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| 1 | Hallmarks in colorectal cancer:Angiogenesis and cancer stem-like cells显示文摘Carcinogenesis is a multistep process that requires the accumulation of various genetic and epigenetic aberrations to drive the progressive malignant transformation of normal human cells.Two major hallmarks of carcinogenesis that have been described are angiogenesis and the stem cell characteristic of limitless replicative potential.These properties have been targeted over the past decade in the development of therapeutic treatments for colorectal cancer(CRC),one of the most commonly diagnosed and lethal cancers worldwide.The treatment of solid tumor cancers such as CRC has been challenging due to the heterogeneity of the tumor itself and the chemoresistance of the malignant cells.Furthermore,the same microenvironment that maintains the pool of intestinal stem cells that contribute to the continuous renewal of the intestinal epithelia also provides the necessary conditions for proliferative growth of cancer stem-like cells.These cancer stem-like cells are responsible for the resistance to therapy and cancer recurrence,though they represent less than 2.5%of the tumor mass.The stromal environment surrounding the tumor cells,referred to as the tumor niche,also supports angiogenesis,which supplies the oxygen and nutrients needed for tumor development.Anti-angiogenic therapy,such as with bevacizumab,a monoclonal antibody against vascular-endothelial growth factor,significantly prolongs the survival of metastatic CRC patients.However,such treatments are not completely curative,and a large proportion of patient tumors retain chemoresistance or show recurrence.This article reviews the current knowledge regarding the molecular phenotype of CRC cancer cells,as well as discusses the mechanisms contributing to their maintenance.Future personalized therapeutic approaches that are based on the interaction of the carcinogenic hallmarks,namely angiogenic and proliferative attributes,could improve survival and decrease adverse effects induced by unnecessary chemotherapy. | Muriel Mathonnet Aurelie Perraud Niki Christou Hussein Akil Carole Melin Serge Battu Marie-Odile Jauberteau Yves Denizot | 2014 | World Journal of Gastroenterology2014，20，15： | 5 |
| 2 | Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia显示文摘AIM:To identify the distribution of hepatitis B virus (HBV) subgenotype and basal core promoter (BCP) mutations among patients with HBV-associated liver disease in Indonesia.METHODS: Patients with chronic hepatitis (CH, n=61), liver cirrhosis (LC, n=62), and hepatocellular carcinoma (HCC,n=48) were included in this study. HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing.RESULTS: HBV genotype B (subgenotypes B2, B3, B4, B5 and B7) the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C (subgenotypes C1, C2 and C3) was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 (84.9%) and C1 (82.2%) were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 (84.9%) and adrq+ (89.4%) were the most prevalent in HBV genotype B and C, respectively. Double mutation (A1762T/G1764A) in the BCP was significantly higher in LC (59.7%) and HCC (54.2%) than in CH (19.7%), suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC (46.8%), but lower in HCC (22.9%) and CH (18.0%), suggesting that this mutation may be an indicator of cirrhosis.CONCLUSION: HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease. | Andi Utama Sigit Purwantomo Marlinang Diarta Siburian Rama Dhenni Rino Alvani Gani Irsan Hasan Andri Sanityoso Upik Anderiani Miskad Fardah Akil Irawan Yusuf Wenny Astuti Achwan Soewignjo Soemohardjo Syafruddin AR Lelosutan Ruswhandi Martamala Benyamin Lukito Unggul Budihusodo Laurentius Adrianus Lesmana Ali Sulaiman Susan Tai | 2009 | World Journal of Gastroenterology2009，15，32： | 4 |
