Effect of piceatannol against malignant melanoma / 华西口腔医学杂志

OBJECTIVES@#To study the antitumor effect of piceatannol (PIC) on malignant melanoma @*METHODS@#B16F10 cells were cultured @*RESULTS@#The cell viability of B16F10 decreased with increasing PIC concentration. The results of the Transwell assay showed that invasion ability decreased with increasing PIC concentration, and healing time was prolonged at increased PIC concentration in the wound healing assay. Western blot results showed that PIC mainly inhibited the phosphorylation of Syk and inhibited the expression of MMP-2, MMP-9, and VEGF. RNA interference pointed out that blocking the expression of Syk can reveal the same inhibition effect on B16F10 cells as PIC. @*CONCLUSIONS@#PIC might block the progression of malignant melanoma by inhibiting spleen tyrosine kinase.

Research Advance on the Role of Spleen Tyrosine Kinase Inhibitors in Hematologic Malignancies / 中国实验血液学杂志

Abstract　　Spleen tyrosine kinase (SYK) is not only a key kinase in the B-cell receptor (BCR) signaling pathway, but also a critical component of other signal transduction pathways such as Fc receptor, complement receptor and integrin. Abnormal activation of SYK closely related to the occurrence and development of hematological malignancies, thus targeting SYK has become a research hotspot. Several SYK inhibitors including Fostamatinib, Entospletinib and Cerdulatinib were being evaluated in clincal trials. As a second generation SYK inhibitor, Entospletinib has achieved good efficacy in lymphoid and myeloid hematologic tumors. Furthermore, Entospletinib can significantly relieve hematopoietic stem cell transplantation(HCT) related graft versus host disease (GVHD). In this review the role of SYK inhibitors in treatment of hematological malignancies is summarized brifely.

Effect of electroacupuncture on expressions of Lyn and Syk in mast cells of subcutaneous loose connective tissue in rats with urticarial / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) preconditioning on the expressions of tyrosine kinase Lyn and spleen tyrosine kinase (Syk) in mast cells of subcutaneous loose connective tissue in the rats with urticaria and explore the potential biological mechanism of EA in the intervention of urticaria.@*METHODS@#A total of 32 SD rats were randomized into a blank group, a model group, an EA group and a positive medication group, 8 rats in each one. Except of the blank group, the passive cutaneous anaphylaxis (PCA) was adopted to prepare the model of urticaria in the rats of the rest three groups. In the EA group, EA was applied to bilateral "Quchi" (LI 11), "Xuehai" (SP 10) and "Zusanli" (ST 36), with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity, once daily, for 20 min each time, consecutively for 7 days. In the positive medication group, loratadine (1 mg•kg•d) was for intragastric administration, once daily, consecutively for 7 days. The samples were collected for index detection 30 min after PCA antigen challenge in the rats of each group. Spectrophotometer was adopted to determine the effusion quantity of Evans blue in the allergized site of skin. HE staining was used to observe the morphological changes in the allergized site of skin. Toluidine blue staining was provided to observe mast cell degranulation in subcutaneous loose connective tissue in the allergized site of skin. Immunohistochemistry was applied to determine the protein expressions of Lyn and Syk during degranulation of mast cells.@*RESULTS@#In the rats of the odel group, the eipdermis of allergized site was thickening, cells were disorganized in hierarchy and inflammatory cells were infiltrated largely in the dermis. In the positive medication group and the EA group, the epidermis was getting thin, cell arrangement was clear and the inflammatory cell infiltration was obviously alleviated as compared with the model group. Compared with the blank group, the OD value of skin dye effusion quantity, the degranulation rate of mast cells and the positive expressions of Lyn and Syk were all increased in the model group (<0.01). Compared with the model group, the OD value of skin dye effusion quantity, the degranulation rate of mast cells and the positive expressions of Lyn and Syk were all reduced in the EA group and the positive medication group (<0.01). Compared with the positive medication group, the degranulation rate of mast cells was increased significantly in the EA group (<0.01).@*CONCLUSION@#Electroacupuncture at "Quchi" (LI 11), "Xuehai" (SP 10) and "Zusanli" (ST 36) reduces vascular permeability and gives play to the role of anti-allergy by the way of regulating and controlling the degranulation of mast cells in the rats with urticaria and the effect mechanism of electroacupuncture may be related to the inhibition of protein expressions of Lyn and Syk in mast cells.

