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)

From the peripheral blood of the melanoma patient (AV), we derived cytolytic T lymphocyte (CTL) clones that lysed the autologous tumor line SK-MEL-29, but not autologous EBV-B cells, K562, and other tumor targets. By immunoselection experiments it was shown that the CTL clones recognized at least three different antigens on the autologous tumor cells. We demonstrate here that these melanoma antigens are presented to the CTL in association with HLA-A2. First, HLA-A2-reactive pregnancy sera as well as an mAb against HLA-A2 inhibited the CTL lysis. Second, immunoselected melanoma subclones that were resistant to lysis by CTL clones against the three antigens described were found to lack expression of HLA-A2. By sensitizing the patient's lymphocytes against an HLA-A2- melanoma clone, we established a new series of CTL clones recognizing autologous AV melanoma cells. However, efficient lysis was only seen when target cells were pretreated with IFN-gamma. The lytic activity of these CTL was selectively inhibited by an mAb against a common HLA-B determinant. These results indicate that in addition to HLA-A2, other class I antigens are involved in the recognition of AV melanoma cells by autologous CTL.
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PMID:Lysis of human melanoma cells by autologous cytolytic T cell clones. Identification of human histocompatibility leukocyte antigen A2 as a restriction element for three different antigens. 278 8

A family of cell surface glycoproteins with a molecular weight of 96,000 (gp96) has recently been implicated in the individually distinct immunogenicity of chemically induced sarcomas of inbred mice. Rabbit antiserum to murine gp96 detects an antigenically related Mr 96,000 cell surface glycoprotein on two cultured human melanoma cell lines, SK-MEL-13 and SK-MEL-177. Molecular probes for 5' and 3' ends of the murine gp96 gene detect a 3.5-kilobase transcript in RNA preparations from melanoma cells, similar to the murine gp96 transcript. While 5' probes do not hybridize to Southern blots of genomic human DNA, the 3' probes identify several distinct bands under stringent hybridization and washing conditions. This suggests that the 3' end of the gp96 gene is more conserved than its 5' end. No gross alterations in gp96 gene organization were detected in melanoma cells. B-lymphoblastoid cell lines derived from four different individuals also showed no restriction fragment polymorphism in the gp96 gene.
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PMID:Identification of a human homologue of the murine tumor rejection antigen GP96. 292 90

In vitro experiments were performed to evaluate the direct cytotoxic and photosensitizing effects of dihematoporphyrin-ether (DHE) on the head and neck squamous cancer cell line, UM-SCC-38. Normal fibroblasts, normal cultured keratinocytes, and the UM-MEL-1 pigmented malignant melanoma cell line were used as controls. The parameters of duration of light exposure, drug concentration, and incubation periods were studied. Uptake of DHE by squamous cancer cells, as assessed microscopically by intensity of fluorescence, was rapid and reached a dose-dependent maximum intensity within 10 minutes. Cells were irradiated with polychromatic light with an energy of one milliwatt/cm2 at a distance of 1.5 ft. Cells growing in plastic dishes were incubated in the dark for 1 to 4 hours with DHE in concentrations that ranged from 1.25 to 50 micrograms/ml. The cell monolayers were washed and irradiated for periods of time ranging from 15 to 120 min. Dose-dependent loss of cell viability could be detected by trypan blue dye uptake as early as 1 hour after radiation and continued to increase until 4 hours after light exposure. No further loss of cell viability was observed over the next 10 hours. There was no phototoxicity in the absence of DHE. UM-SCC-38 cells were more sensitive to the photosensitizing effects of DHE than were either normal fibroblasts or malignant melanoma cells. Recovery from the photosensitizing effects of DHE was observed if the DHE-containing medium was removed and the cells were incubated in the dark for periods that ranged from 1 to 14 hours before light exposure. UM-SCC-38 cells recovered more rapidly than normal fibroblasts, normal keratinocytes, or UM-MEL-1 cells.
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PMID:In vitro photosensitization of human head and neck squamous cancer cells by dihematoporphyrin-ether. 297 11

Melanoma patients were vaccinated with cell-free lysates prepared from vesicular stomatitis virus (VSV)-infected cultured autologous and allogeneic melanoma cells. Eleven patients received vaccines produced from the melanoma cell line SK-MEL-13. This cell line, derived from the melanoma of Patient AH, expresses a differentiation antigen (initially defined by autologous antibody) that is restricted to melanomas and other cells of neural crest origin (an example of a Class 2 melanoma antigen). Thirteen patients received vaccines prepared from autologous melanoma cells, the only known source of autologous unique (Class 1) melanoma antigens. VSV lysates were used for vaccination because VSV infection of tumor cells has been shown to augment the immunogenicity of tumor antigens. All patients but one vaccinated with VSV lysates of autologous melanoma cells developed antibodies against VSV, and all patients vaccinated with VSV lysates of SK-MEL-13 developed antibodies against HLA-related antigens. Antibodies against a Class 1 (unique) melanoma antigen were detected in only one case, and antibodies against Class 2 (shared) melanoma antigens were not found in any of the patients. The authors conclude that VSV lysates of melanoma cells are not effective in increasing the serologic response of melanoma patients to Class 1 or 2 melanoma antigens.
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PMID:Serological response of melanoma patients to vaccines prepared from VSV lysates of autologous and allogeneic cultured melanoma cells. 298 1

