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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphokines represent a new group of substances that have engendered increasing interest in the context of cancer therapy. They are products of the lymphoid system that can now be produced in pure form as a consequence of advances in gene cloning technology. alpha-Interferon has been tested in clinical trials for several years, and has been found effective in the treatment of patients with hairy cell leukemia, chronic myelogenous leukemia, Kaposi's sarcoma (AIDS) and renal cell cancer. Interleukin-2 has shown impressive antitumor activity in patients with melanoma or renal cell cancer, particularly in combination with lymphokine-activated killer cells, although at very high doses with correspondingly severe toxicity. The clinical testing of tumor necrosis factor is in an early stage. The introduction of this class of agents has opened new perspectives for cancer therapy.
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PMID:[Interferons, interleukin-2 and tumor necrosis factor. New approaches to cancer therapy]. 243 34

The objective of this study was to establish whether human recombinant tumor necrosis factor (TNF) can significantly stimulate the proliferation of some tumor cells. Treatment with TNF had little or no effect on the growth of human tumor cells and murine NIH/3T3 cells cultured in medium with high serum concentration. Two tumor lines, SK-MEL-109 melanoma and HOS osteosarcoma cells, were adapted to grow in medium supplemented with 0.5% serum. The growth of these SK-MEL-109 cells was inhibited by TNF, but that of the HOS cells was greatly stimulated by TNF in a dose-dependent way. Treatment with 10 ng/ml of TNF resulted in a two-fold increase in the rate of cell division. This effect of TNF was also shown by measuring DNA and protein synthesis. The continuous presence of TNF was not required for its mitogenic activity on HOS cells cultured with 0.5% serum, since treatment for only one day with TNF resulted in prolonged growth stimulation. The failure of TNF to promote division of cells cultured in medium with 10% serum may possibly be explained by the presence of saturating amounts of growth factors in serum. Interferons abolished the mitogenic activity of TNF on HOS cells. Furthermore, TNF did not show synergism with insulin or epidermal growth factor in stimulating growth of these cells. The level of c-myc mRNA was increased five-fold after 30 minutes of treatment with TNF. This shows that TNF is a growth factor for HOS cells and that it induces accumulation of c-myc mRNA.
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PMID:Tumor necrosis factor stimulates proliferation of human osteosarcoma cells and accumulation of c-myc messenger RNA. 245 Aug 80

The oncolytic strain 73-T of Newcastle disease virus (NDV) has been reported to be beneficial in the treatment of cancer patients, but little is known about its mechanism of action. In this study, NDV strain 73-T and a wild-type isolate of NDV were found to be potent inducers of tumor necrosis factor (TNF) production by both human peripheral blood mononuclear cells (PBMCs) and rat splenocytes. Antibody inhibition experiments identified TNF-alpha as the major species of TNF induced by NDV in PBMCs. The effect of recombinant human TNF-alpha (rHuTNF-alpha) on human cancer cells was then examined. Neither rHuTNF-alpha nor supernatants from NDV-stimulated PBMCs were cytotoxic toward the TNF-resistant human malignant melanoma cell line MEL-14. However, when MEL-14 cells were treated with NDV strain 73-T, both rHuTNF-alpha and supernatants from NDV-stimulated PBMCs killed 48% and 55%, respectively, of these tumor cells. Treatment with NDV also conferred TNF susceptibility to the TNF-resistant human malignant melanoma cell line MEL-21 and the human myelogenous leukemia cell line K562. In contrast to its enhanced cytotoxicity toward NDV-treated cancer cells, rHuTNF-alpha had no effect on NDV-treated normal human PBMCs proliferating in response to concanavalin A. These results suggest two important mechanisms for the antineoplastic activity of NDV: (a) induction of TNF-alpha secretion by human PBMCs and (b) enhancement of the sensitivity of neoplastic cells to the cytolytic effects of TNF-alpha.
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PMID:Newcastle disease virus as an antineoplastic agent: induction of tumor necrosis factor-alpha and augmentation of its cytotoxicity. 245 2

This paper introduces the current status of melanoma treatment with various biologic response modifiers (BRMs) in Japan, with an emphasis on the clinical results of Interferon therapies. The authors also refer briefly to the current situation of interleukin-2 (IL-2) and tumor necrosis factor (TNF) in Japan. Many BRMs have been used in treatment of melanoma, e.g., IFN, IL-2, TNFs, BCG, MY-1 (DNA extracted from BCG), WPG (CWs of Bifidobacterium infantis, ATCC 15697), OK-432 (Picibanil, Streptococcus pyogenes preparation), bestatin, and forphenicinol. Some of these have completed clinical trials, while others are still undergoing clinical testing. Among IFN-alpha, beta, and gamma, intralesional administration of natural IFN-beta was found to be more effective than IFN-alpha for metastatic skin melanoma, the survival time of patients being prolonged by the administration of IFN-beta. IFN-gamma appeared to have lower efficacy than IFN-alpha and beta. The frequency of BRM application to melanoma treatment will increase. The authors foresee that combinations with radio- and/or other chemotherapy will be more common than the single use of a BRM, especially in the case of IFN.
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PMID:Current status of melanoma treatment with interferon, cytokines and other biologic response modifiers in Japan. 246 42