Splenic tyrosine kinase promotes pulmonary angiogenesis in rats with hepatopulmonary syndrome / 生理学报

The present paper was aimed to study the role of spleen tyrosine kinase (Syk) in angiogenesis in hepatopulmonary syndrome (HPS) and the underlying mechanism. Sprague Dawley (SD) rats were randomly divided into three groups: sham operation group (sham group), common bile duct ligation (CBDL) 5-week group (5W group) and R788 intervention group (R788 group). HPS model was established by CBDL. Rats in R788 group were intraperitoneally injected with R788 (20 mg/kg) once daily to week 5 after CBDL operation. The protein expression levels and distribution of Syk, p-Erk1/2, and p-Akt in lung tissue were detected by Western blot and immunohistochemistry. Immunofluorescence staining was used to observe the location of Syk expression and the number of angiogenesis in lung tissue. The results showed that, compared with sham group, 5W group exhibited up-regulated protein expression level of Syk, increased phosphorylation levels of Erk1/2 and Akt, and increased number of pulmonary microvessels. Compared with 5W group, R788 group exhibited down-regulated protein expression level of Syk, decreased phosphorylation levels of Erk1/2 and Akt, and decreased number of pulmonary microvessels. These results suggest that Syk may promote pulmonary angiogenesis in HPS model rats by activating downstream Erk1/2 and Akt signaling pathways, which provides a theoretical basis and potential drug therapeutic targets for the clinical treatment of HPS.

Force-dependent calcium signaling and its pathway of human neutrophils on P-selectin in flow

P-selectin engagement of P-selectin glycoprotein ligand-1 (PSGL-1) causes circulating leukocytes to roll on and adhere to the vascular surface, and mediates intracellular calcium flux, a key but unclear event for subsequent arresting firmly at and migrating into the infection or injured tissue. Using a parallel plate flow chamber technique and intracellular calcium ion detector (Fluo-4 AM), the intracellular calcium flux of firmly adhered neutrophils on immobilized P-selectin in the absence of chemokines at various wall shear stresses was investigated here in real time by fluorescence microscopy. The results demonstrated that P-selectin engagement of PSGL-1 induced the intracellular calcium flux of firmly adhered neutrophils in flow, increasing P-selectin concentration enhanced cellular calcium signaling, and, force triggered, enhanced and quickened the cytoplasmic calcium bursting of neutrophils on immobilized P-selectin. This P-selectin-induced calcium signaling should come from intracellular calcium release rather than extracellular calcium influx, and be along the mechano-chemical signal pathway involving the cytoskeleton, moesin and Spleen tyrosine kinase (Syk). These results provide a novel insight into the mechano-chemical regulation mechanism for P-selectin-induced calcium signaling of neutrophils in flow.

A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells

BACKGROUND: Pathologic vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury promotes the development of occlusive vascular disease. Therefore, an effective chemical agent to suppress aberrant proliferation and migration of VSMCs can be a potential therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. To find an anti-proliferative chemical agent for VSMCs, we screened an in-house small molecule library, and the selected small molecule was further validated for its anti-proliferative effect on VSMCs using multiple approaches, such as cell proliferation assays, wound healing assays, transwell migration assays, and ex vivo aortic ring assay. RESULTS: Among 43 initially screened small molecule inhibitors of kinases that have no known anti-proliferative effect on VSMCs, a spleen tyrosine kinase (Syk) inhibitor (BAY61-3606) showed significant anti-proliferative effect on VSMCs. Further experiments indicated that BAY61 attenuated the VSMC proliferation in both concentration- and time-dependent manner, and it also significantly suppressed the migration of VSMCs as assessed by both wound healing assays and transwell assays. Additionally, BAY61 suppressed the sprouting of VSMCs from endothelium-removed aortic rings. CONCLUSION: The present study identified a Syk kinase inhibitor as a potent VSMC proliferation and migration inhibitor and warrants further studies to elucidate its underlying molecular mechanisms, such as its primary target, and to validate its in vivo efficacy as a therapeutic agent for restenosis and atherosclerosis.

