ABSTRACT
A novel sulfur-bridged metal-organic framework (MOF) [Co(TIC4R-I)0.25Cl2]·3CH3OH (Co-TIC4R-I) based on thiacalix[4]arene derivatives was successfully obtained using a solvothermal method. Remarkably, adjacent TIC4R-I ligands were linked via Co(II) cations to form a three-dimensional (3D) microporous architecture. Subsequently, Co-TIC4R-I was modified on a glassy carbon electrode (Co-TIC4R-I/GCE) to produce an electrochemical sensor for the detection of heavy-metal ions (HMIs), namely, Cd2+, Pb2+, Cu2+, and Hg2+, in aqueous solutions. It was found that Co-TIC4R-I/GCE exhibited wide linear detection ranges of 0.10-17.00, 0.05-16.00, 0.05-10.00, and 0.80-15.00 µM for Cd2+, Pb2+, Cu2+, and Hg2+, respectively, in addition to low limit of detection (LOD) values of 0.017, 0.008, 0.016, and 0.007 µM. Moreover, the fabricated sensor employed for the simultaneous detection of these metals has achieved LOD values of 0.0067, 0.0027, 0.0064, and 0.0037 µM for Cd2+, Pb2+, Cu2+, and Hg2+, respectively. The sensor also exhibited satisfactory selectivity, reproducibility, and stability. Furthermore, the relative standard deviation (RSD) values of Cd2+, Pb2+, Cu2+, and Hg2+ were 3.29, 3.73, 3.11, and 1.97%, respectively. Moreover, the fabricated sensor could sensitively detect HMIs in various environmental samples. The high performance of the sensor was attributed to its sulfur adsorption sites and abundant phenyl rings. Overall, the sensor described herein provides an efficient method for the determination of extremely low concentrations of HMIs in aqueous samples.
ABSTRACT
DNA damage repair (DDR) is essential for maintaining genome integrity and modulating cancer risk, progression, and therapeutic response. DDR defects are common among non-small lung cancer (NSCLC), resulting in new challenge and promise for NSCLC treatment. Thus, a thorough understanding of the molecular characteristics of DDR in NSCLC is helpful for NSCLC treatment and management. Here, we systematically analyzed the relationship between DDR alterations and NSCLC prognosis, and successfully established and validated a six-DDR gene prognostic model via LASSO Cox regression analysis based on the expression of prognostic related DDR genes, CDC25C, NEIL3, H2AFX, NBN, XRCC5, RAD1. According to this model, NSCLC patients were classified into high-risk subtype and low-risk subtype, each of which has significant differences between the two subtypes in clinical features, molecular features, immune cell components, gene mutations, DDR pathway activation status and clinical outcomes. The high-risk patients was characterized with worse prognosis, lower proportion and number of DDR mutations, unique immune profile and responsive to immunetherapy. And the low-risk patients tend to have superior survival, while being less responsive to immunotherapy and more sensitive to treatment with DNA-damaging chemotherapy drugs. Overall, this molecular classification based on DDR expression profile enables hierarchical management of patients and personalized clinical treatment, and provides potential therapeutic targets for NSCLC.
ABSTRACT
A new luminescent CdII compound, poly[[µ2-1,4-bis(1H-imidazol-1-yl)benzene]{µ2-5-[(3-carboxylphenoxy)methyl]isophthalato}cadmium(II)], [Cd(C16H10O7)(C12H10N4)]n or [Cd(HL)(1,4-bib)]n {H3L is 5-[(3-carboxyphenoxy)methyl]isophthalic acid and 1,4-bib is 1,4-bis(1H-imidazol-1-yl)benzene}, I, has been synthesized successfully from CdII and a semirigid tricarboxylic ligand under hydrothermal conditions. Structure analysis shows that I is a two-dimensional structure with the point symbol {44.62}. The three-dimensional framework is constructed by O-H...O hydrogen bonds and π-π stacking interactions. Furthermore, the obtained CdII compound displays high solvent stability and excellent thermal stability, as shown by powder X-ray diffraction and thermogravimetry measurements. Studies of the luminescence properties reveal that compound I can act as a promising luminescent sensor for detecting FeIII cations and CrVI oxyanions with high selectivity and low detection limits (0.19â µM for Fe3+ and 1.13â µM for Cr2O72-), and is additionally free from the interference of other ions. The mechanism of selective quenching was studied by measuring the UV-Vis absorption of the host compound and the target analytes.
