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.
There is a growing interest in the development of organic nanomaterials for biomedical applications. An increasing number of studies focus on the uses of nanomaterials with organic structure for ...regeneration of bone, cartilage, skin or dental tissues. Solid evidence has been found for several advantages of using natural or synthetic organic nanostructures in a wide variety of dental fields, from implantology, endodontics, and periodontics, to regenerative dentistry and wound healing. Most of the research is concentrated on nanoforms of chitosan, silk fibroin, synthetic polymers or their combinations, but new nanocomposites are constantly being developed. The present work reviews in detail current research on organic nanoparticles and their potential applications in the dental field.
Periodontitis represents a complex inflammatory disease that compromises the integrity of the tooth-supporting tissue through the interaction of specific periodontal pathogens and the host's immune ...system. Experimental data help to outline the idea that the molecular way towards periodontitis initiation and progression presents four key steps: bacterial infection, inflammation, oxidative stress, and autophagy. The aim of this review is to outline the autophagy involvement in the pathogenesis and evolution of periodontitis from at least three points of view: periodontal pathogen invasion control, innate immune signaling pathways regulation and apoptosis inhibition in periodontal cells. The exact roles played by reactive oxygen species (ROS) inside the molecular mechanisms for autophagy initiation in periodontitis still require further investigation. However, clarifying the role and the mechanism of redox regulation of autophagy in the periodontitis context may be particularly beneficial for the elaboration of new therapeutic strategies.
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.
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.
Oxidative stress is implicated in the pathogenesis of many systemic and oral diseases such as periodontal disease. The main aim of this study is to explore a possible association between salivary ...markers of OS and alveolar bone loss.
The study included 20 patients with chronic periodontitis and 20 controls. Salivary OS biomarkers 8-hidroxy-desoxguanosine (8-HOdG), malondialdehyde (MDA), uric acid, total antioxidant capacity (TAC) and glutathione peroxidase (GPx) were evaluated. Bone loss markers such as C-terminal telopeptide of type I collagen (CTX I), matrix metalloproteinases-8 (MMP-8), osteocalcin and 25-hydroxy vitamin D3 (25- OH D) were detected in this study. The methods included general biochemical tests and ELISA.
Salivary 8-OHdG, MDA levels were significantly higher in the chronic periodontitis group compared with controls (p < 0.05). Salivary activities for uric acid, TAC and GPx were significantly decreased in patients with chronic periodontitis vs controls (p < 0.05). Salivary levels for CTX I, MMP-8, 25-OH D and Osteocalcin were significantly higher in the chronic periodontitis group compared to the controls (p < 0.05). A significant positive correlation was observed between salivary levels of MDA and CTX I. Significant negative correlations between uric acid and CTX I and between MMP-8 and uric acid have been found. Significant positive correlations were observed between CTX I, MMP-8, 25-OH D, osteocalcin and clinical parameters of periodontal disease.
Important oxidative stress associated with alveolar bone loss biomarkers can be detected in saliva of patients with periodontal disease.
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.
The duration of denture use, oral hygiene, smoking and male sex were identified as risk factors for oral mucosal lesions. As it is well known, all the oral mucosal lesions associated with risk ...factors have an important degree of malignity. Chronic mechanical irritation can be another cause of oral cancer and it is produced by the constant action of a deleterious agent from the oral cavity. Autophagy represents a complex evolutionary conserved catabolic process in which cells self-digest intracellular organelles in order to regulate their normal turnover and remove the damaged ones with compromised function to further maintain homeostasis. Autophagy is modulated by mTOR kinase and indirectly by PI3K/AKT survival pathway. Due to its dual capacity to either induce cell death or promote cell survival, important evidence pointed that autophagy has a two-faced role in response to chemotherapy in cancer. In conclusion, understanding how to overcome cytoprotective autophagy and how to take advantage of autophagic cell death is critical in order to enhance the cancer cells sensitivity to particular therapeutic agents.
PDF
