Breast cancer(BC) is the most common cancer among women worldwide. The aetiology and carcinogenesis of BC are not clearly defined, although genetic, hormonal, lifestyle and environmental risk factors have been establi...Breast cancer(BC) is the most common cancer among women worldwide. The aetiology and carcinogenesis of BC are not clearly defined, although genetic, hormonal, lifestyle and environmental risk factors have been established. The most common treatment for BC includes breast-conserving surgery followed by a standard radiotherapy(RT) regimen. However, radiation hypersensitivity and the occurrence of RT-induced toxicity in normal tissue may affect patients' treatment. The role of DNA repair in cancer has been extensively investigated, and an impaired DNA damage response may increase the risk of BC and individual radiosensitivity. Single nucleotide polymorphisms(SNPs) in DNA repair genes may alter protein function and modulate DNA repair efficiency, influencing the development of various cancers, including BC. SNPs in DNA repair genes have also been studied as potential predictive factors for the risk of RT-induced side effects. Here, we review the literature on the association between SNPs in base excision repair(BER) genes and BC risk. We focusedon X-ray repair cross complementing group 1(XRCC1), which plays a key role in BER, and on 8-oxoguanine DNA glycosylase 1, apurinic/apyrimidinic endonuclease 1 and poly(ADP-ribose) polymerase-1, which encode three important BER enzymes that interact with XRCC1. Although no association between SNPs and radiation toxicity has been validated thus far, we also report published studies on XRCC1 SNPs and variants in other BER genes and RT-induced side effects in BC patients, emphasising that large well-designed studies are needed to determine the genetic components of individual radiosensitivity.展开更多
Parkinson’s disease is one of the most common progressive neurodegenerative disorder. It is characterized by the depletion of dopamine in the dopaminergic neurons of the striatum of the brain. Pharmacological treatme...Parkinson’s disease is one of the most common progressive neurodegenerative disorder. It is characterized by the depletion of dopamine in the dopaminergic neurons of the striatum of the brain. Pharmacological treatment involves the administration of a dopamine precursor, levodo- pa (L-Dopa), which crosses the blood-brain barrier and replaces the loss of dopamine in the brain. One of the main drawbacks of the ad- ministration of L-Dopa is its short half-life, due to the presence of enzymes, such as the amino acid decarboxylase (AADC), able to rapidly me- tabolize L-Dopa. For this reason the intake of L-Dopa takes always place together with an AADC inhibitor such as carbidopa. The assumption of carbidopa increases L-Dopa half-life, but several patients need to increase the dosage of the pharmacological therapy during the progression of the disease. Another area of dispute is represented by the possibility that L-Dopa can exert a toxic effect on the cells, both in peripheral and in central nervous system, increasing the production of ROS following its conversion to dopamine. Past studies reported toxic effects of L-Dopa in vitro and show conflicting data in in vivo experiments. More recent studies have however shown that L-dopa may exert a protective and antioxidant effect on dopaminergic cells, and its combination with carbidopa in pharmacological treatment amplifies antioxidant capability.展开更多
文摘Breast cancer(BC) is the most common cancer among women worldwide. The aetiology and carcinogenesis of BC are not clearly defined, although genetic, hormonal, lifestyle and environmental risk factors have been established. The most common treatment for BC includes breast-conserving surgery followed by a standard radiotherapy(RT) regimen. However, radiation hypersensitivity and the occurrence of RT-induced toxicity in normal tissue may affect patients' treatment. The role of DNA repair in cancer has been extensively investigated, and an impaired DNA damage response may increase the risk of BC and individual radiosensitivity. Single nucleotide polymorphisms(SNPs) in DNA repair genes may alter protein function and modulate DNA repair efficiency, influencing the development of various cancers, including BC. SNPs in DNA repair genes have also been studied as potential predictive factors for the risk of RT-induced side effects. Here, we review the literature on the association between SNPs in base excision repair(BER) genes and BC risk. We focusedon X-ray repair cross complementing group 1(XRCC1), which plays a key role in BER, and on 8-oxoguanine DNA glycosylase 1, apurinic/apyrimidinic endonuclease 1 and poly(ADP-ribose) polymerase-1, which encode three important BER enzymes that interact with XRCC1. Although no association between SNPs and radiation toxicity has been validated thus far, we also report published studies on XRCC1 SNPs and variants in other BER genes and RT-induced side effects in BC patients, emphasising that large well-designed studies are needed to determine the genetic components of individual radiosensitivity.
文摘Parkinson’s disease is one of the most common progressive neurodegenerative disorder. It is characterized by the depletion of dopamine in the dopaminergic neurons of the striatum of the brain. Pharmacological treatment involves the administration of a dopamine precursor, levodo- pa (L-Dopa), which crosses the blood-brain barrier and replaces the loss of dopamine in the brain. One of the main drawbacks of the ad- ministration of L-Dopa is its short half-life, due to the presence of enzymes, such as the amino acid decarboxylase (AADC), able to rapidly me- tabolize L-Dopa. For this reason the intake of L-Dopa takes always place together with an AADC inhibitor such as carbidopa. The assumption of carbidopa increases L-Dopa half-life, but several patients need to increase the dosage of the pharmacological therapy during the progression of the disease. Another area of dispute is represented by the possibility that L-Dopa can exert a toxic effect on the cells, both in peripheral and in central nervous system, increasing the production of ROS following its conversion to dopamine. Past studies reported toxic effects of L-Dopa in vitro and show conflicting data in in vivo experiments. More recent studies have however shown that L-dopa may exert a protective and antioxidant effect on dopaminergic cells, and its combination with carbidopa in pharmacological treatment amplifies antioxidant capability.
