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

A series of alkylating phosphoramidate analogs of 5-fluoro-2'-deoxyuridine has been prepared and their growth inhibitory activity evaluated against murine L1210 leukemia and B16 melanoma cells in vitro. These compounds were designed to undergo intracellular release of the phosphoramidate anions, which it was hoped would function as irreversible inhibitors of thymidylate synthase. The expectation was that binding of the nucleoside moiety would be followed by alkylation of the enzyme via the phosphoramidate. The chloride, bromide, iodide, and tosylate analogs were highly potent inhibitors of L1210 cell proliferation, with increased inhibition observed at both higher drug concentrations and longer exposure times. Addition of thymidine completely reversed the inhibition for all compounds, suggesting that these compounds are acting via inhibition of thymidylate synthase. Although the nonalkylating morpholine analog 1f was ca. 50-fold less potent than the methyl(chloroethyl)amino compound, the piperidine analog 1g was only 2-fold less potent, confirming that nitrogen basicity may be as important as the presence of an alkylating group. Addition of thymidine reversed the growth inhibition of the morpholine and piperidine analogs, suggesting that these compounds may also undergo intracellular conversion to 5-fluoro-2'-deoxyuridine 5'monophosphate. The thymidine and deoxyuridine derivatives 2 and 3 showed minimal growth inhibition in the L1210 assay. The alkylating analogs showed modest cytotoxicity against B16 melanoma cells, and the potency of the analogs was more dependent upon the alkylating moiety than on the 5-substituent.
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PMID:Synthesis and biological evaluation of 5-fluoro-2'-deoxyuridine phosphoramidate analogs. 762 6

The existence and properties of volume-activated Cl- currents were studied in 15 different cell types (endothelium: human umbilical vein, human aorta, bovine pulmonary artery; fibroblasts: Swiss 3T3, L, C3H 10T1/2 and COS-1; epithelium: KB3, HeLa and A6; blood cells: RBL-2H3 and Jurkat; endothelioma cells derived from both subcutaneous and thymic hemangiomas; skin: IGR1 melanoma). Volume-activated Cl- currents with common characteristics, i.e. small conductance, outward rectification, higher permeability for iodide than for chloride and sensitivity to block by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) could be elicited in all cells. The block of this current by tamoxifen and dideoxyforskolin is different for the various cell types, as well as the time course and the amplitude of the responses induced by repetitive applications of hypotonicity. Volume-activated Cl- channels with similar biophysical properties are therefore wide-spread among mammalian cells. This may reflect either a single Cl- channel that is ubiquitously expressed or a family of functionally related Cl- channels with cell specific expression patterns.
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PMID:Volume-activated Cl- currents in different mammalian non-excitable cell types. 781 59

The proliferation of human melanoma cells in vitro after irradiation and/or hyperthermia was studied by means of two-parameter flow cytometry. Cultures were incubated with BrdU for 30 min and fixed either immediately or after a delay of several hours. Cells having synthesized DNA were identified with the help of an antibody against BrdU. DNA was stained quantitatively with propidium iodide. In this way the distribution of cells in the phases of cell cycle could be determined and the movement of labeled cells through the phases of the cycle could be analyzed. Experiments in which the cell cycle distribution was studied at 4-h intervals after treatment showed the following: (1) Irradiation (4 Gy X rays) causes the expected G2 block with a maximum after 12-16 h. The proportion of S-phase cells decreases continually during the first 48 h after treatment. (2) Hyperthermia (1 h, 43 degrees C) alone or in combination with irradiation causes a delay in S phase. The cells begin to move into G2 phase only after 12-16 h and accumulate there to some extent. From the progression of labeled cells through the cycle, the duration of S phase could be determined. Experiments and calculations of this kind were done 0, 24 and 48 h after treatment. The duration of S phase was increased only moderately (by 4 h) after irradiation, but a delay of about 30 h occurred after hyperthermia (alone or in combination with X rays). Smaller delays (up to 9 h) were observed 24 and 48 h after treatment. Two different methods were used to calculate potential doubling times. Both of them gave similar results, but a comparison with the actual population doubling times (determined by cell counting) showed that reasonable estimates could be achieved only for the untreated controls. With cultures subjected to irradiation and/or hyperthermia serious discrepancies were observed. This does not seem to be due to technical problems inasmuch as we are dealing with a whole set of data produced under well-defined in vitro conditions (in contrast to the clinical situation, where potential doubling times have to be estimated from single samples). Our results certainly do not encourage the extension of the method (which was originally intended for the prediction of unperturbed tumor growth) to a post-treatment setting.
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PMID:Determination of potential doubling times in human melanoma cell cultures subjected to irradiation and/or hyperthermia by flow cytometry. 818 21

