Objective:To explore antitumor mechanism of a recombinant vaccinia virus expressing human carcinomembryonic antigen(rV CEA).Methods:C57bl/6 mice were immunized three times with rV CEA.Six weeks later,the splenocytes from rV CEA immunized donors were adoptively tranfered in sublethally irradiated CEA + HePa bearing recipients,meanwhile the antiumor effect of the donor splencytes in virtro was detected.Results:Splenocytes from rV CEA immunized donors expressed strong antiumor activity in CEA positive tumorbearing recipients,whereas W VV immunized and nonimmune donor cell did not.The antiumor activity was abolished when immune T cells were depleted before splencytes transfer.Conclusion:It was demonstrated that antiumor acivity induced by rV CEA was essentially mediated by immune T cells which were activated by CEA specific immune response.Adoptive immunotherapy strategies may have implications for both the study of rV CEA and the development of potential clinical applications for tumor immunotherapy.

The aim of this study was to investigate the clinical significance of vascular endothelial growth factor (VEGF) and interleukin-17 (IL-17) levels in patients with multiple myeloma (MM). 40 newly diagnosed MM patients were enrolled, including 9 in stage I, 18 in stage II, 13 in stage III. 25 patients were treated with VAD regimen, and 15 patients with the bortezomib and dexamethasone (BD) regimen. 20 healthy individuals as controls were enrolled in this study. The serum VEGF and IL-17 levels were determined by ELISA. The results indicated that the serum VEGF and IL-17 levels in the patients with MM were significantly higher than those in healthy controls (P < 0.01). VEGF and IL-17 levels in stage III was significantly higher than that in stage I and II (P < 0.05). There was a positive correlation between IL-17 and serum calcium β2-microglobulin or C-reactive protein (P < 0.01), and there was also a positive correlation between VEGF and serum creatinine serum Bene-Jones protein λ or urinary Bene-Jones protein λ (P < 0.01). Serum VEGF and IL-17 levels significantly decreased in MM patients after treatment, and the serum levels of VEGF and IL-17 was much lower in MM patients treated with VAD regimen than those in patients treated with BD regimen. It is concluded that the detection of serum VEGF and IL-17 levels is helpful to evaluation of the clinical stages and the severity of MM.
Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Interleukin-17 ; blood ; Male ; Middle Aged ; Multiple Myeloma ; blood ; pathology ; Neoplasm Staging ; Vascular Endothelial Growth Factor A ; blood

Objective To investigate the protective effect of basic fibroblast growth factor(bFGF) gene modified mesenchymal stem cells(MSCs-bFGF)on cerebral isehemia in rats.Methods MSCs or MSCs-bFGF were transplanted into rat models of focal cerebral ischemia by intravenous injection.The neurological deficits and infarction volumes were evaluated,and the survival rate and differentiation of grafted MSCs were observed by double immunofiuoreseent labeling.Results In the rat cerebral ischemic model, both MSCs and MSCs-bFGF showed protective effect on the rats in comparison with control group.However, the protective effect was more significant in MSCs-bFGF group.Double immunofluorescent staining showed the number of BrdU-labeled and NeuN co-expression cells in MSCs-bFGF treated animals(127.40?7.43 and 11.20?3.09)were much more than in those of MSCs treated animals.While there was no significant difference between MSCs-bFGF and MSCs group in the number of GFAP co-expression cells.Conclusion MSCs transplantation has protective effect on cerebral ischemia in rats.Basic fibroblast growth factor gene modified MSCs is more effective than MSCs in neuroproteetion.

Carcinoma ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Male ; Pancreatic Neoplasms ; genetics ; Spectral Karyotyping ; methods

