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INTRODUCTION Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer patients’ death in the world, especially in areas such as Eastern Asia and Saharan Africa. Although it is well known that HCC is associated with chronic in- fection with hepatitis B virus and C virus, alcohol consumption, chronic exposure to the mycotoxin or aflatoxin B1 (AFB1), cirrhosis of the liver, the precise molecular mechanism of HCC is not well-understood (Bruix et a…  相似文献   

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Prostate cancer (PCa) incidence and mortality have decreased in recent years. Nonetheless, it remains one of the most prevalent cancers in men, being a disquieting cause of men's death worldwide. Changes in many cell signaling pathways have a predominant role in the onset, development, and progression of the disease. These include prominent pathways involved in the growth, apoptosis, and angiogenesis of the normal prostate gland, such as an- drogen and estrogen signaling, and other growth factor signaling pathways. Understanding the foundations of PCa is leading to the discovery of key molecules that could be used to improve patient management. The ideal scenario would be to have a panel of molecules, preferably detectable in body fluids, that are specific and sensitive biomarkers for PCa In the early stages, androgen deprivation is the gold standard therapy. However, as the cancer progresses, it even- tually becomes independent of androgens, and hormonal therapy fails. For this reason, androgen-independent PCa is still a major therapeutic challenge. By disrupting specific protein interactions or manipulating the expression of some key molecules, it might be possible to regulate tumor growth and metastasis formation, avoiding the systemic side effects of current therapies. Clinical trials are already underway to assess the efficacy of molecules specially designed to target key proteins or protein interactions. In this review, we address that recent progress made towards under- standing PCa development and the molecular pathways underlying this pathology. We also discuss relevant molecular markers for the management of PCa and new therapeutic challenges.  相似文献   

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The protein encoded by CC chemokine receptor 7 (CCR7) is a member of the G protein-coupled receptor family. This receptor was identified as a gene induced by the Epstein-Barr virus (EBV), and is thought to be a mediator of EBV effects on B lymphocytes. This receptor is expressed in various lymphoid tissues and activates B and T lymphocytes. It has been shown to control the migration of memory T cells to inflamed tissues, as well as stimulate dendritic cell maturation. To map the CCR7 gene in chicken chromosome, a 6 000 rads chicken-hamster radiation hybrid panel (ChickRH6) was used. PCR of samples from ChickRH6 revealed that the location of CCR7 gene is linked to the maker SEQ0347 (6 cR away) with LOD score of 16.6 and that the marker SEQ0347 is located on chromosome 27 at 27 cR of RH (radiation hydrid) map. We compared the corresponding human mRNA sequence with the predicted coding sequence of chicken CCR7 gene, and found that the assembled contig shared a high percentage of similarity with that of the human gene.  相似文献   

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An increasing number ofmonopartite begomoviruses are being identified that a satellite molecule (DNAβ) is required to induce typical symptoms in host plants. DNAβ encodes a single gene (termed βCl) encoded in the complementary-sense. We have produced transgenic Nieotiana benthamiana and N. tabaeum plants expressing the βC1 gene of a DNAβ associated with Tomato yellow leaf curl China virus (TYLCCNV), under the control of the Cauliflower mosaic virus 35S promoter. Transgenic plants expressing 13C1 showed severe developmental abnormalities in both species. Microscopic analysis of sections of both transgenic and non-transgenic N. tabaeum leaves showed abnormal outgrowths of transgenic N. tabaeum to be due to disorganizedcell division (hyperplasia) of spongy and palisade parenchyma. Immuno-gold labeling of sections with a polyclonal antibody against the βC1 protein showed that the 13C 1 protein accumulated in the nuclei of cells. The possible biological function of the βC1 1protein was discussed.  相似文献   

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Epstein-Barr virus(EBV),a human gammaherpesvirus carried by more than 90% of the world’s population,is associated with malignant tumors such as Burkitt’s lymphoma(BL),Hodgkin lymphoma,post-transplant lymphoma,extra-nodal natural killer/T cell lymphoma,and nasopharyngeal and gastric carcinomas in immune-compromised patients.In the process of infection,EBV faces challenges:the host cell environment is harsh,and the survival and apoptosis of host cells are precisely regulated.Only when host cells receive sufficient survival signals may they immortalize.To establish efficiently a lytic or long-term latent infection,EBV must escape the host cell immunologic mechanism and resist host cell apoptosis by interfering with multiple signaling pathways.This review details the apoptotic pathway disrupted by EBV in EBV-infected cells and describes the interactions of EBV gene products with host cellular factors as well as the function of these factors,which decide the fate of the host cell.The relationships between other EBV-encoded genes and proteins of the B-cell leukemia/lymphoma(Bcl) family are unknown.Still,EBV seems to contribute to establishing its own latency and the formation of tumors by modifying events that impact cell survival and proliferation as well as the immune response of the infected host.We discuss potential therapeutic drugs to provide a foundation for further studies of tumor pathogenesis aimed at exploiting novel therapeutic strategies for EBV-associated diseases.  相似文献   