ABSTRACT
Parasite infections of humans and animals remain a major global health problem, with limited choice of drugs being available to the treatment of parasitosis in the clinic. Sophora moorcroftiana (S. moorcroftiana) is a shrub that grows in Tibet Plateau of China. Decoction of the seeds has been used as a traditional Tibetan medicine to treat parasitosis for years. But the anti-parasitic effects of water-soluble fractions in the seeds need further investigation. In the present study, the water-soluble alkaloid fractions (E2) were obtained from S. moorcroftiana seeds by refluxing extraction with 60% ethanol and low polarity fraction (E2-a) and high polarity fraction (E2-b) were subsequently isolated from E2 using column chromatography. As a parasite model, Caenorhabditis elegans (C. elegans) were treated with different fractions and their survivals were recorded. The results showed that that E2-a induced a lower survival rate in C. elegans than E2-b and E2. The protoscoleces of Echinococcus granulosus (E. granulosus) were cultured in the presence of E2-a. Compared with E2-b and E2, protoscoleces exhibited decreased survival rate following E2-a treatment. Furtherly, the effects of E2-a on the behavior, brood size, and lifespan of the worms were investigated. Body bend frequencies of the worms treated with the high concentration of E2-a were reduced by two-thirds compared with the control group (P < 0.01). Compared with non-E2-a-treated group, exposure of nematodes to E2-a led to a decrease in head thrashes and pharyngeal pumps frequency (P < 0.01). E2-a treatment resulted in a significantly lower brood size (P < 0.01). Additional E2-a treatment induced a significantly shortened lifespan, compared with the control (P < 0.05). These findings indicated that water-soluble fraction E2-a from S. moorcroftiana seeds was a potential helminthic agent.
Subject(s)
Animals , Humans , Anthelmintics , Caenorhabditis elegans , Physiology , China , Drugs, Chinese Herbal , Echinococcosis , Drug Therapy , Parasitology , Echinococcus granulosus , Physiology , Seeds , Chemistry , Sophora , ChemistryABSTRACT
Parasite infections of humans and animals remain a major global health problem, with limited choice of drugs being available to the treatment of parasitosis in the clinic. Sophora moorcroftiana (S. moorcroftiana) is a shrub that grows in Tibet Plateau of China. Decoction of the seeds has been used as a traditional Tibetan medicine to treat parasitosis for years. But the anti-parasitic effects of water-soluble fractions in the seeds need further investigation. In the present study, the water-soluble alkaloid fractions (E2) were obtained from S. moorcroftiana seeds by refluxing extraction with 60% ethanol and low polarity fraction (E2-a) and high polarity fraction (E2-b) were subsequently isolated from E2 using column chromatography. As a parasite model, Caenorhabditis elegans (C. elegans) were treated with different fractions and their survivals were recorded. The results showed that that E2-a induced a lower survival rate in C. elegans than E2-b and E2. The protoscoleces of Echinococcus granulosus (E. granulosus) were cultured in the presence of E2-a. Compared with E2-b and E2, protoscoleces exhibited decreased survival rate following E2-a treatment. Furtherly, the effects of E2-a on the behavior, brood size, and lifespan of the worms were investigated. Body bend frequencies of the worms treated with the high concentration of E2-a were reduced by two-thirds compared with the control group (P < 0.01). Compared with non-E2-a-treated group, exposure of nematodes to E2-a led to a decrease in head thrashes and pharyngeal pumps frequency (P < 0.01). E2-a treatment resulted in a significantly lower brood size (P < 0.01). Additional E2-a treatment induced a significantly shortened lifespan, compared with the control (P < 0.05). These findings indicated that water-soluble fraction E2-a from S. moorcroftiana seeds was a potential helminthic agent.