Objective To investigate the expression of Foxp3~+ lymphocytes in breast carcinoma tissues and their correlation with other pathological factors,and to investigate the mechanism of action of Treg cells.Methods The expression of Foxp3~+ lymphocytes in the breast cancer tissue and non-cancerous tissue was detected by flow cytometry (FCM) in 30 breast carcinoma patients, and its correlation with other pathological factors was statistically analyzed by multiple linear regression analysis.The expression of TGF-β and IL-10 in the lymphocytes infiltrated in breast cancer tissue and non-cancerous tissue was measured by immunohistochemistry, and their correlation with the expression of Foxp3~+ lymphocytes was statistically analyzed by linear correlation dependability analysis. Results There was significant difference in the expression of Foxp3~+ lymphocytes between the malignant and non-cancerous breast tissues(P<0.05),and it was positively correlated with the clinical stage,blood vessel invasion and the matter of axillary lymph node metastasis(P<0.05). The expression of IL-10 in the tumor infiltrating lymphocytes was positively correlated with the expression of Foxp3~+ lymphocytes(P<0.05).Conclusion The expression level of Foxp3~+ lymphocytes is correlated with invasion and metastasis of breast carcinoma, and the IL-10 secreted by Foxp3~+ lymphocytes may be involved in this effect.Foxp3~+ lymphocytes can be used as an assistant marker for prediction and new therpeutic target of breast cancer.

Death with dignity is now not legislation in our country .This paper mainly discussed about some barriers to the legalization of death with dignity in China , from the viewpoint of Chinese traditional ideas , the lack of death education , risk of abusing , the subject change of the informed consent right , doctor-patient communica-tion and trust lsot and so on .It is proposed that our country should perfect the medical security system , strengthen the education of death at the same time and help the citizen set up the view of science .Outside, still need to fur-ther deepen the reform of medical system in our country , the maintaining patient ’ s autonomy and right of choosing , protect the informed consent right of patients .Create the doctor-patient relationship of mutual trust .

Aim To explore antitumor mechanism of a recombinant vaccinia virus containing the human CEA-cDNA (rV-CEA). Methods C57/BL mice were immunized three times with rV-CEA. Six weeks later, the macrophages(MΦ s)and splenocytes from rV-CEA-immunized donors were transferred to CEA＋ -HePa tnmor-bearing recipients,Meanwhile, the antitumor effects of these donor's MΦ s and splenocytes and that of the recipient's splenocytes were detected in vitro. Results The MΦ s and splenocytes from rV-CEA-immunized donors possessed strong antitumor activity in CEA-positive tumor-bearing recipients. The in vitro antitumor effect of splenocytes from mice inoculated with MΦ s from rV-CEA-immunized donors were markedly stronger than those from W-VV-immunized donors. However,the in vitro antitumor effect of the MΦ s from rV-CEA-immunized donors was the same as those from W-VV-immunized donors. Conclusion It is demonstrated that antitumor activity induced with rV-CEA may be mediated mainly by antigen present cells (the MΦ s), which activated tumor-specific T cells to kill tumor cells.

Background:Pulmonary arterial hypertension (PH) is a progressive disease with limited therapeutic options,ultimately leading to right heart failure and death.Recent findings indicate the role of the Warburg effect (aerobic glycolysis) in the development of PH.However,the effect of the glycolysis inhibitor 3-bromopyruvate (3-BrPA) on the pathogenesis of PH has not been well investigated.This study aimed to determine whether 3-BrPA inhibits PH and its possible mechanism.Methods:PH was induced in adult Sprague-Dawley rats by a single intraperitoneal injection of monocrotaline (MCT).3-BrPA,or phosphate-buffered saline (PBS) was administered via intraperitoneal injection every other day from the first day of MCT-injection to 4 weeks of follow-up,and indices such as right ventricular systolic pressure (RVSP),right ventricular hypertrophy index (RVHI),pulmonary arteriolar remodeling indicated by percent media thickness (％ MT),lactate levels and glucose consumption,were evaluated.Pulmonary arteriolar remodeling and right ventricular hypertrophy were observed in hematoxylin-eosin-stained lung sections.Western blotting,immunohistochemistry,and/or immunofluorescence analyses were used to measure the expression of relevant proteins.A cytochrome C release apoptosis assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining were used to measure cell apoptosis.Results:MCT-induced PH showed a significant increase in glucose consumption (0 vs.4 weeks:0.87 ± 0.23 vs.2.94 ± 0.47,P =0.0042) and lactate production (0 vs.4 weeks:4.19 ± 0.34 vs.8.06 ± 0.67,P =0.0004).Treatment with 3-BrPA resulted in a concomitant reduction in glucose consumption (1.10 ± 0.35 vs.3.25 ± 0.47,P =0.0063),lactate production (5.09 ± 0.55 vs.8.06 ± 0.67,P =0.0065),MCT-induced increase in RVSP (39.70 ± 2.94 vs.58.85 ± 2.32,P =0.0004),pulmonary vascular remodeling (％ MT,43.45％±1.41％ vs.63.66％±1.78％,P＜0.0001),and right ventricular hypertrophy (RVHI,38.57％ ± 2.69％ vs.62.61％ ± 1.57％,P ＜ 0.0001) when compared with those of the PBS-treated group.3-BrPA,a hexokinase 2 inhibitor,exerted its beneficial effect on PH by decreasing aerobic glycolysis and was also associated with inhibiting the expression of glucose transporter protein-1,inducing apoptosis,and suppressing inflammation.Conclusions:3-BrPA might have a potential beneficial effect on the PH treatment.

