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Agar plate assays were used to assess the effect of density, incubation time and age of nematodes and the presence of insect hosts on the dispersal of infective juveniles (IJs) of Heterorhabditis megidis (strain NLH-E87.3). IJs dispersed faster and further at high densities than at low densities. Dispersal was also influenced by the age of the IJs. Individuals stored for a period of 1.5 and 4.5 weeks showed to be more active than those stored for 2.5 and 3.5 weeks. The presence of a host insect enhanced the dispersion of nematodes. The increasing in the incubation period showed that IJs responded positively to host cues from Galleria mellonella but poorly to cues from Otiorhynchus sulcatus larvae. [ABSTRACT FROM AUTHOR]

Background: A possible explanation for the wide interindividual variability in toxicity and efficacy of drug therapy is variation in genes encoding drug-metabolizing enzymes and drug transporters. The allelic frequency of these genetic variants, linkage disequilibrium (LD), and haplotype of these polymorphisms are important parameters in determining the genetic differences between patients. The aim of this study was to explore the frequencies of polymorphisms in drug-metabolizing enzymes (CYP1A1, CYP2C9, CYP2C19, CYP3A4, CYP2D6, CYP3A5, DPYD, UGT1A1, GSTM1, GSTP1, GSTT1) and drug transporters (ABCB1[MDR1] and ABCC2[MRP2]), and to investigate the LD and perform haplotype analysis of these polymorphisms in a Dutch population. Methods: Blood samples were obtained from 100 healthy volunteers and genomic DNA was isolated and amplified by PCR. The amplification products were sequenced and analyzed for the presence of polymorphisms by sequence alignment. Results: In the study population, we identified 13 new single nucleotide polymorphisms (SNPs) in Caucasians and three new SNPs in non-Caucasians, in addition to previously recognized SNPs. Three of the new SNPs were found within exons, of which two resulted in amino acid changes (A428T in CYP2C9 resulting in the amino acid substitution D143V; and C4461T in ABCC2 in a non-Caucasian producing the amino acid change T1476M). Several LDs and haplotypes were found in the Caucasian individuals. Conclusion: In this Dutch population, the frequencies of 16 new SNPs and those of previously recognized SNPs were determined in genes coding for drug-metabolizing enzymes and drug transporters. Several LDs and haplotypes were also inferred. These data are important for further research to help explain the interindividual pharmacokinetic and pharmacodynamic variability in response to drug therapy. [ABSTRACT FROM AUTHOR]

We studied the host-finding and dispersion behaviour of Heterorhabditis megidis (strain NLHE 87.3) in the presence of Galleria mellonella or Otiorhynchus sulcatus larvae and strawberry roots. In large Petri dishes (19 cm diameter) filled with moist sand (8% w/w), and incubated at 15°C over 24 h, infective juveniles (IJs) responded positively to the presence of G. mellonella, to roots of a single strawberry plant and to O. sulcatus larvae in direct contact with roots of a single strawberry plant. A neutral or negative response was observed when IJs were presented with only O. sulcatus larvae or a combination of several strawberry plants with O. sulcatus larvae, either in contact or not in contact with the roots. IJs responded strongly to the combination of plant roots and feeding larvae indicating that the tritrophic interaction formed by IJs - O. sulcatus larvae - strawberry plants may be an infochemical-mediated interaction. [ABSTRACT FROM AUTHOR]

Background:Human papillomavirus (HPV), p16 expression, and TP53 mutations are known prognostic factors in head and neck squamous cell carcinoma, but their role in squamous cell carcinoma of the anal canal (SCCAC) is less well established. The objective of this study was to determine the prognostic significance of tumour HPV status, p16 and p53 expression, and mutations in TP53 in patients with SCCAC receiving (chemo)radiotherapy.Methods:Human papillomavirus DNA was determined using an INNO-LiPA-based assay in tumour tissue of 107 patients with locally advanced SCCAC. Patients were treated with radiotherapy, with or without concurrent chemotherapy consisting of a fluoropyrimidine and mitomycin C. Expression of p16 and p53 was determined using immunohistochemistry. Exons 2-11 of TP53 in tumour tissue were sequenced.Results:DNA of high-risk HPV types was detected in 93 out of 107 tumours (87%), all of which overexpressed p16 (HPV+/p16+). Of 14 HPV-negative (HPV−) tumours (13%), 10 (9%) were p16-negative (HPV−/p16−) and 4 (4%) overexpressed p16 (HPV−/p16+). Patients with HPV−/p16− disease had inferior 3-year locoregional control (LRC) (15%) compared with patients with HPV+/p16+ tumours (82%, P<0.001) and HPV−/p16+ tumours (75%, P=0.078). Similarly, 3-year overall survival (OS) was 35% (HPV−/p16−) vs 87% (HPV+/p16+, P<0.001) and 75% (HPV−/p16+, P=0.219). Disruptive mutations in TP53 were found in 80% of HPV−/p16− tumours vs 6% of HPV+/p16+ tumours (P<0.001). In multivariate analysis, HPV−/p16− status was an independent predictor of inferior LRC and OS.Conclusions:HPV− tumours are frequently TP53 mutated. HPV−/p16− status is a strong predictor for reduced LRC and OS, and alternative treatment strategies for patients with HPV−/p16− disease need to be explored. [ABSTRACT FROM AUTHOR]

Introduction: Deoxycytidine kinase (DCK) is the rate-limiting enzyme of the intracellular phosphorylation of nucleoside anticancer drugs, including gemcitabine and β-arabinofuranosylcytosine, to their active triphosphates. This study was performed to assess the occurrence and frequency of DCK polymorphisms in a predominantly Caucasian population and to choose candidate polymorphisms for subsequent functionality studies. Methods and materials: All seven DCK exons and the promoter region were sequenced from 100 healthy volunteers (79 females and 21 males). With respect to ethnicity, the study cohort comprised 93 Caucasian, one Asian, one African, and five mixed-race individuals. Results: Six novel single nucleotide polymorphisms (SNPs) were found (-243G>T, -135G>C, 261G>A, 364C>T, 727A>C, IVS6+41T>A). Two SNPs are nonsynonymous and lead to changes in the amino acid sequence [C364T in exon 3 (P121S) and A727C in exon 6 (K242Q)]. The presence of the linked promoter polymorphism -360C>G/-201C>T was confirmed in Caucasians, but was less frequent than what has been reported from Asians (allele frequencies 2 versus 15.6%). The most prevalent haplotype was the wild-type plus IVS6+41TT (85.8%). This study found novel DCK polymorphisms, including nonsynonymous SNPs, in exons 3 and 6. A comparison of the data obtained in this study with those reported in a previous study on Asians [Shi et al. (2004) Pharmacogenetics 14:759–768] illustrates marked inter-ethnic differences in the occurrence and frequency of DCK polymorphisms. Conclusion: The higher allelic frequency of the promoter polymorphism -C360G/-C201T in Asians than in Caucasians might predispose Asians to nucleoside drugassociated toxicity. These data will be used to assess the effect of DCK candidate SNPs (promoter, exons 3 and 6) in patients receiving gemcitabine anticancer treatment. [ABSTRACT FROM AUTHOR]

An abstract of the article "Prediction of virological failure in HIV-infected individuals treated with cART in Suriname," by M. P. Bleijenberg and colleagues is presented.