In vitro investigation on the mechanism of cyclooxygenase-2 upregulation induced by spleen tyrosine kinase-nuclear factor κB signaling in cancer pain caused by oral cancer-associated macrophage / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study explores the mechanism of cyclooxygenase-2 (COX-2) upregulation in oral cancers associated with macrophage by using molecular biology techniques and primary culture of murine macrophage.</p><p><b>METHODS</b>Murine macrophage was induced by macrophage colony-stimulating factor (M-CSF) and Cal27 conditional medium (CM). Purity of the macrophage was detected through CD68 immunofluorescence staining. Inhibitors of spleen tyrosine kinase (Syk) and nuclear factor κB (NFκB) were used to inhibit these pathways. In addition, real-time polymerase chain reaction and Western blot analysis were used to detect alterations in COX-2 and pathway-related proteins.</p><p><b>RESULTS</b>All of the induced cells specifically expressed CD68. Cal27 CM could significantly induce COX-2 expression (P<0.001). Moreover, inhibition of Syk pathway attenuated NFκB-P65 phosphorylation and reduced COX-2 expression (P<0.01), and inhibition of NFκB pathway exerted no effects on Syk phosphorylation but significantly inhibited COX-2 upregulation (P<0.01).</p><p><b>CONCLUSIONS</b>Syk-NFκB is responsible for COX-2 overexpression in oral cancer associated with macrophages. Targeting this pathway is possibly a new approach to control oral cancer-related pain.
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Expression of full-length spleen tyrosine kinase in the oral squamous cell carcinoma and its relationship with tumor invasion and metastasis / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the expression of full-length spleen tyrosine kinase [SYK (L)] mRNA and protein in human oral squamous cell carcinoma (OSCC) as well as its possible effects on the invasion and metastasis of OSCC.</p><p><b>METHODS</b>The expression of SYK (L) was detected in 27 cases of OSCC tissues and its matched adjacent non-cancerous tissues by real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry. Fourteen cases of normal oral gingival tissues were also analyzed as a normal control.</p><p><b>RESULTS</b>Reduced mRNA and protein expression of SYK (L) in OSCC tissues was observed compared with that in normal oral gingival tissues (P<0.01) and adjacent non-cancerous tissues (P<0.05). SYK(L) expression was significantly associated with lymph-node metastasis (P<0.05).</p><p><b>CONCLUSION</b>SYK(L) is a candidate tumor suppressor for OSCC tissues, and has an inhibitive effect on the initiation, proliferation, and lymph-node metastasis of human OSCC.</p>

Relationship between promoter methylation of Syk and Runx3 genes and postoperative recurrence and metastasis in gastric carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship between aberrant methylation of Syk and Runx3 genes and recurrence and metastasis after resection of gastric cancer.</p><p><b>METHODS</b>Applying methylation-specific polymerase chain reaction technique, promoter methylation of Syk and Runx3 genes in the tumor tissues and adjacent normal tissues of gastric cancer patients were detected to investigate the relationship between methylation status of the promoter region of Syk and Runx3 genes and postoperative recurrence and metastasis.</p><p><b>RESULTS</b>In the 70 cases of gastric cancer, the frequencies of promoter methylation of Syk and Runx3 genes were 45.7% (32/70) and 55.7% (39/70) in gastric cancer, and 0 (0/70) and 7.1% (5/70), respectively, in the adjacent normal tissues. The rates of promoter methylation of Syk and Runx3 genes in the gastric cancers were significantly higher than that in the adjacent normal tissues (P < 0.001 for all). The promoter methylation of Syk and Runx3 genes was significantly correlated with the degree of tumor differentiation, depth of invasion, lymph node metastasis and pathological staging (P < 0.05 for all). The frequency of postoperative recurrence and metastasis in 32 patients with Syk promoter methylation was 65.6% (21/32) and that in 38 cases with Syk promoter unmethylation was 18.4% (7/38), showing a significant difference between the two subgroups (χ(2) = 16.13, P < 0.001). The rate of postoperative recurrence and metastasis in 39 patients with Runx3 promoter methylation was 61.5% (24/39) and that in 31 patients with Runx3 promoter unmethylation was 12.9% (4/31, P < 0.001).</p><p><b>CONCLUSIONS</b>The methylation of Syk and Runx3 promoters plays an important role in postoperative recurrence and metastasis of gastric cancer. Combined detection of promoter methylation of Syk and Runx3 genes is helpful for early diagnosis and evaluation of prognosis of gastric cancer.</p>

