AIDS-related Kaposi's Sarcoma Lesions Research Articles

Sialoadhesin (CD169) Expression in CD14+ Cells Is Upregulated Early after HIV-1 Infection and Increases during Disease Progression

BackgroundSialoadhesin (CD169, siglec-1 or Sn) is an activation marker seen on macrophages in chronic inflammatory diseases and in tumours, and on subsets of tissue macrophages. CD169 is highly expressed by macrophages present in AIDS-related Kaposi's sarcoma lesions. It is also increased on blood monocytes of HIV-1 infected patients with a high viral load despite antiretroviral treatment.Methodology/Principal FindingsWe investigated expression of sialoadhesin in untreated HIV-1 and HHV-8 infected patients, by real-time PCR and FACS analysis to establish its expression in relation to infection and disease progression. Patients analysed were either HIV-1 seroconverters (n = 7), in the chronic phase of HIV-1 infection (n = 21), or in the AIDS stage (n = 58). Controls were HHV-8 infected, but otherwise healthy individuals (n = 20), and uninfected men having sex with men (n = 24). Sialoadhesin mRNA was significantly elevated after HIV-1, but not HHV-8 infection, and a further increase was seen in AIDS patients. Samples obtained around HIV-1 seroconversion indicated that sialoadhesin levels go up early in infection. FACS analysis of PBMCs showed that sialoadhesin protein was expressed at high levels by approximately 90% of CD14+ and CD14+CD16+cells of HIV-1+ patients with a concomitant 10-fold increase in sialoadhesin protein/cell compared with uninfected controls.Conclusions/SignificanceWe have shown that sialoadhesin is induced to high levels on CD14+ cells early after HIV-1 infection in vivo. The phenotype of the cells is maintained during disease progression, suggesting that it could serve as a marker for infection and probably contributes to the severe dysregulation of the immune system seen in AIDS.

Sustained angiogenesis enables in vivo transplantation of mucocutaneous derived AIDS-related Kaposi's sarcoma cells in murine hosts.

AIDS-related Kaposi's sarcoma (AIDS-KS), the most prevalent HIV-associated malignancy, is a debilitating, potentially fatal disease. Currently, there is a need for development of AIDS-KS therapies that are not only well tolerated, but also capable of providing sustained remission. Preclinical assessment of pharmacological parameters and therapeutic efficacies are dependent upon in vivo parameters. However, there are currently no animal KS models and mucocutaneous KS cell isolates have proved to be non-tumorigenic in animal hosts. This report describes the development of a murine model that enables in vivo transplantation of 'native' low population doubling level AIDS-KS cells from biopsy-confirmed mucocutaneous lesions. The angiogenic phenotype of in situ AIDS-KS lesions is reconstituted via controlled release of a complete angiogenic peptide, recombinant human basic fibroblast growth factor (bFGF), from locally injectable, biodegradable polylactide-co-glycolide implants. Consequential to the sustained local release of bioactive bFGF, a murine vascular network is established, which facilitates the in vivo transplantation of AIDS-KS cells. Desirable aspects of this model include: low cost murine species, transplantation of non-selected patient cells and use of animal hosts that are T cell-deficient. The transplanted human AIDS-KS cells and extensive murine vascular network create lesions that retain a striking resemblance, at both the gross and microscopic levels, to in situ AIDS-KS tumors. Because the bFGF-induced murine vascular network is analogous to the abundant vascularity present in AIDS-KS lesions, this murine model should provide an excellent vehicle for numerous clinically relevant studies, such as assessment of drug clearance at AIDS-KS lesional sites. Finally, applicability of this method is not restricted to AIDS-related malignancies. Establishment and maintenance of an extensive host vascular network should augment success rates for in vivo transplantation of numerous other human cell strains or lines.

Management of ulcerated AIDS-related Kaposi's sarcoma lesions

Management of ulcerated AIDS-related Kaposi's sarcoma lesions

The infra-red coagulator in the treatment of AIDS-related Kaposi's sarcoma and a comparison with radiotherapy

Experience with 1 s pulses of the infra-red coagulator is reported for the treatment of 10 cutaneous AIDS-related Kaposi's sarcoma lesions in seven patients. The infra-red coagulator may be a useful addition in the palliative cosmetic treatment of Kaposi's sarcoma, producing an acceptable result in small (less than 2 cm in diameter) Kaposi's sarcoma lesions of the arms and trunk, but not in those situated on the legs.