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)

Gelonin, a ribosome-inactivating protein from the seeds of Gelonium multiflorum, has been conjugated to antibodies. Previous reports have indicated variable potency of such immunotoxins. The lack of toxicity of gelonin, however, makes it attractive for immunoconjugate production. The ribosome-inactivating protein was covalently linked (using N-succinimidyl-3-(2-pyridyldithio)propionate) to monoclonal antibody, 9.2.27, directed to a human melanoma-associated glycoprotein/proteoglycan. The immunoconjugate showed high selectivity with dose-dependent cytotoxic activity to cultured human melanoma cells (50% inhibitory dose; 1-3 X 10(-11) M versus antigen-positive cells; 1-3 X 10(-7) M versus antigen-negative cells). Specificity and immunoreactivity of the conjugate were similar to those of unconjugated antibody. Biodistribution studies with iodine trace-labeled conjugate in nude mice indicated that tumor localization of the gelonin conjugate was decreased compared to unconjugated antibody. However, a significant therapeutic effect of the conjugate was found with multiple but not single dose i.v. treatment in nude mice bearing established palpable melanoma. These in vivo experiments showed that gelonin conjugates are not toxic up to 2 mg total dose/mouse and significantly retarded the growth of established s.c. tumor. Comparison of gelonin conjugates in vitro and in vivo with other A-chain conjugates of 9.2.27 (abrin and ricin) indicated that gelonin had similar potency, better selectivity, better tumor localization, and more significant therapeutic effects.
 ...
PMID:Immunotoxins to a human melanoma-associated antigen: comparison of gelonin with ricin and other A chain conjugates. 349 29

The efficiency of the membrane attack complex (MAC) in killing M21 melanoma cells was determined varying the molar ratio of cell-bound C9:C8. It was found that C5b-8 produced functional channels as evidenced by 86Rb release and propidium iodide uptake; cell killing occurred in the absence of C9 with greater than 5 X 10(5) C5b-8/cell; the maximal molar ratio of C9:C8 was 6.6:1; using nonlytic numbers of C5b-8 (4.7 X 10(5)/cell), greater than 90% killing ensued at a C9:C8 molar ratio of 2.8:1 at which approximately 9,000 poly C9/cell were formed, and 50% killing at a ratio of 1:1; (e) when the MAC was assembled on cells at 0 degree C, consisting of C5b-8(1)9(1), and unbound C9 was removed before incubation at 37 degrees C, killing was similar to that observed when poly C9 formation was allowed to occur. Thus, MAC lytic efficiency toward M21 cells may be enhanced by but does not depend on poly C9 formation.
 ...
PMID:Killing of human melanoma cells by the membrane attack complex of human complement as a function of its molecular composition. 359 74

Thiouracil and various derivatives are selectively incorporated into the melanin pigment of melanomas during biosynthesis by serving as false melanin precursors. Using the transplantable Harding-Passey melanoma carried in BALB/c mice, we have extended our previous studies with sulfur-35 (35S) thiouracil. The persistence of high levels of [35S]thiouracil in tumor for periods of up to 2 wk has been demonstrated; during this time the drug content in normal tissues returned to near background levels. The variety of iodine isotopes available makes iodothiouracil a particularly promising melanoma-localizing agent. Tumor uptake and biodistribution of [35S]thiouracil and iodothiouracil (both iodine-127 (127I) and iodine-125 (125I) labeled) have been compared and were found to be essentially the same. The selectivity of [125I]thiouracil for melanoma has been qualitatively demonstrated by autoradiography of whole-body sections and quantitated by analysis of tumor and selected tissues. Iodothiouracil was also shown to localize in remote secondary metastases using a metastatic variant of the Harding-Passey melanoma currently being developed in our laboratory. These studies confirm the melanoma localizing capabilities of an iodinated thiouracil, and therefore the potential of using iodinated thiouracil derivatives for diagnosis and therapy of melanotic melanomas.
 ...
PMID:Iodothiouracil as a melanoma localizing agent. 372 91

Within the interval of 0.25-168 h after intraperitoneal administration of 125I-iodo-desoxyuridine (IDUR) to mice with inoculated melanoma B-16 or sarcoma-180 the kinetics of a radionuclide label (RL) in both tumors was almost the same; the difference were of quantitative nature only. X-ray radiation resulted in an increase in the radioactivity change rate on the first section of the curves of RL clearance, plotted in semilogarithmic coordinates, in both tumors. Differences in the rates in the study groups of animals irradiated at doses of 2; 10 and 20 Gy and their distinctions from the control group were significant. Proceeding from the modern concept of IDUR metabolism a simple mathematical model has been devised where it is assumed that at the initial moment t = 0.25 h general radioactivity measured in vivo over a tumor, results from radioactivity incorporated in DNA which is constant for each irradiation regimen up to a certain time, and the radioactivity of iodide which is released from the body by the exponential law. A formula has been deduced associating the rate of a decrease in general radioactivity on the first segment of a kinetic curve of RL clearance with the level of the label incorporation in DNA. Thus, the applicability of RL IDUR was shown for establishing the quantitative relations between the proliferative ability of a tumor and an irradiation dose.
 ...
PMID:[Effect of x-irradiation on the kinetics of 5-iodo-2'-deoxyuridine in a tumor]. 376 49

Confirmation of iodine-125 plaque position was determined with a modified fiberoptic light pipe that directed light at right angles to the long axis of the fiberoptic pipe. While the examiner observed the interior of the eye with indirect ophthalmoscopy, the point source of light from the fiberoptic light pipe was moved along the margins of the episcleral plaque. The position of the plaque relative to the location of the underlying melanoma could then be verified by transillumination.
 ...
PMID:A technique for accurate placement of episcleral iodine-125 plaques. 379 90

