Correlation between the Expression of AHA1 mRNA and LOXL2 mRNA in Osteosarcoma Patients Tissues with mRNA Expression of Invasion and Metastasis Genes and Their Clinical Significance / 现代检验医学杂志

Objective To investigate the correlation between the expression of the activator of HSP90 ATPase-1(AHA1),lysyl oxidase like-2 protein(LOXL2)in osteosarcoma tissues with mRNA expression of invasion and metastasis genes and their clinical significance.Methods A total of 90 osteosarcoma patients diagnosed and treated in North China Medical and Health Group Fengfeng General Hospital from February 2016 to March 2017 were selected as the research object.The expression of AHA1 mRNA,LOXL2 mRNA and invasion and metastasis genes Wnt family member 9A(Wnt9a)mRNA,zinc finger E-box binding homologous box 1(ZEB1)mRNA,zinc finger E-box binding homologous box 1(ZEB2)mRNA,N-cadherin(N-cad)mRNA,and vimentin(Vim)mRNA in tissues were detected by real-time fluorescence quantitative PCR.Pearson correlation analysis was used for correlation analysis.The differences in expression of AHA1 mRNA and LOXL2 mRNA in osteosarcoma patients among different clinical characteristics were compared.Kaplan-Meier survival analysis was used to analyze the effect of AHA1 mRNA and LOXL2 mRNA on the prognosis of osteosarcoma patients.The prognostic factors of osteosarcoma patients were analyzed by univariate and multivariate COX regression.Results The expressions of AHA1 mRNA(3.16±0.59),LOXL2 mRNA(2.84±0.44)and invasion and metastasis genes[Wnt9a mRNA(3.23±0.42),ZEB1 mRNA(2.73±0.39),ZEB2 mRNA(2.52±0.56),N-cad mRNA(2.71±0.65)and Vim mRNA(2.81±0.73)]in osteosarcoma tissues were higher than those in paracancerous tissues(1.10±0.21,0.95±0.18,0.79±0.15,0.64±0.11,0.98±0.19,0.68±0.14,0.72±0.15),and the differences were statissically significant(t=31.206,37.716,51.903,48.931,24.706,28.964,26.605,all P<0.05).There was a significant positive correlation between AHA1 mRNA and LOXL2 mRNA expression in osteosarcoma(r=0.712,P<0.05).The expressions of AHA1 mRNA and LOXL2 mRNA were significantly positively correlated with the expressions of invasion and metastasis genes(Wnt9a,ZEB1,ZEB2,N-cad,and Vim mRNA)in tumor tissue of osteosarcoma group(r=0.504～0.720,all P<0.05).The expressions of AHA1 mRNA and LOXL2 mRNA in osteosarcoma tissues with Eneeking stage Ⅲ,soft tissue infiltration,and lung metastasis were higher than those in patients with Eneeking stage Ⅰ～Ⅱ,no soft tissue infiltration,and no lung metastasis,with significant differences(t=14.122～171.054,all P<0.05).The 5-year survival rates of patients in the AHA1 mRNA high expression group and low expression group were 36.36%(16/44)and 78.26%(36/46),respectively.The 5-year cumulative survival rate of patients in the AHA1 mRNA high expression group was significantly lower than that in the low expression group(Log-rank χ2=16.081,P<0.05).The 5-year survival rates of patients with high and low expression of LOXL2 mRNA were 34.88%(15/43)and 78.72%(37/47),respectively.The 5-year cumulative survival rate of patients in the LOXL2 mRNA high expression group was significantly lower than that in the low expression group(Log-rank χ2=15.880,P<0.05).Lung metastasis(OR=1.921,P<0.05),Eneeking stage Ⅲ(OR=1.906,P<0.05),AHA1 mRNA high expression(OR=1.405,P<0.05),and LOXL2 mRNA high expression(OR=1.733,P<0.05)were independent risk factors affecting the poor survival prognosis of osteosarcoma patients.Conclusion The expressions of AHA1 mRNA and LOXL2 mRNA in osteosarcoma were increased,and they were correlated with the expression of invasion and metastasis genes,indicating they may be independent risk factors affecting the poor survival and prognosis of osteosarcoma patients.

