Accelerated rejection of the second transplants of immunogenic tumor in mice under inhibition of indoleamine 2,3-dioxygenase activity by ethyl pyruvate

Aim: A recently discovered enzyme, indoleamine 2,3-dioxygenase (IDO), is expressed in placenta, dendritic cells and also in many kinds of tumors and in tumor-infiltrating macrophages. By catabolizing tryptophan, IDO causes local depletion of this essential amino acid and excess of kinurenin, and suppresses in situ proliferation and functioning of T lymphocytes. Thus, immune resistance of tumors can be overcome by inhibiting IDO activity. Materials and Methods: C3HA mice immunized with non-syngeneic H-29 tumor were used to study the effect of the IDO inhibitor ethyl pyruvate, under systemic or local (at site of tumor cells localization) administration, on the occurrence and rate of rejection of the second transplants of this tumor. Results: Both systemic and local administration of ethyl pyruvate increases the incidence of and substantially accelerates tumor regression as compared with control. Conclusion: IDO inhibitors impairing immune resistance of tumors may appear useful in leveraging the efficacy of antitumor therapy

Simultaneous T2* mapping of 14N- and 15N-labeled dicarboxy-PROXYLs using CW-EPR-based single-point imaging

This article reports a method of simultaneous T2* mapping of 14N- and 15N-labeled dicarboxy-PROXYLs using 750-MHz continuous-wave electron paramagnetic resonance (CW-EPR) imaging. To separate the spectra of 14N- and 15N-labeled dicarboxy-PROXYLs under magnetic field gradients, an optimization problem for spectral projections was formulated with the spatial total variation as a regularization term and solved using a local search based on the gradient descent algorithm. Using the single-point imaging (SPI) method with spectral projections of each radical, simultaneous T2* mapping was performed for solution samples. Simultaneous T2* mapping enabled visualization of the response of T2* values to the level of dissolved oxygen in the solution. Simultaneous T2* mapping applied to a mouse tumor model demonstrated the feasibility of the reported method for potential application to in vivo oxygenation imaging

In vivo extracellular pH mapping of tumors using electron paramagnetic resonance

An electron paramagnetic resonance (EPR)-based method for noninvasive three-dimensional extracellular pH mapping was developed using a pH-sensitive nitroxyl radical as an exogenous paramagnetic probe. Fast projection scanning with a constant magnetic field sweep enabled the acquisition of four-dimensional (3D spatial +1D spectral) EPR images within 7.5 min. Three-dimensional maps of pH were reconstructed by processing the pH-dependent spectral information on the images. To demonstrate the proposed method of pH mapping, the progress of extracellular acidosis in tumor-bearing mouse legs was studied. Furthermore, extracellular pH mapping was used to visualize the spatial distribution of acidification in different tumor xenograft mouse models of human-derived pancreatic ductal adenocarcinoma cells. The proposed EPR-based pH mapping method enabled quantitative visualization of regional changes in extracellular pH associated with altered tumor metabolism

Paleolithic Man of Denisova Cave and Zoogeography of Pleistocene Mammals of Northwestern Altai

Mammal population of the northwestern Altai included residents, autochthonous species, cosmopolitans, and migrants. The last clearly indicate biogeographical relationships of the biota of the Altai Mountains in the Pleistocene. Most of them penetrated into the Altai from the south. The majority of ungulates and rodents migrated from Central Asia. Yak, red dog, and snow leopard came from the Himalayas, Pamir, and Tien Shan. The natural environment of the Altai Mountains in the Pleistocene enabled migrations of these mammals from the south to north. The same opportunity was true of the ancient man. It is possible to assume that humans migrated from southeastern Asia and Indochina along the eastern foothills of the Himalayas and Nan Shan Mountains to the northwest, to the Zaisan Depression and Altai. This resulted in inevitable exchange of gene material of Paleolithic human populations of southeastern Asia and the Altai