Subject(s)
Animals , Humans , Anthelmintics , Caenorhabditis elegans , Physiology , China , Drugs, Chinese Herbal , Echinococcosis , Drug Therapy , Parasitology , Echinococcus granulosus , Physiology , Seeds , Chemistry , Sophora , ChemistryABSTRACT
Objective To investigate the effect of intravenous dexmedetomidine injection(1 μg/kg)on the intubating conditions after inhalation induction with sevoflurane 8% and nitrous oxide(NO)50% in children. Methods Totally 122 patients aged 4-10 years with an American Society of Anesthesiologists physical statusⅠ undergoing elective plastic surgery under general anesthesia were randomly divided to dexmedetomidine group(intraveneously injected with dexmedetomidine 1μg/kg)and control group(injected with normal saline)by using the random sampling table.On arrival of the operating room,anesthesia was induced with sevoflurane 8% and NO 50% in oxygen 50%.When the patient became unconscious,the intravenous cannula 24was inserted on the dorsum of hand.One minute later,laryngoscopy and tracheal intubation were performed.The intubating conditions were assessed by the scoring system in the previous study. Results The rates of acceptable conditions were 97% and 90% in dexmedetomidine group and in control group(P=0.143),and the rates of excellent conditions were 82% and 67%(P=0.04),respectively.In dexmedetomidine group,there were no signifi-cant differences of mean arterial presser and heart rate between the time-point of before intubation and the time-point of immediately after intubation.Conclusion Intravenous bolus of dexmedetomidine(1 μg/kg)can effectively improve the intubating conditions after inhalation induction of sevoflurane 8% and NO 50% in children and make the hemodynamics more stable during tracheal intubation.
ABSTRACT
Objective To compare the intubating conditions between dexmedetomidine and remifentanil when combined with sevoflurane-nitrous oxide (N2O) for anesthesia induction in the pediatric patients.Methods A total of 122 pediatric patients,aged 4-10 yr,of American Society of Anesthesiologists physical status Ⅰ,undergoing elective plastic surgery,were randomly divided into dexmedetomidine group (group D,n =61) and remifentanil group (group R,n=61).Eight percent sevoflurane and 60% N2O were inhaled for induction of anesthesia,and the fresh gas flow was set at 6 L/min.After disappearance of eyelash reflex,dexmedetomidine 1 μg/kg and remifentanil 1 μg/kg were intravenously injected over 50-60 s in D and R groups,respectively,and 1 min later tracheal intubation was performed.The intubating conditions were graded,and the satisfactory intubating conditions and successful intubation were recorded.The development of adverse cardiovascular reactions and complications such as hyoxemia and laryngospasm before and after intubation and postoperative pharyngodynia was recorded.Results Compared with group D,no significant change was found in the success rate of intubation,rate of satisfactory intubation,intubating condition grade or incidence of postoperative pharyngodynia (P> 0.05),and the incidence of hypertension and sinus tachycardia after intubation was significantly increased in group R (P<0.05).No pediatric patients developed hyoxemia,laryngospasn or sinus tachycardia in two groups.Conclusion When 8% sevoflurane and 60% N2O are inhaled for anesthesia induction,combing with dexmedetomidine 1 μg/kg produces better clinical efficacy than combing with remifentanil 1 μg/kg in improving the intubating conditions for pediatric patients.
