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.

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.

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.

This paper’s primary aim is to outline relevant aspects regarding the biocompatibility of PMMA (poly(methyl methacrylate))-based materials used for obtaining interim prosthetic restorations, such as the interaction with oral epithelial cells, fibroblasts or dental pulp cells, the salivary oxidative stress response, and monomer release. Additionally, the oral environment’s biochemical response to modern interim dental materials containing PMMA (obtained via subtractive or additive methods) is highlighted in this review. The studies included in this paper confirmed that PMMA-based materials interact in a complex way with the oral environment, and therefore, different concerns about the possible adverse oral effects caused by these materials were analyzed. Adjacent to these aspects, the present work describes several advantages of PMMA-based dental materials. Moreover, the paper underlines that recent scientific studies ascertain that the modern techniques used for obtaining interim prosthetic materials, milled PMMA, and 3D (three-dimensional) printed resins, have distinctive advantages compared to the conventional ones. However, considering the limited number of studies focusing on the chemical composition and biocompatibility of these modern interim prosthetic materials, especially for the 3D printed ones, more aspects regarding their interaction with the oral environment need to be further investigated.

Our professional activity is constantly under pressure from a multitude of elements and factors that can be classified into the four components of the VUCA phenomenon—volatility, uncertainty, complexity, and ambiguity—components that define the turbulence and challenges of the external environment. Considering the general elements of this phenomenon, we designed a new VUCA dimension specific to the healthcare field within which we have identified and analyzed all the factors that can influence the main actors of the doctor–patient relationship and the effects that can occur within the healthcare system in which this relationship is born. In this context, we generated the VUCA treatment in healthcare capable of mitigating the impact of this phenomenon; this treatment involves essential elements in overcoming possible crises and vulnerabilities of the medical profession. The VUCA treatment in healthcare requires combating volatility, uncertainty, complexity, and ambiguity through vision, understanding, clarity, and agility, which are grounded in the doctor’s need to acquire cross-functional competencies (soft skills). These competencies are applicable by using functional mechanisms and techniques that support the doctor in developing adaptability and anticipation skills, understanding the patient’s needs and addressing them, and ensuring the functionality and efficiency of the healthcare system by transferring these elements from micro-management to macro-management levels.

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.