Inhibitory effect of full-length spleen tyrosine kinase on invasion and metastasis of human laryngeal squamous cells / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the effect of gene transfection of full length spleen tyrosine kinase (Syk (L)) on the biological behavior of malignant cancer cells.</p><p><b>METHODS</b>Eukaryotic expression vector pIRES2-EGFP-Syk (L) was constrauted and sequenc. Laryngeal carcinoma cell line Hep-2 were transfected with pIRES2-EGFP-Syk (L) vectors or blank vectors. The expressions of mRNA and protein were examined by real time fluorescence quantitative polymerase chain reaction (Q-RT-PCR) and Western blot analysis. CCK-8 method was used for evaluating cell proliferation, Transwell for cell invasion capacity in vitro, and tumor formation in nude mice for in vivo tumorigenicity.</p><p><b>RESULTS</b>pIRES2-EGFP-Syk (L) vectors were successfully construct and transfected to Hep-2 cells. Q-PCR showed that mRNA expression level in Hep-2 cells transfected with Sky (L) (28.395 ± 0.067) was higher than those in Hep-2-neo cells transfected with blank vectors (3.891 ± 0.021) and Hep-2 cells with no transfection (1.005 ± 0.012), with statistically significant difference (F = 104.02, P < 0.01). Western blot showed that protein expression level of transfected-Sky (L) cells (0.821 ± 0.047) was significantly higher than those of Hep-2-neo cells (0.558 ± 0.031) and Hep-2 cells (0.468 ± 0.031), and the difference was statistically significant (F = 112.32, P < 0.01) ; CCK-8 assay showed OD value (1.390 ± 0.067) of transfected-Sky (L) cells was lower than those of Hep-2-neo cells (1.830 ± 0.067) and Hep-2 cells (1.920 ± 0.040), and the difference was statistically significant (F = 107.64, P < 0.01). Transwell assay showed average cell number per field of transfected-Sky (L) cells (176.04 ± 22.32) was higher than those of Hep-2-neo cells (301.02 ± 21.45) and Hep-2 cells (336.04 ± 26.01) with statistically significant difference (F = 123.46, P < 0.01). The volume (250.77 ± 34.83) mm(3) tumor formed from transfected-Sky (L) cells in nude mice, was less than those from Hep-2-neo cells (750.77 ± 40.83) mm(3) and Hep-2 cells (770.77 ± 30.83) mm(3), with statistically significant difference (F = 165.78, P < 0.01).</p><p><b>CONCLUSION</b>Down-regulation of Syk in Hep-2 cells is associated with the malignant biological behaviors of the cells. Syk (L) may be a potential target in gene therapy for laryngeal squamous cell carcinoma.</p>

Regulatory role of Syk gene on vascular endothelial growth factor C expression in breast cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Syk on the VEGF-C expression in breast cancer.</p><p><b>METHODS</b>Immunohistochemical EnVision method was used to detect the protein expression of Syk, NFκB and VEGF-C in breast carcinoma; and the relationship between protein expression of Syk, NFκB, VEGF-C and lymph node metastasis was analysed. MDA-MB-231 cells were transfected with pcDNA3.1(-)-Syk, and the effect of Syk gene on the VEGF-C and NFκB expression was determined.</p><p><b>RESULTS</b>In the lymph node metastatic group, a lower expression rate of Syk and higher expression rate of VEGF-C and NFκB were detected as compared to the non-metastatic group. The expression of Syk was negatively associated with NFκB (r = -0.448, P = 0.002) and VEGF-C (r = -0.620, P = 0.000) expression, and VEGF-C was associated with the nuclear expression of NFκB (r = 0.310, P = 0.036). Compared with the non-transfected cells, the pcDNA3.1(-)-Syk transfected MDA-MB-231 cells showed significantly lower transcriptional level of VEGF-C mRNA, expression level of VEGF-C protein and NFκB activity (P < 0.05).</p><p><b>CONCLUSIONS</b>Syk may play an important role in the lymph node metastasis of breast cancer. It may down-regulate the expression of VEGF-C by inhibiting the activity of NFκB, which thus suppresses lymph node metastasis of breast cancer.</p>

