Possibility of specific expression of the protein toxins at the tumor site with tumor-specialized promoter

The ultimate goal of cancer therapy is to establish a treatment regimen that will ensure complete eradication of cancers with minimal toxicity to the surrounding normal tissues. Protein toxins are highly efficient when they are used as treatment reagents of cancer but are associated with toxicity in normal tissues. Given that specialized promoters have been widely investigated for specific expressions, we speculated that tumor-specialized promoters would play an important role in protein toxin tumor therapy. Therefore, we hypothesize that a tumor-specialized promoter can be inserted into a truncated protein toxin expression vector. Then, the vector can be introduced into the human body by either a viral or nonviral vector. These protein toxin genes would be specifically expressed in tumor cells, but not in normal tissue cells. The proposition may provide a new strategy with the development of protein toxins for specific targeting to neoplastic tumors

Annexin A2 depletion exacerbates the intracerebral microhemorrhage induced by acute rickettsia and Ebola virus infections.

Intracerebral microhemorrhages (CMHs) are small foci of hemorrhages in the cerebrum. Acute infections induced by some intracellular pathogens, including rickettsia, can result in CMHs. Annexin a2 (ANXA2) has been documented to play a functional role during intracellular bacterial adhesion. Here we report that ANXA2-knockout (KO) mice are more susceptible to CMHs in response to rickettsia and Ebola virus infections, suggesting an essential role of ANXA2 in protecting vascular integrity during these intracellular pathogen infections. Proteomic analysis via mass spectrometry of whole brain lysates and brain-derived endosomes from ANXA2-KO and wild-type (WT) mice post-infection with R. australis revealed that a variety of significant proteins were differentially expressed, and the follow-up function enrichment analysis had identified several relevant cell-cell junction functions. Immunohistology study confirmed that both infected WT and infected ANXA2-KO mice were subjected to adherens junctional protein (VE-cadherin) damages. However, key blood-brain barrier (BBB) components, tight junctional proteins ZO-1 and occludin, were disorganized in the brains from R. australis-infected ANXA2-KO mice, but not those of infected WT mice. Similar ANXA2-KO dependent CMHs and fragments of ZO-1 and occludin were also observed in Ebola virus-infected ANXA2-KO mice, but not found in infected WT mice. Overall, our study revealed a novel role of ANXA2 in the formation of CMHs during R. australis and Ebola virus infections; and the underlying mechanism is relevant to the role of ANXA2-regulated tight junctions and its role in stabilizing the BBB in these deadly infections