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)

This article reviews the recent English language literature on dematopathology, with an emphasis on publications appearing between January 1986 and July 1987. Immunohistochemistry continues to grow in importance as a diagnostic as well as a research technique. The advent of in situ deoxyribonucleic acid hybridization technology has raised diagnostic accuracy to a new level; it has already proved valuable in the diagnosis of certain viral infections. Areas that have received particular attention include phenotypic characteristics of lymphomas and lymphoma-like conditions, congenital melanocytic nevi and malignant melanoma, neuroendocrine carcinoma and other small cell tumors of the skin, sweat gland carcinomas, and eosinophil and its associated diseases, and unusual infectious diseases involving the skin.
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PMID:What's new in dermatopathology. 264 37

Tuftsin, a physiological tetrapeptide derived from the Fc region of leukophilic IgG possesses a variety of immunopotentiating properties including the ability to act as an immunotherapeutic agent against the experimental tumors, L1210 leukemia and Cloudman S-91 melanoma. Although the mechanism of action of tuftsin in vivo is not known, several types of leukocytes have been shown to become cytotoxic effector cells following activation with tuftsin. These cells presently include macrophages, natural killer cells, and granulocytes. The possibility that tuftsin can also activate other types of effector cells have not been ruled out. We feel this small peptide has a high potential (largely unrecognized) as an antitumor immunopotentiating agent. It is naturally occurring in man and appears to be relatively non-toxic. Its exact sequence (Thr-lys-Pro-Arg) is known and it can be chemically synthesized. Methods are also available to monitor the levels of tuftsin in body fluids. These properties along with its ability to control infectious disease make this agent one of the more promising immunopotentiators.
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PMID:Antitumor effect of tuftsin. 689 73

Advances in biotechnology have brought gene therapy to the forefront of medical research. The feasibility of gene transfer was first demonstrated in experiments using tumour viruses. This led to the development of a variety of viral and nonviral methods for the genetic modification of somatic cells. Two main approaches emerged: in-vivo modification, in which gene transfer vehicles are delivered directly into patients, and ex-vivo manipulation, in which cells from the patient are grown in culture, genetically modified and then returned to the patient. In 1990, shortly after the safety of retrovirus-mediated gene transfer was demonstrated in patients with malignant melanoma, the first clinical trial of gene therapy was initiated for adenosine deaminase deficiency. Since then, the number of clinical protocols initiated worldwide has increased exponentially. Although some clinical trials now in progress are concerned with relatively rare inborn errors of metabolism, most are concerned with more commonly encountered cancers and infectious diseases. Preliminary results suggest that by the turn of the century the dream of treating diseases by replacing or supplementing the products of defective genes or introducing novel therapeutic genes will become a reality.
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PMID:Gene therapy: here to stay. 774 47

Cells infected with varicella-zoster virus (VZV) express a viral ribonucleotide reductase which is distinct from that present in uninfected cells. VZV open reading frames 18 and 19 (ORF18 and ORF19) are homologous to the herpes simplex virus type 1 genes encoding the small and large subunits of ribonucleotide reductase, respectively. We generated recombinant VZV by transfecting cultured cells with four overlapping cosmid DNAs. To construct a virus lacking ribonucleotide reductase, we deleted 97% of VZV ORF19 from one of the cosmids. Transfection of this cosmid with the other parental cosmids yielded a VZV mutant with a 2.3-kbp deletion confirmed by Southern blot analysis. Virus-specific ribonucleotide reductase activity was not detected in cells infected with VZV lacking ORF19. Infection of melanoma cells with ORF19-deleted VZV resulted in plaques smaller than those produced by infection with the parental VZV. The mutant virus also exhibited a growth rate slightly slower than that of the parental virus. Chemical inhibition of the VZV ribonucleotide reductase has been shown to potentiate the anti-VZV activity of acyclovir. Similarly, the concentration of acyclovir required to inhibit plaque formation by 50% was threefold lower for the VZV ribonucleotide reductase deletion mutants than for parental virus. We conclude that the VZV ribonucleotide reductase large subunit is not essential for virus infection in vitro; however, deletion of the gene impairs the growth of VZV in cell culture and renders the virus more susceptible to inhibition by acyclovir.
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PMID:Deletion of the varicella-zoster virus large subunit of ribonucleotide reductase impairs growth of virus in vitro. 815 92

