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| 1 | Integrating TYMS, KRAS and BRAF testing in patients with metastatic colorectal cancer显示文摘AIM To investigate the impact of thymidylate synthase(TYMS), KRAS and BRAF in the survival of metastatic colorectal cancer(m CRC) patients treated with chemotherapy. METHODS Clinical data were collected retrospectively from records of consecutive patients with m CRC treated with fluoropyrimidine-based chemotherapy from 1/2005 to 1/2007. Formalin-fixed paraffin-embedded tissues were retrieved for analysis. TYMS genotypes were identified with restriction fragment analysis PCR, while KRAS and BRAF mutation status was evaluated using real-time PCR assays. TYMS gene polymorphisms of each of the 3' untranslated region(UTR) and 5'UTR were classified into three groups according to the probability they have for high, medium and low TYMS expression(and similar levels of risk) based on evidence from previous studies. Univariate and multivariate survival analyses were performed.RESULTS The analysis recovered 89 patients with m CRC(46.1% de novo metastatic disease and 53.9% relapsed). Of these, 46 patients(51.7%) had colon cancer and 43(48.3%) rectal cancer as primary. All patients were treated with fluoropyrimidine-based chemotherapy(5FU or capecitabine) as single-agent or in combination with irinotecan or/and oxaliplatin or/and bevacizumab. With a median follow-up time of 14.8 mo(range 0-119.8), 85 patients(95.5%) experienced disease progression, and 63 deaths(70.8%) were recorded. The 3-year and 5-year OS rate was 25.4% and 7.7% while the 3-year progression-free survival rate was 7.1%. Multivariate analysis of TYMS polymorphisms, KRAS and BRAF with clinicopathological parameters indicated that TYMS 3'UTR polymorphisms are associated with risk for disease progression and death(P < 0.05 and P < 0.03 respectively). When compared to tumors without any del allele(genotypes ins/ins and ins/loss of heterozygosity(LOH) linked with high TYMS expression) tumors with del/del genotype(low expression group) and tumors with ins/del or del/LOH(intermediate expression group) have lower risk for disease progression(HR = 0.432, 95%CI: 0.198-0.946, P < 0.04 and HR = 0.513, 95%CI: 0.287-0.919, P < 0.03 respectively) and death(HR = 0.366, 95%CI: 0.162-0.827, P < 0.02 and HR = 0.559, 95%CI: 0.309-1.113, P < 0.06 respectively). Additionally,KRAS mutation was associated independently with the risk of disease progression(HR = 1.600, 95%CI: 1.011-2.531, P < 0.05). The addition of irinotecan in 1st line chemotherapy was associated independently with lower risk for disease progression and death(HR = 0.600, 95%CI: 0.372-0.969, P < 0.04 and HR = 0.352, 95%CI: 0.164-0.757, P < 0.01 respectively).CONCLUSION The TYMS genotypes ins/ins and ins/LOH associate with worst prognosis in m CRC patients under fluoropyrimidine-based chemotherapy. Large prospective studies are needed for validation of our findings. | Anastasios Ntavatzikos Aris Spathis Paul Patapis Nikolaos Machairas George Peros Stefanos Konstantoudakis Danai Leventakou Ioannis G Panayiotides Petros Karakitsos Anna Koumarianou | 2017 | World Journal of Gastroenterology2017，23，32： | 4 |
| 2 | Lymphoedema following xillary lymph node dissection for breast cancer显示文摘 | Sakorafas G H Peros G Cataliotti L | 2006 | Surg Oncol2006，15，3： | 1 |
| 3 | Lymphedema following axillary lymph node dissection for breast cancer 显示文摘 | Sakorafas GH Peros G Cataliotti L | 2006 | Surg Oncol2006，15，3： | 1 |
| 4 | Asymptomatic cholelithiasis: is cholecystectomy really needed? A critical reappraisal 15 years after the introduction of laparoscopic cholecystectomy 显示文摘 | Sakaorafas GH Milingos D Peros G | 2007 | Dig Dis Sci2007，52，5： | 1 |
| 5 | Lymphedema fol- lowing axillary lymph node dissection for breast cancer显示文摘 | Sakorafas GH Peros G Cataliotti L | 2006 | Surg Oncol2006，15，3： | 1 |
| 6 | Thy- roid nodules: does the suspicion for malignancy really justify the increased thyro- idectomy rates显示文摘 | Sakorafas GH Peros G Farley DR | 2006 | Surg Oncol2006，15，1： | 1 |
| 7 | Abdominal desmoid tumors显示文摘 | Sakorafas GH Nissotakis C Peros G | 2007 | Surg Oncol2007，16，2： | 1 |
| 8 | Recent advances and current controversies in the management of DCIS of the breast显示文摘 | Sakorafas GH Farley DR Peros G | 2008 | Cancer Treatment Rev2008，34，6： | 1 |
| 9 | Angiographic follow- up of traumatic carotid cavernous fistulas treated with endovascular stent graft placement 显示文摘 | Archondakis E Pero G Valvassori L | 2007 | AJNR2007，28，2： | 1 |
| 10 | Lymphoedema following axillary lymph node dissection for breast cancer 显示文摘 | Sakorafas GH Peros G Cataliotti L | 2006 | Surg Oncol2006，15，3： | 1 |
| 11 | Asymptomatic cholelithiasis: ischolecystectomy really needed- A critical reappraisal 15 years afterthe introduction of laparoscopic cholecystectomy显示文摘 | Sakorafas GH Milingos D Peros G | 2007 | Dig Dis Sci2007，52，5： | 1 |
| 12 | Lymphoedema following axillary lymph node dissection for breast cancer显示文摘 | Sakorafas GH Peros G Cataliotti L | 2006 | Surg Oncol2006，15，3： | 1 |
| 13 | Lymphedema following axillary lymph node dissection for breast cancer显示文摘 | Sakorafas GH Peros G Cataliotti L | 2006 | Surg Oncol2006，15，： | 1 |
| 14 | Variability among Vitis vinifera cultivars in micropropagation, organogenesis and antibiotic sensitivity显示文摘 | Peros J P Torregrosa Berger G | 1998 | Journal of Experimental Botany1998，49，319： | 1 |
| 15 | Prognostic significance of p53 and Ki67 proteins ex-pression ingreek gastric cancer patients显示文摘 | TZANAKIS N E PEROS G’KARAKITSOS P | 2009 | Acta ChirBelg2009，109，： | 1 |
| 16 | Lymphedema following axillary lymph node dissection for breast cancer 显示文摘 | Sakorafas GH Peros G Cataliotti L | 2006 | Surg Oncol2006，15，3： | 1 |
| 17 | Angiographic follow-up of traumatic carotid cavernous fistulas treated with endovascular stent graft placement显示文摘 | ARCHONDAKIS E PERO G VALVASSORI L | 2007 | AJNR Am J Neuroradiol2007，28，2： | 1 |
| 18 | Lymphoedema following axillary lymph node dissection for breast cancer显示文摘 | Sakorafas GH Peros G Cataliotti L | 2006 | Surg Oncol2006，15，3： | 1 |
| 19 | Preliminary information on feeding and growth of pompano, Trachinotus ovatus(Linnaeus 1758) (Pisces; Car- angidae) in captivity显示文摘 | Pero T Nikga G Valter K | 2004 | Aquaculture International2004，12，45： | 1 |
| 20 | Analysis of tobacco for the Alternaria toxins,Alternariol and Alternariol monomethyl ether显示文摘 | Lucas G B Pero R W Snow J P Harlan D | 1971 | Journal of Agricultural and Food Chemistry1971，19，6： | 1 |
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