ABSTRACT
Objective To compare the Ambu Aura-i with the Air-Q intubating laryngeal airway for fiberoptic-guided tracheal intubation in ear deformity children.Methods Totally 120 children who were scheduled for elective auricular reconstruction surgery requiring general anaesthesia with tracheal intubation were enrolled in this prospective study. They were randomized to receive either the Ambu Aura-i (Aura-i group) or Air-Q (Air-Q group). The time for successful tracheal intubation was assessed. The attempts for successful device insertion, leak pressures, cuff pressures, fiberoptic grade of laryngeal view, time for removal of the device after endotracheal intubation, and complications were recorded. Results Device placement, endotracheal intubation, and removal after endotracheal intubation were successful in all patients. The Air-Q group required longer time than the Aura-i group in device placement[(14.1±7.2) s vs. (10.8±5.2) s, P<0.05], successful endotracheal intubation [(39.8±9.5) s vs. (24.1±8.2) s, P<0.05], and device removal [(18.2±5.1) s vs. (14.7±3.7) s, P<0.05]. There were no differences in fiberoptic grade of view between these devices, and the percentage of glottis seen was 80.0% (Air-Q group) vs. 86.7% (Aura-i group). The leak pressure was (20.5±4.8) cmHO in the Air-Q group and (22.2±5.0) cmHO in the Aura-i group (P<0.05), and the cuff pressure was (22.9±11.5)cmHO in the Air-Q group and (33.9±15.9) cmHO in the Aura-i group (P<0.05). Hemodynamic changes were not significantly different between two group. The incidence rate of sore throat two hours after operation was 6.5% (n=4) in the Air-Q group and 5% (n=3) in the Aura-i group. Conclusion Both Ambu Aura-i and Air-Q intubating laryngeal airway are effective conduits for beroptic-guided tracheal intubation, with advantages including simple operation, high success rate, and fewer complications, especially the Ambu Aura-i.
Subject(s)
Child , Humans , Anesthesia, General , Device Removal , Elective Surgical Procedures , Fiber Optic Technology , Intubation, Intratracheal , Methods , Laryngeal Masks , Pressure , Prospective StudiesABSTRACT
Objective To observe the effects of two different intranasal dexmedetomidine doses as premedication on the ECof sevoflurane for successful laryngeal mask airway placement in children. Methods Children aged 3-6 years, of American Society of Anesthesiologists physical status 1, and scheduled for plastic surgery were enrolled in this study. Children were assigned to receive either spray administration of intranasal dexmedetomidine 1 μg/kg (group D1, n=21) or 2 μg/kg (group D2, n=20) approximately 30 minutes before anesthesia. Anesthesia was induced with sevoflurane up to 8% in 100% O, with fresh gas flow set to 6 L/min. After the pupil fixed to the middle position, sevoflurane dial setting was reduced to 5% and fresh gas flow reduced to 3 L/min. The endtidal sevofluran (ET) concentration for laryngeal mask airway insertion sustained for 10 minutes after vein intubation, which was determined according to the Dixon's up and down method. The initial endtidal sevoflurane concentration in each group was set at 2%. ETwas increased/decreased (1:1.2) in the next patient according to the response to laryngeal mask airway insertion. Bispectral index, mask acceptance, all response to laryngeal mask airway insertion, and ETof laryngeal mask airway insertion of children were recorded. Results The bispectral index value was 77.4±3.6 in group D2, which was significantly lower than that (87.4±1.9) in group D1 when children entered operation room (P<0.05). Mask acceptance was 76.2% in group D1 and 90.0% in group D2. The ECof sevoflurane for laryngeal mask airway insertion was 1.09% (95% CI=0.89%-1.28%) in group D2, which was lower than 1.59% (95% CI=1.41%-1.78%) in group D1 (P<0.05). Conclusion Compared with the dose of 1 μg/kg, spray administration of intranasal dexmedetomidine 2 μg/kg as premedication can reduce the sevoflurane ECfor successful laryngeal mask airway placement in children.
Subject(s)
Child , Child, Preschool , Humans , Administration, Intranasal , Anesthesia , Anesthetics, Inhalation , Dexmedetomidine , Laryngeal Masks , Methyl EthersABSTRACT
Objective To compare two spray administration of intranasal dexmedetomidine (DEX) doses for premedication in children. Methods In this prospective,randomized,double-blind study,41 children aged 3-6 years were enrolled. Children were assigned to receive either spray administration of intranasal DEX 1 μg/kg (Group D1) or 2 μg/kg (Group D2). The Ramsay Sedation Scale scores were evaluated at 5 min intervals. Sedation status at separation from patient was also evaluated. Heart rate (HR) and saturation of peripheral oxygen (SpO) were recorded before and every 15 min after drug administration. Results The median sedation onset time was 30 min and 20 min in group D1 and group D2,respectively. Compared with the children in group D1,those in group D2 were significantly more sedated when they were separated from their parents (61.9% vs. 95.0%,respectively)(χ=5.549,P=0.010). In Group D2,the HR decreased by 15.8% (t=2.415,P=0.021) 30 min after the spray administration of intranasal DEX. Compared with the baseline values,there was no significant difference in both groups in terms of SpO(t=-1.426,P=0.162;t=-1.096,P=0.280)and HR in group D1 (t=-0.299,P=0.767) 30 min after the spray administration of intranasal DEX. Conclusion Spray administration of intranasal DEX 2 μg/kg provides superior sedation in children.
