Background and purpose: Little about the function of p53 isoforms in gastric cancer was reported. This study was designed to explore the role ofΔ133p53 in the effect of recombinant mutant human tumor necrosis factor (rmhTNF) on gastric cancer cells, and provide a new basis for the diagnostics and therapeutics of gastric carcinoma. Methods: MKN45 (withΔ133p53 expression) or SGC7901 (withoutΔ133p53 expression) cells were treated with rmhTNF of different concentrations only or combined with 5-FU (a traditional gastric cancer cellular killer), and the growth inhibition rate and apoptosis was detected by CCK-8 and lfow cytometry. mRNA expressions ofΔ133p53, Gadd45αand CyclinB1 were measured by nested reverse transcription-polymerase chain reaction (nRT-PCR) or real-time polymerase chain reaction(RT-PCR). Results:On MKN-45 cells with positiveΔ133p53 expression, the inhibitory effect of rmhTNF was signiifcant, the inhibition rates of 50 and 500 IU/mL rmhTNF were 24.82%, 72.33%after culturing for 24 h (t=-9.558, P<0.01);also, the inhibitory effect of 5-FU was improved by rmhTNF remarkably in time-and dose-dependence, the inhibition rates of 5-FU (25 μg/mL), rmhTNF (50 IU/mL) combined with 5-FU (25 μg/mL), rmhTNF (500 IU/mL) combined with 5-FU (25 μg/mL) were 18.20%, 48.66%, 59.83%, separately, after culturing for 24 h (F=82.742, P<0.01);the inhibition rates of rmhTNF (50 IU/mL) combined with 5-FU (25 μg/mL) were 48.66%, 68.20%, 85.23%, separately, after culturing for 24 h, 48 h and 72 h (F=128.583, P<0.01). However, on SGC-7901 cells with negativeΔ133p53 expression, no growth inhibition was showed by rmhTNF only, the inhibition rates of 50 and 500 IU/mL were 2.74%, 3.25%after culturing for 24 h (t=-0.121, P>0.05). In apoptosis test, the apopto-sis-enhancing effect of rmhTNF was signiifcant on MKN45 cells, and the apoptosis-enhancing effect of 5-FU was fur-ther promoted signiifcantly by rmhTNF, the apoptosis of rmhTNF (50 IU/mL), rmhTNF (50 IU/mL) combined with 5-FU (25 μg/mL), rmhTNF (500 IU/mL) combined with 5-FU (25 μg/mL) were 18.20%, 48.66%, 59.83%, separately, after culturing for 24 h (F=123.931, P<0.05). In mRNA measurement, down-regulation ofΔ133p53 and CyclinB1, up-regula-tion of Gadd45αwere signiifcant in MKN45 cells treated by rmhTNF alone or combined with 5-FU. In nRT-PCR anal-ysis, the mRNA levels ofΔ133p53 were relatively 0.886, 0.499, 0.330, 0.161 (F=240.927, P<0.01);In real-time PCR analysis, the mRNA levels of Gadd45αwere 1.227, 1.694, 3.394, and the mRNA levels of CyclinB1 were 1.221, 0.722, 0.316, relatively. The expression ofΔ133p53 was positively related to CyclinB1 (r=0.977, P<0.01), but negatively re-lated to Gadd45α(r=-0.950, P<0.01). Conclusion:InΔ133p53 positively expressed MKN45 cells, rmhTNF showed as an effective tumor inhibitor and an enhancer of 5-FU as well, and this effect might be helped by two p53 down-stream molecules CyclinB1 and Gadd45α. The results suggest thatΔ133p53 might be a key target for the biological effect of rmhTNF against gastric cancer.

