Inhaled cidofovir as an adjuvant therapy for recurrent respiratory papillomatosis.
ABSTRACT A previously healthy, full-term, 4-month-old boy presented with progressively weakening cry, hoarseness, and increased work of breathing. Flexible fiberoptic laryngoscopy revealed glottic papillomas, which were endoscopically removed with a microdebrider in the operating room (Derkay score 23). The patient was diagnosed with recurrent respiratory papillomatosis that disseminated throughout his airway. Despite biweekly serial microdebridements, intralesional cidofovir, and systemic interferon-α, the patient's health declined substantially (Derkay score 40), culminating in a 47-day hospitalization due to complications of his disease. Inhaled cidofovir was initiated after all conventional treatments had failed. Within 6 weeks of therapy (40 mg daily per treatment, 12 days on and 2 days off), the papillomatous disease improved substantially (Derkay score 23). While inhaled cidofovir appeared to significantly reduce papillomatous disease burden in this patient, further investigation into its long-term effectiveness and safety profile is necessary.
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ABSTRACT: Insights into the mechanisms associated with chemotherapy-resistance are important for implementation of therapeutic strategies and for unraveling the mode of action of chemotherapeutics. Although cidofovir (CDV) has proven efficacious in the treatment of human papillomavirus (HPV)-induced proliferation, no studies concerning the development of resistance to CDV in HPV-positive tumor cells have been performed yet. From the cervical carcinoma SiHa cells (SiHaparental), which are HPV-16 positive, cidofovir-resistant cells (SiHaCDV) were selected, and differential gene expression profiles were analyzed by means of microarrays. We examined in vitro phenotyping of resistant cells compared to parental cells as well as tumorigenicity and pathogenicity in a mouse-xenograft model. SiHaCDV had a resistant phenotype and a reduced growth both in vitro and in vivo. A markedly diminished inflammatory response (as measured by production of host- and tumor-derived cytokines and number of neutrophils and macrophages in spleen) was induced by SiHaCDV than by SiHaparental in the xenograft model. Gene expression profiling identified several genes with differential expression upon acquisition of CDV-resistance and pointed to a diminished induction of inflammatory response in SiHaCDV compared to SiHaparental. Our results indicate that acquisition of resistance to cidofovir in SiHa cells is linked to reduced pathogenicity. The present study contributes to our understanding on the antiproliferative effects of CDV and on the mechanisms involved, the inflammatory response playing a central role.Molecular Cancer 12/2013; 12(1):158. · 5.40 Impact Factor
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ABSTRACT: Recurrent respiratory papillomatosis or recurrent laryngeal papillomatosis is a disease of the larynx caused by human papilloma virus, characterized by verrucous epithelial lesions and usually recurring. In the literature there are several types of treatment, such as surgery to cold, laser and/or use of microdebrider, as of adjuvant therapies; all possible to decrease the permanent sequelae of the disease. To review the literature regarding this disease with emphasis on surgical techniques and adjuvant therapies used today. We used the literature review, through surveys based electronic data in the public domain, to search for articles between 1992-2012, using keywords: papilloma, human pappiloma virus infection, larynx, therapeutic, papilloma virus vaccine. We surveyed 357 articles, of which 49 were used as the basis for this review. Scientific studies indicate a reduction of relapse in most adjuvant therapeutic presented. However, the survey showed different methodologies and samples, which did not allow to compare the types of treatment and adjuvant therapies. The choice of surgical technique varies among studies, but there is a trend to use the microdebrider. The newer adjuvant therapies, such as cidofovir, quadrivalent vaccine against human papilloma virus and bevacizumab, require further studies.Brazilian journal of otorhinolaryngology 10/2013; 79(5):636-642. · 0.55 Impact Factor
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ABSTRACT: Acyclic nucleoside phosphonates (ANPs) are well-known for their antiviral properties, three of them being approved for the treatment of human immunodeficiency virus infection (tenofovir), chronic hepatitis B (tenofovir and adefovir) or human cytomegalovirus retinitis (cidofovir). In addition, cidofovir is mostly used off-label for the treatment of infections caused by several DNA viruses other than cytomegalovirus, including papilloma- and polyomaviruses, which do not encode their own DNA polymerases. There is considerable interest in understanding why cidofovir is effective against these small DNA tumor viruses. Considering that papilloma- and polyomaviruses cause diseases associated either with productive infection (characterized by high production of infectious virus) or transformation (where only a limited number of viral proteins are expressed without synthesis of viral particles), it can be envisaged that cidofovir may act as antiviral and/or antiproliferative agent. The aim of this review is to discuss the advances in recent years in understanding the mode of action of ANPs as antiproliferative agents, given the fact that current data suggest that their use can be extended to the treatment of non-viral related malignancies.Antiviral Research 10/2014; 114. · 3.43 Impact Factor
Jeremy D Prager