The authors studied the short-term impact of combined episcleral iodine-125 plaque radiotherapy and argon laser treatment in a series of 24 patients with choroidal malignant melanoma. All patients underwent plaque therapy prior to their initial laser session. All laser treatments were performed with an indirect ophthalmoscope argon green laser, using low-power, long-duration exposures. The endpoint of laser therapy was a well-defined atrophic circumbasal chorioretinal laser scar and complete or nearly complete nonfluorescence of the lesion on fluorescein angiography. In a case-by-case matched comparison study, the authors evaluated the relative local regression of tumors treated by combined plaque-laser therapy, iodine-125 plaque therapy alone, and cobalt-60 plaque therapy alone. The tumors treated with supplemental laser regressed substantially faster and more completely than did those treated by either type of plaque therapy alone. However, the short-term visual loss was greater in eyes treated by the combined therapy.
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PMID:Combined iodine-125 plaque irradiation and indirect ophthalmoscope laser therapy of choroidal malignant melanomas: comparison with iodine-125 and cobalt-60 plaque radiotherapy alone. 822 53

Monoclonal antibodies are expected to carry radio-nuclides selectively to cancer tissues and to offer antigen-specific diagnosis and/or therapy of cancer. Monoclonal antibodies tagged with indium (111In) and technetium (99mTc) are clinically used for the localization of malignant melanoma, colorectal and ovarian cancer. They have detected about 80% of tumors, tumors missed by conventional diagnostic methods and tumors in patients with normal serum tumor marker levels. Acute or subacute toxicity was not observed. However, human anti-murine antibodies (HAMA) were detectable in sera of some cases after receiving radiolabeled monoclonal antibodies. Development of protein engineering has made it possible to produce humanized antibodies, which are expected to diminish the HAMA response. The same monoclonal antibodies are also employed for therapy of some cancers using iodine (131I), yttrium (90Y) and rhenium (186Re) labeled antibodies.
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PMID:[Use of monoclonal antibodies for the immuno-imaging of cancers]. 831 87

Preclinical studies established [125I]-N-(2-diethylaminoethyl) 4-iodobenzamide (BZA) as a potential radiopharmaceutical in the management of patients with malignant melanoma. External detection of both murine and human melanotic melanomas was possible after intravenous injection of 125I-BZA in tumor-bearing mice. This article reports a Phase II clinical trial evaluating 123I-BZA as an imaging agent of primary melanomas and metastases. A total of 110 patients with a history of melanoma were investigated in two nuclear medicine departments. Subjects were imaged from 20 to 24 hr after the intravenous injection of 3.5 mCi (130 MBq) of 123I-BZA. After injection, no short-term or long-term side effects were noted. Calculated on a lesion-site basis, diagnostic sensitivity was 81%, accuracy was 87% and specificity was 100%. The melanoma nature of previously occult lesions was confirmed by clinical criteria and/or additional investigations in follow-up studies. The scintigraphies were normal in 44 patients in clinical remission after treatment of malignant melanoma and in seven patients with nonmelanoma disease. No false positive results were observed. Iodine-123-BZA scintigraphy appears to be a safe and useful agent for the detection and follow-up of patients with malignant melanoma. BZA also allowed the detection of unsuspected lesions and the evaluation of the results of various therapeutic procedures such as surgery, chemotherapy, immunobiology, biological therapy or radiotherapy.
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PMID:Phase II scintigraphic clinical trial of malignant melanoma and metastases with iodine-123-N-(2-diethylaminoethyl 4-iodobenzamide). 832 82

In order to evaluate the behaviour of N-(2-diethylaminoethyl)-4-[123I]iodobenzamide in malignant melanotic disease, we synthesized the bromo compound in a simple one-step reaction. Labelling was performed by non-isotopic bromine-iodine-123 exchange in radiochemical yields up to 60%. By means of isocratic high-performance liquid chromatography, the iodinated product could be isolated with high apparent specific activity. First clinical studies in patients with malignant melanoma using N-(2-diethylaminoethyl)-4-[123I]iodobenzamide showed moderate uptake of the tracer in the tumour and the suspected metastases in all patients. Most of the lesions were detectable with technetium-99m-diethylene triamine penta-acetic acid (DTPA) scintigraphy too, but we were able to detect additional, previously unidentified metastases with benzamide scintigraphy. This changed the therapeutic procedure in two of the five cases investigated so far.
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PMID:N-(2-diethylaminoethyl)-4-[123I]iodobenzamide as a tracer for the detection of malignant melanoma: simple synthesis, improved labelling technique and first clinical results. 846 13

