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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated antigenic features associated with different tumor progression steps in primary melanoma, interpreted as different patterns of growth (radial and vertical) in the same and in different lesions. Thirty-eight primary melanomas were examined: 18 superficial spreading malanomas, 13 superficial spreading melanomas with a nodular area and 7 nodular melanomas. 225.28,763.74, CL.203, VF19LL209, VF19LL217, Q5.13, W6.32 and anti-HLA-DR monoclonal antibodies were used. Phenotypic differences between radial and vertical growth areas were observed but no statistical significance could be found.
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PMID:Superficial spreading melanoma with a nodular area: antigenic phenotype of the radial and vertical growth areas. 271 82

CGP 6809 [ethyl-6-deoxy-3,5-di-O-methyl-6-(3-methyl-3-nitrosoureido)-alpha-D- glucofuranoside] is a new methylnitrosoureido-sugar derivative that has been shown to be active against a broad spectrum of transplantable tumours in mice and rats. We investigated the anti-tumour effect of CGP 6809 in ten selected, human tumour xenograft lines growing s.c. in nude mice. The p.o. administration of 125 mg/kg per day for 10-15 days was less toxic (lethality 12% in tumour-bearing nude mice) than the i.p. injection of 62.5 mg/kg per day (lethality 22%). The anti-tumour effect was similar for both application routes; two large bowel cancers responded to treatment with CGP 6809, rectal cancer CXF 158 showed a remission, and the rapidly growing, undifferentiated colonic cancer CXF 280 exhibited a transient no-change. Furthermore, remissions were observed in the epidermoid lung cancer LXF 322 and in thyroid cancer 117. Tumour progression was found in another epidermoid lung cancer and in three stomach cancers, one melanoma, and one soft tissue sarcoma. CGP 6809 is a promising new agent for clinical trials, especially for large bowel and epidermoid lung cancer.
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PMID:CGP 6809--a new nitrosoureido-sugar derivative with activity in human tumor xenografts. 271 55

The gene for familial malignant melanoma and its precursor lesion, the dysplastic nevus, has been assigned to a region of the distal short arm of chromosome 1, which is frequently involved in karyotypic abnormalities in melanoma cells. We have examined loci on chromosome 1p for loss-of-constitutional heterozygosity in 35 melanomas and 21 melanoma cell lines to analyze the role of these abnormalities in melanocyte transformation. Loss-of-heterozygosity at loci on chromosome 1p was identified in 15/35 (43%) melanomas and 11/21 (52%) melanoma cell lines. Analysis of multiple metastases derived from the same patient and of melanoma and lymphoblastoid samples from a family with hereditary melanoma showed that the loss-of-heterozygosity at loci on distal 1p is a late event in tumor progression, rather than the second mutation that would occur if melanoma were due to a cellular recessive mechanism. Comparisons with neuroblastoma and multiple endocrine neoplasia (MEN2) suggest that the frequent 1p loss-of-heterozygosity in these malignancies is a common late event of neuroectodermal tumor progression.
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PMID:Loss of alleles from the distal short arm of chromosome 1 occurs late in melanoma tumor progression. 273 11

Age-matched female C57BL/6 mice given injections i.v. of the syngeneic, poorly metastatic melanomas B16-F1 or JB/RH mount a measurable anti-melanoma antibody (Ab) response. The experiments described here examine the possibility of whether these Ab responses are in fact targeted against metastatically distinct subpopulations of melanoma. Reactivity of antisera and monoclonal antibodies (MoAb) developed by syngeneic immunization were examined by radioimmunoassay, flow cytometry, and Western blot analyses. Anti-melanoma antisera collected at various times after i.v. injection of melanoma cells were tested in radioimmunoassay against C57BL/6 melanoma cell lines and clones of well-characterized experimental metastatic activity. A strong inverse correlation between metastatic activity and Ab binding was observed. Furthermore, i.v. injection of poorly metastatic melanoma lines always resulted in strong Ab response, while highly metastatic clones did not. The relative distribution of Ab-reactive cells in melanoma populations was examined by flow cytometry. Again, the proportion of reactive cells in all melanoma cell lines and clones tested was inversely proportional to the degree of experimental metastatic activity. Hybridoma technology used to capture this selective Ab response yielded monoclonal reagents with distinct anti-melanoma specificity. Monoclonal antibody directed against nonmetastatic melanoma variants defined specific Mr 45,000 and 50,000 bands in Western blot analyses. Finally, melanoma cells nonreactive with the syngeneic Ab response were isolated after immunomagnetic bead plus magnet removal of the positive population. The experimental metastatic potential of these negatively selected cells was then compared with cells similarly fractionated with normal mouse serum or control MoAb. The results of these studies showed a clear increase in metastatic potential of anti-B16-F1 melanoma antiserum or MoAb-depleted cells. These results support the contention that host Ab responses may favor tumor progression and metastasis through selective Ab responses against the poorly metastatic population.
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PMID:Poorly metastatic tumor cell variants as primary targets of syngeneic antibody responses against murine melanoma. 273 12

