SDF-1α/CXCR4 axis promotes migration and invasion of pancreatic cancer cells through inducing epithelial-mesenchymal transition / 中国病理生理杂志

AIM:To investigate the role of SDF-1α/CXCR4 axis in pancreatic cancer cell migration and invasion.METHODS:The mRNA expression of CXCR4 in 4 pancreatic cancer cell lines was detected by RT-qPCR.The migration and invasion abilities of PANC-1 cells with the axis activated by exogenous SDF-1αor inhibited by CXCR4 inhibitor AMD3100 were detected by Transwell assays.The cell viability was measured by MTS assay.The protein expression of the epithelial-mesenchymal transition (EMT) -related molecules in the cells treated with exogenous SDF-1αor AMD3100 was determined by Western blot.RESULTS:All of the 4 pancreatic cancer cell lines expressed CXCR4 mRNA, while the PANC-1 cell line expressed the most.Exogenous SDF-1αpromoted the migration and invasion abilities of PANC-1 cells, which was inhibited by AMD3100.The PANC-1 cells treated with exogenous SDF-1αfor 72 h grew faster, while SDF-1αcombined with AMD3100 made little significance to the viability of PANC-1 cells.Exogenous SDF-1αinduced EMT of PANC-1 cells by up-regulating the expression of SNAIL and TWIST, and AMD3100 reversed this effect.CONCLUSION:SDF-1α/CXCR4 axis enhances the migration and invasion abilities of pancreatic cancer cells through inducing EMT.

Prognosis of 153 patients with decompensated hepatitis B virus-related cirrhosis is improved after 3-year continuous lamivudine treatment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The long-term effectiveness and safety of lamivudine in patients with decompensated hepatitis B virus-related cirrhosis are still not clear. The present study attempted to describe the clinical outcomes of lamivudine therapy in these special patients over three years.</p><p><b>METHODS</b>This study was a retrospective, controlled cohort study which involved 153 patients with decompensated hepatitis B virus-related cirrhosis. Of these, 86 patients received lamivudine 100 mg daily accompanied with general internal treatment, and the other 67 were given general internal treatment only. Significant clinical responses were recorded after years of antiviral treatment.</p><p><b>RESULTS</b>The patients in both groups were matched in terms of age, sex and laboratory results at baseline. After years of therapy, the Child-Pugh-Turcotte scores and laboratory values of the patients receiving lamivudine were remarkably improved compared to the patients in the control group. The mortality rate and the incidence of cirrhosis-related complications were much lower in the lamivudine group than in the control group. Genotypic resistance tyrosine, methionine, aspartate, aspartate mutations developed in 26.7 percent of the patients during 3-year lamivudine treatment, and cirrhosis-related death and the hepatocellular carcinoma were more likely to occur in patients with these mutations than in the other patients who were treated with lamivudine.</p><p><b>CONCLUSIONS</b>Continuous long-term lamivudine treatment in patients with decompensated hepatitis B virus-related cirrhosis delays clinical progression, and significantly improves hepatic function and prognosis. However, the use of a retrospective control cohort precludes drawing definitive conclusions.</p>

Antiviral therapy of decompensated hepatitis B virus-related cirrhosis / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the development, mechanism, necessity and limitation of antiviral therapy in decompensated hepatitis B virus-related cirrhosis.</p><p><b>DATA SOURCES</b>Most information was pulled from a literature search (Pubmed 2000 to 2011) using the keywords of antiviral and decompensated hepatitis B virus-related cirrhosis. Relevant book chapters were also reviewed.</p><p><b>STUDY SELECTION</b>Well-controlled, prospective landmark studies and review articles on antiviral therapy in decompesated hepatitis B virus-related cirrhosis were selected.</p><p><b>RESULTS</b>Specific antiviral agents not only control viral replication, which permits liver transplantation, but also improve liver function so significantly that patients could be removed from the transplant waiting list. However, the emergence of drug-resistant mutants can result in treatment failure. Combination therapy is a save-strategy in drug-resistant.</p><p><b>CONCLUSIONS</b>Although the treatment of end-stage liver disease is still a challenge worldwide, antiviral therapy has altered the natural history of hepatitis B patients with decompensated cirrhosis. The approval of the new generation of antivirals is opening new perspectives for finding the optimal antiviral treatment for patients with decompensated cirrhosis and preventing antiviral resistance. A combination of antivirals may be one of the future strategies for fulfilling these goals.</p>

