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)

Arsenic compounds have been used to treat angiogenic diseases such as cancer, psoriasis, and rheumatoid arthritis in traditional oriental medicine. In recent years, arsenic trioxide (As2O3, diarsenic oxide) has been successfully used to treat acute promyelocytic leukemia. We investigated the antiangiogenic properties of tetraarsenic oxide (As4O6), another trivalent arsenic compound. In in vitro studies, tetraarsenic oxide inhibited the proliferation (IC50 = 99.7 nM), migration into the denuded area (IC50 = 27.4 nM), and invasion through a layer of Matrigel (IC50 = 73.5 nM) of basic fibroblast growth factor (bFGF)-stimulated bovine capillary endothelial (BCE) cells in a dose-dependent manner. Tetraarsenic oxide also inhibited the tube formation of human umbilical vein endothelial cells. Tetraarsenic oxide induced cell cycle arrest of bFGF-stimulated BCE cells in the G2/M phase and inhibited the secretion of matrix metalloproteinase-2 from BCE cells. Orally administered tetraarsenic oxide (50 mg/kg/day) inhibited bFGF-induced new-vessel formation in a rat corneal micropocket assay, and reduced by about 54% the number of experimental pulmonary metastatic nodules in mice implanted with B16F10 melanoma cells. Thus, we provide evidence that tetraarsenic oxide has effective antiangiogenic activities.
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PMID:Tetraarsenic oxide, a novel orally administrable angiogenesis inhibitor. 1273 93

Titan (formerly Trilex) is developing TriGem, a monoclonal antibody directed against I17, for the potential treatment of advanced cancers that express the GD2 ganglioside, including melanoma, small-cell lung cancer, neuroblastoma and sarcoma. Phase II trials of TriGem for use in advanced melanoma were ongoing by June 2002. TriGem also has potential for the treatment of psoriasis, for which phase II trials had begun by 1996.
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PMID:Technology evaluation: TriGem, Titan. 1277 13

Interleukin (IL)-10 is an important immunoregulatory cytokine produced by many cell populations. Its main biological function seems to be the limitation and termination of inflammatory responses and the regulation of differentiation and proliferation of several immune cells such as T cells, B cells, natural killer cells, antigen-presenting cells, mast cells, and granulocytes. However, very recent data suggest IL-10 also mediates immunostimulatory properties that help to eliminate infectious and noninfectious particles with limited inflammation. Numerous investigations, including expression analyses in patients, in vitro and animal experiments suggest a major impact of IL-10 in inflammatory, malignant, and autoimmune diseases. So IL-10 overexpression was found in certain tumors as melanoma and several lymphomas and is considered to promote further tumor development. Systemic IL-10 release is a powerful tool of the central nervous system to prevent hyperinflammatory processes by activation of the neuro-endocrine axis following acute stress reactions. In contrast, a relative IL-10 deficiency has been observed and is regarded to be of pathophysiological relevance in certain inflammatory disorders characterized by a type 1 cytokine pattern such as psoriasis. Recombinant human IL-10 has been produced and is currently being tested in clinical trials. This includes rheumatoid arthritis, inflammatory bowel disease, psoriasis, organ transplantation, and chronic hepatitis C. The results are heterogeneous. They give new insight into the immunobiology of IL-10 and suggest that the IL-10/IL-10 receptor system may become a new therapeutic target.
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PMID:Interleukin-10 therapy--review of a new approach. 1277 29

Psoriasis is a chronic inflammatory disease characterized by epidermal hyperplasia and an inflammatory infiltrate. The normal differentiation from basal to granular keratinocytes with subsequent apoptosis and cornification is disturbed in the akanthotic epidermis. This could be due to both an excess of mitogenic stimuli with hyperproliferation and/or resistance to apoptosis. By mRNA differential display we found HAX-1 to be overexpressed in lesional psoriatic skin. The overexpression of HAX-1 was verified at the mRNA level by Northern blot and in situ hybridization, as well as at the protein level by Western blot and immunohistochemistry. Detection of HAX-1 in mRNA from different tissues showed strong expression in the brain, pancreas, skeletal muscle, and heart. In contrast to primary keratinocytes and melanocytes we found HAX-1 highly expressed in human immortalized keratinocytes (HaCaT) and different melanoma cell lines. In HaCaT cells as a model for psoriatic keratinocytes we found an increased ultraviolet-induced apoptosis after expression of HAX-1 antisense mRNA. In psoriasis, the epidermal differentiation could be disturbed due to the increased expression of HAX-1 and hence a prolonged resistance to terminal differentiation. Antiapoptotic mechanisms are an emerging concept for the understanding of the pathogenesis of this disease possibly leading to clinical applications.
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PMID:HAX-1, identified by differential display reverse transcription polymerase chain reaction, is overexpressed in lesional psoriasis. 1278 33

