Human papillomavirus infection in urine samples from male renal transplant patients.

Renal allograft recipients have a well-documented increased incidence of human papillomavirus (HPV)-related malignancies and preventive strategies should be specifically implemented. While in females the use of the Papanicolau test and HPV detection assay are used currently as a screening test for cervical cancer, no diagnostic procedures have been implemented to monitor HPV infection in males. The aim of this study was to test for HPV infection and to determine the spectrum of viral genotypes in urine samples of men with renal transplants. The study included 88 patients who underwent kidney transplantation between 1999 and 2005. HPV sequences were detected by nested PCR, using the broad-spectrum consensus-primer pairs MY09/MY11 and the new MGP system, and characterized by nucleotide sequence analysis. Overall, 43 (48.9%) samples were found positive for HPV sequences and the most common genotypes were HPV 16 (53.5%) and HPV 54 (9.3%) followed by HPV 6, 53, 56, 58, 66, 11, 12, 20, 45, 62, and 71, in descending order of prevalence. The majority of HPV 16 isolates were classified as European and only one as African-1 variant on the basis of nucleotide signature present within the MGP L1 region. The high prevalence of HPV 16 among renal allograft recipients suggests that an HPV-16-based preventive or therapeutic vaccine may be effective for prevention or treatment of HPV-related neoplasia in this group of immune compromised patients

TP53 codon 72 polymorphism in classic, endemic and epidemic kaposi's sarcoma in African and caucasian patients

Objectives: Several studies have examined the association of codon 72 polymorphism of the TP53 gene, encoding either arginine or proline, in several tumor types but none have investigated its role in Kaposi's sarcoma (KS) development. Methods: In this prevalent case-control study, 67 cutaneous lesions of classic, iatrogenic, endemic as well as epidemic KS from African (n = 22) and Caucasian (n = 45) patients, and blood samples from 150 healthy controls (n = 57 African, n = 93 Caucasian) have been analyzed for arginine and proline allele distribution. Results: Among African cases the proline homozygous, heterozygous and arginine homozygous genotype frequencies were 50.0, 31.8 and 18.2%, respectively, and among controls 54.4, 40.3, and 5.3%, respectively (p = 0.1872). Conversely, among Caucasian cases genotype distributions were 6.7, 55.6, and 37.8%, and among controls 7.5, 34.4, and 58.1%, respectively (p = 0.0567). No significant differences in arginine and proline allele distribution were observed when the cases were stratified by HIV status/tumor type. Conclusions: The results obtained in this study suggest that p53 polymorphism at codon 72 does not represent a risk factor for the development of all forms of KS, either among African or among Caucasian populations. Copyright © 2009 S. Karger AG, Basel

Possibilities of Efficiency Improvement at Creative Industries Companies of Latvia

Radošās industrijas ir viens no visstraujāk augošajiem ekonomikas sektoriem mūsdienās, tādēļ, lai veicinātu Latvijas radošo nozaru konkurētspēju, uzņēmumiem nepieciešams pastāvīgi pilnveidot savas darbības efektivitāti. Maģistra darba mērķis ir izstrādāt radošo industriju uzņēmumu efektivitātes pilnveidošanas metodes un paņēmienus to praktiskai izmantošanai. Darbā apkopotas teorētiskās atziņas par radošo industriju nozīmi, to efektivitātes pilnveidošanas metodēm, vispārīgi raksturotas Latvijas radošās industrijas, kā arī tika veikts pētījums par radošo industriju uzņēmumu radošuma un efektivitātes vadību, un, pamatojoties uz rezultātiem, autore izstrādāja modeli, veica secinājumus un priekšlikumus radošo industriju veiktspējas uzlabošanai. Darba apjoms: 98 lpp., attēlu skaits - 24, tabulu skaits - 4, pielikumu skaits - 8.Creative industries are now one of the most developing sectors of global economy, therefore, to further competitiveness of creative industries of Latvia, companies have to constantly improve their operational efficiency. The objective of the Master’s Thesis is to develop efficiency improvement techniques for practical use of creative industries companies. In the Thesis the theory aspects of creative industries essence, their efficiency improvement methods are described, the creative industries of Latvia are characterized. A study of creative industries business creativity and efficiency management was performed, and on this basis, the author developed a model, made conclusions and proposals for creative industries performance enhancement. The Thesis is written on 98 pages, number of images is 24, number of tables - 4, number of annexes - 8

Human herpesvirus type 8 variants circulating in Europe, Africa and North America in classic, endemic and epidemic Kaposi's sarcoma lesions during pre-AIDS and AIDS era

