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Objective: To investigate the association of single nucleotide polymorphisms (SNP) rs22833188 and rs2833195 in TIAM1 gene with the susceptibility to Kawasaki disease (KD) and its clinical characteristic in children., Methods: A case-control study was performed in this study. One hundred and eighty-eight children with KD and 197 normal children served as controls were enrolled. The genotypes of two SNPs rs22833188 and rs2833195 in TIAM1 gene were detected using PCR-RFLP., Results: There were no significant differences in the genotype (AA, AG and GG) and allele frequencies of SNP rs2833188 between the KD and control groups. Significant differences in the genotype (CC, GC and GG) frequency of SNP rs2833195 were noted between the KD and control groups (P=0.017). The frequency of C allele in the KD group was higher than in the control group (P=0.015). The polymorphism of SNP rs2833188 was associated with the occurrence of rash (P=0.011), and the polymorphism of SNP rs2833195 was associated with the occurrence of conjunctival hyperemia (P=0.021)., Conclusions: The polymorphism of rs2833195 in TIAM1 gene is associated with the susceptibility to KD. The polymorphisms rs2833188 and rs2833195 in TIAM1 gene may be associated with some clinical characteristics in children with KD.

Purpose: T lymphoma invasion and metastasis inducing factor 1 (TIAM1) overexpression has been reported in a variety of human cancers. However, the investigation of TIAM1 in oral squamous cell carcinoma (OSCC) was extremely rare. The aim of the study was to assess TIAM1 expression and explore its role in OSCC., Methods: Immunohistochemistry staining was performed in 80 primary OSCC patients and 20 normal oral mucosa samples. The expression of TIAM1 and its association with clinicopathological parameters were analyzed using SPSS19.0 software package., Results: TIAM1 expression was significantly stronger in OSCC tissues (91.25%) compared with normal oral mucosa (10.00%); TIAM1 overexpression was significantly correlated with histological grade (P=0.019), clinical stage (P<0.001) and lymph node metastasis (P=0.004), but not significantly correlated with sex or age., Conclusions: TIAM1 may play an important role in the occurrence, development and metastasis of OSCC, which may be a potentially therapeutic target in the future.

Objective: To investigate the effect of T lymphoma invasion and metastasis 1 (Tiam 1) overexpression in head and neck squamous cell carcinoma (HNSCC) cells., Method: Endogenous expression of Tiam 1 in 8 head and neck squamous cell carcinoma cell (HNSCC) lines was investigated by real-time RT-PCR. A lentivirus vector containing Tiaml was transfected into UM-SCC-47 cells, a head and neck squamous cell carcinoma cell line with little endogenous Tiaml expression. Stable clone, obtained by G418 screening, were assayed by RT-PCR and Western blot to validate the gene expression efficiency. The biological behaviors of the transduced cells were determined by cell counting, MTT and in-vitro migration assay., Result: Tiam 1 gene was highly expressed in M2 cell line and it's low level expression was found in UM-SCC-47. Cell counting and MTT assay showed that over-expression of Tiaml significantly promoted cell proliferation (P < 0.05). The cell monolayers overexpressed Tiaml that resulted in a significant increasment of cell migration in infected head and neck squamous cell carcinoma cell lines (P < 0.05)., Conclusion: Tiam 1 gene plays an important role in the growth and migration in head and neck squamous cell carcinoma cell lines. It may be a useful marker for metastasis of head and neck squamous cell carcinoma.

