OBJECTIVE AND DESIGN: Treatment of human immunodeficiency virus (HIV)-infected women with the highly active antiretroviral therapy (HAART) has reduced the onset of uterine cervical intraepithelial neoplasia (CIN), and halted its progression to cervical carcinoma. We and others demonstrated that the HIV protease inhibitors (HIV-PIs) used in HAART can exert direct antitumour activities also in HIV-free preclinical or clinical models. As uterine cervical carcinoma is a leading cause of death in women independently of HIV infection, herein we assessed the impact of therapeutic concentrations of HIV-PIs including indinavir (IDV), saquinavir (SQV) or ritonavir (RTV) on cells obtained from CIN or cervical carcinoma lesions of HIV-negative women. METHODS: HIV-PI effects were evaluated by cell invasion, growth or toxicity assays, and by RNA, protein or zymogram analyses. RESULTS: Both SQV and RTV inhibited CIN cell invasion, and this was paralleled by a reduced expression and proteolytic activity of the matrix metalloproteinase (MMP)-2 and 9 in treated cells. SQV and RTV also reduced CIN cell growth rate, but did not affect the invasion or growth of cells derived from highly progressed cervical carcinoma. CONCLUSION: As MMP-2 and MMP-9 have a key role in CIN evolution into cervical carcinoma, these results support the use of SQV or RTV for the block of CIN clinical progression in either HIV-infected or uninfected patients.
OBJECTIVE AND DESIGN: Treatment of human immunodeficiency virus (HIV)-infectedwomen with the highly active antiretroviral therapy (HAART) has reduced the onset of uterine cervical intraepithelial neoplasia (CIN), and halted its progression to cervical carcinoma. We and others demonstrated that the HIV protease inhibitors (HIV-PIs) used in HAART can exert direct antitumour activities also in HIV-free preclinical or clinical models. As uterine cervical carcinoma is a leading cause of death in women independently of HIV infection, herein we assessed the impact of therapeutic concentrations of HIV-PIs including indinavir (IDV), saquinavir (SQV) or ritonavir (RTV) on cells obtained from CIN or cervical carcinoma lesions of HIV-negative women. METHODS:HIV-PI effects were evaluated by cell invasion, growth or toxicity assays, and by RNA, protein or zymogram analyses. RESULTS: Both SQV and RTV inhibited CIN cell invasion, and this was paralleled by a reduced expression and proteolytic activity of the matrix metalloproteinase (MMP)-2 and 9 in treated cells. SQV and RTV also reduced CIN cell growth rate, but did not affect the invasion or growth of cells derived from highly progressed cervical carcinoma. CONCLUSION: As MMP-2 and MMP-9 have a key role in CIN evolution into cervical carcinoma, these results support the use of SQV or RTV for the block of CIN clinical progression in either HIV-infected or uninfected patients.
Authors: Pamela A Mbang; Marc A Kowalkowski; E Susan Amirian; Thomas P Giordano; Peter A Richardson; Christine M Hartman; Elizabeth Y Chiao Journal: PLoS One Date: 2015-12-02 Impact factor: 3.240
Authors: Richard E Kast; John A Boockvar; Ansgar Brüning; Francesco Cappello; Wen-Wei Chang; Boris Cvek; Q Ping Dou; Alfonso Duenas-Gonzalez; Thomas Efferth; Daniele Focosi; Seyed H Ghaffari; Georg Karpel-Massler; Kirsi Ketola; Alireza Khoshnevisan; Daniel Keizman; Nicolas Magné; Christine Marosi; Kerrie McDonald; Miguel Muñoz; Ameya Paranjpe; Mohammad H Pourgholami; Iacopo Sardi; Avishay Sella; Kalkunte S Srivenugopal; Marco Tuccori; Weiguang Wang; Christian R Wirtz; Marc-Eric Halatsch Journal: Oncotarget Date: 2013-04
Authors: Lynne Hampson; Innocent O Maranga; Millicent S Masinde; Anthony W Oliver; Gavin Batman; Xiaotong He; Minaxi Desai; Parmenas M Okemwa; Helen Stringfellow; Pierre Martin-Hirsch; Alex M Mwaniki; Peter Gichangi; Ian N Hampson Journal: PLoS One Date: 2016-01-29 Impact factor: 3.240