Granulocyte colony‐stimulating factor (G‐CSF) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) modulate progression of certain solid tumors. The G‐CSF‐ or GM‐CSF‐secreting cancers, albeit not very common are, however, among the most rapidly advancing ones due to a cytokine‐mediated immune suppression and angiogenesis. Similarly, de novo angiogenesis and vasculogenesis may complicate adjuvant use of recombinant G‐CSF or GM‐CSF thus possibly contributing to a cancer relapse. Rapid diagnostic tools to differentiate G‐CSF‐ or GM‐CSF‐secreting cancers are not well developed therefore hindering efforts to individualize treatments for these patients. Given an increasing utilization of adjuvant G‐/GM‐CSF in cancer therapy, we aimed to summarize recent studies exploring their roles in pathophysiology of solid tumors and to provide insights into some complexities of their therapeutic applications.

Signaling pathways activation profiles make better markers of cancer than expression of individual genes Signaling pathways activation profiles make better markers of cancer than expression of individual genes

The investigation of alkylresorcinols has drawn an increasing interest recently. Alkylresorcinols (ARs) are natural chemical compounds synthesized by bacteria, fungi, sponges, and higher plants, possessing a lipophilic polyphenol structures and a myriad of biological properties. Human takes ARs as a component of a whole grain diet (from whole grain rye, wheat, and barley products), and thus, alkylresorcinols are frequently used as whole grain intake markers. Besides, ARs are considered as promising bioregulators of metabolic and immune processes, as well as adjuvant therapeutic agents for antimicrobial and anticancer treatment. In this review, we attempted to systematize the accumulated information concerning ARs origin, metabolism, biological properties, and their effect on human health.

Significance: We identified a human-specific endogenous retroviral insert (hsERV) that acts as an enhancer for humanPRODH, hsERV_PRODH.PRODHencodes proline dehydrogenase, which is involved in neuromediator synthesis in the CNS. We show that the hsERV_PRODH enhancer acts synergistically with the CpG island ofPRODHand is regulated by methylation. We detected highPRODHexpression in the hippocampus, which was correlated with the undermethylated state of this enhancer.PRODHregulatory elements provide neuron-specific transcription in hippocampal cells, and the mechanism of hsERV_PRODH enhancer activity involves the binding of transcriptional factor SOX2. BecausePRODHis associated with several neurological disorders, we hypothesize that the human-specific regulation ofPRODHby hsERV_PRODH may have played a role in human evolution by upregulating the expression of this important CNS-specific gene.

For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.

In solid cancers, myeloid derived suppressor cells (MDSC) infiltrate (peri)tumoral tissues to induce immune tolerance and hence to establish a microenvironment permissive to tumor growth. Importantly, the mechanisms that facilitate such infiltration or a subsequent immune suppression are not fully understood. Hence, in this study, we aimed to delineate disparate molecular pathways which MDSC utilize in murine models of colon or breast cancer. Using pathways enrichment analysis, we completed interactome maps of multiple signaling pathways in CD11b+/Gr1(high/low) MDSC from spleens and tumor infiltrates of mice with c26GM colon cancer and tumor infiltrates of MDSC in 4T1 breast cancer. In both cancer models, infiltrating MDSC, but not CD11b+ splenic cells, have been found to be enriched in multiple signaling molecules suggestive of their enhanced proliferative and invasive phenotypes. The interactome data has been subsequently used to reconstruct a previously unexplored regulation of MDSC cell cycle by the c-myc transcription factor which was predicted by the analysis. Thus, this study represents a first interactome mapping of distinct multiple molecular pathways whereby MDSC sustain cancer progression.