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1.
Sci Rep ; 14(1): 8742, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627441

RESUMO

Building structures are subjected to strong earthquakes, which result in lateral collisions between them. Such collisions often cause severe structural damage and exacerbate the seismic hazard risk of building structures during earthquake events. This paper discusses the application of vibration control devices based on negative stiffness inerter damper in single-story adjacent building structures. The dynamic equations of the vibration control system containing different types of negative stiffness inerter damper under seismic excitation are established as a unified model. The H2 norm theory and Monte Carlo pattern search method are used to optimize the design parameters to improve the vibration control performance of the system, and the dynamic characteristics of the system are investigated. The results demonstrate that attaching negative stiffness inerter damper to adjacent building structures can effectively improve the overall seismic capacity reserve of the building and reduce the risk of collision of adjacent building structures; improve the robustness and stability of the system, and better reduce the displacement response of the building structure under seismic excitation. In addition, the potential of NSID-based vibration control devices to convert seismic energy into usable electricity has been investigated.

2.
J Chem Phys ; 160(5)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38341710

RESUMO

Within the confines of a densely populated cell nucleus, chromatin undergoes intricate folding, forming loops, domains, and compartments under the governance of topological constraints and phase separation. This coordinated process inevitably introduces interference between different folding strategies. In this study, we model interphase chromatins as block copolymers with hetero-hierarchical loops within a confined system. Employing dissipative particle dynamics simulations and scaling analysis, we aim to explain how the structure and distribution of loop domains modulate the microphase separation of chromatins. Our results highlight the correlation between the microphase separation of the copolymer and the length, heterogeneity, and hierarchically nested levels of the loop domains. This correlation arises from steric repulsion intrinsic to loop domains. The steric repulsion induces variations in chain stiffness (including local orientation correlations and the persistence length), thereby influencing the degree of phase separation. Through simulations of block copolymers with distinct groups of hetero-hierarchical loop anchors, we successfully reproduce changes in phase separation across diverse cell lines, under fixed interaction parameters. These findings, in qualitative alignment with Hi-C data, suggest that the variations of loop constraints alone possess the capacity to regulate higher-order structures and the gene expressions of interphase chromatins.


Assuntos
Núcleo Celular , Cromatina , Polímeros/química
3.
Curr Protoc ; 4(2): e1002, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38406972

RESUMO

The widespread application of high-throughput sequencing technology has generated massive sequences of B-cell receptor (BCR) immune repertoires. Computational analysis of these data has gained significant attention due to the increasing importance of immunotherapy and precision medicine. It not only reveals the diversity and dynamic changes in immune responses, contributing to the study of associated diseases, but also provides valuable information for immunodiagnostics and drug development. Recently, we introduced a BCR-specific multiple sequence alignment (MSA) method along with a comprehensive platform software called Abalign, which stands out as an excellent choice for analyzing BCR immune repertoires due to its unique high-throughput processing capability. It offers ultra-fast MSA functionality and a wide range of analytical features, including BCR/antibody extraction, clonal grouping, lineage tree construction, mutation profiling, diversity statistics, VJ gene assignment, antibody humanization, and more. Importantly, users can perform these analyses using the graphical user interface without any programming skills or scripts. In this article, we present a series of protocols that integrate Abalign's analysis modules into a cohesive workflow. This step-by-step workflow provides detailed instructions for software installation, data preparation, and comprehensive analysis of BCR immune repertoires. This workflow facilitates the efficient acquisition of comprehensive results in profiling BCR immune repertoires, offering insights into the impacts of infectious diseases, allergies, autoimmune disorders, tumor immunology, and antibody drugs. Abalign is freely available at http://cao.labshare.cn/abalign/. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Resource preparation Basic Protocol 2: Analyzing BCR immune repertoires Support Protocol 1: Aiding antibody humanization Support Protocol 2: Constructing B-cell lineage trees Alternate Protocol: Running with Linux command line Basic Protocol 3: Comparing BCR immune repertoires.


