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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 | 重组脊髓灰质炎病毒用于治疗复发胶质母细胞瘤(英文)显示文摘Background The prognosis of patients with recurrent World Health Organization(WHO)grade IV malignant glioma is dismal,and there is currently no effective therapy.We conducted a dose-finding and toxicity study in this population of patients,evaluating convection-enhanced,intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera(PVSRIPO).PVSRIPO recognizes the poliovirus receptor CD155,which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor microenvironment.Methods We enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV malignant glioma,confirmed on histopathological testing,with measurable disease(contrast-enhancing tumor of≥1 cm and≤5.5 cm in the greatest dimension).The study evaluated seven doses,ranging between 107 and 1010 50%tissue-culture infectious doses(TCID50),first in a dose-escalation phase and then in a dose-expansion phase.Results From May 2012 through May 2017,a total of 61 patients were enrolled and received a dose of PVSRIPO.Dose level-1(5.0×107TCID50)was identified as the phase 2 dose.One dose-limiting toxic effect was observed;a patient in whom dose level 5(1010TCID50)was administered had a grade 4 intracranial hemorrhage immediately after the catheter was removed.To mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use,dose level 5 was deescalated to reach the phase 2 dose.In the dose-expansion phase,19%of the patients had a PVSRIPO-related adverse event of grade 3 or higher.Overall survival among the patients who received PVSRIPO reached a plateau of 21%(95%confidence interval,11 to 33)at 24 months that was sustained at 36 months.Conclusions Intratumoral infusion of PVSRIPO in patients with recurrent WHO grade IV malignant glioma confirmed the absence of neurovirulent potential.The survival rate among patients who receivedPVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls. | Desjardins A Gromeier M Herndon JE 2nd Beaubier N Bolognesi DP Friedman AH Friedman HS McSherry F Muscat AM Nair S Peters KB Randazzo D Sampson JH Vlahovic G Harrison WT McLendon RE Ashley D Bigner DD | 2018 | 中华神经外科疾病研究杂志2018，17，4： | 2 |
| 3 | Emerging role of caldesmon in cancer:A potential biomarker for colorectal cancer and other cancers显示文摘Colorectal cancer(CRC) is a devastating disease, mainly because of metastasis. As a result, there is a need to better understand the molecular basis of invasion and metastasis and to identify new biomarkers and therapeutic targets to aid in managing these tumors. The actin cytoskeleton and actin-binding proteins are known to play an important role in the process of cancer metastasis because they control and execute essential steps in cell motility and contractility as well as cell division. Caldesmon(CaD) is an actin-binding protein encoded by the CALD1 gene as multiple transcripts that mainly encode two protein isoforms: High-molecular-weight CaD, expressed in smooth muscle, and low-molecular weight CaD(l-CaD), expressed in nonsmooth muscle cells. According to our comprehensive review of the literature, CaD, particularly l-CaD, plays a key role in the development, metastasis, and resistance to chemoradiotherapy in colorectal, breast, and urinary bladder cancers and gliomas, among other malignancies. CaD is involved in many aspects of the carcinogenic hallmarks, including epithelial mesenchymal transition via transforming growth factor-beta signaling, angiogenesis, resistance to hormonal therapy, and immune evasion. Recent data show that CaD is expressed in tumor cells as well as in stromal cells, such as cancerassociated fibroblasts, where it modulates the tumor microenvironment to favor the tumor. Interestingly, CaD undergoes selective tumor-specific splicing, and the resulting isoforms are generally not expressed in normal tissues, making these transcripts ideal targets for drug design. In this review, we will analyze these features of CaD with a focus on CRC and show how the currently available data qualify CaD as a potential candidate for targeted therapy in addition to its role in the diagnosis and prognosis of cancer. | Alya R Alnuaimi Vidhya A Nair Lara J Bou Malhab Eman Abu-Gharbieh Anu Vinod Ranade Gianfranco Pintus Mohamad Hamad Hauke Busch Jutta Kirfel Rifat Hamoudi Wael M Abdel-Rahman | 2022 | World Journal of Gastrointestinal Oncology2022，14，9： | 2 |