Deciphering the suppressive effects of CBX8 on prostate cancer cell invasion / 上海交通大学学报（医学版）

Objective·To elucidate the regulatory mechanisms of the chromobox protein homolog 8(CBX8)in prostate cancer metastasis from transcriptome and epigenetic modification perspectives.Methods·The correlation between the expression of CBX proteins and prostate adenocarcinoma(PRAD)in The Cancer Genome Atlas(TCGA)was examined through an analysis based on cBioPortal database.A stable CBX8 knockdown DU 145 prostate cancer cell line was established via short hairpin RNA(shRNA)transfection.Subsequently,the proliferation and invasion of the CBX8 knockdown cells were analyzed by CCK-8 assay and Transwell assay,respectively.Transcriptome changes of the CBX8 knockdown cells were investigated through RNA sequencing(RNA-seq)coupled with Gene Set Enrichment Analysis(GSEA).To further evaluate the functional implications of these transcriptomic alterations,Gene Ontology(GO)for functional analysis was deployed.Moreover,to identify potentially affected signalling pathways,the Kyoto Encyclopedia of Genes and Genomes(KEGG)was utilized for pathway enrichment analysis.Lastly,the levels of H3K27me3,a key histone modification associated with CBX8,in the knockdown cells were determined by chromatin immunoprecipitation sequencing(ChIP-seq).Results·Bioinformatic analysis with cBioPortal database,based on TCGA-PRAD cohorts,unveiled a high CBX8 mRNA expression in PRAD.Knockdown of CBX8 did not significantly affect the proliferation of DU 145 cells(P＞0.05),but caused a a significant increase in their invasiveness(P＜0.05).The RNA-seq analysis revealed that CBX8 knockdown led to the upregulation of 750 genes and the downregulation of 951 genes.Notably,branched-chain-amino-acid aminotransferase 1(BCAT1),a gene implicated in the metastasis of various types of cancers,showed a significant increase in expression following CBX8 knockdown.GSEA showed that the expression levels were of the affected genes were related to the functions of the polycomb repressive complex 1(PRC1).A further investigation using GO and KEGG analyses identified several enriched pathways in the CBX8 knockdown cells,including transfer RNA(tRNA)aminoacylation,DNA replication,changes in aminoacyl-tRNA ligase activity,and cadherin binding.Interestingly,in terms of cell component of GO functional analysis,cell-substrate junction-related genes associated with tumor metastasis appeared to be enriched.ChIP-seq results showed a global decrease in H3K27me3 levels.Significantly,97 reduced H3K27me3 peaks were found located nearby genes that were upregulated upon CBX8 knockdown,including the transcriptional start site of BCAT1.Conclusion·CBX8 is highly expressed in prostate cancer.CBX8 suppresses prostate cancer cell invasion,possibly by recruiting the transcriptional repressive PRC1 complex to the transcription site of BCAT1,thereby inhibiting BCAT1 transcription and tumor metastasis.

Clinicopathologic study on expression of CK19 and COX-2 in papillary thyroid carcinoma / 中华内分泌外科杂志

Objective:To investigate CK19 and COX-2 expression in papillary thyroid carcinoma (PTC) and their relationship with clinicopathologic parameters.Methods:Retrospective study of 120 consecutive patients with PTC who underwent resection from May. 2017 to Dec. 2020 was conducted. The expression of CK19 and COX-2 in 120 pieces of primary PTC tissue and 30 pieces of adjacent carcinoma tissue were detected by EliVision TM plus two-step immunohistochemical method. The relationship between the expression of CK19 and COX-2 and the clinicopathologic parameters including patient age, TI-RADS classification, TNM staging, carcinomatous infiltration, lymph node metastasis was studied. The analysis was performed using SPSS 22.0 software. The numerical data were presented as numbers and percentages, and chi-test ( χ2 test) and Pearson’s correlation were used to analyze the difference and association between two groups. P<0.05 was considered statistically significant. Results:The positive immunostaining of CK19 and COX-2 were mainly localized in the cytoplasm. The positive rates of CK19 and COX-2 were 87.50% (105/120) and 72.50% (87/120) in cancer tissues and 10.00% (3/30) and 3.33% (1/30) in paracancerous tissues, respectively, with statistically significant differences (both P<0.05 by χ2 test) . In the groups with patients aged <45 years versus ≥45 years, the CK19 positive rates were 88.16% (67/76) and 86.36% (38/44) , and the COX-2 positive rates were 69.74% (53/76) and 77.27% (34/44) , respectively. In the groups of TI-RADS (grade 4 and 5) versus grade 6, the CK19 positive rates were 85.26% (81/95) and 96.00% (24/25) , and the COX-2 positive rates were 69.47% (66/95) and 84.00% (21/25) , respectively, with no statistically significant differences between the two groups (both P>0.05) . In the groups of TNM (stage T1 and T2) versus stage T3, the CK19 positive rates were 82.28% (65/79) and 97.56% (40/41) , and the COX-2 positive rates were 65.82% (52/79) and 85.36% (35/41) , respectively. In the groups with versus without cancer infiltration, the CK19 positive rates were 94.44% (68/72) and 77.08% (37/48) , and the COX-2 positive rates were 83.33% (60/72) and 56.25% (27/48) , respectively. In the groups with versus without lymph node metastasis, the CK19 positive rates were 95.59% (65/68) and 76.92% (40/52) , and the COX-2 positive rates were 83.82% (57/68) and 57.69% (30/52) , respectively, and the differences between the above groups were statistically significant (all P<0.05 by χ2 test) . The co-positive and co-negative expression rates of CK19 and COX-2 in 120 patients were 70.83% (85/120) and 10.83% (13/120) , respectively, with a positive correlation ( r=0.45, P<0.05 by Pearson’s correlation) . Conclusions:The positive rates of CK19 and COX-2 expressions are not related to patient’s age or TI-RADS classification, but closely related to TNM stage, cancer invasion and lymph node metastasis. The up-regulation of both CK19 and COX-2 expressions predicts higher tumor stage, more aggressive invasion and more prone to lymph node metastasis.

Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis / 医学前沿

Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism, which is manifested by increased endogenous fat mobilization, hypertriglyceridemia, and increased fatty acid synthesis. Fatty acid synthase (FASN) is a key enzyme for the de novo synthesis of fatty acids, and monoacylglycerol esterase (MGLL) is an important metabolic enzyme that converts triglycerides into free fatty acids. Both enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways, the most common of which is the PI3K-AKT signaling pathway. They can also regulate the immune microenvironment, participate in epithelial-mesenchymal transition, and then regulate tumor invasion and metastasis. Current literature have shown that these two genes are abnormally expressed in many types of tumors and are highly correlated with tumor migration and invasion. This article introduces the structures and functions of FASN and MGLL, their relationship with abnormal lipid metabolism, and the mechanism of the regulation of tumor invasion and metastasis and reviews the research progress of the relationship of FASN and MGLL with tumor invasion and metastasis.

Inhibitory effect of toosendanin on gastric cancer cells BGC-823 by downregulating circDLST / 上海交通大学学报（医学版）

Objective: To investigate the effect of toosendanin (TSN) on the growth and invasion of gastric cancer cells BGC-823 by regulating circDLST expression. Methods: After gastric cancer cells BGC-823 were exposed to different con-centrations of TSN (0, 0.5, 1.0, and 2.0 μmol/L) for 24 h, quantitative PCR was used to detect the expression of circDLST. BGC-823 cells were transfected with the circDLST overexpression lentiviral vector or its control vector (CON), and then treated with 0.5 μmol/L TSN or PBS. So the cells were divided into circDLST+TSN group, CON+TSN group and CON+PBS group. The viability and invasive potential of BGC-823 cells were observed by MTT proliferation test and Transwell invasion assay. The subcutaneous transplanted tumor models were established by using circDLST-transfected cell line BGC-823 or the control cell line in nude mice, and then 200 μg/kg TSN or the same volume of PBS was injected intraperitoneally every day. So the mice were divided into circDLST+TSN group, CON+TSN group and CON+PBS group. Results: Compared with the control group (0 μmol/L), all 3 concentrations of TSN decreased the expression levels of circDLST in a concentration dependent manner (P<0.01). TSN could significantly reduce the cell viability, cell invasion and subcutaneous xenograft tumor growth (P=0.000), while circDLST overexpression reversed the inhibitory effect of TSN (P<0.01). Conclusion: TSN may inhibit the growth and invasion of gastric cancer cells BGC-823 by downregulating circDLST expression.

The mechanism of Annexin A1 regulating the proliferation, apoptosis and migration of bladder cancer cells / 中华泌尿外科杂志