Follicular variant of peripheral T-cell lymphoma: a clinicopathologic and genetic study of 2 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To observe the clinicopathologic and genetic features of follicular variant of peripheral T-cell lymphoma (FV-PTCL), with particular attention to the relationship of this type of lymphoma with angioimmunoblastic T-cell lymphoma (AITL).</p><p><b>METHODS</b>The clinical data, hematoxylin and eosin-stained sections of lymph node biopsies from 2 FV-PTCL cases were reviewed. Immunohistochemical phenotyping and detection of EBV-encoded RNAs (EBER) through in situ hybridization (ISH) were performed. The EnVision two-step method was used for all antibodies except CXCL13 (by using three-step streptavidin immunoperoxidase method). Analysis of clonality and ITK/SYK gene rearrangement was conducted using PCR and RT-PCR assays, respectively.</p><p><b>RESULTS</b>Clinically, the two patients presented with superficial lymphadenopathy similarly. Histologically, case 1 showed a follicular/nodular lymphoid proliferation without marked germinal centers. The neoplastic cells comprised mainly medium sized cells with abundant, sometimes clear cytoplasms. Similar histologic findings were seen in case 2 in addition to a concurrent component mimicking typical AITL noticed. Of both cases, the neoplastic cells showed positive reactivity to CD3, CD4, CD10, PD1, and CXCL13. Positive hybridization signals for EBER were only seen in case 2, and double stains demonstrated that those EBV-positive cells were mostly the reactive transformed B-cells. Monoclonal T-cell proliferation was proved by the rearranged TCR gene detection in both cases. Neither of the current cases expressed ITK/SYK fusion transcripts.</p><p><b>CONCLUSION</b>FV-PTCL shows the similar or overlapped morphological and immunophenotypic features to those of AITL, possibly suggesting the presence of a potential relationship between these two types of lymphomas.</p>

Progress in the study of allergic disease drugs targeting on IgE/FcepsilonRI signaling pathway / 药学学报

Allergic diseases have become global social health problems. The binding of IgE with its high affinity receptor FcepsilonRI plays a key step in I-type allergy. Recently, more and more key molecules on the IgE/FcepsilonRI signaling transduction pathway were to be the drug candidates against allergic diseases, with in-depth study of FcepsilonRI signal pathway gradually. The main drugs include molecule antibodies, peptides, vaccines, fusion proteins, small molecules, and other drugs related to IgE/FcepsilonRI. The recent progress in the study of mechanisms of representative drugs targeting on IgE/FcepsilonRI signaling pathway was reviewed in this article.

Effect of spleen tyrosine kinase on the proliferation of pulmonary vascular smooth muscle cells in rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the role of spleen tyrosine kinase (Syk) in rat pulmonary vascular smooth muscle cells (PVSMCs) proliferation induced by platelet-derived growth factor-BB (PDGF-BB).</p><p><b>METHODS</b>PVSMCs from male Sprague-Dawley rats were cultured in vitro and the cells of passages 3-5 were used in the experiment. PVSMCs were stimulated by PDGF-BB and were treated with three different doses of piceatannol, a Syk selective inhibitor. Cell proliferation was assessed by methyl thiazolyl tetrazolium (MTT) assay. DNA synthesis was measured by ³H-thymidine incorporation (³H-TdR). Cellular cycle was observed by flow cytometry. Syk mRNA and protein expression were detected using real-time quantitative PCR and Western blot, respectively.</p><p><b>RESULTS</b>The expression of Syk protein of PVSMCs was significantly up-regulated following PDGF-BB stimulation. PDGF-BB stimulation dramatically increased PVSMCs proliferation. After piceatannol treatment, both Syk mRNA and protein expression decreased and the proliferation of PVSMCs was inhibited in a dose-dependent manner.</p><p><b>CONCLUSIONS</b>Syk may promote PVSMCs proliferation induced by PDGF-BB.</p>

