Viruses have been shown to be responsible for 10%-15% of cancer cases. Epstein-Barr virus(EBV) is the first virus to be associated with human malignancies. EBV can cause many cancers, including Burkett's lymphoma,...Viruses have been shown to be responsible for 10%-15% of cancer cases. Epstein-Barr virus(EBV) is the first virus to be associated with human malignancies. EBV can cause many cancers, including Burkett's lymphoma, Hodgkin's lymphoma, post-transplant lymphoproliferative disorders, nasopharyngeal carcinoma and gastric cancer. Evidence shows that phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) plays a key role in EBV-induced malignancies. The main EBV oncoproteins latent membrane proteins(LMP) 1 and LMP2 A can activate the PI3K/Akt pathway, which, in turn, affects cell survival, apoptosis, proliferation and genomic instability via its downstream target proteins to cause cancer. It has also been demonstrated that the activation of the PI3K/Akt pathway can result in drug resistance to chemotherapy. Thus, the inhibition of this pathway can increase the therapeutic efficacy of EBV-associated cancers. For example, PI3 K inhibitor Ly294002 has been shown to increase the effect of 5-fluorouracil in an EBV-associated gastric cancer cell line. At present, dual inhibitors of PI3 K and its downstream target mammalian target of rapamycin have been used in clinical trials and may be included in treatment regimens for EBV-associated cancers.展开更多
The search for diagnostic and prognostic markers in Alzheimer's disease(AD) has been an area of active research in the last decades. Biochemical markers are correlates of intracerebral changes that can be identifi...The search for diagnostic and prognostic markers in Alzheimer's disease(AD) has been an area of active research in the last decades. Biochemical markers are correlates of intracerebral changes that can be identified in biological fluids, namely: peripheral blood(total blood, red and white blood cells, platelets, plasma and serum), saliva, urine and cerebrospinal fluid. An important feature of a biomarker is that it can be measured objectively and evaluated as(1) an indicator of disease mechanisms(markers of core pathogenic processes or the expression of downstream effects of these processes), or(2) biochemical responses to pharmacological or therapeutic intervention, which can be indicative of disease modification. Platelets have been used in neuropharmacological models since the mid-fifties, as they share several homeostatic functions with neurons, such as accumulation and release of neurotransmitters, responsiveness to variations in calcium concentration, and expression of membrane-bound compounds. Recent studies have shown that platelets also express several components related to the pathogenesis of AD,in particular to the amyloid cascade and the regulation of oxidative stress: thus they can be used in the search for biomarkers of the disease process. For instance, platelets are the most important source of circulating forms of the amyloid precursor protein and other important proteins such as Tau and glycogen synthase kinase-3B. Moreover, platelets express enzymes involved in membrane homeostasis(e.g., phospholipase A2), and markers of the inflammatory process and oxidative stress. In this review we summarize the available literature and discuss evidence concerning the potential use of platelet markers in AD.展开更多
文摘Viruses have been shown to be responsible for 10%-15% of cancer cases. Epstein-Barr virus(EBV) is the first virus to be associated with human malignancies. EBV can cause many cancers, including Burkett's lymphoma, Hodgkin's lymphoma, post-transplant lymphoproliferative disorders, nasopharyngeal carcinoma and gastric cancer. Evidence shows that phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) plays a key role in EBV-induced malignancies. The main EBV oncoproteins latent membrane proteins(LMP) 1 and LMP2 A can activate the PI3K/Akt pathway, which, in turn, affects cell survival, apoptosis, proliferation and genomic instability via its downstream target proteins to cause cancer. It has also been demonstrated that the activation of the PI3K/Akt pathway can result in drug resistance to chemotherapy. Thus, the inhibition of this pathway can increase the therapeutic efficacy of EBV-associated cancers. For example, PI3 K inhibitor Ly294002 has been shown to increase the effect of 5-fluorouracil in an EBV-associated gastric cancer cell line. At present, dual inhibitors of PI3 K and its downstream target mammalian target of rapamycin have been used in clinical trials and may be included in treatment regimens for EBV-associated cancers.
基金Supported by Associao Beneficente Alzira Denise Hertzog da Silva(ABADHS)FAPESPFundao de Amparo à Pesquisa do Estado de So Paulo(Project 02/13633-7)
文摘The search for diagnostic and prognostic markers in Alzheimer's disease(AD) has been an area of active research in the last decades. Biochemical markers are correlates of intracerebral changes that can be identified in biological fluids, namely: peripheral blood(total blood, red and white blood cells, platelets, plasma and serum), saliva, urine and cerebrospinal fluid. An important feature of a biomarker is that it can be measured objectively and evaluated as(1) an indicator of disease mechanisms(markers of core pathogenic processes or the expression of downstream effects of these processes), or(2) biochemical responses to pharmacological or therapeutic intervention, which can be indicative of disease modification. Platelets have been used in neuropharmacological models since the mid-fifties, as they share several homeostatic functions with neurons, such as accumulation and release of neurotransmitters, responsiveness to variations in calcium concentration, and expression of membrane-bound compounds. Recent studies have shown that platelets also express several components related to the pathogenesis of AD,in particular to the amyloid cascade and the regulation of oxidative stress: thus they can be used in the search for biomarkers of the disease process. For instance, platelets are the most important source of circulating forms of the amyloid precursor protein and other important proteins such as Tau and glycogen synthase kinase-3B. Moreover, platelets express enzymes involved in membrane homeostasis(e.g., phospholipase A2), and markers of the inflammatory process and oxidative stress. In this review we summarize the available literature and discuss evidence concerning the potential use of platelet markers in AD.
