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Dr.
Stephen J. Meltzer is Professor of Medicine and Oncology at
the Johns
Hopkins University, Department of Medicine,
Gastroenterology Division. He is also
Director
of the GI Early Detection Biomarkers Laboratory.
His research
interests concern several areas: gastrointestinal cancer and precancer biomarker
discovery, development and validation; genomics, epigenomics and
bioinformatics; early detection of cancer; outcomes research in
cancer and precancer; risk stratification prediction in cancer and precancer; Barrett's esophagus; inflammatory bowel
disease-associated cancer; liver cancer; and gastric cancer.
After
receiving his degree in Medicine at the State University of New York at Buffalo Medical School, Dr. Meltzer
did his internal medicine internship at Tulane University in New
Orleans, LA and his
internal medicine residency at the University of Texas Medical Branch in Galveston, TX.
He did a split GI fellowship at the University of
Colorado, Denver, CO and
at Lenox Hill Hospital,
New York, NY. He did his molecular biology
postdoctoral training, then became an Assistant Professor
in Residence at UCLA Center for
the Health Sciences in 1987. Prior to joining the
faculty at Johns Hopkins in 2006, he was Professor of Medicine and
Pharmacology, Founder and Head of the Aerodigestive Cancer/Biomarker
Program at the University of Maryland at Baltimore
School of Medicine.
He is an Associate Editor of Cancer Research and a member of the
editorial board of Esophagus as well as of
Bioinformatics and Biology.
He has published 142 original
scientific research articles in high-impact scientific journals. He also has
authored 42
chapters, review articles, editorials, or letters to the editor; 1
book; and 130 abstracts. He has presented a plethora of
invited lectures around the world, all concerning
his principal field
of esophageal and gastrointestinal cancer research. He has been the
recipient of numerous prestigious national and international awards,
including the Robert and Sally D. Funderburg Award in Gastric Cancer
Biology, and is a member of the American Society for Clinical
Investigation.
Models for tumor formation and lymph node metastasis in vivo. Paper on the cover of Gastroenterology. Paper on the cover of Cancer Research. Array-based genome-wide search for novel cancer genes.
Targeted gene therapy of cancer
Promoter methylation biomarker
Serum Proteomics utilizing mass spectrometry techniques
Novel cancer genes (i.e., oncogenes and tumor suppressor genes) are identified by utilizing various microarray platforms designed to detect cancer-specific abnormalities in genomic copy number (CGH), promoter methylation status (CpG), gene expression (mRNA), and microRNA (miR). These array platforms enable the simultaneous analysis of entire genome. The candidate cancer genes are selected based upon the individual- and interplatform correlational array data, existing genetic/proteomic/functional knowledge, and clinicopathological data of the specimens. Then, the selected candidates are further validated in a larger sample cohort using more quantitative methodologies (e.g., quantitative PCR). Finally, the validated novel cancer genes are subjected to the in-depth analyses as potential therapeutic targets and/or diagnostic biomarkers. Top: Gene knock-down by short interfering RNA (siRNA). An ongogene identified in our microarray-based screening was subjected to the target gene knock-down therapy using siRNA. Esophageal cancer cells were transfected with siRNA directed against the target gene (target siRNA) or non-targeting control (control siRNA); (A) Immunofluorescence staining (top) shows the suppression of the target gene protein (red) expression by the target siRNA. Migration assay by Transwell chamber (bottom) shows that a reduced number of cells migrated when target siRNA was transfected. (B) The siRNA-transfected cancer cells were subcutaneously injected to nude mice. In vivo bioluminescence imaging shows that the target siRNA suppressed tumor formation in vivo.
Bottom: Gene overexpression by adeno-associated virus (AAV). A fibrosarcoma cell line was infected with GFP-expressing AAV. The successful expression of GFP by AAV infection is demonstrated in Fluorescence microscope image (left, green signal) and Flow cytometry data(right) DNA methylation and transcriptional regulation: Methylated DNA is closely associated with chromosomal packaging with Histones and transcriptional inactivation DNA methylation in the gene promoter region inhibits the access of transcriptional factors to DNA and, consequently, transcription. In cancer, multiple tumor suppressor genes are known to be inactivated by abnormal promoter methylation (e.g., p16, CDH1, and MLH1).
Tumor methylation status is associated with survival: TAC1 is a promoter methylation target in gastrointestinal tract cancer identified by one of or microarray-based genome-wide search strategy (Mori Y., et al, Gastroenterology, 2007). This Caplan-Meyer plot shows that TAC1 methylation in esophageal squamous cell cancer is a biomarker to indicate poor overall survival. Significantly shorter overall survival was observed for patients positive for the TAC1 promoter methylatior (red plot) than those negative for TAC1 gene promoter methylation (blue plot; mean, 22 months vs. 110 months, p=0.01) Top: Matrix-assisted laser desorption/ionization (MALDI) diagnostic model for Barrett metaplasia. Global protein expression pattern in serum was obtained by MALDI for 60 Barrett metaplasia (B) and 60 normal control (N) patients. A representative composite spectra of MALDI analysis for N and B (left panel). These MALDI spectra were used to construct diagnostic models to detect Barrett metaplasia patients based upon the linear discriminant analysis (LDA). The Receiver-Operator characteristic curve analysis of the developed models demonstrates that the sensitivity and specificity of the best diagnostic scriptsl was 0.90 and 0.90, respectively (right panel, indicated by an read arrow).
Bottom: Isobaric Tag for Relative and Absolute Quantitation (iTRAQ) analysis for biomarker discovery. iTRAQ analysis was performed to identify the differentially expressed serum proteins among various gastrointestinal diseases. Sixteen differentially expressed proteins are listed in this table.
Models for tumor formation and lymph node metastasis in vivo.
Publications:
1. Meltzer SJ,
Korelitz BI. Budd-Chiari Syndrome. Gastroent. Obs. 1985; 4:3-8.
2. Haber CJ, Meltzer SJ, Present DH, Korelitz BI. The nature and
course of pancreatitis caused by 6-mercaptopurine in the treatment
of inflammatory bowel disease. Gastroenterol. 1986; 91:982-986.
3. Meltzer SJ, Goldberg MD. Recurrent pancreatitis caused by
vegetable matter obstruction. Am. J. Gastro., 1986; 81:1091-1092.
4. Meltzer SJ, Goldberg MD, Meltzer RM, Claps F. Appendiceal
obstruction by a toothpick removed at colonoscopy. Am. J. Gastro.
1986; 81:1107-1108.
5. Meltzer SJ, Rotterdam HZ, Korelitz BI. Kaposi’s sarcoma occurring
in association with ulcerative colitis. Am. J. Gastro. 1987;
82:378-381.
6. Meltzer SJ, Ahnen DJ, Battifora H, Yokota J, Cline MJ.
Proto-oncogene abnormalities in colon cancers and adenomatous
polyps. Gastroenterol. 1987; 92:1174-1180.
7. Masuda H, Yokota J, Battifora H, Meltzer SJ, Cline MJ.
Specificity of proto-oncogene amplification in human malignant
diseases. Molec. Biol. Med. 1987; 4:213-227.
8. Meltzer SJ, Korelitz BI. Pancreatitis and duodenopancreatic
reflux in Crohn's disease. J. Clin. Gastro. 1988; 10:555-558.
9. Mallet MK, Mane SM, Meltzer SJ, Needleman SW. C-myc amplification
coexistent with activating c-N-ras point mutation in the
biphenotypic leukemic cell line RED-3. Leukemia 1989; 3:511-515.
