Search

Kenneth Lundstrom PanTherapeutics, Lutry, Switzerland Abstract: Oncolytic viruses have demonstrated selective replication and killing of tumor cells. Different types of oncolytic viruses – adenoviruses, alphaviruses, herpes simplex viruses, Newcastle disease viruses, rhabdoviruses, Coxsackie viruses, and vaccinia viruses – have been applied as either naturally occurring or engineered vectors. Numerous studies in animal-tumor models have demonstrated substantial tumor regression and prolonged survival rates. Moreover, clinical trials have confirmed good safety profiles and therapeutic efficacy for oncolytic viruses. Most encouragingly, the first cancer gene-therapy drug – Gendicine, based on oncolytic adenovirus type 5 – was approved in China. Likewise, a second-generation oncolytic herpes simplex virus-based drug for the treatment of melanoma has been registered in the US and Europe as talimogene laherparepvec. Keywords: immunotherapy, viral vectors, clinical trials, drug approval

Androstenone is one of the main compounds responsible for boar taint, and 3[beta]-hydroxysteroid dehydrogenase (3[beta]HSD) might be involved in its metabolism. In this study, the gene expression of 33HSD and 17[beta]-hydroxysteroid dehydrogenase (17[beta]HSD) were determined by real-time PCR analysis and related to the concentrations of androstenone, testosterone, and estrone sulphate (E1S). The experiments were performed on gonadally intact male pigs classified based on high or low fat androstenone concentrations, as predetermined by HPLC, as well as on immunocastrated and surgically castrated male pigs. The male pigs with high androstenone concentrations in fat had low 3[beta]HSD gene expression in liver and testis. Moreover, the 17[beta]HSD gene expression in liver, but not in testis, varied negatively with fat androstenone concentrations. Immunocastrated and surgically castrated male pigs had nondetectable concentrations of fat androstenone and plasma testosterone and EIS, and the castration procedure induced a significant increase of 3[beta]HSD and 17[beta]HSD gene expression. The mRNA expression was generally much greater from the 3[beta]HSD than from the 17[beta]HSD gene. Furthermore, fat androstenone was negatively correlated with liver 3[beta]HSD gene expression (Pearson correlation, r = -0.69; P < 0.05), and the 17[beta]HSD gene expression in liver was negatively correlated with plasma E1S (r = -0.95; P < 0.001), indicating an important role of liver 17[beta]HSD in the estrogen metabolism of gonadally intact male pigs. Another strong correlation was found between 3[beta]HSD and 17[beta]HSD gene expression in liver of the gonadally intact male pigs (r = 0.86; P < 0.01), possibly reflecting similar regulation mechanisms of these genes. Key words: androstenone, estrone sulphate, 3[beta]-hydroxysteroid dehydrogenase, 17[beta]-hydroxysteroid dehydrogenase, pig, testosterone

A study was conducted to elucidate the effects of social factors on the concentrations of boar taint substances, androstenone and skatole, in boars. The factors included dominance (social rank) and the effects of strongly tainted animals on other members of the group. Four successive replicates of 100 pigs (50 boars + 50 gilts) with an average live weight of 24 kg were randomly allocated to 10 pens of 10. Data for this study were collected during the period of 67 to 114 kg of live weight and included the repetitive recording of agonistic behavior during competitive feeding; blood sampling for determination of plasma androstenone, skatole and testosterone in boars; feces sampling for determination of skatole content; and collection of bulbourethral glands in boars, and uteri plus ovaries in gilts at slaughter, for the assessment of sexual maturity. Results show an influence of social rank on plasma concentrations of androstenone (P = .0001) and testosterone (P = .0001), the weight of the bulbourethral glands (P = .0001), and plasma skatole (P = .02). Pens were classified according to the pig with the highest concentration of androstenone in the pen into high, medium, and low maximum pens. In pens with high maximum concentrations of androstenone, the second-highest androstenone concentration (P = .0001), and the average concentration (P = .0003) in the pen were higher than those in pens with medium or low maximum concentrations of androstenone. Mean aggression level was also higher (P = .02), but pens with high maximum aggression level did not have higher mean androstenone concentration. Rank effect on androstenone was more important than aggression effect. Neither maximum androstenone concentration nor maximum aggression level in a pen was related to the pen mean stage of sexual maturity in either sex. No influences of rank, aggression, or aggression received were found on the feces skatole level, and no pheromonal communicative function was demonstrated for skatole. High androstenone concentrations did not have a suppressive effect on androstenone concentrations in other males of the group; on the contrary, the levels were increased. This may be due to a stimulating effect of androstenone and, possibly, mating activity. Consequently, in the production of boars for slaughter, strongly tainted animals should be avoided or removed and mating activity minimized. This could be facilitated by, for instance, slaughtering before sexual maturity or separate rearing of the sexes. Key Words: Aggression, Boar Taint, Androstenone, Sexual Maturity, Pigs

An intercross between wild boar and a domestic Large White pig population was used to map quantitative trait loci (QTL) for body proportions, weight of internal organs, carcass composition, and meat quality. The results concerning growth traits and fat deposition traits have been reported elsewhere. In the present study, all 200 [F.sub.2] animals, their parents, and their grandparents were genotyped for 236 markers. The marker genotypes were used to calculate the additive and dominance coefficients at fixed positions in the genome of each [F.sub.2] animal, and the trait values were regressed onto these coefficients in intervals of 1 cM. In addition, the effect of proportion of wild boar alleles was tested for each chromosome. Significant QTL effects were found for percentage lean meat and percentage lean meat plus bone in various cuts, proportion of bone in relation to lean meat in ham, muscle area, and carcass length. The significant QTL were located on chromosomes 2, 3, 4, and 8. Each QTL explained 9 to 16% of the residual variance of the traits. Gene action for most QTL was largely additive. For meat quality traits, there were no QTL that reached the significance threshold. However, the average proportion of wild boar alleles across the genome had highly significant effects on reflectance and drip loss. The results show that there are several chromosome regions with a considerable effect on carcass traits in pigs. Key Words: Gene Mapping, Quantitative Traits, Carcass Composition, Meat Quality, Wild Pigs