Objective Explore the function and regulatory mechanism of Annexin A1 (ANXA1) in bladder cancer cell proliferation,apoptosis and migration.Methods From February 2018 to June 2019,we use T24 cells as the model and divide it into over-expression control group (ctrl),ANXA1 over-expression group (ANXA1),knockdown control group (shctrl),ANXA1 knockdown group 1 (shANXA1-1),ANXA1 knockdown group 2 (shANXA1-2) and ANXA1 knockdown group 3 (shANXA1-3).24 hours after the culture,the cells were collected and the mRNA expression level of ANXA1 was detected by Real-Time quantitative PCR.The cell activity was detected by CCK-8;the cell apoptosis and cycle were detected by flow cytometry.The cell migration was detected by Transwell assay.Results The Real-Time quantitative PCR showed that the expression of ANXA1 in the over expression group was significantly higher than that in the over expression control group (15 369.00 ± 874.20 and 1.00 ± 0.07,P ＜ 0.001).The expression of ANXA1 in the knockdown group 2 and 3 were significantly lower than that in the knockdown control group (0.51 ± 0.04,0.51 ± 0.02 and 1.00 ± 0.04,P ＜ 0.001).Compared with the over expression control group (1.61 ± 0.01),the cell activity of the over expression group(2.04 ± 0.02) was significantly increased (P ＜ 0.001),while the activity of the knockdown group 2 and 3 (1.40 ± 0.002 and 1.31 ± 0.003) were significantly decreased than the knockdown ctrl group (1.73 ± 0.01) (P ＜ 0.001).The results of flow cytometry showed that the number of G0/G1 cells in the over-expression group was significantly lower than that in the over-expression control group (28.14 ± 0.33 and 46.19 ± 0.73,P ＜ 0.001),while that in the knockdown group 2 and 3 were significantly higher than that in the knockdown control group (58.670 ± 0.49,62.34 ± 4.01 and 45.59 ± 0.19,P ＜ 0.001 and P ＜ 0.05).There was no significant difference in the number of apoptosis between the over-expression group and the over-expression control group (P ＞ 0.05),while the number of apoptosis in the knockdown group 2 and 3 were significantly higher than that in the knockdown control group (13.04％,14.58％ and 7.76％,P ＜ 0.001).Cell function analysis showed that the number of cells passing through the membrane of the over expression group was significantly higher than that of the over expression group (525.00 ± 9.30 and 385.70 ± 13.40,P ＜ 0.01),while that of the knockdown group 2 and 3 were significantly lower than that of the knockdown control group (214.70 ± 6.40,226.00 ± 5.30 and 398.70 ± 10.00,P ＜ 0.001).Conclusions Over-expression of ANXA1 significantly promoted the proliferation,cycle and migration of T24 cells and inhibited apoptosis.On the contrary,ANXA1 knockdown inhibited the proliferation,cycle and migration of T24 cells and promoted apoptosis.

The mechanism of Annexin A1 regulating the proliferation, apoptosis and migration of bladder cancer cells / 中华泌尿外科杂志

Objective@#Explore the function and regulatory mechanism of Annexin A1 (ANXA1) in bladder cancer cell proliferation, apoptosis and migration.@*Methods@#From February 2018 to June 2019, we use T24 cells as the model and divide it into over-expression control group (ctrl), ANXA1 over-expression group (ANXA1), knockdown control group (shctrl), ANXA1 knockdown group 1 (shANXA1-1), ANXA1 knockdown group 2 (shANXA1-2) and ANXA1 knockdown group 3 (shANXA1-3). 24 hours after the culture, the cells were collected and the mRNA expression level of ANXA1 was detected by Real-Time quantitative PCR. The cell activity was detected by CCK-8; the cell apoptosis and cycle were detected by flow cytometry. The cell migration was detected by Transwell assay.@*Results@#The Real-Time quantitative PCR showed that the expression of ANXA1 in the over expression group was significantly higher than that in the over expression control group (15 369.00±874.20 and 1.00±0.07, P<0.001). The expression of ANXA1 in the knockdown group 2 and 3 were significantly lower than that in the knockdown control group (0.51±0.04, 0.51±0.02 and 1.00±0.04, P<0.001). Compared with the over expression control group(1.61±0.01), the cell activity of the over expression group(2.04±0.02)was significantly increased (P<0.001), while the activity of the knockdown group 2 and 3 (1.40±0.002 and 1.31±0.003)were significantly decreased than the knockdown ctrl group (1.73±0.01)(P<0.001). The results of flow cytometry showed that the number of G0/G1 cells in the over-expression group was significantly lower than that in the over-expression control group (28.14±0.33 and 46.19±0.73, P<0.001), while that in the knockdown group 2 and 3 were significantly higher than that in the knockdown control group (58.670±0.49, 62.34±4.01 and 45.59± 0.19, P<0.001 and P<0.05). There was no significant difference in the number of apoptosis between the over-expression group and the over-expression control group (P>0.05), while the number of apoptosis in the knockdown group 2 and 3 were significantly higher than that in the knockdown control group (13.04%, 14.58% and 7.76%, P<0.001). Cell function analysis showed that the number of cells passing through the membrane of the over expression group was significantly higher than that of the over expression group (525.00±9.30 and 385.70±13.40, P<0.01), while that of the knockdown group 2 and 3 were significantly lower than that of the knockdown control group (214.70±6.40, 226.00±5.30 and 398.70±10.00, P<0.001).@*Conclusions@#Over-expression of ANXA1 significantly promoted the proliferation, cycle and migration of T24 cells and inhibited apoptosis. On the contrary, ANXA1 knockdown inhibited the proliferation, cycle and migration of T24 cells and promoted apoptosis.