To discuss the effect of puerarin (Pue) on the proliferation of hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) and discuss whether the extracellular signal PI3K/AKT pathway was involved in the Pue-induced PASMC apoptosis. With the serum starvation group (SD group) as the control group, the MTT colorimetry method, Annexin V-FITC apoptosis detection kit and Western blot were used to detect Pue's effect on apoptosis of rat PASMCs. The protein immunoblot assay was used to detect whether PI3K/AKT pathway was involved in the inhibition of hypoxia-induced PASMC apoptosis process. The results show that under normoxic conditions, Pue had no effect on PASMC apoptosis; Under hypoxia conditions, Pue can inhibit PASMC apoptosis; Under normoxic and hypoxic conditions, Pue had no effect on TNF-α expression. Pue can reverse hypoxia-induced Bcl-2 (P <0.01), up-regulate it and down-regulated Bax (P <0.01). Under normoxic conditions, Pue had no effect on P-AKT expression. Both LY294002 and Pue can inhibit hypoxia-induced Bcl-2, up-regulation of P-AKT expression and down-regulation of Bax expression. Compared with the hypoxia + Pue group or the hypoxia + LY294002 group, the hypoxia + Pue + LY294002 group showed more significantly changes in Bcl-2, Bax, P-AKT expressions. The results show that, Pue can inhibit the hypoxic-induced PASMC apoptosis, which may be regulated through PI3K/AKT pathway.
Animals ; Apoptosis ; drug effects ; Cells, Cultured ; Chromones ; pharmacology ; Isoflavones ; pharmacology ; Morpholines ; pharmacology ; Myocytes, Smooth Muscle ; drug effects ; Phosphatidylinositol 3-Kinases ; physiology ; Proto-Oncogene Proteins c-akt ; physiology ; Pulmonary Artery ; cytology ; drug effects ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects

To discuss the effect of puerarin (Pue) on the proliferation of hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) and discuss whether its mechanism is achieved by regulating reactive oxygen. PASMCs of primarily cultured rats (2-5 generations) were selected in the experiment. MTT, Western blot, FCM and DCFH-DA were used to observe Pue's effect the proliferation of PASMCs. The Western blot was adopted to detect whether ROS participated in Pue's effect in inhibiting PASMC proliferation. The PASMCs were divided into five groups: the normoxia group, the hypoxia group, the hypoxia + Pue group, the hypoxia + Pue + Rotenone group and the hypoxia + Rotenone group, with Rotenone as the ROS blocker. According to the results, under the conditions of normoxia, Pue had no effect on the PASMC proliferation; But, under the conditions of hypoxia, it could inhibit the PASMC proliferation; Under the conditions of normoxia and hypoxia, Pue had no effect on the expression of the tumor necrosis factor-α (TNF-α) among PASMCs, could down-regulate the expression of hypoxia-induced cell cycle protein Cyclin A and proliferative nuclear antigen (PCNA). DCFH-DA proved Pue could reverse ROS rise caused by hypoxia. Both Rotenone and Pue could inhibit the up-regulated expressions of HIF-1α, Cyclin A, PCNA caused by anoxia, with a synergistic effect. The results suggested that Pue could inhibit the hypoxia-induced PASMC proliferation. Its mechanism may be achieved by regulating ROS.
Animals ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Hypoxia ; pathology ; Isoflavones ; pharmacology ; Male ; Myocytes, Smooth Muscle ; drug effects ; physiology ; Proliferating Cell Nuclear Antigen ; analysis ; Pulmonary Artery ; cytology ; drug effects ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism