Serum Plasminogen Activator Inhibitor-1, α 1-Acid Glycoprotein, C-Reactive Protein, and Platelet Factor 4 Levels-Promising Molecules That Can Complete the "Puzzle" of the Biochemical Milieu in Severe Burns: Preliminary Results of a Cohort Prospective Study.

Background: Burns represent a serious health problem, associated with multiple-organ failure, prolonged hospitalization, septic complications, and increased rate of mortality. The main aim of our study was to evaluate the levels of various circulating molecules in children with severe burns (more than 25% TBSA), in three different moments: 48 h, day 10, and day 21 post-burn. Materials and Methods: This study included 32 children with burns produced by flame, hot liquid, and electric arc and 21 controls. Serum plasminogen activator inhibitor-1 (PAI-1), α 1-acid glycoprotein (AGP), C-reactive protein (CRP), and platelet factor 4 (PF4) were detected using the Multiplex technique. Several parameters, such as fibrinogen, leucocyte count, thrombocyte count, triiodothyronine, thyroxine, and thyroid-stimulating hormone were also determined for each patient during hospitalization. Results: Significant statistical differences were obtained for CRP, AGP, and PF4 compared to the control group, in different moments of measurements. Negative correlations between CRP, AGP, and PF4 serum levels and burned body surface, and also the hospitalization period, were observed. Discussions: CRP levels increased in the first 10 days after burn trauma and then decreased after day 21. Serum PAI-1 levels were higher immediately after the burn and started decreasing only after day 10 post-burn. AGP had elevated levels 48 h after the burn, then decreased at 7-10 days afterwards, and once again increased levels after 21 days. PF4 serum levels increased after day 10 since the burning event. Conclusions: Serum CRP, AGP, PAI-1, and PF4 seem to be promising molecules in monitoring patients with a burn within the first 21 days.

Perceptions of the Conditions and Barriers in Implementing the Patient Blood Management Standard by Anesthesiologists and Surgeons.

Patient Blood Management (PBM) as a multidisciplinary practice and a standard of care for the anemic surgical patient is playing an increasingly important role in reducing transfusions and optimizing both clinical outcomes and costs. The success of PBM implementation depends on staff awareness and involvement in this approach. The main objective of our study was to explore physicians' perceptions of the conditions for implementing PBM in hospitals and the main obstacles they face in detecting and treating anemic patients undergoing elective surgery. This cross-sectional descriptive study includes 113 Romanian health units, representing 23% of health units with surgical wards nationwide. A 12-item questionnaire was distributed to the participants in electronic format. A total of 413 questionnaires representing the perceptions of 347 surgeons and 66 anesthesia and intensive-care specialists were analyzed. Although a lack of human resources was indicated by 23.70% of respondents as the main reason for not adhering the guidelines, the receptiveness of medical staff to implementing the PBM standard was almost 90%. In order to increase adherence to the standard, additional involvement of anesthesia and intensive-care physicians would be necessary from the perception of 35.70% of the responders: 23.60% of surgeons and 18.40% of hematologists.

The importance of the enzyme Gamma-glutamyltransferase in the pathogenic cluster in type2 diabetic patient.

Introduction. Gamma-glutamyltransferase (GGT) is a liver enzyme involved in inflammation and oxidative stress. It is already known that MCP-1 (Monocyte Chemoattractant Protein-1) and TNF-α (tumour necrosis factor) as inflammatory markers, ICAM-1 (Intercellular Adhesion Molecule-1) as an endothelial dysfunctional marker, and glutathione, as an antioxidant, have abnormal levels in type 2 diabetic patients. The aim of this study was to evaluate the specific biological picture of type 2 diabetic patients that also associate higher GGT activity. Methods. Eighty-five type 2 diabetes, aged 40-70 years with a duration of diabetes less than 6 years without infections, epilepsy, chronic liver or cardiac diseases, without alcohol consumption (>20 g/day) were divided in two subgroups, those with normal and those with high abnormal GGT. Results. The diabetic patients with high GGT (n=31) had dysglycaemia, dyslipidemia, higher inflammatory markers (CRP, TNF-α, MCP-1) and endothelial dysfunction (high leptin and sICAM). sICAM, serum MCP-1 and TNF-α levels had significant correlations with GGT activity (r= 0.38, r=0.30 and 0.26 respectively, p<0.05). Conclusion. This study underlines that in non-alcoholic diabetic patients, with a duration of the metabolic disease less than 6 years, sICAM, serum MCP-1 and TNF-α might play an important role in dysmetabolism, and higher level for GGT represents the "red flag" for this condition.

Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer.

Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year. Helicobacter pylori represents the main risk factor, being responsible for 78% of the cases. Increased amounts of salt, pickled food, red meat, alcohol, smoked food, and refined sugars negatively affect the stomach wall, contributing to GC development. Several gene mutations, including PIK3CA, TP53, ARID1A, CDH1, Ras, Raf, and ERBB3 are encountered in GC pathogenesis, leading to phosphatidylinositol 3-kinase (PI3K) protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-PI3K/AKT/mTOR-and mitogen-activated protein kinase (MAPK) signaling pathway activation and promoting tumoral activity. Helicobacter pylori, growth factors, cytokines, hormones, and oxidative stress also activate both pathways, enhancing GC development. In clinical trials, promising results have come from monoclonal antibodies such as trastuzumab and ramucirumab. Dual inhibitors targeting the PI3K/AKT/mTOR and MAPK signaling pathways were used in vitro studies, also with promising results. The main aim of this review is to present GC incidence and risk factors and the dysregulations of the two protein kinase complexes together with their specific inhibitors.

A Potential Indicator for Assessing Patient Blood Management Standard Implementation.

(1) Background: Patient blood management (PBM) program as a multidisciplinary practice and a standard of care for the anemic surgical patient has an increasingly important role in reducing transfusions and optimizing both clinical outcomes and costs. Documented success of PBM implementation is not sufficient for implementation of recommendations and correct use at hospital level. The primary objective of our study was to define a composite patient blood management process safety index-Safety Index in PBM (SIPBM)-that measures the impact of screening and treating anemic patients on the efficiency and effectiveness of the patient care process undergoing elective surgery. (2) Methods: We conducted a retrospective comparative study in a tertiary hospital by collecting data and analyzing the Safety Index in PBM (SIPBM) in patients undergoing major elective surgical procedures. (3) Results: The percentage of patients from the total of 354 patients (178 in 2019 and 176 in 2022) included in the study who benefited from preoperative iron treatment increased in 2022 compared to 2019 from 27.40% to 36.71%. The median value of the SIPBM was 1.00 in both periods analyzed, although there is a significant difference between the two periods (p < 0.005), in favor of 2022. (4) Conclusions: Measuring the effectiveness of PBM implementation and providing ongoing feedback through the Safety Index in PBM (SIPBM) increases the degree to which opportunities to improve the PBM process are identified. The study represents a first step for future actions and baselines to develop tools to measure the safety and impact of the patient blood management process in the surgical field.

PI3K/AKT/mTOR Dysregulation and Reprogramming Metabolic Pathways in Renal Cancer: Crosstalk with the VHL/HIF Axis.

Renal cell carcinoma (RCC) represents 85-95% of kidney cancers and is the most frequent type of renal cancer in adult patients. It accounts for 3% of all cancer cases and is in 7th place among the most frequent histological types of cancer. Clear cell renal cell carcinoma (ccRCC), accounts for 75% of RCCs and has the most kidney cancer-related deaths. One-third of the patients with ccRCC develop metastases. Renal cancer presents cellular alterations in sugars, lipids, amino acids, and nucleic acid metabolism. RCC is characterized by several metabolic dysregulations including oxygen sensing (VHL/HIF pathway), glucose transporters (GLUT 1 and GLUT 4) energy sensing, and energy nutrient sensing cascade. Metabolic reprogramming represents an important characteristic of the cancer cells to survive in nutrient and oxygen-deprived environments, to proliferate and metastasize in different body sites. The phosphoinositide 3-kinase-AKT-mammalian target of the rapamycin (PI3K/AKT/mTOR) signaling pathway is usually dysregulated in various cancer types including renal cancer. This molecular pathway is frequently correlated with tumor growth and survival. The main aim of this review is to present renal cancer types, dysregulation of PI3K/AKT/mTOR signaling pathway members, crosstalk with VHL/HIF axis, and carbohydrates, lipids, and amino acid alterations.

A Brief Assessment of Patient Safety Culture in Anesthesia and Intensive Care Departments.