Subject(s)
Child , Child, Preschool , Female , Humans , Male , Administration, Intranasal , Anesthesia , Methods , Dexmedetomidine , Double-Blind Method , Heart Rate , Hypnotics and Sedatives , Oxygen , Prospective StudiesABSTRACT
1H NMR-based metabolomic approach combined with multivariate statistical analysis was used to evaluate the quality of 21 Farfarae Flos (FF) samples from different growth regions. Principal component analysis showed that wild and cultivated FF could be separated clearly, suggesting a big chemical difference existed between them. Supervised PLS-DA analysis indicated that the wild samples showed higher levels of secondary metabolites, such as bauer-7-ene-3β, 16α-diol, chlorogenic acid, rutin, 7-(3'-ethylcrotonoyloxy)-1α-(2'-methyl-butyryloxy)-3, 14-dehydro-Z-notonipetranone (EMDNT), tussilagone, β-sitosterol and sitosterone. This is consistent with traditional experience that the quality of wild samples are better than that of cultivated ones. The content of pyrrolizidine alkaloids senkirkine also differed greatly among samples from different habitats. The Pearson correlation analysis showed that senkirkine is positively correlated with 4, 5-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 3,4-O-dicaffeoylquinic acid, rutin, kampferol analogues, to a statistically significant extent. The correlation between the toxic compounds and the bioactive components in FF should be further studied.
Subject(s)
Chlorogenic Acid , Drugs, Chinese Herbal , Chemistry , Flowers , Chemistry , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Metabolomics , Quinic Acid , Rutin , Sitosterols , Tussilago , ChemistryABSTRACT
OBJECTIVE: The purpose of this study was to determine influences of cervical spine positions, turning times, and cervical segments on cadaver intradiscal pressure (IDP) during cervical spinal manipulative therapy (SMT). METHODS: We simulated cervical SMT with stretching and rotation on 7 fresh adult cadaver specimens in the material test system machine. The changes in IDP for cervical intervertebral disks (C3/4, C4/5, and C5/6) during 4 different stages of cervical SMT (physiologic state, end of the traction stage, turning stage, and finish time) were monitored. Five different cervical positions (extension 20°, extension 10°, neutral position, flexion 10°, flexion 20°) and 3 different turning times (0.06, 0.11, 0.16 second) of IDP were monitored, using micropressure sensors. RESULTS: The variable tendency of cervical IDP presents a "V"-shaped curve during SMT. The 4 stages of SMT had significantly different IDP (F=5498.956; P<.001). There were also significant differences in IDP between 5 cervical positions ([F=1371.216; P<.001], [flexion 20°>flexion 10°>neutral position>extension 10°>extension 20°]), 3 turning times ([F=419.530; P<.001], [0.06>0.11>0.16 seconds]), and 3 cervical segments ([F=84.282; P<.001], [C3/4Subject(s)
Cervical Vertebrae/physiology
, Manipulation, Spinal/methods
, Posture/physiology
, Range of Motion, Articular/physiology
, Adult
, Biomechanical Phenomena
, Cadaver
, Female
, Humans
, Magnetic Resonance Imaging/methods
, Male
, Pressure
, Rotation
, Sensitivity and Specificity
, Time Factors
, Weight-Bearing
ABSTRACT
OBJECTIVE: To investigate clinicopathological features of DiGeorge syndrome (DGS). METHOD: The clinical features, histological and immunohistochemical findings were analyzed in 5 cases of DGS by autopsy. RESULTS: Five cases of DGS in male infants aged 4 days, 1 month, 7 months, 10 months, and 13 months respectively. Gross and microscopic observations revealed that thymic cortex was depleted of lymphocytes or showed few, dispersed lymphocytes. The thymic medulla showed predominantly epithelial cells with calcified Hassall bodies as well as lymphocyte depletion. T lymphocytes were also scarce in the tonsils, lymph nodes, spleen, and mucosa-associated lymphatic tissue of ileum. In addition, 3 of the 5 patients also showed parathyroid aplasia or dysplasia, and congenital hypertrophy of the ventricular septum. CONCLUSIONS: The pathological changes indicate that clinicians should be aware of defects of immune system if the infants suffer from severe infections. Pathologists should recognize the importance of abnormalities of lymphohematopoietic tissues in the diagnosis of primary immunodeficiency diseases such as DGS.
