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)

The results of complement fixation tests on 202 sera from people without cancer and from patients with cancer in 29 different areas of the body indicated that only those with nine varieties of advanced cancer (lip, mouth, oropharynx, nasopharynx, kidney, urinary bladder, prostate, cervix uteri, and vulva-all of 56 tested) gave positive specific reactions with nonvirion antigens induced by the DNA herpes simplex (HSV 1) and herpes genitalis (HSV 2) viruses. None of 57 people without cancer (including 10 with current and 18 with recurrent HSV 1 or HSV 2 infections), none of 81 patients with 20 other varieties of advanced cancer (gum, tongue, tonsil, salivary gland, accessory sinus, epiglottis, lung-bronchus, stomach, colon, breast, corpus uteri, ovary, testis, liver, thyroid, Wilms' embryonal kidney, melanoma, Hodgkin's disease, acute lymphocytic leukemia, and acute myelocytic leukemia), and none of four women with early malignant changes in the cervix uteri gave positive results. The seven patients with advanced cancer of the lip or oropharynx gave positive reactions with HSV 1 but not with HSV 2 nonvirion antigens (compatible with involvement of only HSV 1), all of the 13 women with advanced cancer of the cervix uteri and the one woman with advanced cancer of the vulva gave positive reactions with both HSV 1 and HSV 2 nonvirion antigens (compatible with involvement of only HSV 2), while among the 35 other positive patients only two (one with cancer of the kidney and one with cancer of the bladder) reacted with HSV 1 and not at all with HSV 2 nonvirion antigens. Positive sera failed to react with cells harvested at different times after high-multiplicity infection with the DNA vaccinia virus. Massive absorption of positive sera with trypsinized, uninfected human embryonic kidney cells failed to remove, or lower the titer of, the HSV 1 and HSV 2 nonvirion antibodies. All of these data taken together are interpreted as indicating that HSV 1 and HSV 2 play an etiologic role in certain human cancers, because they provide the kind of evidence by which virus-free experimental cancers can be proved to have been originally induced by such DNA viruses as polyoma, Simian Virus 40, or certain types of adenovirus.
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PMID:Herpes simplex and herpes genitalis viruses in etiology of some human cancers. 436 85

Interferons, glycoproteins originally investigated as antiviral agents, are now known to be active as anticancer agents, immune system modulators, and growth control regulators. For these reasons, interferons have definite and documented relevance to dermatologists. In regard to viral diseases, therapeutic trials in humans have shown promising results in herpes simplex infections, vaccinia, laryngeal papillomas, and condyloma acuminatum, as well as in rabies and hepatitis B. Pilot studies with interferon treatment of melanoma have been so promising that the American Cancer Society has selected this area to receive additional research support. Also, the antiproliferative effects of interferons have potential application to proliferative diseases such as psoriasis.
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PMID:Interferon: status in treatment of skin disease. 616 67

Clinical trials of the antiviral action of interferon have shown an effect on the replication of several viruses including varicella zoster, herpes simplex, cytomegalovirus and hepatitis B. These studies indicate that administration early in the course of infection, or in some clinical circumstances, prophylactic administration, is likely to result in viral inhibition. The studies of interferon efficacy in topical application, as in prevention of recurrent herpes simplex keratitis, have shown limited efficacy except with very high doses. These studies are being pursued with more concentrated preparations of interferon. The evaluation of interferon in human malignancy is just beginning, but some encouraging results have been obtained in open trials of the drug in patients with non-Hodgkin's lymphoma, melanoma, osteogenic sarcoma, and other diseases. With newer methods for the production of interferon, it may be possible to evaluate its antiviral and anti-tumor effects in carefully controlled studies with larger numbers of subjects.
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PMID:Interferon as an antiviral and anti-tumor therapeutic agent. 616 51