Mig- gene silencing inhibits vasculogenic mimicry formation and invasion of glioma U251 cells by suppressing MEK/ERK signaling / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effects of silencing migration-inducing gene-7 (Mig-7) on vasculogenic mimicry formation, migration and invasion of human glioma cells and whether MEK/ERK signaling pathway mediates these effects.@*METHODS@#Human glioma U251 cells were infected by lentiviral vectors carrying a small interfering RNA targeting Mig-7 gene (sh-Mig-) or a negative control shRNA (sh-NC), and real-time quantitative PCR was used to detect the expression level of Mig- mRNA in the cells. Three-dimensional culture and Transwell chamber invasion assay were used to observe the effect of Mig- gene silencing on vasculogenic mimicry formation and invasion ability of the U251 cells. Western blotting was performed to detect the changes in the protein expression levels of MEK/ERK in the infected cells.@*RESULTS@#We successfully obtained a U251 cell line with stable low expression of Mig- gene using RNA interference technique. Compared with the cells infected with sh-NC lentivirus and the non- infected cells, U251 cells infected with the lentiviral vector carrying sh-Mig- showed significantly decreased expression level of Mig- ( < 0.01) with obviously lowered vasculogenic mimicry formation and invasion abilities ( < 0.05). Mig- silencing also significantly lowered the expressions of MEK and ERK proteins in U251 cells ( < 0.05).@*CONCLUSIONS@#Silencing of Mig-7 gene inhibits vasculogenic mimicry formation and invasion of U251 cells possibly by suppressing MEK/ERK signaling, suggesting the important role of Mig-7 gene in vasculogenic mimicry formation and invasion of human glioma cells.

Role of cytokine signal suppressor 3 in the regulatory mechanism of colon cancer invasion and proliferation / 南方医科大学学报

OBJECTIVE@#To investigate the expression of cytokine signal suppressor 3 (SOCS3) in colon cancer tissue and the mechanism by which SOCS3 regulates the proliferation and invasion of colon cancer.@*METHODS@#We collected the specimens of tumor tissues and paired adjacent tissues from 80 patients with colon cancer undergoing radical resection in our hospital between July, 2014 and May, 2017, and the expression of SOCS3 in the tissue samples was analyzed using Western blotting. We also transfected colon cancer cell line SW480 with a SOCS3-overexpressing plasmid or a small interference RNA (siRNA) for SOCS3 knockdown, and the changes in the cell proliferation and invasion capacity were evaluated using CCK-8 assay and Transwell assay, respectively. The effect of demethylation and IL-6 treatment on SOCS3 expression and the proliferation and invasion of SW480 cells were observed.@*RESULTS@#Colon cancer tissues showed a lowered expression of SOCS3 compared with the adjacent tissues. Over-expression of SOCS3 significantly inhibited while SOCS3 knockdown obviously promoted the proliferation and invasion of SW480 cells . Demethylation treatment up-regulated SOCS3 expression and inhibited the proliferation and invasion capacity of SW480 cells; IL-6 treatment of the cells caused the reverse changes.@*CONCLUSIONS@#SOCS3 participates in the development and progression of colon cancer and serves as a potential target for colon cancer treatment. In patients with colon cancer, the low expression of SOCS3 possibly as a result of methylation may promote the proliferation and invasion of the cancer cells.

Four-Dimensional Thoracic CT in Free-Breathing Children

In pediatric thoracic CT, respiratory motion is generally treated as a motion artifact degrading the image quality. Conversely, respiratory motion in the thorax can be used to answer important clinical questions, that cannot be assessed adequately via conventional static thoracic CT, by utilizing four-dimensional (4D) CT. However, clinical experiences of 4D thoracic CT are quite limited. In order to use 4D thoracic CT properly, imagers should understand imaging techniques, radiation dose optimization methods, and normal as well as typical abnormal imaging appearances. In this article, the imaging techniques of pediatric thoracic 4D CT are reviewed with an emphasis on radiation dose. In addition, several clinical applications of pediatric 4D thoracic CT are addressed in various thoracic functional abnormalities, including upper airway obstruction, tracheobronchomalacia, pulmonary air trapping, abnormal diaphragmatic motion, and tumor invasion. One may further explore the clinical usefulness of 4D thoracic CT in free-breathing children, which can enrich one's clinical practice.

Tumor invasion inhibition of thiophene substituted long chain chalcones / 中国药理学通报

Aim To elucidate the structure-activity re-lationship between a new class of long chain chalcone compounds and tumor invasion. Methods The basic idea of the research was to enhance the specificity by prolonging the molecular structure. Based on the lead compound TSAHC, the thiophene was used as the main derivative at the carbonyl groups to obtain six new chalcones. Then we evaluated the anti-tumor activities of the compounds and the expression of key protein MMP-2 of the tumor invasion. Finally, six new com-pounds were docked to the protein by the SYBYL soft-ware. Results The structures of the six compounds were confirmed by H-NMR and MS. Among them, compound 2,3 showed fine capability to inhibit tumor invasion. The docking results also showed that the sul-fonamide and thiophene groups of the compounds had positive contribution to the target binding of the com-pounds. Conclusion Cell experiments and molecular docking show that the long chain modification of chal-cone by using thiophene as a derivative group can sig-nificantly enhance the anti-tumor invasion.