Subject(s)
DiGeorge Syndrome/pathology , Parathyroid Glands/pathology , T-Lymphocytes/pathology , Thymus Gland/pathology , Autopsy , DiGeorge Syndrome/immunology , DiGeorge Syndrome/virology , Hepatitis, Viral, Human/pathology , Humans , Hypertrophy, Left Ventricular/pathology , Infant , Infant, Newborn , Lymphocyte Count , Male , Pneumonia, Viral/pathology , T-Lymphocytes/immunologyABSTRACT
<p><b>OBJECTIVE</b>To investigate clinicopathological features of DiGeorge syndrome (DGS).</p><p><b>METHOD</b>The clinical features, histological and immunohistochemical findings were analyzed in 5 cases of DGS by autopsy.</p><p><b>RESULTS</b>Five cases of DGS in male infants aged 4 days, 1 month, 7 months, 10 months, and 13 months respectively. Gross and microscopic observations revealed that thymic cortex was depleted of lymphocytes or showed few, dispersed lymphocytes. The thymic medulla showed predominantly epithelial cells with calcified Hassall bodies as well as lymphocyte depletion. T lymphocytes were also scarce in the tonsils, lymph nodes, spleen, and mucosa-associated lymphatic tissue of ileum. In addition, 3 of the 5 patients also showed parathyroid aplasia or dysplasia, and congenital hypertrophy of the ventricular septum.</p><p><b>CONCLUSIONS</b>The pathological changes indicate that clinicians should be aware of defects of immune system if the infants suffer from severe infections. Pathologists should recognize the importance of abnormalities of lymphohematopoietic tissues in the diagnosis of primary immunodeficiency diseases such as DGS.</p>
Subject(s)
Humans , Infant , Infant, Newborn , Male , Autopsy , DiGeorge Syndrome , Allergy and Immunology , Pathology , Virology , Hepatitis, Viral, Human , Pathology , Hypertrophy, Left Ventricular , Pathology , Lymphocyte Count , Parathyroid Glands , Pathology , Pneumonia, Viral , Pathology , T-Lymphocytes , Allergy and Immunology , Pathology , Thymus Gland , PathologyABSTRACT
To understand the molecular mechanisms of metastasis and prognosis of colorectal cancer (CRC), we isolated single cell-derived progenies (SCPs) from SW480 cells in vitro and compared their metastatic potential in an orthotopic CRC tumour model in vivo. Two groups of SCPs with the capability of high and low metastasis, respectively, were obtained. By analysing the gene expression profiles of high (SCP51), low (SCP58) metastatic SCPs, and their parental cell line (SW480/EGFP), we demonstrated that 143 genes were differentially expressed either between SCP51 and SCP58 or between SCP58 and SW480/EGFP. Gene-annotation enrichment analysis of DAVID revealed 80 genes in the top ten clusters of the analysis (gene enrichment score > 1). Of the 80-gene set, 32 genes are potentially involved in metastasis, as revealed by Geneclip. Five putative metastatic genes (LYN, SDCBP, MAP4K4, DKK1, and MID1) were selected for further validations. Immunohistochemical analysis in a cohort of 181 CRC clinical samples showed that the individual expression of LYN, MAP4K4, and MID1, as well as the five-gene signature, was closely correlated with lymph node metastasis in CRC patients. More importantly, the individual expression of LYN, MAP4K4, SDCBP, and MID1, as well as the five-gene signature, was significantly correlated with overall survival in CRC patients. Thus, our five-gene signature may be able to predict metastasis and survival of CRC in the clinic, and opens new perspectives on the biology of CRC.
