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1.
Foods ; 13(2)2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38254567

ABSTRACT

Different storage conditions can influence microbial community structure and metabolic functions, affecting rice grains' quality. However, the microbiological mechanisms by which different storage conditions affect the quality of rice grains are not yet well understood. This study monitored the quality (the content of starch, protein, etc.) and microbial community structure of rice grains stored under different storage conditions with nitrogen gas atmosphere (RA: normal temperature, horizontal ventilation, RB: normal temperature, vertical ventilation, RC: quasi-low temperature, horizontal ventilation). The results revealed that the rice grains stored under condition RB exhibited significantly lower quality compared to condition RA and RC. In addition, under this condition, the highest relative abundance of Aspergillus (16.0%) and Penicillium (0.4%) and the highest levels of aflatoxin A (3.77 ± 0.07 µg/kg) and ochratoxin B1 (3.19 ± 0.05 µg/kg) were detected, which suggested a higher risk of fungal toxin contamination. Finally, co-occurrence network analysis was performed, and the results revealed that butyl 1,2-benzenedicarboxylate was negatively correlated (p < 0.05) with Moesziomyces and Alternaria. These findings will contribute to the knowledge base of rice storage management and guide the development of effective control measures against undesirable microbial activities.

2.
J Sci Food Agric ; 104(6): 3458-3467, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38133630

ABSTRACT

BACKGROUND: Okara cellulose is a highly abundant, green, sustainable, and biodegradable polymer with many potential industrial applications. In this study, we fabricated composite hydrogels with okara cellulose nanofibers (CNFs) and chitosan (CH) by hydrating, sonicating, and heating them at 100 °C for 30 min, and then induced their assembly by cooling. The effects of okara CNF (with and without 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) oxidation) and CH concentration on the structure and properties of the hydrogels was examined, including their microstructure, surface properties, rheological properties, and thermal stability. RESULTS: Our results indicate that there was an electrostatic attraction between the anionic okara CNF and cationic CH, which facilitated hydrogel formation. The surface, textural, rheological, and thermal stability properties were better for the composite hydrogels than for the single CH ones, as well as for the CNF that had undergone TEMPO oxidation. For the TC-CH hydrogels, the contact angle was 39.5°, the interfacial tension was 69.1 mN m-1 , and the surface tension was 1.44 mN m-1 . CONCLUSION: In this study, the novel hydrogels developed may be useful as a soft material in a range of applications in foods, supplements, health care products, cosmetics, and drugs. © 2023 Society of Chemical Industry.


Subject(s)
Chitosan , Nanofibers , Cellulose/chemistry , Chitosan/chemistry , Hydrogels/chemistry , Nanofibers/chemistry , Sonication
3.
Int J Biol Macromol ; 258(Pt 2): 129079, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38161024

ABSTRACT

Currently, there is great interest in converting edible agro-waste, such as okara from soybean production, into value-added products. For this study, we focus on fabricating composite hydrogels from okara cellulose nanofibers (CNFs) and carrageenan (CA). We also examined the effects of TEMPO oxidation of the okara CNFs, as well as CA concentration, on the microstructure and physicochemical properties of the composite hydrogels. The water holding capacity, oil holding capacity, surface tension, gel strength, and viscoelasticity of the composite microgels increased with increasing CA concentration, and it was found that the highest values were obtained for TC-CA2 hydrogel: contact angle = 43.6° and surface tension = 45.12 mN/m, which was attributed to the formation of a more regular and dense three-dimensional gel network. All the CNF-CA microgels had highly anionic ζ-potential values (-38.8 to -50.1 mV), with the magnitude of the negative charge increasing with TEMPO oxidation and carrageenan concentration. These results suggest there would be strong electrostatic repulsion between the composite hydrogels. The composite microgels produced in our work may be useful functional materials for utilization within the food industry, thereby converting a waste product into a valuable commodity.


Subject(s)
Microgels , Nanofibers , Cellulose/chemistry , Carrageenan , Nanofibers/chemistry , Hydrogels/chemistry
4.
Food Chem ; 382: 132331, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35149465

ABSTRACT

This study aimed to investigate the in vitro digestion of curcumin-myofibrillar protein (MP) complexes characterized by antioxidant activity and structure changes. Curcumin-MP nanocomplexes were prepared by pH-shifting (from 12 to 7) method and then digested in vitro. Results showed that the protein released by dissolved nitrogen and the scavenging rates of DPPH and ABTS free radicals were enhanced significantly by the formation of nanocomplex with curcumin. During simulated digestion, curcumin can reduce the α-helix of protein, along with red shifted and significantly decreased maximum fluorescence intensity. This structural difference may change the restriction sites of MP, resulting in substantial changes in the digested products composition and 11 unique peptides with potential bioactivity appearance in the digested products of curcumin-MP complex. Our finding revealed the Curcumin-MP nanocomplexes has unique protein digestion fate which has potential application on functional enhanced food.


