Normal HLA class I, II, and MICA gene distribution in uveal melanoma.

Purpose: The molecules of the HLA class I and II molecules as well as the MHC class I chain-related gene A (MICA), a polymorphic and stress-induced cell surface molecule, are involved in T-cell and natural killer-cell (NK-cell) mediated immune responses. In this study we looked for any genetic susceptibility contributed by HLA class I, class II, or MICA genes with regard to the development of uveal melanoma.

Methods: Between 1998 and 2001, 159 uveal melanoma patients were typed for HLA class I and II, and 168 uveal melanoma patients were evaluated for MICA by microsatellite typing.

Prognostic value of the disodium phosphate 32P uptake test in uveal melanoma: a long-term study.

Objective: To evaluate whether nuclear activity as measured by the disodium phosphate 32P (32P) uptake test for uveal melanoma is of prognostic value and corresponds to known prognostic factors.

Methods: A retrospective analysis of 121 patients with choroidal and/or ciliary body melanoma, tested with the 32P uptake test before enucleation between January 1, 1973, and December 31, 1976, at the Leiden University Medical Center. We obtained the 25-year follow-up information of this group of patients and compared the 32P test results and histopathological variables with the long-term survival rates.

Prognostic value of S-100-beta serum concentration in patients with uveal melanoma.

Background: In cutaneous melanoma, the S-100-beta serum level is recognized as a marker of metastatic disease.

Objectives: To determine whether S-100-beta is present in the serum of patients with uveal melanoma and to test whether the serum concentration of S-100-beta is related to known clinical and histopathological prognostic factors in these patients.

Methods: The S-100-beta concentration was measured in serum samples collected from 64 patients with uveal melanoma before enucleation and from 58 healthy control subjects.

HLA expression in uveal melanoma: there is no rule without some exception.

A decrease in the expression of HLA antigens is considered a characteristic of tumor progression and is considered an important tumor-escape mechanism. In general, HLA Class I expression is even further decreased on metastases. Tumor cells that loose their HLA Class I antigens become less susceptible to lysis by specific T cells, but may become more sensitive to Natural Killer cells.

Uveal melanoma: no expression of HLA-G.

Purpose: To investigate whether uveal melanoma cells express HLA-G, a nonclassical HLA class I molecule that has been shown to be a critical mediator in the inhibition of natural killer (NK) cell-mediated cytolysis.

Methods: Eleven human uveal melanoma cell lines were analyzed for the expression of HLA-G by flow cytometry, immunocytochemistry, Western blot analysis, and RT-PCR followed by Southern blot analysis. Two HLA-G-specific monoclonal antibodies were used, 87G and MEM-G/1.

Characterization of melanocortin-1 receptor gene variants in uveal melanoma patients.

Purpose: Allelic variations of the melanocortin-1 receptor (MC1R) gene have been linked to red hair and sun-sensitive skin types and may play a role in the susceptibility to develop cutaneous malignant melanoma (CMM). To define the role of MC1R gene in uveal melanoma, a case control study was performed, in which the presence of MC1R gene variations in uveal melanoma patients was compared with that of healthy controls.

Methods: MC1R gene variants were analyzed in 162 uveal melanoma patients and 255 healthy controls.

Promoter hypermethylation: a common cause of reduced p16(INK4a) expression in uveal melanoma.

Tumors often display unrestricted cell cycling attributable to a dysfunctional G(1)-S checkpoint. One of the mechanisms leading to such a defect is the inactivation of the cyclin-dependent kinase inhibitor p16(INK4a). Although inactivation of p16(INK4a) is observed in a wide range of tumors, including cutaneous melanoma, genetic alteration of p16(INK4a) is reportedly uncommon in uveal melanoma.

Expression of epidermal growth factor receptor: risk factor in uveal melanoma.

Purpose: To investigate the prognostic significance of the expression of epidermal growth factor receptor (EGFR) in uveal melanoma. EGFR is a transmembrane glycoprotein, and its expression has been correlated with the development of metastases in various malignancies.

Methods: Frozen sections from 22 primary uveal melanomas were examined for EGFR expression by a three-step immunoperoxidase staining, using a mouse anti-human EGFR IgG2b monoclonal antibody.

High frequency of allele-specific down-regulation of HLA class I expression in uveal melanoma cell lines.