Assuntos
Linfócitos B , Receptores de Antígenos de Linfócitos B , Receptores de Antígenos de Linfócitos B/genética , Software , Anticorpos , Células Clonais
4.
Carbohydr Polym ; 326: 121590, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38142089

RESUMO

The utilization of biomass waste has attracted much interest, but such attention hasn't been paid to the abundant fallen maple leaves in Canada. Herein, we aim to obtain cellulose nanocrystals (CNCs) from maple leaves and explore their potential applications as sustainable stabilizers of Pickering emulsions for the preservation of food products with complicated structures. The results reveal that two types of CNCs were extracted from maple leaves at different alkaline conditions. Octenyl succinic anhydride was selected to modify rod-like CNCs, and the CNC-stabilized oil-in-water Pickering emulsions showed excellent stability. Cinnamaldehyde, a model antibacterial compound, was incorporated in the Pickering emulsions, which exhibited the improved storage stability and sustained antibacterial capacity towards both Gram-positive and Gram-negative bacteria. Shrimp was chosen as an example that has complicated surface structure and is hard to disinfect, and the CNC-stabilized Pickering emulsions could be easily sprayed on the surface of shrimp to inhibit the proliferation of bacteria and inactivate the psychrophilic bacteria responsible for shrimp spoilage at refrigerated condition, so as to preserve the quality of shrimp. Therefore, the current work suggests the possibility to utilize fallen maple leaves as a promising source of CNCs and the applications of CNC-stabilized Pickering emulsions in seafood preservation.


Assuntos
Acer , Nanopartículas , Emulsões/química , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Celulose/química , Alimentos Marinhos , Nanopartículas/química
5.
iScience ; 24(9): 102945, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34458697

RESUMO

The Laplace pressure is one of the most fundamental regulators that determine cell shape and function, and thus has been receiving widespread attention. Here, we systemically investigate the effect of the Laplace pressure on the shape and function of the cells during cytokinesis. We find that the Laplace pressure during cytokinesis can directly control the distribution and size of cell blebbing and adjust the symmetry of cell division by virtue of changing the characteristics of cell blebbing. Further, we demonstrate that the Laplace pressure changes the structural uniformity of cell boundary to regulate the symmetry of cell division. Our findings provide further insights as to the important role of the Laplace pressure in regulating the symmetry of cell division during cytokinesis.

6.
J Phys Chem B ; 125(32): 9092-9101, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34351763

RESUMO

It is generally agreed that the nuclei of eukaryotic cells at interphase are partitioned into disjointed territories, with distinct regions occupied by certain chromosomes. However, the underlying mechanism for such territorialization is still under debate. Here we model chromosomes as coarse-grained block copolymers and to investigate the effect of loop domains (LDs) on the formation of compartments and territories based on dissipative particle dynamics. A critical length of LDs, which depends sensitively on the length of polymeric blocks, is obtained to minimize the degree of phase separation. This also applies to the two-polymer system: The critical length not only maximizes the degree of territorialization but also minimizes the degree of phase separation. Interestingly, by comparing with experimental data, we find the critical length for LDs and the corresponding length of blocks to be respectively very close to the mean length of topologically associating domains (TADs) and chromosomal segments with different densities of CpG islands for human chromosomes. The results indicate that topological constraints with optimal length can contribute to the formation of territories by weakening the degree of phase separation, which likely promotes the chromosomal flexibility in response to genetic regulations.


Assuntos
Núcleo Celular , Cromossomos , Cromatina , Cromossomos/genética , Ilhas de CpG , Humanos , Interfase
7.
J Chem Phys ; 153(23): 234902, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33353321

RESUMO

With simplified interactions and degrees of freedom, coarse-grained (CG) simulations have been successfully applied to study the translational and rotational diffusion of proteins in solution. However, in order to reach larger lengths and longer timescales, many CG simulations employ an oversimplified model for proteins or an implicit-solvent model in which the hydrodynamic interactions are ignored, and thus, the real kinetics are more or less unfaithful. In this work, we develop a CG model based on the dissipative particle dynamics (DPD) that can be universally applied to different types of proteins. The proteins are modeled as a group of rigid DPD beads without conformational changes. The fluids (including solvent and ions) are also modeled as DPD beads. The electrostatic interactions between charged species are explicitly considered by including charge distributions on DPD particles. Moreover, a surface friction between the protein and fluid beads is applied to control the slip boundary condition. With this model, we investigate the self-diffusion of a single globular protein in bulk solution. The translational and rotational diffusion coefficients of the protein can be tuned by the surface frictional constant to fit the predictions of the Stokes-Einstein (SE) relation. We find that both translational and rotational diffusion coefficients that meet with the prediction of the SE relation based on experimental results of the hydrodynamic radius are reached at almost the same frictional constant for different types of proteins. Such scaling behavior indicates that the model can be applied to simulate the translational and rotational diffusion together for various types of proteins.