Objective: To explore the effect of downregulation of Tiam1 by siRNA on the esophageal squamous cell carcinoma (ESCC) EC9706 cells, and provide theoretical basis for gene therapy of ESCC using Tiam1 as a molecular target., Methods: Tiam1 siRNA was transfected into EC9706 cells, and expression changes of Tiam1 mRNA and protein after transfection were detected by quantitative real-time PCR and Western blotting. Cell proliferation was analyzed using CCK-8 kit. Cell cycle and apoptosis of the EC9706 cells were assessed by flow cytometry. Cell cycle-related proteins and cell apoptosis-associated proteins were analyzed by Western blotting., Results: Compared with the untreated group and control siRNA group, the relative expression levels of Tiam1 mRNA (1.00 and 0.11 ± 0.02) were not significantly different (P > 0.05). The relative expression levels of Tiam1 mRNA in the Tiam1 siRNA group at 24, 48 and 72 h after transfection were 0.30 ± 0.04, 0.09 ± 0.01 and 0.09 ± 0.006, respectively, significantly lower than that of the untreated group (P < 0.05 for all). The expression level of Tiam1 protein at 24 h after Tiam1 siRNA transfection in the EC9706 cells was 0.11 ± 0.02, significantly lower than that in the un-treated group (0.44 ± 0.05) and control siRNA group (0.44 ± 0.04, P < 0.05 for all). The percentages of G0/G1 cells in the Tiam1 siRNA group, untreated group and control siRNA group were (54.48 ± 2.14)%, (40.69 ± 1.85)% and (41.78 ± 1.31)%, respectively (P < 0.01). The percentages of S phase cells in the Tiam1 siRNA group, untreated group and control siRNA group were (27.18 ± 1.65)%, (32.32 ± 1.15)% and (30.35 ± 1.09)%, respectively (P < 0.01). The expression levels of cyclin D1 protein in the untreated group, control siRNA group and Tiam1 siRNA group were 0.43 ± 0.02, 0.41 ± 0.01 and 0.11 ± 0.02, respectively (P < 0.05). The expression levels of p27 protein in the untreated group, control siRNA group and Tiam1 siRNA group were 0.10 ± 0.01, 0.09 ± 0.02 and 0.20 ± 0.02, respectively (P < 0.05). The ratios of early apoptotic cells in the untreated group, control siRNA group and Tiam1 siRNA group were (10 ± 0.9)%, (10 ± 0.5)% and (27 ± 0.7)%, respectively (P < 0.01). The expression levels of Mcl-1 protein in EC9706 cells of untreated group, control siRNA group and Tiam1 siRNA group were 0.47 ± 0.12, 0.48 ± 0.13 and 0.16 ± 0.02, respectively (P < 0.05). The expression levels of Bcl-2 protein in EC9706 cells of the untreated group, control siRNA group and Tiam1 siRNA group were 0.49 ± 0.08, 0.50 ± 0.05 and 0.04 ± 0.03, respectively (P < 0.05). The caspase-3 activities in the untreated group, control siRNA group and Tiam1 siRNA group were 2.3 ± 0.09, 2.3 ± 0.10 and 16.0 ± 1.50, respectively; and that of caspase-9 were 2.3 ± 0.08, 2.3 ± 0.11 and 14.5 ± 0.9, respectively (P < 0.05 for all)., Conclusions: Tiam1 siRNA can significantly inhibit the proliferation of esophageal cancer EC9706 cells, induce cell cycle arrest and cell apoptosis. These effects are related to the regulation of the expressions of cell cycle-related genes (cyclin D1 and p27) and cell apoptosis-related genes (Mcl-1, Bcl-1, caspase-3 and caspase-9) by Tiam1 siRNA.

Objective: To investigate the significance of Tiam1 in invasion and metastasis of breast carcinoma and its mechanisms., Methods: Immunohistochemistry was used to detect Tiam1 expression in tumor tissue of 126 breast carcinomas. Tiam1 was silenced by siRNA in breast carcinoma cell line MDA-MB-435, then the expressions of phosphor-ERK 1, ERK 2 and VEGF were detected, and electrophoretic mobility shift assay (EMSA) was used to examine the transcription activiy of AP-1., Results: There was a significant relationship between Tiam1 expression and lymph node metastasis (P < 0.05). Furthermore, after silencing of Tiam1, the expressions of phosphor-ERK 1, ERK 2 and VEGF were decreased, and the transcription activity of AP-1 was down-regulated in the MDA-MB-435 cells., Conclusion: Tiam1 is closely related with invasion and metastasis of breast carcinoma, and the cascade Tiam1 through ERK, AP-1 and VEGF pathways may play an important role in enhancing angiogenesis, therefore, to promote invasion and metastasis of breast carcinoma.

