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| 1 | Loss of disabled-2 expression is an early event in esophageal squamous tumorigenesis显示文摘AIM: Disabled-2 (DAB2) is a candidate tumor-suppressor gene identified in ovarian cancer that negatively influences mitogenic signal transduction of growth factors and blocks ras activity. In a recent study, we observed down-regulation of DAB2 transcripts in ESCCs using cDNA microarrays. In the present study, we aimed to determine the clinical significance of loss of DAB2 protein in esophageal tumorigenesis, hypothesizing that DAB2 promoter hypermethylation-mediated gene silencing may account for loss of the protein. METHODS: DAB2 expression was analyzed by immunohistochemistry in 50 primary esophageal squamous cell carcinomas (ESCCs), 30 distinct hyperplasia, 15 dysplasia and 10 non-malignant esophageal tissues. To determine whether promoter hypermethylation contributes to loss of DAB2 expression in ESCCs, methylation status of DAB2 promoter was analyzed in DAB2 immuno-negative tumors using methylation-specifi c PCR. RESULTS: Loss of DAB2 protein was observed in 5/30 (17%) hyperplasia, 10/15 (67%) dysplasia and 34/50 (68%) ESCCs. Significant loss of DAB2 protein was observed from esophageal normal mucosa to hyperplasia, dysplasia and invasive cancer (Ptrend < 0.001). Promoter hypermethylation of DAB2 was observed in 2 of 10 (20%) DAB2 immuno-negative ESCCs. CONCLUSION: Loss of DAB2 protein expression occurs in early pre-neoplastic stages of development of esophageal cancer and is sustained down the tumorigenic pathway. Infrequent DAB2 promoter methylation in ESCCs suggests that epigenetic genesilencing is only one of the mechanisms causing loss of DAB2 expression in ESCCs. | Kumar Anupam Chatopadhyay Tusharkant Siddhartha Datta Gupta Ralhan Ranju | 2006 | World Journal of Gastroenterology2006，12，37： | 11 |
| 2 | siRNA-mediated downregulation of TC21 sensitizes esophageal cancer cells to cisplatin显示文摘AIM:To determine the functional significance of TC21 in esophageal squamous cell carcinoma(ESCC).METHODS:TC21 siRNA transfection was carried out using Hyperfectamine to knock down TC21,and transcripts were analyzed by reverse transcription-polymerase chain reaction and protein by Western blotting.We demonstrated the effect of TC21 downregulation of cell signaling in esophageal cancer cells by assessing the phosphorylation status of its downstream targets,phosphoinositide 3-kinase(PI3K),phosphatase and tensin homolog(PTEN),protein kinase B(pAkt),nuclear factor-B(NF-B) and cyclinD1 using specific antibodies.Cell survival analysis after cisplatin treatment was carried out by cell viability assay and cell cycle analysis using flow cytometry.RESULTS:TC21 knockdown in human ESCC cell line TE13 cells,showed only a marginal increase(14.2%) in cell death compared with control cells.The expressions of the signaling proteins PI3K and pAkt,transcription factor NF-B,and cell cycle protein cyclin D1 were markedly decreased in response to TC21 downregulation,whereas the level of pPTEN,an antagonist of PI3K,was increased.In addition,we evaluated the potential of TC21 as a putative target for sensitizing ESCC cells to the chemotherapeutic agent cisplatin.Increased cell death(38.4%) was observed in cells treated with cisplatin after TC21 knockdown compared with cells which were treated with cisplatin alone(20% cell death).CONCLUSION:Results suggest that TC21 mediates its effects via the PI3K-Akt pathway,NF-B and cyclin D1,and enhances chemoresistance in esophageal cancer cells. | Md.Raghibul Hasan Shyam Singh Chauhan Rinu Sharma Ranju Ralhan | 2012 | World Journal of Gastroenterology2012，18，31： | 3 |
