1.Stochastic Initiation and Propagation of Intracellular Ca~(2+) Wave in Cardiac Myocytes
Progress in Biochemistry and Biophysics 2006;0(08):-
The Ca2+ wave is a chain reaction of intracellular Ca2+ release channels through a Ca2+-induced Ca2+ release mechanism. In cardiac myocytes, Ca2+ wave has drawn much attention because it is found to induce arrhythmia genesis. To investigate the microscopic process of wave propagation, Ca2+ imaging was performed with high spatial and temporal resolution via a laser-scanning confocal microscope combined with loose-seal patch clamp. These observation and analysis revealed that Ca2+ waves originated from a stochastic recruiting of Ca2+ release units (CRUs) by a pioneer Ca2+ spark, which had a low possibility in normal cells. During wave propagation, the 'waiting' time that the wave propagate between two neighboring CRUs along propagation direction distributed normally, and cells with a lower speed had a more dispersive distribution of 'waiting' time. To study the cause of the randomicity, the wave propagation was simulated with a numerical model. The simulation showed that the intrinsic stochastic open process of CRUs can fully explain the above phenomenon. Increasing the maximal open probability of CRUs reduced the randomness of wavefront propagation and enhanced the average velocity of wave meantime. These experimental and numerical results provided an unequivocal quantification for the stochastic behavior of wave initiation and propagation.
2.Urothelial carcinoma-associated 1 enhances tamoxifen resistance in breast cancer cells through competitively inhibiting miR-18a
Xiunan LI ; Aihui LIU ; Xin TANG ; Yu REN
Journal of Peking University(Health Sciences) 2017;49(2):295-302
Objective:To investigate how urothelial carcinoma-associated 1 (UCA1) and miR-18a modulates acquired tamoxifen resistance and the relevant mechanisms in estrogen receptor (ER) positive cancer cells.Methods: qRT-PCR was performed to detect UCA1 and miR-18a expression in breast cancer cells.Dual luciferase assay was performed to detect the binding between miR-18a and UCA1 3′UTR.Tamoxifen sensitive MCF-7 cells were transfected with UCA1 expression vector or miR-18a inhi-bitors.Tamoxifen resistant LCC9 and BT474 cells were transfected with UCA1 siRNA or miR-18a mi-mics.CCK-8 assay was performed to detect cell viability.Soft agar assay was performed to assess cell colony formation.Flow cytometric analysis was performed to check cell cycle distribution.Results: UCA1 was significantly upregulated in tamoxifen resistant LCC2,LCC9,and BT474 cells than in tamoxifen sensitive MCF-7 cells.UCA1 expression was significantly upregulated in MCF-7 cells after treatment with 0.1 μmol/L tamoxifen.UCA1 overexpression enhanced cell viability of MCF-7 cells after tamoxifen treatment,while UCA1 siRNA significantly suppressed viability of LCC9 and BT474 cells after tamoxifen treatment.In MCF-7 cells,compared with vector control+tamoxifen group,the average cell colony number and colony size of the UCA1+tamoxifen group was 19.0% more and 29.0% larger respectively,while the proportions of the cells in G1 phase and in S phase were 7.3% lower and 6.7% higher respectively.In BT474 cells,compared with siRNA control+tamoxifen group,the average cell colony number and colony size of the si-UCA1+tamoxifen group were 54.0% less and 42.0% smaller respectively,while the proportions of the cells in G1 phase and in S phase were 9.0% higher and 6.2% lower respectively.UCA1 directly interacted with miR-18a and reduced its expression in ER positive breast cancer cells.Knockdown of miR-18a increased viability of MCF-7 cells after tamoxifen treatment,while miR-18a overexpression significantly reduced viability of BT474 cells after tamoxifen treatment.In MCF-7 cells,compared with miRNA inhibitor control+tamoxifen group,the average cell colony number and colony size of the miR-18a inhibitor+tamoxifen group were 15.0% more and 33.0% larger respectively,while the proportions of the cells in G1 phase and in S phase were 8.8% lower and 5.3% higher respectively.In BT474 cells,compared with miRNA control+tamoxifen group,the average cell colony number and colony size of the miR-18a mimics+tamoxifen group were 47.0% less and 25.0% smaller respectively,while the proportions of the cells in G1 phase and in S phase were 13.3% higher and 7.9% lower respectively.Conclusion: UCA1 can increase tamoxifen resistance of ER positive breast cancer cells via competitively inhibiting of miR-18a.
3.Clinical Study of Direct-covering Pancreaticojejunostomy with Remaining Jejunal Mucosa
Qian QIN ; Libin WANG ; Hong LI ; Aihui LI ; Shilong TANG ; Jie OUYANG ; Shuqin XIE ; Zhuohong LIANG
Chinese Journal of Clinical Oncology 2010;37(1):52-55
Objective:To investigate and summarize the procedures of direct-covedng pancreaticojejunostomy with remaining jejunal mucosa in pancreaticoduodenectomy and to analyze the incidence of pancreatic fistula and other postoperative complications.Methods:A total of 21 patients were treated with pancreaticoduodenectomy between May 2005 and June 2009.During the surgery,we dissected 3cm long remnant of the pancreas out of ambient tissues.Near the 2.0-3.0cm of the pancreatic remnant.we fixed partial posterior wall with the full-thickness jejunum without mucosa destroyed by interrupted suture,and then pushed the remnant into the jejunum and fixed the anterior wall.Finally,at the 1.0cm of the panceratic remnant,we binded the iejunum to surround the pancreas through 7-silk sutures.Results:One case was treated with secondary surgery due to bleeding of the pancreatic remnant.The other patients recovered smoothly without pancreatic fistula or other complications.Conclusion:Postoperative pancreatic fistula is related to the texture of pancreas,method of pancreaticojejunostomy,surgical skills and perioperative treatment.Compared with other types of pancreaticojejunostomy,direct-covering pancreaticojejunostomy with remaining jejunal mucosa is simpler.
4.The clinical study of jejunal mucus preserving plus end to end pancreaticoenterostomy
Qian QIN ; Hong LI ; Libin WANG ; Aihui LI ; Shilong TANG ; Yangjie OU ; Zhuohong LIANG ; Shuqin XIE
Journal of Endocrine Surgery 2010;04(3):179-182
Objective To investigate the pancreaticoenterostomy technique using end to end anastomosis of remianing pancreas and jejunum with jejunum mucus preserved. Methods 28 cases underwent pancreatectomy were observed and analyzed from May 2005 to August 2009. There were 26 cases underwent duodenopancreatectomy and 2 cases underwent the pancreatectomy of pancreas body and tail. All cases used the end to end pancreaticoenterostomy, remnant pancreas was directly anastomosed with jejunum without destroy of jejunal mucosa. During the operation, 2.0 cm~2.5 cm long remnant of pancreas was pulled into jejunum without mucosa destroyed. Then, the cut end of the jejunum was fixed on the pancreatic remnant correspondingly by interrupted suture. Finally, a 7-silk suture was used to bind the jejunum and the pancreatic remnant together 1 cm away from the cut surface of the pancreatic remnant. Results 1 case underwent operated again due to bleeding of the pancreatic remnant. 28 patients recovered and discharged from hospital without having the complication of pancreatic fistula. Conclusions Because of the complicated suturation methods, the conventional pancreaticoenterostomy consumes more time. But it still has rather high incidence of pancreatic fistula.The new pancreaticoenterostomy which we used can shorten the operating time and integrity and binding stomas. It is effective to lower the incidence of pancreatic fistula.