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Biomedical subjects

M Heenen

Publications and source records attributed to M Heenen.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Molecular markers associated to prognosis of melanoma].

Melanoma prognosis is based on histological criteria such as tumor thickness (measured by Breslow index), level of invasion (Clarck's level), presence of ulceration and number of mitoses per mm2. However, these parameters do not provide a precise prognosis in all cases: thin melanomas may develop metastases and thick melanomas may remain focalized for many years. For these reasons, the search for other prognostic factors is still ongoing. Many molecules play a part in the invasiveness and metastatic dissemination of melanoma have now been identified. Expression of these molecules has been studied in primary melanoma and correlated with prognosis. An increase in the number of cells positive for Ki67 (detected by Mib1), cycline A, cycline D, p35, MMp-2, beta1 and beta3 integrins, osteonectin, the presence of an intense inflammatory infiltrate and capillary invasion are considered as factors of poor prognosis as well as the decrease in p16, p27, Melan A and nm23. The significance of CD44 modifications is still controversial. Only a small number of these different proteins has a prognostic value independent of tumor thickness. These results need to be confirmed on larger series of patients. Additional hope is given to new techniques such as the analysis of the genes implied in tumor progression by microarray technique in such a way as to provide a molecular map of each tumor.

Biomarkers, Tumor↗
PubMed2002

[The dermatology department].

The department of dermatology has developed a broad clinical activity with a particular expertise in oncology, allergology, psoriasis and gynecological dermatology. Research has also been developed in these areas.

Belgium↗
PubMed2002

[Renaissance of thalidomide].

Thalidomide comes back forty years after the discovery of its teratogenicity. Due to its antiangiogenic and immunomodulating properties, thalidomide is proposed in the treatment of multiple myeloma but also in the management of erythema nodosus leprosis, cutaneous lupus erythematosus and severe aphtosis.

Humans↗
PubMed2001

Effects of antiinflammatory triterpenes isolated from Leptadenia hastata latex on keratinocyte proliferation.

Several triterpenes isolated from Leptadenia hastata latex were tested for their anti-inflammatory activity. Lupeol (1), its acetate (2) and palmitate (3) esters were found to be the main antiinflammatory constituents in the croton oil-induced ear oedema test. Furthermore, lupeol hemisuccinate (4), synthesized from lupeol, exhibited a higher activity than lupeol in the test. These results prove that the triterpenes play a pivotal role in the topical antiinflammatory effect of this latex. In addition, an in vitro model of human skin keratinocytes (epidermal explants) cultured at an air-liquid interface on a de-epidermized human dermis (DED) was used to investigate the effects of lupeol esters on skin repair in vitro. Compared with the control, compounds 2 and 3 improved keratinocyte proliferation at a concentration of 5 microM in the culture medium; however, they remained less active than compounds 1 and 4. In contrast to compound 1, all the lupeol esters (2-4), and particularly compound 4, induced a good differentiation of keratinocytes with a well-formed stratum corneum without parakeratosis. These results substantiate the topical use of Leptadenia hastata latex in traditional medicine and showed that both antiinflammatory activity and the effect on keratinocyte proliferation of compound 1 could be improved by its hemisuccinylation; on the contrary, esterification by acetylation or palmitoylation decreased these activities.

Adult↗
PubMed2001

Individual variations in the correlation between erythemal threshold, UV-induced DNA damage and sun-burn cell formation.

A linear correlation between erythema intensity and DNA damage upon exposure to UV has not been firmly established. Many of the deleterious effects of UV exposure do occur after exposure to suberythemal doses. After DNA damage, cells undergo DNA repair. It is commonly accepted that when the burden of damage is beyond the repair capacities, the cell undergoes programmed cell death or apoptosis. The aim of this study is to quantify the amount of UV-induced DNA damage (estimated via the measurement of DNA repair or unscheduled DNA synthesis or UDS) and cellular damage (estimated via the determination of the density of sunburn cells or SBC). If DNA damage and erythema are correlated, similar intensity of UDS and similar density of SBC should be found in volunteers irradiated with a UV dose equal to two minimal erythema doses (MED). Our results show that in 15 different individuals the same relative dose (2 MEDs) provokes UDS values, which vary within a factor of 4. An even larger variability affects SBC counts after the same relative dose. When DNA damage or SBC are plotted versus the absolute dose (i.e. the dose expressed in J/m(2)), there is a rough correlation (with several exceptions) between dose and extent of UDS and SBC counts. It seems possible to divide the volunteers into two subpopulations with different susceptibilities to UV damage. It is well known that UDS and SBC measurements are often affected by large experimental indeterminacy, yet, the analysis of our results makes it plausible to suggest that for the triggering of erythema, a common threshold value for DNA damage or for SBC count are not to be found. In conclusion, the erythema response seems to be loosely correlated with DNA damage. This suggests that the protection offered by the sunscreens against DNA damage, the molecular basis of UV-induced mutagenesis, might not be related to the sun protection factor (SPF) indicated on the label of sunscreens, which is evaluated using the erythema as an endpoint.

