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.
Important oxidative stress associated with alveolar bone loss biomarkers can be detected in saliva of patients with periodontal disease.
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.
Oral lichen planus (OLP) is a relatively common disorder whose cause is still unknown. Oral cancer is preceded in most cases by pre malignant lesions-leukoplasia, submucous fibrosis and lichen planus. Free radicals and reactive oxygen species play important roles in both pathogenesis of lichen planus and carcinogenesis. Thus monitoring systemic and saliva compounds important for the antioxidant defence (oxidative balance) could be important for the clinician's treatment strategy. Thorough medical management and early active treatment are necessary to improve symptoms and might also be a relevant prevention strategy from squamous cell carcinoma risk, although data to fully support this statement still need investigation. The principal aim of this study was to determine the systemic uric acid, GGT, and albumin levels as well as the levels of uric acid and albumin in 20 patients diagnosed with lichen planus and 20 controls. Extensive medline search failed to reveal any study of this type. Our results showed a significant decrease of saliva (p < 0.005) uric acid and an increase in serum gamma glutamyl transpherase (GGT) (p < 0.01) as well as in the total antioxidant capacity of saliva in patient group with respect to the control one. The preliminary conclusion of our study is that uric acid, the most important salivary antioxidant and GGT could be considered in the future as useful markers of oxidative stress for elaboration of treatment strategy and monitoring.
Our results revealed that periodontal destruction such as periodontal pockets, gingival bleeding and suppuration are related to higher ALP and AST levels in saliva. Salivary AST could be used as a useful marker for monitoring periodontal disease. The increase in salivary ALP activity in periodontitis demonstrated could be associated with alveolar bone loss, a key feature of periodontal disease. More studies are necessary to evaluate which specific clinical, microbiological and histological characteristics of periodontal disease are associated with elevated levels of AST and ALP in saliva.
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