Consumption of tobacco is hazardous to the health. It leads to cardiovascular diseases, and increases the incidence of numerous neoplasms. The adverse effects on the skin are less well-known and often ignored. Changes in the rheologic characteristics of the blood, increased vasoconstriction and damage to the epithelial layer of the vessel play an important pathogenic role in impaired wound healing, thromboangiitis obliterans and peripheral arterial obstructive diseases. Interactions with collagen metabolism are of special significance in wound healing and skin aging. The immunological effects, such as the induction of an inflammation reaction play a role in palmoplantar pustulosis, psoriasis, atopic dermatitis, acne vulgaris, acne inversa, thromboangiitis obliterans and lupus erythematodes. In addition, immunosuppression caused by nicotine consumption may contribute to the pathogenesis of human papilloma-virus infections, malignant melanoma and epithelial tumors of the skin and neighboring mucous membranes.
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PMID:[Addiction to tobacco and the consequences for the skin]. 1502 39

Chondroitin sulfate (CS) belongs to the group of glycosaminoglycans (GAGs), which are linear polysaccharides, located in the extracellular matrix and on the cell surface. To study the structure and distribution of CS in human skin and skin disorders, we have selected antibodies using phage display technique against CS. Four unique human anti-CS single-chain antibodies were selected: IO3D9, IO3H10, IO3H12, and IO4C2. We determined their amino acid sequence and evaluated their CS reactivity using ELISA and immunohistochemistry. Antibodies were reactive with CS, but not with other GAGs except for IO4C2, which was also reactive with heparin. Antibody IO3D9 showed a strong reactivity with highly sulfated CS (CSE). All antibodies displayed a different staining pattern in rat kidney, indicating the recognition of unique CS epitopes. In normal skin, the papillary dermis but not the reticular dermis was strongly stained. Antibody IO3H12 also stained basal keratinocytes. We applied these antibodies to study CS expression and localization in melanoma and psoriasis. A strong immunoreactivity with the extracellular matrix of melanoma metastases could be observed for all four antibodies, while in atypical nevi a less extensive reactivity with only the papillary dermis was observed. In psoriatic lesions, CS could be observed in the papillary dermis and in the reticular dermis, whereas the specific location in the papillary dermis found in normal skin was completely lost. In conclusion, human phage-display-derived anti-CS antibodies have been selected, characterized, and applied to detect CS alterations in skin conditions. Altered CS composition was detected in melanoma and psoriasis.
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PMID:Human single-chain antibodies reactive with native chondroitin sulfate detect chondroitin sulfate alterations in melanoma and psoriasis. 1508 57

Overexpression of the epidermal growth factor (EGF) pathway has been implicated in melanoma pathogenesis, and a recent case-control study identified a single nucleotide polymorphism (G to A) in the EGF gene where the G allele was associated with increased EGF expression and an increased risk of melanoma. To further evaluate this association, we conducted a case-control analysis from the Genes, Environment, and Melanoma study at the University of Michigan site using two different study designs. Incident cases of histopathologically confirmed first primary melanoma that were diagnosed between January 1, 2000 and December 31, 2000 from the University of Michigan Melanoma Clinic (n = 330) were compared with the following two different sources of nonmelanoma controls: spouse/friend controls (n = 84) and healthy volunteer controls from a case-control study of psoriasis (n = 148). Using a second analytic design, comparisons between multiple primary melanoma cases (n = 62) and single primary melanoma cases (n = 330) were also evaluated to estimate odds ratios (ORs). Genotyping for the single nucleotide substitution (G to A) at position 61 in the 5' untranslated region of the EGF gene was performed from genomic DNA, and epidemiological risk factors were assessed through a telephone interview. When EGF genotypes were compared between incident primary melanoma cases and the nonmelanoma controls, the risk associated with the homozygous G/G genotype was not statistically significantly associated with an increased risk for incident primary melanoma compared with the homozygous A/A genotype [OR, 1.09; 95% confidence interval (CI); 0.65-1.85]. No strong associations with EGF G/G genotype were observed in comparisons of multiple primary and single primary melanoma cases (OR, 0.66; 95% CI; 0.25-1.73). Case subjects with tumors >/=3.5 mm compared with those <3.5 mm were not significantly associated with the G/G genotype (OR, 0.54; 95% CI; 0.12-2.35). Our data do not support a significant association between melanoma and the EGF 61*G allele or the homozygous G/G genotype. The EGF polymorphism is not a reproducible risk factor for melanoma or thick melanoma in our data. The two analytic approaches used in the study provide evidence against a strong association between EGF 61*G and melanoma and demonstrate the potential utility of case-case designs for evaluating the role of single nucleotide polymorphisms and cancer. Additional independent studies will be required to elucidate relationships between genetic variation in the EGF gene and risk of melanoma.
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PMID:EGF gene polymorphism and the risk of incident primary melanoma. 1508 76