10. Present DH, Meltzer SJ, Krumholz MP, Wolke A, Korelitz BI.
6-mercaptopurine in the management of inflammatory bowel disease:
short and long-term toxicity. Ann. Int. Med. 1989; 111:641-649.
11. Meltzer SJ, Zhou D, Weinstein WM. Tissue-specific expression of
c-Ha-ras in premalignant gastrointestinal mucosae. Exper. Mol.
Pathol. 1989; 51:264-274.
12. Meltzer SJ, Mane SM, Wood PK, Johnson LN, Needleman SW.
Sequencing products of the polymerase chain reaction directly,
without purification. Bio Techniques 1990; 8:142-148.
13. Meltzer SJ, Mane SM, Wood PK, Resau JH, Newkirk C, Terzakis JA,
Korelitz BI, Weinstein WM, Needleman SW. Activation of c-Ki-ras in
gastrointestinal dysplasias determined by direct sequencing of
polymerase chain reaction products. Cancer Res. 1990; 50:3627-3630.
14. Mane SM, Meltzer SJ, Gutheil JV, Kapil V, Lee EJ, Schiffer CA,
Needleman SW. Ras gene mutations in acute myeloid leukemia: Analysis
by in vitro amplification and base sequence determination. Genes
Chrom. Cancer 1990; 2:71-77.
15. McDaniel TK, Huang Y, Yin J, Needleman SW, Meltzer SJ. Direct
labeling of PCR products using Klenow fragment. BioTechniques 1991;
11:164-166.
16. Meltzer SJ, Yin J, Huang Y, McDaniel TK, Newkirk C, Iseri O,
Vogelstein B, Resau JH. Reduction to homozygosity involving p53 in
esophageal cancers demonstrated by the polymerase chain reaction.
Proc. Natl. Acad. Sci., USA 1991; 88:4976-4980.
17. McDaniel T, Carbone D, Takahashi T, Chumakov P, Chang EH,
Pirollo KF, Yin J, Huang Y, Meltzer SJ. A polymorphism in intron 6
of p53 detected by digesting PCR products with Msp I. Nucleic Acids
Res. 1991; 19:4796.
18. Boynton RF, Huang Y, Blount PL, Reid BJ, Raskind WH, Haggitt RC,
Newkirk C, Resau JH, Yin J, McDaniel T, Meltzer SJ. Frequent loss of
heterozygosity at the retinoblastoma locus in human esophageal
cancers. Cancer Res. 1991; 51:5766-5769.
19. Greenwald BD, Harpaz N, Yin J, Huang Y, Tong Y, Brown VL,
McDaniel T, Newkirk C, Resau JH, Meltzer SJ. Loss of heterozygosity
affecting the p53, Rb, and MCC/APC tumor suppressor gene loci in
dysplastic and cancerous ulcerative colitis. Cancer Res. 1992;
52:741-745.
20. Boynton RF, Blount PL, Yin J, Brown VL, Huang Y, Tong Y,
McDaniel T, Newkirk C, Resau JH, Haggitt RC, Raskind WH, Reid BJ,
Meltzer SJ. Loss of heterozygosity involving the APC and MCC genetic
loci occurs in the majority of human esophageal cancers. Proc. Natl.
Acad. Sci., USA 1992; 89:3385-3388.
21. D’Amico D, Carbone D, Johnson B, Meltzer SJ, Minna JD.
Polymorphic sites within the MCC and APC loci reveal frequent loss
of heterozygosity in human small cell lung cancer. Cancer Res. 1992;
52:1996-1999.
22. Greenwald BD, Huang Y, Baum R, Meltzer SJ. Barrett's carcinoma
in a 25-year-old man with point mutation of the p53 tumor suppressor
gene. Int. J. Oncol. 1992; 1:271-275.
23. Huang Y, Boynton RF, Blount PL, Silverstein RJ, Yin J, Tong Y,
McDaniel TK, Newkirk C, Resau JH, Sridhara R, Reid BJ, Meltzer SJ.
Loss of heterozygosity involves multiple tumor suppressor genes in
human esophageal cancers. Cancer Res. 1992; 52:6525-6530.
24. Largey JS, Meltzer SJ, Yin J, Norris K, Sauk JJ, Archibald DW.
Loss of heterozygosity of p53 in oral cancers demonstrated by the
polymerase chain reaction. Cancer 1993; 71:1933-1937.
25. Blount PL, Meltzer SJ, Yin J, Huang Y, Krasna MJ, Reid BJ.
Clonal ordering of 17p and 5q allelic losses in Barrett's dysplasia
and adenocarcinoma. Proc. Natl. Acad. Sci., USA 1993; 90:3221-3225.
26. Huang Y, Meltzer SJ, Yin J, Tong Y, Chang EH, Srivastava S,
McDaniel T, Boynton RF, Zou Z-Q. Altered mRNA and unique mutational
profiles of p53 and Rb in human esophageal carcinomas. Cancer Res.
1993; 53:1889-1894.
27. Yin J, Harpaz N, Tong Y, Huang Y, Laurin J, Greenwald BD,
Hontanosas M, Newkirk C, Meltzer SJ. p53 point mutations in
dysplastic and cancerous ulcerative colitis lesions. Gastroenterol.
1993; 104:1633-1639.
28. Rosenblum-Vos LS, Meltzer SJ, Leanna-Cox J, Schwartz S.
Cytogenetic studies in primary cultures of esophageal squamous cell
carcinoma. Cancer Genet. Cytogenet. 1993; 70:127-131.
29. Rhyu M-G, Park W-S, Meltzer SJ. Microsatellite instability
occurs frequently in human gastric carcinoma. Oncogene 1994;
9:29-32.
30. Largey JS, Meltzer SJ, Sauk JJ, Hebert CA, Archibald DW. Loss of
heterozygosity involving the APC gene in oral squamous cell
carcinomas. Oral Surg. Oral Med. Oral Pathol. 1994; 77:260-263.
31. Blount PL, Galipeau PC, Sanchez CA, Neshat K, Levine DS, Yin J,
Suzuki H, Abraham JM, Meltzer SJ, Reid BJ. 17p allelic losses in
diploid cells of patients with Barrett's esophagus who develop
aneuploidy. Cancer Res. 1994; 54:2292-2295.
32. Rhyu M-G, Park W-S, Jung Y-J, Choi S-W, Meltzer SJ. Allelic
deletions of APC/MCC and p53 are frequent late events in human
gastric carcinogenesis. Gastroenterol. 1994; 106:1584-1588.
33. Meltzer SJ, Yin J, Manin B, Rhyu M-G, Cottrell J, Hudson E, Redd
JL, Krasna MJ, Abraham JM, Reid BJ. Microsatellite instability
occurs frequently and in both diploid and aneuploid cell populations
of Barrett's-associated esophageal adenocarcinomas. Cancer Res.
1994; 54:3379-3382.
34. Togawa K, Jaskiewicz K, Takahashi H, Meltzer SJ, Rustgi AK.
Human papillomavirus DNA sequences in esophageal squamous cell
carcinoma. Gastroenterol. 1994; 107:128-136.
35. Huang Y, Yin J, Meltzer SJ. A unique p53 intragenic deletion
flanked by short direct repeats results in loss of mRNA expression
in human esophageal carcinoma. Carcinogenesis 1994; 8:1653-1655.
