ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Elevated levels of c-SRC activity have been found In human melanocytes and some human melanoma cell lines. We examined c-SRC In B16 murine melanoma cells. B16-F0 non-metastatic melanoma cells contained threefold more c-SRC activity and protein than NIH 3T3 murine fibroblasts. Differentiation of B16-F1 metastatic melanoma cells with retinoic acid resulted in an elevation in c-SRC activity, protein and mRNA. The increase in c-SRC was detectable after about 48 h of retinoic acid treatment, as were changes in cellular morphology and growth rate. Thus, there is a correlation between differentiation and expression of c-SRC in B16 murine melanoma cells. These findings suggest a role for c-SRC in murine melanocyte differentiation or function.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Transfection of class IH-2Kbor H-2Kdinto cells of a pigmented subclone of B16–F10 BL6 (termed BL6–8) results In the loss of melanin production. In contrast, transfected BL6–8 cells expressing H-2Dd, H-2Ld, class I H-21Akand/or the neorgenes maintained their pigmented phenotype. Melanogenesis was also inhibited in cells which expressed the endogenous H-2Kb, but not the endogenous H-2Db, gene. In order to identify the specific defects in the melanogenic pathway responsible for the absence of melanin production, factors known to be related to the regulation of pigment formation were evaluated in H-2K-expresslng cells. These studies showed that: (1) transfection of BL6–8 cells with the H-2Kbor H-2Kd, but not with the H-2Dd, H-2Ldor H-21Ak, genes was associated with complete inhibition of tyrosinase activity; (2) α-melanocyte-stimulating hormone (MSH) and theophylline (an Inhibitor of cAMP phosphodiesterase) failed to stimulate tyrosinase activity in H-2K-positive cells, whereas tyrosinase activities in untransfected, or H-2DdH-2Ld, neoror H-21Ak-transfected cells were dramatically increased by those agents; (3) treatment with MSH had no effect on cAMP levels in H-2K-positive cells but stimulated cAMP levels more than 100-fold in H-2K-negative cells; (4) in contrast to MSH, forskolin, a stimulator of adenylate cyclase, was able to stimulate cAMP levels in all cell lines tested, but in H-2Kb-posltlve cells the levels of forskolininduced cAMP were significantly less than those elicited in H- 2Kb-negative cells; (5) electron microscopy showed that H-2Kposltive cells lacked mature melanosomes; (6) Northern blot analyses showed that H-2K-positive cells lacked mRNA for tyrosinase or for the MSH receptor. Taken together, expression of the endogenous or transfected H-2K gene In BL6 melanoma cells results in down-regulation of the entire melanogenic pathway, including the inhibition of tyrosinase and MSH receptor gene expression, cAMP responses and melanosomal biogenesis.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Since there is much indirect evidence for dominant suppressor genes for melanoma, we sought to isolate such a gene. Metastatic B16–F10 murine melanoma cells were lipofected with a normal human genomic library in a cosmid vector that also confers resistance to the drug G418. A few of the G418-resistant colonies acquired combinations of properties resembling those of normal melanocytes, including differentiated features (pigmentation, dendriclty), slower growth, flat shape, monolayered colony form, stimulation of proliferation by a phorbol ester, and anchorage dependence. Four out of eight also showed reduced tumorigenicity in mice. Southern blotting indicated the presence of numerous cosmids in the melanocyte-like transfectants. DNA from one such line was used for secondary transfection. One secondary G418-resistant line showed pronounced melanocytic properties and marked tumour suppression in syngeneic and nude mice. A human repetitive sequence detected in this line was used in the polymerase chain reaction (PCR) to isolate intervening unique DNA sequences. One unique human sequence was attenuated in all tumours arising from both primary and secondary transfectants, suggesting close linkage with the sequence responsible for tumour suppression.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