The effects of IL-8-activated tumor-associated macrophages on hepatocellular carcino-ma invasion and metastasis / 中国肿瘤临床

Objective:To study the effects of IL-8 on the polarization of monocytes and the effects of IL-8-induced tumor-associated macrophages(TAMs)on the invasion and metastasis of hepatocellular carcinoma(HCC).Methods:After exogenous IL-8 stimulation of THP-1 cells for 72h,the percentages of M1 and M2 TAMs were examined.RT-PCR and Western blot assays were used to study epitheli-al-mesenchymal transition(EMT),and wound-healing and transwell assays were preformed to study the invasion potential of HCC cells after co-culturing with TAMs and HCC cell lines in vitro.Lastly,100 cases of HCC tissue samples were used to validate the correlation among TAM numbers,IL-8,and EMT features of HCC cells via immunohistochemistry(IHC)staining methods.Results:Exogenous IL-8 induced significant M2 polarization of TAMs in THP-1 cells.TAMs further promoted EMT in HCC and enhanced the invasion potential of HCC in vitro.Finally,significant positive correlations among the numbers of TAMs,IL-8 expression,and N-cadherin expression were identified in primary HCC tissue samples(r=0.22,r=0.20,P<0.05).Conclusions:IL-8 locally attracted and activated TAMs,and promot-ed M2 polarization of TAMs,which further promoted the EMT and invasion potential of HCC cells both in vitro and in vivo.

Effects and mechanisms of microRNA-122 on invasion and migration of hepatocellular carcinoma cells / 中华肝胆外科杂志

Objective To detect the expression of miR-122 in hepatocellular carcinoma (HCC) cells and tissues,and to explore the role and the underlying mechanisms of miR-122 in HCC cells on invasion and migration.Methods Real-time quantitative polymerase chain reaction of analysis was used to examine the expression of miR-132 in HCC cell lines,a normal liver cell line,HCC tissues and adjacent non-tumor tissues.Over express or inhibit miR-122 by transfection.The invasion and migration of HCC cells were analyzed by Transwell assays.Meanwhile,related mechanism proteins were detected by western blot,including insulin like growth factor 1 receptor(IGF-1 R),E-cadherin,vimentin.Results The expression of miR-122 was decreased in HCC tissue samples compared with the adjacent non-tumor tissues[(20.5 ± 4.2) × 10-4 vs.(30.3 ± 5.6) × 10-4],especially in HCC tissue samples with HBV [(25.6 ± 3.5) × 10-4 vs.(19.1 ±3.2) × 10-4].The same results were observed in HCC cell lines.MHCC-97H cells exhibited lowest level of miR-122 expression[(33.7 ± 1.3) × 10-3],whereas SMMC-7721 exhibited the highest level of miR-122 expression [(65.3 ± 1.3) × 10-3].MiR-122 over-expression suppressed the invasion and migration of MHCC-97H[(218.7±24.0) vs.(418.0 ±23.4),(392.7±12.8) vs.(706.6±19.8)].Knocking down miR-122 promoted the invasion and migration of SMMC-7721 [(233.0 ± 14.4) vs.(145.0-±8.0),(561.3 ±9.6) vs.(218.0 ± 11.3)].Western blot revealed that miR-122 suppressed the expression of IGF-1R,Vimentin and facilitated the expression of E-cadherin.Conclusions The study indicates that miR-122 is downregulated in HCC,especially in HCC tissue samples with HBV.MiR-122 can suppress invasion and migration of hepatocellular carcinoma by regulating IGF-1R and epithelial mesenchymal transition,and may provide a new therapeutic option for HCC.

Effect of PTP4A3 gene on tumor growth and metastasis / 中国病理生理杂志

PTP4A3 is an oncogene,which encodes phosphatase of regenerating liver(PRL)-3 protein that is a metastasis-associated phosphorylase. At present,a number of studies have found that it promotes cell proliferation, cell motility,cell invasion,tumor metastasis and epithelial-mesenchymal transition. Therefore,it is inseparable with the occur-rence and development of cancer. Here,we summarize the relationship between PTP4A3 gene and the occurrence and de-velopment of cancer,the alteration of PTP4A3 gene expression and the functional role of PTP4A3 gene in a variety of canc-ers. This review will help us to understand the correlation between PTP4A3 gene and cancer as well as the mechanism of signaling pathway,providing new insights of PTP4A3 gene targeting strategy for treating cancer.