To detect shared human melanoma Ag that are recognized by HLA-A2 restricted, melanoma-specific CTL derived from tumor infiltrating lymphocytes, we have developed a convenient method to insert and express foreign HLA genes capable of presenting Ag on target cell lines. Seventeen melanoma cell lines and 11 nonmelanoma cell lines were infected with recombinant vaccinia virus containing the HLA-A2.1 gene. Infection by the vaccinia virus resulted in expression of functional HLA-A2 molecules on the cell surface of virtually 100% of infected cells within a 3.5-h period. The results showed that 11 of 17 (65%) naturally HLA-A2- melanoma cell lines were specifically lysed by the HLA-A2-restricted, melanoma-specific TIL after infection with the vaccinia-HLA-A2.1 virus. None of the nine human nonmelanoma cell lines tested (three colon cancer, four breast cancer, or two immortalized non-tumor cell lines) or two murine melanoma cell lines were lysed by the HLA-A2-restricted TIL after vaccinia-HLA-A2.1 infection. Coinfection of the vaccinia virus containing the beta 2-microglobulin gene with the vaccinia-HLA-A2.1 virus increased the surface expression of HLA-A2 and subsequent lysis by melanoma-specific tumor infiltrating lymphocytes. With this new method we could extend previous findings demonstrating that shared melanoma Ag recognized by HLA-A2-restricted tumor infiltrating lymphocytes exist among melanoma cells from different patients regardless of HLA type. These Ag represent excellent candidates for the development of vaccines to induce T cell responses for the immunotherapy of patients with melanoma.
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PMID:Detection of shared MHC-restricted human melanoma antigens after vaccinia virus-mediated transduction of genes coding for HLA. 833 37

Stratospheric ozone depletion threatens to increase exposure to ultraviolet (UV) radiation which is known to be a factor in a number of diseases. There is little doubt that cumulative exposure to UV radiation is important in the aetiology of non-melanoma skin cancers. Evidence is also strong for a link with cutaneous malignant melanoma, although here it appears to be intermittent intense exposure that is most damaging. More controversial is the view that exposure to solar radiation is a significant factor in ocular damage, particularly in the formation of cataracts. Earlier studies pointing to such an effect have been criticized and alternative aetiological hypotheses have been proposed. However, other studies do show an effect of UV exposure on cortical cataract. Concern is also growing that UV may be capable of activating viruses and have immunological effects that might exacerbate infectious disease. Very worrying is the possibility that UV exposure can activate the human immunodeficiency virus which might accelerate the onset AIDS. Any such health effects that have been observed in human populations are the result of exposure to existing, naturally occurring levels of UV radiation. There is, therefore, great concern about the possible exacerbation of these impacts as a result of increased exposure to UV radiation associated with stratospheric ozone depletion. However, any assessment of the nature and scale of such impacts on human health has to deal with several major problems and these are the focus of this paper. There are uncertainties about recent trends in stratospheric ozone and problems in the prediction of future changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Depletion of the ozone layer: consequences for non-infectious human diseases. 848 70

The human melanoma tumor Ags, MART1 and gp100, are specifically recognized by HLA-A2-restricted CD8+ CTLs derived from melanoma patients and appear to be involved in tumor regression. In order to develop immunizing vectors for the treatment of patients with metastatic melanoma, replication-defective recombinant adenoviruses, Ad2CMV-MART1 and Ad2CMV-gp100, which encode these tumor Ags, have been generated. Infection of non-Ag expressing HLA-A2+ cell lines A375 and MDA-231 with the vectors resulted in recognition by Ag-specific CTLs as demonstrated by specific target cell lysis and release of cytokines, including IFN-gamma, TNF-alpha, and granulocyte-macrophage-CSF. Sodium butyrate and TNF-alpha can further augment adenovirus-mediated transgene expression and increase recognition by specific CTLs. Although adenovirus-infected cells expressed the E3/19K protein at detectable levels, significant reduction of surface MHC class I expression was observed in only 3 of 10 tumor cell lines infected with either Ad2CMV-MART1 or Ad2CMV-gp100. Because of the suspected homology between the human MART1 and gp100 genes and their murine counterparts, we immunized C57BL/6 mice with these recombinant adenoviruses and demonstrated that immunization with Ad2CMV-gp100 could protect mice from murine melanoma B16 challenge administered intradermally. Depletion of CD8+ but not CD4+ T cells in vivo from Ad2CMV-gp100-vaccinated mice eliminated the protective effect. The anti-gp100 T cells induced by Ad2CMV-gp100 vaccinated appeared to be responsible for the protection. Thus, these recombinant adenoviruses encoding tumor Ags may be useful as vaccines to induce specific T cell immunity for cancer therapy.
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PMID:Antigen-specific tumor vaccines. Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy. 854 23