Psoriasis is a chronic condition that shows variability in phenotype and severity. The disease can seriously compromise patients' quality of life, regardless of disease extent. Systemic treatment is indicated when lesional burden is extensive and/or frequently relapsing, and when quality of life is severely altered. Furthermore, surveys have indicated that patients are dissatisfied with their current topical or phototherapy. The efficacy of ciclosporin in the treatment of psoriasis is well established. However, widespread use of this drug has been limited by concerns over adverse effects, such as renal impairment, hypertension and the potential risk of malignancy. Data from many clinical trials designed to examine the efficacy and safety of long-term continuous and intermittent short-course (< 12 weeks) therapy are now available. Information from these studies has aided dermatologists in developing treatment guidelines. Intermittent short-course therapy is well tolerated, safe, and highly effective in sustaining disease control and promoting quality of life. Long-term continuous ciclosporin therapy may be useful in some patients with refractory psoriasis. If treatment guidelines are followed, the risk of nephrotoxicity and hypertension is low. Ciclosporin therapy is associated with an increased risk of non-melanoma skin cancer (mainly squamous cell carcinoma) when patients have been previously exposed to psoralen-ultraviolet A (PUVA). The incidence of non-skin malignancy shows no significant difference to that observed in the general population.
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PMID:The use of ciclosporin in psoriasis: a clinical review. 1511 40

Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in last few decades has certified several such claims of use of several plants of traditional medicine. Popularity of Momordica charantia (MC) in various systems of traditional medicine for several ailments (antidiabetic, abortifacient, anthelmintic, contraceptive, dysmenorrhea, eczema, emmenagogue, antimalarial, galactagogue, gout, jaundice, abdominal pain, kidney (stone), laxative, leprosy, leucorrhea, piles, pneumonia, psoriasis, purgative, rheumatism, fever and scabies) focused the investigator's attention on this plant. Over 100 studies using modern techniques have authenticated its use in diabetes and its complications (nephropathy, cataract, insulin resistance), as antibacterial as well as antiviral agent (including HIV infection), as anthelmintic and abortifacient. Traditionally it has also been used in treating peptic ulcers, interestingly in a recent experimental studies have exhibited its potential against Helicobacter pylori. Most importantly, the studies have shown its efficacy in various cancers (lymphoid leukemia, lymphoma, choriocarcinoma, melanoma, breast cancer, skin tumor, prostatic cancer, squamous carcinoma of tongue and larynx, human bladder carcinomas and Hodgkin's disease). There are few reports available on clinical use of MC in diabetes and cancer patients that have shown promising results.
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PMID:Pharmacological actions and potential uses of Momordica charantia: a review. 1518 17

Phototherapy of skin diseases such as psoriasis is an effective and safe treatment modality. However, increasing the risk of skin cancer by phototherapy is a serious concern. An increased skin cancer risk occurs after prolonged photochemotherapy (PUVA). In contrast, the role of broadband UVB or narrowband UVB therapy in skin carcinogenesis of humans with psoriasis is less clear. Therefore, we investigated the incidence of skin tumours in a total of 195 psoriasis patients, receiving broadband (n=69) or narrowband (n=126) UVB from 1994 to 2000 with follow-up until 2003. Data were raised from the regional interdisciplinary cancer centre of the University of Tuebingen, Germany and compared with the tumour incidences given for the German population. In this study, with 80% statistical power to detect a 6-7-fold increase in skin cancer with broadband UVB and 83% power to detect a 5-6-fold increase with narrow band UVB at p=0.05, only one patient developed skin cancer - an in situ melanoma. The tumour occurred within the same year that phototherapy was initiated. Thus, the present study does not provide evidence for an increased skin cancer risk for patients treated with either broadband or narrowband UVB phototherapy
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PMID:No evidence for increased skin cancer risk in psoriasis patients treated with broadband or narrowband UVB phototherapy: a first retrospective study. 1537 Jul 3


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