Biomedical subjects

Yulian Wu

Publications and source records attributed to Yulian Wu.

13 recordsLinked to original sources

PubMed2006

High operative risk of cool-tip radiofrequency ablation for unresectable pancreatic head cancer.

BACKGROUND AND OBJECTIVES: To report and discuss the effect, complications and mortality of cool-tip radiofrequency ablation (RFA) for unresectable pancreatic cancer. METHODS: During October 2003 to July 2004, sixteen patients with unresectable pancreatic cancer were treated by open cool-tip RFA. One-half of the 16 patients had tumors located in the pancreatic head. A 5-mm minimum safe distance between RFA site and major peripancreatic vessels was kept to avoid injury to the vessels. RESULTS: Six of twelve patients with back pain got pain relief postoperatively. Pancreatic fistula occurred in three patients (18.8%) and healed smoothly in 7-10 days with routine abdominal drainage. The mortality was 25% (4/16). In the four death cases, tumors were all located in the pancreatic head; three patients with tumor close to portal vein died suddenly of massive gastrointestinal hemorrhage on the 4th, 30th, 40th postoperative day respectively and a 79-year-old patient died of acute renal failure on the 2nd postoperative day. CONCLUSIONS: Standard use of cool-tip RFA was dangerous for pancreatic head cancer close to portal vein, in which a 5-mm minimum safe distance between RFA site and major peripancreatic vessels might not be enough to avoid injury to the vessels.

Acute Kidney Injury↗

PubMed2006

A practical scoring system based upon ROC analysis for evaluating potential lymph nodes metastasis during gastric surgery.

BACKGROUND AND OBJECTIVES: Current preoperative N staging does not offer an accurate estimation of lymph node involvement. We establish a new scoring system for predicting N stages to guide a rational lymphadenectomy for gastric cancer. METHODS: Variables correlated with N stages were selected by multivariate stepwise logistic regression analysis. Variables granted the different scores according to the odds ratio (OR). Receiver operating characteristic (ROC) analysis was used to generate scoring ranges from N0 to N3. The agreement between predicted N staging and actual pN classification was analyzed using kappa statistics. RESULTS: Tumor size, depth of invasion, and histological types were selected to establish the scoring system. Scores 0-4, 5-7, 8-9, and 10-13 were postulated to predict N0-3, respectively. The predicted N stage has good agreement with the actual pN classifications. The negative predictive values for N0-3 were 87.0, 86.4, 90.4, and 90.2%; the positive predictive values were 74.7, 62.8, 57.3, and 69.6%, respectively. The accuracy is 82% for N0-1, and 83.7% for N2-3. CONCLUSIONS: The new scoring system can predict the N stage of gastric cancer. With its good negative predictive value, it is possible to minimize the potential hazards of applying a more extensive lymph node dissection than necessary.

Adult↗

PubMed2006

Ephrin-B1 is critical in T-cell development.

Eph kinases are the largest family of receptor tyrosine kinases, and their ligands, ephrins (EFNs), are also cell surface molecules. In this study, we investigated the role of EFNB1 and the Ephs it interacts with (collectively called EFNB1 receptors) in mouse T-cell development. In the thymus, CD8 single positive (SP) and CD4CD8 double positive (DP) cells expressed high levels of EFNB1 and EFNB1 receptors, whereas CD4 SP cells had moderate expression of both. Soluble EFNB1-Fc in fetal thymus organ culture caused significant subpopulation ratio skew, with increased CD4 SP and CD8 SP and decreased DP percentage, while the cellularity of the thymus remained constant. Moreover, in EFNB1-treated fetal thymus organ culture, CD117(+), CD25(+), DP, CD4 SP, and CD8 SP cells all had significantly enhanced proliferation history, according to bromodeoxyuridine uptake. In vitro culture of isolated thymocytes revealed that EFNB1-Fc on solid-phase protected thymocytes from anti-CD3-induced apoptosis, with concomitant augmentation of several antiapoptotic factors, particularly in CD4 SP and CD8 SP cells; on the other hand, soluble EFNB1-Fc promoted anti-CD3-induced apoptosis, as was the case in vivo. This study reveals that EFNB1 and EFNB1 receptors are critical in thymocyte development.

Animals↗

PubMed2004

EphrinB1 is essential in T-cell-T-cell co-operation during T-cell activation.