In recent years, several studies have documented that melanoma cell lines produce various cytokine/growth factors and their receptors. Since cell lines can acquire altered properties, such as changes In growth requirements, we studied constitutive cytokine gene expression In melanoma cells from 20 fresh surgical specimens: seven primary melanomas and 13 metastases (12 lymph-node metastases and one subcutneous metastasis). After tumour cell Isolation by discontinuous gradient, we tested for mRNA expression by means of reverse-transcriptase polymerase chain reaction. Most melanoma cells tested expressed growth factors: basic flbroblast growth factor (bFGF), interieukin (IL)1α IL-1β, IL-6 and IL-8 and, In five cases out of 20, expressed granulocyte–macrophage colony-stimulating factor (GM-CSF) (two out of five were also positive for GM-CSF receptor). Our results do not point to a direct correlation between cytokine expression and clinical stage at the time when the bioptic specimen was obtained. However, they allow us to suggest a possible metastatic tumour cell phenotype, in which autogenous GM-CSF expression could modulate immune response against the tumour cell Itself or could potentiate metastatic colonization properties.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We evaluated thein vitrocytotoxic effects of combined human tumour necrosis factor alpha (TNF), human Interferon gamma (IFN-γ), melphalan (L-PAM) and hyperthermia (HTX) on human melanoma cell lines using the crystal violet assay. HTX (40°C, 1 h) alone had no effect. The responses of the cell lines to TNF were in the rank order of 939 cells > 987 > 284 > C8161 > 852 > A2058 ˜ 0, and all displayed shallow dose–response curves; no significant thermal enhancement of TNF cytotoxicity was apparent with this heat dose. All cell lines were sensitive to L-PAM, with 284 cells being the most sensitive; HTX caused only slightly increased sensitization to L-PAM. The combination of TNF and L-PAM resulted in generally subadditive or additive cytotoxicity, with or without HTX. The response to IFN-γ alone was heterogeneous; the 939,284 and 852 cell lines were sensitive to a dose as low as 20 ng/ml, whereas the 987 line was resistant to 2.0 μg/ ml, even with HTX. IFN-γ enhanced the response to TNF only of the TNF-resistant A2058 cell line, but there was no enhancement of the response to L-PAM for any line. Thus, this tetramodality combination achieved generally subadditive or additive cytoxicityin vitro.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The relation between use of sunscreens, different host factors and malignant melanoma was investigated in a population-based, matched case–control study of malignant melanoma in the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, between 1 July 1988 and 30 June 1990. In total, 400 melanoma patients and 640 healthy controls aged 15–75 years answered a comprehensive questionnaire regarding different epidemiologic variables, including questions on use of sunscreens and different constitutional factors. The use of sunscreens was not found to protect against developing malignant melanoma. Instead, an unexpected relation between the use of sunscreens and the risk of developing malignant melanoma was seen (odds ratio (OR) 1.8 for almost always vs never using sunscreens). A tentative dose–response relation was found. Virtually the same ORs were seen in both sexes. Furthermore, persons younger than 50 years had a higher OR than persons older than 50 years. When different melanoma presentation sites were considered, lesions of the trunk were associated with sunscreen use in females (adjusted OR=3.7 for almost always vs never using sunscreens), while lesions of the extremity or head and neck were associated with sunscreen use in males (adjusted OR=3.2 for almost always vs never using sunscreens). Raised naevi on the left arm and freckling were shown to be the major constitutional risk factors (OR=3.9 for more than three naevi vs none and OR=1.4, respectively). The results were essentially unaltered in a histopathologically re-examined material. Further investigations are needed in order to form a basis for melanoma prevention.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Interleukin-10 (IL-10), originally described as a product of TH2 cell clones, has been recognized as a potential Immunosuppresslve cytokine. To Investigate the relevance of IL-10 in melanoma patientsin vivo, we studied IL-10 serum levels in 104 untreated patients in different stages of the disease; 20 healthy subjects and 22 patients with inflammatory dermatoses served as controls. Serum levels were measured by ELISA. Only one of 31 patients with stage I melanoma (3%) and one of 16 stage II patients (6%) showed detectable IL-10 levels. Interestingly, six of 17 patients with lymph node metastases (stage III, 35%) and 29 of 40 patients with widespread disease (stage IV, 73%) revealed IL-10 levels of 15–480 pg/ml. No healthy person and only one control patient had a detectable IL-10 serum level. The data suggest that IL-10 in melanoma patients may contribute to down-modulation of anti-tumour responsesin vivo.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The EORTC Melanoma Group was created in 1969 by people of different disciplines who were, and still are, motivated by the need for a pluridisciplinary approach to melanoma. Table 1 lists the chairmen and secretaries who have served on the organization. The core organization is devoted to treatment of melanoma. In addition, there are subgroups for specific programs, listed below.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID