BackgroundAmong ocular vector-borne pathogens, Onchocerca volvulus, the agent of the so-called “river blindness”, affects about 37 million people globally. Other Onchocerca spp. have been sporadically reported as zoonotic agents. Cases of canine onchocerciasis caused by Onchocerca lupi are on the rise in the United States and Europe. Its zoonotic role has been suspected but only recently ascertained in a single case from Turkey. The present study provides further evidence on the occurrence of O. lupi infesting human eyes in two patients from Turkey (case 1) and Tunisia (case 2). The importance of obtaining a correct sample collection and preparation of nematodes infesting human eyes is highlighted.MethodsIn both cases the parasites were identified with morpho-anatomical characters at the gross examination, histological analysis and anatomical description and also molecularly in case 1.ResultsThe nematode from the first case was obviously O. lupi based on their morphology at the gross examination, histological analysis and anatomical description. In the second case, although the diagnostic cuticular characters were not completely developed, other features were congruent with the identification of O. lupi. Furthermore, the morphological identification was also molecularly confirmed in the Turkish case.ConclusionsThe results of this study suggest that O. lupi infestation is not an occasional finding but it should be considered in the differential diagnosis of other zoonotic helminths causing eye infestation in humans (e.g., D. immitis and Dirofilaria repens). Both cases came from areas where no cases of canine onchocerciasis were previously reported in the literature, suggesting that an in depth appraisal of the infestation in canine populations is necessary. Physicians and ophthalmologists are advised on how to preserve nematode samples recovered surgically, to allow a definitive, correct etiological diagnosis.

Diffuse large B-cell lymphomas (DLBCL) are the most common type of aggressive lymphomas, with considerable heterogeneity in clinical presentation, molecular characteristics, and outcome. Previous studies have showed significant correlations between DNA methyltransferase (DNMT) overexpression and unfavorable prognosis in human cancers. Therefore, we investigated in this study the biological and prognostic significance of DNMT1, DNMT3a, and DNMT3b protein expression in DLBCL. DNA methyltransferase (DNMT) expression was analyzed by immunohistochemistry in 81 DLBCL cases and correlated with clinicopathological parameters. Kaplan-Meier curves were used to estimate survival rates, and the Cox proportional hazard regression model was used to evaluate the prognostic impact of DNMT expression. Our results showed that overexpression of DNMT1, DNMT3a, and DNMT3b were detected in 48%, 13%, and 45% of investigated cases, respectively. DNA methyltransferase 1 (DNMT1) and DNMT3b overexpression was significantly correlated with advanced clinical stages (P = 0.028 and P = 0.016, respectively). Moreover, concomitant expression of DNMT1 and DNMT3b was significantly correlated with resistance to treatment (P = 0.015). With regard to survival rates, although data was available only for 40 patients, DNMT3b overexpression was significantly correlated with shorter overall survival (P = 0.006) and progression-free survival (P = 0.016). Interestingly, multivariate analysis demonstrated that DNMT3b overexpression was an independent prognostic factor for predicting shortened overall survival (P = 0.004) and progression-free survival (P = 0.024). In conclusion, DNMT3b overexpression was identified as an independent prognostic factor for predicting shortened survival of patients with DLBCL and could be, therefore, useful in identifying patients who would benefit from aggressive therapy. (Cancer Sci 2010; 101: 1722-1730 D iffuse large B-cell lymphomas (DLBCL) are the most common form of aggressive lymphoma.(1,2) Although curable in the majority of cases with anthracycline-based combination chemotherapy and the monoclonal antibody rituximab, approximately 40% of patients with DLBCL will relapse after standard first-line therapy.(1,2) Several biological markers have been studied in attempting to identify high-risk patients, but none has proved to be completely effective, (2,3) and the international prognostic index (IPI) has remained the gold standard for predicting prognosis.(4) Recently, microarray gene expression studies have identified multiple genes of potential prognostic significance in DLBCL, and have led to the subdivision of DLBCL into two major biological categories based on presumed cell of origin: germinal centre B-cell like (GCB), and non-GCB ⁄ activated B-cell like.(5) However, the prognostic value of genetic markers in DLBCL remains controversial. The identification of new molecular prognostic markers would therefore improve the prognostic predictability and understanding of the clinical behavior of those lymphomas. (2,3) DNA me...

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This study demonstrates that DLBCLs with hypermethylated P16, VHL, DAPK, and SHP1 commonly show a biologically aggressive phenotype and worse prognosis. Interestingly, hypermethylation of DAPK was found to be an independent prognostic factor that may be used in conjunction with the conventional prognostic factors such as the IPI and the germinal center status.

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The simian virus SV40 (SV40), a potent DNA oncogenic polyomavirus, has been detected in several human tumors including lymphomas, mainly in diffuse large B-cell type (DLBCL). However, a causative role for this virus has not been convincingly established. Hypermethylation in promoter regions is a frequent process of silencing tumor suppressor genes (TSGs) in cancers, which may be induced by oncogenic viruses. In this study, we investigated the relationship between the presence of SV40 DNA sequences and the methylation status of 13 TSGs in 108 DLBCLs and 60 nontumoral samples from Tunisia. SV40 DNA presence was investigated by PCR assays targeting the large T-antigen, the regulatory and the VP1 regions. Hypermethylation was carried out by methylationspecific PCR. SV40 DNA was detected in 63/108 (56%) of DLBCL and in 4/60 (6%) of nontumoral samples. Hypermethylation frequencies for the tested TSGs were 74% for DAPK, 70% for CDH1, SHP1, and GSTP1, 58% for p16, 54% for APC, 50% for p14, 39% for p15, 19% for RB1, 15% for BLU, 3% for p53, and 0% for p300 and MGMT. No hypermethylation was observed in nontumoral samples. Hypermethylation of SHP1, DAPK, CDH1, GSTP1 and p16 genes were significantly higher in SV40-positive than in SV40-negative DLBCL samples (p values ranging from 0.0006 to <0.0001). Our findings showed a high prevalence of SV40 DNA in DLBCLs in Tunisia. The significant association of promoter hypermethylation of multiple TSGs with the presence of SV40 DNA in DLBCLs supports a functional effect of the virus in those lymphomas. ' 2007 Wiley-Liss, Inc.Key words: diffuse large B-cell lymphomas; simian virus 40; hypermethylation; tumor suppressor genes; Tunisia Simian virus 40 (SV40) is a potent DNA oncogenic polyomavirus of rhesus monkey origin which seems to have spread to human beings via contamination of poliovirus stocks between 1955 and 1963 as well as by other means, 1 and mounting evidence suggests that it is an emergent human pathogen. 2-4 SV40 DNA sequences have been detected in pediatric and adult brain tumors, 5,6 mesotheliomas, 7 osteosarcomas, 8 bronchopulmonary carcinomas, 9 bone tumors 10 and papillary thyroid carcinomas. 11 There also increasing evidence that SV40 is associated with non-Hodgkin's lymphomas, particularly with diffuse large B-cell lymphomas (DLBCL), 12-21 in spite of several negative studies. [22][23][24] However, although these observations indicate an association between this virus and specific human tumors, they do not demonstrate a causal role, and the molecular mechanism by which SV40 thought to be involved is still unclear.SV40 oncogenic potential is assumed to be associated with the primary viral gene product, large T-antigen (Tag), protein responsible for SV40 replication and SV40-mediated cell transformation. 1 In vitro, the infection of human cells by SV40 has showed that SV40 Tag can promote malignancy transformation by blocking the products of several tumor suppressor genes (TSGs), 1,25 inducing telomerase activity, 26 and stimulating other oncogenes and growth facto...

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