Role of spleen tyrosine kinase in phenotypic modulation of vascular smooth muscle cell induced by platelet-derived growth factor-BB / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the role of spleen tyrosine kinase (syk) in the phenotypic modulation induced by platelet-derived growth factor (PDGF-BB) in rat pulmonary vascular smooth muscle cells (VSMC).</p><p><b>METHODS</b>Vascular smooth muscles were isolated from pulmonary media of SD rats, cultured, adopted, and divided into 3 groups: blank control group, control group and medicine intervention group. The changes of proliferation and ultrastructure of vascular smooth muscle cells by using [(3)H] thymidine incorporation and electron microscopy. The mRNA and protein expression level of syk, alpha-smooth muscle-actin (α-SM-actin) and smooth muscle protein 22alpha (SM22α) were detected by RT-PCR and Western blotting. The change of fluorescence intensity was detected by laser scanning confocal microscope.</p><p><b>RESULTS</b>Treatment with PDGF-BB for 24 h resulted in a significant increase in [(3)H] thymidine incorporation (2429.25 ± 253.36 vs. 242.75 ± 14.33,P < 0.01) and marked change in phenotype and cytoskeleton, the level of average optical density decreased significantly (263.75 ± 19.21 vs.1146.23 ± 62.61, P < 0.01). Meanwhile, the mRNA (1.70 ± 0.25 vs. 1.01 ± 0.12, P < 0.05) and protein level of syk significantly increased, the mRNA and protein expression of α-SM-actin (0.10 ± 0.00 vs. 1.00 ± 0.00, P < 0.01) and SM22α (0.18 ± 0.00 vs. 1.00 ± 0.01, P < 0.01) significantly decreased in VSMC induced by PDGF-BB. Piceatannol could inhibit significantly these biological effects. Compared with control group, the level of [(3)H] thymidine incorporation (527.00 ± 27.76 vs. 2429.25 ± 253.36,P < 0.01) was significantly down-regulated and the VSMC presented an apoptotic status in medicine intervention group, the level of average optical density increased significantly (810.65 ± 37.94 vs. 263.75 ± 19.21,P < 0.01) in medicine intervention group. Meanwhile, the mRNA (0.36 ± 0.07 vs. 1.70 ± 0.25, P < 0.01) and protein level of syk significantly decreased. The mRNA and protein levels of α-SM-actin (0.22 ± 0.00 vs. 0.10 ± 0.00, P < 0.01) and SM22α (0.31 ± 0.00 vs. 0.18 ± 0.00, P < 0.01) were significantly higher in medicine intervention group than in control group. The level of average optical density increased significantly (810.65 ± 37.94 vs. 263.75 ± 19.21, P < 0.01).</p><p><b>CONCLUSION</b>Syk plays an important role in vascular remodeling by changing the phenotypes and cytoskeleton of VSMC stimulated by PDGF-BB.</p>

Effects of Bufalin on SYK and CBL family proteins in induction of HL-60 cell apoptosis / 中国实验血液学杂志

The study was aimed to explore the mechanism of SYK and CBL family of ubiquitin ligases in Bufalin-induced HL-60 cells apoptosis. Cell viability was tested by trypan blue staining and apoptosis was detected by using flow cytometry. The expressions of CBL and CBL-b and the phosphorylation of SYK were detected by using immunoprecipitation and Western blot. The results showed that Bufalin inhibited HL-60 cell proliferation in time- and dose-dependent manners. IC(50) of suppressing cell viability at 24, 48 and 72 hours were about 26.3, 7.8 and 2.0 nmol/L respectively. The high dose of bufalin already induced apoptosis of HL-60 cells at 8 hours. SYK was quickly phosphorylated, and the expressions of CBL and CBL-b were down-regulated after treatment with Bufalin. It is concluded that SYK activation and CBL protein down-regulation may be involved in Bufalin-induced HL-60 cell apoptosis.

