Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for Hepatocellular Carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across TNM stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types

An Overview of Three Promising Mechanical, Optical, and Biochemical Engineering Approaches to Improve Selective Photothermolysis of Refractory Port Wine Stains

During the last three decades, several laser systems, ancillary technologies, and treatment modalities have been developed for the treatment of port wine stains (PWSs). However, approximately half of the PWS patient population responds suboptimally to laser treatment. Consequently, novel treatment modalities and therapeutic techniques/strategies are required to improve PWS treatment efficacy. This overview therefore focuses on three distinct experimental approaches for the optimization of PWS laser treatment. The approaches are addressed from the perspective of mechanical engineering (the use of local hypobaric pressure to induce vasodilation in the laser-irradiated dermal microcirculation), optical engineering (laser-speckle imaging of post-treatment flow in laser-treated PWS skin), and biochemical engineering (light- and heat-activatable liposomal drug delivery systems to enhance the extent of post-irradiation vascular occlusion)

Role of Cancer Microenvironment in Metastasis: Focus on Colon Cancer

One person on three will receive a diagnostic of cancer during his life. About one third of them will die of the disease. In most cases, death will result from the formation of distal secondary sites called metastases. Several events that lead to cancer are under genetic control. In particular, cancer initiation is tightly associated with specific mutations that affect proto-oncogenes and tumour suppressor genes. These mutations lead to unrestrained growth of the primary neoplasm and a propensity to detach and to progress through the subsequent steps of metastatic dissemination. This process depends tightly on the surrounding microenvironment. In fact, several studies support the point that tumour development relies on a continuous cross-talk between cancer cells and their cellular and extracellular microenvironments. This signaling cross-talk is mediated by transmembrane receptors expressed on cancer cells and stromal cells. The aim of this manuscript is to review how the cancer microenvironment influences the journey of a metastatic cell taking liver invasion by colorectal cancer cells as a model

Lipid (per) oxidation in mitochondria:an emerging target in the ageing process?

Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation. In addition, senescent cells, which are known to contribute significantly to age-related pathologies, are also associated with impaired mitochondrial function and changes in lipid metabolism. Therapeutic targeting of dysfunctional mitochondrial and pathological lipid metabolism is an emerging strategy for alleviating their negative impact during ageing and the progression to age-related diseases. Such therapies could include the use of drugs that prevent mitochondrial uncoupling, inhibit inflammatory lipid synthesis, modulate lipid transport or storage, reduce mitochondrial oxidative stress and eliminate senescent cells from tissues. In this review, we provide an overview of lipid structure and function, with emphasis on mitochondrial lipids and their potential for therapeutic targeting during ageing and age-related disease

Factors Associated with Healing Outcomes in Primary Care Patients with Diabetic Foot Ulcers: A Retrospective Study in a Multiethnic Sample

OBJECTIVE To identify and determine patient- and ulcer-related factors associated with healing outcomes within 3 months for patients with diabetic foot ulcer (DFU) in a multiethnic primary care sample. METHODS Retrospective data were collected over 3 months from 520 primary care patients with a DFU between April 1, 2016 and March 31, 2017. Multivariable prevalence ratios (PRs) were calculated using Poisson regression to find associations between patient- and ulcer-related factors and healing outcomes. RESULTS Most patients were male (66%) and Chinese (49.8%) and had a diabetes mellitus duration longer than 5 years (81.8%). Toe ulcers (64%) were most common. Healing occurred for 33.9% of participants; 19.1% and 1.5% underwent minor and major amputation, respectively. Wound sizes between 1 and 10 cm2 (PR, 0.61; 95% confidence interval [CI], 0.46–0.76; P < .001) and over 10 cm2 (PR, 0.55; 95% CI, 0.33–0.76; P = .003), ulcer duration 6 months or longer (PR, 0.36; 95% CI, 0.19–0.53; P < .001), ischemic ulcers (PR, 0.54; 95% CI, 0.22–0.86; P = .044), and neuroischemic ulcers (PR, 0.73; 95% CI, 0.53–0.93; P = .027) were negatively associated with healing outcomes. Women were more likely to experience healing (PR, 1.18; 95% CI, 0.91–1.45; P = .157). CONCLUSIONS Ulcer healing varied by sex and was affected by wound size, wound duration, and ischemic etiology, regardless of ethnicity. Prompt attention to these risk factors may reduce healing time. Further studies are warranted to elucidate the mechanism underlying sex differences in association with DFU healing