antibiotics and examined weekly for tumour growth, weight and secondary effects; blood urea nitrogen levels were measured every two weeks. Autopsies and histopathological studies were performed after death or euthanasia at the end of week 12. The difference between the groups in the development of ophthalmoscopic tumours was not statistically significant 5 weeks after implantation. Tumours in group 1 grew progressively throughout the experiment, whereas group 2 tumours showed marked regression 3-4 weeks after discontinuing CsA. Tumours in group 1 were significantly larger and had greater mitotic activity and showed more ciliary body, optic nerve and extrascleral invasion than tumours in group 2, which showed massive fibrosis, minimal mitotic activity and marked inflammatory cell infiltration. Continuous immunosuppression with CsA seems to be necessary to maintain tumour growth in this experimental model of uveal melanoma.
Melanoma Res 2002 Oct
PMID:The need for continuous immunosuppression with cyclosporin A to maintain an experimental model of uveal melanoma. 1239 85

Large excisions or Mohs' micrographic surgery (MMS) are often the suggested treatments for non-melanoma skin cancers (NMSCs) of the external ear. This five-year follow-up attempts to evaluate whether curettage-cryosurgery could be an alternative therapy for selected auricular NMSCs. One hundred auricular NMSCs, selected at a skin tumour clinic, were treated by a thorough curettage, with different-sized curettes, followed by cryosurgery in a double freeze-thaw cycle. Seventy-seven basal cell carcinomas (BCCs), 13 squamous cell carcinomas (SCCs), six SCCs in situ, and four basosquamous carcinomas were included. The mean diameter of the tumours was 18 mm (range 5-70). Morphoeiform BCCs, recurrent BCCs with fibrotic component, and most of the SCCs were selected for MMS. Seventy-one patients with 81 tumours were followed-up for at least five years with only one recurrence. Nineteen patients with 19 tumours, followed-up for two to four years, died from other causes with no sign of recurrence at their last visit. Patients followed-up for less than two years were excluded. No major problems were registered after treatment. The cosmetic result was good or acceptable in most patients. In carefully selected patients a thorough curettage followed by freezing with liquid nitrogen in a double freeze-thaw cycle could be a safe and inexpensive therapy even for large NMSCs of the external ear.
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PMID:Five-year results of curettage-cryosurgery for 100 consecutive auricular non-melanoma skin cancers. 1248 65


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