Due to the nature of their activity, anesthesia and critical care have generally well-developed patient safety cultures, which are linked to a greater level of incident awareness and reporting during clinical activity. In order to determine the status quo and identify and adopt, where appropriate, techniques and instruments for further improving patient safety, it is necessary to evaluate the culture and barriers in these departments. The main objective of our study was to assess patient safety culture in Romanian anesthesia and intensive care departments (AICDs), to pinpoint the areas that may need improvement, and to examine the correlation between the prevalence of adverse event reporting, as well as the level of self-reported patient safety culture. To determine how anesthesia and intensive care department staff perceived patient safety, the Hospital Survey on Patient Safety Culture (HSOPSC) was used in a translated Romanian version. In total, 1200 employees from 36 anesthesiology and intensive care departments across 32 hospitals in Romania received the questionnaire, representing 42.66% of all anesthesia and intensive care departments in the country. In 7 of the 12 examined dimensions, significant differences between tertiary and secondary hospitals were observed. Among all dimensions, the highest positive score was for "organizational learning and continuous development". In general, our study revealed a positive view on patient safety in anesthesia and intensive care departments. Further studies are required to determine a threshold of the level of culture development.

Chronic Pelvic Puzzle: Navigating Deep Endometriosis with Renal Complications.

This case report delves into the intricacies of a challenging clinical scenario involving deep pelvic endometriosis, which manifested with renal complications. Endometriosis, a complex gynecological condition, is explored in this case, highlighting its multifaceted nature. The patient presented with a complex interplay of symptoms, including chronic pelvic pain, urinary tract issues, and severe deep adenomyosis. The diagnostic journey was protracted, emphasizing the need for early recognition and intervention in such cases. A thorough evaluation, including laparoscopic examination and histopathological analysis, revealed the extensive presence of endometriotic lesions in various pelvic and renal structures, ultimately leading to left hydronephrosis. The report underscores the significance of timely diagnosis and surgical intervention to prevent irreversible renal damage. This case provides valuable insights into the management of deep endometriosis with renal involvement and the importance of interdisciplinary collaboration. Understanding the complexities of this condition can aid in improving patient outcomes and enhancing the quality of care provided.

Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects.

Although pancreatic cancer (PC) was considered in the past an orphan cancer type due to its low incidence, it may become in the future one of the leading causes of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of PC, being a highly aggressive malignancy and having a 5-year survival rate of less than 10%. Non-modifiable (family history, age, genetic susceptibility) and modifiable (smoking, alcohol, acute and chronic pancreatitis, diabetes mellitus, intestinal microbiota) risk factors are involved in PC pathogenesis. Chronic inflammation induced by various factors plays crucial roles in PC development from initiation to metastasis. In multiple malignant conditions such as PC, cytokines, chemokines, and growth factors activate the class I phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) (PI3K/AKT/mTOR) signaling pathway, which plays key roles in cell growth, survival, proliferation, metabolism, and motility. Currently, mTOR, AKT, and PI3K inhibitors are used in clinical studies. Moreover, PI3K/mTOR dual inhibitors are being tested in vitro and in vivo with promising results for PC patients. The main aim of this review is to present PC incidence, risk factors, tumor microenvironment development, and PI3K/AKT/mTOR dysregulation and inhibitors used in clinical, in vivo, and in vitro studies.

The Yin and Yang dualistic features of autophagy in thermal burn wound healing.

Burn healing should be regarded as a dynamic process consisting of two main, interrelated phases: (a) the inflammatory phase when neutrophils and monocytes infiltrate the injury site, through localized vasodilation and fluid extravasation, and (b) the proliferative-remodeling phase, which represents a key event in wound healing. In the skin, both canonical autophagy (induced by starvation, oxidative stress, and environmental aggressions) and non-canonical or selective autophagy have evolved to play a discrete, but, essential, "housekeeping" role, for homeostasis, immune tolerance, and survival. Experimental data supporting the pro-survival roles of autophagy, highlighting its Yang, luminous and positive feature of this complex but insufficient explored molecular pathway, have been reported. Autophagic cell death describes an "excessive" degradation of important cellular components that are necessary for normal cell function. This deadly molecular mechanism brings to light the darker, concealed, Yin feature of autophagy. Autophagy seems to perform dual, conflicting roles in the angiogenesis context, revealing once again, its Yin-Yang features. Autophagy with its Yin-Yang features remains the shadow player, able to decide quietly whether the cell survives or dies.