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Peroxynitrite(ONOO) is a powerful oxidant and nitrosative agent and has in vivo existence.The half life of ONOO at physiological pH is less than 1 s.It can react with nucleic acids,proteins,lipoproteins,saccharides,cardiolipin,etc.,and can modify their native structures.Action of ONOO,synthesized in the authors’ laboratory by a rapid quenched flow process,on structural changes of commercially available RNA was studied by ultraviolet(UV),fluorescence,and agarose gel electrophoresis.Compared to native RNA,the ONOO-modified RNA showed hyperchromicity at 260 nm.Furthermore,the ethidium bromide(EtBr) assisted emission intensities of ONOO-modified RNA samples were found to be lower than the emission intensity of native RNA-EtBr complex.Agarose gel electrophoresis of ONOO-modified RNA showed a gradual decrease in band intensities compared to native RNA,an observation clearly due to the poor intercalation of EtBr with ONOO-modified RNA.Native and ONOO-modified RNA samples were used as an antigen to detect autoantibodies in sera of patients with clinically defined breast cancer.Both direct binding and inhibition enzyme-linked immunosorbent assay(ELISA) confirmed the prevalence of native and 0.8 mmol/L ONOO-modified RNA specific autoantibodies in breast cancer patients.Moreover,the progressive retardation in the mobility of immune complexes formed with native or 0.8 mmol/L ONOO-modified RNA and affinity purified immunoglobulin G(IgG) from sera of breast cancer patients supports the findings of the direct binding and inhibition ELISAs.The peroxynitrite treatment to RNA at a higher concentration appears to have damaged or destroyed the typical epitopes on RNA and thus there was a sharp decrease in autoantibodies binding to 1.4 mmol/L ONOO-modified RNA.It may be interpreted that cellular nitrosative stress can modify and confer immunogenicity on RNA molecules.Higher concentrations of nitrogen reactive species can be detrimental to RNA.However,the emergence of native as well as 0.8 mmol/L ONOO-modified RNA as a novel antigen/substrate for autoantibodies in breast cancer patients indicates that,in future,these molecules might find a place on the panel of antigens for early diagnosis of breast cancer.  相似文献   

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Randomness plays a major role in the interpretation of many interesting traffic flow phenomena, such as hysteresis, capacity drop and spontaneous breakdown. The analysis of the uncertainty and reliability of traffic systems is directly associated with their random characteristics. Therefore, it is beneficial to understand the distributional properties of traffic variables. This paper focuses on the dependence relation between traffic flow density and traffic speed, which constitute the fundamental diagram (FD). The traditional model of the FD is obtained essentially through curve fitting. We use the copula function as the basic toolkit and provide a novel approach for identifying the distributional patterns associated with the FD. In particular, we construct a rule-of-thumb nonparametric copula function, which in general avoids the mis-specification risk of parametric approaches and is more efficient in practice. By applying our construction to loop detector data on a freeway, we identify the dependence patterns existing in traffic data. We find that similar modes exist among traffic states of low, moderate or high traffic densities. Our findings also suggest that highway traffic speed and traffic flow density as a bivariate distribution is skewed and highly heterogeneous.  相似文献   

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Generation of mutants with clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)is commonly carried out in fish species by co-injecting a mixture of Cas9 messenger RNA(mRNA)or protein and transcribed guide RNA(gRNA).However,the appropriate expression system to produce functional gRNAs in fish embryos and cells is rarely present.In this study,we employed a poly-transfer RNA(tRNA)-gRNA(PTG)system driven by cytomegalovirus(CMV)promoter to target the medaka(Oryzias latipes)endogenous gene tyrosinase(tyr)or paired box 6.1(pax6.1)and illustrated its function in a medaka cell line and embryos.The PTG system was combined with the CRISPR/Cas9 system under high levels of promoter to successfully induce gene editing in medaka.This is a valuable step forward in potential application of the CRISPR/Cas9 system in medaka and other teleosts.  相似文献   

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Tissue homeostasis requires a carefully-orchestrated balance between cell proliferation, cellular senescence and cell death. Cells proliferate through a cell cycle that is tightly regulated by cyclin-dependent kinase activities. Cellular senescence is a safeguard program limiting the proliferative competence of cells in living organisms. Apoptosis eliminates unwanted cells by the coordinated activity of gene products that regulate and effect cell death. The intimate link between the cell cycle, cellular senes- cence, apoptosis regulation, cancer development and tumor responses to cancer treatment has become eminently apparent. Extensive research on tumor suppressor genes, oncogenes, the cell cycle and apoptosis regulatory genes has revealed how the DNA damage-sensing and -signaling pathways, referred to as the DNA-damage response network, are tied to cell proliferation, cell-cycle arrest, cellular senescence and apoptosis. DNA-damage responses are complex, involving “sensor” proteins that sense the damage, and transmit signals to “transducer” proteins, which, in turn, convey the signals to numerous “effector” proteins implicated in specific cellular pathways, including DNA repair mechanisms, cell-cycle checkpoints, cellular senescence and apoptosis. The Bcl-2 family of proteins stands among the most crucial regulators of apoptosis and performs vital functions in deciding whether a cell will live or die after cancer chemotherapy and irradiation. In addition, several studies have now revealed that members of the Bcl-2 family also interface with the cell cycle, DNA repair/recombination and cellular senescence, effects that are generally distinct from their function in apoptosis. In this review, we report progress in understanding the molecular networks that regulate cell-cycle checkpoints, cellular senescence and apoptosis after DNA damage, and discuss the influence of some Bcl-2 family members on cell-cycle checkpoint regulation.  相似文献   

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With the recent upsurge of studies in the field of microbiology,we have learned more about the complexity of the gastrointestinal microecosystem.More than 30 genera and 1000 species of gastrointestinal microflora have been found.The structure of the normal microflora is relatively stable,and is in an interdependent and restricted dynamic equilibrium with the body.In recent years,studies have shown that there is a potential relationship between gastrointestinal microflora imbalance and gastric cancer(GC)and precancerous lesions.So,restoring the balance of gastrointestinal microflora is of great significance.Moreover,intervention in gastric premalignant condition(GPC),also known as precancerous lesion of gastric cancer(PLGC),has been the focus of current clinical studies.The holistic view of traditional Chinese medicine(TCM)is consistent with the microecology concept,and oral TCM can play a two-way regulatory role directly with the microflora in the digestive tract,restoring the homeostasis of gastrointestinal microflora to prevent canceration.However,large gaps in knowledge remain to be addressed.This review aims to provide new ideas and a reference for clinical practice.  相似文献   

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Genome stability can be threatened by both endogenous and exogenous agents.Organisms have evolved numerous mechanisms to repair DNA damage,including homologous recombination(HR)and non-homologous end joining(NHEJ).Among the factors associated with DNA repair,the MRE11-RAD50-NBS1(MRN)complex(MRE11-RAD50-XRS2 in Saccharomyces cerevisiae)plays important roles not only in DNA damage recognition and signaling but also in subsequent HR or NHEJ repair.Upon detecting DNA damage,the MRN complex activates signaling molecules,such as the protein kinase ataxia-telangiectasia mutated(ATM),to trigger a broad DNA damage response,including cell cycle arrest.The nuclease activity of the MRN complex is responsible for DNA end resection,which guides DNA repair to HR in the presence of sister chromatids.The MRN complex is also involved in NHEJ,and has a species-specific role in hairpin repair.This review focuses on the structure of the MRN complex and its function in DNA damage repair.  相似文献   

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Dynamic responses of a multi-storey building without or with a sliding base-isolation device for ground shock induced by an in-tunnel explosion are numerically analyzed. The effect of an adjacent tunnel in between the building and the explosion tunnel, which affects ground shock propagation , is considered in the analysis. Different modeling methods, such as the eight-node equal-parametric finite element and mass-lumped system, are used to establish the coupling model consisting of the two adjacent tunnels, the surrounding soil medium with the Lysmer viscous boundary condition, and the multi-storey building with or without the sliding base-isolation device. In numerical calculations , a continuous friction model, which is different from the traditional Coulomb friction model, is adopted to improve the computational efficiency and reduce the accumulated errors. Some example analyses are subsequently performed to study the response characteristics of the building and the sliding base-isolation device to ground shock. The effect of the adjacent tunnel in between the building and the explosion tunnel on the ground shock wave propagation is also investigated. The final conclusions based on the numerical results will provide some guidance in engineering practice.  相似文献   

