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| 1 | Autophagy inhibition by chloroquine sensitizes HT-29 colorectal cancer cells to concurrent chemoradiation显示文摘AIM:To investigate whether the inhibition of autophagy by chloroquine(CQ)sensitizes rectal tumors to radiation therapy(RT)or concurrent chemoradiation(chemoRT).METHODS:In vitro,HCT-116 and HT-29 colorectal cancer(CRC)cell lines were treated as following:(1)PBS;(2)CQ;(3)5-fluorouracil(5-FU);(4)RT;(5)CQ and RT;(6)5-FU and RT;(7)CQ and 5-FU;and(8)5-FU and CQ and RT.Each group was then exposed to various doses of radiation(0-8 Gy)depending on the experiment.Cell viability and proliferative capacity were measured by3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and clonogenic assays.Clonogenic survivalcurves were constructed and compared across treatment groups.Autophagy status was determined by assessing the LC3-Ⅱto LC3-Ⅰratio on western blot analysis,autophagosome formation on electron microscopy and identification of a perinuclear punctate pattern with GFPlabeled LC3 on fluorescence microscopy.Cell cycle arrest and cell death were evaluated by FACS and AnnexinⅤanalysis.All experiments were performed in triplicate and statistical analysis was performed by the student’s t test to compare means between treatment groups.RESULTS:RT(2-8 Gy)induced autophagy in HCT-116and HT-29 CRC cell lines at 4 and 6 h post-radiation,respectively,as measured by increasing LC3-Ⅱto LC3-Ⅰratio on western blot.Additionally,electron microscopy demonstrated autophagy induction in HT-29 cells24 h following irradiation at a dose of 8 Gy.Drug treatment with 5-FU(25μmol/L)induced autophagy and the combination of 5-FU and RT demonstrated synergism in autophagy induction.CQ(10μmol/L)alone and in combination with RT effectively inhibited autophagy and sensitized both HCT-116 and HT-29 cells to treatment with radiation(8 Gy;P<0.001 and 0.00001,respectively).Significant decrease in clonogenic survival was seen only in the HT-29 cell line,when CQ was combined with RT at doses of 2 and 8 Gy(P<0.5 and P=0.05,respectively).There were no differences in cell cycle progression or Annexin V staining upon CQ addition to RT.CONCLUSION:Autophagy inhibition by CQ increases CRC cell sensitivity to concurrent treatment with 5-FU and RT in vitro,suggesting that addition of CQ to chemoRT improves CRC treatment response. | Caitlin A Schonewolf Monal Mehta Devora Schiff Hao Wu Bruce G Haffty Vassiliki Karantza Salma K Jabbour | 2014 | World Journal of Gastrointestinal Oncology2014，6，3： | 12 |
| 2 | Two-state option pricing: binomial models revisited 显示文摘 | JABBOUR G M KRAMIN M V YOUNG S D | 2001 | Journal of Futures Markets2001，21，11： | 1 |
| 3 | Superovulation of Merino ewes with an ovine pituitary follicle stimulating hormone extract显示文摘 | Jabbour H N Evans G | 1991 | Reprod Fertil Dev1991，3，5： | 1 |
| 4 | Pretransplant positive positron emission tomography/gallium scans predict poor outcome in patients with recurrent/refractory Hodgkin lymphoma 显示文摘 | Jabbour E Hosing C Ayers G | 2007 | Cancer2007，109，12： | 1 |
| 5 | Effect of low - dose dexmedetomidine or clonidine on the charac- teristics of bupivacaine spinal block 显示文摘 | KANAZI G E AOUAD M T JABBOUR KHOURY S I | 2006 | Acta Anaesthesiol Scand2006，50，2： | 1 |