Assuntos
Proteínas/química , Difusão , Simulação de Dinâmica Molecular , Tamanho da Partícula
8.
Soft Matter ; 16(15): 3621-3627, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32101215

RESUMO

Gradients in temperature, concentration or electrostatic potential cannot exert forces on a bulk fluid; they can, however, exert forces on a fluid in a microscopic boundary layer surrounding a (nano)colloidal solute, resulting in so-called phoretic flow. Here we present a simulation study of phoretic flow around a spherical colloid held fixed in a concentration gradient. We show that the resulting flow velocity depends non-monotonically on the strength of the colloid-fluid interaction. The reason for this non-monotonic dependence is that solute particles are effectively trapped in a shell around the colloid and cannot contribute to diffusio-phoresis. We also observe that the flow depends sensitively on the anisotropy of solute-colloid interaction.

9.
Biochem Biophys Res Commun ; 513(4): 997-1004, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31005253

RESUMO

The aim of this study is to investigate the effect of PMVs on mice with ischemic cerebral infarction and its mechanism. Male C57BL/6 mice were selected, and the right focal cortical infarction model was established via cauterization under a microscope and randomly divided into sham operation (Sham) group, normal saline control (Saline) group and platelet microvesicles intervention (PMVs) group. At 1 h after modeling, 5 µL of PMVs (50 µg/mL) or normal saline was injected into the lateral ventricle. The neurological function of mice in each group was evaluated at 1, 3, 7, 14 and 28 d after modeling. After 28 d, the cerebral infarction area was detected via 2,3,5-triphenyltetrazolium chloride (TTC) staining. At 7 and 28 d after modeling, the blood vessel density, proliferation rate of new vessels and encapsulation rate of pericytes were detected via immunofluorescence staining. Moreover, the changes in cerebral cortical blood flow at the infarction side were detected before modeling and at 7 and 28 d after modeling, respectively. Finally, the expressions of proangiogenic factors vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and N-Cadherin were detected via Western blotting at 3, 7 and 28 d after modeling. PMVs could promote the improvement of neurological function and significantly reduce the cerebral infarction volume in mice with cerebral infarction. PMVs promoted proliferation of new vessels and increased blood vessel density at the infarction edge in mice with cerebral infarction. PMVs could increase the encapsulation rate of pericytes at the infarction edge and improve the permeability of blood-brain barrier in mice with cerebral infarction. PMVs could increase the cerebral cortical blood flow perfusion in mice with cerebral infarction. PMVs could increase proangiogenic factors in brain tissues in mice with cerebral infarction. PMVs could significantly improve the recovery of neurological function in mice with cerebral infarction, which is closely related to the ability of PMVs to promote angiogenesis at the infarction edge. The possible mechanism is that PMVs facilitate angiogenesis after cerebral infarction through promoting the expressions of VEGF, Ang-1 and N-Cadherin. More importantly, the new vessels promoted by PMVs have complete structure and perfect function, and can improve the cerebral blood flow perfusion at the infarction side.


