Epigallocatechin-3-gallate Enhances Radiation Sensitivity in Colorectal Cancer Cells Through Nrf2 Activation and Autophagy.

BACKGROUND/AIM: Epigallocatechin-3-gallate (EGCG) is a major polyphenolic component of green tea. EGCG plays a potential role in radio-sensitizing cancer cells. The combined effect of EGCG and radiation was investigated in a colorectal cancer cell line, focusing on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) autophagy signalling. MATERIALS AND METHODS: HCT-116 cells were treated with 12.5 µM EGCG for different periods of time, 2 Gy radiation, or both. Cell viability was determined with the WST-8 assay. The number of colonies was determined with the colony formation assay. mRNA expression of LC3 and caspase-9 was analyzed with quantitative real-time polymerase chain reaction. RESULTS: Combination treatment with EGCG and radiation significantly decreased the growth of HCT-116 cells. The number of colonies was reduced to 34.2% compared to the control group. Immunofluorescence microscopy images showed that nuclear translocation of Nrf2 was significantly increased when cells were treated with the combination of EGCG and radiation compared to the control and single-treatment groups. Combined treatment with EGCG and radiation significantly induced LC3 and caspase-9 mRNA expression. CONCLUSION: EGCG increased the sensitivity of colorectal cancer cells to radiation by inhibiting cell proliferation and inducing Nrf2 nuclear translocation and autophagy.

Programmed Cell Death Ligand 1 Expression Is an Independent Prognostic Factor in Colorectal Cancer.

BACKGROUND/AIM: Programmed cell death protein 1 (PD-1)/ programmed cell death ligand 1(PD-L1) axis is associated with immune tolerance via inhibition of T cell activation. The aim of this study was to clarify the significance of PD-1 and PD-L1 expressions and analyze the relationships between PD-1, PD-L1, transforming growth factor-ß (TGF-ß) and Forkhead box P3 (Foxp3) expressions in colorectal cancer (CRC). PATIENTS AND METHODS: A total of 116 patients who underwent curative colectomy for stage II/III CRC were included in the study. PD-1, PD-L1, TGF-ß, and Foxp3 expressions were examined by immunohistochemistry and related to prognostic factors by Kaplan-Meier. RESULTS: PD-1 expression was correlated with PD-L1, TGF-ß, and Foxp3 expressions. Overall survival rates were significantly poorer in the PD-1 and PD-L1-positive groups. Multivariate analysis showed that PD-L1-positive is an independent risk factor. Disease-free survival (DFS) was tended in the PD-L1-positive group. The group with double-positive expression had significantly poorer prognosis. CONCLUSION: PD-1 and PD-L1 expressions were associated with a poor prognosis and correlated with TGF-ß and Foxp3 expressions in patients with CRC.

Usefulness of Virtual 3D image analysis in laparoscopic gastrectomy for trainee surgeons / Шинэ санаа Шинэ нээлт

Background: Laparoscopic gastrectomy has several difficult points including, lymph node dissection and resection of several blood vessels for trainee surgeons. Recently, preoperative evaluation of vasculature based three-dimensional (3D) imaging technique resulted in a significantly improved clinical outcome in abdominal surgery. The aim of this study is to investigate the usefulness of the 3D image in laparoscopic gastrectomy for trainee surgeons. Method: We adopted a multiphase CT protocol to acquire 3 image sets (arterial, portal, and equilibrium phases). 3D-reconstruction of gastric vasculature was made using data from a contrast enhanced MDCT and SYNAPSE VINCENT software. Whole pancreas, spleen, gastric vasculature were extracted from MDCT scans and traced. Thirty three patients, who underwent laparoscopic gastrectomy for gastric cancer during the period between Jan 2013 and May 2014 were examined in this study. Four trainees performed a 19 laparoscopic gastrectomy, while 14 laparoscopic gastrectomy were conducted by the two trainers. The surgical outcomes in both groups and the pattern of gastric vasculatures were evaluated. Result: 3D imaging technique showed a correct positional relationship between the stomach, gastric vessels, pancreas and spleen. Surgical outcome including estimated blood loss, and operative time in trainee group were not significantly different compared to trainer group. 3D imaging technique showed a correct positional relationship between the stomach, gastric vessels, pancreas and spleen. Regarding vascular pattern detected by 3D imaging, the origins of IPA were RGEA in 12 cases (36%), GDA in 8 cases (24%).bifurcation of RGEA and GDA in7 cases (21%), and not detected in 1 case (3%), respectively. The types of confluence of IPV were RGEV in 16 cases (48%), ASPDV in 10 cases (30%), and not detected in 7 cases (21%), respectively. Conclusions: 3D imaging technique might contribute to successful laparoscopic gastrectomy. Preoperative 3D-simulation techniques enabled trainee surgeons to easily and safely perform laparoscopic gastrectomy.

Usefulness of Virtual 3D image analysis in laparoscopic gastrectomy for trainee surgeons / Шинэ санаа Шинэ нээлт

Background: Laparoscopic gastrectomy has several difficult points including,lymph node dissection and resection of several blood vessels for trainee surgeons.Recently, preoperative evaluation of vasculature based three-dimensional (3D)imaging technique resulted in a significantly improved clinical outcome inabdominal surgery. The aim of this study is to investigate the usefulness of the 3Dimage in laparoscopic gastrectomy for trainee surgeons.Method: We adopted a multiphase CT protocol to acquire 3 image sets (arterial,portal, and equilibrium phases). 3D-reconstruction of gastric vasculature wasmade using data from a contrast enhanced MDCT and SYNAPSE VINCENTsoftware. Whole pancreas, spleen, gastric vasculature were extracted from MDCTscans and traced. Thirty three patients, who underwent laparoscopic gastrectomyfor gastric cancer during the period between Jan 2013 and May 2014 wereexamined in this study. Four trainees performed a 19 laparoscopic gastrectomy,while 14 laparoscopic gastrectomy were conducted by the two trainers. Thesurgical outcomes in both groups and the pattern of gastric vasculatures wereevaluated.Result: 3D imaging technique showed a correct positional relationship betweenthe stomach, gastric vessels, pancreas and spleen. Surgical outcome includingestimated blood loss, and operative time in trainee group were not significantlydifferent compared to trainer group. 3D imaging technique showed a correctpositional relationship between the stomach, gastric vessels, pancreas and spleen.Regarding vascular pattern detected by 3D imaging, the origins of IPA were RGEAin 12 cases (36%), GDA in 8 cases (24%).bifurcation of RGEA and GDA in7 cases(21%), and not detected in 1 case (3%), respectively. The types of confluence ofIPV were RGEV in 16 cases (48%), ASPDV in 10 cases (30%), and not detectedin 7 cases (21%), respectively.Conclusions: 3D imaging technique might contribute to successful laparoscopicgastrectomy. Preoperative 3D-simulation techniques enabled trainee surgeons toeasily and safely perform laparoscopic gastrectomy.

Хавдрын үүдэл эсийн зохицуулгад “sonic hedgehog” дохиоллын үүрэг / Шинэ санаа Шинэ нээлт

Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigenic capacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs. METHODS: Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for 14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44, EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJ genes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM). RESULTS: The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathway Ptch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal marker Vimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited. CONCLUSION: EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.

Хавдрын үүдэл эсийн зохицуулгад “sonic hedgehog” дохиоллын үүрэг / Шинэ санаа Шинэ нээлт

Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigeniccapacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs.METHODS:Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44,EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJgenes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM).RESULTS:The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathwayPtch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal markerVimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited.CONCLUSION:EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.