| 3 | Induction of apoptosis by abrogation of HSP70 expression in human oral cancer cells显示文摘 | Kaur J Kaur J Ralhan R | 2000 | Cancer2000，85，： | 1 |
| 4 | ldentification of a highly reactive sulphydryl group in human placental glutathione transferase by a site-directed fluorescent reagent显示文摘 | Lo Bello M Nath N Ralhan R | 1990 | FEBS Let1990，263，4： | 1 |
| 5 | 14-3-3 zeta as novel molecular target for cancer therapy显示文摘 | Matta A Siu KW Ralhan R | 2012 | Expert Opin Ther Targets2012，16，5： | 1 |
| 6 | Replication of association between a common variant near melanocortin-4 receptor gene and obesity-related traits in Asian Sikhs 显示文摘 | Been LF Nath SK Ralhan SK | 2010 | Obesity ( Silver Spring)2010，18，2： | 1 |
| 7 | Discovery and verification of head and neck cancer bi- omarkers by differential protein expression analysis u- sing iTRAQ labeling, multidimensional liquid chro- matography, and tandem mass spectrometry显示文摘 | RALHAN R DESOUZA L V MATTA A | 2008 | Mol Cell Proteomics2008，7，： | 1 |
| 8 | Serem p53 antibodies in patients with oral lesions:Correlation with p53/HSP70 complexes显示文摘 | Kaur J Srivastava A Ralhan R | 1997 | Int J Cancer1997，74，6： | 1 |
| 9 | Nuclear and cytoplasmic accumula- tion of Ep-ICD is frequently detected in human epithelial cancers 显示文摘 | Ralhan R He HC So AK | 2010 | PLoS One2010，5，14： | 1 |
| 10 | Induction of apoptosis by abrogation of HSP70 expression in human oral cancer cells显示文摘 | Kaur J Kaur J Ralhan R | 2000 | Int J Cancer2000，85，1： | 1 |
| 11 | Soluble and Membranous Vascular Endothelial Growth Factor Receptor-2 in Pregnancies Complicated by Pre-Eclampsia显示文摘 | Tripathi R Rath G Ralhan R | 2009 | Yonsei Med J2009，50，5： | 1 |
| 12 | Discovery and verification of head and neck cancer biomarkers by differential protein expression analysisusing iTRAQ labeling,multidimensional liquid chromatography,and tandem mass spectrometry显示文摘 | Ralhan R Desouza LV Matta A | 2008 | Mol Cell Proteomics2008，7，6： | 1 |
| 13 | EpCAM nuclear localization iden- tifies aggressive thyroid cancer and is a marker for poor prog- nosis显示文摘 | Ralhan R Cao J Lim T | 2010 | BMC Cancer2010，10，1： | 1 |
| 14 | Hyperthemia potentiates antitumor effect of thermosensitive liposome encapsulated mephalan and radiation in murine melanoma显示文摘 | Ralhan R | 1997 | Tumour Biol1997，18，4： | 1 |
| 15 | Impact of nine common type 2 diabetes risk polymor- phisms in Asian Indian Sikhs:PPARG2 (Pro12Ala), IGF2BP2, TCFTL2 and FTO variants confer a significant risk显示文摘 | Sanghera D K Ortega L Han S Singh J Ralhan S K Wander G S | 2008 | BMC Med Genet2008，9，： | 1 |
| 16 | Circulating p53 antibodies, p53 gene mutational profile and product accumulation in esophageal squamous cell carcinoma in India显示文摘 | Ralhan R Arora S Chattopadhyay TK | 2000 | Int J Cancer2000，85，6： | 1 |
| 17 | EpCAM nuclear localizationidentifies aggressive thyroid cancer and is a marker for poorprognosis显示文摘 | Ralhan R Cao J Lim T | 2010 | BMC Cancer2010，10，： | 1 |
| 18 | Small interfering RNA targeting 14-3-3ζincreases efficacy of chemotherapeutic agents in head and neck cancer cells显示文摘 | Matta A De Souza LV Ralhan R | 2010 | Mol Cancer Ther2010，9，10： | 1 |
| 19 | Induction of apoptosis by abrogation of HSP70 expression in human oral cancer cells显示文摘 | Kaur J Kaur J Ralhan R | 2000 | Int J Cancer2000，85，1： | 1 |
| 20 | Establishment and characterization of a cell line from smokeless tobacco associated oral squamous cell carcinoma显示文摘 | KAUR J RALHAN R | 2003 | Oral Oncol2003，39，8： | 1 |
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