In order to distinguish those chromosomal aberrations associated with tumorigenesis from those associated with tumor progression of malignant melanoma, chromosome analysis was performed on eight tumors derived from one patient. Three common marker chromosomes, a deletion of chromosome 1, a deletion of chromosome 9, and a translocation involving chromosomes 7 and 12, were identified in each tumor. The presence of common markers in these intrapatient tumors indicates the monoclonal origin of these tumors. Furthermore, the consistent and specific involvement of chromosome 9 in both interpatient and intrapatient studies suggests the crucial role that chromosome 9 plays during the development of human malignant melanoma. In addition to common markers, different overlapping markers including those involving chromosomes 2, 3, and 6, were also identified, suggesting that chromosomes 2, 3, and 6 are most likely associated with the progression, instead of the genesis, of the tumor. Finally, lesion-specific marker chromosomes were identified in each tumor indicating the nonrandom selection and modification of the metastatic process. The nature of chromosomal evolution among the eight tumors was clearly demonstrated by the retention and amplification of specific marker chromosomes, with the latter tumors containing more overlapping markers than the early tumors and the recurrence of identical markers in the different branches of evolution. One of the last three tumors obtained immediately before the death of the patient contained all the overlapping markers identified in other tumors, which may indicate that a plateau of chromosomal evolution of these tumors has been reached. These observations demonstrate a nonrandom or programmed chromosome evolution of human neoplasia that could be intrinsic to the aneuploid nature of neoplasia.
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PMID:Chromosomal evolution in the progression and metastasis of human malignant melanoma. A multiple lesion study. 277 22

Over the years 1977-1987 142 patients with malignant melanoma of the uvea were admitted to the Department of Ophthalmology, Teaching Hospital, Comenius University in Bratislava. Of the 119 patients treated by enucleation of the bulb 74.8% were alive after a mean follow up period of 5.9 years, whereas 25.2% of these patients died of consequences of metastases of the melanoma of the eye. The highest death rate was recorded in the first and second year following enucleation (57%) and then in the fourth year (17%). After the eighth year following enucleation of the bulb not a single case of death from consequences of metastases of melanoma was recorded. Eight patients with localization of the tumor in the anterior part of the uveal tract (iris, ciliary body) were treated by microsurgical removal of the tumor from the bulb. Two patients developed relapse of the tumor and the eyeballs had to be enucleated. After a mean follow up period of 6.6 years all these patients are alive and so far no signs of metastases have been observed. Moreover, the visual acuity has remained good in the patients whose eyes were not enucleated. Electrocoagulation was applied in six patients. Within a year the eyes had to be enucleated in three of them due to tumor progression. In two patients the growth of the tumor seems to have been stopped, yet regression of the tumor has not been observed. Complete healing was recorded only in one patient. After a mean follow up period of 4.5 years all the patients are alive without signs of metastases. A series of eight patients refused any kind of treatment of melanoma. Over a follow up period of 8.5 years six of them (75%) died of consequences of metastases within an average of 3.2 years from the establishment of diagnosis. Although the majority of these cases had small and middle sized melanomas, at present only two patients (25%) are still alive. In 127 patients with histologically proved malignant melanoma of the uvea the LAI test for the determination of uveal tumor antigen was also performed. The test was positive in 78.7% of the patients and negative in 23.3%. In a control group of patients with nontumorous eye diseases the LAI test was positive only in 2.9% and negative in 91.1%. Four months after enucleation of the bulb the LAI test was repeated and positivity was found to persist in 57.8% of the patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Antitumor immunity in patients with melanoma of the uveal tract]. 279 May 4