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Eukaryotic initiation factor subunit c(eIF3c) has been identified as an oncogene that is over-expressed in tumor cells and,therefore,is a potential therapeutic target for gene-based cancer treatment.This study was focused on investigating the effect of small interfering RNA(siRNA)-mediated eIF3c gene knockdown on colon cancer cell survival.The eIF3c gene was observed to be highly expressed in colon cancer cell models.The expression levels of the gene in eIF3c siRNA infected and control siRNA infected cells were compared via real-time polymerase chain reaction(PCR) and western blotting analysis.Cell proliferation levels were analyzed employing 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyltetrazolium bromide(MTT) and colony formation assays.Furthermore,the effects of eIF3c gene knockdown on the cell cycle and apoptosis were analyzed using flow cytometry.The results showed that suppression of eIF3c expression significantly(P<0.001) reduced cell proliferation and colony formation of RKO colon cancer cells.The cell cycle was arrested by decreasing the number of cells entering S phase.Further,apoptosis was induced as a result of eIF3c knockdown.Collectively,eIF3c deletion effectively reduced the survival of colon cancer cells and could be used as a therapeutic tool for colon cancer therapy.  相似文献   

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Appressorium is an infection structure of the phytopathogenic fungus Magnaporthe grisea. Analysis of gene expression profiles ofappressorium development provides insight into the molecular basis of pathogenicity and control of this fungal plant disease. A cDNA array representing 2927 unique genes based on a large EST (expressed sequence tag) database ofM. grisea strain Y34 was constructed and used to profile the gene expression patterns at mycelium and appressorium maturation stages. Compared with mycelia, 55 up-regulated and 22 down-regulated genes were identified in mature appressoria. Among 77 genes, 16 genes showed no similarity to the genome sequences of M. grisea. A novel homologue of peptidyl-prolyl cis-trans isomerase was found to be expressed at low-level in mature appressoria of M. grisea. The results indicated that the genes such as pyruvate carboxylase, phospholipid metabolism-related protein and glyceraldehyde 3-phosphate dehydrogenase involved in gluconeogenesis, lipid metabolism and glycolysis, showed differential expression in mature appressoria. Furthermore, genes such as PTHll, beta subunit of G protein and SGTI involved in cell signalling, were expressed differentially in mature appressoria. Northern blot analysis was used to confirm the cDNA array results.  相似文献   

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The protein encoded by CC chemokine receptor 7 (CCR7) is a member of the G protein-coupled receptor family. This receptor was identified as a gene induced by the Epstein-Barr virus (EBV), and is thought to be a mediator of EBV effects on B lymphocytes. This receptor is expressed in various lymphoid tissues and activates B and T lymphocytes. It has been shown to control the migration of memory T cells to inflamed tissues, as well as stimulate dendritic cell maturation. To map the CCR7 gene in chicken chromosome, a 6000 rads chicken-hamster radiation hybrid panel (ChickRH6) was used. PCR of samples from ChickRH6 revealed that the location of CCR7 gene is linked to the maker SEQ0347 (6 cR away) with LOD score of 16.6 and that the marker SEQ0347 is located on chromosome 27 at 27 cR of RH (radiation hydrid) map. We compared the corresponding human mRNA sequence with the predicted coding sequence of chicken CCR7 gene, and found that the assembled contig shared a high percentage of similarity with that of the human gene.  相似文献   

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Immunomodulatory function of orally administered thymosin α1   总被引:1,自引:0,他引:1  
INTRODUCTION The thymus is a vital immune organ and plays a very important role in the development and mainte- nance of the lymph system. The extract of animal thymus has been used in clinical practice as an ad- junct treatment in patients with carcinoma, viral in- fection and immunodeficiency, but the extract con- taining miscellaneous animal proteins may easily lead to allergy in patients. Thymosin α1 (Tα1) is the most potent ingredient in thymosin and the biological ac- tivity of pur…  相似文献   

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冯政 《海外英语》2011,(6):355-357
By analysing the nature of inference and discourse comprehension as well as the role and classification of inference, it is concluded that inference is a productive mode of thinking that decides from something known or assumed, and the inference in discourse works out the underlying propositions, necessary or elaborative, and the unsaid speaker’s meaning. To derive a good inference, one has to make use of world knowledge and share some experiences with the speaker.  相似文献   

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