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NY State AIDS Cancer Incidence (1981-1994) PowerPoint Presentation
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NY State AIDS Cancer Incidence (1981-1994)

NY State AIDS Cancer Incidence (1981-1994)

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NY State AIDS Cancer Incidence (1981-1994)

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  1. NY State AIDS Cancer Incidence (1981-1994) Kaposi’s sarcoma 97.5 NHL 37.4 Liver primary 5.1 Skin, non-KS 20.9 Hodgkin’s disease 8.0 Melanoma 1.4 Rectum and Anus 3.3 Cervix 9.1 Colon 0.8 Breast 0.8 Prostate 0.7 Ovary 0.8 Am J Epid 2001, 154: 544-556

  2. Herpesvirus taxonomy HVS KSHV/HHV-8  EBV HSV-1 HSV-2  VZV HHV-7  HHV-6 HCMV

  3. Detection of KSHV in Kaposi's Sarcoma Whitby et al.,JNCI, 1999

  4. SOUTH AFRICA MOTHER-TO-CHILD TRANSMISSION Age of children, years MOTHER STATUS0-4 5-9 10-14 All KSHV seropositive 29% 29% 80% 42% KSHV seronegative 0% 0% 13% 1% Bourboulia et al., JAMA 1998, 280: 31 NEJM 1999, 341:1241

  5. Cellular Homologues in the KSHV Genome Cellular proliferation v-Cyclin D v-GPCR v-IRF Apoptosis inhibitors v-bcl-2 v-FLIP v-IL-6 Chemokines v-MIP1 v-MIP2 v-MIP3 >15% of the viral genes are pirates from the eukariotic cellular DNA

  6. AIDS-associated lymphoproliferations

  7. Naïve B-cell KSHV KSHV EBV or EBV +KSHV Memory B-cell EBV MCD (KSHV) GLD (KSHV + EBV) BL (EBV) Germinal Centre PEL (KSHV) PEL (KSHV + EBV) Plasma cell PERIPHERY TONSIL EBNA-1+ LANA1+ vIL-6+ vIRF1+ EBNA2+, LMP1, 2+ LANA1+ vIL6+

  8. Reasons for Response of KS to ART ACTION MECHANISM KSHV immune reconstitution KSHV CTLs target and kill KSHV infected spindle Restoration of cellular immune response cells Reduction of HIV-1 Tat and other Cytokines involved in the stimulation of KS inflammatory cytokine levels angiogenesis (eg. bFGF) Protease inhibitor (PI) based regimens PI has been shown to block KS spindle cell growth have a direct anti-spindle cells and and KS-induced angiogenesis in experimental anti-angiogenic effect models