Eph kinases are the largest family of receptor tyrosine kinases, and their ligands are ephrins (EFNs), which are also cell surface molecules. We have very limited knowledge about the expression and function of these kinases and their ligands in the immune system. In this study we investigated the effect of EFNB1 on mouse T-cells. EFNB1 and the Eph kinases it interacts with (collectively called EFNB1 receptors (EFNB1R)) were expressed on T-cells, B cells, and monocytes/macrophages. Some T-cells were double positive for EFNB1 and EFBB1R. Solid phase EFNB1 in the presence of suboptimal TCR ligation augmented T-cell responses in terms interferon-gamma secretion, proliferation, and cytotoxic T lymphocyte activity but not interleukin-2 production. After T-cell receptor (TCR) ligation, EFNB1R congregated to TCR caps, and then both of them translocated to raft caps. This provides a morphological basis for EFNB1R to enhance TCR signaling. Further downstream of the signaling pathway, EFNB1R stimulation led to increased LAT (linker for activation of T-cells) phosphorylation and p44/42 and p38 MAPK activation. Similar to CD28 costimulation, EFNB1R costimulation was insensitive to cyclosporin A inhibition. On the other hand, unlike the former, EFNB1R costimulation failed to activate Akt, which is essential in triggering interleukin-2 production. Our study suggests that EFNB1 is pivotal in T-cell-T-cell costimulation and in reducing T-cell response threshold to antigen stimulation.

Animals↗

PubMed2004

Dipeptide boronic acid, a novel proteasome inhibitor, prevents islet-allograft rejection.

BACKGROUND: We have demonstrated previously in vitro that proteasome inhibitors suppress the proliferation, and induce the apoptosis, of activated T cells. This implies that they could be used as a novel category of immunosuppressants to block allograft rejection. Therefore, in this study, dipeptide boronic acid (DPBA) was tested for its effect on mouse islet transplantation. METHODS: First, DPBA was investigated in vitro for its effect on mouse mixed lymphocyte reaction (MLR) and cytotoxic T-lymphocyte (CTL) activity. DPBA was then used in vivo to treat mouse islet-allograft rejection. RESULTS: Both MLR and CTL were dose dependently suppressed by the proteasome inhibitor. A 17-day DPBA regimen resulted in islet-allograft survival in 50% of the recipients for a duration of up to 60 days, whereas the control group without immunosuppressants rejected the islet graft in 7 days. DPBA showed moderate side effects according to blood biochemistry; the function of endogenous islets after treatment appeared normal on glucose challenge. CONCLUSIONS: The proteasome inhibitor could inhibit islet-allograft rejection in mice without serious side effects at therapeutic dose levels. This has opened a new dimension in the development of better immunosuppression regimens for islet transplantation.

Animals↗

PubMed2003

Death decoy receptor TR6/DcR3 inhibits T cell chemotaxis in vitro and in vivo.

TR6/DcR3 is a secreted molecule belonging to the TNFR family. Its ligands are LIGHT, Fas ligand, and TL1A, all TNF family members. TR6 is expressed in some tumors and is hypothesized to endow tumor cells with survival advantages by blocking Fas-mediated apoptosis. It can also inhibit T cell activation by interfering with two-way T cell costimulation between LIGHT and HveA. In this study, we discovered a novel function of TR6: inhibition of T cell chemotaxis. Human T cells pretreated with soluble or solid-phase TR6-Fc showed compromised migration toward CXCL12/stromal cell-derived factor 1alpha in vitro in a Transwell assay. Such an effect could also be observed in T cells pretreated with soluble or solid-phase HveA-Fc or anti-LIGHT mAb, suggesting that LIGHT reverse signaling was likely responsible for chemotaxis inhibition. TR6 pretreatment also led to T cell chemotaxis suppression in vivo in the mice, confirming in vivo relevance of the in vitro observation. Mechanistically, a small GTPase Cdc42 failed to be activated after TR6 pretreatment of human T cells, and further downstream, p38 mitogen-activated protein kinase activation, actin polymerization, and pseudopodium formation were all down-regulated in the treated T cells. This study revealed a previously unknown function of TR6 in immune regulation, and such an effect could conceivably be explored for therapeutic use in controlling undesirable immune responses.

Actins↗

PubMed2003

Mouse ephrinB3 augments T-cell signaling and responses to T-cell receptor ligation.

Ephrins (EFN) are cell-surface ligands of Ephs, the largest family of cell-surface receptor tyrosine kinases. The function of EFNs in the immune system has not been well studied, although some EFNs and Ephs are expressed at high levels on certain leukocytes. We report here that EFNB3 and its receptors (collectively called EFNB3Rs, as EFNB3 binds to multiple EphBs) were expressed in peripheral T cells and monocytes/macrophages, with T cells being the dominant EFNB3+ and EFNB3R+ cell type. Solid-phase EFNB3-Fc in the presence of suboptimal anti-CD3 crosslinking enhanced T-cell responses in terms of proliferation, activation marker expression, interferon-gamma but not interleukin-2 production, and cytotoxic T-cell activity. EFNB3R costimulation in the presence of phorbol 12-myristate 13- acetate was insensitive to cyclosporin A, similar to CD28 costimulation, suggesting they might share a part of the signaling pathway. After crosslinking, T-cell receptor and EFNB3R congregated into aggregated rafts, and this provided a morphological basis for signaling pathways of T-cell receptor and EFNB3R to interact. Solid-phase EFNB3-Fc augmented p38 and p44/42 MAPK activation further downstream of the signaling pathway. These data suggest that EFNB3 is important in T-cell/T-cell and T-cell/antigen-presenting cell collaboration to enhance T-cell activation and function.

