Human tankyrases are aberrantly expressed in colon tumors and contain multiple epitopes that induce humoral and cellular immune responses in cancer patients

PURPOSE: Tankyrases 1 and 2 are telomere-associated poly(ADP-ribose) polymerases (PARP) that can positively regulate telomere elongation and interact with multiple cellular proteins. Recent reports implicated tankyrases as tumor antigens and potential targets of anticancer treatment. We examined expression of tankyrases in colon tumors and immune response to these enzymes in patients with different types of cancer. METHODS: mRNA and protein expression was evaluated by quantitative real-time RT-PCR and Western blotting, respectively. Humoral immune response to recombinant tankyrases was investigated by modified enzyme-linked immunoassays. Cellular immune response was analysed by ELISPOT and (51)Cr release assays. RESULTS: We found that both mRNA and protein levels of tankyrase 2 (TNKL) are upregulated in colon tumors. In contrast, protein level of tankyrase 1 (TNKS) is downregulated, while mRNA level shows variable changes. More than a quarter of colon cancer patients develop humoral immune response to at least one of the two tankyrases. In this study we mapped common and unique B-cell epitopes located in different domains of the two proteins. Additionally, we present evidence for T-cell responses both to epitopes that are unique for TNKL and to those shared between TNKL and TNKS. CONCLUSION: Our study favors a biomarker usage of antibody response to tankyrases. Spontaneous CD8(+) T-cell responses to these enzymes are rare and further investigation is needed to evaluate tankyrases as potential targets for cancer immunotherapy

New features in the subsurface structure model of El Hierro island (Canaries) from low-frequency microseismic sounding: an insight into the 2011 seismo-volcanic crisis

To study the deep structure of El Hierro Island, Canarian Archipelago, we have used a microseismic sounding method (MSM) based on the fact that heterogeneities of the Earth's crust disturb the spectrum of the low-frequency microseismic field in their vicinity. So, at the Earth's surface, the spectral amplitudes of definite frequency f above the high-velocity heterogeneities are decreasing, and above the low-velocity ones they are increasing. Moreover, the frequency f is connected with the depth of a heterogeneity H and the velocity of the fundamental mode of Rayleigh waves V (R)(f) through the relation H a parts per thousand 0.4V (R)(f)/f. From these relations, the MSM lets us model the subsurface structure in a 3D context by inverting the amplitude-frequency spatial distribution of the microseismic field of low frequency. The validity of the method is shown through of numerical simulations and previous applications with known or verified solutions. This MSM is now used to invert the microseismic data registered in El Hierro Island. The obtained subsurface model reveals two large intrusive bodies beneath the island. Joint interpretation of microseismic and gravimetric data and their comparison with the available geological studies relate the central-eastern intrusive body to the early stage of the island formation. With respect to the western intrusive body, at the depths of 15-25 km, an area with lowest seismic velocities is identified, where we suggest that a modern magmatic reservoir is located. This reservoir could be associated with the recent submarine eruption in October 2011 and the accompanying seismic swarm, which started in July 2011. Several correlations between the shallowest structures identified by the gravity and MSM approaches are also found. Besides the numerical simulation and previous studies of this method, the correlation between gravity results, the MSM model, the geological information and the possible explanation of the features of the seismic swarm through the model obtained offer us a valid proof about the plausibility of the subsurface structures identified from MSM