Subject(s)
Curcumin , Antioxidants/chemistry , Curcumin/chemistry , Digestion , Peptides , Proteins
5.
J Sci Food Agric ; 102(10): 4162-4170, 2022 Aug 15.
Article in English | MEDLINE | ID: mdl-35018651

ABSTRACT

BACKGROUND: Aiming to address the practical problems of a low utilization rate and the serious waste of soybean residue, novel composite hydrogels based on okara cellulose before and after 2,2,6,6-tetramethylpiperidine oxide (TEMPO) oxidation and high polymers of chitosan (CH), carrageenan (CA) or Arabic gum (AG) were prepared by a homogeneous mixture in ionic liquid. RESULTS: In the present study, composite hydrogels fabricated from okara cellulose and CH, CA or AG were prepared by dissolving them in an ionic liquid, followed by heating (100 °C, 3 h) and then soaking them in a 1:1 water-isopropanol solution. The composite hydrogels prepared from TEMPO oxidation-treated cellulose were physically cross-linked to CH, CA or AG. The results showed that the intramolecular hydrogen bonds in the amorphous regions of the cellulose were disrupted, whereas the intermolecular hydrogen bonds between the biopolymers were increased, which promoted the formation of composite gels with crystalline structures. The TEMPO treatment increased the gel strength. For example, for the cellulose/CA gels, the hardness, fracturability, springiness and cohesiveness values were 5.9-, 4.3-, 2.4- and 3.6-fold higher compared to the non-treated ones, respectively. The composite hydrogels exhibited good thermal stability, swelling properties and mechanical properties. These novel composite polysaccharide-based hydrogels may therefore have great potential in various food and non-food fields. CONCLUSION: In summary, the addition of polymers (CH, CA or AG) and TEMPO oxidized cellulose was suitable for increasing the swelling, textural properties, thermal stability and rheological properties of hydrogels, which provides new ideas and new methods for the preparation of bio-based composite hydrogels. © 2022 Society of Chemical Industry.


Subject(s)
Cellulose, Oxidized , Chitosan , Ionic Liquids , Carrageenan , Cellulose/chemistry , Cellulose, Oxidized/chemistry , Chitosan/chemistry , Hydrogels/chemistry
6.
J Food Sci ; 86(10): 4566-4576, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34431100

ABSTRACT

The structural andphysicochemical properties of okara protein (OP) subjected to different cavitation jet (CJ) treatment times (0-15 min) were analyzed. In this study, the microstructure and apparent morphology of OP were analyzed by Raman spectrum, fluorescence spectrum, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and atomic force microscopy (AFM). Physicochemical properties, such as emulsion ability (EA), emulsion stability index (ESI), foaming characteristics (FC), foaming stability (FS), and solubility analysis of the OPs, were characterized. Raman spectrum analysis showed that CJ treatment caused increases in the ordered structure of OPs (α-helix, ß-sheet, and ß-turn), and the disulfide bond g-g-g and g-g-t modes, while it caused a decrease in the t-g-t mode. However, the tertiary structure of OP unfolded and mostly degraded into small subunits because of higher cavitation, shear and temperature effects. AFM observation indicated that CJ resulted in a more uniform distribution of OP. Moreover, changes in the structure of OP significantly affected its functional properties. The results showed that when CJ treatment time was 10 min, the solubility of OP was up to (28.72 ± 1.26)%, the soluble protein content of okara was up to (10.44 ± 0.03) g/100 g, and interface properties were better. In summary, OP has great potential for application in the food area, especially in emulsifying agent and foam system. PRACTICAL APPLICATION: The cavitation jet technology improves the structure and physical and chemical properties of the protein extracted from soybean residue (okara) and provides new ideas for the further development and utilization of soybean residue protein, which may lead to the production of high-value-added functional ingredients from the processing of soybean byproducts.