Assuntos
Indutores da Angiogênese/farmacologia , Plaquetas/citologia , Micropartículas Derivadas de Células/fisiologia , Infarto Cerebral/terapia , Animais , Micropartículas Derivadas de Células/química , Circulação Cerebrovascular/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Fatores de Tempo
10.
Langmuir ; 34(46): 14096-14101, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30380889

RESUMO

Surface nanobubbles have been presumed to lead to the experimental observation that liquid boiling often occurs at a much lower supersaturation than expected, yet no qualitative theory exists to explain how they participate in the process. Here, we report through a simple theoretical analysis on how the metastable nanobubbles nucleate the liquid-to-vapor transition by serving as an intermediate phase. The appearance of metastable nanobubbles inhibits the shrink of the bubble nucleus and changes bubble nucleation into a multistep process. We show three possible mechanisms for heterogeneous nucleation starting from metastable surface nanobubbles: nucleation from pinned nanobubbles, nucleation via nanobubble depinning, and nucleation through nanobubble coalescence, each predicting a significant reduction in a nucleation barrier. The occurrence of a specific nucleation pathway of bubble nucleation depends on the detailed geometry of local substrate roughness. These results give insight into how the appearance of surface nanobubbles changes the nucleation mechanisms of liquid boiling.

11.
J Chem Phys ; 148(6): 064704, 2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-29448769

RESUMO

The formation of gas bubbles presents a frequent challenge to microfluidic operations, for which fluids are geometrically confined to a microscale space. Here, to understand the mechanism of nucleating gas bubbles in microfluidic devices, we investigate the formation and stability of nanobubbles in confined solutions. Our molecular dynamics simulations show that while pinning of the contact line is a prerequisite for the stability of surface nanobubbles in open systems that can exchange gas with surrounding environment, in confined solutions, stable nanobubbles can exist even without pinning. In supersaturated condition, stable bubbles can be found in confined solutions with acute or obtuse contact angle, depending on the substrate hydrophobicity. We also demonstrate that when open to the bulk solution, the stable nanobubbles in closed systems would become unstable unless both supersaturation and pinning of the contact line are satisfied. Our results not only shed light on the design of novel heterogeneous surfaces for generating nanobubbles in confined space with controllable shape and stability but also address the crucial effect of gas exchange with the surroundings in determining the stability of nanobubbles.

12.
Langmuir ; 32(49): 13003-13008, 2016 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-27951686

RESUMO

Recent experimental measurements have shown that there exists a population of nanobubbles with different curvature radii, whereas both computer simulations and theoretical analysis indicated that the curvature radii of different nanobubbles should be the same at a given supersaturation. To resolve such inconsistency, we perform molecular dynamics simulations on surface nanobubbles that are stabilized by heterogeneous substrates either in the geometrical heterogeneity model (GHM) or in the chemical heterogeneity model (CHM) and propose that the inconsistency could be ascribed to the substrate-induced nanobubble deformation. We find that, as expected from theory and computer simulation, for either the GHM or the CHM, there exists a universal upper limit of contact angle for the nanobubbles, which is determined by the degree of supersaturation alone. By analyzing the evolution of the shape of nanobubbles as a function of substrate hydrophobicity that is controlled here by the liquid-solid interaction, two different origins of nanobubble deformation are identified. For substrates in the GHM, where the contact line is pinned by surface roughness, variation in the liquid-solid interaction changes only the location of the contact line and the measured contact angle, without causing a change in the nanobubble curvature. For substrates in the CHM, however, the liquid-solid interaction exerted by the bottom substrate can deform the vapor-liquid interface, resulting in variations in both the curvature of the vapor-liquid interface and the contact angle.

13.
Oncotarget ; 7(51): 85464-85471, 2016 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-27863428

RESUMO

We investigated the correlation between type 2 diabetes (T2D)-related genes and the clinical characteristics of T2D in the Chinese Han population. Our study included 319 patients and 387 controls. Age, gender, clinical features, medications intake and biochemical blood profiles were analyzed. Genotyping was performed on a total of 18 single nucleotide polymorphisms previously reported to be associated with T2D. Our analyses revealed that the CT genotype of ARHGAP22 rs4838605 is associated with T2D risk. Upon analyzing the subjects' clinical characteristics, we found that for rs2811893, the TT genotype correlated with high creatinine levels, while the AA genotype of rs17045754 and the TT genotype of rs4838605 correlated with elevated triglyceride levels. In addition, the AA genotype of rs17376456 and the TT genotype of rs6214 (p = 0.006) correlated with elevated hemoglobin A1c levels. Lastly, those carrying the TT genotype of rs7772697 and the CA genotype of rs3918227 exhibited higher mean body mass index and Cystatin C than controls. Our results showing that the ARHGAP22 gene is associated with an increased risk of T2D, and that seven SNPs in MYSM1, PLXDC2, ARHGAP22 and HS6ST3 promote T2D progression and could help predict the clinical course of T2D in patients at risk.