Compressive and Flexural Strength of 3D-Printed and Conventional Resins Designated for Interim Fixed Dental Prostheses: An In Vitro Comparison.

A provisionalization sequence is essential for obtaining a predictable final prosthetic outcome. An assessment of the mechanical behavior of interim prosthetic materials could orient clinicians towards selecting an appropriate material for each clinical case. The aim of this study was to comparatively evaluate the mechanical behavior-with compressive and three-point flexural tests-of certain 3D-printed and conventional resins used to obtain interim fixed dental prostheses. Four interim resin materials were investigated: two 3D-printed resins and two conventional resins (an auto-polymerized resin and a pressure/heat-cured acrylic resin). Cylindrically shaped samples (25 × 25 mm/diameter × height) were obtained for the compression tests and bar-shaped samples (80 × 20 × 5 mm/length × width × thickness) were produced for the flexural tests, observing the producers' recommendations. The resulting 40 resin samples were subjected to mechanical tests using a universal testing machine. Additionally, a fractographic analysis of failed samples in bending was performed. The results showed that the additive manufactured samples exhibited higher elastic moduli (2.4 ± 0.02 GPa and 2.6 ± 0.18 GPa) than the conventional samples (1.3 ± 0.19 GPa and 1.3 ± 0.38 GPa), as well as a higher average bending strength (141 ± 17 MPa and 143 ± 15 MPa) when compared to the conventional samples (88 ± 10 MPa and 76 ± 7 MPa); the results also suggested that the materials were more homogenous when produced via additive manufacturing.

Hypoxia-Inducible Factors and Burn-Associated Acute Kidney Injury-A New Paradigm?

O2 deprivation induces stress in living cells linked to free-radical accumulation and oxidative stress (OS) development. Hypoxia is established when the overall oxygen pressure is less than 40 mmHg in cells or tissues. However, tissues and cells have different degrees of hypoxia. Hypoxia or low O2 tension may be present in both physiological (during embryonic development) and pathological circumstances (ischemia, wound healing, and cancer). Meanwhile, the kidneys are major energy-consuming organs, being second only to the heart, with an increased mitochondrial content and O2 consumption. Furthermore, hypoxia-inducible factors (HIFs) are the key players that orchestrate the mammalian response to hypoxia. HIFs adapt cells to low oxygen concentrations by regulating transcriptional programs involved in erythropoiesis, angiogenesis, and metabolism. On the other hand, one of the life-threatening complications of severe burns is acute kidney injury (AKI). The dreaded functional consequence of AKI is an acute decline in renal function. Taking all these aspects into consideration, the aim of this review is to describe the role and underline the importance of HIFs in the development of AKI in patients with severe burns, because kidney hypoxia is constant in the presence of severe burns, and HIFs are major players in the adaptative response of all tissues to hypoxia.

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

Colorectal cancer (CRC) is a predominant malignancy worldwide, being the fourth most common cause of mortality and morbidity. The CRC incidence in adolescents, young adults, and adult populations is increasing every year. In the pathogenesis of CRC, various factors are involved including diet, sedentary life, smoking, excessive alcohol consumption, obesity, gut microbiota, diabetes, and genetic mutations. The CRC tumor microenvironment (TME) involves the complex cooperation between tumoral cells with stroma, immune, and endothelial cells. Cytokines and several growth factors (GFs) will sustain CRC cell proliferation, survival, motility, and invasion. Epidermal growth factor receptor (EGFR), Insulin-like growth factor -1 receptor (IGF-1R), and Vascular Endothelial Growth Factor -A (VEGF-A) are overexpressed in various human cancers including CRC. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and all the three major subfamilies of the mitogen-activated protein kinase (MAPK) signaling pathways may be activated by GFs and will further play key roles in CRC development. The main aim of this review is to present the CRC incidence, risk factors, pathogenesis, and the impact of GFs during its development. Moreover, the article describes the relationship between EGF, IGF, VEGF, GFs inhibitors, PI3K/AKT/mTOR-MAPK signaling pathways, and CRC.

Drugs Interfering with Insulin Resistance and Their Influence on the Associated Hypermetabolic State in Severe Burns: A Narrative Review.

It has become widely accepted that insulin resistance and glucose hypermetabolism can be linked to acute pathologies, such as burn injury, severe trauma, or sepsis. Severe burns can determine a significant increase in catabolism, having an important effect on glucose metabolism and on muscle protein metabolism. It is imperative to acknowledge that these alterations can lead to increased mortality through organ failure, even when the patients survive the initial trauma caused by the burn. By limiting the peripheral use of glucose with consequent hyperglycemia, insulin resistance determines compensatory increased levels of insulin in plasma. However, the significant alterations in cellular metabolism lead to a lack of response to insulin's anabolic functions, as well as to a decrease in its cytoprotective role. In the end, via pathological insulin signaling associated with increased liver gluconeogenesis, elevated levels of glucose are detected in the blood. Several cellular mechanisms have been incriminated in the development of insulin resistance in burns. In this context, the main aim of this review article is to summarize some of the drugs that might interfere with insulin resistance in burns, taking into consideration that such an approach can significantly improve the prognosis of the burned patient.

Growth Factors, Reactive Oxygen Species, and Metformin-Promoters of the Wound Healing Process in Burns?

Burns can be caused by various factors and have an increased risk of infection that can seriously delay the wound healing process. Chronic wounds caused by burns represent a major health problem. Wound healing is a complex process, orchestrated by cytokines, growth factors, prostaglandins, free radicals, clotting factors, and nitric oxide. Growth factors released during this process are involved in cell growth, proliferation, migration, and differentiation. Reactive oxygen species are released in acute and chronic burn injuries and play key roles in healing and regeneration. The main aim of this review is to present the roles of growth factors, reactive oxygen species, and metformin in the healing process of burn injuries.

ILs and MMPs Levels in Inflamed Human Dental Pulp: A Systematic Review.

A wide range of mediators are released from the pulp tissue because of bacterial invasion which causes inflammation. Interleukins (ILs) and matrix metalloproteinases (MMPs) have a leading role in initiating and spreading of inflammation because of their synergic action. Biomarkers such as ILs and MMPs can be identified via several methods, establishing the inflammatory response of the dental pulp. The aim of this systematic review is to evaluate the levels of ILs and/or MMPs in human dental pulp. PubMed, OVID, Cochrane, Scopus, Web of Science and Wiley online library databases were searched for original clinical studies. After applying inclusion and exclusion criteria, a quality assessment of studies was performed based on a modified Newcastle-Ottawa scale. In the review were included articles that evaluated the presence of ILs and/or MMPs in pulp tissue using enzyme-linked immunosorbent assay (ELISA) or western blot or multiplex assay. Six articles were included in the present synthesis. Although various diagnostic methods were used, statistically significant higher levels of ILs and/or MMPs were mostly found in the experimental groups compared to healthy pulp samples. The biomarkers studied can be a promising tool to evaluate pulp tissue health or even in pulpitis treatment.

Mediators of extracellular matrix degradation and inflammation: A new team of possible biomarkers for oral squamous cell carcinoma stage.

Oral cancer represents one of the most common types of cancer worldwide, with oral squamous cell carcinoma (OSCC) being the most frequently diagnosed. Cytokines play a crucial role in inflammation, apoptosis and metastasis. Interleukin (IL)-8 promotes the direct migration of inflammatory cells. IL-6 induces tumor cell proliferation, increases expression of invasiveness and angiogenetic factors or matrix metalloproteinases (MMPs), promoting metastasis. Tissue inhibitor of metalloproteinases (TIMPs) blocks the action of MMPs controlling extracellular matrix degradation and inhibiting metastasis. The aim of our study was to analyze the existence of correlations between inflammation markers (IL-6 and IL-8) and extracellular degradation protection markers such as TIMP-1 in OSCC tumors. Our study included 20 patients (12 females and 8 males) diagnosed with OSCC, recruited from January to April, 2020. IL-8, IL-6 and TIMP-1 levels were measured in the tumor cell lysates by ELISA technique, using relevant assay kits. Our results showed a positive and significant correlation between IL-6 and IL-8 (P=0.005, R=0.517) indicating that high IL-8 levels can be associated with high IL-6 levels. We also found a significant and high negative correlation (P<0.001, R=-0.673) between IL-6 and TIMP-1 and a significant and high negative correlation (P<0.001, R=-0.684) between IL-8 and TIMP-1 indicating that high levels of IL-8 and IL-6 are significantly associated with lower levels of TIMP-1. In conclusion, our study confirms the available literature data on IL-6 and IL-8 as potential markers for oral cancers such as OSCC and affect the tumor microenvironment by decreasing TIMPs. All three biomarkers included in this study have the potential to be used as detection or prognostic factors for oral cancer.

