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- Wolmer-Solberg, N., et al.
(författare)
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Frequent detection of human cytomegalovirus in neuroblastoma: A novel therapeutic target?
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 133:10, s. 2351-2361
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma is the most common and deadly tumor of childhood, where new therapy options for patients with high-risk disease are highly warranted. Human cytomegalovirus (HCMV) is prevalent in the human population and has recently been implicated in different cancer forms where it may provide mechanisms for oncogenic transformation, oncomodulation and tumor cell immune evasion. Here we show that the majority of primary neuroblastomas and neuroblastoma cell lines are infected with HCMV. Our analysis show that HCMV immediate-early protein was expressed in 100% of 36 primary neuroblastoma samples, and HCMV late protein was expressed in 92%. However, no infectious virus was detected in primary neuroblastoma tissue extracts. Remarkably, all six human neuroblastoma cell lines investigated contained CMV DNA and expressed HCMV proteins. HCMV proteins were expressed in neuroblastoma cells expressing the proposed stem cell markers CD133 and CD44. When engrafted into NMRI nu/nu mice, human neuroblastoma cells expressed HCMV DNA, RNA and proteins but did not produce infectious virus. The HCMV-specific antiviral drug valganciclovir significantly reduced viral protein expression and cell growth both in vitro and in vivo. These findings indicate that HCMV is important for the pathogenesis of neuroblastoma and that anti-viral therapy may be a novel adjuvant treatment option for children with neuroblastoma. What's new? Relapse and invasiveness of neuroblastoma, a frequently fatal cancer of early childhood, may be linked to the presence of human cytomegalovirus (HCMV), one of the most common congenital viral infections known. In this study, HCMV was observed in primary neuroblastoma tumors and in six neuroblastoma cell lines. Although no infectious virus was isolated from tumors, the HCMV-specific drug valganciclovir significantly reduced viral protein expression and tumor cell growth both in vitro and in vivo. The results suggest that HCMV may be important in the pathogenesis of neuroblastoma and that antiviral therapy may represent a possible future treatment option for affected children. We have shown that all examined primary neuroblastoma tumors and six neuroblastoma cell lines were infected with HCMV, but no infectious virus was isolated from tumors. The HCMV-specific drug Valganciclovir significantly reduced viral protein expression and tumor cell growth in vitro and in vivo. Thus, HCMV may be important in the pathogenesis of neuroblastoma and anti-viral therapy may provide a novel treatment option for children with neuroblastoma.
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- El Serafi, Ibrahim Taher, et al.
(författare)
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Effect of interleukin-6 and insulin resistance on early virological response of Egyptian chronic hepatitis C patients to combined pegylated interferon plus ribavirin therapy
- 2013
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Ingår i: Egyptian Liver Journal. - Heidelberg, Germany : Wolters Kluwer. - 2090-6218. ; 3:2, s. 21-27
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim: Response to hepatitis C virus (HCV)-specific therapy is variable but might be influenced by host factors. We studied whether interleukin-6 (IL-6) level, IL-6–174G>C gene polymorphism, and insulin resistance affect the response to antiviral treatment in HCV-infected patients.Patients and methods: Fifty-five chronic hepatitis C patients and 13 healthy individuals as controls were included in this study. Liver function tests, HCV RNA titer, ultrasonography, and histopathological examination of liver tissues were performed for all patients. Pretreatment plasma IL-6 levels and homeostasis model assessment-insulin resistance were estimated. The IL-6–174G>C polymorphism was detected by the PCR/RFLP method. After 12 weeks of combined pegylated interferon-α and ribavirin therapy, patients were classified into responders or nonresponders according to whether they achieved an early virological response.Results: The responders had significantly high IL-6 levels (P=0.01), low mean stage of fibrosis (P=0.03), and low viral load (P=0.04) compared with nonresponders. Although not significant, patients with the IL-6–174 CC genotype reported a higher response rate (81%) compared with those with the CG genotype (50%) and GG genotype (62%). IL-6 level at a cutoff point of 2.15 pg/ml had 81.1% sensitivity and 72.7% specificity and showed significant relation with early virological response (P=0.04).Conclusion: Estimation of basal IL-6 level could be used as a predictor of response to pegylated interferon-α and ribavirin therapy in CHC patients.