Animals↗

PubMed2003

Clinical significance of detecting elevated serum DcR3/TR6/M68 in malignant tumor patients.

TR6/DcR3/M68 is a soluble receptor that belongs to the TNF receptor family. It is expressed in malignant cells of several tumor types and has been postulated to help tumor cells to gain survival advantage by inhibiting apoptosis and by interfering with immune surveillance. In our study, we assessed for the first time serum TR6 in tumor patients to explore its diagnostic and prognostic value. We examined serum TR6 levels with ELISA in 146 tumor patients, 19 patients with acute infection, 5 patients with liver cirrhosis and 29 healthy individuals. TR6 expression in tumor mass was studied with immunohistochemistry. TR6 gene copy number in tumor tissues was evaluated by real time PCR. Ninety-seven point nine percent (47 of 48 cases) of healthy individuals and patients with acute infection were serum TR6-negative. In contrast, 56.2% (82 of 146 cases) of the tumor patients were serum TR6-positive. Almost all serum TR6-positive individuals (98.8%, 82 out of 83 cases) had malignancy, excluding the cases of liver cirrhosis. In gastric carcinomas, serum TR6 levels were closely correlated with tumor differentiation status and TNM classification. Tumor mass was the source of serum TR6 because its levels decreased drastically after curative tumor resection. TR6 gene amplification occurred in about half of liver carcinomas, but not in gastric or pancreatic carcinomas, indicating plural mechanisms of TR6 upregulation. Our study demonstrated that serum TR6 should be considered as a novel parameter for the diagnosis, treatment and prognosis of malignancies.

Adenocarcinoma, Follicular↗

PubMed2003

Ephrin B2 induces T cell costimulation.

Eph kinases form the largest family of receptor tyrosine kinases, and their ligands are ephrins (EFNs), which are cell surface proteins. Some Eph kinases and EFNs are expressed on T cells, B cells, and dendritic cells, but their functions in the immune system are largely unknown. In this study, we investigated the effect of EFNB2 on murine T cells. EFNB2 mRNA was expressed in the cortex of the thymus and white pulp of the spleen. At the protein level, it was expressed on T cells and monocytes/macrophages, but not on B cells. EFNB2Rs were expressed mainly on T cells. Solid-phase EFNB2 along with suboptimal anti-CD3 strongly stimulated T cell proliferation, with concomitant augmentation of IFN-gamma but not IL-2 or IL-4 secretion. The activity of cytotoxic T cells was also significantly enhanced in the presence of solid-phase EFNB2. These results indicate that EFNB2R cross-linking results in costimulation of T cells. EFNB2Rs were normally scattered on the T cell surface; after TCR cross-linking, they rapidly congregated to capped TCR complexes and then to patched rafts. This provides a morphological base for EFNB2Rs to participate in T cell costimulation. We also demonstrated that EFNB2R signaling led to augmented p38 and p44/42 mitogen-activated protein kinase activation. Our study shows that EFNB2 plays important roles in immune regulation.

Adjuvants, Immunologic↗

PubMed2003

DcR3/TR6 effectively prevents islet primary nonfunction after transplantation.

Islet primary nonfunction (PNF) is defined as the loss of islet function after transplantation for reasons other than graft rejection. It is a major obstacle to successful and efficient islet transplantation. DcR3/TR6 is a soluble death decoy receptor belonging to the tumor necrosis factor (TNF) receptor family, and it can block apoptosis mediated by several TNF receptor family members such as Fas and LT beta R. In this study, we used TR6 to protect islets from PNF after transplantation. Untreated isogeneic or allogeneic islet transplantation had PNF incidence of 25 and 26.5%, respectively. Administration of TR6 totally prevented PNF in allogeneic islet transplantation. In vitro experiments showed an increased apoptosis among islets that were treated with FasL and gamma-interferon (IFN-gamma) in combination. TR6 significantly reduced such apoptosis. Functional study showed that insulin release was compromised after FasL and IFN-gamma treatment, and the compromise could be prevented with TR6-Fc. This indicates that TR6 indeed protected beta-cells from damage caused by FasL and IFN-gamma. Further in vivo experiments showed that syngeneic islet transplantation between lpr/lpr and gld/gld mice was significantly more efficacious than that conducted between wild-type mice. These results suggest that Fas-mediated apoptosis plays an important role in PNF, and use of TR6 may be a novel strategy to prevent PNF in clinical islet transplantation.