Human herpesvirus-8 (HHV-8) variants have been found heterogeneously distributed among human populations living in diverse geographic regions, but their differential pathogenicity in Kaposi's sarcoma development remains controversial. In the present study, HHV-8 variant distribution has been analyzed in classic, iatrogenic, endemic as well as epidemic Kaposi's sarcoma (KS) during pre-AIDS and AIDS period (1971-2008) in countries with different KS incidence rate. DNA samples from cutaneous KS lesions of 68 patients living in Africa (n = 23, Cameroon, Kenya and Uganda), Europe (n = 34, Greece and Italy) and North America (n = 11) have been subjected to PCR amplification of HHV-8 ORF 26, T0.7, K1 and K14.1/15, followed by direct nucleotide sequencing and phylogenetic analysis. Among the 23 African samples, the majority of HHV-8 ORF 26 variants clustered with the subtype R (n = 12) and B (n = 5). Conversely, the viral sequences obtained from 45 European and North European tumors belonged mainly to subtype A/C (n = 36). In general, HHV-8 and K1 variant clustering paralleled that of ORF 26 and T0.7. Genotyping of the K14.1/15 loci revealed a large predominance of P subtype in all tumors. In conclusion, comparison of the HHV-8 sequences from classic or endemic versus AIDS-associated KS showed a strong linkage of the HHV-8 variants with specific populations, which has not changed during AIDS epidemic. © 2009 Elsevier Inc. All rights reserved

MDM2 and CDKN1A gene polymorphisms and risk of Kaposi's sarcoma in African and Caucasian patients

A single-nucleotide polymorphism in the MDM2 promoter (SNP309; rs2279744) causes elevated transcription of this major negative regulator of p53 in several cancer types. We investigated MDM2 SNP309 and CDKN1A (p21/Waf1/Cip1) codon 31 (rs1801270) polymorphisms in 86 cases of cutaneous Kaposi's sarcoma (KS) from African and Caucasian patients, and 210 healthy controls. A significant increase of the MDM2 SNP309 T/G genotype was observed among classic KS cases (odds ratio 2.38, 95% confidence interval 1.0-5.5). Frequencies of CDKN1A codon 31 genotypes were not significantly different between cases and controls. The results suggest that the MDM2 SNP309 G allele may act as a susceptibility gene for the development of classic KS in Caucasian patients. © 2011 Informa UK, Ltd

Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy

BACKGROUND: We have previously shown that HCC patients and healthy subjects are equally responsive to a RNAdjuvant®, a novel TLR-7/8/RIG-I agonist based on noncoding RNA developed by CureVac, by an ex vivo evaluation. However, the immunological effect of adjuvants on immune cells from cancer patients undergoing chemotherapy remains to be demonstrated. Different adjuvants currently used in cancer vaccine clinical trials were evaluated in the present study on immune cells from cancer patients before and after chemotherapy in an ex vivo setting. METHODS: PBMCs were obtained from 4 healthy volunteers and 23 patients affected by either colon (OMA) or lung cancer (OT). The effect of CpG, Poly I:C, Imiquimod and RNA-based adjuvant (RNAdjuvant®) was assessed using a multiparametric approach to analyze network dynamics of early immune responses. Evaluation of CD80, CD86 and HLA-DR expression as well as the downstream effect on CD4+ T cell phenotyping was performed by flow cytometry; cytokine and chemokine production was evaluated by Bio-Plex ProTM. RESULTS: Treatment with RNAdjuvant® induced the strongest response in cancer patients in terms of activation of innate and adoptive immunity. Indeed, CD80, CD86 and HLA-DR expression was found upregulated in circulating dendritic cells, which promoted a CD4+ T cell differentiation towards an effector phenotype. RNAdjuvant® was the only one to induce most of the cytokines/chemokines tested with a pronounced Th1 cytokine pattern. According to the different parameters evaluated in the study, no clear cut difference in immune response to adjuvants was observed between healthy subjects and cancer patients. Moreover, in the latter group, the chemotherapy treatment did not consistently correlate to a significant altered response in the different parameters. CONCLUSIONS: The present study is the first analysis of immunological effects induced by adjuvants in cancer patients who undergo chemotherapy, who are enrolled in the currently ongoing cancer vaccine clinical trials. The results show that the RNAdjuvant® is a potent and Th1 driving adjuvant, compared to those tested in the present study. Most importantly, it is demonstrated that chemotherapy does not significantly impair the immune system, implying that cancer patients are likely to respond to a cancer vaccine even after a chemotherapy treatment