Effect of quercetin on apoptosis of PANC-1 cells.

PURPOSE: To investigate the chemotherapeutic effect of quercetin against cancer cells, signaling pathway of apoptosis was explored in human pancreatic cells. METHODS: Various anticancer drugs including adriamycin, cisplatin, 5-fluorouracil (5-FU) and gemcitabine were used. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphe-nyltetra zolium bromide assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole nuclei staining and flow cytometry in PANC-1 cells treated with 50 µg/mL quercetin for 24 hours. Expression of endoplas mic reticulum (ER) stress mediators including, Grp78/Bip, p-PERK, PERK, ATF4, ATF6 and GADD153/CHOP proteins were measured by Western blot analysis. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. Quercetin induced the apoptosis of PANC-1, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G0/G1 fraction of cell cycle increase. But not adriamycin, cisplatin, gemcitabine, and 5-FU. PANC-1 cells were markedly sensitive to quercetin. RESULTS: Treatment with quercetin resulted in the increased accumulation of intracellular Ca(2+) ion. Treatment with quercetin also increased the expression of Grp78/Bip and GADD153/CHOP protein and induced mitochondrial dysfunction. Quercetin exerted cytotoxicity against human pancreatic cancer cells via ER stress-mediated apoptotic signaling including reactive oxygen species production and mitochondrial dysfunction. CONCLUSION: These data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents.

Optimal timing of surgery after neoadjuvant chemoradiation therapy in locally advanced rectal cancer.

PURPOSE: The optimal time between neoadjuvant chemoradiotherapy (CRT) and surgery for rectal cancer has been debated. This study evaluated the influence of this interval on oncological outcomes. METHODS: We compared postoperative complications, pathological downstaging, disease recurrence, and survival in patients with locally advanced rectal cancer who underwent surgical resection <8 weeks (group A, n = 105) to those who had surgery ≥8 weeks (group B, n = 48) after neoadjuvant CRT. RESULTS: Of 153 patients, 117 (76.5%) were male and 36 (23.5%) were female. Mean age was 57.8 years (range, 28 to 79 years). There was no difference in the rate of sphincter preserving surgery between the two groups (group A, 82.7% vs. group B, 77.6%; P = 0.509). The longer interval group had decreased postoperative complications, although statistical significance was not reached (group A, 28.8% vs. group B, 14.3%; P = 0.068). A total of 111 (group A, 75 [71.4%] and group B, 36 [75%]) patients were downstaged and 26 (group A, 17 [16.2%] and group B, 9 [18%]) achieved pathological complete response (pCR). There was no significant difference in the pCR rate (P = 0.817). The longer interval group experienced significant improvement in the nodal (N) downstaging rate (group A, 46.7% vs. group B, 66.7%; P = 0.024). The local recurrence (P = 0.279), distant recurrence (P = 0.427), disease-free survival (P = 0.967), and overall survival (P = 0.825) rates were not significantly different. CONCLUSION: It is worth delaying surgical resection for 8 weeks or more after completion of CRT as it is safe and is associated with higher nodal downstaging rates.

Feasibility and impact on surgical outcomes of modified double-stapling technique for patients undergoing laparoscopic anterior resection.

BACKGROUND: Anastomotic leakage is a major cause of postoperative morbidity and mortality in the treatment of colorectal cancer. The aim of this study was to investigate the modified double-stapling technique (MDST), as an alternative for conventional double-stapling technique (DST), and whether it could reduce the anastomotic leakage rate in laparoscopic anterior resection (Lapa-AR). STUDY DESIGN: Between March 2009 and October 2010, a total of 189 patients who underwent Lapa-AR for the treatment of adenocarcinoma of the sigmoid colon or rectosigmoid colon were divided into the MDST group (n = 95) and the DST group (n = 94) according to the anastomotic technique. Data were analyzed retrospectively. Morbidity and anastomotic leakage rate were compared between the two groups. RESULTS: Patient demographics, preoperative comorbidity, tumor size, stage, and operative details were comparable between the two groups. There was no difference in operation time between the two groups. The overall complication rate was significantly lower in the MDST group than in the DST group (3.2 vs. 10.6 %, p = 0.042), including anastomotic leakage rate (0 vs.4.6 %, p = 0.029). The anastomotic technique was the only factor associated with anastomotic leakage in univariate analysis. CONCLUSIONS: Our comparative study demonstrates MDST to have better short-term outcome in reducing anastomotic leakage compared with DST. This technique could be an alternative approach to maximize the patients' benefit in laparoscopic anterior resection.