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| 1 | Role of AXL in invasion and drug resistance of colon and breast cancer cells and its association with p53 alterations显示文摘AIM To characterize AXL receptor tyrosine kinase(AXL)expression in relationship to tumor protein P53(TP53gene,p53 protein)and its role in tumor invasion and response to therapy.METHODS We used 14 cell lines,including 3 isogenic pairs carrying mutant/knockout p53,to gain insight into the relationship between AXL and TP53.These included HCT116,HCT116.p53 mutant,RKO,and RKO.p53-/-lines(all from colon cancers)as well as breast cancer cell lines MCF7 and 1001(MCF7-p53 mutant clone).He La cell line was used as a positive control for epithelial to mesenchymal transition(EMT).AXL expression was determined by Western blotting using rabbit monoclonal antibody clone C89E7.AXL si RNA silencing was performed and followed by collagen invasion assay.Cell viability analysis using the sulforhodamine B assay and the invasion assay were performed after exposure to chemotherapeutic agents(doxorubicin for breast cancer cells;5FU or irinotecan for colon cancer cells).RESULTS We showed that the introduction of p53 mutations or knockout increased expression levels of AXL in isogenic cells compared to the matching p53 wild-type parental cells.Overall,we found a trend for correlation between the potential EMT candidate AXL,p53 alterations,and EMT markers in colorectal and breast cancers.The expression of AXL in RKO cells,a rare colon cancer cell line with inactive Wnt signaling,suggests that the AXL oncogene might provide an alternative genetic pathway for colorectal carcinogenesis in the absence of Wnt signaling activation and TP53 mutation.AXL silencing in the TP53 mutant isogenic cell lines 1001,HCT116.p53 mutant and RKO.P53-/-was>95%efficient and the silenced cells were less invasive compared to the parental TP53 wild-type cells.AXL silencing showed a subtle trend to restore colon cancer cell sensitivity to5FU or irinotecan.Importantly,AXL expressing cells developed more invasive potential after exposure to chemotherapy compared to the AXL-silenced cells.CONCLUSION AXL is influenced by p53 status and could cause the emergence of aggressive clones after exposure to chemotherapy.These findings could have applications in cancer management. | Wael M Abdel-Rahman Noura A Al-khayyal Vidhya A Nair S R Aravind Maha Saber-Ayad | 2017 | World Journal of Gastroenterology2017，23，19： | 7 |
| 2 | Rivaroxaban versus warfarin in nonvalvular atrial fibrillation显示文摘 | Patel M R Maha ffey K W G ar g J | 2011 | N Engl J Med2011，365，10： | 1 |
| 3 | Displaced pediatric supracondyLarhumerus:biomechanical analysis of percutaneous pinning techniques显示文摘 | Steven SL Andrew T Maha R | 2002 | Jouurnal of Orthopedics2002，22，4： | 1 |
| 4 | Three cases of macrofollic- ular variant of papillary thyroid carcinoma 显示文摘 | Emad R Maha A Kfoury H K | 2011 | Ann Saudi Med2011，31，6： | 1 |
| 5 | Association of polymorphisms in estrogen and thyroid hormone receptors with thyroid cancer risk 显示文摘 | Maha R Kallel I Charfeddine S | 2009 | J Recept Signal Transdnet Res2009，29，2： | 1 |
| 6 | Three cases of macrofollicu- lar variant of papillary thyroid carcinoma 显示文摘 | Emad R Maha A Kfoury HK | 2011 | Ann Saudi Med2011，31，6： | 1 |
| 7 | Emerging therapies in metastatic castration-sensitive and castration-resistant prostate cancer显示文摘 | MacVicar Gary R Hussain Maha HB | 2013 | Current opinion in oncology2013，25，3： | 1 |
| 8 | Expression of multidrugresistance (MDR) proteins and in vitro drug resistance in acuteleukemias显示文摘 | Fazlina N Maha A Jamal R | 2007 | Hematolc^y2007，12，1： | 1 |
| 9 | Manual mid-stromal dissection as a low risk procedure to stabilize mild to moderate progressive keratoconus显示文摘Background:To evaluate the efficacy of manual mid-stromal dissection in stabilizing progressive keratoconus.Methods:Surgeries were performed in 16 eyes of 14 patients with progressive keratoconus.All eyes were examined before and at 1 day,1 week,1,3,6 and 12 months after surgery,and every 6 months thereafter.Pentacam(simK,Kmax and pachymetry),best corrected visual acuity(BCVA)and subjective refraction were recorded up to the latest follow-up visit(mean follow-up time 6.6±2.4 years).Results:All surgeries were uneventful,and no postoperative complications occurred.Keratometry values(n=15)stabilized in 6/11 eyes(55%)with a preoperative Kmax<60.0 diopter(D),while all eyes>60 D showed continued progression.In 11/15 eyes(73%)pachymetry was unchanged.BCVA with spectacles remained stable in 7/12 eyes(58%)and improved≥2 Snellen lines in 5/12 eyes(42%).BCVA with a contact lens remained stable in 4/9 eyes(44%),improved≥2 Snellen lines in 3/9 eyes(33%)and deteriorated in 2/9 eyes(22%).Conclusions:Manual mid-stromal dissection was effective in 50%of keratoconic corneas with Kmax values<60 D and may be considered in cases ineligible for other interventions such as UV-crosslinking,stromal ring implantation or Bowman layer transplantation.An advantage of the procedure may be that the tissue is unaltered and that no synthetic or biological implant is required. | Rénuka S Birbal Korine van Dijk Jack S Parker Henny Otten Maha Belmoukadim Lisanne Ham Lamis Baydoun Isabel Dapena Gerrit R J Melles | 2018 | Eye and Vision2018，5，1： | 0 |
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