The effects of ursolic acid on the proliferation of B16, a mouse melanoma cell line, were studied. During investigations of the anti-proliferative effects of this triterpene, we observed that MTT colorimetric and colony forming assays show that ursolic acid is a potent inhibitor of B16 cell growth. Cell cycle analysis was performed by propidium iodide staining and flow cytometry technique. This triterpene exerts an early effect on cell cycle at G1, which explains its anti-proliferative activity. These results suggest that alterations in cell cycle phase redistribution of B16, by ursolic acid, may significantly influence the proliferation of B16, melanoma cells.
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PMID:Inhibitory effect of ursolic acid on B16 proliferation through cell cycle arrest. 884 72

An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin conjugate is currently under clinical evaluation as a new antitumour agent. It has been shown previously that such conjugates exhibit selective tumour accumulation. In this study HPMA copolymer doxorubicin conjugates of low (LMW) or high (HMW) molecular weight were synthesised (which had a weight average molecular weight (Mw) of 25,000 and 94,000 respectively) and additionally contained a small amount (1 mol%) of the comonomer methacryloyltyrosinamide to permit labelling with [123I or 125I]iodide. Gamma camera imaging using the 123I-labelled probes was used to follow time-dependent biodistribution after intraperitoneal (i.p.) or intravenous (i.v.) administration to mice bearing subcutaneously either B16F10 melanoma or a mammary carcinoma. Imaging showed more rapid clearance of LMW conjugate from the peritoneal cavity than HMW conjugate. The images of mice given the LMW conjugate revealed rapid urinary excretion of radioactivity after both i.p. and i.v. injection with an early high concentration of tracer in the bladder, and subsequently a very high concentration in the kidneys, which came to dominate the views. Dissection analysis 2 days after administration of the LMW conjugate revealed a kidney level of radioactivity corresponding to 25-40% dose/g tissue in mice bearing the two tumour models. Following administration of the HMW conjugate kidney accumulation at 2 days was less due to retention of the higher molecular weight polymer molecules in the circulation, and spleen and liver displayed the highest concentrations of radioactivity. The tumour accumulation of LMW and HMW conjugates was; mammary carcinoma 3.18 and 5.29% dose/g respectively; B16F10 melanoma 3.23 and 8.82 %dose/g although these levels of tracer enabled visualisation in the images of the mammary carcinoma with HMW conjugate at later time points. The smaller size of the B16F10 tumour masses did not permit clear visualisation.
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PMID:Gamma scintigraphy of the biodistribution of 123I-labelled N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates in mice with transplanted melanoma and mammary carcinoma. 886 56

Two peptides of potential utility for targeting melanoma cells, alpha-melanocyte-stimulating hormone (alpha-MSH) and its more potent analogue [Nle4,D-Phe7]-alpha-MSH, were radioiodinated in 45-65% yield using N-succinimidyl 3-[125I]iodobenzoate (SIB). To determine whether this labeling method resulted in improved in vitro and in vivo characteristics, these peptides also were labeled with 131I by direct iodination with the iodogen method. For alpha-MSH, the rapid tissue clearance of both radionuclides in mice was consistent with rapid degradation of the peptide; however, significantly lower levels of 125I were observed in thyroid and stomach, reflecting a greater inertness to deiodination. More extensive comparisons were performed with [Nle4,D-Phe7]-alpha-MSH. The in vitro binding of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH (prepared using SIB) to the murine B-16 melanoma cell line, 34.1 +/- 4.7%, was more than twice as high as that for [Tyr2(131I),Nle4,D-Phe7]-alpha-MSH (15.0 +/- 0.1%), and its KD was more than 10-fold lower than that for conventionally labeled peptide (10 +/- 5 versus 140 +/- 14 pM). The normal tissue clearance of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH in mice was faster than that of [Tyr2(131I),-Nle4,D-Phe7]-alpha-MSH. The 19-40-fold lower activity concentrations of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH in tissues accumulating free iodide (thyroid and stomach) suggest a greater inertness of this peptide to deiodination. The primary urinary catabolite of [Nle4,D-Phe7, Lys11-(125I)IBA]-alpha-MSH was the lysine conjugate of iodobenzoic acid, whereas radioiodide was the chief catabolite generated from [Tyr2(131I),Nle4,D-Phe7]-alpha-MSH. We conclude that further evaluation of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH for targeting alpha-MSH receptors is warranted and that SIB may be a useful method for the radioiodination of peptides.
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PMID:Enhanced binding and inertness to dehalogenation of alpha-melanotropic peptides labeled using N-succinimidyl 3-iodobenzoate. 898 45


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