Identification of a functional ITAM-like sequence within G1 cytoplasmic tail of Hantaan virus / 病毒学报

The G1 cytoplasmic tail of Hantaan virus (HTNV) harbors a highly conserved region, which is homologous to immunoreceptor tyrosine-based activation motifs (ITAM) and is termed the ITAM-like sequence. To demonstrate the potential signal-transducing activity of G1 ITAM-like sequence resembling the canonical ITAM within immune and endothelial cells, a series of experiments were performed to define its interaction with cellular kinases. The synthesized G1 ITAM-like peptide was shown to coprecipitate with cellular phosphoprotein complexes by an immune-complex kinase assay. Mutational analyses showed that this ITAM-like sequence was a substrate for the Src family kinase Fyn, and two conserved tyrosine residues were required for coprecipitating Lyn, Syk, and ZAP-70 kinases. These findings demonstrated that HTNV envelope glycoprotein G1 contains a functional ITAM-like sequence in its cytoplasmic tail, which can bind critical cellular kinases that regulate immune and endothelial cell functions.

Effect of spleen tyrosine kinase expression re-activation by inhibition of DNA methylation on oncogenesis growth of gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the effects of 5-Aza-2'-deoxycytidine on spleen tyrosine kinase (Syk) expression by inhibition of DNA methylation and the effect of re-activation of Syk on oncogenesis of gastric cancer.</p><p><b>METHODS</b>Syk mRNA of SGC7901, MGC803, MKN28 and MKN45 cell lines were analyzed by RT-PCR, and Syk methylation were detected by MSP. 5-aza-CDR was used to incubate with human gastric cancer cell line SGC7901, Methylation of Syk promoter region was detected by MSP and RT-PCR technique was used to detected Syk gene in the methylated and silenced Syk gene in the cell line SGC7901. Meanwhile, cell lines were inoculated into subcutaneous tissue of nude mice.</p><p><b>RESULTS</b>No Syk mRNA were found in SGC7901 and MKN45 gastric cancer cell lines, but methylation of Syk were detected in those cell lines. No methylation of Syk promoter region was found and Syk gene was detected in the Syk-negative cell line SGC7901 after incubated with 5-aza-CDR. Of 10 nude mice which were inoculated SGC7901(Syk(+)), 3 were observed macroscopic tumor 8 weeks after the injection. On contrast, tumors were found in 10 nude mice which were inoculated SGC7901 (Syk(-)) 8 weeks after the injection, a significant difference was noted between the two groups (chi (2)=7.91, P<0.05).</p><p><b>CONCLUSION</b>Syk gene is re-expressed in the cell line SGC7901 by demethylation with 5-aza-CDR. Syk gene re-expression suppress the malignant oncogenesis and growth of human gastric cancer.</p>

Platelet activation through signal transduction--review / 中国实验血液学杂志

Platelet is activated through signal transduction, that mainly includes phospholipase-beta (PLCbeta) pathway, protein tyrosine kinases (PTK) pathway, phosphatidylinositol3-kinase (PI3-K) pathway, mitogen-activated protein kinases (MAPK) pathway, cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway and phospholipase A2 (PLA2) pathway. This article focuses on the relationship between signal transduction and platelet activation.

Expression of tyrosine kinase Syk in breast cancer and their clinical significance / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the effects of the Syk mRNA expression in human breast cancer on tumor growth and metastasis, and to study the correlation of expression of the Syk gene with ER, PR, p53 and HER2/neu.</p><p><b>METHODS</b>Specimens from 40 breast cancer patients (tumor tissues, adjacent normal tissues), 15 fibroadenoma were detected for their expression of the Syk gene and level of Syk mRNA by semi-RT-PCR technique. Meanwhile, ER, PR, p53, HER2/neu were detected in 40 tumor tissues from breast cancer with immunohistochemical staining.</p><p><b>RESULTS</b>All normal breast tissues were detected the expression of the Syk gene. Unlike normal breast tissue, 31 out of 40 breast cancer tissue did not show any detectable Syk mRNA expression, there were significant difference in two groups (chi(2) = 47.4, P < 0.05). The level of Syk mRNA in the primary breast cancer tissues were significantly lower than that in the adjacent non-cancerous breast tissues (t = 3.41, P < 0.05). Furthermore, only one breast cancer tissue in 18 patients with lymph node metastasis had the Syk mRNA expression, the rate and level of Syk mRNA expression in the patients with lymph node metastasis were lower than those without lymph node metastasis (chi(2) = 3.77, P < 0.05, t = 2.74, P < 0.05). Syk expression was correlated to p53 expression.</p><p><b>CONCLUSION</b>The expression of the Syk gene may play an important role in suppressing growth and metastasis of breast cancer.</p>