| 3 | Trophic factors are essential for the survival of grafted oligodendrocyte progenitors and for neuroprotection after perinatal excitotoxicity显示文摘The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent causes of acquired myelin deficiency in the human neonate leading to cerebral palsy and cognitive impairment.In the developing brain,oligodendrocyte(OL)maturation occurs perinatally,and immature OLs are particularly vulnerable.Cell replacement therapy is often considered a viable option to replace progenitors that die due to glutamate excitotoxicity.We previously reported directed specification and mobilization of endogenous committed and uncommitted neural progenitors by the combination of transferrin and insulin growth factor 1(TSC1).Here,considering cell replacement and integration as therapeutic goals,we examined if OL progenitors(OLPs)grafted into the brain parenchyma of mice that were subjected to an excitotoxic insult could rescue white matter injury.For that purpose,we used a well-established model of glutamate excitotoxic injury.Four-day-old mice received a single intraparenchymal injection of the glutamate receptor agonist N-methyl-D-aspartate alone or in conjunction with TSC1 in the presence or absence of OLPs grafted into the brain parenchyma.Energetics and expression of stress proteins and OL developmental specific markers were examined.A comparison of the proteomic profile per treatment was also ascertained.We found that OLPs did not survive in the excitotoxic environment when grafted alone.In contrast,when combined with TSC1,survival and integration of grafted OLPs was observed.Further,energy metabolism in OLPs was significantly increased by N-methyl-D-aspartate and modulated by TSC1.The proteomic profile after the various treatments showed elevated ubiquitination and stress/heat shock protein 90 in response to N-methyl-D-aspartate.These changes were reversed in the presence of TSC1 and ubiquitination was decreased.The results obtained in this pre-clinical study indicate that the use of a combinatorial intervention including both trophic support and healthy OLPs constitutes a promising approach for long-term survival and successful graft integration.We established optimal conditioning of the host brain environment to promote long-term survival and integration of grafted OLPs into an inflamed neonate host brain.Experimental procedures were performed under the United States Public Health Service Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care Committee at(UCLA)(ARC#1992-034-61)on July 1,2010. | Megumi Hirose-Ikeda Brian Chu Paul Zhao Omar Akil Elida Escalante Laurent Vergnes Carlos Cepeda Araceli Espinosa-Jeffrey | 2020 | Neural Regeneration Research2020，15，3： | 4 |
| 4 | Tropomyosin-related kinase B/brain derived-neurotrophicfactor signaling pathway as a potential therapeutic targetfor colorectal cancer显示文摘Colorectal cancer(CRC) is the second most common cause of cancer-related death in western countries. Approximately one-quarter of newly diagnosed patients for CRC have metastases, and a further 40%-50% experience disease recurrence or develop metastases after all standard therapies. Therefore, understanding the molecular mechanisms involved in the progression of CRC and subsequently developing novel therapeutic targets is crucial to improve management of CRC and patients' long-term survival. Several tyrosine kinase receptors have been implicated in CRC development, progression and metastasis, including epidermal growth factor receptor(EGFR) and vascular EGFR. Recently, tropomyosin-related kinase B(Trk B), a tyrosine kinase receptor, has been reported in CRC and found to clearly exert several biological and clinical features, such as tumor cell growth and survival in vitro and in vivo, metastasis formation and poor prognosis. Here we review the significance of Trk B and its ligand brain derived-neurotrophic factor in CRC. We focus on their expression in CRC tumor samples, and their functional roles in CRC cell lines and in in vivo models. Finally we discuss therapeutic approaches that can lead to the development of novel therapeutic agents for treating Trk B-expressing CRC tumors. | Hussein Akil Aurélie Perraud Marie-Odile Jauberteau Muriel Mathonnet | 2016 | World Journal of Gastroenterology2016，22，2： | 3 |