Animals↗

PubMed2002

[The expression and significance of heparanase and nm23-H1 in hepatocellular carcinoma].

OBJECTIVE: To explore the relation between heparanase (HPA) and nm23-H1 in hepatocellular carcinoma (HCC), and judge whether they may be used as valuable markers in predicting postoperative metastasis and recurrence of HCC. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (S-P method) were used to measure the expressions of the HPA mRNA and nm23-H1 protein in the primary tumor tissue and paracancer tissue of 33 cases of HCC. The paracancer tissues of 9 cases of benign liver tumor were used as normal controls. The results were analyzed in combination with the results of clinicopathological examination and follow-up. RESULTS: The expression of HPA gene was positive in 16 cases of primary tumor tissues of HCC with a positive rate of 48.5%, significantly higher than those in paracancer tissues of HCC cases and in normal controls (P < 0.01). The HPA expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state and cirrhosis of liver. The positive rates of HPA mRNA in the group with high tendency to metastasis or recurrence and the group with metastasis or recurrence during follow-up were significantly higher than that in the group with low tendency to metastasis or recurrence group (P < 0.05) and that in the group without metastasis or recurrence (P < 0.01). The poorly differentiated tumor and tumor of TNM stage III-IV had higher positive rates of HPA gene expression than the well-mediate differentiated tumor and tumor of TNM stage I-II (P < 0.05). The positive expression rates of nm23-Hl protein in HCC tissue was significantly lower than that in corresponding non-cancerous or normal liver tissue (P < 0.05). nm23-Hl expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state, cirrhosis of liver, Edmondson grade, and TNM stage (P > 0.05). The positive rate of nm23-Hl in the group with high tendency to metastasis and recurrence and in patients with metastasis or recurrence during follow-up was obviously higher than that in the group with low tendency to metastasis and recurrence (P = 0.018) and that in the patients without metastasis and recurrence (P = 0.024), but no significant difference was found between HPA positive and negative groups (P = 0.082). According to the results of follow-up, the rates of accuracy in predicting metastasis of positive HPA, negative nm23-H1 and combination of positive HPA with negative nm23-H1 were 78.6% (11/14), 68.8% (11/16) and 88.9% (8/9) respectively. CONCLUSION: Expression of HPA and/or nm23-Hl are related with metastasis and recurrence of HCC. Combining the expression rate of HPA with the expression rate of nm23-H1 may increase the accuracy in predicting HCC postoperative metastasis and recurrence.

Adult↗

PubMed2002

[Binding pancreaticojejunostomy: clinical report of 150 cases].

OBJECTIVE: To study the safety and feasibility of a new operative procedure called binding pancreaticojejunostomy (BPJ) used to prevent anastomotic leakage following pancreatoduodenectomy (PD). METHODS: From 1996 to 2001, a newly developed operative procedure, binding pancreaticojejunostomy, was performed upon 150 cases undergoing PD. The remnant of pancreas was sutured with and invaginated into the jejunum, with the suture needle only penetrating the mucosa and not the seromuscular layer. The mucosa of jejunum near the pancreatic remnant was destroyed by electric coagulation or phenol. The pancreas and jejunum were bound together so that they were pressed close to each other. The clinical data were reviewed and analysed. RESULTS: The operation of BPJ was performed smoothly on all 150 patients. No pancreatic leakage occurred. CONCLUSION: The BPJ procedure is effective in avoiding anastomotic leakage following PD.

Adult↗

PubMed2002

EphB6 crosslinking results in costimulation of T cells.

Erythropoietin-producing hepatocyte (Eph) kinases represent the largest receptor tyrosine kinase family. Some of them are expressed in the T cell compartment, but their function in T cells is unknown. In peripheral blood, EphB6 was predominantly expressed on T cells, and was upregulated after culture. EphB6 crosslinking by anti-EphB6 mAb or ephrinB2 in the presence of suboptimal T cell receptor (TCR) stimulation led to drastic T cell proliferation, suggesting that EphB6 can co-stimulate T cells. The proliferation was accompanied by enhanced production of several lymphokines, such as IFN-gamma, IL-6, IL-10, TGF-beta, TNF-alpha, and GM-CSF, but not IL-2 and IL-4. Sorted EphB6(+) T cells had significantly stronger response to anti-CD3 and anti-CD28 stimulation than EphB6(-) T cells had. Taken together, these data suggest an important role of EphB6 in normal T cell activation. Within two minutes of anti-CD3 and anti-CD28 stimulation, EphB6 aggregated and colocalized with TCR, and this provides a morphological basis for EphB6 to enhance TCR signaling. The capping was followed by p38 MAPK activation, showing that EphB6 is capable of signaling, in spite of its lack of intrinsic kinase activity. This study demonstrates that interaction between EphB6 and its ligands facilitates T cell responses to antigen.

Animals↗