Uveal melanoma is the most common primary intra-ocular tumor in adults and has a high mortality rate due to liver metastases, for which no effective treatment is available. To investigate whether immunotherapy might be feasible in uveal melanoma, the HLA class I surface expression of 6 uveal melanoma cell lines was analyzed by flow cytometry using a broad panel of allele-specific monoclonal antibodies. To up-regulate HLA expression, cells were also cultured with IFN-alpha or -gamma.

Comparative immunotoxicology of ultraviolet B exposure I. Effects of in vitro and in situ ultraviolet B exposure on the functional activity and morphology of Langerhans cells in the skin of different species.

Ultraviolet (UV) B-induced morphological and functional changes in the skin of mice, rats and humans were investigated. Changes in the morphological structure of Langerhans cells (LC), the major antigen-presenting cells in the skin, using confocal laser scanning microscopy, were found in mouse and rat skin after in situ exposure to high doses of UVB radiation (FS40) (3-9 kJ/m2). Similar UVB doses failed to induce alterations in the morphological structure of human LC.

Efficacy of micronized titanium dioxide-containing compounds in protection against UVB-induced immunosuppression in humans in vivo.

Micronized pigment-containing sunscreens may provide a good alternative to chemical sunscreens in protection against ultraviolet (UV) B-induced immunosuppression. The metal particles in these products are likely to remain on the skin surface where they can offer broadband protection for both the UVA and UVB regions. We have tested the protective capacity of three titanium dioxide (TiO2)-containing compounds in humans in vivo.

Differential effects of sunscreens on UVB-induced immunomodulation in humans.

Ultraviolet radiation has been shown to suppress the (skin) immune system both in animal species and in humans. Whether sunscreens can prevent immunosuppression is a matter of debate. This study investigated the protective capacity of a commercial sunscreen lotion in humans.

In situ action spectra suggest that DNA damage is involved in ultraviolet radiation-induced immunosuppression in humans.

The mixed epidermal cell lymphocyte reaction (MECLR) is a commonly used method to study the immunomodulatory effects of UV radiation. The in vitro action spectrum for the MECLR showed that the UV-induced suppression of the MECLR responses is associated with UV-induced DNA damage. To investigate whether in vivo DNA damage also leads to the abrogation of the MECLR, in situ action spectra were made for the MECLR and the induction of thymine dimers (T < > T).

Differential suppression of the human mixed epidermal cell lymphocyte reaction (MECLR) and mixed lymphocyte reaction (MLR) by cis-urocanic acid.

Cis-urocanic acid (UCA), formed in the stratum corneum by UV irradiation of trans-UCA has been proposed as a mediator of UV-induced immunosuppression in the skin. In this study, we examined the in vitro effect of cis-UCA (6-100 micrograms/mL) on the human mixed lymphocyte reaction (MLR) and the mixed epidermal cell lymphocyte reaction (MECLR). Addition of cis-UCA (purified or in a mixture with trans-UCA) did not affect the MLR but was able to induce a 20% suppression of the MECLR responses.

UVB-induced suppression of the mixed epidermal cell lymphocyte reaction is critically dependent on irradiance.

The mixed epidermal cell lymphocyte reaction (MECLR) is a commonly used method to study the effects of ultraviolet B (UVB) radiation on the skin immune system. In UVB experiments dosimetry is very important. The influence of irradiance on the MECLR was studied in vitro using Philips FS40 lamps with variable UV intensities.

The action spectra for UV-induced suppression of MLR and MECLR show that immunosuppression is mediated by DNA damage.

Ultraviolet-B (UVB, 280-320 nm) radiation can promote the induction of skin cancer by two mechanisms: damage of epidermal DNA and suppression of the immune system, allowing the developing tumor to escape immune surveillance. The mixed lymphocyte reaction (MLR) and the mixed epidermal cell lymphocyte reaction (MECLR) are commonly used methods to study the immunosuppressive effects of UVB radiation. To obtain a better understanding of the mechanism by which UVB radiation decreases the alloactivating capacity of in vitro-irradiated cells, action spectra for the MLR and MECLR were determined.

Advancement of meiotic resumption in graafian follicles by LH in relation to preovulatory ageing of rat oocytes.

After ovulation, the fertile life of oocytes is short. In the present study, the fertile life of oocytes was studied in relation to the resumption of meiosis. Early on the day of pro-oestrus, meiotic resumption was advanced in rats by a brief infusion of LH; ovulation was induced 8 h later by Ovalyse, a GnRH analogue; rats were mated 13 h after receiving Ovalyse, that is at about the time of ovulation.