Malignant melanoma is no longer a rare neoplasm. Recreational exposure to sunlight is undoubtedly an etiologic factor. Among all cancers, its rate of increase is exceeded only by that of bronchogenic carcinoma. Before administration of systemic therapy, histologic confirmation of the diagnosis and assessment of both the relative medical fitness of the patient and the available psychosocial support are important. Chemotherapeutic and interferon-alpha regimens may offer transient reprieve in 15 to 20% of patients but yield few long-term survivors. Other biologic response modifiers, such as tumor necrosis factor and interleukin 2, are promising but without established consistent efficacy. Postoperative systemic treatment programs for patients at risk for disseminated disease are of no proven benefit in randomized trials and cannot be endorsed outside of the context of a clinical trial. Radiation therapy may provide useful palliation, especially with a fraction of 400 cGy rather than the more traditional dose of 200 cGy/fraction. Selected patients with metastatic disease may benefit from surgical resection, but residual disease after attempted extirpation is usually associated with prolonged disability.
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PMID:Regional and systemic strategies for metastatic malignant melanoma. 247 28

Only the recent production of large amounts of highly purified recombinant interferons has made it possible to elucidate precisely the in vitro and in vivo effect of alpha- and gamma-interferon. Interferon-alpha has significantly widened the treatment modalities for some rare tumors such as hairy cell leukemia and chronic myelogenous leukemia. Although treatment results in solid tumors are disappointing, tumor regression greater than 50% is achieved in 15-25% of patients with hypernephroma or melanoma, cancers highly resistant to cytotoxic drugs. The solid tumors must be treated with high doses of interferon-alpha which causes severe side effects. Interferon-induced toxicity can be reduced by continuous subcutaneous infusion. Interferon-alpha is also used for the treatment of viral diseases such as chronic hepatitis-B, as well as for patients with AIDS and Kaposi sarcoma. Other virus infections such as herpes simplex and condylomata acuminata represent the few established indications for treatment with interferon-beta. Interferon-gamma has distinct immunomodulatory effects in vitro and in vivo, although the clinical significance of this potential has not yet been established. Thus far the treatment results in tumor patients have been poor. The future will show if the combination of interferons with other biological response modifiers, such as tumor necrosis factor or interleukin-2, or with cytotoxic drugs, brings further progress in cancer treatment.
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PMID:[Possibilities and limits of the use of interferons in the clinic]. 247 77

It seems to be generally agreed that periodontal disease is a local manifestation of a systemic immune response. Interleukin-1 (IL-1), which has multiple biologic activities, is detected in the gingival sulcus fluid of periodontitis sites. Recent investigations have revealed that IL-1 and tumor necrosis factor (TNF) are analogous to osteoclast activating factor and promote bone resorption. These findings have suggested the possibility that IL-1 and TNF may play a significant role in the initiation and development of periodontal disease. However, it remains to be determined whether these cytokines influence periodontal tissue breakdown in periodontitis. To elucidate the mechanisms of tissue breakdown in periodontitis, we examined cytokine production by human periodontitis gingival tissue. Twelve periodontitis patients were included in this study. Control subjects with healthy periodontium consisted of nine individuals. Gingival samples were biopsied from inflamed or healthy gingival tissues. Biopsy specimens were dissected into fragments 3 mm in diameter and plated onto 24 well culture plates with RPMI 1640 medium. IL-1 activity was measured by a growth inhibition assay using melanoma cell line A 375. An enzyme-linked immunosorbent assay (ELIZA) was used for measuring levels of human IL-1 alpha, IL-1 beta. TNF alpha activity was measured by a growth inhibition assay using cell line LM2D6. IL-1 activity was detected in significantly (p less than 0.001) higher levels in culture supernatants from gingival tissues in periodontitis (48.0 +/- 23.3 units/ml) than in control tissues (2.3 +/- 0.6 units/ml), however, levels of IL-1 activity were not associated with periodontal pocket depth or extent of alveolar bone resorption in periodontitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Study of cytokine production in inflamed human gingival tissues in periodontitis. Interleukin-1 (IL-1 alpha, beta) and tumor necrosis factor (TNF alpha)]. 248 32

In this study we evaluated human pancreatic cancer xenotransplanted into nude mice as a model suitable for adoptive immunotherapy studies. A pancreatic cancer cell line (MIA PaCa-2) was chosen and its growth in nude mice and sensitivity to lysis by human lymphokine-activated killer (LAK) cells were characterized. This line grew in 96% of the cases when young (4- to 6-week-old) Swiss/NIH nude mice were used. The line was highly sensitive to lysis by LAK cells in a standard chromium-51 release assay (67.8%), similarly to other cell lines known to be highly sensitive, such as K562 (75.6%) and the melanoma cell line SU.102 (53.1%). To assess their in vivo distribution, human peripheral blood lymphocytes (PBLs) and LAK cells were adoptively transferred into nude mice after labeling with indium-111 oxine. The results of this study show that adoptively transferred PBLs and LAK cells localize in this heterologous system as they do in autologous systems. PBLs are taken up mostly by the liver and spleen. The percentage of the administered dose of radioactivity taken up corrected by weight (percent dose per gram tissue) is 64.3 +/- 15.6%d/gm (liver) and 43.5 +/- 9.5%d/gm (spleen). LAK cells are taken up by liver (43.2 +/- 5.3%d/gm) and spleen (28.0 +/- 4.9%d/gm) but also localize significantly more than PBLs in other organs such as lungs (12.9 +/- 3.5%d/gm vs 1.4 +/- 0.3%d/gm, p less than 0.01), kidneys (19.1 +/- 2.1%d/gm vs 6.3 +/- 1.5%d/gm, p less than 0.001), and pancreatic tumors growing in orthotopic position (1.93 +/- 0.36%d/gm vs 0.56 +/- 0.06%d/gm, p less than 0.05). When the nude mice are pretreated with human recombinant tumor necrosis factor, localization of LAK cells compared with PBLs is even further enhanced both in tumors implanted in the pancreas (3.1 +/- 0.5%d/gm vs 0.56 +/- 0.06%d/gm, p less than 0.01) and in the subcutis (12.5 +/- 8.3%d/gm vs 0.95 +/- 0.29%d/gm, p less than 0.001).
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PMID:The in vivo distribution of human peripheral blood lymphocytes and lymphokine-activated killer cells adoptively transferred in human pancreatic cancer-bearing nude mice. 249 21

Human blood monocytes were isolated by counter-flow centrifugal elutriation from healthy donors and these noncytotoxic monocytes were rendered tumoricidal to allogeneic melanoma (A375) cells by activation with a synthetic acyltripeptide (FK-565), as assessed by measuring release of [125I]iododeoxyuridine in 72 h. When monocytes were treated with FK-565 for 16 h, and then fixed with paraformaldehyde, they showed cytotoxicity to A375 melanoma cells. The fixed-monocyte-mediated cytotoxicity to A375 cells was induced by the synergistic actions of FK-565 and recombinant interferon-gamma (rIFN-gamma), but not other cytokines [rIFN-alpha A, rIFN-beta, tumor necrosis factor (TNF), interleukin (IL)-2, -3 and -6]. For synergistic activation of monocytes with induction of a membrane-associated antitumor monokine, the monocytes had to be incubated first with rIFN-gamma and then with FK-565. FK-565 also acted synergistically with rIFN-gamma to stimulate monocytes to produce membrane-associated IL-1 activity, which induced C3H/HeJ thymocyte blastogenesis in response to phytohemagglutinin P. The tumoricidal and thymocyte-stimulating activities of the fixed monocytes were almost completely inhibited by a specific anti-(IL-1 alpha) antiserum, but not by a specific anti-(IL-1 beta) antiserum or monoclonal anti-TNF antibody. These results suggest that membrane-associated IL-1 alpha of human blood monocytes can be induced by two activation signals (rIFN-gamma then FK-565) at their suboptimal concentrations.
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PMID:Tumor cytotoxicity of human monocyte membrane-bound interleukin-1 alpha induced by synergistic actions of interferon-gamma and synthetic acyltripeptide, FK-565. 249 87

Normal cultured human epidermal melanocytes and melanoma cells derived from three different malignant melanomas were examined for synthesis of extracellular matrix components before and after treatment for one day with interferon-gamma, tumor necrosis factor-alpha, or both. Treatment of the cells with either cytokine individually had minimal effects on fibronectin levels. Treatment of the cells with the two agents in combination greatly stimulated fibronectin production as indicated by biosynthetic labeling and immunoprecipitation and by enzyme-linked immunosorbent assay. Synthesis of laminin was decreased slightly by the same treatment whereas thrombospondin production was stimulated slightly. The same treatment reduced melanocyte viability slightly but significantly inhibited proliferation and altered the morphology of the melanocytes. The treated cells became flattened and polygonal in shape while the untreated cells exhibited a bipolar shape with one or more long dendritic processes. These morphologic changes were not seen in cultures treated with interferon-gamma or tumor necrosis factor-alpha individually. The effects of interferon-gamma and tumor necrosis factor-alpha on fibronectin production by epidermal melanocytes are in contrast to the effects of the same treatments on fibronectin production by epidermal keratinocytes where fibronectin production is decreased but are similar to the effects of transforming growth factor-beta on a number of other cell types in which increased synthesis of fibronectin occurs and is associated with decreased growth.
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PMID:Modulation of fibronectin production in normal human melanocytes and malignant melanoma cells by interferon-gamma and tumor necrosis factor-alpha. 249 26


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