Preparation of As2O3 nanoparticles and its drug release characteristics in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To prepare arsenic trioxide (As2O3)-loaded biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles (NPS) and evaluate the glomeration ability, appearance, structure, surface and release characteristics of the NPs.</p><p><b>METHODS</b>With PLGA as the carrier material, As2O3 NPs (As2O3-NPS) were prepared with the method of matrix and ultrasound emulsification. According to the criteria of the diameter of the NPs, drug loading (DL) and embedding ratio (ER), the process of NP preparation was optimized by scanning electron microscopy (SEM), ultraviolet spectroscopy (UV), and XPS.</p><p><b>RESULTS</b>The As2O3-NPS prepared were uniformly spherical with an average diameter of 210-/+23 nm, DL of 29.6% and ER of 82.1%. The drug release assay in vitro showed a sustained drug-release capacity of the preparation.</p><p><b>CONCLUSION</b>As2O3-NPS may serve as a carrier of As2O3 to change the pharmacokinetics of As2O3 in vivo, allow slow drug release, and prolong the drug circulation time after intravenous injection, thereby producing better antitumor effects.</p>

Clinical features of panereatic disease-associated portal hypertension / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the clinical features and management of pancreatic disease-associated portal hypertension.</p><p><b>METHODS</b>A retrospective analysis was carried out in patients with portal hypertension and concurrent pancreatic diseases. The medical records of these patients were reviewed including the data of demographics, etiologies, venous involvement, clinical presentations, laboratory tests, imaging studies, therapeutic modalities and outcomes.</p><p><b>RESULTS</b>Fifty-two patients with portal hypertension resulting from pancreatic diseases were found in our hospital, accounting for 4% of all the patients with portal hypertension in 11 years. The underlying pancreatic diseases were chronic pancreatitis (21 cases, 35.6%), pancreatic carcinoma (20 cases, 33.9%), acute pancreatitis (8 cases, 13.6%), pancreatic pseudocyst (3 cases, 5.1%). Of the 40 patients whose venous involvement was identified, splenic vein obstruction occurred in 27 cases (67.5%) and portal vein obstruction in 16 cases (40.0%). Mild or moderate splenomegaly was present in 48 cases (81.4%), with leukocytopenia as the most common manifestation of the 31 cases (52.5%) with concomitant hypersplenism. Forty-five patients (76.3%) developed gastroesophageal varices (including 35 with isolated gastricvarices), and among them 22 experienced bleeding (42.3%). Conservative treatment was effective in controlling acute bleeding, but could not prevent re-bleeding. Splenectomy was performed in 18 patients mainly due to gastrointestinal hemorrhage. No postoperative bleeding occurred during the follow-up ranging from 8 months to 9 years.</p><p><b>CONCLUSION</b>Pancreatic diseases may compromise portal vein and its tributaries, leading to generalized or regional portal hypertension. Pharmacological therapy can effectively control acute variceal bleeding, while surgical treatment is the appropriate procedure of choice in case of hemorrhagic recurrence.</p>

Prognostic factor analysis of 116 cases of primary gastrointestinal non-Hodgkin's lymphoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the factors that affect the prognosis of primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL).</p><p><b>METHODS</b>The clinical data of 116 patients with pathologically confirmed PGI-NHL we treated from January 1993 to December 2003 were analyzed retrospectively. Kaplan-Meier survival analysis was used for analyzing the survival of the patients, and Log-rank test was performed to compare the survival rates in relation to different prognostic factors.</p><p><b>RESULTS</b>The 3-year and 5-year survival rates of the patients were 63.8% (74/116) and 48.2% (40/83), respectively. Univariate analysis revealed that the factors affecting the prognosis of the patients included the presence of B symptom, tumor size, clinical stage, pathological type, depth of invasion, and treatment methods. The patients with B symptom, tumor size no less than 10 cm, advanced clinical stage (stages III(E) and IV(E)), T-cell type, and invasion beyond the serosa who received only surgical management had poorer prognosis than those free of B symptom with tumor size <10 cm, early clinical stage (stages I(E) and II(E)), B-cell type, and submucosal or serosal invasion managed with chemotherapy alone or in combination with surgery. Multivariate analysis showed that B symptom, tumor size no less than 10 cm, advanced clinical stage (stages III(E) and IV(E)), T-cell type, invasion beyond the serosa, and surgery alone were independently associated with poor prognosis.</p><p><b>CONCLUSION</b>The tumor size, clinical stage, pathological type, treatment methods are the independent factors affecting the prognosis of patients with PGI-NHL.</p>