Nevus cells were isolated from the three cutaneous components, epidermis, basal layer, and dermis, of nonmalignant pigmented lesions and were cultured separately in the presence or absence of the phorbol ester 12-0-tetradecanoyl phorbol-13-acetate in medium that supports the rapid proliferation of melanocytic cells. The separation procedure used provided cultures that were essentially free from normal melanocytes (dermis) or fibroblasts (epidermis). In short term culture, nevus cells of all skin compartments expressed markers associated with differentiated melanocytes, such as presence of premelanosomes and melanosomes and elevated tyrosinase levels. Nevus cells also expressed melanoma-associated antigens, such as NGF-receptor, transferrin-related p97, proteoglycan, and HLA-DR as detected with monoclonal antibodies. After several subpassages, cells showed a decreased expression of melanoma-associated antigens, decreased tyrrosinase levels, and melanosomes could no longer be detected. Morphologically, these cells were similar to fibroblasts. The disappearance of melanoma-associated cell surface antigens was concomitant with the appearance of a melanocyte-associated 145 kd protein that might serve as a marker of fibroblast-like differentiation in nevus cells and normal melanocytes. Nevus cell cultures grown in the presence of 12-0-tetradecanoyl phorbol-13-acetate maintained a stable differentiated phenotype throughout their lifespan. As reported earlier, nevus cells in culture, irrespective of the presence or absence of 12-0-tetradecanoyl phorbol-13-acetate, have a finite lifespan in vitro, grow anchorage-independent in soft agar, but do not form tumors when xenografted to nude mice. These studies demonstrate that nevus cells isolated from the epidermal, basal layer, and dermal components of lesional skin can serve as models to characterize the initial steps of tumor progression in a human cell system.
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PMID:Growth and phenotypic characteristics of human nevus cells in culture. 282 80

Monoclonal antibodies (MAbs) to the human epidermal growth factor (EGF) receptor, the type I insulin-like growth factor (IGF) receptor, and the nerve growth factor (NGF) receptor were used to study the growth regulation of malignant cells. Anti-EGF receptor MAb 425 inhibited the growth of A 431 squamous carcinoma cells which express high numbers of EGF receptors on their surfaces. Growth inhibition induced by MAb 425 was accompanied by alterations of the cell-cycle distribution of these cells, indicating the ability of a monoclonal antibody to act as a biologically active ligand. Growth stimulation of melanoma cells by EGF was unrelated to EGF receptor expression on the cell surface. Insulin- and IGF-I-induced growth stimulation of melanoma cells was inhibited by MAb alpha IR-3 which reacts with the type I IGF receptor. This result indicates that the type I IGF receptor mediated growth stimulation not only by IGF-I but also by insulin. Normal melanocytes and cells of all stages of tumor progression expressed in tissue culture the receptor for NGF, but no effect on the growth of these cells has been observed.
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PMID:Interactions between growth factor receptors and corresponding monoclonal antibodies in human tumors. 283 Dec 41

Restriction fragment length polymorphisms at 61 autosomal and 7 X-linked loci were screened for heterozygosity in cell lines derived from 6 independent metastases and autologous B-cells from a patient with melanoma. Segregations resulting in the loss of heterozygosity were detected in the tumor cells at 8 of 16 autosomes with at least 1 informative locus and at the 3 informative X-linked loci. With a single exception, karyotypic abnormalities were not detected in the region of loci where loss of heterozygosity had been detected. Three patterns of loss were identified: unique segregations in cells from a single metastasis; segregation of the same alleles in different subsets of metastases; and identical segregations in all 6 metastases. The monoclonal derivation of the 6 metastases is supported by the inactivation of the same X-chromosome and the presence of identical segregation at loci on chromosomes 9 and X. Analysis of the patterns of segregation in the metastatic tumor cells permitted the development of a genealogy of tumor progression in this patient and the development of a model of tumor progression which describes the accumulation of selectively neutral and advantageous segregations in metastatic tumor cells.
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PMID:Loss of heterozygosity at autosomal and X-linked loci during tumor progression in a patient with melanoma. 288 13

Based on the clinicopathological delineation of distinct steps of tumor progression in the melanocytic system, the in vitro behavior of melanocytes with increasing malignant potential has been investigated. Tumor progression in melanocytes is characterized by an increasing growth autonomy and decreased requirement but enhanced utilization of exogenously provided polypetide growth factors (EGF, IGF-I). The endogenous production of growth factors such as alpha-TGF, PDGF, and bFGF by metastatic melanoma cells might contribute to their independence from exogenously provided factors. Although expression of some melanoma-associated antigens in vivo is detectable only on malignant cells, propagation of normal melanocytes in tissue culture leads to expression of the majority of these antigens. Many of these antigens can be grouped into functionally defined categories, including growth factor receptors, extracellular matrix proteins, and cell-substrate interacting antigens. One cell-substrate interacting antigen, the GD2/GD3 ganglioside, appears to play a critical role in the metastatic process of melanoma cells. The successful propagation and characterization of melanocytic cells of all stages of tumor progression in tissue culture provide a unique human experimental model for the study of mechanisms of malignant transformation.
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PMID:Characteristics of cultured human melanocytes from different stages of tumor progression. 290 75


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