The Serine/Threonine Protein Kinase (Akt)/ Protein Kinase B (PkB) Signaling Pathway in Breast Cancer

According to statistical data published in 2019, breast cancer is among the leading causes of death in women worldwide. The serine/threonine kinase (AKT) or protein kinase B (PkB) signaling pathway is activated by phosphorylation processes, which further is associated with cell growth, proliferation, and survival, but also with activation of glucose metabolism. Mutations of the AKT signaling pathway components (especially PI3KCA and PTEN) have been observed in breast cancer patients, which are associated with resistance to hormonal treatment. Many clinical trials are testing the effect of AKT inhibition in order to block the growth and proliferation of breast cancer cells. The purpose of this review is to present the incidence of this neoplastic disease, to describe AKT signaling pathways activation, mutations that occur at its level, and inhibitors that can block this protein kinase

The Serine/Threonine Protein Kinase (Akt)/ Protein Kinase B (PkB) Signaling Pathway in Breast Cancer

According to statistical data published in 2019, breast cancer is among the leading causes of death in women worldwide. The serine/threonine kinase (AKT) or protein kinase B (PkB) signaling pathway is activated by phosphorylation processes, which further is associated with cell growth, proliferation, and survival, but also with activation of glucose metabolism. Mutations of the AKT signaling pathway components (especially PI3KCA and PTEN) have been observed in breast cancer patients, which are associated with resistance to hormonal treatment. Many clinical trials are testing the effect of AKT inhibition in order to block the growth and proliferation of breast cancer cells. The purpose of this review is to present the incidence of this neoplastic disease, to describe AKT signaling pathways activation, mutations that occur at its level, and inhibitors that can block this protein kinase

LYSYL OXIDASE (LOX) – A FUTURE NEW ALLY ON THE STAGE OF THE FIGHT AGAINST CANCER

The local extracellular matrix (EM) remodelling is considered one of the critical events in metastasis, both at primary and the secondary sites. One of the main actors on the EM remodelling is lysyl oxidase (LOX). In this connection, the aim of this paper is to bring to light a possible future systemic (and why not, salivary) biomarker of the metastatic process. LOX best-characterized role is in the EM remodelling by oxidative deamination of collagens and elastin peptidyl lysine residues, in order to facilitate covalent cross-linking. The LOX family members seem to play extremely important roles in these extracellular matrix interactions. Future research is needed to confirm whether simple LOX blocking or its downstream actions control could be regarded as target of preventive treatment in patients at a higher risk of metastasis. This is how the portrait of the future biomarker of LOX is becoming more and more outlined

URIC ACID – HISTORY, PRESENT AND FUTURE

2,6,8-trioxypurine known as uric acid represents a heterocyclic derivative of purine, with a molecular weight of 158 Da. In contrast to primates and humans, in the other animals uric acid is further oxidized by the uricase enzyme (urate oxidase) to allantoin, 100 times more water-soluble than uric acid and, consequently, more efficient excreted in the urine. Humans and higher pri¬mates lack a functional uricase gene. The uricase activity loss in higher primates and humans occurred about 15 million years ago, re¬sulting in a relatively higher plasma uric acid level than that in lower ani¬mals. This was an impressive and very important evolutionary event, providing essential survival advantages for humans. Uric acid represents a powerful antioxidant capable of scavenging singlet oxygen molecules, oxygen radicals, and peroxynitrite (ONOO−) molecules. However, in vivo and cellular research studies are interestingly illustrating that, depending on its chemical microenvironment, the uric acid molecule plays a duplicate role, being also a pro-oxidant. Uric acid represents the most important salivary antioxidant, in the circumstances of very low salivary thiols concentrations. Uric acid plays an important role in oral pathology and may be regarded as a very useful future salivary biomarker

HYPERLEPTINEMIA AND CARDIOVASCULAR SYSTEM

Leptin is the satiety hormone, synthesized in the adipose tissue that reduces food intake, being involved in glucose and lipid metabolism. Hyperleptinemia correlates with obesity and represents a risk factor in the pathology of the cardiovascular system. Increased concentrations of leptin have been observed in patients with hypertension or atherosclerosis. In vitro studies suggest the angiogenic role of leptin. The purpose of this review is to present the metabolic effects of hyperleptinemia in the cardiovascular system

OBESITY INDUCES DNA DAMAGE

A diet rich in saturated lipids, refined carbohydrates associated with a sedentary lifestyle leads to obesity in both adults and children. Obesity is associated with the existence of a chronic inflammatory process, that will further lead to systemic oxidative stress and DNA oxidative damage. There is currently a positive correlation between obesity and cancer due to nuclear but also mitochondrial DNA injury. Obesity is a risk factor for the development of several types of cancer such as breast, prostate or colorectal. The purpose of this review is to present the effects of obesity on human body, by describing the chronic inflammatory process, oxidative stress, and the molecular mechanisms involved in cancer progression

ADIPOSE TISSUE BIOMARKERS AND SYSTEMIC HEALTH

Adipose tissue consists primarily of adipocytes, being responsible for storing the body's energy reserves. Adipokines secreted by adipose tissue play important roles in the human body. The purpose of this review is to present the most important adipokines and their involvement in the physiological processes but also in the pathogenesis of numerous systemic diseases commonly associated with obesity

DUOX2, A NEW PLAYER ON THE SCENE OF THYROID HORMONES

Introduction. Thyroid disorders have very high frequency both in Romania and around the world. Nowadays new parameters are needed to diagnose thyroid disease. Clinicians need new parameters, with rapid determination, low cost, high affinity and specificity. The aim of our study was to investigate possible relationships between thyroid hormones (TH), TSH and DUOX2, and thus a possible involvement of oxidative stress (OS) in thyroid malfunction. Material and methods. The study included 66 patients (men and women), divided on 2 lots: 33 patients with hypothyroidism and 33 patients with hyperthyroidism. The control group was represented by 33 healthy volunteers. All the participants, patients and controls, provided the informed consent to participate in the study.The parameters analyzed were serum TSH, FT4, FT3 and DUOX2. Results. Our results showed that in hypothyroidism patients we have lower levels of TH, and higher level of DUOX2. This suggest an accumulation of enzyme, unused for synthesis. In the meantime, in hyperthyroidism group we can observe a lower level of serum DUOX2, due to massive synthesis of TH. Conclusions. We can assume that DUOX2 has a crucial role in TH and, by producing hydrogen peroxide, an important role in OS. Additional studies are still needed in order to establish whether DUOX2 should be regarded as useful OS biomarker in thyroid patholog

EFFECT OF PLATELET RICH PLASMA IN DIABETIC FOOT HEALING

PRP (platelet rich plasma) is a natural source of growth factors obtained from the patient's blood which are involved in the wound healing process. PRP therapy is successfully applied in the medical field, being used nowadays in diabetic patients who develop as complication the diabetic foot. The purpose of this review is to present the composition of PRP growth factors, PRP preparation stages and the results obtained in patients diagnosed with diabetic foot

VITAMIN D DEFICIENCY AND INSULIN RESISTANCE

Vitamin D or cholecalciferol is active in the human body after two hydroxylation reactions. Once activated, it is involved in bone metabolism, but can also influence other biological processes such as cell growth and proliferation or angiogenesis. Studies conducted so far suggest a link between vitamin D deficiency and insulin resistance. The purpose of this review is to analyze the effects of hypovitaminosis D as well as the administration of vitamin D rich supplements on the insulin resistance provided by the specialized literature