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Anti-angiogenic therapies for cancer such as VEGF neutralizing antibody bevacizumab have limited durability. While mechanisms of resistance remain undefined, it is likely that acquired resistance to anti-angiogenic therapy will involve alterations of the tumor microenvironment. We confirmed increased tumor-associated macrophages in bevacizumab-resistant glioblastoma patient specimens and two novel glioblastoma xenograft models of bevacizumab resistance. Microarray analysis suggested downregulated macrophage migration inhibitory factor (MIF) to be the most pertinent mediator of increased macrophages. Bevacizumab-resistant patient glioblastomas and both novel xenograft models of resistance had less MIF than bevacizumab-naive tumors, and harbored more M2/protumoral macrophages that specifically localized to the tumor edge. Xenografts expressing MIF-shRNA grew more rapidly with greater angiogenesis and had macrophages localizing to the tumor edge which were more prevalent and proliferative, and displayed M2 polarization, whereas bevacizumab-resistant xenografts transduced to upregulate MIF exhibited the opposite changes. Bone marrow-derived macrophage were polarized to an M2 phenotype in the presence of condition-media derived from bevacizumab-resistant xenograft-derived cells, while recombinant MIF drove M1 polarization. Media from macrophages exposed to bevacizumab-resistant tumor cell conditioned media increased glioma cell proliferation compared with media from macrophages exposed to bevacizumab-responsive tumor cell media, suggesting that macrophage polarization in bevacizumab-resistant xenografts is the source of their aggressive biology and results from a secreted factor. Two mechanisms of bevacizumab-induced MIF reduction were identified: (1) bevacizumab bound MIF and blocked MIF-induced M1 polarization of macrophages; and (2) VEGF increased glioma MIF production in a VEGFR2-dependent manner, suggesting that bevacizumab-induced VEGF depletion would downregulate MIF. Site-directed biopsies revealed enriched MIF and VEGF at the enhancing edge in bevacizumab-naive patients. This MIF enrichment was lost in bevacizumab-resistant glioblastomas, driving a tumor edge M1-to-M2 transition. Thus, bevacizumab resistance is driven by reduced MIF at the tumor edge causing proliferative expansion of M2 macrophages, which in turn promotes tumor growth.

The He isotopic composition and the He and Ne ratio of fluid inclusions in magnetite and pyrite from carbonatite breccias of the Sallanlatva alkali-ultramafic complex of the Kola alkaline province (Northwest Russia) are studied using the step-crushing method. The results indicate the highly likely involvement of fluids from several sources trapped in various proportions during the formation of the Sallanlatva explosive carbonatite breccias. The R/Ra ratio, where R is the measured 3He/4He ratio and Ra of 1.382 × 10–6 is the same ratio of atmospheric air, reaches 2.3, which is a reliable indicator of the presence of mantle gases. A low (1–44) 4He/20Ne ratio allows us to suggest the involvement of atmospheric gases dissolved in paleometeoric waters. A combination of these two facts favors a hypothesis of the phreatomagmatic nature of the studied breccias, i.e., their formation at the expense of interaction between the intruding hot orthomagmatic fluids and meteoric waters with dissolved atmospheric gases. [ABSTRACT FROM AUTHOR]

The Sallanlatva massif belongs to the group of Paleozoic alkaline-ultrabasic complexes wide spread in the Kola Region (the northwestern part of the Fennoscandian Shield). In the central part of this massif, the host ijolite and urtites contain calcite, ankerite, ankerite-dolomite and siderite carbonatites. The explosive processes that led to the formation of carbonatite breccias in the calcite and ankerite-dolomite carbonatites occurred in Sallanlatva massife in the last stages of the carbonatite magmatism. There are two types of explosive carbonatite breccias in the Sallanlatva massif: (1) glimmerite-calciocarbonatite breccias, and (2) siderite-dolomite breccias. Analysis of the mineral composition of fragments and matrix and the shape of fragments in breccias has shown that the first material to intrude into the host calcite and ankerite-dolomite carbonatites was calcite melt. After that, dolomite melt penetrated through the fracture zones, which resulted in the formation of siderite-dolomite breccias. The differences in the mineral composition of the breccia matrix suggest that the residual carbonatite melts originate from separate magma chambers. The chamber with calcite melt was located at great depth, and some captured glimmerite fragments were abraded during the melt upwelling. Silicate-dolomite melts lifted from a shallower depth; the captured fragments of siderite carbonatites retained their angular shape. Late hydrothermal processes yielded veins and caverns with Ba-Sr-P-S-Ti-REE mineralization in the breccias and host rocks.