Subject(s)
Glycine max , Soybean Proteins , Emulsifying Agents , Emulsions/chemistry , Microscopy, Atomic Force , Solubility , Soybean Proteins/chemistry , Soybean Proteins/ultrastructure , Glycine max/chemistry
7.
J Food Sci ; 86(5): 1737-1750, 2021 May.
Article in English | MEDLINE | ID: mdl-33822377

ABSTRACT

This study examined the effects of different sequential treatments of dextran glycation and succinic anhydride acylation on the structure and physicochemical properties of soy protein isolate (SPI). The tested properties included electrophoresis (SDS-PAGE), Fourier transform infrared spectroscopy, endogenous fluorescence spectroscopy, surface hydrophobicity (H0 ), free sulfhydryl (-SH), solubility, interfacial properties, rheological properties, and scanning electron microscope (SEM). The results show that the two treatments significantly improved the structure and functional characteristics of the SPI. The order of the methods had an important effect on the SPI. The lowest H0 (231.76 ± 11.92), the highest free -SH content (3.09 ± 0.09 µmol/g), and the highest solubility at pH = 7 (77 ± 3.97%) were obtained when the acylation treatment was followed by the glycation treatment. Emulsification, emulsion stability, foaming, and foam stability were also the highest. Glycation and acylation caused the viscosity coefficient (k) of the SPI solution to decrease compared with SPI alone, but the flow index (n) value increased, and the sum G' value of the conjugate system decreased as gel time increased. SEM showed that its microstructure has changed significantly. Therefore, this research provided an effective method for improving the functional characteristics of SPI and had potential industrial application prospects. PRACTICAL APPLICATION: Glycation and acylation of soybean protein isolate improved the chemical modification method of protein, improved the functional properties of soybean protein, widened its application in food and materials, and provided a new idea for the further development and utilization of soybean protein.


Subject(s)
Chemical Phenomena , Soybean Proteins/chemistry , Acylation , Dextrans/chemistry , Emulsions/chemistry , Glycosylation , Hydrophobic and Hydrophilic Interactions , Molecular Structure , Rheology , Solubility , Succinic Anhydrides/chemistry , Viscosity
8.
Food Chem ; 352: 129395, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-33677211

ABSTRACT

Myofibrillar proteins (MPs), as a food-grade material, have the potential to improve the solubility and bioavailability of curcumin. However, the interaction mechanism between MPs and curcumin under charge regulation induced by alkaline pH and NaCl was unclear. In this study, the binding between curcumin and MPs at pH 12 was confirmed by the fluorescence quenching under different NaCl concentration (0, 0.3, 0.6 and 0.9 mol/L). Further kinetic experiments showed, MPs possessed a higher affinity to bind curcumin in the presence of NaCl, especially at 0.6 M NaCl. Followed pH shifting from 12 to 7 does not affect UV-Vis absorption spectra of protein-curcumin dispersions. The secondary structure of MPs was not affected by binding with curcumin. Formation of this stable complex can be explained by hydrophobic other than electrostatic interaction. Therefore, the presence of NaCl facilitated exposure of hydrophobic pocket to improve the binding affinity between curcumin and MPs due to the importance of hydrophobic interaction.


Subject(s)
Curcumin/metabolism , Muscle Proteins/metabolism , Curcumin/chemistry , Hydrophobic and Hydrophilic Interactions , Kinetics , Muscle Proteins/chemistry , Protein Binding , Sodium Chloride/chemistry , Solubility , Static Electricity
9.
Carbohydr Polym ; 255: 117364, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33436197

ABSTRACT

Nanocellulose was isolated from okara using either ultrasound or high-pressure homogenization treatments. Dynamic light scattering, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, swelling behavior, rheological properties, and thermal analysis were used to characterize the physical-chemical and structural properties of the cellulose obtained. Sonication at 600 W for 15 min led to a cellulose material with a small mean particle diameter (d =0.22 µm), narrow polydispersity index (PDI = 0.21), strong negative charge (ζ = -36 mV), high swelling ratio (SR = 7.6), high crystallinity index (CI = 72 %), and formed viscous solutions. The initial pyrolysis temperature of the cellulose increased from 212 to 225 ℃, while the pyrolysis residue decreased from 26 to 12 %, after the sonication/homogenization treatment. The cellulose material produced in this study may be applied in various food and non-food applications as a texture modifier, stabilizer, structural component, or digestion modifier.

