In breast cancer, the tumor microenvironment plays a critical role in the tumor progression and responses to therapy. Tumor-associated macrophages (TAMs) are major innate immune cells in tumor microenvironment that regulate intratumoral immunity and angiogenesis by secretion of cytokines, growth factors as well as chitinase-like proteins (CLPs), that combine properties of cytokines and growth factors. YKL-39 is a chitinase-like protein found in human and absent in rodents, and its expression in TAMs and role in breast cancer progression was not studied to date. Here for the first time we demonstrate that YKL-39 is expressed on TAMs, predominantly positive for stabilin-1, but not by malignant cells or other stromal cells in human breast cancer. TGF-beta in combination with IL-4, but not IL-4 alone was responsible of the stimulation of the production of YKL-39 in human primary macrophages. Mechanistically, stabilin-1 directly interacted with YKL-39 and acted as sorting receptor for targeting YKL-39 into the secretory pathway. Functionally, purified YKL-39 acted as a strong chemotactic factor for primary human monocytes, and induced angiogenesis in vitro. Elevated levels of YKL-39 expression in tumors after neoadjuvant chemotherapy (NAC) were predictive for increased risk of distant metastasis and for poor response to NAC in patients with nonspecific invasive breast carcinoma. Our findings suggest YKL-39 as a novel therapeutic target, and blocking of its activity can be combined with NAC in order to reduce the risk of metastasis in breast cancer patients.
A semiempirical method is suggested to construct the dipole moment function for a diatomic molecule in the form of a piecewise-continuous function that exhibits physically correct behaviour at small and large internuclear separations and agrees with the dipole moment function near the equilibrium position of molecule nuclei. The dipole moment functions are calculated for the ground electron states of the molecules HF, HCl, HBr, HI, OH, NO and CO for all ranges of internuclear separations.
Transition to an all-metal wall was realized on T-10 by replacement of graphite limiters with tungsten ones. Light impurity levels remained high and W accumulation in the plasma core was revealed. A movable lithium (Li) limiter was added to investigate the possibility of the limitation of tungsten and light impurity levels in plasma. For the first time, tokamak results on tungsten protection with Li were obtained in OH and ECRH regimes. After lithization the tungsten density in the core dropped more than an order of magnitude, while W influx into plasma decreased 2–4 times. Drastic drops of light impurities in plasma were observed together with improvement of energy confinement time and density limit values. Nevertheless, Li levels in plasma remained low in both OH and ECRH regimes. Li density in the core as low as 0.5% of ne was obtained. Tungsten transport in T-10 plasma was investigated and results on prevention of W accumulation with central ECRH were obtained. Effects of plasma exposure on ITER-grade tungsten plates from limiters were studied. Investigations of density fluctuation with correlation reflectometry confirmed a decrease of fluctuation amplitude on high field side. Modeling showed that this effect can be, to a great extent, explained by the non-locality of reflectometry. Toroidal correlations at a distance of 2.5 m along field lines were studied. Three-wave interaction between geodesic acoustic modes and broad-band turbulence was found by analysis of heavy ion beam probe diagnostics data. The possibility of plasma current control and the prevention of non-thermal electron beams formation at density limit disruption by means of ECR heating and the controlled operation of OH power supply system has been demonstrated. The study of plasma density decay after gas puff switch off during density ramp-up phase in OH regimes and the effect of ‘density pump out’ during ECRH showed that both effects can be explained by the assumption regarding electron transport growth upon reaching marginal pressure profile. A new type of internal transport barrier in the narrow zone near q = 1 surface has been found.
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