Abnormalities, Radiation-Induced↗
PubMed2001

Early- and late-stage Kaposi's sarcoma-derived cells but not activated endothelial cells can invade de-epidermized dermis.

Whether Kaposi's sarcoma is a true neoplasm or a reactive endothelial cell outgrowth triggered by inflammatory cytokines remains unclear. In this study, we investigated the differential invasive properties of activated endothelial cells and Kaposi's sarcoma cells in a model of de-epidermized dermis, supplying the cells with matrix barriers similar to those found in vivo. Cells derived from early "patch-stage" and from late "nodular-stage" Kaposi's sarcoma lesions exhibited similar invasive properties, which indicates that cells with an invasive potential are present in the early stages of tumor development. Slow accumulation of the cells into the extracellular matrix, together with a low proliferation index and with expression of anti-apoptotic proteins, suggest that the progression of Kaposi's sarcoma may be related to escape from cell death rather than to increased proliferation. The Kaposi's sarcoma-Y1 cell line, which is tumorigenic in nude mice, also exhibited invasive properties. By contrast to the Kaposi's sarcoma-derived spindle cells, however, which were scattered between the collagen bundles, the Kaposi's sarcoma-Y1 cell population had a higher proliferation index and displayed a multilayer arrangement. Inflammatory cytokines and Kaposi's sarcoma cell supernatant could activate and stimulate the growth of human dermal microvascular endothelial cell, but could not induce their invasion in this model, showing that activated endothelial cells do not fit all the requirements to traverse the various barriers found in the dermal extracellular matrix. These results confer to Kaposi's sarcoma cells a tumor phenotype and suggest that the in vivo dominant endothelial cell population represents a reactive hyperplasia rather than the true tumor process.

Cell Division↗
PubMed2001

Iron induces Bcl-2 expression in human dermal microvascular endothelial cells.

Iron is suspected to be involved in the induction and/or progression of various human tumors. The present study was designed to investigate the effects of iron on endothelial cells, keeping in mind that the homeostasis of microvessels plays a critical role in neo-angiogenesis. Applying a model of human dermal microvascular endothelial cell terminal differentiation and death induced by serum deprivation, we found that iron salts (iron chloride and ferric nitrilotriacetate) provided a survival advantage to endothelial cells. Using immunohistochemistry and Western Blot analysis, we found that the extended cellular life span induced by iron was paralleled by an increase of Bcl-2 protein expression. Taken together, these observations suggest that iron may give a survival advantage to endothelial cells and represent a novel mechanism through which iron may contribute to tumorigenesis.

Cell Line↗
PubMed2001

Value of standard laboratory tests for the early recognition of group A beta-hemolytic streptococcal necrotizing fasciitis.

The laboratory data for 17 patients with group A beta-hemolytic streptococcal necrotizing fasciitis (GAS NF) were compared with data for 145 patients hospitalized for cellulitis during the same period. Admission values of C-reactive protein and creatine kinase were higher for patients in the group with GAS NF than for patients in the group with cellulitis (P<.001), suggesting that standard laboratory tests may be useful for the early differential diagnosis of GAS NF and cellulitis.

Adolescent↗
PubMed2001

Treatment of idiopathic palmar hyperhidrosis with botulinum toxin. Report of 23 cases and review of the literature.

BACKGROUND: Botulinum toxin represents a novel therapeutic option for idiopathic palmar hyperhidrosis. However, so far there is no consensus on the way to administer botulinum toxin in this indication. Moreover, its use is limited by severe pain during the injections, especially with subepidermal injections close to 'free nerve endings'. OBJECTIVES: To analyze the effectiveness and tolerability of intracutaneous injections of botulinum toxin after nerve blocks and to review the techniques of injections and the results reported by other groups. METHODS: Twenty-three adult patients with refractory palmar hyperhidrosis were treated with intracutaneous injections of botulinum toxin after ulnar and median nerve blocks. Patients were followed up on a monthly basis. RESULTS: In all patients botulinum toxin abolished sweating in the injected areas within 1 week. Anhidrosis lasted for 4-13 months. The intensity of pain was rated as absent (n = 13), mild (n = 8) or moderate (n = 2). Other side effects included hematoma (n = 2) and pain consecutive to nerve block (n = 1). DISCUSSION: Intracutaneous injections of botulinum toxin after median and ulnar nerve block represent an effective and mildly painful technique to treat palmar hyperhidrosis and may be as safe as subepidermal injections.

Adolescent↗
PubMed2000

Iron chelators inhibit the growth and induce the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors.

