Little is known about the antigens expressed in nascent tumour cells, whether they are sufficient to induce protective antitumour immune responses or whether their expression is modulated by the immune system. Here, using selleck compound massively parallel sequencing, we characterize expressed mutations in highly immunogenic methylcholanthrene-induced sarcomas derived from immunodeficient Rag2(-/-) mice that phenotypically resemble nascent primary tumour cells(1,3,5). Using class I prediction algorithms, we identify mutant spectrin-beta 2 as a potential rejection antigen of the d42m1 sarcoma and validate this
prediction by conventional antigen expression cloning and detection. We also demonstrate that cancer immunoediting of d42m1 occurs via a T-cell-dependent immunoselection process that promotes outgrowth of pre-existing tumour cell clones lacking highly antigenic mutant spectrin-beta 2 and other potential strong antigens. These results demonstrate that the strong immunogenicity of an P505-15 unedited tumour can be ascribed to expression of highly antigenic mutant proteins and show that outgrowth of tumour cells that lack these strong antigens via a T-cell-dependent immunoselection process represents one mechanism of cancer immunoediting.”
“A strategy for the production
of virus-like particles (VLPs) from simian rotavirus in larvae of the lepidopteran Spodoptera frugiperda is described. VP2 and VP6 coding sequences were co-expressed in larvae co-infected with recombinant baculovirus and these structural proteins self-assembled into VLPs that were secreted and accumulated in the haemolymph. Under electron microscopy, VLPs produced in larvae were indistinguishable from those produced in Sf9 insect cell cultures. The results showed that it is possible to obtain rotavirus VLPs in larvae reducing significantly the costs of production, making this approach an alternative for the manufacture of live rotavirus vaccines. (C) 2007 Elsevier B.V. All rights reserved.”
“The hepatoprotective potential
of saponarin, isolated from Gypsophila trichotoma, was evaluated in vitro/in vivo using a hepatotoxicity model of paracetamol-induced liver injury. In freshly MLN2238 ic50 isolated rat hepatocytes, paracetamol (100 mu mol) led to a significant decrease in cell viability, increased LDH leakage, decreased levels of cellular GSH, and elevated MDA quantity. Saponarin (60-0.006 mu g/mL) preincubation, however, significantly ameliorated paracetamol-induced hepatotoxicity in a concentration-dependent manner. The beneficial effect of saponarin was also observed in vivo. Rats were challenged with paracetamol alone (600 mg/kg, i.p.) and after 7-day pretreatment with saponarin (80 mg/kg, oral gavage). Paracetamol toxicity was evidenced by increase in MDA quantity and decrease in cell GSH levels and antioxidant defence system. No changes in phase I enzyme activities of AH and EMND and cytochrome P 450 quantity were detected.