Airway epithelial cell-derived insulin-like growth factor-1 triggers skewed CD8 +T cell polarization / 中国药理学通报

Aim To investigate the effects of airway epithelial cell-derived insulin-like growth factor-1 (IGF1) on CD8 +T cell polarization. Methods Hu-man airway epithelial cell line, RPMI2650 cells, was cultured in the presence of a mice allergen, Der p1, for 72 h. IGF1 expression was checked with quantita-tive RT-PCR and Western blot. Der p1-primed RP-MI2650 cells, recombinant IGF1 and anti-IGF1 anti-body was cocultured respectively with CD8 + T cells, which were activated by anti-CD3/CD8 Ab. Apoptotic cells frequency was calculated with flow cytometry. The alteration of p53 gene hypermethylation in CD8 + T cells elicited by Der p1-primed airway epithelial cell and IGF1 was plotted. Results Both mRNA(23. 1%± 5. 2% vs 5. 2% ± 2. 3%, P < 0. 01 ) and protein (33. 4 ± 6. 4 vs 9. 2 ± 4. 6, P <0. 01 ) expression of IGF1 in RPMI2650 cells markedly increased after ex-posure to Der p1 . The increase of apoptotic CD3/CD28 Ab-activated CD8 + T cells was abolished by the pres-ence of Derp1-primed epithelial cells ( 41. 7% ± 8. 2%vs 5. 2% ± 1. 8%, P <0. 01 ) . The results were con-firmed by the addition of recombinant IGF1 . Anti-IGF1 antibody abolished the effect of the epithelial cells. Derp1-primed epithelial cells inhibited p53 gene mR-NA( 29. 1% ± 5. 9% vs 16. 2% ± 4. 3%, P <0. 01 ) and protein ( 63. 3 ± 8. 9 vs 26. 9 ± 5. 6 , P <0. 01 ) ex-pression. Anti-IGF1 antibody abolished the effect. Re-combinant IGF1 promoted CD8 + T cells′p53 gene hy-permethylation. Conclusion Der p1 induces RP-MI2650 cells to produce IGF1 , and this factor prevents CD8 + T cell apoptosis by inducing p53 gene hyperm-ethylation.

PLCE1 suppresses apoptosis of lung adenocarcinoma cells via modulating p53 expression / 中国病理生理杂志

AIM:To investigate the role of phospholipase C epsilon 1 ( PLCE1 ) in modulating the apoptotic mechanism in lung adenocarcinoma A 549 cells.METHODS:PLCE1 inhibitor U-73122 was used to suppress the expres-sion of PLCE1.The expression of PLCE1 and p53 in A549 cells was evaluated by quantitative real-time PCR and Western blotting.Apoptosis was assessed by flow cytometry .RESULTS:A549 cells expressed high level of PLCE1 and low level of p53.Inhibition of PLCE1 markedly increased the expression of p 53, and increased the apoptosis of A 549 cells.CON-CLUSION:PLCE1 suppresses apoptosis of A549 cells via inhibiting the expression of p53.

PLCE1 modulates p53 expression and apoptosis in esophageal cancer cells / 中国药理学通报

Aim To investigate the role of phospho-lipase C epsilon 1 ( PLCE1 ) in modulating the apoptot-ic mechanism in esophageal cancer ( Eca ) cells. Methods Eca cell lines, OE33 and CP-C cells were cultured to assess the expression of PLCE1 . siRNA suppress expression of PLCE1 . The expression of PLCE1 and p53 was evaluated by quantitative real time PCR and Western blot. Methylation analyses of p53 were performed by bisulfite conversion of genomic DNA. Apoptosis was assessed by flow cytometry. Results OE33 and CP-C cells expressed high levels of PLCE1 . Knockdown of PLCE1 markedly increased the expression and hypomethylation of p53 , and in-creased the frequency of apoptosis. Conclusion PLCE1 suppresses apoptosis of Eca cells via promoting p53 promoter methylation and inhibiting expression of p53 .

Activation of protease-activated receptor 2 inhibits apoptosis of lung cancer cells / 中国药理学通报

Aim To investigate the activation of prote-ase-activated receptor 2 ( PAR2 ) in regulation of the expression of epidermal growth factor receptor ( EGFR) and apoptosis of lung cancer ( LC) cells. Methods LC cells A549 and its EGFR-silenced counterpart were incubated in the medium added with tryptase. Quanti-tative RT-PCR and Western blotting were used to de-tect the expression of EGFR in A 5 4 9 cells . The apop-tosis and Bax/Bcl-xL of cells were also recorded. Re-sults Treating A549 cells with tryptase in the culture for 48 hrs resulted in a marked increase in the expres-sion of EGFR in A549 cells. Marked decreases in a tryptase dose-dependent manner in apoptotic A549 cells were detected in the presence of tryptase. Expo-sure to tryptase markedly decreased the levels of Bax and increased the levels of Bcl-xL in A549 cells, which were not shown in EGFR-deficient A549 cells. Conclusion Tryptase can increase the expression of EGFR in LC cell line, A549 cells, which protects A549 cells from apoptosis, increases Bcl-xL, and sup-presses Bax in A549 cells.