| 6 | Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy 显示文摘 | Jabbour E Garcia-Manero G Batty N | 2010 | Cancer2010，116，16： | 1 |
| 7 | Twice-daily fludarabine and cytarabine combination with or without gentuzumab ozogamicin is effective in patients with relapsed/refractory acute myeloid leukemia, high-rlsk myelodysplastic syndrome, and blast- phase chronic myeloid leukemia 显示文摘 | Jabbour E Garcia-Manero G Cortes J | 2012 | Clin Lymphoma Myeloma Leuk2012，12，4： | 1 |
| 8 | Pretransplant positive positron emission tomography/gallium scans predict poor outcome in patients with recurrent/re- fractory Hodgkin lymphoma 显示文摘 | Jabbour E Hosing C Ayers G | 2007 | Cancer2007，109，： | 1 |
| 9 | Prognostic fac- tors associated with disease progression and overall survival in patients with myelodysplastic syndromes treated with decitabine 显示文摘 | Jabbour E Garcia-Manero G Ravandi F | 2013 | Clin Lymphoma Myeloma Leuk2013，13，2： | 1 |
| 10 | Effect oflow-dose dexmedetomidine or clonidine on the characteristics ofbupivacaine spinal block 显示文摘 | Kanazi G E Aouad M T Jabbour Khoury S I | 2006 | Acta Anaesthesiol Scand2006，50，2： | 1 |
| 11 | Adherence to BCR-ABLinhibitors: issues for CML therapy 显示文摘 | Jabbour E Saglio G Radich J | 2012 | Clin Lymphoma MyelomaLeuk2012，12，4： | 1 |
| 12 | Pretransplant positive positron e- mission tomography/gallium scans predict poor outcome in patients with recurrent/refractory Hodgkin lymphoma 显示文摘 | Jabbour E Hosing C Ayers G | 2007 | Cancer2007，109，12： | 1 |
| 13 | Early response with dasatinib or imatinib in chronic myeloid leukemia:3-year follow-up from a rando- mized phase 3 trial (DASISION) 显示文摘 | Jabbour E Kantarjian HM Saglio G | 2014 | Blood2014，123，4： | 1 |
| 14 | Ran- domized open-label phase Ⅱ study of decitabine in pa- tients with low-or intermediate-risk myelodysplasticsyn- dromes 显示文摘 | Garcia-Manero G Jabbour E Borthakur G | 2013 | Journal of Clinical Oncology2013，31，20： | 1 |
| 15 | Mechanical efficiency during a cycling test is not lower in children with excess body weight and low aerobic fitness显示文摘 | Jabbour G Lambert M O'Loughlin J | 2013 | Obesity (Silver Spring)2013，21，1： | 1 |
| 16 | Stage I of a phase 2 study assessing the efficacy, safety, and tolerability of barasertib (AZDl152) versus low-dose cytosine arabinoside in elderly patients with acute myeloid leukemia 显示文摘 | Kantarjian HM Martinelli G Jabbour E J | 2013 | Cancer2013，119，14： | 1 |
| 17 | Application ofscreen printing in the fabrication of organic light-emittingdevices显示文摘 | Pardo D A Jabbour G E Peyghambarian N | 2000 | Advanced Materials2000，12，17： | 1 |
| 18 | Stage I of a phase 2 study assessing the efficacy, safety, and tolerability of barasertib (AZD1152) versus low-dose cytosine arabinoside in elderly patients with acute myeloid leukemia显示文摘 | Kantarjian HM Martinelli G Jabbour EL | 2013 | Cancer2013，119，14： | 1 |
| 19 | Randomized Open-Label Phase II Study of Decitabine in Patients With Low-or Intermediate-Risk Myelodysplastic Syndromes 显示文摘 | GARCIA-MANERO G JABBOUR E BORTHAKUR G | 2013 | J Clin Oncol2013，，： | 1 |
| 20 | Application of screen printing in the fabrication of organic light-emitting devices 显示文摘 | Pardo D A Jabbour G E & Peyghambarian N | | Adv Mater0，12，： | 1 |
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