The open-ended coaxial line method for colorectal cancer detection and depth evaluation of tumor invasion / 实用医学杂志

Objective To confirm whether the open-ended coaxial line is effective in detection of the differences in dielectric properties between colorectal cancer tissues and surrounding normal tissues and evaluation of the depth of tumor invasion. Methods The open-ended coaxial line system at frequencies ranging from 50 to 500 MHz in 98 freshly excised colorectal cancerous specimens obtained from the operating theatre of Zhujiang Hospital, was used to detect both the relative permittivity and conductivity on the serosal surface of the carcinoma nidus, the mucosa of the carcinoma nidus, and the mucosa of the surgical resection margin. Pathological examinations were conducted on each specimen after surgery. Results The values for relative permittivity and conductivity of the colorectal cancerous mucosa were significantly higher than those of the normal mucosa (P < 0.01). For the tumor which had invaded or penetrated the serosa (stage ≥ T3), the dielectric properties of both the cancerous serosa and mucosa were higher than the one restricted to muscularis propria or less intestine wall (stage < T3) over the measured frequency range, and there existed statistical differences at the common frequencies of 213 MHz and 426 MHz. Conclusion The open-ended coaxial line system may result in fast and effective diagnostic differentiation between cancerous and normal colorectal tissues as well as reasonable assessment of the tumor infiltration depth.

The expression and significance of Slug,EMMPRIN and E-cadherin in salivary adenoid cystic carcinoma / 实用口腔医学杂志

Objective:To investigate the expression of Slug,EMMPRIN and E-cadherin in salivary adenoid cystic carcinoma (SACC)and its correlation with clinicopathological characteristics,and the correlation among themselves.Methods:Slug,EMMPRIN and E-cadherin expression in 1 1 5 SACC cases of SACC was examined by immunohistochemical staining.The results and clinicopatho-logical data were statistically analyzed.Results:High positive expression frequencies of Slug(76.5%)and EMMPRIN(69.6%)and low positive expression frequency of E-cadherin(51 .3%)were found in 1 1 5 SACC cases.The expression of Slug and EMMPRIN was positively associated with the histopathological types,clinical stages,perineural invasion,recurrence and distance metastasis(P <0.05).The expression of E-cadherin was negatively associated with the histopathological types,clinical stages,perineural invasion and distance metastasis(P <0.05).There was a significant correlation between Slug and EMMPRIN expression(P <0.05),negative correlation between EMMPRIN and E-cadherin expression(P <0.05)and between Slug and E-cadherin expression(P <0.05).Con-clusion:The expression of Slug,EMMPRIN and E-cadherin is closely correlated to the clinicopathological characteristics of SACC.

The effects of morphine combined with cisplatin on invasionon and migration of human lung adenocarci-noma cell A549 / 临床麻醉学杂志

Objective To investigate the effect of morphine combined with cisplatin on inva-sionon and migration of human lung adenocarcinoma cell A549.Methods Human lung adenocarcino-ma A549 cells were inoculated on cultured for 24 h,then were randomly divided into 5 groups:control group (group CON),cisplatin group (group CIS),morphine 0.3 μg/ml+ cisplatin group (group MT1),morphine 3 μg/ml+ cisplatin group (group MT2),morphine 30 μg/ml+ cisplatin group (group MT3).Cisplatin concentration was 4μg/ml.Each group was medicated immediately after 48 h incubation,invasion detection cells by Transwell assay,cell scratch assay cell migration ability, Western-blot detection of matrix metalloproteinase-2 (MMP-2),the expression of MMP-9,Ezrin protein and Fascin protein.Results Compared with group CON,group CIS and morphine combined with cisplatin group reduced tumor cell invasion and migration ability,group MT3 and CIS down-reg-ulated MMP-2,MMP-9,Ezrin and Fascin expression (P<0.05).Compared with group CIS,com-bined with cisplatin group enhanced tumor cell invasion and migration ability group MT3,up-regula-ted MMP-2,MMP-9,Ezrin and Fascin expression (P<0.05).Conclusion Morphine may dose de-pendently reduce cisplatin on invasion and migration of human lung adenocarcinoma cell line A549, and up-regulation of MMP-2,MMP-9,Ezrin,Fascin expression is one of its possible mechanisms.