10.
Foods ; 10(1)2020 Dec 22.
Article in English | MEDLINE | ID: mdl-33374903

ABSTRACT

This study examined the ability of cavitation jet processing to regulate the oxidation concentrations with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) (0.2, 1, and 5 mmol/L) and the structure and emulsification of soy protein isolate (SPI). The tested properties included particle size distribution, hydrophobic properties (sulfhydryl group (SH) and disulfide bond (S-S) contents, surface hydrophobicity (H0)), emulsifying properties (particle size and ζ-potential of emulsions, emulsification activity index (EAI), and emulsification stability index (ESI)), as well as conformational characteristics. The high shear force of cavitation jet treatment reduced the particle size of oxidized SPI and distributed uniformly. Cavitation jet (90 MPa)-treated SPI (AAPH with 1 mmol/L) demonstrated a high H0 (4688.70 ± 84.60), high EAI (71.78 ± 1.52 m2/g), and high ESI (86.73 ± 0.97%). The ordered secondary structure (α-helix and ß-turn content) of SPI was enhanced by the cavitation jet. Meanwhile, the distribution of SPI-oxidized aggregates was observed under an atomic force microscope. Therefore, cavitation jet processing combined with oxidation treatment is an effective method to improve the characteristics of SPI and has potential industrial application prospects.

11.
Sci Rep ; 10(1): 14010, 2020 08 19.
Article in English | MEDLINE | ID: mdl-32814779

ABSTRACT

Phosphatidylcholine-soybean protein isolate (PC-SPI) nanoemulsions were prepared by ultrasonication. The effects of preparation conditions (SPI and PC addition, ultrasonic power and time) on the structural properties of the nanoemulsions and their storage stability were investigated. The results showed that the most optimal adsorption capacity and adsorption tightness at the oil-water interface under optimal conditions (1.5% SPI, 0.20% PC, 500 W ultrasonic power and 9 min ultrasonic time) were exhibited by the SPI-PC conjugate, which demonstrated that this nanoemulsions can be categorized as a high-quality emulsion suitable for research. To test its stability, and the high-quality nanoemulsion of ß-carotene was stored. After degradation of the nanoemulsions during storage, ß-carotene was released. The ß-carotene retention rate of the high-quality emulsion was maintained above 86% at different temperatures in the absence of light for up to 30 days. This study provides new information for the development of transport and stability systems for nanoemulsions.

12.
Food Res Int ; 134: 109251, 2020 08.
Article in English | MEDLINE | ID: mdl-32517904

ABSTRACT

The ability of cavitation jet processing to alter the structural and physicochemical properties of dietary fiber extracted from okara was examined. The impact of processing time (0 to 15 min) on the morphology and composition of the dietary fiber was monitored using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Atomic force microscopy (AFM), and Scanning electron microscopy (SEM). The water holding, oil holding, and swelling capacities of the okara dietary fibers were measured, which increased after processing, reaching values of 10.0 ± 0.2 g/g, 5.04 ± 0.07 g/g, and 13.9 ± 0.4 mL/g, respectively after 10 min. Cavitation jet processing had little impact on the total dietary fiber content, but increased soluble dietary fiber content more than 5-fold, which led to a pronounced increase in the shear viscosity. FTIR and XRD indicated that intermolecular hydrogen bonds and crystalline structures within the dietary fibers were disrupted by cavitation jet processing, while AFM and SEM indicated that there were appreciable changes in microstructure.


Subject(s)
Dietary Fiber , Water , Dietary Fiber/analysis , Microscopy, Electron, Scanning , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
13.
Foods ; 8(12)2019 Nov 20.
Article in English | MEDLINE | ID: mdl-31756907

ABSTRACT

Use of soy protein isolate (SPI) as the encapsulating material in emulsions is uncommon due to its low solubility and emulsification potential. The aim of this study was to improve these properties of SPI via heat treatment-induced modifications. We modified SPI under various heating conditions and demonstrated the relationship between structure and in vitro digestibility in simulated gastric fluid by means of Sodium Dodecyl Sulphide-Polyacrylamide Gel Electrophoresis (SDS-PAGE) and Raman spectroscopy. It was found that the degree of hydrolysis (DH) of SPI increased and then decreased upon increasing exposure to heat. Different subunits of conglycinin were digested and degraded by pepsin. Heat treatment improved digestion characteristics that would reduce e the unnecessary loss of protein, offering potential for the efficient delivery of nutrients in nanoemulsions. These results could have significant relevance for research groups that are interested in the biological interactions and activity of functional SPI.

