Background: Evidences have shown that local anaesthetics are clinically useful compounds that exert a pharmacological effect by blocking nerve impulse propagation and also it is able to provoke proliferation and cell ...Background: Evidences have shown that local anaesthetics are clinically useful compounds that exert a pharmacological effect by blocking nerve impulse propagation and also it is able to provoke proliferation and cell growth. Aims: The aim of this study was to investigate the proliferation and cell growth capacity of lidocaine on human gingival fibroblast cells and the different signal pathways involved in its effect. Method: For this purpose in vitro cultures of human gingival fibroblasts were assayed and the effects of lidocaine on proliferation and cell DNA synthesis, Na+-K+-ATPase and PKC activities and K+ efflux were also evaluated. Results: Lidocaine stimulated in a concentration-dependent manner proliferation and cell growth of human gingival cells and the mechanism involve an increment in Na+-K+-ATPase and PKC activities, which led to an increase in K+ release. All of these effects were blocked by tetrodotoxin, ouabain and calphostin C. In addition, PMA (activator of PKC) increased per se the DNA synthesis of human gingival fibroblast cells. Conclusions: This work demonstrates that lidocaine increase human gingival fibroblasts DNA synthesis and proliferation through an activation of PKC pathway accompanied by the stimulation of Na+-K+-ATPase activity with an increase in K+ efflux. These results contribute to showing another action of lidocaine different to its general use as a drug that relieves odontologic pain or acts as an anti-arrithmogenic agent.展开更多
Deficiencies in DNA repair due to inherited germ-line mutations in DNA repair genes cause increased risk of gastrointestinal(GI) cancer. In sporadic GI cancers, mutations in DNA repair genes are relatively rare. Howev...Deficiencies in DNA repair due to inherited germ-line mutations in DNA repair genes cause increased risk of gastrointestinal(GI) cancer. In sporadic GI cancers, mutations in DNA repair genes are relatively rare. However, epigenetic alterations that reduce expression of DNA repair genes are frequent in sporadic GI cancers. These epigenetic reductions are also found in field defects that give rise to cancers. Reduced DNA repair likely allows excessive DNA damages to accumulate in somatic cells. Then either inaccurate translesion synthesis past the un-repaired DNA damages or error-prone DNA repair can cause mutations. Erroneous DNA repair can also cause epigenetic alterations(i.e., epimutations, transmitted through multiple replication cycles). Some of these mutations and epimutations may cause progression to cancer. Thus, deficient or absent DNA repair is likely an important underlying cause of cancer. Whole genome sequencing of GI cancers show that between thousands to hundreds of thousands of mutations occur in these cancers. Epimutations that reduce DNA repair gene expression and occur early in progression to GI cancers are a likely source of this high genomic instability. Cancer cells deficient in DNA repair are more vulnerable than normal cells to inactivation by DNA damaging agents. Thus, some of the most clinically effective chemotherapeutic agents in cancer treatment are DNA damaging agents, and their effectiveness often depends on deficient DNA repair in cancer cells. Recently, at least 18 DNA repair proteins, each active in one of six DNA repair pathways, were found to be subject to epigenetic reduction of expression in GI cancers. Different DNA repair pathways repair different types of DNA damage. Evaluation of which DNA repair pathway(s) are deficient in particular types of GI cancer and/or particular patients may prove useful in guiding choice of therapeutic agents in cancer therapy.展开更多
