T. Simonart

Constitutive release of metalloproteinase-9 (92-kd type IV collagenase) by Kaposi's sarcoma cells

Kaposis sarcoma (KS) is an angioproliferative disease characterized by proliferating spindle-shaped cells, angiogenesis, and inflammatory cell infiltration. Several lines of evidence suggest that KS is a multifocal cytokine-mediated disease of vascular origin. Because metalloproteinases (MMPs) are important enzymes involved in angiogenesis, we studied their activity in five different KS-derived cell lines and compared these data with those obtained with human umbilical vein endothelial cells (HUVEC). We focused on the activity of the 72- and 92-kd type IV collagenases because these enzymes are thought to play an important role in the process of tumoral invasion. Nonstimulated HUVEC released a weak 72-kd collagenase activity and no 92-kd collagenase activity, as determined by zymographic analysis. Stimulation of HUVEC with phorbol myristate acetate (PMA) or TNF-alpha increased the 72-kd collagenase activity and also induced a 92-kd collagenase activity. By contrast, KS-derived cells constitutively released significant 72- and 92-kd collagenase activities. The basal release of these enzymes by KS cells was further enhanced by TNF-alpha or PMA. Conversely after in vivo exposure to chemotherapy, KS-derived cells showed a downregulation of the production of MMPS that could be reversed by the addition of TNF or PMA. These results suggest that KS cells have constitutive features of activated cells that have an invasive and metastasizing potential.

p53 protein overexpression is a common but late event in the pathogenesis of iatrogenic and AIDS-related Kaposi’s sarcoma

Kaposi’s sarcoma (KS) is characterized by microvascular proliferation (angiogenesis) in the initial stage of lesion development that is soon followed by the proliferation of spindle-shaped cells which are considered to be the KS ‘tumor’ cells [1]. Despite intensive research over the past few years, the pathogenesis of KS remains unclear, and it is not known whether KS is a true neoplasm, since it shows multicentric origin, frequent regression and normal karyotypes. The latest hypotheses suggest that KS results from a multistep pathway involving cytokine dysregulation, the presence of HIV and/or human herpesvirus 8, overexpression of integrins and resistance to apoptosis [2–6]. Recently, one of the best known proteins involved in the regulation of cell growth, the p53 protein, has been suggested to play a role in the pathogenesis of KS. Indeed, mutations of the p53 gene have been detected in up to 29% of KS [7]. The loss of p53 function, by allelic loss or by mutations of its corresponding gene, has been shown to result in increased cell proliferation or in defective apoptosis in numerous human cancers [8]. In this study, we investigated iatrogenic and AIDS-related KS for the presence of p53 alterations in correlation with the different progressive histological stages (patch, plaque and nodular). Routinely processed, formalin-fixed and paraffin-embedded tissue samples of KS were obtained from patients with AIDS (n = 37) and from renal transplant recipients receiving immunosuppressive therapy (n = 6). All samples were classified according to their histological stage, as described elsewhere [1] (patch stage, 17 cases; plaque or nodular stages, 26 cases). p53 accumulation was detected immunohistochemically with the monoclonal antibody DO7 (Dako, Glostrup, Denmark) which recognizes both wild-type and mutant p53 [9]. Immunohistochemistry was performed using the antigen retrieval method as previously described [10]. All the 26 plaque or nodular stage KS samples (‘late KS’) displayed p53 immunoreactivity (100%) whereas only three patch stage KS (‘early KS’) showed p53 imJ.-C. Noel · F. De Thier · Th. Simonart · J. Andre · P. Hermans · J. P. Van Vooren · M. Heenen

Treatment of Kaposi's sarcoma with human chorionic gonadotropin.

Clinical-grade preparations of human chorionic gonadotropin (hCG) have been shown to be toxic to Kaposi’s sarcoma (KS) cells. However, the mechanism of the anti-KS activity achieved with these preparations remains unclear. The results of clinical studies using commercial hCG preparations in human KS are also highly contradictory. The apparent controversy between different studies may be due to the fact that pro- and anti-KS components are present in varying proportions in different hCG preparations. As certain hCG preparations could not only lack the ability to control KS but also contain some contaminant KS growth factor(s), we suggest a cautious use of crude hCG for the treatment of KS.

Phenotypic characteristics of Kaposi's sarcoma tumour cells derived from patch-, plaque- and nodular-stage lesions: analysis of cell cultures isolated from AIDS and non-AIDS patients and review of the literature: KAPOSI's SARCOMA PHENOTYPE

Background  Kaposis sarcoma (KS) is commonly thought to be derived from endothelial cells because of the predominant expression of endothelial markers in KS lesions. However, the heterogeneity of the spindle‐cell compartment makes the precise lineage relationship of KS tumour cells unclear. Cultured KS‐derived spindle cells constitutively overexpress antiapoptotic proteins and exhibit invasive properties, which suggests that they may adequately represent the tumour cells of KS. Objectives We aimed to investigate the expression of a wide variety of immunohistochemical markers by spindle cells derived from patch‐, plaque‐ and nodular‐stage lesions from patients with iatrogenic, sporadic and acquired immune deficiency syndrome‐related KS, and to review the data reported by other laboratories. Methods Cells from six KS cell cultures derived from four subjects were examined by immunostaining. Results Comparison of these data indicates that KS‐derived spindle cells generally express myofibroblast antigens but lack endothelial and/or leucocyte markers. Conclusions As the myofibroblast phenotype is not the predominant feature of KS tissues, our findings further substantiate the view that the in vivo dominant endothelial population represents a reactive hyperplasia rather than the true KS tumour process.

Enhancement of classic Kaposi's sarcoma growth after intralesional injections of desferrioxamine

We have previously shown that iron may be involved in the pathogenesis of Kaposi’s sarcoma (KS) and that the iron chelator desferrioxamine (DFO) inhibits the growth and induces the apoptosis of KS cells in vitro. We treated an 85-year-old man with classic KS with 5 weekly intralesional injections of DFO and observed the opposite effect in vivo. The DFO-treated lesion was characterised by the development of numerous KS papules within the drug diffusion area, whereas no change was noted in untreated or control saline-treated lesions. This suggests that intralesional iron chelators are not indicated in patients with KS.

Hepatitis C virus is not a cofactor for Kaposi's sarcoma development in HIV-infected patients.

professionals are constantly exposed to sensitizers, such as hair dyes, fragrances, ammonium persulfate, preservatives, and irritant substances. The education of hair professionals on safe practices and the application of low irritant moisturizing creams before and after work improve this condition. Moreover, a recent epidemiologic study suggested that subjects who worked as hairdressers for 10 years or more experienced a fivefold increased risk of bladder cancer. Interdigital trichogranulomas are the result of penetration of the skin by short, sharp, hair clippings. They are the result of a foreign body reaction to the presence of hair keratin in the dermis. Multiple interdigital trichogranulomas are unusual. Trichogranulomas may also occur subungually. Hogan reported a case of subungual trichogranuloma in a hairdresser with psoriatic onycholysis. Onycholysis may be a risk factor for cut hairs embedded subungually. Trichogranulomas, once developed, are difficult to manage. Training and prevention are the best approach to the management of this disorder.