Background and purpose:Δ133p53 can promote tumor cell growth, but the exact mechanism is not clear. This study was aimed to observe the expression and signiifcant of the p53 isoformsΔ133p53 and p53 gene downstream molecules MDM2 and cyclin G1 genes by 5-FU-MKN45 gastric cancer cell line model. Methods:Af-ter using different concentrations of 5-FU (50μg/mL, 100μg/mL) to human gastric cancer cell line MKN45, inhibition rate should be detected by MTT assay, the changes ofΔ133p53 mRNA, MDM2 mRNA and cyclin G1 mRNA express-ing were detected by reverse transcription-polymerase chain reaction (RT-PCR). Differences between these groups were analyzed by ANOVA, comparisons within groups were analyzed by t-test, bivariate correlation was analyzed by Pearson linear correlation. Results:MTT results showed that with the increased concentration of 5-FU and the extension of time, the cell inhibition rates increased gradually. The inhibition rates of 50μg/mL 5-FU were 41.10%, 54.79%and 68.48%, for culturing 24, 48 and 72 hours. There were statistically signiifcant differences between the groups(F=45.52, P=0.00). The inhibition rates of 100μg/mL 5-FU were 69.53%, 78.21%and 86.92%, for culturing 24, 48 and 72 hours. There were statistically signiifcant differences between the groups(F=85.58,P=0.00). The inhibition rates of 50 and 100μg/mL were 41.10%and 69.53%, for culturing 24 hours. There were statistically signiifcant differences between the groups(F=51.29, P=0.00). The inhibition rates of 50 and 100μg/mL were 54.79%and 78.21%, for culturing 48 hours. There were statistically signiifcant differences between the groups(F=51.29, P=0.00). The inhibition rates of 50 and 100μg/mL were 68.48%and 86.82%, for culturing 72 hours. There were statistically signiifcant differences between the groups(104.91, P=0.00). RT-PCR results showed that with the increase of the concentration of 5-FU, theΔ133p53 mRNA, MDM2 mRNA and cyclin G1 mRNA expression gradually declined in gastric cancer cell line MKN45 cells, and there were statistically signiifcant differences between the groups(F=738.532, 1 396.607, 2 785.56,P=0.00). Cor-relation analysis showed that the expressions ofΔ133p53 mRNA and MDM2 mRNA in gastric cancer were positively correlated (r=0.871, P=0.01), while the expression of cyclin G1 mRNA and p53 mRNA had no obvious relevance (P=0.13). Conclusion:In the 5-FU-MKN45 gastric cancer cell line model, anti-tumor pathway ofΔ133p53 isomers is related with MDM2 but was not related with cyclin G1.

Objective To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) in the treatment of patients with polypus protrusion lesion on esophagogastric junction ( EGJ ). Methods A retrospective analysis was made on the data of 111 cases ( 114 lesions) with EGJ polypus protrusion undergoing ESD. The main observation indicators included ESD resection rate, operation time, complication, and recurrence. Results The diameter of the 114 lesions was 1. 0-6. 0 cm ( mean 2. 47 ± 0. 80 cm). Among the lesions, 30 had smooth surface, 59 had congestion anabrosis, 11 had nodular rough, 3 were lobulated, 8 had villiform,1 had slight anabrosis, and 2 had local dent. The postoperative pathology analysis showed 19 lesions were intraepithelial neoplasia and 2 were adenocarcinoma. The rate of neoplasia and cancerization was 18. 42%(21/114). The monolithic resection rate of ESD was 100. 0%(114/114), complete resection rate was 99. 1%( 113/114), complete healing resection rate was 97. 4%( 111/114). The mean operation time was 32. 45±7. 32 min (17. 0-60. 0 min). Tardive bleeding after operation occurred in 3 cases, perforation in operation occurred in 1 case, and all the 4 cases were successfully treated by endoscopy. After operation, 2 cases underwent additional surgical procedures. A total of 96 cases were followed-up, with average follow-up time of 28. 8 months, and 1 patient ( 1. 04%, 1/96 ) relapsed. Conclusion The intraepithelial neoplasia and cancerization rate caused by polypus protrusion lesion on EGJ is generally higher than prediction. ESD can monolithic resect lesions with higher complete healing resection rate, fewer complications, and lower recurrence rate.