Infection of human erythrocytes with the malaria parasite, Plasmodium falciparum, results in the exposure of amino acid residues 542-555 of the anion-exchange protein, band 3, in a conformation that enables the cell to adhere to C32 amelanotic melanoma cells. Attempts to isolate this adhesive form from infected cells by immunoaffinity were unsuccessful, and so other approaches were utilized. Chinese hamster ovary (CHO) cells transfected with cDNA encoding the first 578 amino acid residues of human band 3 protein transiently expressed the protein efficiently. A murine monoclonal antibody (MAb) that specifically recognizes the adhesin exposed on the surface of erythrocytes bearing mature stages of P. falciparum immunostained some transfected cells, confirming that the first 578 amino residues are sufficient for the adhesive conformation. As a more efficient alternative to transgenic expression of the adhesin, microspheres with covalently bound peptides fashioned on band 3 sequences previously found to be adherent (residues 546-553 and 820-829 and called pfalhesin) were produced. The pfalhesin-coated microspheres specifically bound to C32 amelanotic melanoma cells, whereas microspheres coupled with a scrambled version of residues 546-553 had little binding capacity for melanoma cells. These results demonstrate that the previously identified band 3-related peptides that inhibit cytoadherence interact directly with target cells and suggest that microspheres with covalently coupled peptides might constitute novel 'artificial' P. falciparum-infected erythrocytes for use in in vitro and in vivo studies.
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PMID:Plasmodium falciparum: the adherence of erythrocytes infected with human malaria can be mimicked using pfalhesin-coated microspheres. 864 Mar 78

A cytokine produced by the subpopulation of activated helper lymphocytes T has been called interleukin-2 (IL-2). The obtaining of recombinant cytokine has facilitated the study of its biological properties and its application in the treatment of certain neoplastic and infectious diseases. IL-2 affects the target cells by means of a receptor of great affinity consisting of three independent chains: alpha, beta, gamma. The cytokine is the most important growth factor of lymphocytes T, conditioning their clonal expansion. Antigen stimulation is the condition for the expression of IL-2 does not, however, affect resting lymphocytes T. The expression of the receptor for this cytokine on NK cells is, however, continuous in character but only a very small percentage of these cells has receptors of great affinity. IL-2 plays a great role in adoptive immunotherapy consisting in intravenous administration of cells with cytotoxic properties. Cells obtained from peripheral blood and grown in vitro are called LAK cells (lymphocyte activated killer cells), while cells obtained from neoplasms and grown in similar conditions are named TIL cells (tumor infiltrated lymphocytes). LAK and TIL cells reveal a similar antineoplastic activity in vivo. At present, however, recombinant IL-2 alone is used more often, either intravenously or subcutaneously. The cytokine is effective in the treatment of patients with disseminate cancer of the kidney and melanoma, and in adjuvant therapy of acute myeloid leukemia. Attempts have been made to apply it in the treatment of AIDS and leprosy. The toxic effect of IL-2 depends on the dose and the mode of administration. In the majority of patients parainfluenza symptoms appear. Most undesirable effects are connected with multisystemic syndrome of capillary vessels hyperpermeability leading to the increased fluid retention into extravascular spaces, oedema, hypotonia and oliguria.
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PMID:[Biological properties and therapeutic use of interleukin 2 (IL-2)]. 865 37

Pathologic integration is the basic phenomenon of comparative pathology. Since man evolved as earth's most influential species, he was unequally influenced the progression and prevention of diseases in himself and other species. This has both positive and negative ramifications. Positive influences have been life-style, the prolongation of life under healthy conditions and medical progress as seen in the treatment of diabetes mellitus, dental hygiene and other factors, such as the decrease of infectious and parasitic diseases, which are still dominating factors in developing nations. Negative influences are side effects of medical treatments, the appearance of occupational, and certain recreational diseases. These are the pathologic effects of man's life-style to which car accidents, smoking and other factors can be added. Different species are affected by environmental changes such as pollution, ozone, acidic rain, polluted food, and transmission of different diseases from one species to another. Interspecies-specifically the direct influence of man in the extermination of other species, or the indirect influence such as through pollutants in the environment producing chain reactions in different species, can be distinguished. The physical environment has been changed as can be seen in air pollution in large cities, the damage to the ozone layer and the increase of malignant melanoma in certain regions of western Australia. The industrialized nations are dominated by non-infectious diseases such as atherosclerosis and neoplasms, whereas in the developing nations parasitic and infectious diseases stand in the fore-front. Particular diseases like acquired immunodeficiency syndrome increase in both types of nations. These diseases may have developed from other species, e.g. the plague which was originally a disease of rodents, especially rats where it was transmitted by the flea, Xenopsylla cheopis, Rothschild. The principle of foremost importance is the disruption of biologic integration of normal processes leading to different types of pathologic progression. A typical problem affecting man and many other fellow species is crowding. Man's pathology and the pathology of other species exhibit continued integration which is the central problem for understanding diseases where similar functions are performed by various structures, such as is the case in gaseous exchange, or differences in size and life span. The broad spectrum of comparative pathology which centers around human pathology provides a source of increased knowledge for a better understanding of diseases. The present issue is based on the two symposia organized by the International Society for the Study of Comparative Ongology during the Fifth International Conference of Anticancer Research, 17-22 October 1995, Corfu, Greece.
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PMID:Introduction: human pathology within the broad scope of comparative pathology. 874 90


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