Hypoxia represents a frequent player in a number of malignancies, contributing to the development of the neoplastic disease. This review will discuss the means by which hypoxia powers the mechanisms behind cancer progression, with a majority of examples from lung cancer, the leading malignancy in terms of incidence and mortality rates (the frequent reference toward lung cancer is also for simplification purposes and follow up of the global mechanism in the context of a disease). The effects induced by low oxygen levels are orchestrated by hypoxia-inducible factors (HIFs) which regulate the expression of numerous genes involved in cancer progression. Hypoxia induces epithelial-to-mesenchymal transition (EMT) and metastasis through a complex machinery, by mediating various pathways such as TGF-β, PI3k/Akt, Wnt, and Jagged/Notch. Concomitantly, hypoxic environment has a vast implication in angiogenesis by stimulating vessel growth through the HIF-1α/VEGF axis. Low levels of oxygen can also promote the process through several other secondary factors, including ANGPT2, FGF, and HGF. Metabolic adaptations caused by hypoxia include the Warburg effect—a metabolic switch to glycolysis—and GLUT1 overexpression. The switch is achieved by directly increasing the expression of numerous glycolytic enzymes that are isoforms of those found in non-malignant cells.

Atherosclerosis is a key pathological process that causes a plethora of pathologies, including coronary artery disease, peripheral artery disease, and ischemic stroke. The silent progression of the atherosclerotic disease prompts for new surveillance tools that can visualize, characterize, and provide a risk evaluation of the atherosclerotic plaque. Conventional ultrasound methods—bright (B)-mode US plus Doppler mode—provide a rapid, cost-efficient way to visualize an established plaque and give a rapid risk stratification of the patient through the Gray–Weale standardization—echolucent plaques with ≥50% stenosis have a significantly greater risk of ipsilateral stroke. Although rather disputed, the measurement of carotid intima-media thickness (C-IMT) may prove useful in identifying subclinical atherosclerosis. In addition, contrast-enhanced ultrasonography (CEUS) allows for a better image resolution and the visualization and quantification of plaque neovascularization, which has been correlated with future cardiovascular events. Newly emerging elastography techniques such as strain elastography and shear-wave elastography add a new dimension to this evaluation—the biomechanics of the arterial wall, which is altered in atherosclerosis. The invasive counterpart, intravascular ultrasound (IVUS), enables an individualized assessment of the anti-atherosclerotic therapies, as well as a direct risk assessment of these lesions through virtual histology IVUS.

Global statistics show an increasing percentage of patients that develop non-alcoholic fatty liver disease (NAFLD) and NAFLD-related hepatocellular carcinoma (HCC), even in the absence of cirrhosis. In the present review, we analyzed the diagnostic performance of ultrasonography (US) in the non-invasive evaluation of NAFLD and NAFLD-related HCC, as well as possibilities of optimizing US diagnosis with the help of artificial intelligence (AI) assistance. To date, US is the first-line examination recommended in the screening of patients with clinical suspicion of NAFLD, as it is readily available and leads to a better disease-specific surveillance. However, the conventional US presents limitations that significantly hamper its applicability in quantifying NAFLD and accurately characterizing a given focal liver lesion (FLL). Ultrasound contrast agents (UCAs) are an essential add-on to the conventional B-mode US and to the Doppler US that further empower this method, allowing the evaluation of the enhancement properties and the vascular architecture of FLLs, in comparison to the background parenchyma. The current paper also explores the new universe of AI and the various implications of deep learning algorithms in the evaluation of NAFLD and NAFLD-related HCC through US methods, concluding that it could potentially be a game changer for patient care.

Long non-coding RNAs (lncRNA) have recently been identified as key regulators of oxidative stress in several malignancies. The level of reactive oxygen species (ROS) must be constantly regulated to maintain cancer cell proliferation and chemoresistance and to prevent apoptosis. This review will discuss how lncRNAs alter the ROS level in cancer cells. We will first describe the role of lncRNAs in the nuclear factor like 2 (Nrf-2) coordinated antioxidant response of cancer cells. Secondly, we show how lncRNAs can promote the Warburg effect in cancer cells, thus shifting the cancer cell’s “building blocks” towards molecules important in oxidative stress regulation. Lastly, we explain the role that lncRNAs play in ROS-induced cancer cell apoptosis and proliferation.

Advancement in cancer research has shown that the tumor microenvironment plays a crucial role in the installation, progression, and dissemination of cancer cells. Among the heterogeneous panel of cells within the malignant microenvironment are tumor-associated macrophages that are sustaining the malignant cells through strict feedback mechanisms and spatial distribution. Considering that the presence of metastasis is one of the main feature associated with decreased survival rates among patients, in the present article we briefly present the involvement of tumor-associated macrophages in the hallmarks of metastasis and their microRNA-related regulation with a focus on lung cancer in order to coordinate the vast information under one pathology. As shown, these cells have emerged as coordinators of immunosuppression, angiogenesis and lymphangiogenesis, vessel intravasation and extravasation of cancer cells, and premetastatic niche formation, transforming the macrophages in potential therapeutic targets and also prognostic markers according to their density within the tumor and polarization phenotype. An indirect therapeutic approach on tumor-associated macrophages can be also represented by regulation of microRNAs involved in their polarization and implicit oncogenic features. Examples of these microRNAs consist in the highly studied miR-21 and miR-155, but also other microRNA with less feedback in the literature: miR-1207-5p, miR-193b, miR-320a, and others.