14.
J Thorac Dis ; 11(5): 1831-1837, 2019 May.
Article in English | MEDLINE | ID: mdl-31285875

ABSTRACT

BACKGROUND: The current regimens for advanced non-small cell lung cancer (NSCLC) patients are deficient due to failings in standard treatments. This retrospective study aimed to assess the efficacy and safety of low-dose apatinib in combination with S-1 therapy in a NSCLC setting. METHODS: In this retrospective study, advanced NSCLC patients who failed standard treatment in Changzhou Cancer Hospital of Soochow University were screened for eligibility. Progression-free survival (PFS) was set as the primary endpoint. Overall response rate (ORR), disease control rate (DCR), overall survival (OS), and the safety profile were considered to be the secondary endpoints. RESULTS: A total of 31 eligible patients were included. The median PFS (mPFS) was 102 days (95% CI: 57-147 days). ORR was achieved in 7 patients (22.6%; 95% CI: 11.1-38.2%) and DCR was maintained in 23 patients (74.2%; 95% CI: 58.2-86.5%). The median OS (mOS) was 422 days (95% CI: 148-696 days). Patients with a history of smoking tended to have a shorter OS without significant differences (HR =4.105, 95% CI: 0.874-19.288, P=0.074). Treatment-related grade III toxicity was observed in 5 patients (16%) and common grade I or II adverse events (AEs) were fatigue (42%), hypertension (32%), and hand-foot-skin reaction (23%). CONCLUSIONS: Combination of low-dose apatinib and S-1 could be an effective and tolerable choice for advanced NSCLC patients who are unable to benefit from standard treatment; however, further exploration in larger clinical trials is needed.

15.
Sci Rep ; 9(1): 6985, 2019 05 06.
Article in English | MEDLINE | ID: mdl-31061497

ABSTRACT

Ultrasound treatment and high-pressure homogenization were used to prepare soybean protein (SP)-phosphatidylcholine (PC) nanoemulsions in this study. Nanoemulsions prepared by high-pressure homogenization were more stable. The structural changes of SP and PC under ultrasound treatment and high-pressure homogenization treatment were investigated by Raman spectroscopy. It could be concluded that ultrasound and high-pressure homogenization treatments increased both the content of α-helix and unordered structure but decreased that of ß-structures of SP, while the interaction between SP and PC decreased α-helix content and also reduced unordered structure and ß-sheet structure. Ultrasound treatment and high-pressure homogenization exposed more tryptophan and tyrosine residues to promote hydrophobic interaction between SP and PC, which was beneficial for stabilizing the nanoemulsion. The SP-PC interaction exerted a more significant effect on side chain structure than those observed under ultrasound treatment and high-pressure homogenization. The dominant g-g-t vibrational mode of the disulfide bond of soybean protein was not appreciably changed by the two preparations. High-pressure homogenization increased the disorder of lipid chains of PC, promoting SP-PC interaction and thereby increasing the stability of the nanoemulsion. The structural change provided a theoretical basis for preparation of two nanoemulsions.


Subject(s)
Nanostructures/chemistry , Phosphatidylcholines/chemistry , Soybean Proteins/chemistry , Emulsions , Hydrophobic and Hydrophilic Interactions , Nanostructures/ultrastructure , Particle Size , Pressure , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Sonication , Soybean Proteins/isolation & purification , Glycine max/chemistry , Spectrum Analysis, Raman
16.
Langmuir ; 34(30): 8848-8856, 2018 07 31.
Article in English | MEDLINE | ID: mdl-29945444

ABSTRACT

Protein conformational rearrangement triggered by adsorption to the hydrophobic interface of oil droplets has long been considered as a key factor in emulsification. In this study, an alkaline pH-shifting-driven conformational adaptation enhanced interfacial proteins was used to improve their stability against heat-induced flocculation of myosin emulsions. We used the unfolded myosin at pH 12 to emulsify soy oil and then readjusted the pH of the emulsion to neutral. The corresponding myosin emulsion (0.5% w/v protein, 10% v/v soy oil, and 0.6 M NaCl) almost not flocculated when heated at 75 °C for 30 min. Moreover, after thermal treatment, the particle size of the emulsion was not significantly increased ( P > 0.05) and the emulsion did not exhibit a creaming phenomenon after a week. Based on the circular dichroism and Fourier transform infrared analysis, we speculated the superiority of the emulsion is closely related to the alkaline pH-shifting-driven conformational adaptation enhanced interfacial protein. Additionally, the resulting steric stabilization in overcoming the attractive hydrophobic forces between denatured protein molecules coated droplets might be the main factor for the inhibition of heat-induced flocculation of the emulsion. Our research may have important implications for the formulation of protein-stabilized oil-in-water emulsions.


