To improve the delivery of so-called suicide genes into immunoblot and polymerase chain reaction (PCR). The tumors, recombinant retroviruses were constructed by functionality of the suicide genes was determined by a inserting the herpes virus type 1 (HSV-1) thymidine kinase metabolic assay on virus vector infected cells and (tk), the E. coli cytosine deaminase (cd) and polynucleotreatment with the respective prodrugs. In terms of vector side phosphorylase (pnp), or the jellyfish gene for the stability and effectiveness of specific cell killing a virus green fluorescent protein (gfp) into a foamy virus (FV)-transducing the pnp gene (FOV-7/pnp) was superior to derived replication-competent vector (pFOV-7). Expression those using the other two suicide genes. FOV-7/pnp is a and stability of the inserted foreign gene was analyzed by candidate virus for suicide gene delivery into solid tumors.Keywords: foamy virus vectors; suicide gene therapy; thymidine kinase; cytosine deaminase; polynucleoside phosphataseVirus vector-mediated intratumoral delivery of enzymes neuropathy. 12,13 In these animals the expression of an accessory viral gene product of unknown function that is which convert prodrugs to toxic active drugs has gained increasing interest among experimental cancer theranot required for viral replication, 14 the Bet protein, has been identified as the most likely candidate for inducing pists.1,2 Common retrovirus vector-mediated delivery is often used in experimental protocols, and human trials the neural damage in these animals. 12,15 On the basis of the so-called human FV (HFV), which most likely rephave been initiated using a murine leukemia virus (MLV)-derived packaging cell line and a MLV-derived resents a chimpanzee virus variant, 4-6 replicating viral vectors have been constructed in which most of the bet vector expressing the HSV-1 TK.3 After injection of vector producing packaging cells into tumors, the virus vector open reading frame (ORF) has been deleted. 16 We investigated the possibility of replacing the bet ORF by different is able to perform one round of reverse transcription and integration. Since MLV-derived vectors only integrate suicide genes and tested their stability and functionality in the context of the replicating virus in vitro (criterion into proliferating cells, tumor cells are much more susceptible to infection by the virus vector than normal (4) as described above). As shown in Figure 1, control and suicide genes were tissue. 3 We decided to test the possibility of introducing suicinserted into the replicating vector pFOV-7. 16 Compared with the wild-type HFV, pFOV-7 has a large deletion in ide genes into a replicating retrovirus vector to improve the strategy of virus-mediated destruction of tumor cells. the U3 region of the long terminal repeat (LTR). This deletion has been recently shown to improve HFV repliWe reasoned that such a virus vector should be (1) nonpathogenic; (2) of primate origin to ensure efficient infeccation in fibroblastoid cells. 17 In addition, most of the b...
A replication competent foamy virus derived retroviral vector expressing suicide genes has been constructed and characterized in vitro. Here we used vectors expressing the purine nucleoside phosphorylase (FOV-7/pnp), the nitroreductase (FOV-7/ntr), or the thymidine kinase (FOV-7/tk) suicide gene in an in vivo athymic (nude) mice/human glioblastoma tumor model. Gliomas were induced by subcutanous injection of U87 tumor cells. The virus vector was injected when the tumor became visible. Mice with vector virus-injected tumors were treated with the respective prodrug. The treatment resulted in significant inhibition of tumor growth. Surprisingly, in mice with vector virus-injected tumors without prodrug treatment a similar suppression of tumor growth was observed. In 65% (pnp vector), 75% (ntr vector) and 37% (tk vector) of these mice the tumors stopped growing or vanished and the animals remained tumor free for the 25 weeks of the experiment, whereas all mice of the control groups had to be killed because of the tumor growth. In control experiments, the suppression of tumor growth could also be observed when wild-type foamy virus was injected instead of the suicide gene-transducing vectors. Similar results were obtained using the nude mice/G59 human glioblastoma tumor model. In conclusion, the experiments demonstrate an oncolytic activity of foamy virus replication in a nudemice glioblastoma xenograft tumor model. The analysis of vector virus DNA by PCR revealed that the vector persisted in different organs of the animals irrespective of the use of a prodrug or the elimination of a tumor. Cancer Gene Therapy (2005) 12, 947-953.
Drilling predation is a common reason for mortality of benthic mollusks but did not become common until the late Mesozoic. The scarcity of drill holes in the early Mesozoic fossil record limits our understanding of the evolution of drilling behavior and its role on shaping early Mesozoic marine communities. Here, we use drilling traces on several bivalve taxa from the Lower Jurassic (Pliensbachian) marine soft-bottom deposits in northern Germany to explore behavioral patterns of the predator (e.g., site selectivity, change in site-selective behavior with age). Although none of the known drilling gastropod groups existed in the Pliensbachian, including the studied localities, the drill-hole morphology suggests that the predator was probably a gastropod. The ecology and identity of the target prey changes from a diverse array of epifaunal to infaunal taxa in older deposits to focus on a single, large, deep infaunal taxon, Gresslya intermedia, in younger deposits, suggesting a potential trend in prey selectivity over time. Spatial point pattern analysis of traces (SPPAT) reveals an aggregated pattern of drill holes on Gresslya, suggesting strong selectivity in drill-hole location. Drilling on a single large infaunal taxon and site selectivity are common patterns also inferred previously from the drilled deep infaunal Eothyasira from the Pliensbachian of southern Germany. In addition to the scarcity of predators, the highly specialized behavior of the early drilling predators, including strong prey selectivity in terms of prey identity and life habit, can partly explain the rarity of the early Mesozoic drill holes.
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