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Biomedical subjects

F Lejeune

Publications and source records attributed to F Lejeune.

179 records · Page 10Linked to original sources

Cutaneous malignant melanoma and exposure to sunlamps and sunbeds: a descriptive study in Belgium.

Two recently published case-control studies have highlighted the possibility of an association between the development of cutaneous malignant melanoma and exposure to sunlamps and sunbeds. Little is known about the behaviour patterns with regard to exposure to sunlamps and sunbeds in Western Europe. This descriptive study compares usage patterns of sunlamps and sunbeds of melanoma patients with the general population in Belgium. Evidence is given that melanoma patients are greater users of artificial ultraviolet sources than the general population, and that the incidence of melanoma in different geographical areas increases proportional to the percentage of people using tanning devices. Although this descriptive study may well be biased or refuted, it does advocate the need for further epidemiological research addressing specifically the issue of melanoma and exposure to artificial sources of ultraviolet radiation.

Adolescent↗

Human melanoma targeting with alpha-MSH-melphalan conjugate.

A conjugate made of alpha-MSH as a drug carrier and melphalan has been designed in order to target human melanoma cells. Iodination of the alpha-MSH moiety led to a relatively stable tracer which could be easily separated and analysed by reverse phase high pressure liquid chromatography. The conjugate was found to be unstable at neutral pH and a serious denaturation can take place at concentrations exceeding 100 micrograms/ml, especially in plasma. Receptor-mediated cytotoxicity has been shown by the use of cultured alpha-MSH receptor positive/negative cells as well as in vivo B16 murine melanoma model. Body distribution and uptake of the labelled compound were unaltered as compared to those of labelled free hormone. alpha-MSH receptor recognition properties also remained unchanged with a better apparent affinity of the conjugate probably due to the alkylating activity of melphalan itself. Using human melanoma dendritic cells expressing more than 10,000 alpha-MSH binding sites per cell as an in vitro model, we were able to demonstrate higher cytotoxicities as compared to melphalan-treated cells. In contrast, melanoma cells with low receptivity did not show higher cytotoxicity. P388D1 mouse plasmocytoma cells lacking receptors were much more sensitive to melphalan than the conjugate. This phenomenon appeared to be related with the number of binding sites expressed at the time of the experiment as well as cell differentiation and the doubling time. Our findings strongly support the concept of a receptor-mediated cytotoxicity and may enable the in vivo melphalan delivery to target tissues to be increased, achieving an improvement of drug penetration inside melanoma cells.

Amino Acid Sequence↗

Alpha-melanocyte-stimulating hormone immunoreactivity in human melanoma metastases extracts.

Seven human melanoma metastases were extracted in order to check the possible presence of any alpha-melanocyte stimulating hormone (MSH) immunoreactivity. The aim of that study was to provide some explanation for, mainly, two observations that we have already made and reported: 1) increased plasma alpha-MSH levels in melanoma of tumour-bearing patients as compared with tumour-free patients; 2) the presence of specific alpha-MSH receptors on human melanoma cells in culture. We could measure large amounts of immunoreactive alpha-MSH in all tumours ranging from 0.31 to 4.27 pmoles per g of wet tissue. Further identification of the extracted material by high-performance liquid chromatography revealed compounds of higher molecular weight and more hydrophobic than synthetic alpha-MSH. In addition, purified extracts could also displace 125I-labelled alpha-MSH from its cellular binding sites in an alpha-MSH specific radio-receptor binding assay. Our findings would suggest a possible presence of some hormone precursor(s) inside the melanoma tumours.

Aged↗

[Not Available].

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France↗

[Ewing's sarcoma: literature review and presentation of 4 cases].

Ewing's sarcoma occurs most often in young males of caucasian type and affects the medio-diaphysis of a long bone of the lower extremity, the pelvis and the humerus. Radiologically there is bone destruction, onion skin appearance, a Codman triangle and extension into the surrounding soft tissues. Microscopically, this tumor is composed of small round cells and it can be differentiated from non Hodgkin lymphoma, metastatic neuroblastoma and embryonal rhabdomyosarcoma. Recent immunological studies suspect a neuroectodermal origin. Ewing's sarcoma growths rapidly and spreads to lung and other bone locations. Without treatment, survival at 5 years is less than 5%. The actual therapeutic approach is multidisciplinary including surgery, chemotherapy and if necessary radiotherapy. With this approach actual survival rates at 5 years reaches 75%.

Adolescent↗

Studies on factors influencing human plasma alpha-MSH.