Low-energy radiation sources, such as iodine-125, are suitable for treating choroidal melanoma because of their physical characteristics. Iodine-125 emits x-rays and gamma-rays between 27 and 35 keV. Gold plaques can direct radiation toward the tumor and minimize radiation to normal ocular structures. Effective treatment requires the cooperation of the ophthalmologist, radiotherapist, and radiation physicist. The preparation of the radioactive plaque and methods for its accurate surgical placement are detailed.
 ...
PMID:New techniques for iodine-125 radiotherapy of intraocular tumors. 382 64

The LS-174T human colon carcinoma line and A375 human melanoma line were used to establish primary tumor xenografts at three sites (subcutaneous, spleen, and kidney) in congenitally athymic mice. A monoclonal antibody (MAb) reactive with the LS-174T line, B72.3 IgG, was labeled with iodine 125, and an isotype-identical control antibody MOPC-21, was labeled with iodine 131. Labeled antibodies were injected intravenously in tumor-bearing mice, and animals were killed at varying intervals. Tumor-to-blood and tumor-to-organ ratios of MAb 72.3 indicated no significant difference at any of the three primary tumor sites in LS-174T tumor-bearing mice. The percent injected dose per gram was higher at visceral sites on day 3, but was similar on days 5 and 7 at all sites. Localization indices on all days ranged from 4 to 1 to greater than 16 to 1, confirming the specificity of the B72.3 reactivity at all sites. Athymic mice bearing tumor xenografts were scanned on day 7, and the LS-174T spleen and kidney tumors were imaged, with efficacy similar to that of the subcutaneous site. The visceral tumor model is more representative of the human disease, and may therefore be a better model for evaluation of monoclonal antibodies for radioimmunodetection and therapy for cancer in intra-abdominal organs.
 ...
PMID:Radioimmunodetection of human colon carcinoma xenografts in visceral organs of congenitally athymic mice. 394 82

We have developed and used a thermoradiotherapy (TRT) plaque to treat choroidal melanoma (Greene strain) in rabbits. A dual-therapy scleral plaque delivers localized hyperthermia (4.8-gigahertz microwave) and ionizing radiation (iodine I 125). Transscleral treatment involves placement of a TRT plaque on bare sclera at the base of an intraocular tumor. Therapeutic doses of ionizing and hyperthermic radiation are then simultaneously delivered to the intraocular tumor. Sparing of normal ocular structures outside the treatment area after the combined therapy has been noted on clinical, gross, and histologic examinations. Our study suggests that the TRT plaque described satisfies the requirements for dual-modality treatment of choroidal melanoma.
 ...
PMID:Thermoradiotherapy for intraocular tumors. 405 61

The effect of tumoricidal macrophages on the cell cycle progression of six different cell lines was studied using an anti-bromodeoxyuridine (BrdUrd) monoclonal antibody to follow the traverse of BrdUrd-labeled cells. Exponentially growing cultured mammalian cells, from six different cell lines, were prepulsed with BrdUrd before exposure to tumoricidal macrophages. The cultured cells were then analyzed as a function of time for DNA content (by propidium iodide staining) and for BrdUrd incorporation (using a fluoresceinisothiocyanate [FITC]-conjugated anti-BrdUrd monoclonal antibody). The position of the cells in cycle and the progression of the BrdUrd-labeled cohort was followed using flow cytometry. The cell lines examined were: Colon 26, BALB/c-3T3, ST3T3 (a spontaneously transformed, tumorigenic clone of 3T3), WCHE5 (a clone of whole Chinese hamster embryo cells), RIF (a radiation-induced fibrosarcoma), and A101D (a human melanoma). The bivariate distributions showed that for all six cell lines the BrdUrd-labeled cohort in the control cultures progressed around the cell cycle during the first 12 h of culture, as the cells exponentially increased. In contrast, when each cell line was incubated with tumoricidal macrophages, the BrdUrd-labeled cohort did not progress through cell cycle but remained in S phase throughout the 12-h culture period. There was also no evidence for progression of cells out of G1. The data show that cells were arrested in every phase of cell cycle. This study suggests that cytostasis, as manifested by the termination of progression in all phases of the cell cycle, is a universal phenomenon induced by tumoricidal macrophages.
 ...
PMID:Macrophage-induced cytostasis: kinetic analysis of bromodeoxyuridine-pulsed cells. 406 39

The damage to monoclonal anti-melanoma antibodies caused by iodination was investigated by comparing the results obtained using the chloramine-T method and the 1,3,4,6-tetrachloro-3 alpha, 6 alpha-diphenyl-glycoluril (IODOGEN) method at different levels of iodine substitution to the molecule. The level of substitution at which losses in immunoreactivity occurred was evaluated in each monoclonal antibody (MAb) studied. This phenomenon was not dependent on the method of substitution, provided that mild conditions of reaction were used. Lineweaver-Burk plots and--in cases of alterations in binding affinity--Scatchard plots were found to provide an adequate description of the binding behaviour of individual MAbs after labelling. Immunoreactivity was shown to be determined not only by the proportion of bona fide reactive MAb molecules, but also by a substitution-dependent decrease in affinity constants. The practical consequences of altered binding parameters were demonstrated by quantitating specific antibody accumulation in melanoma transplants in vivo.
 ...
PMID:Immunoreactivity of monoclonal anti-melanoma antibodies in relation to the amount of radioactive iodine substituted to the antibody molecule. 407 33


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