The antiviral and antiproliferative effects of highly purified Escherichia coli-derived human interferons (IFNs) were examined in human melanoma cells (Hs294T). Antiproliferative activity was monitored by measuring inhibition of cell multiplication, and antiviral activity was determined by inhibition of herpes simplex virus type 1 replication. Treatment of cells with IFN-gamma in combination with IFN-alpha A or IFN-beta 1 resulted in potentiation of both antiproliferative and antiviral activities. In contrast, combination treatments composed of IFN-alpha A and IFN beta 1 yielded inconsistent results. Some combinations reflected additive responses, whereas others were antagonistic. To examine correlations between IFN-induced biological activities and interactions of the different IFNs with cell surface receptors, in vivo [35S]methionine-labeled IFN-alpha A was prepared. Binding studies indicated the presence of 2,980 +/- 170 receptors per cell, each with an apparent Kd of (8.4 +/- 1.3) X 10(-11) M. Results from competitive binding studies suggested that Hs294T cells possess at least two types of IFN receptors: one which binds IFN-alpha A and IFN-beta 1 and another to which IFN-gamma binds.
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PMID:Synergistic antiviral and antiproliferative activities of Escherichia coli-derived human alpha, beta, and gamma interferons. 631 48

To evaluate the usefulness of host resistance assays for measurement of immunotoxicologic effects of chemicals, the immunosuppressive effects of exposure to diethylstilbestrol (DES) were compared with the effects of treatment with the known immunosuppressive drug cyclophosphamide (CPS). A panel of six host resistance models was evaluated, including infection with the bacterium Listeria monocytogenes, herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMC), the yeast Cryptococcus neoformans, the parasite Naegleria fowleri, and transplantation of the B16F10 melanoma tumor. The results demonstrate a general correlation between the effects of CPS and DES on host resistance. Acute treatment with CPS (200 mg/kg) markedly depressed resistance to the microbial infections with L. monocytogenes and HSV, and exposure to DES usually also decreased resistance in a dose dependent manner. Moreover, CPS had no marked effect on resistance to N. fowleri and EMC virus, and exposure to DES also had a neglible or slight effect. There were, however, two model systems in which the effects of CPS and DES diverged. Whereas treatment with DES produced no significant effect on resistance to C. neoformans, acute treatment with CPS prior to the fungal infection produced a marked increase in resistance. Also, while treatment with CPS markedly increased B16F10 lung metastases, treatment with DES significantly decreased the incidence and number of lung metastases. The data support the general validity of host resistance assays, particularly with models of short disease course, for measuring immunosuppression. However, the results also emphasize the complexity of interpreting effects of environmental chemicals on host resistance, because of the interplay of such factors as relative times of exposure to the chemical in relation to pathogenesis of infection, the length of the disease course, the nature of the operative host defense mechanisms, and the compensatory recovery of these mechanisms.
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PMID:Immunotoxic effects of diethylstilbestrol on host resistance: comparison with cyclophosphamide. 632 3

In the dermatological field, interferon is used in clinical trials for viral skin diseases and for malignant skin tumors such as malignant melanoma. In regard to viral diseases, clinical trials have shown promising results in viral warts, herpes simplex and herpes zoster. In the double-blind trial, patients with bilateral common warts of the extremities were treated at weekly intervals with intralesional injections of either human fibroblast interferon or placebo. More than 81% of the interferon-treated extremities were either cured by or responded effectively to the therapy, while only 17% of the placebo responded. Although our data has confirmed that interferon is effective in the treatment of common warts diseases, the method of application and repeated injections indicate that this therapy may not be helpful in routine cases but only in selected patients in whom other therapy has failed. However, development of new delivery systems or modification of dosages may increase the value of interferon therapy for warts disease. Interferon seems also effective for herpes zoster. But herpes zoster usually regresses spontaneously within three weeks, therefore, it is not easy to define efficacy of interferon in this disease. Therefore, we need to examine the effect of interferon on herpes zoster both in placebo controlled and double-blind trials involving patients with immunocompromised diseases.
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PMID:[Interferon in skin diseases]. 636 93

Tunicates provide a rich source of biologically active compounds with potentially useful medicinal properties. The most interesting compounds identified thus far are the didemnins, depsipeptides from a Caribbean Trididemnum species, which are potent inhibitors of L1210 leukemia cells in vitro and are also active in vivo against P388 leukemia and B16 melanoma. In addition the didemnins inhibit growth of a variety of RNA and DNA viruses in vitro and protect mice infected intravaginally with herpes simplex virus type 2. Didemnin B, a derivative of didemnin A, is far more active than A, which argues for the likelihood of further useful chemical modifications in the series.
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PMID:Antiviral and antitumor compounds from tunicates. 668 37