Association of Bmi-1 mRNA expression with differentiation, metastasis and prognosis of gastric carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the association of B cell-specific MLV integration site-1 (Bmi-1) mRNA expression level with the differentiation, metastasis and prognosis of gastric carcinoma.</p><p><b>METHODS</b>Tissue specimens were obtained from 42 patients undergoing surgery for gastric carcinomas. Reverse transcriptional PCR (RT-PCR) was performed for amplification of Bmi-1 mRNA from the 42 tumor tissues and matched adjacent normal tissues, and the differential Bmi-1 mRNA expression was analyzed for its association with the clinical manifestations of the patients.</p><p><b>RESULTS</b>Bmi-1 mRNA expression was detected in all the gastric carcinoma tissues and normal tissues adjacent to the carcinoma using fluorescence method, and in 29 cases, Bmi-1 mRNA expression was significantly higher in the tumor tissues than in the adjacent tissues. Expression of Bmi-1 mRNA was highly correlated with tumor size, lymph node metastasis and T classification (P<0.05), but not with the patients' gender, age, or tumor differentiation (P>0.05). The survival rate was much lower in patients positive for Bmi-1 mRNA expression than in those without Bmi-1 mRNA expression.</p><p><b>CONCLUSIONS</b>Bmi-1 mRNA expression is correlated to differentiation and metastasis of gastric carcinoma and may facilitate its prognostic evaluation. Bmi-1 may serve as a marker for assessing the progression of gastric carcinoma and provide assistance for clinical therapeutic decisions.</p>

Biodistribution of (99m)Tc-labeled anti-VEGF mAb 5-FU loaded polylactic acid nanoparticles in human gastric carcinoma xenografts / 南方医科大学学报

<p><b>OBJECTIVE</b>To prepare (99m)Tc-labeled Anti-VEGF mAb 5-FU loaded polylactic acid nanoparticles ((99m)Tc-Ab-5-FU-NPs) and investigate its biodistribution in human gastric carcinoma xenografts.</p><p><b>METHODS</b>(99m)Tc-Ab-5-FU-NPs were prepared by labeling Ab-5-FU-NPs with (99m)Tc using improved Schwarz method. After isolation of (99m)Tc-Ab-5-FU-NPs using SephadexG250 column, the labeling ratio and radiochemical purity were determined using chromatography. The immunocompetence of (99m)Tc- Ab-5-FU-NPs was detected by ELISA and immunohistochemistry. (99m)Tc-Ab-5-FU-NPs were then injected via the tail vein into SCID mice bearing human gastric carcinoma, and (99m)Tc labeled mice-derived monoclonal IgG loaded polylactic acid nanoparticles were used as the control, followed by radioimmunoscintigraphic imaging at 2 and 6 h. The radioactive count and radioactive ratio of the tumor and non-tumor tissue (T/NT) in the animal models were calculated using ROI technique. After imaging at 24 h, SCID mice were sacrificed and the radioactive distribution, the %ID/g, as well as the T/NT radioactive ratio were examined, respectively. The concentrations of 5-FU in the tumor and blood were also detected using HPLC method.</p><p><b>RESULTS</b>The labeling ratio of (99m)Tc-Ab-5-FU-NPs was 90%-95%. (99m)Tc-Ab-5-FU-NPs were detected in the tumor tissues by radioimmunoimaging 2 h after the injection. ID%/g in the tumor tissues at 2 and 6 h were both significantly higher than that of the control group. Both the ID%/g in tumor tissues and radioactive ratio of tumor and blood at 6 h were higher than those at 2 h, and the concentration of 5-FU in experimental group increased continuously with time and was significantly higher than that in control group.</p><p><b>CONCLUSIONS</b>(99m)Tc-Ab-5-FU-NPs prepared in this study can meet the demands of radioimmunoimaging, and the anti-VEGF monoclonal antibody possesses reliable immune targeting ability. Six hours after injection, (99m)Tc-Ab-5-FU-NPs can specifically accumulate in the tumor tissues in human gastric carcinoma xenografts at high concentration.</p>