36. Suzuki H, Harpaz N, Tarmin Y, Yin J, Jiang H-Y, Bell JD,
Hontanosas M, Groisman GM, Abraham JM, Meltzer SJ. Microsatellite
instability in ulcerative colitis-associated colorectal dysplasias
and cancers. Cancer Res. 1994; 54:4841-4844.
37. Harpaz N, Peck AL, Yin J, Fiel I, Hontanosas M, Tong TR, Laurin
JN, Abraham JM, Greenwald BD, Meltzer SJ. p53 protein expression in
ulcerative colitis-associated colorectal dysplasia and carcinoma.
Human Pathol. 1994; 25:1069-1074.
38. Powell S, Papadopoulos N, Kinzler KW, Smolinski K, Meltzer SJ.
Truncating APC gene mutations in the mutation cluster region are
rare in esophageal cancers. Gastroenterol. 1994; 107:1759-1763.
39. Zhou X, Tarmin L, Yin J, Jiang H-Y, Suzuki H, Rhyu M-G, Abraham
JM, Meltzer SJ. The MTS1 gene is frequently mutated in primary human
esophageal tumors. Oncogene 1994; 9:3737-3741.
40. Tarmin L, Yin J, Zhou X, Suzuki H, Jiang H-Y, Abraham JM, Krasna
MJ, Cottrell J, Meltzer SJ. Frequent loss of heterozygosity on
chromosome 9 in adenocarcinoma and squamous cell carcinoma of the
esophagus. Cancer Res. 1994; 54:6094-6096.
41. Tarmin L, Yin J, Harpaz N, Kozam M, Noordzij J, Antonio L, Jiang
H-Y, Cymes K, Chan O, Meltzer SJ. APC gene mutations in ulcerative
colitis-associated dysplasias and cancers versus sporadic colon
neoplasms. Cancer Res. 1995; 55:2035-2038.
42. Balcer-Kubiczek EK, Yin J, Lin K, Harrison GH, Abraham JM,
Meltzer SJ. p53 mutational status and survival of human breast
cancer MCF7 cell variants after exposure to X-rays or fission
neutrons. Radiation Res. 1995; 142:256-262.
43. Zhou X, Suzuki H, Shimada Y, Imamura M, Yin J, Jiang H-Y, Tarmin
L, Abraham JM, Meltzer SJ. Genomic DNA and messenger RNA expression
alterations of the CDKN2B and CDKN2 genes in esophageal squamous
carcinoma cell lines. Genes, Chromosomes & Cancer 1995; 13:285-290.
44. Suzuki H, Zhou X, Yin J, Lei J, Jiang H-Y, Suzuki Y, Abraham JM,
Chan T, Hannon GJ, Mergner WJ, Abraham JM, Meltzer SJ. Intragenic
mutations of p15 and p16 in primary human esophageal cancers. Human
Molec. Genet. 1995; 4:1883-1888.
45. Berg PE, Liu J, Yin J, Rhyu M-G, Frantz CN, Meltzer SJ.
Microsatellite instability is infrequent in neuroblastoma. Cancer
Epidemiology, Biomarkers & Prevention 1995; 4:907-909.
46. Nakagawa H, Zukerberg LR, Togawa K, Meltzer SJ, Nishihara T,
Rustgi AK. Human cyclin D1 oncogene and esophageal squamous cell
carcinoma. Cancer 1995; 76:541-549.
47. Abraham JM, Wang S, Suzuki H, Jiang H-Y, Rosenblum-Vos LS, Yin
J, Meltzer SJ. Esophagin cDNA cloning and characterization: a
tissue-specific member of the small proline-rich protein family that
is not expressed in esophageal tumors. Cell Growth & Different.
1996; 7:855-860.
48. Zhou X, Suzuki H, Lei J, Cole K, Yin J, Suzuki Y, Abraham JM,
Shimada Y, Imamura T, Chan JT, Hannon GJ, Meltzer SJ. Growth
suppression of esophageal cancer cells by p16INK4 and p15INK4B in
vitro. Cancer J. Sci. Am. 1996; 2:221-224.
49. Garrigue Antar L, Souza RF, Vellucci VF, Meltzer SJ, Reiss M.
Loss of transforming growth factor type II receptor gene
expression in human esophageal cancer. Lab. Invest. 1996; 75:263
272.
50. Souza RF, Appel R, Yin J, Wang S, Smolinski KN, Abraham JM, Zou
T-T, Shi Y-Q, Lei J, Cottrell J, Cymes K, Biden K, Simms L, Leggett
B, Lynch PM, Frazier M, Powell SM, Harpaz N, Sugimura H, Young J,
Meltzer SJ. Microsatellite instability in the insulin-like growth
factor II receptor gene in gastrointestinal tumors. Nature Genet.
1996; 14:255-257.
51. Lei J, Zou T-T, Shi Y-Q, Smolinski KN, Yin J, Souza RF, Appel R,
Wang S, Cymes K, Chan O, Harpaz N, Abraham JM, Meltzer SJ.
Infrequent DPC4 gene mutation in esophageal cancer, gastric cancer,
and ulcerative colitis-associated neoplasms. Oncogene 1996;
13:2459-2462.
52. Wilson KT, Ramanujam KS, Mobley HLT, Musselman RF, James SP,
Meltzer SJ. Helicobacter pylori stimulates inducible nitric oxide
synthase expression and activity in macrophages. Gastroenterol.
1996; 111:1524-1533.
53. Balcer-Kubiczek EK, Harrison GH, Zhang X-F, Shi Z-M, Abraham JM,
McCready WA, Ampey III LL, Meltzer SJ, Jacobs MC, Davis CC. Rodent
cell transformation and immediate early gene expression following
60-Hz magnetic field exposure. Envir. Health Perspect. 1996;
104:1188-1198.
54. Meltzer SJ, O'Doherty SP, Frantz CN, Smolinski K, Yin J, Cantor
AB, Liu J, Valentine M, Brodeur GM, Berg PE. Allelic imbalance on
chromosome 5q predicts long-term survival in neuroblastoma. Br. J.
Cancer 1996; 74:1855-1861.
55. Souza RF, Lei J, Yin J, Appel R, Zou T-T, Zhou X, Wang S, Rhyu
M-G, Cymes K, Chan O, Park W-S, Krasna MJ, Greenwald BD, Cottrell J,
Abraham JM, Harpaz N, Meltzer SJ. A transforming growth factor-1
receptor type II mutation occurs in ulcerative colitis-associated
and sporadic colorectal neoplasms. Gastroenterol. 1997; 112:40-45.
56. Simms LA, Zou T-T, Young J, Shi Y-Q, Lei J, Appel R, Rhyu M-G,
Sugimura H, Chevenix-Trench G, Souza RF, Meltzer SJ, Leggett BA.
Apparent protection from instability of repeat sequences in
cancer-related genes in replication error positive gastrointestinal
cancers. Oncogene 1997; 14:2613-2617.
57. Ouyang H, Shiwaku HO, Hagiwara H, Miura K, Abe T, Kato Y, Ohtani
H, Shiiba K, Souza RF, Meltzer SJ, Horii A. The insulin-like growth
factor II receptor gene is mutated in genetically unstable cancers
of the endometrium, stomach, and colorectum. Cancer Res. 1997;
57:1851-1854.
58. Balcer-Kubiczek EK, Meltzer SJ, Han L-H, Zhang X-F, Zhong M-S,
Harrison GH, Qin JT, Abraham JM. Csa-19, a radiation-responsive
human gene, identified by an unbiased two-gel cDNA library screening
method. Oncogene 1997; 14:3051-3058.
59. Souza RF, Yin J, Smolinski KN, Zou T-T, Wang S, Shi Y-Q, Rhyu
M-G, Cottrell J, Abraham JM, Biden K, Simms L, Leggett B, Bova GS,
Frank T, Powell SM, Sugimura H, Young J, Harpaz N, Shimizu K,
Matsubara N, Meltzer SJ. Frequent mutation of the E2F-4 cell cycle
gene in primary human gastrointestinal tumors. Cancer Res. 1997;
57:2350-53.
60. Zou T-T, Lei J, Shi Y-Q, Yin J, Wang S, Souza RF, Smolinski KN,
Greenwald BD, Abraham JM, Harpaz N, Meltzer SJ. FHIT gene
alterations in ulcerative colitis (UC) and esophageal cancer.
Oncogene 1997; 15:101-105.
61. Wang S, Souza RF, Kong D, Yin J, Smolinski KN, Zou T-T, Young J,
Flanders K, Sugimura H, Abraham JM, Meltzer SJ. Deficient
transforming growth factor-1 activation and excessive insulin-like
growth factor II expression in IGFII receptor-mutant tumors. Cancer
Res. 1997; 57:2543-2546.
62. Kong D, Suzuki A, Zou T-T, Sakurada A, Kemp LW, Wakatsuki S,
Yokoyama T, Yamakawa H, Furukawa T, Sato M, Ohuchi N, Sato S, Yin J,
Wang S, Abraham JM, Souza RF, Smolinski KN, Meltzer SJ, Horii A.
PTEN1 is frequently mutated in primary endometrial carcinomas.
Nature Genet. 1997; 17:143-144.
63. Yin J, Kong D, Wang S, Zou T-T, Souza RF, Smolinski KN, Lynch
PM, Frazier M, Hamilton SR, Sugimura H, Powell SM, Young J, Abraham
JM, Meltzer SJ. Mutation of the hMSH3 and hMSH6 mismatch repair
genes in genetically unstable human colorectal and gastric
carcinomas. Human Mutation 1997; 10:474-478.
64. Cawley HM, Meltzer SJ,* de Benedetti VMG, Hollstein MC,
Muehlbauer K-R, Liang L, Bennett WP, Souza RF, Greenwald BD,
Cottrell J, Salabes A, Bartsch H, Trivers GE. Anti-p53 antibodies in
Barrett’s esophagus or esophageal carcinoma patients can predate
cancer diagnosis. Gastroenterol. 1998; 115:19-27. * = co-first
author
65. Wilson KT, Fu S, Ramanujam KS, Meltzer SJ. Increased expression
of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett’s
esophagus and associated adenocarcinomas. Cancer Res. 1998;
58:2929-2934.
66. Dolan K, Garde J, Gosney J, Sissons M, Wright T, Kingsnorth AN,
Walker SJ, Sutton R, Meltzer SJ, Field JK. Allelotype analysis of
oesophageal adenocarcinoma: loss of heterozygosity occurs at
multiple sites. Br. J. Cancer 1998; 78:950-957.
67. Simms LA, Radford-Smith G, Biden KG, Buttenshaw R, Cummings M,
Jass JR, Young J, Meltzer SJ, Leggett BA. Reciprocal relationship
between the tumor suppressors p53 and BAX in primary colorectal
cancers. Oncogene 1998; 17:2003 2008.
68. Zou T, Fleisher AS, Kong D, Yin J, Souza RF, Wang S, Smolinski
KN, Abraham JM, Meltzer SJ. Sequence alterations of IGFBP-3 in
neoplastic and normal gastrointestinal tissues. Cancer Res. 1998;
58:4802-4804.
69. Balcer-Kubiczek EK, Zhang XF, Han LH, Harrison GH, Davis CC,
Zhou XJ, Ioffe V, McCready WA, Abraham JM, Meltzer SJ. BIGEL
analysis of gene expression in HL60 cells exposed to X rays or 60 Hz
magnetic fields. Radiation Res. 1998; 150:663-672.
70. Dunn J, Garde J, Dolan K, Gosney JR, Sutton R, Meltzer SJ, Field
JK. Multiple target sites of allelic imbalance on chromosome 17 in
Barrett’s oesophageal cancer. Oncogene 1999; 18:987-994.
71. Biden K, Simms L, Cummings M, Buttenshaw R, Schoch E, Searle J,
Gobe G, Jass J, Meltzer SJ, Leggett BA, Young J. Expression of Bcl 2
protein is decreased in colorectal adenocarcinomas with
microsatellite instability. Oncogene 1999; 18:1245 1249.
72. Fleisher AS, Esteller M, Wang S, Tamura G, Suzuki H, Yin Y, Zou
T-T, Abraham JM, Kong D, Smolinski KN, Shi Y-Q, Rhyu M-G, Powell SM,
James SP, Wilson KT, Herman JG, Meltzer SJ. Hypermethylation of the
hMLH1 gene promoter in human gastric cancers with microsatellite
instability. Cancer Res. 1999; 59:1090-1095.
73. Fu S, Ramanujam KS, Wong A, Fantry GT, Drachenberg CB, James SP,
Meltzer SJ, Wilson KT. Increased expression and cellular
localization of inducible nitric oxide synthase and cycloxygenase-2
in Helicobacter pylori gastritis. Gastroenterol. 1999;
116:1319-1329.
74. Yin J, Harpaz N, Souza RF, Zou T, Kong D, Wang S, Leytin AL,
Medalie NS, Smolinski KN, Abraham JM, Fleisher AS, Meltzer SJ. Low
prevalence of the APC I1307K sequence in patients with inflammatory
bowel disease. Oncogene 1999; 18:3902-3904.
75. Jass JR, Biden KG, Cummings M, Simms LA, Walsh M, Schoch E,
Meltzer SJ, Wright C, Searle J, Young J, Leggett BA.
Characterization of a subtype of colorectal cancer combining
features of the suppressor and mild mutator pathways. J. Clin.
Pathol. 1999; 52:455-460.
76. Souza RF, Wang S, Thakar M, Grubb J, Smolinski KN, Yin J, Zou
T-T, Kong D, Gable CA, Sly WS, Abraham JM, Toretsky JA, Meltzer SJ.
Expression of the wild-type insulin-like growth factor II receptor
gene suppresses growth and causes death in colorectal carcinoma
cells. Oncogene 1999; 18:4063-4068.
77. Sheikh MS, Huang Y, Fernandez-Salas EA, El-Deiry WS, Amundson S,
Meltzer SJ, Yin J, Holbrook NJ, Fornace AJ. The antiapoptotic decoy
receptor TRID/TRAIL-R3 is a p53-regulated DNA damage-inducible gene
and is overexpressed in primary tumors of the gastrointestinal
tract. Oncogene 1999; 18:4153 4159.
78. Krasna MJ, Mao YS, Sonett JR, Tamura G, Jones R, Suntharalingam
M, Meltzer SJ. p53 gene protein expression predicts response and
survival in esophageal cancer patients treated by trimodality
therapy. Ann. Thorac. Surg. 1999; 68:2021-2025.
79. Simms LA, Young J, Wicking C, Meltzer SJ, Jass JR, Leggett BA.
The apoptotic regulatory gene, BCL10, is mutated in sporadic
mismatch repair deficient colorectal cancers. Cell Death Diff. 2000;
7:236-237.
80. Fleisher AS, Meltzer SJ, James SP. Colon polyps in Beckwith-Wiedmann
syndrome: role of imprinted genes. Gastroenterology 2000; 118:637.
81. Tamura G, Yin J, Wang S, Fleisher AS, Zou T, Abraham JM, Kong D,
Smolinski KN, Wilson KT, James SP, Silverberg SG, Nishizuka S,
Motoyama T, Meltzer SJ. E-cadherin gene promoter hypermethylation in
primary gastric carcinomas. J. Natl. Cancer Inst. 2000; 92:569-573.
82. Tsuchiya T, Tamura G, Sato K, Endoh Y, Sakata K, Jin Z, Motoyama
T, Usuba O, Kimura W, Nishizuka S, Yin J, Fleisher AS, Zou T, Kong
D, Meltzer SJ. Distinct methylation patterns of two APC gene
promoters in normal and cancerous gastric epithelium. Oncogene 2000;
19:3642-6.
83. Esteller, M, Sparks, A, Toyota, M, Sanchez-Cespedes, M, Capella,
G, Peinado, MA, Gonzalez, S, Tarafa, G, Sidransky, D, Meltzer, SJ,
Baylin, SB, Herman, JG. Analysis of Adenomatous Polyposis Coli
promoter hypermethylation in human cancer. Cancer Res. 2000;
60:4366-4371.
84. Fleisher AS, Esteller M, Leytin A, Harpaz N, Rashid A, Xu Y,
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James SP, Herman JG, Meltzer SJ. Microsatellite instability in IBD-associated
neoplastic lesions is associated with hypermethylation and
diminished expression of the DNA mismatch repair gene, hMLH1. Cancer
Res. 2000; 60:4864-4868.
85. Kawakami, K., Brabender, J., Lord, R.V., Groshen, S., Greenwald,
B.D., Krasna, M.J., Yin, J., Fleisher, A.S., Abraham, J.M., Beer,
D.G., Sidransky, D., Huss, H.T., DeMeester, T.R., Eads, C.A., Laird,
P.W., Ilson, D.H., Kelsen, D.P., Harpole, D., Moore, M.-B.,
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86. Fleisher AS, Esteller M, Tamura G, Rashid A, Stine OC, Yin J,
Zou TT, Abraham JM, Kong D, Nishizuka S, James SP, Wilson KT, Herman
JG, Meltzer SJ. Hypermethylation of the hMLH1 gene promoter is
associated with microsatellite instability in early human gastric
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87. Akhtar M, Cheng Y, Magno RM, Ashktorab H, Smoot DT, Meltzer SJ,
Wilson KT. Promoter methylation regulates Helicobacter
pylori-stimulated cyclooxygenase-2 expression in gastric epithelial
cells. Cancer Res. 2001; 61:2399-2403.
88. Esteller M, Cordon-Cardo C, Corn PG, Meltzer SJ, Pohar KS,
Watkins NG, Capella G, Peinado MA, Matias-Guiu X, Prat J, Baylin SB,
Herman JG. p14 (ARF) silencing by promoter hypermethylation mediates
abnormal intracellular localization of MDM2. Cancer Res. 2001;
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89. Mori Y, Yin J, Rashid A, Leggett BA, Young J, Kuehl PM,
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identification of novel cancer-related genes by large-scale probing
for mutations in coding region microsatellites. Cancer Res. 2001;
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90. Brabender J, Usadel H, Danenberg KD, Metzger R, Schneider PM,
Lord RV, Wickramasinghe K, Lum CE, Park JM, Salonga D, Sidransky D,
Hölscher AH, Meltzer SJ, Danenberg PV. Adenomatous Polyposis Coli
gene promoter hypermethylation in non-small cell lung cancer is
associated with survival. Oncogene 2001; 20:3528-3532.
91. Trojan J, Plotz G, Brieger A, Raedle J, Meltzer SJ, Wolter M,
Zeuzem S. Activation of a cryptic splicing site of PTEN and allelic
imbalance in benign skin lesions in Cowden disease. J. Invest.
Dermatol. 2001; 117:1650-1653.
92. Takashima H, Matsumoto Y, Matsubara N, Shirakawa Y, Kawashima R,
Tanino M, Ito S, Isozaki H, Ouchida M, Meltzer SJ, Tanaka N, Shimizu
K. Effect of naturally occurring E2F-4 alterations on
transcriptional activation and proliferation in transfected cells.
Lab Invest. 2001; 81:1565-1573.
93. Umansky M, Yasui W, Hallak A, Brill S, Shapira I, Halpern Z,
Nibshoosh H, Rattan J, Meltzer S, Tahara E, Arber N. Proton pump
inhibitors reduce cell cycle abnormalities in Barrett’s esophagus.
Oncogene 2001; 20:7987-7991.
94. Toretsky JA, Zitomersky NL, Eskenazi AE, Voigt RW, Strauch ED,
Sun CC, Huber R, Meltzer SJ, Schlessinger D. Glypican-3 expression
in Wilms tumor and hepatoblastoma. J. Ped. Hematol./Oncol. 2001;
23:496-499.
95. Selaru F, Zou T, Shustova V, Xu Y, Yin J, Mori Y, Sato F, Wang
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Global gene expression profiling in Barrett’s esophagus and
esophageal cancer: a comparative analysis using cDNA microarrays.
Oncogene 2002; 21:475-478.
96. Sato F, Harpaz N, Shibata D, Xu Y, Yin J, Mori Y, Zou T-T, Wang
S, Desai K, Leytin A, Selaru F, Abraham JM, Meltzer SJ.
Hypermethylation of the p14ARF gene in ulcerative colitis-associated
colorectal carcinogenesis. Cancer Res. 2002; 62:1148-1151.
97. Selaru F, Xu Y, Yin J, Zou T, Liu TC, Mori Y, Abraham JM, Sato
F, Wang S, Twigg C, Olaru A, Shustova V, Leytin A, Shibata D, Harpaz
N, Meltzer SJ. Artificial neural networks distinguish among subtypes
of neoplastic colorectal lesions. Gastroenterol. 2002; 122:606-613.
98. Sato K, Tamura G, Tsuchiya T, Endoh Y, Sakata K, Motoyama T,
Usuba O, Kimura W, Terashima M, Nishizuka S, Zou T, Meltzer SJ.
Analysis of genetic and epigenetic alterations of the PTEN gene in
gastric cancer. Virchows Arch. 2002; 440:160-165.
99. Smolinski KN, Abraham JM, Souza RF, Yin J, Wang S, Xu Y, Zou
T-T, Kong D, Fleisher AS, Meltzer SJ. A functional promoter for the
squamous differentiation marker esophagin that is activated during
differentiation of cultured esophageal cells. Genomics 2002;
79:875-880.
100. Toyooka S, Toyooka KO, Harada K, Miyajima K, Makarla P,
Sathyanarayan UG, Yin J, Sato F, Shivapurkar N, Meltzer SJ, Gazdar
AF. Aberrant methylation of the CDH13 (H-cadherin) promoter region
in colorectal cancers and adenomas. Cancer Res. 2002; 62:3382-3386.
101. Xu Y, Selaru FM, Yin J, Zou TT, Shustova V, Mori Y, Sato F, Liu
TC, Olaru A, Wang S, Kimos MC, Perry K, Desai K, Greenwald BD,
Krasna MJ, Shibata D, Abraham JM, Meltzer SJ. Artificial neural
networks and gene filtering distinguish between global gene
expression profiles of Barrett’s esophagus and esophageal cancer.
Cancer Res. 2002; 62:3493-3497.
102. Zou T, Selaru F, Xu Y, Yin J, Shustova V, Mori Y, Sato F, Liu
TC, Abraham JM, Meltzer SJ. Application of cDNA microarrays to
generate a molecular taxonomy capable of distinguishing between
colon cancer and normal colon. Oncogene 2002; 21:4855-4862.
103. Mori Y, Selaru FM, Olaru A, Perry K, Kimos MC, Tamura G,
Matsubara N, Sato F, Wang S, Xu Y, Yin J, Zou T-T, Leggett B, Young
J, Nukiwa T, Stine OC, Abraham JM, Shibata D, Meltzer SJ.
Instabilotyping reveals novel unique mutational spectra in
microsatellite-unstable gastric cancers. Cancer Res. 2002;
62:3641-3645.
104. Moriyama H, Sasamoto H, Kambara T, Matsubara N, Ikeda M, Baba
S, Meltzer SJ, Lynch HT, Shimizu K, Tanaka N. E2F-4 mutation in
hereditary non-polyposis colorectal cancer. J Exp Clin Cancer Res.
2002 Jun; 21(2):185-9.
105. Shibata DM, Sato F, Mori Y, Perry K, Yin J, Wang S, Xu Y, Olaru
A, Selaru F, Spring K, Young J, Abraham JM, Meltzer SJ.
Hypermethylation of HPP1 is associated with hMLH1 hypermethylation
in gastric adenocarcinomas. Cancer Res. 2002 Oct 15; 62(20):5637-40.
106. Whitehall VLJ, Wynter CVA, Walsh MD, Simms LA, Purdie D,
Pandeya N, Young J, Meltzer SJ, Leggett BA, Jass JR. Morphological
and molecular heterogeneity within non-microsatellite
instability-high colorectal cancer. Cancer Res. 2002 Nov 1;
62(21):6011-6014.
107. Sato F, Shibata D, Harpaz N, Xu Y, Yin J, Mori Y, Wang S, Olaru
A, Deacu E, Selaru F, Kimos M, Hytiroglou P, Young J, Leggett B,
Gazdar AF, Toyooka S, Abraham JM, Meltzer SJ. Aberrant methylation
of the HPP1 gene in ulcerative colitis-associated colorectal
carcinoma. Cancer Res. 2002 Dec 1; 62(23):6820-6822.
108. Yamashita K, Upadhyay S, Osada M, Hoque MO, Xiao Y, Mori M,
Sato F, Meltzer SJ, Sidransky D. Pharmacologic unmasking of
epigenetically silenced tumor suppressor genes in esophageal
squamous cell carcinoma. Cancer Cell 2002, Dec; 2(12):485-495.
109. Wang S, Mori Y, Sato F, Yin J, Xu Y, Zou TT, Olaru A, Kimos MC,
Perry K, Selaru FM, Deacu E, Sun M, Shi YC, Shibata D, Abraham JM,
Greenwald BD, Meltzer SJ. An LOH and mutational investigation of the
ST7 gene locus in human esophageal carcinoma. Oncogene 2003 Jan 23;
22(3):467-470.
110. Mori Y, Selaru F, Sato F, Xu Y, Wang S, Yin J, Abraham JM,
Olaru A, Deacu E, Kimos M, Perry K, Shibata D, Young J, Leggett B,
Meltzer SJ. The impact of microsatellite instability on the
molecular phenotype of colorectal tumors. Cancer Res. 2003 Aug 1;
63(15):4577-4582.
111. Olaru A, Mori Y, Yin J, Wang S, Kimos MC, Perry K, Xu Y, Sato
F, Selaru FM, Deacu E, Shibata D, Abraham JM, Meltzer SJ. An LOH and
mutational analysis of the ACTRII gene locus in human colorectal
tumors. Lab. Invest. 2003 Dec; 83(12):1867-1861.
112. Selaru FM, Yin J, Xu Y, Epstein S, Sato F, Mori Y, Olaru A,
Deacu E, Wang S, Sterian A, Fulton A, Abraham JM, Shibata D, Baquet
C, Stass SA, Meltzer SJ. An unsupervised approach to identify
molecular phenotypic components influencing breast cancer features.
Cancer Res. 2004 Mar 1; 64(5):1584-1588.
113. Mori Y, Yin J, Sato F, Sterian A, Simms LA, Selaru FM, Xu Y,
Olaru A, Wang S, Deacu E, Abraham JM, Young J, Leggett BA, Meltzer
SJ. Identification of genes uniquely involved in MSI-H colon
carcinogenesis by expression profiling combined with epigenetic
scanning. Cancer Res. 2004 Apr 1; 64(7):2434-2438.
114. Brabender J, Marjoram P, Salonga D, Metzger R, Schneider PM,
Park JM, Schneider S, Holscher AH, Danenberg KD, Yin J, Meltzer SJ,
Danenberg PV, Lord RV. A multigene expression panel for the
molecular diagnosis of Barrett’s esophagus and Barrett’s
adenocarcinoma of the esophagus. Oncogene 2004 Jun 10;
23(27):4780-4788.
115. Stokes NR, Zhou X, Meltzer SJ, Kaper JB. Transcriptional
responses of intestinal epithelial cells to infection with Vibrio
cholerae. Infect Immun. 2004 Jul; 72(7):4240-4248.
116. Ma X, Yang Q, Wilson KT, Kundu N, Meltzer SJ, Fulton AM.
Promoter methylation regulates cyclooxygenase (COX-2) expression in
human and murine breast cancer. Breast Cancer Res. 2004;
6(4):R316-321.
117. Schulmann K, Yin J, Sterian A, Xu T, Sato F, Bryant L, Mori Y,
Olaru A, Deacu E, Wang S, Brenner DE, Krasna MJ, Abraham JM, Baron
JA, Greenwald BD, Meltzer SJ. Methylation profiling for the
prediction of Barrett’s esophagus progression. Gastroenterol. 2004
Jul; 127(1):331.
118. Kimos MC, Borkowski A, Wang LD, Yang CS, Perry K, Olaru A,
Sisodia L, Selaru FM, Mori Y, Xu Y, Yin J, Wang S, Abraham JM,
Meltzer SJ. Esophagin and proliferating cell nuclear antigen (PCNA)
as biomarkers of human esophageal epithelial differentiation and
proliferation in carcinogenesis. Int. J. Cancer 2004 Sep 1;
111(3):415-417.
119. Deacu E, Mori Y, Sato F, Yin J, Olaru A, Sterian A, Xu Y, Wang
S, Schulmann K, Bryant L, Kan T, Abraham JM, Meltzer SJ. Activin
type II receptor restoration in ACVR2-deficient colon cancer cells
induces TGF-beta response pathway genes. Cancer Res. 2004 Nov 1;
64(21):7690-7696.
120. Kan T, Shimada Y, Sato F, Ito T, Kondo K, Watanabe G, Maeda M,
Yamasaki S, Meltzer SJ, Imamura M. Prediction of lymph node
metastasis with use of artificial neural networks based on gene
expression profiles in esophageal squamous cell carcinoma. Ann.
Surg. Oncol. 2004 Dec; 11(12):1070-1078.