The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain. Recent studies linked it to many diseases, such as drug addition, Alzheimer's disease, stroke, depression, and even cancer. Sigma-1 receptor is enriched in lipid rafts, which are membrane microdomains essential in signaling processes. One of those signaling processes is ADAM17- and ADAM10-dependent ectodomain shedding. By using an alkaline phosphatase tagged substrate reporter system, we have shown that ADAM10-dependent BTC shedding was very sensitive to both membrane lipid component change and sigma-1 receptor agonist DHEAS treatment while ADAM17-dependent HB-EGF shedding was not; and overexpression of sigma-1 receptor diminished ADAM17- and ADAM10-dependent shedding. Our results indicate that sigma-1 receptor plays an important role in modifying the function of transmembrane proteases.
ADAM Proteins ; metabolism ; ADAM10 Protein ; ADAM17 Protein ; Amyloid Precursor Protein Secretases ; metabolism ; Animals ; Betacellulin ; COS Cells ; Cercopithecus aethiops ; Gene Expression ; HEK293 Cells ; Heparin-binding EGF-like Growth Factor ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Membrane Microdomains ; metabolism ; Membrane Proteins ; metabolism ; Receptors, sigma ; agonists ; metabolism

Objective To study the short-term and medium-term effects of mini- strip anchor and capsulotomy in the treatment of first metacarpophalangeal joint dislocation in rheumatoid arthritis (RA). Methods From January 2015 to December 2016,fifty-eight RA patients with first metacarpophalangeal joint dislocation were randomly divided into study group (20 cases),joint replacement group (19 cases) and non-operation group (19 cases). Postoperative evaluation indexes: the wound healing was observed in accordance with ＂trial standard of functional evaluation of upper limbs of Chinese Medical Association Hand Surgery Society＂. The surgical outcomes of the three groups were compared. The hand function and quality of life were assessed by Michiga Hand Outcomes Questionnaire ( MHQ ) and arthritis impact measurement scale 2 (AIMS2) before treatment, 6 months after treatment and 12 months after treatment. Results All the patients in the study group and the joint replacement group healed by first intention without any early complications. According to the criteria of upper extremity functional evaluation of Chinese Medical Association,the curative effect of the operation was evaluated. In the study group,15 cases were excellent,3 cases were good,2 cases were poor,the excellent and good rate was 90. 0%. In the joint replacement group, 15 cases were excellent,3 cases were good,1 case was poor,and the excellent and good rate was 94. 7%. After treatment for 6months, the MHQ scores were improved significantly in the three groups (( 48. 36 ±8. 24) vs. (73. 06±10. 55); (47. 56±7. 75) vs. (81. 42±8. 54); (48. 75±8. 85) vs. (65. 91±8. 26)) (F＝33. 19,35. 12,28. 42, P＜0. 05). The MHQ scores of study group ( (73. 06±10. 55)points) and joint replacement group ( ( 81. 42 ± 8. 54) points) were significantly higher than those of non-operation group ((65. 91± 8. 26) points) ( P＜0. 05), and the MHQ scores of joint replacement group were significantly higher than those of study group (P＜0. 05). At 12 months after treatment,there was no significant difference in MHQ score between the study group ((82. 45±7. 18)points) and the arthroplasty group ((84. 36±6. 33) points) (P＞0. 05) . At 6 and 12 months after treatment, AIMS2 scores of each group were significantly improved,but AIMS2 scores of study group (( 216. 51 ± 35. 28) points, ( 230. 28 ± 23. 51) points) and arthroplasty group ((221. 45±31. 63) points,(234. 15±21. 42) points) were significantly higher than those of non-operation group ((192.69±41.31) points,(200.43 ±28.42) points) (P＜0.05).At 6 and 12 months after treatment,there was no significant difference in AIMS2 scores between the study group and the arthroplasty group ( P ＞ 0. 05 ) . Conclusion Micro-strip line anchors combined with posterior capsulorrhaphy in the treatment of first metacarpophalangeal joint dislocation in rheumatoid arthritis can achieve good stability of articular reduction,significantly improve the joint function and quality of life and have ideal short-term and mid-term effect.