C.M. Farber

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.

Metalloproteinases and TIMPs production by AIDS-Kaposi sarcoma derived cells

ABSTRACT Kaposis Sarcoma is the most common malignancy in HIV infected patients. The origin of the main cells involved (spindle-like cells) is controversial: many believe in its endothelial origin. We developped cultures of Kaposis sarcoma biopsies and used immunofluorescence techniques to try to establish their origin. Since metalloproteinases are involved in cellular invasiveness, we have studied the metalloproteinases / Tissue Inhibitors of metalloproteinases ratio in the supernatant of the cells after different treatment by different factors: Tumor Necrosis Factor α, Interferon α, forskolin and Phorbol Myristate Acetate

Faux négatif de la tomographie par émission de positrons dans le diagnostic d'un lymphome primitif du système nerveux central

Summary We report the case of an AIDS patient with a biopsy-proven primary CNS lymphoma who presented a solitary lesion of the brain which was hypometabolic on PET but with a high number of EBV genome copies in his cerebrospinal fluid (CSF). Considering the contradiction between EBV, PCR, and PET, a brain biopsy was carried out. Histological analysis of the lesion revealed an extensively necrotic intermediate grade immunocytoma of the brain. The importance of the necrosis offered a possible explanation for the hypometabolic activity of the lesion on PET. We disagree with a recent publication and conclude that the hypometabolic activity of a brain lesion does not rule out the diagnosis of lymphoma.