Human HT-29 colon carcinoma and HeLa D98/AH2 and SK-MEL-109 melanoma cells were sensitive to synergistic growth inhibition by concentrations of recombinant human tumor necrosis factor (rTNF) and interferon-gamma (rIFN-gamma) which individually were only slightly inhibitory. We investigated whether this synergism could be explained by the presence of an increased number of TNF receptors in cells treated with rIFN-gamma. These receptors were measured by incubating cells resuspended from monolayers with 125I-rTNF. HT-29 cells treated for a few hours with rIFN-gamma could bind more 125I-rTNF than control untreated cells, but this binding returned to the level of control cells after 24 hr. The treatment with rIFN-gamma did not change the binding affinity of TNF receptors, but increased their number to 1800 per cell from a basal level of about 800 per cell. Inhibitors of RNA synthesis prevented this increase. HT-29 cells were significantly more growth-inhibited when treated first for 6 to 12 hr with rIFN-gamma and then with rTNF, than when treated first with rTNF and then with rIFN-gamma. Untreated HeLa D98/AH2 and SK-MEL-109 cells had 2400 and 9000 receptors per cell, with a KD similar to that of HT-29 cells (approximately 2 X 10(-10)M). A significant increase in TNF receptors after treatment with rIFN-gamma was observed in HeLa D98/AH2, but not in SK-MEL-109 cells. No increase in TNF receptors was detected in cells treated with rIFN-alpha 2. These results indicate that the synergism between rTNF and rIFN-gamma may be due, at least in part, to a transient induction of the synthesis of TNF receptors by rIFN-gamma in cells with a relatively low number of these receptors.
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PMID:Induction of the synthesis of tumor necrosis factor receptors by interferon-gamma. 300 11

Purified human natural tumor necrosis factor (n-TNF) was prepared by stimulating human leukemic B cell line (BALL-1) with Sendai virus. The colony formations of all of 18 human cancer-derived abnormal cell lines were suppressed by 10(1)-10(6) U/ml of n-TNF, while n-TNF was nontoxic to all human normal fibroblast cells. This in vitro inhibition of cell growth was reversible. In breast adenocarcinoma MCF7 cells treated with n-TNF a specific decrease of DNA synthesis was observed, and DNA histograms showed a block at G1 in the cell cycle. In vivo studies revealed that n-TNF suppressed the tumor growth of murine Meth A sarcoma, human renal adenocarcinoma (ACHN), malignant melanoma (SK-MEL-28) and glioblastoma (U-373 MG). Isobologram analysis showed that n-TNF synergistically inhibited cell growth in combination with human natural interferon (IFN)-a. In vivo synergism of n-TNF and IFN-a was also found in the U-373 MG tumor model implanted into nude mice.
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PMID:The inhibition of neoplastic cell proliferation with human natural tumor necrosis factor. 303 Sep 86

The cytostatic and cytotoxic activity of human recombinant tumor necrosis factor (rTNF) was assayed on different tumor cell lines. Human BT-20 breast and ME-180 cervix cancer cells were growth-inhibited by rTNF, whereas two other cell lines were not significantly inhibited. However, when protein synthesis was inhibited by cycloheximide, rTNF was cytotoxic for these cells but not for BT-20 cells. This finding suggested that different mechanisms are responsible for the cytostatic and cytotoxic activity of rTNF. The sensitivity of different cell lines to rTNF could not be correlated with a high number or affinity of rTNF receptors. Occupancy of only a few receptors was sufficient for rTNA cytotoxicity, but an increase in receptor number after treatment with interferon-gamma, or a decrease after pretreatment with cycloheximide, correspondingly enhanced or depressed the cytotoxicity of rTNF. It seemed possible that some cells could be protected from this effect of rTNF by synthesizing "protective" proteins. While searching for such proteins, we observed that rTNF induced the synthesis of two polypeptides in SK-MEL-109 melanoma cells, but not in other cancer cells. Actinomycin D added with rTNF abolished synthesis of these polypeptides, suggesting that rTNF induced transcription of the corresponding mRNAs. Surprisingly, rTNF stimulated growth of SK-MEL-109 cells cultured in medium with low serum.
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PMID:Cytostatic and cytotoxic activity of tumor necrosis factor on human cancer cells. 303 Nov 63