Iron is suspected to be involved in the induction and/or progression of various human tumors. More particularly, iron may be involved in the pathogenesis of Kaposi's sarcoma, a tumor of probable vascular origin. This study was designed to investigate the effect of iron deprivation on Kaposi's sarcoma. The effects of iron chelators and iron deprivation associated with serum withdrawal were investigated on Kaposi's sarcoma-derived spindle cells, on a transformed Kaposi's sarcoma cell line (Kaposi's sarcoma Y-1) and on endothelial cells, which are the probable progenitors of Kaposi's sarcoma cells. Desferrioxamine and deferiprone, two chemically unrelated iron chelators, induced a time- and concentration-dependent inhibition of endothelial and Kaposi's sarcoma cell growth. The inhibition of cell growth was associated with a decrease in Ki-67 and in both stable and total proliferating cell nuclear antigen expression. Inhibition of the progression through the G1-phase of the cell cycle was further evidenced by decreased expression of cyclin D1 and of p34 cyclin-dependent kinase 4. Terminal deoxynucleotidyl transferase-mediated desoxyuridinetriphosphate nick end labeling assay, flow cytometry with annexin-V-fluorescein and morphologic analysis indicated that iron chelation also induced a time- and concentration-dependent apoptosis. This apoptotic effect was prevented by the addition of exogenous iron. Induction of iron deprivation in the culture medium by serum withdrawal led to similar cell cycle effects, which, however, could only be partly reverted by the addition of exogenous iron. In conclusion, these results show that iron deprivation inhibits the growth and induces the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors. This suggests that iron chelators may represent a potential therapeutic approach for the treatment of Kaposi's sarcoma.

Apoptosis↗
PubMed2000

Role of iron in dermatology.

Iron is involved in several biological reactions and is essential to almost all forms of life. In contrast, iron is potentially toxic. It may participate in many dermatological disorders, including pigmentation changes, inflammation, porphyrias, infections and cancers. The involvement of iron in these disorders entails a variety of mechanisms, including among others simple deposition processes, activation or inactivation of enzymatic systems, impairment of phagocyte functions and interference with apoptosis. A better understanding of the role of iron might provide novel therapeutic strategies based on iron-chelating and/or anti-oxidant agents.

Humans↗
PubMed2000

Apoptosis in established and healing psoriasis.

BACKGROUND: Previous studies have described apoptosis in the stratum granulosum and in the stratum corneum, but not in the germinative compartment in normal skin. In psoriasis, an increased epidermal apoptosis has been observed in the differentiated compartment, suggesting that apoptosis has a key role in the pathogenesis of psoriasis, as a counteracting factor to the overproduction of cells. Little is known on apoptosis in the germinative compartment. METHODS: Apoptosis was studied on biopsies of normal skin, established lesions of psoriasis and PUVA-treated psoriasis using the transferase-mediated uridine nick end labelling method, which detects fragmented DNA, and electron microscopy. Counting of apoptotic cells was restricted to the germinative compartment as defined by Mib1 staining to evaluate the impact of cell loss on cell production and tissue architecture. RESULTS: The apoptotic index was 0.12% in normal epidermis, 0.035% in established psoriasis and 0.31% in regressive psoriasis. CONCLUSION: These results have three implications: (1) they show the physiological presence of apoptosis in the germinative compartment in normal epidermis; (2) they suggest that induction of apoptosis is involved in the regression of psoriatic hyperplasia after PUVA therapy; (3) the decrease of physiological apoptosis in the psoriatic lesion suggests that this phenomenon could play a role in the induction of psoriatic hyperplasia.

Apoptosis↗
PubMed1999

Cyclosporin in atopic dermatitis: review of the literature and outline of a Belgian consensus.

This paper reflects the consensus reached among Belgian professors of dermatology on the place of cyclosporin (CsA) in the treatment of atopic dermatitis (AD). Existing therapeutic modalities and ways to evaluate efficacy of treatment are reviewed briefly. Based on data from the literature and personal experience, guidelines for the use of CsA in AD are proposed. CsA can be prescribed in recalcitrant cases of AD on a short-term basis, both in adults and children. Long-term treatment, up to 1 year, should be considered only in exceptional cases that cannot be controlled by short-time therapy. Contraindications, drug interactions and necessary controls during treatment are also discussed.

Cyclosporine↗
PubMed1999

[Photoprotection, cancer protection and solar protection factor].

Sun protection factor of sunscreens is assessed by their ability to inhibit UV-induced erythema. A correlation between sun sensitivity and density of DNA damage has been established. However the ability of suberythematous irradiation to induce DNA damage suggests that this correlation is not linear. Therefore, exposure to sunrays, extended because of a delayed erythema, can lead to more DNA damage than it is usually believed. The danger of long term of sunscreens use is therefore real, more especially as they may offer different protection factors for different biological end-points.

DNA Damage↗