Expression of TRPC6 in human breast cancer cells and its influence in invasion potential of breast cancer cells / 吉林大学学报(医学版)

Objective To explore the expression of transient receptor potential channel 6(TRPC6)in human breast cancer cells, and to clarify the correlation of TRPC6 with the invasion potential of breast cancer cells. Methods The human breast cancer cell strains MCF-7 (hypo-invasion group)and MDA-MB-231 (hyper-invasion group)were cultured.The expressions of TRPC6 mRNA and protein in in two groups were detected by RT-PCR and Western blotting methods.Then the MDA-MB-231 cells were divided into control group and SKF96365 group, the effects of SKF96365 on the invasion ability of MDA-MB-231 cells invitro were explored by wound healing assay and Transwell experiment.Results The results of Western blotting and RT-PCR showed that the expression levels of TRPC6 mRNA and protein in MDA-MB-231 cells were higher than that in MCF-7 cells(P<0.05).The wound healing assay showed the numbers of migrating cells in 5,25 and 40μmol·L-1 SKF96365 groups (76.24±7.54, 45.33±4.50,25.12±1.57)were lower than those in control group (130.48±9.55)(P<0.05).The Transwell experiment results indicated that the invasiveness of MDA-MB-231 cells were inhibited significantly by SKF96365 compared with control group (P<0.05).Conclusion The invasion ability of human breast cancer MDA-MB-231 cells is promoted by upregulating the TRPC6 expression, which indicates that the TRPC6 may play role in the metastasis of human breast cancer.

Effects of PTEN on the migration and invasion of endometrial carcinoma cells / 中国癌症杂志

Background and purpose: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene is a kind of tumor suppressors, which has been reported to be underexpressed in endometrial carcinoma (EC) tissues by several reports. However, the biological effects and possible mechanisms of PTEN on EC have been known less. In this study, we tried to investigate the effects and possible mechanisms of PTEN on the invasion and migration of endometrial carcinoma cells and to provide a potential target for endometrial carcinoma therapy. Methods:The recombinant plasmid pIRES2-ZsGreen1-PTEN was rebuilt by gene recombination technology;The plasmid was transferred into HEC-1B cells and the cells transfected with pIRES2-ZsGreen1 plasmid were used as control;The expression of PTEN was observed by fluorescence microscope and Western blot assay;Cell migration and invasion was determined by the wound healing assay, transwell migration and invasion assays respectively;The Western blot analysis was performed to detect the expression of ATP-dependent tyrosine kinase (AKT), phosphorylated-AKT (p-AKT) and matrix metalloproteinase-2 (MMP-2). Results:The agarose gel electrophoresis showed a stripe of 1.2 kb which was same to PTEN cDNA;The sequence analysis showed the PCR products owned the same sequence with the coding region of PTEN cDNA in GenBank, suggesting the recombinant plasmid was constructed successfully;The green light of cells observed by fluorescence microscope and the Western blot analysis showed the expression of PTEN was upregulated in the cells transfected with the recombinant plasmid, suggesting the plasmid expressed successfully in HEC-1B cells;The wound healing assay as well as transwell migration assay showed ectopic expression of PTEN suppressed cell migration;The invasive capacity of HEC-1B cells was significantly decreased upon transfection with PTEN plasmid compared to control and untreated groups;Moreover, compared with the control groups, the expression of p-AKT and MMP-2 was downregulated, while there was no significant alteration of the expression of AKT. Conclusion:PTEN could suppress cell migratory and invasive ability of endometrial carcinoma cells by suppressing the phosphorylation of AKT followed by the decrease of MMP-2.

Histopathological Features of Invasion of Breast Invasive Ductal Carcinoma and Safety of Breast-conserving Surgery / 华中科技大学学报（医学）（英德文版）

In order to investigate the relationship between the extent of tumor invasion and the tu-mor size,axillary lymph nodes metastasis,Her-2 gene overexpression,and histologic grading in breast invasive ductal carcinoma as well as the optimal extent of excision during the breast-serving surgery,the clinical data of 104 patients with breast invasive ductal carcinoma who had received modified radical mastectomy were analyzed.The correlation analysis on invasive extent,which was evaluated by serial sections at an interval of 0.5 cm from 4 different directions taking the focus as the centre,and the tumor size,axillary lymph nodes metastasis,Her-2 gene overexpression,and his-tologic grading was processed.There was a significant correlation between invasive extent and tumor size (r=0.766,P<0.01),and lymph nodes metastases (r=0.574,P<0.01),but there was no significant correlation between invasive extent and Her-2 expression (r=0.106,P>0.05),and histologic grading (r=0.228,P>0.05).The 100% negative rate of infiltration in patients without nipple discharge with tumor size <2,2-3 and >3 cm was obtained at 1.5,2.0 and 2.5 cm away from the tumor respectively.It is concluded that the performance of breast-serving surgery in patients with breast invasive ductal carcinoma should be evaluated by tumor size in combination with axillary lymph nodes involvement to decide the possibility of breast-serving and the secure excision extent.