| 4 | Calponin 3 promotes invasion and drug resistance of colon cancer cells显示文摘BACKGROUND Calponin 3(CNN3)is an actin-binding protein expressed in smooth muscle and non-smooth muscle cells.It is required for cytoskeletal rearrangement and wound healing.AIM To dissect the role of CNN3 in carcinogenesis with a focus on colon cancer.METHODS A total of 20 cancer cell lines(8 breast,11 colon,and HeLa cervical cancer cell as a positive control for mesenchymal phenotype)and 57 formalin-fixed,paraffinembedded sections from archived sporadic colorectal carcinomas were included in this study.CNN3 expression analysis by western blot or immunohistochemistry was followed by functional analyses.The CNN3 gene was silenced by specific small interfering RNA(commonly known as siRNA),followed by confirmation of the silencing efficiency by western blotting.Then,the silenced cells and control siRNA-transfected cells were analyzed for changes in epithelial and mesenchymal markers,invasion,and response to 5-fluoruracil treatment.We also performed proteomics analysis using a phospho-kinase array-based panel of 45 proteins.RESULTS CNN3 showed positive expression in 6/8 breast and 9/11 colon cancer lines and in HeLa cells.Interestingly,the colorectal adenocarcinoma line SW480 was negative,while the cell line developed from its matching lymph node metastasis(SW620)was positive for CNN3.CNN3 expression was fairly consistent with the metastatic phenotype in colon cancer because it was absent in one other colon cell line from a primary site and expressed in all others.We selected SW620 for subsequent functional analyses.CNN3-silenced SW620 cells showed a reduction in collagen invasion and loss of mesenchymal markers.CNN3 silencing caused an increase in the SW620 colon cancer cell sensitivity to 5-fluorouracil.Phosphokinase array-based proteomics analysis showed that CNN3 silencing in SW620 reduced extracellular signal-regulated kinase,β-Catenin,mutant p53,c-Jun,and heat shock protein 60 activities but increased that of checkpoint kinase 2.CNN3 was expressed in 20/57(35%)colon cancer cases as shown by immunohistochemistry.CNN3 was associated with a decrease in overall survival in colon cancer in silico.CONCLUSION These results show the involvement of CNN3 in lymph node metastasis and resistance to chemotherapy in colon cancer and suggest that significant oncogenic pathways are involved in these CNN3-related actions. | Vidhya A Nair Noura A Al-khayyal Sivaramakrishnan Sivaperumal Wael M Abdel-Rahman | 2019 | World Journal of Gastrointestinal Oncology2019，11，11： | 2 |
| 5 | Expression of a truncated Pasteurella multocida toxin antigen in Bordetella bronchiseptica显示文摘 | Rajeev S Nair R V Kania SA Bemis D A | 2003 | Vet Microbiol2003，94，4： | 1 |
| 6 | Application of k0- based INAA method in the studies of rare earth and other elements in manganese nodules from Indian Ocean 显示文摘 | Dutta K charya R Nair A G C etal | 2005 | Journal of Nuclear and Radiochemical Sciences2005，6，： | 1 |
| 7 | One-pot synthesis of 2,4-benzodiazepin-l-ones using benzotriazole methodology显示文摘 | Katrizky A R Nair S K | 2002 | J Org Chem2002，67，23： | 1 |
| 8 | Cardiac tumours:diagnosis and management显示文摘 | Butany J Nair V Naseemuddin A | 2005 | Lancet Oncol2005，6，4： | 1 |
| 9 | Genetic characterization of 2006 - 2008 isolates of chikungunya virus from Kerala, South Indi- a,by whole genome sequence analysis显示文摘 | Sreekumar E Issac A Nair S | 2010 | Virus Genes2010，40，1： | 1 |
| 10 | NF-κB is constitutively activated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the human uterine cervix显示文摘 | Nair A Venkatraman M Maliekal TT | 2003 | Oncogene2003，22，： | 1 |
| 11 | Selective removal of impulse noise based on homogeneity level information显示文摘 | Pok G Liu J C Nair A S | 2003 | IEEE Trans on Image Processing2003，12，1： | 1 |
| 12 | Estrogen stimulates microglia and brain recovery from hypoxia-ischemia in normoglycemic but not diabetic female mice 显示文摘 | Zhang L Nair A Krady K | 2004 | J Clin Invest2004，113，1： | 1 |
| 13 | Biocompatibility of b-tricalcium phosphate root replicas in porcine tooth extraction sockets-A correlative histological,ultrastructural,and Xray microanalytical pilot study显示文摘 | Nair P N R Luder H U Maspero F A | 2006 | J Biomater Appl2006，20，： | 1 |
| 14 | Adsorption and Photocatalytic Oxidation of Acetone on TiO2 :An in Situ Transmission FT-IR Study显示文摘 | El-Maazawi M Finken A N Nair A B | 2000 | Catal2000，191，： | 1 |
| 15 | Jaw lift causes less laryngeal in- terference during lightwand-guided intubation than combined jaw and tongue traction applied by single operator显示文摘 | Goneppanavar U Nair A Kini G | 2011 | In J Anaesth2011，55，2： | 1 |
| 16 | Clinical, diagnostic, and management per- spectives of aortic dissection显示文摘 | Khan I A Nair C K | 2002 | Chest2002，122，1： | 1 |
| 17 | Injectable hydrogels for bone and cartilage repair 显示文摘 | A:nini A A Nair L S | 2012 | Biomed Mater2012，7，02： | 1 |
| 18 | Fine Structure Constant Defines Visual Transparency of Graphene显示文摘 | Nair R R Blake P Grigorenko A N | 2008 | Science2008，320，5881： | 1 |
| 19 | Global association of air pollution and heart failure: a systematic review and meta-analysis显示文摘 | Anoop SV Shah Jeremy P Langrish Harish Nair David A McAllister Amanda L Hunter Ken Donaldson David E Newby Nicholas L Mills | 2013 | The Lancet2013，，： | 1 |
| 20 | Confronting the stigma of epilepsy显示文摘 | Thomas SV Nair A | 2011 | Ann Indian Acad Neurol2011，14，3： | 1 |
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