The various physiological effects of alpha-MSH, mainly on the CNS and on pigmentation in animal models, are well documented in the literature. Only a few investigators have confirmed similar properties in the human. However, the possible physiopathological role played by this hormone in human melanoma is still poorly defined. In order to approach this subject in a manner as complete as possible, we have performed, during the past four years, three different series of experiments: 1) alpha-MSH measurements in plasma samples from: a. melanoma and other cancer patients, b. whole body UVA irradiated healthy adults, c. circadian rhythm determinations in melanoma patients and in healthy male adults; 2) alpha-MSH measurements in human melanoma tumours; 3) alpha-MSH receptor expression on human melanoma cells in culture involving: a. alpha-MSH radio-binding assays and b. tyrosinase assay. Our results so far show 1) increased alpha-MSH levels in melanoma patients' plasma, alpha-MSH responsiveness to UVA stimulated skin, large immunoreactive alpha-MSH content in melanoma metastases and an alpha-MSH circadian rhythm in some individuals different from cortisol; 2) alpha-MSH receptor expression in melanoma cells could be increased by various effectors able to stimulate melanogenesis.

Aged↗

Production of interleukin 1 by activated blood monocytes and alveolar macrophages from melanoma patients.

The production of Interleukin 1 (Il1) by circulating blood monocytes and alveolar macrophages was studied in melanoma patients. There were 144 patients in the monocytes study and 5 patients in the alveolar macrophages study. The Il1 activity was tested by a bioassay and reported in units based on the integration of the area under the curve. This was shown to be preferable to the standard method, i.e. probit analysis. Results showed that there was no depression of Il1 activity in melanoma patients as compared to control (98 + 32 units, versus 100 units). There was no difference when the values were compared according to sex, age and stage of the disease. However, a significant difference was found between phototype I and phototype IV. Alveolar macrophages, in all experiments (n = 5), had a significantly lower Il1 activity than the autologous monocytes. It is concluded that we can question the relevance of Il1 production by peripheral blood monocytes to the state of the immunity of melanoma patients.

Adult↗

[Autoimmune hemolytic anemia followed by acute granulocytic leukemia (author's transl)].

The authors report a case of acute myeloid leukemia developing 5 years after the onset of an autoimmune hemolytic anemia. The cytological origin of the proliferation is difficult to assess: the presence of prominent membranous complexes and a strong positivity of acid phosphatase reaction favour its megacaryocytic origin. However the cytological evolution pleads for the development of successive clones of monocytic origin, may be modified by the treatment. Are the two diseases successive consequences of preexisting state of immunodepression or was such a state created by the autoimmune anemia?

Aged↗

Monoclonal antibodies to human melanoma associated antigens: study of their specificity and visualization at the cellular level of the antigenic distribution.

Six monoclonal antibodies(Mabs) including 4 anti-melanoma, one anti-glioma, and one anti-HLA-DR have been tested in a 125I-protein A antibody binding assay using a panel of 34 different cell lines. This panel included 19 melanomas from different clinical and geographical origins, 10 fibroblast lines out of which 9 were established from melanoma patients, 2 glial cell lines, 1 osteosarcoma, 1 teratocarcinoma, and 1 murine melanoma. The reactivity pattern of the 4 anti-melanoma Mabs showed that they were not directed against antigens strictly restricted to melanoma, but rather against antigenic structures preferentially expressed on melanoma cells. These Mabs were found to crossreact with gliomas, thus they seem to recognize neuroectoderm associated differentiation antigens. The high crossreactivity of the anti-glioma Mab for melanoma was confirmed in this study. As expected from the literature, HLA-DR antigens were found to be expressed on more than 50% of the melanoma lines tested. The cellular distribution of the antigens recognized by two anti-melanoma Mabs on melanoma cells could be visualized by an autoradiographic procedure. From the labeling pattern it was concluded that only a proportion of the cells, varying from 13 to 38%, expressed the relevant antigen.

Antibodies, Monoclonal↗

Electrospray mass spectrometric analysis of new alpha-MSH analogues carrying nitrogen mustard at their amino terminus.

Two different chlorinated drugs, chlorambucil and melphalan, have been linked to the carrier alpha-melanocyte-stimulating hormone at the end of the solid-phase peptide synthesis of the hormone. The [Nle4, D-Phe7] and the [Nle4, L-Phe7] derivatives of the hormone have both been used. It was found by electrospray mass spectrometric analysis that the products undergo hydrolysis of the chlorinated moiety of the drugs, most likely due to the acidic conditions necessary for cleavage of the peptide from the resin. Only the melphalan-O(ethyl)-N(succinyl)-derivative of alpha-melanocyte-stimulating hormone [Nle4, L-Phe7] did not show a bis-hydroxylated form. It was proven by blank experiments with commercially available melphalan that this mustard occurs for some 45%-50% in the mono-hydroxylated form, which is known to be pharmacologically poorly active.

Amino Acid Sequence↗