The synergism of anticellular and antiviral activities of recombinant human interferon-gamma (ReIFN-gamma) and recombinant human interferon-beta (ReIFN-beta) was examined in vitro using human melanoma SK-MEL-28 cells. Some differences were detected in the kinetics of anticellular activity between both IFNs, namely the inhibitory effect of ReIFN-beta occurred earlier than that of ReIFN-gamma. Significant synergism was detected in the anticellular activity of both IFNs when growth curves and isobolograms were examined. A difference between ReIFN-gamma and ReIFN-beta was also detected in antiviral activity. The antiviral activity of ReIFN-gamma against vesicular stomatitis virus (VSV) was significantly weaker than that of ReIFN-beta, even though both IFNs exhibited almost equivalent antiviral activities against Sindbis virus. However, ReIFN-gamma and ReIFN-beta exhibited synergistic antiviral activities against both VSV and Sindbis virus. The analysis of cell cycle distribution by flow cytometry revealed that there were some differences in the distribution pattern between cells treated with ReIFN-gamma alone, ReIFN-beta alone, or ReIFN-gamma and ReIFN-beta in combination. ReIFN-beta induced a prolongation or accumulation of S phase, whereas the effect of ReIFN-gamma was cycle-nonspecific. The combination of ReIFN-gamma and ReIFN-beta induced a decrease of G1 phase and an increase of G2M phase. These results suggest that ReIFN-gamma and ReIFN-beta used in combination were more effective in inhibiting the growth of human tumor cells and the proliferation of viruses than IFN used individually.
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PMID:Synergistic anticellular and antiviral activities of human recombinant interferon-gamma and -beta. 303 Dec 63

The authors examined the adhesion of seven human melanoma cell lines to cultured human umbilical vein endothelial cells (HEC) that were activated by cytokines or bacterial endotoxin. The adhesion of Hs 294T and MEL-24 cells was markedly increased (approximately 2 to 12-fold) after pretreatment of HEC monolayers for 6 hours with tumor necrosis factor, interleukin-1, or endotoxin. Smaller increases were noted with the cell lines RPMI 7951, HT 144, Malme-3M, MEL-2, and no significant increase was observed with MEL-5. Cytokine and endotoxin effects on melanoma-HEC adhesion were concentration- and time-dependent, with onset by 2 hours, peak at 6-8 hours and maintenance through 48 hours. Cytokine induction of increased HEC adhesiveness for melanoma cells was blocked by actinomycin-D or cycloheximide, suggesting the requirement for RNA and protein synthesis. Interaction of melanoma cells with subendothelial matrix did not appear to play a primary role because: 1) phase contrast and electron microscopy revealed direct contact between tumor cells and endothelial cells in standardized monolayer adhesion assays; 2) increased adhesion (rosette formation) of tumor cells to activated HEC was also observed after nonenzymatic resuspension of HEC, and 3) the matrix peptide GRGDSP partially blocked (approximately 45%) Hs 294T cell adhesion to subendothelial matrix, but had little or no effect on adhesion to activated HEC monolayers. Taken together, these data suggest that inducible HEC surface changes may mediate the adhesion of certain melanoma cells, thereby exerting an active influence over the metastatic process.
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PMID:Tumor cell-endothelial interactions. Increased adhesion of human melanoma cells to activated vascular endothelium. 305 20

Three human melanoma cell lines (G-361, HT-144, and SK-MEL-3) that were highly sensitive to growth inhibition in vitro by recombinant human interferon (rHuIFN-gamma) were adapted to grow as s.c. xenografts in athymic nude mice. Take rates were greater than 90% for all three tumors, with in vivo doubling times of 15, 4, and 15 days for G-361, HT-144, and SK-MEL-3, respectively. Commencing 3 days posttumor implantation mice were treated with daily s.c. injections of rHuIFN-gamma for 30 days over a dose range of 2.4-326 megaunits/mouse/day at a site distinct from the tumor implant. Tumors were measured twice weekly and mice were observed daily for deaths and morbidity until day 60 postimplantation. No apparent antitumor activity was observed in either the G-361 or HT-144 tumors at any dose despite the achievement of high rHuIFN-gamma blood levels. Intralesional treatment of the HT-144 xenograft with rHuIFN-gamma at 240 megaunits/mouse/day did not significantly retard tumor growth or increase lifespan. However, the SK-MEL-3 tumor showed a significant response at the 326-megaunit dose as noted by a tumor growth delay of 11.8 days in treated versus control animals and by an increased number of 60-day survivors. The tumor growth suppression appeared to be greater during the treatment period than during the subsequent observation period. Other experiments employing 326, 530, and 860 megaunits rHuIFN-gamma/mouse/day in mice bearing the SK-MEL-3 tumor demonstrated tumor growth delays of 4.2, 4.8, and 19.8 days, respectively, suggesting a dose response. These data support the conclusions that (a) in vitro antiproliferative activity of rHuIFN-gamma is not necessarily predictive of in vivo efficacy; and (b) relatively high doses of rHuIFN-gamma appear to be required for demonstrating an in vivo antitumor effect in this model.
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PMID:Evaluation of the antitumor activity of recombinant human gamma-interferon employing human melanoma xenografts in athymic nude mice. 311 65


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