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Radiotherapy characterized by invasive, localization and low toxicity has been recognized as one of the standard cancer therapy regimes, especially for non-surgically resectable advanced cancers. However, inherent and acquired resistance of cancer cells has significantly impeded the efficacy of radiotherapy. Of all the resistance determinants, varieties of anti-apoptotic signaling pathways or anti-survival proteins aberrant activation in malignant tumor cells play crucial roles in radiation insensitivity. This paper mainly focuses on clarifying the roles of the interesting key molecular signals including Ras, insulin-like growth factor type 1 receptor, transforming growth factor-beta, histone deacetylase and heat shock protein 90 in regulating radiotherapy sensitivity, in order to find the potential targets to improve the efficacy of radiotherapy.
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Ionizing radiation (IR) including X-ray and X-ray can induce apoptosis of cancer cells, mainly due to telomere damage and genome DNA breaks caused by IR. Although IR has been used clinically to cure some types of malignant tumors, the inherent or acquired resistance of cancer cells to IR has increasingly been an impediment for its usage. Overwhelming evidence has shown that telomerase is able to repair IR-induced telomere and chromosome damages, which may play key roles in mediating IR resistance. Unfortunately, the underlying mechanisms remain poorly known. This paper reviews the advances in research on telomerase-mediated regulation of IR sensitivity in recent 10 years, in order to clarify the molecular mechanism and the roles of telomerase-mediated regulation of IR sensitivity in cancer therapy and hope to provide useful clues and instructions for IR in cancer therapy.
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Objective The objective of this study was to investigate effects of miR-34a on the proliferation,invasion and migration of colon cancer SW480 cell and its possible mechanism.Methods miR-34a overexpressed lentivirus and empty virus vector were transfected into SW480 cells and untreated cells were used as blank control group.Real-time PCR was used to detect the expression of miR-34a in each group.The cell proliferation was detected by CCK8 assay.The cell migration and invasion ability were detected by wound healing and transwell assays.The expression of E-cadherin and Vimentin protein was detected by Western blotting.Results Compared with the empty virus vector group and the blank control group,the expression of miR-34a was increased in the transfected cells,and the cell proliferation efficiency,invasion and migration ability were decreased in the transfected cells (P ＜ 0.05).miR-34a significantly increased the expression of E-cadherin protein and decreased Vimentin protein expression in the transfected cells.Conclusion miR-34a can inhibit the proliferation,invasion and migration of colon cancer SW480 cells,and affect the expression of E-cadherin and Vimentin.MR-34a is expected to be a potential molecular target for the metastasis and recurrence of colorectal cancer.
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P53 abnormality or mutation is commonly seen in patients with hepatocellular carcinoma (HCC), and therefore, restoration of P53 function has become a research hotspot in the treatment of HCC.This article reviews the association of P53 with Bcl-2 protein family, microRNA, TGFβ, HBV, HCV, and AKT and the role of P53 in regulating cell apoptosis, in order to provide clues for improving the therapeutic outcome of HCC.
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Currently, sorafenib is the multi-target inhibitor for the treatment of advanced primary liver cancer, and can effectively prolong the progression-free survival and overall survival in patients with advanced primary liver cancer. The application of sorafenib in the targeted therapy for liver cancer has become a hot topic. Major targets or signaling pathways include Raf/Mek/Erk, Jak/Stat, PI3K/Akt/mTOR, VEGFR and PDGFR, STAT, microRNA, Wnt/β-catenin, autolysosome, and tumor-related proteins, and sorafenib can regulate the proliferation, differentiation, metastasis, and apoptosis of liver cancer cells through these targets. This article reviews the current research on the action of sorafenib on these targets or signaling pathways to provide useful references for further clinical research on sorafenib.
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In recent years, studies have shown that the expression of pyruvate kinase muscle isozyme 2 (PKM2) is increased significantly in various tumor cells. PKM2 acts like a signal molecule in tumor cells and participates in the expression and regulation of genes related to tumor cell proliferation, cell autophagy, and cell cycle progression. This article summarizes the expression of PKM2 in liver cancer tissues and cell lines, elaborates on the role of PKM2 in the proliferation, differentiation, and metastasis of liver cancer cells and prognostic evaluation, and points out that PKM2 can be used in the clinical diagnosis, treatment, and prognostic evaluation of liver cancer.