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- El-Seedi, Hesham R., et al.
(författare)
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Chemical Composition and Repellency of Essential Oils From Four Medicinal Plants Against Ixodes ricinus Nymphs : (Acari Ixodidae)
- 2012
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Ingår i: Journal of medical entomology. - 0022-2585 .- 1938-2928. ; 49:5, s. 1067-1075
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Tidskriftsartikel (refereegranskat)abstract
- In our search for effective tick repellents from plant origin, we investigated the effect of essential oils of four medicinal and culinary plants belonging to the family Lamiaceae on nymphs of the tick Ixodes ricinus (L.). The essential oils of the dry leaves of Rosmarinus officinalis (Rosemary) (L.), Mentha spicata (Spearmint) (L.), Origanum majorana (Majoram) (L.), and Ocimum basilicum (Basil) (L.) were isolated by steam distillation and 15 mu g/cm(2) concentration of oils was tested against ticks in a laboratory bioassay. The oils of R. officinalis, M. spicata, and O. majorana showed strong repellency against the ticks 100, 93.2, and 84.3%, respectively, whereas O. basilicum only showed 64.5% repellency. When tested in the field, the oils of R. officinalis and M. spicata showed 68.3 and 59.4% repellency at a concentration of 6.5 mu g/cm(2) on the test cloths. The oils were analyzed by gas chromatography mass spectrometry and the major compounds from the most repellent oils were 1,8-cineole, camphor, linalool, 4-terpineol, borneol, and carvone.
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- Filippov, A., et al.
(författare)
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NMR self-diffusion study of a phosphonium bis(mandelato)borate ionic liquid
- 2013
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 15:23, s. 9281-9287
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Tidskriftsartikel (refereegranskat)abstract
- Newly synthesised halogen-free boron based ionic liquids (hf-BILs) composed of chelated orthoborate anions and phosphonium cations have hydrolytic stability, low melting point and outstanding wear and friction reducing properties. We report here the peculiarities of self-diffusion in one representative from this class, trihexyltetradecylphosphonium bis(mandelato)borate, [P6,6,6,14][BMB], in the temperature range of its practical interest, 20-100 °C. NMR techniques demonstrated complicated diffusional behaviour-the ionic liquid can exist in one or two liquid "phases". In the low-temperature range (20-50 °C), two phases coexist where the cations, [P6,6,6,14], are contained mainly in the phase with slower diffusion coefficients while the anions, [BMB], are in the phase with faster diffusion coefficients. Cations have lower diffusion coefficients with a factor of 20 as compared with the anions, an effect which is caused by aggregation of cations into domains due to so-called "hydrophobic interaction" of their hydrocarbon chains. As the temperature rises above 60 °C, the two phases merge into one where both ions have equal diffusion coefficients. This is caused by thermal motion making the cation domains smaller in size and more easily interacting with anions. As a result, anions and cations diffuse in this high-temperature range as a pair.
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- Ibrahim, G.H., et al.