Assuntos
Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único , Idoso , Povo Asiático/genética , Biomarcadores/sangue , Estudos de Casos e Controles , China , Creatinina/sangue , Cistatina C/análise , Proteínas de Ligação a DNA/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/etnologia , Progressão da Doença , Feminino , Proteínas Ativadoras de GTPase/genética , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Hemoglobinas Glicadas/análise , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Receptores de Superfície Celular/genética , Fatores de Risco , Sulfotransferases/genética , Transativadores , Fatores de Transcrição/genética , Triglicerídeos/sangue , Proteases Específicas de Ubiquitina
14.
Langmuir ; 32(36): 9321-8, 2016 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-27536958

RESUMO

We present a theoretical and simulation study of anchored magneto-elastic filaments in external magnetic field. The filaments are composed of a mixture of superparamagnetic and nonmagnetic colloidal beads interlinked with elastic springs. We explore the steady-state structures of filaments with various composition and bending rigidity subject to external magnetic field parallel to the surface. The interplay of elastic and induced magnetic interactions results in a rich phase behavior with morphologies reminiscent of macromolecular folding: bent filaments, loops, sheets, helicoids, and other collapsed structures. Our results provide new insights into the design of hierarchically assembled supramolecular structures with controlled response to external stimuli.

15.
PLoS One ; 11(3): e0151159, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26954357

RESUMO

In living systems proteins are typically found in crowded environments where their effective interactions strongly depend on the surrounding medium. Yet, their association and dissociation needs to be robustly controlled in order to enable biological function. Uncontrolled protein aggregation often causes disease. For instance, cataract is caused by the clustering of lens proteins, i.e., crystallins, resulting in enhanced light scattering and impaired vision or blindness. To investigate the molecular origins of cataract formation and to design efficient treatments, a better understanding of crystallin association in macromolecular crowded environment is needed. Here we present a theoretical study of simple coarse grained colloidal models to characterize the general features of how the association equilibrium of proteins depends on the magnitude of intermolecular attraction. By comparing the analytic results to the available experimental data on the osmotic pressure in crystallin solutions, we identify the effective parameters regimes applicable to crystallins. Moreover, the combination of two models allows us to predict that the number of binding sites on crystallin is small, i.e. one to three per protein, which is different from previous estimates. We further observe that the crowding factor is sensitive to the size asymmetry between the reactants and crowding agents, the shape of the protein clusters, and to small variations of intermolecular attraction. Our work may provide general guidelines on how to steer the protein interactions in order to control their association.


Assuntos
Cristalinas/metabolismo , Substâncias Macromoleculares/metabolismo , Modelos Teóricos , Algoritmos , Ligação Proteica , Soluções , Termodinâmica
16.
J Chem Phys ; 142(3): 034504, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25612717

RESUMO

Percolation or aggregation in colloidal system is important in many fields of science and technology. Using molecular dynamics simulations, we study the percolation behavior for systems consisting of spheres interacting with short-range square-well (SRSW) which mimic colloidal particles, with different interaction ranges. We specifically focus on how the interaction range affects the percolation thresholds in the supercritical region. We find that the contact percolation boundaries are strongly dependent on the interaction ranges of SRSW, especially away from the liquid-liquid critical point. However, varying the interaction ranges of SRSW does not affect much the structure along percolation boundaries especially for low packing fractions. For instance, along the percolation boundary, distributions of coordination number show convergence, and distributions of cluster size are universal for different interaction ranges considered. In addition, either the bond percolation boundaries or isolines of average bond coordination number collapse to those for Baxter sticky model on phase diagram, which confirms the extended law of corresponding states.