The objects of the study are apocarbonatitic titanium metasomatites ("titanium carbonatites") associated with the rare earth carbonatites of the Petyayan-Vara area of the Vuoriyarvi complex (the Kola region). In this paper, the following mechanism for the formation of these rocks has been substantiated based on the agreed results of mineralogical and geochemical studies. Prior to the onset of carbonatite genesis, a fluorine-enriched fluid phase originated in the lower horizons of the complex passed along the deep-permeating fracture system of several hundred meters length up to the level of the modern erosion surface. It transported Al, Fe2+, Mg, Ti, P into the pyroxenites and Si, Ca and Na out of them, as a result of which the pyroxenites were transformed into giant-grained phlogopite rocks – glimmerites. The most probable source of this fluid is alkaline aluminosilicate magma. Then carbonate melts intruded along the same fractures. In the course of carbonatite genesis, F-fluid caused a local migration of K, Al, Si, Fe, P, Ti, Nb, Ta, Zr, Hf and HREE out of glimmerites into igneous dolomite carbonatites, which led to the formation of apocarbonatitic titanium metasomatites. They represent several paragenetic associations superimposed on each other, the mineral composition and the formation sequence of which correspond to the metasomatic column zones directly observed within the contact "carbonatite – altered pyroxenite". The separation of HFSE and REE is controlled by the same metasomatic column: Ti, Nb and Ta were accumulated in titanium carbonatites, i. e. in associations of the frontal and intermediate zones, and Zr, Hf and HREE – in apatitized fields corresponding to the rear zone of the column. Accordingly, the fractionation of these elements occurred due to the "fluid – rock" interaction. Subsequently, the same long-lived fractures served as a channel for REE-Sr-Ba-S fluids, but the recrystallization caused by K-Al-Si-Ti-F-metasomatism made titanium carbonatites dense and fine-grained in texture, what, in most cases, "protected" these rocks from the influences of later processes.

The paper presents data on the study of iron-bearing minerals formed in the oxidation zone of massive sulfide ores. The minerals are represented by two groups: oxides, i. e. goethite and lepidocrocite, and sulfates, i. e. melanterite and rozenit. Mineral identification has been produced by Raman spectroscopy, these data have been confirmed by scanning electron microscopy and X-ray powder diffraction. The resulting Raman spectra have been compared with the spectra of the known database and the results of previous studies of these minerals. Goethite and lepidocrocite are polymorphic modifications formed under the specific conditions by the influence of special solutions. Goethite has diagnostic bands at 243 cm–1, 300 cm–1, 391 cm–1, 480 cm–1, 552 cm–1, 681 cm–1 , and 995 cm–1, diagnostic bands of lepidocrocite – 252 cm–1, 381 cm–1, 528 cm–1, and 652 cm–1. Discovered small crystals in the lepidocrocite veins have been diagnosed as magnetite, with diagnostic bands at 678 cm–1, 549 cm–1 , and 316 cm–1. Goethite and lepidocrocite are formed on the surface of a complex pyrrhotite-marcasite aggregate with "bird's-eye" structure. The presence of pyrite and marcasite is confirmed by Raman spectrum which has pyrite bands (343 cm–1 and 403 cm–1) and marcasite bands (323 cm–1 and 386 cm–1). Melanterite and rozenite are formed under the influence of surface water on sulfide ores or other readily degradable iron-bearing minerals, as well as in confined spaces with high humidity. Raman spectra of these minerals well differ from each other allowing them reliably diagnose. There are sulfate anion [SO4]2– vibrations in the range of 990–1010 cm–1, and vibrations of the H–O–H in the range of 3 000–4000 cm–1 and 1 500–1700 cm–1 on the spectra. As a result of the research the authors can certainly confirm that Raman spectroscopy can be used as a reliable method for mineral identification