Objective: To investigate the relationship between the expression of T lymphoma invasion and metastasis inducing factor 1 (Tiam1) and the progression, metastasis, TNM stage, and histological types of lung carcinoma., Methods: Immunohistochemistry was performed to detect the expression of Tiam1 in 116 lung carcinoma specimens. The expression intensity (measured in positive unit, PU) of Tiam1 in these tissues was assessed quantitatively using Imagepro Plus image analysis software., Results: The PU of Tiam1 was significantly greater in primary lung carcinomas with lymph node metastases than in those without metastases (t=-2.089, P=0.039). Lung cancers of TNM stage II-IV had stronger expression than those of stage I (t=-2.272, P=0.025). The PU of Tiam1 differed significantly between different histological types of lung cancer, and squamouscell cell carcinoma had a lower PU than adenocarcinoma, large cell carcinoma and small cell carcinoma (P<0.05). The intensity of Tiam1 expression was not associated with the patients' gender, age, general types, smoking history, pneumoconiosis or differentiation of lung carcinoma., Conclusion: These results strongly suggest that Tiam1 is an invasion and metastasis inducing factor of lung carcinoma. The overexpression of Tiam1 is closely associated with lymph node metastases, TNM stage and histological types of lung carcinoma.

Objective: To observe the subcellular localization of Rac1 and the expression of Tiam1 and Rac1 in gastric carcinoma, in order to reveal the relationship between the distribution of Rac1 and progression of gastric carcinoma., Methods: Both carcinoma and adjacent normal tissue of 48 patients with gastric carcinoma were studied in this study. Tissue distribution and expression of Rac1 and Tiam1 were analyzed by immunohistochemistry and real-time polymerase chain reaction (PCR)., Results: Compared with that of adjacent non-cancerous gastric mucosa, the expression of Rac1 in cancer tissues was significantly increased. The positive rate of Rac1 expression was 18.8% (9/48 cases) in adjacent non-neoplastic gastric and 79.2% (38/48 cases) in cancer tissues. The positive staining was mainly located in the cell nuclei (31 samples). The real-time PCR results demonstrated that the expression levels of Tiam1 and Rac1 mRNA in cancerous tissues with nuclear localization of Rac1 were evidently increased. Furthermore, nuclear localization of Rac1 was associated with tumor stage and metastasis., Conclusions: The majority of gastric cancer tissues show nuclear dislocalization of Rac1 expression, which may be a sign of abnormal activation of Tiam1-Rac1 pathway. It may suggest enhanced invasion ability of the gastric carcinoma.

Objective: To investigate the expression of T lymphoma invasion and metastasis inducing factor 1 (Tiam1) in breast carcinomas, and explore its association with the clinicopathological features of breast carcinoma., Methods: Immunohistochemistry was used to detect Tiam1 expression in normal breast tissue and 126 breast carcinoma tissues, and the expression levels of Tiam1 mRNA and protein were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting, respectively., Results: The expression of Tiam1 was significantly higher in breast carcinomas than in normal breast tissue (P<0.05). Tiam1 expression was not correlated to the age of the patients or the histological type (P>0.05), but to lymph node metastasis and clinical stages of the tumor (P<0.01). Tiam1 mRNA and protein expressions were stronger in breast carcinoma cell line MDA-MB-435 with high metastatic potential than in breast carcinoma cell line MCF-7., Conclusion: Tiam1 is closely related to the metastasis of breast carcinoma, and may play an important role in promoting metastasis of breast carcinoma.

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.