121. Xu H, Chatuvedi R, Cheng Y, Bussiere FI, Asim M, Yao MD,
Potosky D, Meltzer SJ, Rhee JG, Kim SS, Moss SF, Hacker A, Wang Y,
Casero RA, Wilson KT. Spermine oxidation by Helicobacter pylori
results in apoptosis and DNA damage: Implications for gastric
carcinogenesis. Cancer Res. 2004 Dec. 1; 64(23):8521-8525.
122. Schulmann K, Brasch FE, Kunstmann E, Engel C, Pagenstecher C,
Vogelsang H, Kruger S, Vogel T, Knaebel HP, Ruschoff J, Hahn SA,
Knebel-Doeberitz MV, Moeslein G, Meltzer SJ, Schackert HK, Tympner
C, Mangold E, Schmiegel W. HNPCC-associated small bowel cancer:
Clinical and molecular characteristics. Gastroenterol. 2005 Mar;
128(3):590-599.
123. Sato F, Shimada Y, Selaru FM Maeda M, Shibata D, Watanabe G,
Mori Y, Stass SA, Imamura M, Meltzer SJ. Prediction of survival in
esophageal cancer using artificial neural networks. Cancer 2005 Apr
15; 103(8):1596-1605.
124. Takahashi T, Suzuki M, Shigematsu H, Shivapurkar N, Echebiri C,
Nomura M, Stastny V, Augustus M, Wu CW, Wistuba II, Meltzer SJ,
Gazdar AF. Aberrant methylation of Reprimo in human malignancies.
Int. J. Cancer 2005 Jul 1; 115(4):503-510.
125. Schulmann K, Sterian A, Berki A, Yin J, Sato F, Xu Y, Olaru A,
Wang S, Mori Y, Deacu E, Hamilton J, Kan T, Krasna MJ, Beer DG, Pepe
MS, Abraham JM, Feng Z, Schmiegel W, Greenwald BD, Meltzer SJ.
Inactivation of p16, RUNX3, and HPP1 occurs early in
Barrett's-associated neoplastic progression and predicts progression
risk. Oncogene 2005 Jun 9; 24(25):4138-4148.
126. Schulmann K, Mori Y, Croog V, Yin J, Olaru A, Sterian A, Sato
F, Wang S, Xu Y, Deacu E, Abraham JM, Schmiegel W, Harpaz N, Meltzer
SJ. Molecular phenotype of inflammatory bowel disease-associated
neoplasms with microsatellite instability. Gastroenterol. 2005 Jul;
129:74-85.
127. Brabender J, Marjoram P, Lord RVN, Metzger R, Salonga D,
Vallbohmer D, Schafer H, Danenberg KD, Danenberg PV, Baldus SE,
Holscher AH, Meltzer SJ, Schneider PM. The molecular signature of
normal squamous esophagus identifies the presence of a field effect
and can discriminate between patients with Barrett’s esophagus and
Barrett’s-associated adenocarcinoma. Cancer Epidemiol. Biomarkers &
Prev. 2005 Sep; 14(9):2113-2117.
128. Baquet CR, Commiskey P, Mack K, Meltzer SJ, Mishra SI.
Esophageal cancer epidemiology in blacks and whites: racial and
gender disparities in incidence, mortality, survival rates and
histology. J. Natl. Med. Assoc. 2005 Nov; 97(11);1471-1478.
129. Kan T, Yamasaki S, Kondo K, Teratani N, Kawabe A, Kaganoi J,
Meltzer SJ, Imamura M, Shimada Y. A new specific gene expression in
squamous cell carcinoma of the esophagus detected using
representational difference analysis and cDNA microarray. Oncology
2006 Jan 27; 70(1):25-33.
130. Takahashi T, Shigematsu H, Shivapurkar N, Reddy J, Zheng Y,
Feng Z, Suzuki M, Nomura M, Augustus M, Yin J, Meltzer SJ, Gazdar
AF. Aberrant promoter methylation of multiple genes during multistep
pathogenesis of colorectal cancers. Int. J. Cancer 2006 Feb 15;
118(4):924-931.
131. Shibata D, Mori Y, Cai K, Zhang L, Yin J, Elahi A, Hamelin R,
Wong YF, Lo WK, Chung TKH, Sato F, Karpeh MS, Jr., Meltzer SJ. RAB32
hypermethylation and microsatellite instability in gastric and
endometrial adenocarcinomas. Int. J. Cancer 2006 Mar 23;
119:801-806.
132. Sato F, Abraham JM, Yin J, Kan T, Ito T, Mori Y, Hamilton JP,
Jin Z, Cheng Y, Paun B, Berki AT, Wang S, Shimada T, Meltzer SJ.
Polo-like kinase (PLK) and Survivin are Esophageal Tumor-Specific
Promoters. Biochem. Biophys. Res. Commun. 2006 Apr 7;
342(2):465-471.
133. Wang S, Zhan M, Yin J, Abraham JM, Mori Y, Sato F, Xu Y, Olaru
A, Li H, Schulmann K, Sterian A, Kan T, Hamilton JP, Chai K, Deacu
E, Berki AT, Greenwald BD and Meltzer SJ. Transcriptional profiling
suggests that Barrett's metaplasia is an advanced intermediate stage
in esophageal adenocarcinoma. Oncogene 2006 Jun 1; 25(23):3346-3356.
134. Hamilton JP, Sato F, Greenwald BD, Suntharalingam M, Krasna MJ,
Edelman MJ, Doyle LA, Berki AT, Abraham JM, Mori Y, Kan T, Mantzur
C, Paun T, Wang S, Ito T, Jin Z, Meltzer SJ. Promoter
hypermethylation and response to chemotherapy and radiation in
esophageal cancer. Clin. Gastroenterol. Hepatol. 2006 Jun;
4(6):701-708.
135. Sterian A, Kan T, Mori Y, Berki A, Olaru A, Schulmann K, Sato
F, Wang S, Paun B, Cai K, Hamilton JP, Abraham JM, Greenwald BD,
Meltzer SJ. Mutational and deletion analyses of the chromosome
4q24-31 region in esophageal adenocarcinoma. Oncology 2006 Jul 7;
70(3):168-172.
136. O’Neill JP, Velalar CN, Lee DI, Zhang B, Nakanishi T, Tang Y,
Selaru FM, Ross D, Meltzer SJ, Hussain A. Thapsigarin resistance in
human prostate cancer cells. Int. J. Cancer 2006 Aug 1;
107(3):649-659.
137. Mori Y, Cai K, Cheng Y, Wang S, Paun B, Hamilton JP, Jin Z,
Sato F, Berki AT, Kan T, Ito T, Mantzur C, Abraham JM, Meltzer SJ. A
genome-wide search identifies epigenetic silencing of somatostatin,
tachykinin-1, and five other genes in colon cancer. Gastroenterol.
2006 Sep; 131(3): 797-808.
138. Hamilton JP, Sato F, Jin Z, Greenwald BD, Ito T, Mori Y, Paun
B, Kan T, Cheng Y, Wang S, Mantzur C, Abraham JM, Meltzer SJ.
Reprimo methylation is a potential early biomarker of
Barrett’s-associated neoplastic progression. Clin. Cancer Res. 2006
Nov 15; 12(22):6637-6642.
139. Kanner WA, Drachenberg CB, Papadimitriou JC, Wang S, Meltzer
SJ, Sklar GN. Urethral stromal tumor with pacemaker cell phenotype.
