SGK1 in Cancer: Biomarker and Drug Target.

Serum- and glucocorticoid-regulated kinases (SGKs) are members of the AGC family of serine/threonine kinases, consisting of three isoforms: SGK1, SGK2, and SGK3. SGK1 was initially cloned as a gene transcriptionally stimulated by serum and glucocorticoids in rat mammary tumor cells. It is upregulated in some cancers and downregulated in others. SGK1 increases tumor cell survival, adhesiveness, invasiveness, motility, and epithelial to mesenchymal transition. It stimulates tumor growth by mechanisms such as activation of K+ channels and Ca2+ channels, Na+/H+ exchanger, amino acid and glucose transporters, downregulation of Foxo3a and p53, and upregulation of ß-catenin and NFκB. This chapter focuses on major aspects of SGK1 involvement in cancer, its use as biomarker as well as potential therapeutic target.

Correction to: Prevalence and prognostic value of late gadolinium enhancement on CMR in aortic stenosis: meta-analysis.

The original version of this article, published on 12 August 2019, unfortunately contained a mistake. The funding note was incorrect; the correct funding note is given below.

Prevalence and prognostic value of late gadolinium enhancement on CMR in aortic stenosis: meta-analysis.

OBJECTIVES: The aim of this study was to investigate the prevalence and prognostic value of late gadolinium enhancement (LGE), as assessed by cardiovascular magnetic resonance (CMR) imaging, in patients with aortic stenosis. METHODS AND RESULTS: A systematic search of PubMed and EMBASE was performed, and observational cohort studies that analysed the prevalence of LGE and its relation to clinical outcomes in patients with aortic stenosis were included. Odds ratios were used to measure an effect of the presence of LGE on both all-cause and cardiovascular mortality. Nineteen studies were retrieved, accounting for 2032 patients (mean age 69.8 years, mean follow-up 2.8 years). We found that LGE is highly prevalent in aortic stenosis, affecting half of all patients (49.6%), with a non-infarct pattern being the most frequent type (63.6%). The estimated extent of focal fibrosis, expressed in % of LV mass, was equal to 3.83 (95% CI [2.14, 5.52], p < 0.0001). The meta-analysis showed that the presence of LGE was associated with increased all-cause (pooled OR [95% CI] = 3.26 [1.72, 6.18], p = 0.0003) and cardiovascular mortality (pooled OR [95% CI] = 2.89 [1.90, 4.38], p < 0.0001). CONCLUSIONS: LGE by CMR is highly prevalent in aortic stenosis patients and exhibits a substantial value in all-cause and cardiovascular mortality prediction. These results suggest a potential role of LGE in aortic stenosis patient risk stratification. KEY POINTS: • Up to the half of aortic stenosis patients are affected by myocardial focal fibrosis. • Sixty-four percent of focal fibrosis detected by LGE-CMR is non-infarct type. • The presence of focal fibrosis triples all-cause and cardiovascular mortality.

Transthyretin cardiac amyloidosis in aortic stenosis: Prevalence, diagnostic challenges, and clinical implications.

Transthyretin cardiac amyloidosis (ATTR-CA) is a challenging and underdiagnosed cause of heart failure. Advances in cardiac imaging have enabled noninvasive diagnosis of ATTR-CA, causing the recent upsurge in disease awareness and detection. ATTR-CA has been increasingly recognized in patients with degenerative aortic stenosis (AS). With the growing number of elderly patients undergoing aortic valve intervention, the identification of ATTR-CA in this group of patients is of high clinical importance. Timely and correct diagnosis is essential for amyloid-directed therapies, as well as deciding on the AS treatment strategy. This review provides a comprehensive overview of the recent studies investigating coexistence of these two entities. We present the data on the prevalence of ATTR-CA in AS and their prognostic associations. As the diagnosis of ATTR-CA may be challenging, special attention is paid to the diagnostic utility of different imaging modalities, namely, echocardiography, cardiovascular magnetic resonance, nuclear imaging, and distinctive imaging features, in patients with dual pathology. We also present a flowchart summarizing integrated imaging in patients with suspected ATTR-CA.

JNK, p38, ERK, and SGK1 Inhibitors in Cancer.

Mitogen-activated protein kinases (MAP kinases) are a family of kinases that regulates a range of biological processes implicated in the response to growth factors like latelet-derived growth factor (PDGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and stress, such as ultraviolet irradiation, heat shock, and osmotic shock. The MAP kinase family consists of four major subfamilies of related proteins (extracellular regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38, and extracellular regulated kinase 5 (ERK5)) and regulates numerous cellular activities, such as apoptosis, gene expression, mitosis, differentiation, and immune responses. The deregulation of these kinases is shown to be involved in human diseases, such as cancer, immune diseases, inflammation, and neurodegenerative disorders. The awareness of the therapeutic potential of the inhibition of MAP kinases led to a thorough search for small-molecule inhibitors. Here, we discuss some of the most well-known MAP kinase inhibitors and their use in cancer research.

Metabolomics in pancreatic cancer biomarkers research.

Pancreatic cancer is one of the worst prognoses of all malignancies. More than 40,000 deaths a year from this disease are observed in European Union alone. The only possibly curative treatment of pancreatic cancer is surgery, yet only 15-20% of patients have operable disease and even patients, which go through surgery and adjuvant chemotherapy, survival is less than 30%. The sensitive and specific biomarkers which could be used for the advance of early diagnostics are needed and constantly researched. Metabolomics is a technology which analyzes the concentrations of low-molecular-weight metabolites (the metabolome) has lately effectively developed due to the improvements in analytical technology. Metabolome analysis can be a one of the useful approaches for the biomarker discovery and disease diagnosis. Here we discuss recent discoveries in the field of pancreatic cancer metabolomics as well as the most promising biomarkers for diagnostics, prognosis and prediction.