Eighty-nine tissue specimens from the urinary tract and prostate were analyzed for the presence and physical state of BK virus (BKV) DNA. Large T antigen gene sequences were amplified by PCR from prostate, kidney, ureter, and bladder with prevalences ranging from 50 to 83%. Sequence analysis of PCR products from the high variable BKV regulatory region showed that these tissues contained a new BKV strain (URO1). URO1 presents a duplication of part of the 68- and 39-bp elements of the viral enhancer, and a 68-bp deletion spanning part of the 39- and 63-bp enhancer elements. Six neoplastic specimens (11.5%), but none of the control tissues, contained viral DNA in amounts detectable by Southern blot hybridization (P < 0.05). The tumors positive by Southern blot hybridization harbored rearranged and/or integrated DNA sequences whose size was apparently incompatible with assembly into a viral particle. A full-length, macroscopically intact BKV early region was amplified from these tumors by PCR. The restriction pattern of the rearranged sequences was simple, suggesting that tumors were clonal and that DNA rearrangement occurred at an early stage of neoplastic initiation or progression.
In this study the prevalence of human herpesvirus (HHV) 8 DNA was determined in biopsies from persons with lymphoproliferative disorders and in peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-seronegative and HIV-infected persons. The results show that HHV-8 is present in 10% of biopsies from HIV-seronegative persons: HHV-8 is detected with similar prevalence values in HIV-infected patients with lymphoproliferative diseases, but the virus load is higher. HHV-8 was also found in PBMC. The presence of monoclonal Epstein-Barr virus (EBV) genomes in malignant lymphoproliferations was only infrequently associated with HHV-8 infection. Therefore, HHV-8 is fairly common in the population, and the lymphoid system could represent a reservoir of latently infected cells from which the virus may reactivate in conditions of immunodepression; furthermore, HHV-8 and EBV do not seem to act in conjunction in lymphomagenesis.
BackgroundPancreatic cancer (PC) is the fourth most common cause of cancer death. Combination therapies with classical chemotherapeutic agents improved treatment of advanced PC at the cost of a relevant toxicity, but the 5-year survival rate remains below 5%. Consequently, new therapeutic options for this disease are urgently needed. In this study, we explored the effect of two repurposed drug candidates nelfinavir and nitroxoline, approved for non-anticancer human use, in PC cell lines. Nelfinavir and nitroxoline were tested as single agents, or in combinations with or without erlotinib, a targeted drug approved for PC treatment.MethodsThe effects of the drugs on the viability of AsPC-1, Capan-2 and BxPC-3 PC cell lines were assessed by MTT. The impact of the treatments on cell cycle distribution and apoptosis was analyzed by flow cytometry. The effects of treatments on proteins relevant in cell cycle regulation and apoptosis were evaluated by western blot. Self-renewal capacity of PC cell lines after drug treatments was assessed using a clonogenic assay.ResultsWhen used as single agents, nelfinavir and nitroxoline decreased viability, affected cell cycle and reduced the expression of relevant cell cycle proteins. The effects on apoptosis were variable among PC cell lines. Moreover, these agents drastically impaired clonogenic activity of the three PC cell lines. Combinations of nelfinavir and nitroxoline, with or without erlotinib, resulted in dose- and cell-dependent synergistic effects on cell viability. These effects were paralleled by cell cycle alterations and more consistent apoptosis induction as compared to single agents. Treatments with drug combinations induced drastic impairment of clonogenic activity in the three cell lines.ConclusionsThis study shows that two non-antitumor drugs, nelfinavir and nitroxoline, as single agents or in combination have antitumor effects that appear comparable, or in some case more pronounced than those of erlotinib in three PC cell lines. Our results support repurposing of these approved drugs as single agents or in combination for PC treatment.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0904-2) contains supplementary material, which is available to authorized users.
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