Subject(s)
Emulsions , Hot Temperature , Myosins , Emulsions/chemistry , Flocculation , Hydrogen-Ion Concentration , Myosins/chemistry , Protein Stability
17.
Nanomaterials (Basel) ; 8(5)2018 May 07.
Article in English | MEDLINE | ID: mdl-29735918

ABSTRACT

The nanoemulsions of soy protein isolate-phosphatidylcholine (SPI-PC) with different emulsion conditions were studied. Homogenization pressure and homogenization cycle times were varied, along with SPI and PC concentration. Evaluations included turbidity, particle size, ζ-potential, particle distribution index, and turbiscan stability index (TSI). The nanoemulsions had the best stability when SPI was at 1.5%, PC was at 0.22%, the homogenization pressure was 100 MPa and homogenization was performed 4 times. The average particle size of the SPI-PC nanoemulsions was 217 nm, the TSI was 3.02 and the emulsification yield was 93.4% of nanoemulsions.

18.
Lung Cancer ; 102: 118-121, 2016 12.
Article in English | MEDLINE | ID: mdl-27987579

ABSTRACT

Approximately 10% of lung adenocarcinomas harbor aberrations that are targetable using the approved multitargeted TKI crizotinib. MET exon 14 skipping mutation predicts for response to crizotinib in human lung adenocarcinomas. However, a substantial part of patients still has no sufficient tissue to perform genomic analysis. As a promising noninvasive biomarker and potential surrogate for the entire tumor genome, circulating tumor DNA (ctDNA) has been applied to the detection of driver gene mutations. Here we described the MET exon 14 splicing mutations in cell-free circulating-tumor DNA by next-generation sequencing (NGS) technology. Patient firstly responded to crizotinib therapy within four months, however, three acquired mutation in the MET kinase domain, D1228N/H and Y1230H, were found at the time of disease progression. To our knowledge, this is the first clinical report of three mutations simultaneously arising in a patient with MET exon 14 splicing mutation.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Proto-Oncogene Proteins c-met/genetics , Pyrazoles/pharmacology , Pyridines/pharmacology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Alternative Splicing , Antineoplastic Agents/therapeutic use , Asian People , Circulating Tumor DNA/genetics , Crizotinib , Disease Progression , Drug Resistance, Neoplasm , Exons , Female , High-Throughput Nucleotide Sequencing/methods , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Middle Aged , Mutation , Protein Kinase Inhibitors/pharmacology , Tomography Scanners, X-Ray Computed , Treatment Outcome
19.
Med Oncol ; 32(3): 44, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25631633

ABSTRACT

CD137 ligand (CD137L), a member of the tumor necrosis factor superfamily, is expressed on antigen-presenting cells and also on various tumor cells. Crosslinking of CD137L transmits signals that evoke different cellular responses in a variety of tumor cells. This study was designed to investigate signaling pathways activated by CD137L and its physiologic role in the progression of NSCLC. We investigated the expression of CD137L in tissues from 102 cases of human non-small cell lung cancer (NSCLC) using immunohistochemistry and analyzed the correlation with clinicopathological features using Fisher's exact test and overall survival using Kaplan-Meier curves and the log-rank test. The effect of CD137L reverse signaling induced by recombinant human CD137-Fc protein on NSCLC cell lines was assessed using proliferation and apoptosis assays, flow cytometry and Western blotting. Positive CD137L expression was observed in 53/102 (52.0%) of the NSCLC samples and correlated with early TNM stage (P = 0.046), well-differentiated tumors (P = 0.009) and better overall survival (P = 0.004). Moreover, induction of CD137L reverse signaling using CD137-Fc inhibited proliferation and induced apoptosis and cell cycle arrest in H1650 cells, which express high levels of CD137L; CD137L reverse signaling had no significant effects in PC9 cells, which express low levels of CD137L. In addition, CD137L reverse signaling-induced apoptosis occurred via activation of the intrinsic pathway and depended on phosphorylation of JNK. This study demonstrates a hitherto unrecognized role for CD137L reverse signaling in the development of NSCLC and indicates that CD137L has potential as a novel therapeutic target in NSCLC.


Subject(s)
4-1BB Ligand/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Adult , Aged , Apoptosis , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/surgery , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Lung Neoplasms/surgery , MAP Kinase Signaling System , Male , Middle Aged , Phosphorylation , Survival Analysis , Tumor Necrosis Factor Receptor Superfamily, Member 9/genetics , Tumor Necrosis Factor Receptor Superfamily, Member 9/pharmacology
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