No abstract

Histone deacetylases (HDACs) are a vast family of enzymes involved in chromatin remodeling and have crucial roles in numerous biological processes, largely through their repressive influence on transcription. In addition to modifying histones, HDACs also target many other non-histone protein substrates to regulate gene expression. Recently, HDACs have gained growing attention as HDAC-inhibiting compounds are being developed as promising cancer therapeutics. Histone deacetylase inhibitors (HDACi) have been shown to induce differentiation, cell cycle arrest, apoptosis, autophagy and necrosis in a variety of transformed cell lines. In this review, we mainly discuss how HDACi may elicit a therapeutic response to human cancers through different cell death pathways, in particular, apoptosis and autophagy.

Quercetin can inhibit the growth of cancer cells with the ability to act as chemopreventers. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. Nuclear factor kappa-B (NF-κB) is a signaling pathway that controls transcriptional activation of genes important for tight regulation of many cellular processes and is aberrantly expressed in many types of cancer. Inhibitors of NF-κB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in colon cancer. In this study, we demonstrate that quercetin induces apoptosis in human colon cancer CACO-2 and SW-620 cells through inhibiting NF-κB pathway, as well as down-regulation of B-cell lymphoma 2 and up-regulation of Bax, thus providing basis for clinical application of quercetin in colon cancer cases.

A growing understanding of the molecular interactions between immune effector cells and target tumor cells, coupled with refined gene therapy approaches, are giving rise to novel cancer immunotherapeutics with remarkable efficacy in the clinic against both solid and liquid tumors. While immunotherapy holds tremendous promise for treatment of certain cancers, significant challenges remain in the clinical translation to many other types of cancers and also in minimizing adverse effects. Therefore, there is an urgent need for functional potency assays, in vitro and in vivo, that could model the complex interaction of immune cells with tumor cells and can be used to rapidly test the efficacy of different immunotherapy approaches, whether it is small molecule, biologics, cell therapies or combinations thereof. Herein we report the development of an xCELLigence real-time cytolytic in vitro potency assay that uses cellular impedance to continuously monitor the viability of target tumor cells while they are being subjected to different types of treatments. Specialized microtiter plates containing integrated gold microelectrodes enable the number, size, and surface attachment strength of adherent target tumor cells to be selectively monitored within a heterogeneous mixture that includes effector cells, antibodies, small molecules, etc. Through surface-tethering approach, the killing of liquid cancers can also be monitored. Using NK92 effector cells as example, results from RTCA potency assay are very well correlated with end point data from image-based assays as well as flow cytometry. Several effector cells, i.e., PBMC, NK, CAR-T were tested and validated as well as biological molecules such as Bi-specific T cell Engagers (BiTEs) targeting the EpCAM protein expressed on tumor cells and blocking antibodies against the immune checkpoint inhibitor PD-1. Using the specifically designed xCELLigence immunotherapy software, quantitative parameters such as KT50 (the amount of time it takes to kill 50% of the target tumor cells) and % cytolysis are calculated and used for comparing the relative efficacy of different reagents. In summary, our results demonstrate the xCELLigence platform to be well suited for potency assays, providing quantitative assessment with high reproducibility and a greatly simplified work flow.

The association between vascular stiffening and blood pressure is likely bidirectional. The present study was designed to examine temporal relationships among vascular stiffness, blood pressure progression, and hypertension. The Asymptomatic Polyvascular Abnormalities Community study is a community-based, prospective, long-term follow-up observational study. The present investigation is based on the baseline examinations (2010)(2011) and the first follow-up measurements (2012)(2013) included in the study. A total of 4025 participants were followed for an average of 27 months. Of 2153 participants free of hypertension at the baseline examination, 432 (20.07%) had incident hypertension. The authors observed that brachial-ankle pulse wave velocity (baPWV) was an independent predictor of incident hypertension. baPWV during baseline examination was positively associated with higher systolic blood pressure, diastolic blood pressure, pulse pressure, and mean arterial pressure during the first follow-up examination. baPWV but not blood pressure during baseline examination was associated with baPWV during the first follow-up examination. This study not only provides evidence that baPWV is an independent predictor of blood pressure progression and incident hypertension, but also provides evidence that blood pressure is not associated with baPWV after adjusting for baseline baPWV. J Clin Hypertens (Greenwich). 2015;17:582-591. ª 2015 Wiley Periodicals, Inc.Arterial stiffness and blood pressure (BP), which increase with age, are associated with increased morbidity and mortality of cardiovascular diseases.1,2 It is traditionally believed that elevated BP may cause structural and functional alterations in the walls of the central elastic arteries and accelerated conduit artery stiffening.3,4 Conversely, conduit artery stiffening may increase pressure pulsatility and thereby may increase systolic BP (SBP). Temporal relationships between vascular stiffness and BP remain incompletely elucidated. Moreover, arterial stiffness is increasingly recognized as an important prognostic index and potential therapeutic target in patients with hypertension. 5,6 The 2013 guidelines for the management of arterial hypertension acknowledge the potential role of arterial stiffness measurement in clinical management. 7Several previous observational studies have revealed that aortic stiffness predicts progression to hypertension in normotensive individuals. [8][9][10][11][12][13][14][15] However, assessment of aortic stiffness using echocardiography is not the most suitable method since specialized equipment and expertise is required. Carotid-femoral pulse wave velocity (cf-PWV) is considered a "gold-standard" method for assessing central artery stiffness, but the technique is hindered by the intimate nature of femoral pulse acquisition and is not the most suitable method for mass examination of individuals to identify those with increased risk of hypertension. Brachial-ankle pulse wave velocity (baPWV) is an alternatively developed technique with...