Assuntos
Simulação de Dinâmica Molecular
17.
Hepatobiliary Pancreat Dis Int ; 3(2): 226-9, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15138115

RESUMO

BACKGROUND: FasL expression was reported to be associated with hepatic metastasis of colorectal cancer. The aim of this study was to study FasL gene expression in colorectal carcinoma and its influences on biological behavior and hepatic metastasis of colorectal carcinoma. METHODS: FasL gene expressions were examined with reverse transcriptase-polymerase chain reaction (RT-PCR) in the primary focus of colorectal carcinoma, adjacent cancerous mucosae, and metastasized liver focus from colorectal cancer. HR-8348 cells of human rectal cancer cell line were transfected with FasL cDNA. Cell growth suppression rate and response to 5-FU and carboplatin were observed and analyzed with the MTT method. RESULTS: FasL gene expression was detected in the primary focus of colorectal cancer (n=58), adjacent cancerous mucosae (n=58), and metastasized hepatic tumor tissues (n=28). The positive rate of FasL expression was 24% (14/58), 8% (5/58), and 100% (58/58) in the primary focus, adjacent cancerous mucosae and metastasized hepatic tumor tissues respectively. FasL expression rate in the metastasized hepatic tumor tissues was higher than that in the primary focus (X(2)=43.49, P<0.01) and adjacent cancerous mucosae (X(2)=57.66, P<0.01). In a group of patients with hepatic metastasis, the FasL expression rate in primary focus was higher than that in patients without hepatic metastasis (X(2)=3.96, P<0.05). In vitro study positive expression of FasL was shown in transfected HR-8348 cells. When 5-FU or carboplatin was added, there was a significant difference in growth suppression rate between FasL positive and controlled cancer cells (t=9.02, t=11.93, P<0.01). Under the same concentration of chemotherapeutic agents, the survival rate of FasL positive HR-8348 cells was higher than that of controlled cells. CONCLUSIONS: FasL positive cancer cells are powerfully resistant to chemotherapeutic agents. The expression of the FasL gene in colorectal cancer cells is related to immune evasion to escape from being killed by immune cells, showing stronger drug-resistance, and it facilitates hepatic metastasis.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Hepáticas/genética , Glicoproteínas de Membrana/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Carboplatina/farmacologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , DNA Complementar/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Proteína Ligante Fas , Feminino , Fluoruracila/farmacologia , Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Transfecção/métodos
18.
Zhonghua Wai Ke Za Zhi ; 41(9): 646-468, 2003 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-14680559

RESUMO

OBJECTIVE: To study FasL gene expression in colorectal carcinoma and its influences on biological behaviour of colorectal cancer and hepatic metastasis. METHODS: FasL gene expressions were examined with RT-PCR technique in the primary locus of colorectal cancer, mucosa adjacent to cancer, and hepatic metastasis. HR-8348 cells of human rectal cancer cell line were transfected with FasL cDNA. Cell growth suppression rates and cell response to 5-FU and carboplatin were observed and analysed with MTT method. RESULTS: FasL gene expressions were detected in the primary site of colorectal cancer (n = 58), cancer adjacent mucosa (n = 58), and hepatic metastasis (n = 28). The positive rate of FasL expression was 24% (14/58), 14% (8/58), 100% (28/28), respectively, in primary site, tumor adjacent mucoca and hepatic metastasis. FasL expression rate in hepatic metastasis was higher than that in the primary site (chi2 = 43.49, P < 0.01) and tumor adjacent mucosa (chi2 = 57.66, P < 0.01). In a group of patients with hepatic metastasis, FasL expression rate in primary site was higher than that in patients without hepatic metastasis (chi2 = 3.96, P < 0.05). In vitro experiment, positive expression of FasL was found in transfected HR-8348 cells. When 5-FU or carboplatin was added, there was a significant difference in growth suppression rate between FasL positive and control cancer cells (t = 9.02, t = 11.93, P < 0.01). Under same concentration of chemotheraputic agent, survival rate of FasL positive HR-8348 cells was higher than that of control cells. CONCLUSIONS: FasL positive cancer cells have more powerful resistance to chemotheraputic drugs. Expression of FasL gene in colorectal cancer cells is related with immune evasion to escape killing by immune cells, showing stronger drug-resistance, and it facilitates hepatic metastasis.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Glicoproteínas de Membrana/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Resistencia a Medicamentos Antineoplásicos , Proteína Ligante Fas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transfecção
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