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Liver fibrosis is the final outcome of various chronic liver diseases, and various cells, cytokines, and miRNAs are involved in the development and progression of liver fibrosis and liver cirrhosis. Hepatic fibrosis and pathologic angiogenesis are interdependent processes and promote each other, but the physiopathological mechanism of arterial capillary proliferation in liver fibrosis remains unknown. Aquaporins not only transport water molecules, but also promote angiogenesis. This article briefly introduces the expression of aquaporins in the hepatobiliary system and their physiological and biochemical characteristics and summarizes the role of aquaporins in the progression of liver fibrosis and liver cirrhosis, in order to provide new thoughts and guidance for aquaporins as the target in the treatment of liver fibrosis and liver cirrhosis.
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Hepatocellular carcinoma ( HCC ) is one of the commonest malignant tumors in China .The therapeutic effects of conventional therapies including surgery resection at early stage ,chemotherapy or radiothera-py are greatly less than expected .One of the most possible reasons is the blockage of apoptosis in HCC cells .This review collects literatures about the studies on the roles of key signal pathways including RA ,STAT3,PDT,p53,β-catenin,TRAIL,microRNA and RAS in HCC therapy .This study may contribute greatly to providing outline in-sights for using apoptosis induction in liver cancer therapy .We hope it can promote the development liver cancer therapy in China .
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Pancreatic adenocarcinoma ( PAC) is still a refractory human digest malignancies due to multi-faceted causes ,late diagnosis and insensitive to traditional chemo -and radio-therapy .Resistance to apoptosis could be one of the most relevant mechanisms for PAC to escape any non -surgical therapy .This review aims to clear up the main deregulated apoptosis signal pathways over the years and to find out the abnormal molecule tar -get(s),and therefore,provide novel concepts for PAC molecular targeting therapy .
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Hepatocellular carcinoma ( HCC ) is one of the most malignant tumors, transcatheter arterial chemoembolization( TACE) is a new treatment for HCC,which is currently considered as the standard care for pa-tients with unresectable HCC.MicroRNAs( miRNAs) ,a class of small non-coding RNAs,the correlations within miRNA dictions and tumor prognosis have been documented,and a part of miRNAs has been proposed as biomar-kers to reliably predict the outcomes before HCC patients being treated with TACE.
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Transforming growth factor-β (TGF-β) exerts apoptotic effects on various types of malignant cells, including liver cancer cells. However, the precise mechanisms by which TGF-β induces apoptosis remain poorly known. In the present study, we have showed that threonine 32 (Thr32) residue of FoxO3 is critical for TGF-β to induce apoptosis via Bim in hepatocarcinoma Hep3B cells. Our data demonstrated that TGF-β induced FoxO3 activation through specific de-phosphorylation at Thr32. TGF-β-activated FoxO3 cooperated with Smad2/3 to mediate Bim up-regulation and apoptosis. FoxO3 (de)phosphorylation at Thr32 was regulated by casein kinase I-ε (CKI-ε). CKI inhibition by small molecule D4476 could abrogate TGF-β-induced FoxO/Smad activation, reverse Bim up-regulation, and block the sequential apoptosis. More importantly, the deregulated levels of CKI-ε and p32FoxO3 were found in human malignant liver tissues. Taken together, our findings suggest that there might be a CKI-FoxO/Smad-Bim engine in which Thr32 of FoxO3 is pivotal for TGF-β-induced apoptosis, making it a potential therapeutic target for liver cancer treatment.
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Humanos , Apoptose , Genética , Proteínas Reguladoras de Apoptose , Proteína 11 Semelhante a Bcl-2 , Carcinoma Hepatocelular , Genética , Patologia , Linhagem Celular Tumoral , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead , Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Genética , Patologia , Proteínas de Membrana , Proteínas Proto-Oncogênicas , Treonina , Genética , Fator de Crescimento Transformador beta , GenéticaRESUMO
Interventional therapy has become the first choice of non-surgical treatment for hepatocellular carcinoma (HCC) due to its advantages such as little trauma and marked local effect. However, the clinical efficiency is less than expected. One of the possibilities is the resistance of cancer cells to anti-cancer drugs. Increasing attention has been paid to the combination of traditional Chinese medicine (TCM) and interventional therapy in HCC treatment. This paper reviews the progress in TCM combined with interventional therapy for HCC at animal experiment and clinical study levels in recent ten years. It is pointed out that the combination therapy with TCM and intervention for HCC has a unique advantage.