Study of the anti-tumor effect of anti-vascular endothelial growth factor McAb 5-fluorouracil loaded polylactic acid nanoparticles / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the anti-tumor efficacy of anti- vascular endothelial growth factor (VEGF) McAb 5-fluorouracil (5-FU) loaded polylactic acid (PLA) nanoparticles (NPS) in human gastric carcinoma xenografts of nude mice.</p><p><b>METHODS</b>Anti-VEGF McAb 5-FU loaded PLA NPS were made by ultrasound emulsification. Nude mice model of human gastric carcinoma xenografts was established. Therapeutic effects of drugs on human gastric carcinoma xenografts and side effects concerned were observed.</p><p><b>RESULTS</b>The tumor inhibition rates of control group, nanosphere without 5-FU group, 5-FU (20 mg/kg) group, anti-VEGF McAb nanosphere without 5-FU group, anti-VEGF McAb group, nanosphere with 5-FU group, 5-FU (20 mg/kg) combined with anti-VEGF McAb group, anti-VEGF McAb 5-FU loaded nanosphere group was 0, 6.61%, 24.26%, 27.94%, 35.29%, 37.50%, 39.71% and 52.21% respectively, and there were no significant differences between anti-VEGF McAb 5-FU loaded nanosphere group and nanosphere group without 5-FU in WBC count, serum alanine transferase level or creatinine level. Compared with control group and anti-VEGF McAb 5-FU loaded nanosphere group, the 5-FU group decreased by 34.43% and 37.38% respectively in WBC count (P< 0.05), and increased by 93.17% and 66.56% respectively in alanine transferase. There were significant differences between experimental groups and control group in apoptosis index, especially between anti-VEGF McAb 5-FU loaded nanosphere group and control group (P< 0.05). The microvessel density (MVD) of experimental groups containing anti-VEGF McAb was significantly lower than that of control group or groups containing 5-FU (P< 0.05).</p><p><b>CONCLUSION</b>Anti-VEGF McAb 5-FU loaded nanosphere can increase the tumor inhibitory rate of 5-FU, induce apoptosis by inhibiting tumor angiogenesis with less side effect, and then enhance therapeutic effect, which indicate its potential as a novel, safe nano-tumor-targeting drug.</p>

Postoperative abdominal endogenic field hyperthermia combined with FOLFOX regimen in the treatment of 68 cases of advanced gastric cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the therapeutic efficacy and adverse effects of endogenetic field hyperthermia (EFH) in combination with L-OHP /LV / 5-FU in the treatment of advanced gastric cancer.</p><p><b>METHODS</b>This study included 147 surgical patients with stage II-IV gastric cancer, who received postoperative chemotherapy with FOLFOX (L-OHP 85 mg /m square, 3 h intravenous infusion, followed by infusion of LV at 200 mg /m square in 2 h, intravenous injection of 5-Fu at 400 mg /m square, and intravenous infusion of 5-FU at 3000 mg /m square in 48 h). Eight treatment cycles (each lasting for 14 days) were administered. In 68 cases randomly selected from the cohort, EFH was performed on the first and third days (treatment group), but not in the other 79 cases (control group).</p><p><b>RESULTS</b>The response rate was 68.4% in the treatment group and 36.4% in the control group, showing significant difference between them (P<0.05). The 1-year survival rate was 88.2% in the treatment group, similar to the rate of 81.0% in the control group (P< 0.05), but the 3, 5-year survival rates in treatment group (67.6% and 30.9%) was significantly higher than those in the control group (47.6% and 15.4%, P<0.05). The adverse effects were similar between the two groups.</p><p><b>CONCLUSION</b>EFH combined with the chemotherapeutic regimen FOLFOX might improve the therapeutic effect of stage II-IV gastric cancer without obviously increasing the adverse effects.</p>