Effect of quercetin on apoptosis of PANC-1 cells / 대한외과학회지

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 microg/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 Ca2+ 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 / 대한외과학회지

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 or =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.

Hepatoid Adenocarcinoma of the Stomach Misconceived as a Primary Liver Tumor

Hepatoid adenocarcinomas of the stomach are gastric carcinomas with both adenocarcinomatous and hepatocellular differentiations. The tumor was characterized by high serum alpha-fetoprotein (AFP) levels. A 73-year-old male patient was admitted to the hospital with abdominal pain. Gastrofiberscopy revealed a gastric tumor occupying the antrum and pylorus. Radical subtotal gastrectomy was done and the result of biopsy was poorly differentiated adenocarcima of stomach and stage 3B. At postoperation 8 month, AFP was elevated and liver mass was detected on CT. Right extended hepatectomy was done under the impression of primary liver tumor. But, the biopsy revealed metastatic hepatoid adenocarcinoma of the stomach. Re-examination of the resected stomach was done and the result was hepatoid adenocarcinoma of the stomach. Two months later, after the hepatic resection, multiple metastases developed. This type of tumor has frequent early liver metastasis and poor prognosis. Therefore, early diagnosis and more careful investigation for liver metastasis are recommended.

The Prognostic Value of the S-phase Fraction and Ki-67 Expression in Early Breast Cancer

PURPOSE: The aim of this study was to compare the S-phase fraction (SPF) and Ki-67 with other biologic factors, and to assess the prognostic value of Ki-67 and SPF in 108 breast cancer patients. MEHOODS: The SPF and Ki-67 level were determined in formalin-fixed, paraffin-embedded tissue specimens from 108 patients with early breast cancer who underwent surgery between January 1997 and December 2000 at the Wonkwang University Hospital. The clinicopathological characteristics of the early breast cancer such as the tumor size, node status, histological grade, hormone receptor, various tumor markers and cancer recurrence were compared with the SPF and Ki-67 values. RESULTS: The median SPF was 9.03% (range 0~43%). The SPF correlated with CD31 (P=0.020) and DNA diploidy (P=0.000). Ki-67 correlated with the histological grade (P= 0.010) and p53 (P=0.035). No correlation was found between the SPF and Ki-67. Eight cases recurred during the follow-up period. Strong expression of Ki-67, p53, DNA aneuploidy and a young age were correlated with recurrence (P=0.001, P=0.029, P=0.021 and P=0.002, respectively). However, the SPF was not related to recurrence. CONCLUSION: In early breast cancer, Ki-67 expression is correlated with the histological grade and p53 expression. In addition, strong Ki-67 expression is associated with a recurrence. Further studies regarding the prognostic significance of the proliferation markers, such as Ki-67 and SPF, will be needed to confirm these results.