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Cholangiocarcinoma (CCA) is a common cancer in hepatobiliary system .Because CCA is in sensitive to conventional chemotherapy and radiotherapy ,the current treatment is mainly depending on the surgical operation when diagnosed early .Tumor necrosis factor related apoptosis inducing ligand ( TRAIL) plays a key role in the process of controlling cell proliferation by binding with its receptor and therefore mediated cell apoptosis . Although the characteristic of selectively killing tumor cells by TRAIL makes it become the new direction of clini -cal treatment of cancer ,the condition that CCA cells are resistant to TRAIL mediated apoptosis restricts its scope of application.Nowadays many studies demonstrate that multiple signaling pathways can regulate the sensitive of CCA cells to TRAIL mediated apoptosis .In this review,we summarize the expression and effects of TRAIL and its receptor in CCA , and conclude the mechanism of multiple pathways restoring the sensitivity of CCA cells to TRAIL mediated apoptosis .
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<p><b>OBJECTIVE</b>To explore the relationship of Ghrelin gene polymorphism with the occurrence of human anorectal malformations (ARMs) and Hirschsprung disease(HSCR).</p><p><b>METHODS</b>PCR and DNA sequencing were used to detect the single nucleotide polymorphism (SNPs) of 3 loci (rs139684563, rs149447194, rs186599567) genotype of Ghrelin gene in 100 children with ARMs, 100 children with HSCR, and 100 healthy children (normal group). Genovariation and gene mutation were analyzed with case-control method.</p><p><b>RESULTS</b>Three loci SNPs were in accordance with Hardy-Weinberg genetic equilibrium. No significant differences were found in rs139684563 allele and genotype frequencies between the cases and the normal groups (P>0.05). The allele and genotype frequencies of rs149447194 and rs186599567 were significantly different between cases and normal group (P<0.05). DNA sequencing results showed that wild-type homozygous deletion (176th and 191th base A deletion, respectively) were found in rs149447194 and rs186599567of ARMs and HSCR children, and single base substitution was detected in rs149447194 of ARMs children (194th codon nucleotide CCT to CTC).</p><p><b>CONCLUSIONS</b>The rs149447194 and the rs186599567 polymorphism changes may be associated with the pathogenesis of ARMs and HSCR.</p>
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Humanos , Alelos , Sequência de Bases , Frequência do Gene , Genótipo , Grelina , Doença de Hirschsprung , Mutação , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Doenças Retais , Análise de Sequência de DNARESUMO
BACKGROUND:There is no simple and effective method to relieve delayed muscle soreness. OBJECTIVE:To conclude the injured mechanism and therapies of delayed muscle soreness by reviewing literature about damage and repair of the skeletal muscle. METHODWanfang and PubMed databases (from January 1991 to January 2014) were retrieved for articles related to morphological structure of the skeletal muscle, mechanism of delayed muscle soreness, and treatment and repair of the skeletal muscle using the keywords of“molecular mechanisms;delayed onset muscle soreness;pain;skeletal muscle;injury”in Chinese and English, respectively. Final y, 24 articles were included in result analysis. RESULTS AND CONCLUSION:Studies have shown that skeletal muscle injury is related to calcium imbalance, energy imbalance and high concentration of active oxygen. Skeletal muscle injury includes metabolic injury, mechanical injury and inflammatory injury. Insulin-like growth factor, peroxisome proliferator-activated receptorγ-coactivator-1αpromoter and tumor necrosis factorαplay important roles in skeletal muscle repair process. Animal experiments have demonstrated that edaravone may reduce secondary damage and inflammatory infiltration by means of directly preventing rapid peroxidation injury of free radicals in the skeletal muscle. Clinical studies have shown that Chinese medicine preparations, massage and acupuncture can delay the occurrence of exercise-induced muscle injury and fatigue, to improve the speed and quality of the recovery of damaged muscles. The treatment of delayed muscle soreness can achieve satisfactory results by combining physiotherapy with traditional Chinese medicine.