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Macrophages constitute a major part of tumor microenvironment, and most of existing data demonstrate their ruling role in the development of anti-drug resistance of cancer cell. One of the most powerful protection system is based on heat shock proteins whose synthesis is triggered by activated Heat Shock Factor-1 (HSF1); the inhibition of the HSF1 with CL-43 sensitized A549 lung cancer cells to the anti-cancer effect of etoposide. Notably, analyzing A549 tumor xenografts in mice we observed nest-like pattern of co-localization of A549 cells demonstrating enhanced expression of HSF1 with macrophages, and decided to check whether the above arrangement has a functional value for both cell types. It was found that the incubation of A549 or DLD1 colon cancer cells with either human monocytes or THP1 monocyte-like cells activated HSF1 and increased resistance to etoposide. Importantly, the same effect was shown when primary cultures of colon tumors were incubated with THP1 cells or with human monocytes. To prove that HSF1 is implicated in enhanced resistance caused by monocytic cells, we generated an A549 cell subline devoid of HSF1 which did not respond to incubation with THP1 cells. The pharmacological inhibition of HSF1 with CL-43 also abolished the effect of THP1 cells on primary tumor cells, highlighting a new target of tumor-associated macrophages in a cell proteostasis mechanism. [ABSTRACT FROM AUTHOR]

The paper presents the results of biomedical investigations of sutures made of polyhydroxyalkanoates (PHAs) of two types (poly-3-hydroxybutyrate (PHB) and poly-3-hydroxybutyrate-co-poly-3-hydroxyvalerate (PHB/PHV)), synthesized by the bacteria Ralstonia eutropha B 5786 in the experiment on test animals in vivo, in comparison with silk and catgut sutures. PHB and PHB/PHV (PHBV) implants produced no adverse effect on physiological, biochemical and functional parameters of the animals during the post-surgery period. The tested PHA sutures featured the necessary strength throughout the healing period of the muscle-fascial cuts. The reaction of tissues to the implantation of PHB and PHB/PHV fibers fitted into the usual scheme characteristic of the wound process and of the reaction to a foreign-body invasion. This reaction and the reaction of tissues to silk had the similar nature and period of inflammation, but it was much less pronounced than the reaction to catgut. The tissue response to the implantation of PHAs consisted in a short-duration (up to 2 weeks) post-traumatic inflammation and the formation of a fibrous capsule less than 200 μm thick during weeks 4–8, which in 4–6 months was reduced to 40–60 μm in the course of reverse development. There were no adverse changes, such as suppurative inflammation, necrosis, calcification, and malignization of the cicatrice, at the site of implantation of PHA filaments, unlike in the cases with silk and catgut. In the case of PHA implantation there was a typical prolonged (throughout the post-surgery monitoring period) pronounced macrophagal stage with a large number of macrophages present. The macrophages were of the phagocytic type and multinucleate giant foreign cells, with a high activity of acid phosphomonoesterase that correlated with the activity of the enzyme in blood. Throughout the period of monitoring no differences in the tissue response to the implantation of the polymer filaments of two PHA types were recorded. [Copyright &y& Elsevier]