Subject(s)
Colorectal Neoplasms/genetics , Neoplasm Metastasis/genetics , Animals , Cell Proliferation , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Female , Gene Expression Profiling/methods , Humans , Male , Mice , Mice, Nude , Neoplasm Metastasis/pathology , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Neoplasm Transplantation , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/physiology , Oligonucleotide Array Sequence Analysis/methods , Prognosis , Reverse Transcriptase Polymerase Chain Reaction/methods , Survival Analysis , Tumor Cells, CulturedABSTRACT
The protein and mRNA expression of focal adhesion plaque associated cytoskeletons, including talin, vinculin, paxillin, and tensin, was studied using immunofluorescence in combination with confocal laser scanning microscopy and fluorescent quantitative polymerase chain reaction in 41 matched samples of human normal colorectal mucosae, primary colorectal adenocarcinomas, and 19 separate lymph node metastases. All specimens showed expression. The results showed talin, vinculin, tensin, and paxillin expression were correlated with carcinogenesis, invasion, and metastasis of colorectal carcinoma (CRC). Talin, vinculin, and tensin underwent downregulation while paxillin went up. So these cytoskeletons may play bidirectional regulating roles during the progression of CRC.
Subject(s)
Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Cytoskeletal Proteins/metabolism , Focal Adhesions/metabolism , Neoplasm Invasiveness , Humans , Intestinal Mucosa/metabolism , Lymphatic MetastasisABSTRACT
OBJECTIVE: To explore biological aspects of Tiam1 gene expression in nasopharyngeal carcinoma cells. METHODS: Tiam1/C1199HA expression plasmids were transfected into nasopharyngeal carcinoma cells of C666-1 and CNE1 by lipofectamine2000. RT-PCR, real-time PCR and Western blot Analyses were performed to evaluate the expression of Tiam1 mRNA and protein levels, respectively. In vitro cell adhesion, wound healing and matrigel invasion assays were used to study the biological impact of Tiam1 on cell adhesion, mobility and invasion. RESULTS: Tiam1 over expression significantly increased the abilities of adhesion, migratory and invasion of C666-1 and CNE1 cells, comparing with that of the control untransfected cells (P < 0.05). CONCLUSION: Tiam1 expression correlates with the invasion and metastasis of nasopharyngeal carcinoma cells.
Subject(s)
Cell Adhesion , Cell Movement , Guanine Nucleotide Exchange Factors/metabolism , Nasopharyngeal Neoplasms/pathology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Guanine Nucleotide Exchange Factors/genetics , Guanine Nucleotide Exchange Factors/physiology , Humans , Nasopharyngeal Neoplasms/metabolism , Neoplasm Invasiveness , Neoplasm Metastasis , Plasmids , RNA, Messenger/metabolism , T-Lymphoma Invasion and Metastasis-inducing Protein 1ABSTRACT
To identify novel biomarkers of metastasis of colorectal cancer (CRC), we developed an orthotopic implantation model of murine CRC and selected in vivo M5, a subclone of the SW480 CRC cell line with enhanced potential for metastasis to the liver. We compared the differences in the gene expression profiles between M5 and SW480 cells using gene expression profiling. We found that expression of special AT-rich sequence-binding protein 2 (SATB2) was down-regulated in M5 cells. Immunohistochemical analysis of 146 colorectal tumour samples showed that underexpression of SATB2 was strongly correlated with poor prognosis, tumour invasion, lymph node metastasis, distant metastasis, and Dukes' classification for CRC. Univariate and multivariate survival analyses further showed that SATB2 expression was a potential favourable prognostic factor for CRC. These results demonstrated not only that SATB2 is a potential novel prognostic factor for CRC, but also that selection of a highly metastatic clone of SW480 in vivo coupled with gene expression profiling is a powerful approach to identifying prognostic markers for CRC.
Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/secondary , Liver Neoplasms/secondary , Matrix Attachment Region Binding Proteins/genetics , Transcription Factors/genetics , Animals , Biomarkers, Tumor/genetics , Blotting, Western/methods , Cell Line, Tumor , Colorectal Neoplasms/metabolism , Down-Regulation , Female , Gene Expression , Gene Expression Profiling , Humans , Immunohistochemistry , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Lymphatic Metastasis , Male , Matrix Attachment Region Binding Proteins/analysis , Matrix Attachment Region Binding Proteins/metabolism , Mice , Mice, Nude , Middle Aged , Models, Animal , Neoplasm Staging , Neoplasm Transplantation , Oligonucleotide Array Sequence Analysis , Prognosis , Proportional Hazards Models , RNA, Small Interfering/pharmacology , Reverse Transcriptase Polymerase Chain Reaction/methods , Survival Analysis , Transcription Factors/analysis , Transcription Factors/metabolism , Transfection/methodsABSTRACT
OBJECTIVE: To investigate the relationship between the protein expression of T-lymphoma invasion and metastasis gene 1 (Tiam-1) and the biological behaviors of nasopharyngeal carcinoma (NPC). METHODS: Immunohistochemistry was performed to detect the expressions of Tiam-1 protein in 60 specimens of NPC tissue, 20 specimens of chronic nasopharyngitis (CN) tissue, and 6 tumor tissues from nude mice inoculated with metastatic human NPC cells. RESULTS: The positivity rate and average score for Tiam-1 expression were significantly higher in NPC tissues than in CN tissue (63.33% vs 36.67%, 2.9167 +/- 1.3057 vs 0.7000 +/- 0.9234; chi(2)=20.429, P=0.001; t=7.0162, P=0.0000, respectively). No difference was found in Tiam-1 expression among NPC patients in different T stages (F=2.36, P=0.0811), while the expression differed significantly between the patients with lymph node metastasis and those without metastasis, and also between patients with organ metastasis and those without (P=0.0001). High Tiam-1 expressions were found in the tumor tissues in nude mice inoculated with metastatic NPC cells. CONCLUSION: Tiam-1 expression is closely associated with the invasiveness and metastasis of NPC, indicating that Tiam-1 is an important factor that promotes the invasion and metastasis of NPC.
Subject(s)
Guanine Nucleotide Exchange Factors/metabolism , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/pathology , Adult , Aged , Animals , Female , Guanine Nucleotide Exchange Factors/genetics , Humans , Male , Mice , Mice, Nude , Middle Aged , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Transplantation , T-Lymphoma Invasion and Metastasis-inducing Protein 1ABSTRACT
<p><b>OBJECTIVE</b>To investigate the relationship between the protein expression of T-lymphoma invasion and metastasis gene 1 (Tiam-1) and the biological behaviors of nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>Immunohistochemistry was performed to detect the expressions of Tiam-1 protein in 60 specimens of NPC tissue, 20 specimens of chronic nasopharyngitis (CN) tissue, and 6 tumor tissues from nude mice inoculated with metastatic human NPC cells.</p><p><b>RESULTS</b>The positivity rate and average score for Tiam-1 expression were significantly higher in NPC tissues than in CN tissue (63.33% vs 36.67%, 2.9167 +/- 1.3057 vs 0.7000 +/- 0.9234; chi(2)=20.429, P=0.001; t=7.0162, P=0.0000, respectively). No difference was found in Tiam-1 expression among NPC patients in different T stages (F=2.36, P=0.0811), while the expression differed significantly between the patients with lymph node metastasis and those without metastasis, and also between patients with organ metastasis and those without (P=0.0001). High Tiam-1 expressions were found in the tumor tissues in nude mice inoculated with metastatic NPC cells.</p><p><b>CONCLUSION</b>Tiam-1 expression is closely associated with the invasiveness and metastasis of NPC, indicating that Tiam-1 is an important factor that promotes the invasion and metastasis of NPC.</p>