Epidermal growth factor receptor-containing exosomes induce tumor-specific regulatory T cells / 中国药理学通报

Aim Toinvestigatewhetherepidermal growth factor receptor ( EGFR )-containing exosomes could induce tumor-specific regulatory T cells, and the effects of those T cells on tumor protein-specific CD8+Tcells.Methods TheexosomeswithEGFRwerepu-rified from NSCLC tumor, which modulated tolerogenic property of DCs. Then the induced TolDCs generated tumor-specific Tregs, with which the tumor protein-specific CD8 + T cells were suppressed. Results 80%exosomeswereEGFRpositivefromLCpatients while less than 2% exosomes were EGFR positive from control lung tissue. After exposed to the exosomes in the culture for 7 days, the IDO+ DCs proportion was much higher than that in control group ( 80. 8% ± 3. 2% vs 65. 6% ± 6. 4%, P <0. 05 ) . The induced Tregs was also higher ( 24. 1% ± 5. 2% vs 4. 2% ± 2. 3%,P<0. 01 ) , which suppressed the proliferation of CD8+ T cells(5. 4% ± 0. 2% vs 86. 7% ± 9. 3%, P<0.01).Conclusion Thepurifiedexosomesin-duce tolerogenic DCs. Coculture of the tolerogenic DCs and Th0 cells generates the tumor antigen-specific reg-ulatory T cells. The Tregs could suppress the tumor an-tigen specific CD8+ T cells.

High-strength glass ionomer with atraumatic restorative treatment for prevention of deciduous caries / 中国组织工程研究

BACKGROUND: It has been reported that glass ionomer sealants have a poor wear resistance and low rupture strength that are easy to fall off on the occlusal surfaces. OBJECTIVE: To observe the effects of high-strength glass ionomer via the atraumatic restorative treatment (ART) on the pit and fissure of deciduous teeth in the young children. METHODS: A self-controlled method was used to compare ART glass ionomer-based pit and fissure seal on unilateral molars with resin sealant on the contralateral side in 89 children aged 3 years. RESULTS AND CONCLUSION: The retention rates of ART glass ionomer sealant after 6 and 18 months were 94.15% and 77.72%, respectively. At 6 months after treatment, ART gliass ionomer sealant was more caducous in mandibular second deciduous molars > mandibular first deciduous molars > maxillary second deciduous molars > maxillary first deciduous molars; at 18 months after treatment, the rank was mandibular second deciduous molars > maxillary second deciduous molars > mandibular first deciduous molars > maxillary first deciduous molars. The second deciduous molar of the lower mandible, but the caducous position of resin sealant was the second deciduous molar of the upper mandible. The caries prevalence rate of the deciduous teeth treated with ART glass ionomer sealant was significantly lower than that without sealant at 6 and 18 months (P < 0.01). These findings indicate that ART glass ionomer pit and fissure sealant is of a lower drop-out rate, easy to operate and of low cost with excellent caries-preventing effect.

Application of glass ionomer and light-cured resin sealant to the pit and fissure of deciduous teeth / 中国组织工程研究

BACKGROUND: Traditional glass ion sealant has a poor abradability and a low rupture strength. The sealant on the occlusal surfaces easily fell off, and is difficult to replace resin sealant. OBJECTIVE: To observe the effects of traditional resin sealant and atraumatic restorative treatment (ART) glass ionomer-based pit and fissure sealant for the young children. METHODS: Randomized comparison method was used to compare ART glass ionomer-based pit on molars of one side with resin sealant on the opposite side in 89 3-year-old children. RESULTS AND CONCLUSION: The retention rates of ART glass ionomer sealant after 6 and 18 months were significantly lower than those of resin sealant (P < 0.05). The caducous position of ART gliass ionomer sealant was the second deciduous molar of the lower mandible, but the caducous position of resin sealant was the second deciduous molar of the upper mandible. The secondary caries rate of ART glass ionomer sealant was significantly lower than that of resin sealant at 6 months. No significant difference was determined between groups at 18 months. These suggest that ART glass ionomer pit and fissure sealant has lower drop-out rate, simple operation and low cost with excellent caries-preventing effect. Since it is economically superior to resin sealant, the method is worth popularizing in caries-preventing projects.

The preliminary results of a phase II randomized clinical trial of high-dose toremifene chemosensitization in stage IIIB/IV non-small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>To investigate whether high-dose toremifene can enhance the efficacy of chemotherapy in non small cell lung cancer.</p><p><b>METHODS</b>Untreated stage IIIB/IV non-small cell lung cancer patients were randomly devided into group A (high-dose toremifene combined with the platinum-based chemotherapy) or group B (the same platinum-based chemotherapy alone).</p><p><b>RESULTS</b>A total of 30 eligible patients had been recruited. Hemotologic and nonhemotologic toxicities were similar with no statistic difference. The median survival for group A was 8 months, 95% CI (6.63-9.37) versus 7.5 months, 95% CI (4.75-10.25) for group B ( P =0.9). One year-survival rate was 31% for group A versus 28% for group B ( P =0.87). The response rate was 25% for group A versus 21% for group B ( P =0.99).</p><p><b>CONCLUSIONS</b>The results suggest that high-dose toremifene does not enhance the efficacy of platinum-based chemotherapy for IIIB/IV non-small cell lung cancer but toxicities are well tolerated.</p>