| 5 | Analysis of MIF,FCGR2A and FCGR3A gene polymorphisms with susceptibility to pulmonary tuberculosis in Moroccan population显示文摘In order to investigate the influence of functional polymorphisms of macrophage migration inhibitory factor(MIF),Fcg receptors CD16A(FCGR3A) and CD32A(FCGR2A) genes on susceptibility to pulmonary tuberculosis(PTB) in the Moroccan population,we analyzed 123 patients with PTB and 154 healthy controls.The genotyping for MIF-173(G/C)(rs755622),FCGR2A-131H/R(rs1801274) and FCGR3A-158V/F(rs396991) was carried out using TaqMan SNP Genotyping Assay method.We found a statistically significant increase of the MIF-173CC homozygote genotype and MIF-173C allele frequencies in PTB patients compared with healthy controls(17.07% versus 5.84%,P=0.003;and 35.37% versus 26.30%,P=0.02;respectively).In contrast,no association was observed between FCGR2A-131H/R and FCGR3A-158V/F polymorphisms and tuberculosis disease.Our finding suggests that MIF-173C variant may play an important role in the development of active tuberculosis. | Khalid Sadki Hoda Lamsyah Blanca Rueda ELmahfoud Akil Abderrahim Sadak Javier Martin Rajae El Aouad | 2010 | Journal of Genetics and Genomics2010，37，4： | 2 |
| 6 | Endogenous opioids: biology and function 显示文摘 | Akil H Watson SJ Young E | 1984 | Annu Rev Neurosci1984，7，： | 1 |
| 7 | Neural circuits mediating stress显示文摘 | Lopez JF Akil H Watson SJ | 1999 | Bio Psychiatry1999，46，11： | 1 |
| 8 | Impact response of fiber metal lami- nate sandwich composite structure with polypropylene honey- comb core 显示文摘 | TAN C Y AKIL H M | 2012 | Composites Part B2012，43，3： | 1 |
| 9 | The psychiatric presentations of Wilson's disease显示文摘 | Akil M Schwartz J A Dutchak D | 1991 | J Neuropsychiatry Clin Neurosci1991，3，： | 1 |
| 10 | Associations of genetic variants inthe transcriptional coactivators EP300 and PCAF with hepatocellularcarcinoma显示文摘 | Akil A Ezzikouri S E1 F A | 2012 | Cancer Epidemiol2012，36，5： | 1 |
| 11 | The low velocity impact response of foam-based sandwich structures显示文摘 | Md. Akil Hazizan W.J. Cantwell | 2002 | Composites Part B2002，，3： | 1 |
| 12 | Delayed effects of chronic variable stress during peripubertal-juvenile period on hippocampal morphology and on cognitive and stress axis functions in rats显示文摘 | Isgor C Kabbaj M Akil H | 2004 | Hippocampus2004，14，5： | 1 |
| 13 | Surface-activated nanosilica treated with silane coupling agents/polypropylene composites:Mechanical,morphological,and thermal studies显示文摘 | Lin 0 H Akil H M Mohd Ishak Z A | 2011 | Polymer Composites2011，32，10： | 1 |
| 14 | Nociceptin/orphanin FQ regulates neuroendocrine function of the limbic-hypothalamic-pituitary-adrenal axis显示文摘 | Watson SJ Akil H | 2001 | Neuroscience2001，102，： | 1 |
| 15 | Effect of zinc supplementation on the distribution of virous elements in serum of diabetic rats subjected to an acute swimming exercise显示文摘 | Bicer M Akil M Sivrikaya A | | 0，，： | 1 |
| 16 | Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and rheumatoid arthritis 显示文摘 | Nile C J Read R C Akil M | 2008 | Arthritis Rheum2008，58，： | 1 |
| 17 | Effect of inorganic fillers on theflammability behavior of polypropylene composites显示文摘 | Razak J A Akil H M Ong H | 2007 | Journal ofThermoplastic Composite Materials2007，20，2： | 1 |
| 18 | Guidelines for the management of dyspepsia显示文摘 | Talley NJ akil N | 2005 | Am J Gastroenternl2005，100，10： | 1 |
| 19 | Role of the copper transporter, CTR1, in platinum-induced oto- toxicity 显示文摘 | More SS Akil O Ianculescu AG | 2010 | J Neurosci2010，30，28： | 1 |
| 20 | Catechol-O-methyltransferase genotype and dopamine regulation in the human brain显示文摘 | Akil M Kolachana BS Rothmond DA | 2003 | J Neurosci2003，23，6： | 1 |
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