Objective: To investigate the relationship between T lymphoma invasion and metastasis 1 (Tiam1) and epithelial-mesenchymal transition (EMT) in human colorectal carcinomas., Methods: Tiam1, E-cadherin, CK, and vimentin expressions in normal colorectal epithelium, colorectal carcinomas (CRC) and CRC with lymphatic metastasis were determined by immunohistochemistry using a two-step method., Results: Tiam1 expression was significantly higher in CRC than in normal colorectal epithelium (P<0.01) in close correlation to the degree of tumor differentiation (P<0.05). Higher Tiam1 expression was detected in CRC with lymphatic metastasis than in primary CRC (P<0.05). The expressions of E-cadherin and CK in CRC tissues were significantly lowered in comparison with those in normal colorectal epithelium (P<0.01), showing a correlation to tumor differentiation (P<0.01) but not to lymphatic metastasis. Vimentin was significantly overexpressed in CRC (P<0.01) and correlated to tumor differentiation (P<0.01) but not to lymphatic metastasis. Tiam1 expression was inversely correlated to E-cadherin and CK, but positively to vimentin., Conclusion: Tiam1 is related to the metastasis of colorectal carcinoma, and may induce EMT to promote CRC metastasis.

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.

Objective: To investigate the effects of T lymphoma invasion and metastasis inducing factor 1 antisense oligodeoxynucleotides (Tiam 1 ASODN) transfection on the morphology and invasive migration potential of gastric cancer cells., Methods: The higher invasive and migratory subgroup (M(H)) were separated from human gastric cancer cell line MKN-45 (M(0)) by laminin adhesion method in vitro. Tiam 1 ASODN was transfected into M(H) cells with liposome, and the expression of Tiam 1 mRNA and protein was determined by RT-PCR and flowcytometry respectively. The changes in morphology, the invasive and migratory potential between Tima 1 ASODN transfected M(H) cells and no transfected M(H) cells were observed by HE stain, cytoskeletal protein stain, scanning electronic microscope (SEM) and Boyden chamber test., Results: Compared with the control, the expression of Tiam 1 mRNA and protein in M(H) cells was significantly decreased after transfected with 0.43 micromol/L ASODN(P< 0.01). The invasive and migratory potential of M(H) cells in vitro was also much more decreased than that of no transfected cells (P< 0.05 or P< 0.01). At the same time, transfected M(H) cells had less membrane surface projections, fewer or shorter pseudopodia, less irregular cytoskeletal network and less spotted-like actin bodys than no transfected M(H) cells did., Conclusion: Tiam 1 ASODN transfection can effectively suppress the expression of Tiam 1 in gastric cancer cells and impair its invasive and migratory potential in vitro, which may be fulfilled through modulating the reconstruction of cytoskeleton and decreasing the deforming and migratory potential of gastric cancer cells.

Objective: To observe the effect of Tiam-l gene silencing on the metastasis of human colorectal carcinoma cell line SW480 in nude mice by real-time whole-body fluorescence imaging., Methods: Enhanced green fluorescence protein (EGFP)-labeled human colorectal carcinoma cells, SW480/EGFP(+)/Tiam-1(-) and SW480/EGFP(+), were implanted into nude mice via tail vein injection or orthotopic colonal inoculation, and real-time whole-body fluorescence imaging was performed to compare the difference in tumor progression and metastasis between the two cells., Results: Both SW480/EGFP(+) and SW480/ EGFP(+)/Tiam-1(-) cells stably expressed EGFP, and Tiam1 gene expression was reduced in SW480/EGFP(+)Tiam-1(-) to 30% of the expression level in SW480/EGFP(+) cells. The growth rate of the two cell lines had no significant difference in vitro (P>0.05), but SW480/EGFP(+)/Tiam1(-) cell proliferation and metastasis were depressed obviously in comparison with SW480/EGFP(+) in vivo (P<0.05)., Conclusion: Tiam-1 gene may play an important role in invasion and metastasis of human colorectal cancer.