Lutein Treatment Effects on the Redox Status and Metalloproteinase-9 (MMP-9) in Oral Cancer Squamous Cells-Are There Therapeutical Hopes?

Carotenoids loaded in nanoparticles should be regarded as a promising way to increase the availability in healthy cells and to induce apoptosis in cancer. Lutein is a carotenoid that, in contrast to beta-carotene, has no known toxicities. Oral cancer represents one of the most frequent types of cancer world-wide with an incidence rate of about 9% of all types of cancer. Almost 95% of all oral cancers are represented by squamous cell carcinomas (OSCC). The aim of this study was to review and analyse the effects of lutein and Poly(d,l-lactide-co-glycolide) (PLGA) Nps containing lutein (Lut Nps) on oxidative stress biomarkers (OXSR-1, FOXO-3, TAC) and collagen degradation biomarker-MMP-9, in human cells BICR10 of buccal mucosa squamous carcinoma. Lut Nps were prepared by the emulsion-solvent evaporation method. MMP, OXSR-1, TAC, FOXO-3 and MMP-9 were measured in tumour cell lysates by the ELISA technique. Our results have shown that in Lut 100 cells and Lut Nps the OXSR1 (p < 0.001, p < 0.001) and TAC (p < 0.001, p < 0.001) values were significantly higher than in control cells. The Lut 100 and Lut Nps FOXO-3 levels revealed no significant differences versus the control. MMP-9 levels were significantly reduced (p < 0.001) in the Lut Nps cells versus control cells. In our study conditions, lutein and lutein Nps did not trigger an oxidative stress by ROS induction. However, lutein Nps treatment seemed to have a positive effect, by downregulating the MMP-9 levels. Loaded in Nps, lutein could be regarded as a protective factor against local invasiveness, in whose molecular landscape MMPs, and especially MMP-9 are the main actors.

Glucose Metabolism in Burns-What Happens?

Severe burns represent an important challenge for patients and medical teams. They lead to profound metabolic alterations, trigger a systemic inflammatory response, crush the immune defense, impair the function of the heart, lungs, kidneys, liver, etc. The metabolism is shifted towards a hypermetabolic state, and this situation might persist for years after the burn, having deleterious consequences for the patient's health. Severely burned patients lack energy substrates and react in order to produce and maintain augmented levels of glucose, which is the fuel "ready to use" by cells. In this paper, we discuss biological substances that induce a hyperglycemic response, concur to insulin resistance, and determine cell disturbance after a severe burn. We also focus on the most effective agents that provide pharmacological modulations of the changes in glucose metabolism.

PI3K/AKT/mTOR Signaling Pathway in Breast Cancer: From Molecular Landscape to Clinical Aspects.

Breast cancer is a serious health problem worldwide, representing the second cause of death through malignancies among women in developed countries. Population, endogenous and exogenous hormones, and physiological, genetic and breast-related factors are involved in breast cancer pathogenesis. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) is a signaling pathway involved in cell proliferation, survival, invasion, migration, apoptosis, glucose metabolism and DNA repair. In breast tumors, PIK3CA somatic mutations have been reported, located in exon 9 and exon 20. Up to 40% of PIK3CA mutations are estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) -negative in primary and metastatic breast cancer. HER2 is overexpressed in 20-30% of breast cancers. HER1, HER2, HER3 and HER4 are membrane receptor tyrosine kinases involved in HER signaling to which various ligands can be attached, leading to PI3K/AKT activation. Currently, clinical studies evaluate inhibitors of the PI3K/AKT/mTOR axis. The main purpose of this review is to present general aspects of breast cancer, the components of the AKT signaling pathway, the factors that activate this protein kinase B, PI3K/AKT-breast cancer mutations, PI3K/AKT/mTOR-inhibitors, and the relationship between everolimus, temsirolimus and endocrine therapy.