目的:探讨表观遗传修饰在三阴性乳腺癌(triple negative breast cancer,TNBC)检测、诊断和靶向治疗中的机制及作用。方法:应用PubMed、CNKI全文数据库及Google学术搜索等检索系统,以"乳腺癌或三阴性乳腺癌和表观遗传学或DNA甲基化&...目的:探讨表观遗传修饰在三阴性乳腺癌(triple negative breast cancer,TNBC)检测、诊断和靶向治疗中的机制及作用。方法:应用PubMed、CNKI全文数据库及Google学术搜索等检索系统,以"乳腺癌或三阴性乳腺癌和表观遗传学或DNA甲基化"等为关键词,检索2003-01-2013-12的相关文献,共检索到英文文献1 055条,中文文献35条。纳入标准:1)TNBC癌诊断与治疗;2)表观遗传学修饰机制;3)表观遗传学对TNBC癌的意义。根据纳入标准,符合分析的文献47篇。结果:DNA甲基化、组蛋白修饰及miRNA调控在TNBC的发生、发展中扮演重要角色,通过表观遗传修饰与TNBC相关基础研究的总结,以及在已有的实验研究或临床研究的基础上进行理论推测,对TNBC的临床诊断、预后和治疗具有借鉴意义。结论:通过研究表观遗传学修饰改变在TNBC发生、发展中的作用,可为将来TNBC患者的临床治疗提供新思路。展开更多
文摘Background: Evidences have shown that local anaesthetics are clinically useful compounds that exert a pharmacological effect by blocking nerve impulse propagation and also it is able to provoke proliferation and cell growth. Aims: The aim of this study was to investigate the proliferation and cell growth capacity of lidocaine on human gingival fibroblast cells and the different signal pathways involved in its effect. Method: For this purpose in vitro cultures of human gingival fibroblasts were assayed and the effects of lidocaine on proliferation and cell DNA synthesis, Na+-K+-ATPase and PKC activities and K+ efflux were also evaluated. Results: Lidocaine stimulated in a concentration-dependent manner proliferation and cell growth of human gingival cells and the mechanism involve an increment in Na+-K+-ATPase and PKC activities, which led to an increase in K+ release. All of these effects were blocked by tetrodotoxin, ouabain and calphostin C. In addition, PMA (activator of PKC) increased per se the DNA synthesis of human gingival fibroblast cells. Conclusions: This work demonstrates that lidocaine increase human gingival fibroblasts DNA synthesis and proliferation through an activation of PKC pathway accompanied by the stimulation of Na+-K+-ATPase activity with an increase in K+ efflux. These results contribute to showing another action of lidocaine different to its general use as a drug that relieves odontologic pain or acts as an anti-arrithmogenic agent.
文摘Deficiencies in DNA repair due to inherited germ-line mutations in DNA repair genes cause increased risk of gastrointestinal(GI) cancer. In sporadic GI cancers, mutations in DNA repair genes are relatively rare. However, epigenetic alterations that reduce expression of DNA repair genes are frequent in sporadic GI cancers. These epigenetic reductions are also found in field defects that give rise to cancers. Reduced DNA repair likely allows excessive DNA damages to accumulate in somatic cells. Then either inaccurate translesion synthesis past the un-repaired DNA damages or error-prone DNA repair can cause mutations. Erroneous DNA repair can also cause epigenetic alterations(i.e., epimutations, transmitted through multiple replication cycles). Some of these mutations and epimutations may cause progression to cancer. Thus, deficient or absent DNA repair is likely an important underlying cause of cancer. Whole genome sequencing of GI cancers show that between thousands to hundreds of thousands of mutations occur in these cancers. Epimutations that reduce DNA repair gene expression and occur early in progression to GI cancers are a likely source of this high genomic instability. Cancer cells deficient in DNA repair are more vulnerable than normal cells to inactivation by DNA damaging agents. Thus, some of the most clinically effective chemotherapeutic agents in cancer treatment are DNA damaging agents, and their effectiveness often depends on deficient DNA repair in cancer cells. Recently, at least 18 DNA repair proteins, each active in one of six DNA repair pathways, were found to be subject to epigenetic reduction of expression in GI cancers. Different DNA repair pathways repair different types of DNA damage. Evaluation of which DNA repair pathway(s) are deficient in particular types of GI cancer and/or particular patients may prove useful in guiding choice of therapeutic agents in cancer therapy.
文摘目的:探讨表观遗传修饰在三阴性乳腺癌(triple negative breast cancer,TNBC)检测、诊断和靶向治疗中的机制及作用。方法:应用PubMed、CNKI全文数据库及Google学术搜索等检索系统,以"乳腺癌或三阴性乳腺癌和表观遗传学或DNA甲基化"等为关键词,检索2003-01-2013-12的相关文献,共检索到英文文献1 055条,中文文献35条。纳入标准:1)TNBC癌诊断与治疗;2)表观遗传学修饰机制;3)表观遗传学对TNBC癌的意义。根据纳入标准,符合分析的文献47篇。结果:DNA甲基化、组蛋白修饰及miRNA调控在TNBC的发生、发展中扮演重要角色,通过表观遗传修饰与TNBC相关基础研究的总结,以及在已有的实验研究或临床研究的基础上进行理论推测,对TNBC的临床诊断、预后和治疗具有借鉴意义。结论:通过研究表观遗传学修饰改变在TNBC发生、发展中的作用,可为将来TNBC患者的临床治疗提供新思路。