Ultrastruct Pathol. 2007 Jan-Feb;31(1):63-71.
140. Konishi K, Shen L, Wang S, Meltzer SJ, Issa J-PJ. Rare CpG
island methylator phenotype in ulcerative colitis-associated
neoplasias. Gastroenterol. 2007 Apr; 132(4):1254-1260.
141. Liu Z, Jiang F, Tian G, Wang S, Sato F, Meltzer SJ, Tan M.
Sparse logistic regression with Lp penalty for biomarker
identification. Statistical Applics. Genet. Molec. Biol. 2007 Feb
10; 6:Article6.
142. Jin Z, Mori Y, Yang J, Sato F, Ito T, Cheng Y, Paun B, Hamilton
JP, Kan T, Olaru A, David S, Agarwal R, Abraham JM, Beer D,
Montgomery E, Meltzer SJ. Hypermethylation of the nel-like 1 gene is
a common and early event and is associated with a poor prognosis in
early-stage esophageal adenocarcinoma. Oncogene 2007 Sep
20;26(43):6332-40.
143. Kan T, Paun B, Mori Y, Sato F, Jin Z, Hamilton JP, Ito T, Cheng
Y, David S, Olaru A, Yang J, Agarwal R, Abraham JM, Meltzer SJ.
Rarity of somatic mutation and frequency of normal sequence
variation detected in sporadic colon adenocarcinoma using
high-throughput cDNA sequencing. Bioinformatics & Biology Insights
2007; 1:1-16.
144. Abraham JM, Sato F, Cheng Y, Paun B, Ito T, Kan T, Olaru A, Jin
Z, Yang J, Agarwal R, David S, Hamilton JP, Mori Y, Meltzer SJ. A
Novel Decapeptide that Binds Avidly and Delivers Radioisotope to
Colon Cancer Cells. PLoS ONE 2007 Oct 3;2(10):e964.
145. Jin Z, Olaru A, Yang J, Sato F, Cheng Y, Mori Y, Mantzur C,
Paun B, Hamilton JP, Ito T, Kan T, Wang S, David S, Agarwal R, Beer
DG, Abraham JM, Meltzer SJ. Hypermethylation of Tachykinin-1 is
Associated with a Poor Prognosis in Human Esophageal Squamous Cell
Carcinoma. Clin. Cancer Res. 2007 Nov 1;13(21):6293-6300.
146. Jin Z, Mori Y, Hamilton JP, Olaru A, Sato F, Yang J, Ito T,
Paun B, Kan T, Agarwal R, Meltzer SJ. Hypermethylation of the
somatostatin promoter is a common, early event in human esophageal
carcinogenesis. Cancer 2008 Jan 1;112(1):43-49.
147. Jin Z, Hamilton JP, Yang J, Mori Y, Olaru A, Sato F, Ito T, Kan
T, Cheng Y, Paun B, David S, Agarwal R, Abraham JM, Meltzer SJ.
Hypermethylation of the AKAP12 Promoter is a Potential Biomarker of
Barrett's-Associated Esophageal Neoplastic Progression. Cancer
Epidemiology, Biomarkers & Prevention 2008 Jan; 17(1):1-16.
148. Selaru FM, Wang S, Yin J, Schulmann K, Xu Y, Yuriko Mori Y,
Olaru A, Sato F, Hamilton JP, Abraham JM, Schneider P, Greenwald BD,
Brabender J, Meltzer SJ. Beyond Field Effect: Analysis of Shrunken
Centroids in Normal Esophageal Epithelia Detects Concomitant
Esophageal Adenocarcinoma. Bioinformatics & Biology Insights, 2007;
1:127-136.
149. Ito T, Shimada Y, Kan T, David S, Abraham JM, Mori Y, Agarwal
R, Cheng Y, Paun B, Jin Z, Olaru A, Hamilton JP, Yang J, Meltzer SJ,
Sato F. PTTG1 promotes lymph node metastasis in esophageal squamous
cell carcinoma by increasing cell motility. Cancer Research 2008 May
1;68(9):3214-3224.
150. Sato F, Jin Z, Schulmann K, Wang J, Greenwald BD, Ito T, Kan T,
Hamilton JP, Yang J, Paun B, David S, Olaru A, Cheng Y, Mori Y,
Abraham JM, Yfantis HG, Wu T, Fredericksen MB, Wang KK, Canto M,
Romero Y, Feng Z, Meltzer SJ. Three-tiered risk stratification
method to predict progression in Barrett’s esophagus using
epigenetic and clinical features. PLoS ONE 2008 Apr 2; 3(4):e1890.
151. Ito T, Tanaka E, Kadowaki T, Kan T, Higashiyama M, Shiojima S,
Tomoda S, Myoumoto A, Akiyama H, Nobumasa H, Matsumoto S, Miyamoto
S, Mitsumori M, Sato F, Watanabe G, Itami A, Meltzer SJ, Tsujimoto
G, Shimada Y. An ultrasensitive new DNA microarray chip provides
gene expression profiles for preoperative esophageal cancer biopsies
without RNA amplification. Oncology 2008 May 30, 73(5-6):366-375.
152. Abraham JM, Cheng Y, Hamilton JP, Paun B, Jin Z, Agarwal R, Kan
T, David S, Olaru A, Yang J, Ito T, Selaru FM, Mori Y, Meltzer SJ.
Generation of small 32P-labeled peptides as a potential approach to
colorectal cancer therapy. PLoS ONE 2008 Jun 25; 3(6):e2508.
153. Jin Z, Hamilton JP, Yang J, Mori Y, Olaru A, Sato F, Ito T, Kan
T, Cheng Y, Paun B, David S, Agarwal R, Abraham JM, Meltzer SJ.
Promoter hypermethylation of CDH13 is a common, early event in human
esophageal adenocarcinogenesis and correlates with clinical risk
factors. Int. J. Cancer 2008 Nov 15;123(10):2331-2336.
154. Selaru FM, Olaru AV, Kan T, David S, Cheng Y, Mori Y, Yang J,
Paun B, Jin Z, Agarwal R, Hamilton JP, Abraham JM, Georgiades C,
Alvarez H, Vivekanandan P, Maitra A, Torbenson M, Thuluvath PJ,
Gores GJ, LaRusso NF, Hruban R, Meltzer SJ. MicroRNA-21 is
overexpressed in human cholangiocarcinoma and regulates programmed
cell death 4 and tissue inhibitor of metalloproteinase 3. Hepatology
2009 Feb 4;49(5):1595-1601.
155. Kan T, Sato F, Ito T, Matsumura N, David S, Cheng Y, Agarwal R,
Paun BC, Jin Z, Olaru AV, Selaru FM, Hamilton JP, Yang J, Abraham
JM, Mori Y, Meltzer SJ. The miR-25-93-106b polycistron, activated by
de novo genomic amplification, functions as an oncogene by
suppressing p21 and Bim.
Gastroenterology. 2009 May;136(5):1689-700.
156. Jin Z, Cheng Y, Zheng Y, Gu J, Sato F, Olaru AV, Paun B, Yang
J, Kan T, Ito T, Hamilton JP, Selaru FM, Mori Y, Agarwal R, David S,
Abraham JM, Wolfsen H, Shaheen NJ, Wang J, Canto M, Washington K,
Romero Y, Wang KK, Feng Z, Sampliner RD, Meltzer SJ. A multi-center,
double-blinded validation study of methylation biomarkers for
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