Objective: To confirm the role of Tiam1 (T lymphoma invasion and metastasis 1) gene in the proliferation and metastasis of colorectal cancer., Methods: Proliferative and metastatic abilities of Tiam1 transfectant were investigated by subcutaneous injection of cells and surgical orthotopic transplantation (SOI) in mice., Results: The expression of Tiam1 led to a pronounced increase in HT29/Tiam1 cell growth starting from day 7, up to 2.5 fold increase of tumor volume at day 20 post injection. Tumors in the HT29/Tiam1 group receiving surgical orthotopic implantation were significantly heavier than those in HT29/mock group (t = -14.916, P < 0.01). In vivo metastasis assay by SOI showed that in HT29/Tiam1 group, 7/7 of mice developed peritoneal metastases and 4/7 had hepatic lesions. In addition, one of the seven HT29/Tiam1 group mice had tumors in lung, spleen and lymph nodes. In the HT29/mock group, only 2/7 of animals had peritoneal metastases and none produced detectable tumor in the liver., Conclusions: Tiam1 gene plays an important role in the proliferation, invasion and metastasis of colorectal cancer. It may serve as a useful clinical marker for tumor progression and metastasis of colorectal cancer.

Objective: To investigate whether the Tiam1 gene expression enhances the invasive and metastatic capabilities of colorectal carcinoma cells., Methods: Endogenous expression of Tiam1 in five colorectal carcinoma cell lines was investigated by RT-PCR. Tiam1/C1199HA cDNA was transfected into HT29, a colorectal carcinoma cell line without endogenous Tiam1 expression. RNA and protein expression of Tiam1 gene in the transfectants were detected by RT-PCR, immunohistochemistry and Western blot respectively. The biological behaviors of the transfectants were investigated by MTT and in-vitro invasion assays., Results: Tiam1 gene was highly expressed in LoVo and SW620 cells. Low level expression was seen in HCT116 and SW480 and no expression was found in HT29. Transfection of Tiam1 significantly increased the proliferation of HT29 cells along with markedly enhanced in-vitro invasion and metastasis., Conclusions: Tiam1 gene plays an important role in the invasion and metastasis of colorectal carcinoma. It may be a useful marker for metastasis of colorectal carcinoma.

Objective: To study the relation between T lymphoma invasion/metastasis1 (Tiam1) gene and nasopharyngeal carcinoma progression., Method: Using of reverse transcription polymerase chain (RT-PCR) technique on 41 nasopharyngeal carcinoma tissue and 20 normal nasopharyngeal tissue to proceed the test of mRNA overexpression., Result: Average expression of the Tiam1 gene in nasopharyngeal carcinoma tissue (1.183 +/- 0.73) is higher than in normal nasopharyngeal tissue (0.87 +/- 0.45) (P < 0.01). The positive relationship between the frequency of Tiam1 overexpression and clinical staging and T staging was very significant (P < 0.05) and increased gradually; The frequency of Tiam1 overexpression was 59.3% (16/27) in patients with lymph node metastasis, 21.4% (3/ 14) in patients without lymph node metastasis, overexpression between them was very significant (P < 0.05)., Conclusion: Average expression of the Tiam1 gene in nasopharyngeal carcinoma tissue is higher than in normal nasopharyngeal tissue. Our data suggest that the overexpression of the Tiam1 gene correlates invasion and metastasis of nasopharyngeal carcinoma.

Objective: To study the role of T lymphoma invasion/metastasis gene 1 (Tiam1) and protein in ovarian tumor cells., Methods: Expressions of Tiam1 mRNA, Rac1 mRNA, and Tiam1 protein in four ovarian tumor cells A2780, Caov3, Skov3, and SW626 were studied by using RT-PCR and Western blot, respectively. The cell migration ability was analyzed by in vitro invasion assay., Results: Expressions of Tiam1 mRNA and protein, as well as Rac1 mRNA were detected in all four ovarian tumor cells. There was a strong direct correlation between the levels of Tiam1 and Rac1 mRNA expression and migration potentials of all four ovarian cancer cells in vitro experiments. The increased expressions of Tiam1 mRNA were coincident with those of Rac1 mRNA, with a parallel relationship (P = 0.003, r = 0.874). Levels of Rac1 mRNA expression were significantly correlated with the potentials of tumor cell migration (P = 0.042, r = 0.814)., Conclusion: Tiam1-Rac1 signaling pathway plays a positive role in assessing tumor cell invasion and metastasis and provides a new target for gene therapy of ovarian cancer.