To target therapeutic genes specifically to melanoma cells, we have constructed recombinant retroviruses where transcriptional control of the murine interleukin-2 (mIL-2) or herpes simplex virus thymidine kinase (HSVtk) genes is provided by the 5' promoter region of the murine tyrosinase gene. Tissue-specific expression of these genes is observed both at the mRNA and protein levels in the B16 melanoma line compared with NIH3T3 fibroblasts. Thus, B16 cells infected with one such retrovirus containing the HSVtk gene exhibited a > 90% reduction in colony-forming efficiency after exposure to 1 microgram/ml ganciclovir, relative to controls, whereas similarly infected NIH3T3 cells showed < 10% reduction in colony-forming efficiency under comparable conditions. The degree of preservation of tissue-specific expression from the internal tyrosinase promoter depended upon the exact molecular design of the vector, possibly as a consequence of the interference between closely juxtaposed promoters within the provirus. Our results show that retroviral vectors can be prepared with the capacity to regulate expression of inserted genes specifically in a particular cell type and may be useful for developing efficient, targeted vectors for the in vivo delivery of genetic therapies for malignant melanoma.
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PMID:A comparison of the properties of different retroviral vectors containing the murine tyrosinase promoter to achieve transcriptionally targeted expression of the HSVtk or IL-2 genes. 758 96

To assess the potential of an in vivo, adenovirus-mediated gene therapy approach for the treatment of malignant melanoma, the efficacy of adenovirus-mediated herpes simplex virus thymidine kinase gene (HSV-Ek) transfer and administration of ganciclovir (GCV) was investigated using a nude mouse model. Initially, B16 murine melanoma cells were efficiently transduced in vitro by a recombinant replication-defective adenovirus containing the HSV-tk gene (ADV/RSVtk), and rendered sensitive to cell killing by 10 micrograms/ml GCV. A significant "bystander effect" was observed at low multiplicity of infection in comparison of cell killing to control B16 transduction by adenovirus containing the beta-galactosidase gene (ADV/RSV-beta-gal). In vivo, melanomas established from subcutaneous injection of 4 x 10(5) B16 cells were injected after 14 d with 1 x 10(10) ADV/RSV-tk viral particles. Subsequent treatment for 6 d with GCV resulted in an inhibition of melanoma growth, with an approximately 40-50% reduction in melanoma volume in comparison to controls in repeated experiments. These data demonstrate that adenovirus-mediated gene transfer can function as an efficient delivery system to reduce established tumor burden in vivo. This result may hold significant promise for the development of effective in situ gene therapy for melanoma in humans.
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PMID:Inhibition of melanoma growth by adenoviral-mediated HSV thymidine kinase gene transfer in vivo. 786 Sep 93

The retrovirus-mediated transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene into tumor cells renders them sensitive to the cytocidal effect of the antiviral drug ganciclovir. This method has shown promising results as a treatment for experimental brain tumors. These experiments indicate that a major mechanism for the effectiveness of HSV-tk retroviral gene therapy may be the bystander tumoricidal effect. The bystander effect was hypothesized to explain tumor eradication, given that the efficacy of in vivo gene transfer to tumor cells was less than 100%. We demonstrate, in this report, that the bystander tumoricidal effect is a major contributor to the tumoricidal effect of ganciclovir in cell culture experiments using the mouse K1735 C19 cerebral melanoma line, thereby expanding the observation of the bystander phenomenon to a broader range of tumor types. The bystander effect was studied in vitro by coculturing wild-type C19 melanoma cells with HSV-tk-expressing C19 (C19-STK) cells. A maximal tumoricidal effect was seen when only 1 in 10 tumor cells expressed the HSV-tk gene. This suggests that in effect, 1 tumor cell with the HSV-tk gene, when given ganciclovir, will destroy 10 neighboring or bystander cells. The destruction of bystander cells does not appear to be mediated by a soluble factor(s) released into the media but, rather, requires close cell proximity or cell contact. In addition, HSV-tk-expressing C19 cells can exert an antitumoral effect not only on wild-type C19 cells but also on cells from a variety of different tumor cell lines, including a human glioblastoma multiforme cell line, indicating that the bystander effect is not a cell line-specific phenomenon. Finally, we observed that the bystander tumoricidal effect could be harnessed directly without using retrovirus-producing cells to increase survival in the mouse C19 brain tumor model. The potential implications of our findings in treating human brain tumors are discussed.
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PMID:Bystander tumoricidal effect in the treatment of experimental brain tumors. 788 54


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