(författare)
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Impact of Interleukin-28B gene polymorphism [rs12979860] on Egyptian patients infected with hepatitis C virus genotype-4
- 2013
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Ingår i: Eastern Mediterranean Health Journal. - Alexandria, Egypt : World Health Organization Regional Office for the Eastern Mediterranean (WHO/EMRO). - 1020-3397 .- 1687-1634. ; 19:Supp. 3, s. 98-104
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Tidskriftsartikel (refereegranskat)abstract
- Single nucleotide polymorphisms (SNPs) in the Interleukin (IL)-28B gene, namely rs12979860, could predict response to pegylated interferon-α-ribavirin (PR) therapy in hepatitis C virus genotype 1 (HCV-1)-infected patients. A similar role was investigated in a case-control study conducted on 93 Egyptian patients chronically infected with HCV-4 in comparison to 22 individuals with spontaneous HCV clearance and 70 healthy volunteers. The homozygous C allele genotype (CC) was associated with sustained viral response (SVR) to therapy compared with the homozygous T allele genotype (TT) and the heterozygous genotype (CT). In the SVR group, the response rate was statistically significantly higher in CC genotypes (58.6%) compared with CT/TT (20.3%). There was no correlation between SVR patients' genotypes and early response to therapy or HCV baseline viral load. Our findings describe how IL-28B SNP genotyping may guide appropriate selection of HCV-4-infected patients for PR therapy.
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- Lindblom, Rickard P. F., et al.
(författare)
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Unbiased expression mapping identifies a link between the complement and cholinergic systems in the rat central nervous system
- 2014
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 192:3, s. 1138-1153
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Tidskriftsartikel (refereegranskat)abstract
- The complement system is activated in a wide spectrum of CNS diseases and is suggested to play a role in degenerative phenomena such as elimination of synaptic terminals. Still, little is known of mechanisms regulating complement activation in the CNS. Loss of synaptic terminals in the spinal cord after an experimental nerve injury is increased in the inbred DA strain compared with the PVG strain and is associated with expression of the upstream complement components C1q and C3, in the absence of membrane attack complex activation and neutrophil infiltration. To further dissect pathways regulating complement expression, we performed genome-wide expression profiling and linkage analysis in a large F2(DA × PVG) intercross, which identified quantitative trait loci regulating expression of C1qa, C1qb, C3, and C9. Unlike C1qa, C1qb, and C9, which all displayed distinct coregulation with different cis-regulated C-type lectins, C3 was regulated in a coexpression network immediately downstream of butyrylcholinesterase. Butyrylcholinesterase hydrolyses acetylcholine, which exerts immunoregulatory effects partly through TNF-α pathways. Accordingly, increased C3, but not C1q, expression was demonstrated in rat and mouse glia following TNF-α stimulation, which was abrogated in a dose-dependent manner by acetylcholine. These findings demonstrate new pathways regulating CNS complement expression using unbiased mapping in an experimental in vivo system. A direct link between cholinergic activity and complement activation is supported by in vitro experiments. The identification of distinct pathways subjected to regulation by naturally occurring genetic variability is of relevance for the understanding of disease mechanisms in neurologic conditions characterized by neuronal injury and complement activation.
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- Torkan, Hajar, et al.
(författare)
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Positive Imagery Cognitive Bias Modification in Treatment-Seeking Patients with Major Depression in Iran : A Pilot Study
- 2014
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Ingår i: Cognitive Therapy and Research. - : SPRINGER/PLENUM PUBLISHERS. - 0147-5916 .- 1573-2819. ; 38:2, s. 132-145
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive bias modification paradigms training positive mental imagery and interpretation (imagery CBM-I) hold promise for treatment innovation in depression. However, depression is a global health problem and interventions need to translate across settings and cultures. The current pilot study investigated the impact of 1 week of daily imagery CBM-I in treatment-seeking individuals with major depression in outpatient psychiatry clinics in Iran. Further, it tested the importance of instructions to imagine the positive training materials. Finally, we examined the effects of this training on imagery vividness. Thirty-nine participants were randomly allocated to imagery CBM-I, a non-imagery control program, or a no treatment control group. Imagery CBM-I led to greater improvements in depressive symptoms, interpretive bias, and imagery vividness than either control condition at post-treatment (n = 13 per group), and improvements were maintained at 2-week follow-up (n = 8 per group). This pilot study provides first preliminary evidence that imagery CBM-I could provide positive clinical outcomes in an Iranian psychiatric setting, and further that the imagery component of the training may play a crucial role.
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