BACKGROUND Natural killer (NK) cells have a spontaneous cytotoxic capacity against tumor cells. These cells represent a small proportion of human colon carcinoma‐infiltrating lymphocytes. Their prognostic significance in these tumors has yet to be determined. METHODS One hundred and fifty‐seven patients who each had a colectomy for large bowel adenocarcinoma were studied. No patient received adjuvant therapy. Immunohistochemical stains were performed for NK cells using the monoclonal antibody CD57. The number of NK cells was counted using a MICRON image analyzer. The total area studied for each tumor was 1 cm². In this area, 50 intratumoral fields of 0.173 mm² were selected. The degree of NK infiltration was classified as little (150 NK cells). The Kaplan‐Meier method was used to obtain survival figures. Multivariate analyses were performed using the Cox regression model. RESULTS At 5 years, patients with little and moderate NK infiltration showed significantly shorter survival rates (overall and disease free survival) than those with extensive infiltration (P < 0.01). Three significant factors affecting survival were selected in a stepwise fashion in increasing order as follows: TNM stage, NK infiltration, and lymphocytic infiltration. Patients with TNM Stage III disease and extensive NK infiltration showed significantly longer survival rates than those with little or moderate infiltration (P < 0.001). In these patients, multivariate analysis using the Cox regression model identified two significant variables: number of involved lymph nodes and NK cell infiltration. CONCLUSIONS In patients with colorectal carcinoma, an extensive intratumoral infiltration of NK cells is associated with a favorable tumor outcome. Intratumoral infiltration of NK cells can be used as a variable with prognostic value, especially in patients with TNM Stage III disease. Cancer 1997; 79:2320‐8. © 1997 American Cancer Society.

Hyperbaric oxygen therapy (HBOT) consists of using of pure oxygen at increased pressure (in general, 2–3 atmospheres) leading to augmented oxygen levels in the blood (Hyperoxemia) and tissue (Hyperoxia). The increased pressure and oxygen bioavailability might be related to a plethora of applications, particularly in hypoxic regions, also exerting antimicrobial, immunomodulatory and angiogenic properties, among others. In this review, we will discuss in detail the physiological relevance of oxygen and the therapeutical basis of HBOT, collecting current indications and underlying mechanisms. Furthermore, potential areas of research will also be examined, including inflammatory and systemic maladies, COVID-19 and cancer. Finally, the adverse effects and contraindications associated with this therapy and future directions of research will be considered. Overall, we encourage further research in this field to extend the possible uses of this procedure. The inclusion of HBOT in future clinical research could be an additional support in the clinical management of multiple pathologies.

The placenta is a central structure in pregnancy and has pleiotropic functions. This organ grows incredibly rapidly during this period, acting as a mastermind behind different fetal and maternal processes. The relevance of the placenta extends far beyond the pregnancy, being crucial for fetal programming before birth. Having integrative knowledge of this maternofetal structure helps significantly in understanding the development of pregnancy either in a proper or pathophysiological context. Thus, the aim of this review is to summarize the main features of the placenta, with a special focus on its early development, cytoarchitecture, immunology, and functions in non-pathological conditions. In contraposition, the role of the placenta is examined in preeclampsia, a worrisome hypertensive disorder of pregnancy, in order to describe the pathophysiological implications of the placenta in this disease. Likewise, dysfunction of the placenta in fetal growth restriction, a major consequence of preeclampsia, is also discussed, emphasizing the potential clinical strategies derived. Finally, the emerging role of the placenta in maternal chronic venous disease either as a causative agent or as a consequence of the disease is equally treated.

In recent years, the importance of epigenetic markers in the carcinogenesis of different malignant neoplasms has been demonstrated, also demonstrating their utility for understanding metastatic spread and tumor progression in cancer patients. Among the different biomarkers, microRNAs represent a set of non-coding RNAs that regulate gene expression, having been involved in a wide variety of neoplasia acting in different oncogenic pathways. Both the overexpression and downregulation of microRNAs represent a complex interaction with various genes whose ultimate consequence is increased cell proliferation, tumor invasion and interaction with various driver markers. It should be noted that in current clinical practice, even though the combination of different microRNAs has been shown to be useful by different authors at diagnostic and prognostic levels, there are no diagnostic kits that can be used for the initial approach or to assess recurrences of oncological diseases. Previous works have cited microRNAs as having a critical role in several carcinogenic mechanisms, ranging from cell cycle alterations to angiogenesis and mechanisms of distant metastatic dissemination. Indeed, the overexpression or downregulation of specific microRNAs seem to be tightly involved in the modulation of various components related to these processes. For instance, cyclins and cyclin-dependent kinases, transcription factors, signaling molecules and angiogenic/antiangiogenic products, among others, have been recognized as specific targets of microRNAs in different types of cancer. Therefore, the purpose of this article is to describe the main implications of different microRNAs in cell cycle alterations, metastasis and angiogenesis, trying to summarize their involvement in carcinogenesis.

Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO₄³⁻ and ionized calcium (Ca²⁺). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic.