Prevention of Esophageal Cancer with Berries

Summary

Principal Investigator: Gary Stoner
Abstract: DESCRIPTION (provided by applicant): Esophageal cancer is the eighth most prevalent cancer, and the sixth leading cause of cancer death worldwide. There are two histologic types of esophageal cancer;squamous cell carcinoma (SCC) and adenocarcinoma. SCC is by far the most common type worldwide, accounting for about 90% of all esophageal cancer. This disease has a poor prognosis with a 5-year survival rate of about 12%. The major risk factors for esophageal SCC are tobacco and alcohol use, consumption of salty and moldy foods that are frequently contaminated with N-nitrosamine carcinogens, vitamin and trace mineral deficiencies, and diets high in starch but low in fruits and vegetables. Our laboratory has been evaluating the use of freeze-dried berries, mainly black raspberries (BRBs), for the prevention of esophageal squamous cell carcinoma in rats. In the rat, esophageal tumors are induced within 25-30 weeks by repeated s.c. injections of the N-nitrosamine carcinogen, N-nitrosomethylbenzylamine (NMBA). The addition of 5% and 10% BRB powder to the diet of NMBA-treated rats reduces the number of esophageal tumors by 50-60%. During the past 5 years, we demonstrated that BRBs reduce NMBA-induced DNA damage in the rat esophagus and they inhibit proliferation, inflammation and angiogenesis, and stimulate apoptosis in premalignant esophageal cells and tissues. They also modulate the expression levels of genes associated with all of these cellular functions. Using bio-directed fractionation, we and our collaborators found that the anthocyanins in BRBs are important for their chemopreventive effects. The anthocyanins are responsible for the color of BRBs and much of their antioxidant activity. Because we rarely observe more than 50-60% inhibition of esophageal carcinogenesis with BRBs or the anthocyanins alone, we now propose to use the anthocyanins in combination with phenethyl isothiocyanate (PEITC) for the prevention of esophageal cancer. In the 1990's we identified PEITC as a very potent inhibitor of tumor initiation in the rat esophagus, however, unlike BRBs, PEITC failed to inhibit esophageal tumor progression when given in the diet post-initiation. We propose therefore, to identify low dietary concentrations of BRB anthocyanins (Specific Aim 1) and of PEITC (Specific Aim 2) that inhibit NMBA- induced esophageal tumorigenesis, and then evaluate these agents in combination (Specific Aim 3) with the objective of achieving a high level of chemopreventive efficacy using minimal dietary levels of these agents. We also propose to examine the effects of dietary anthocyanins and PEITC, alone and in combination, on the formation of NMBA-induced DNA adducts in rat esophagus as well as their effects on the expression of genes associated with cell proliferation, inflammation, angiogenesis and apoptosis (Specific Aim 4). Ultimately, we plan to evaluate these agents for prevention of esophageal SCC in humans at high risk for the disease. PUBLIC HEALTH RELEVANCE: Esophageal cancer is the eighth most prevalent cancer, and the sixth leading cause of cancer death worldwide. Our laboratory is developing strategies for the prevention of esophageal cancer using freeze-dried berries and isothiocyanate compounds found in vegetables. We now propose to evaluate the anthocyanins in berries in combination with phenethyl isothiocyanate in vegetables for their ability to prevent esophageal cancer at low, non-toxic, dietary concentrations.
Funding Period: 2003-08-01 - 2014-04-30
more information: NIH RePORT

Top Publications

  1. ncbi Chemoprevention of esophageal cancer with black raspberries, their component anthocyanins, and a major anthocyanin metabolite, protocatechuic acid
    Daniel S Peiffer
    Authors Affiliations Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center Agro BioSciences Inc, Milwaukee, Wisconsin and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
    Cancer Prev Res (Phila) 7:574-84. 2014
  2. pmc Anthocyanins and their role in cancer prevention
    Li Shu Wang
    Department of Internal Medicine and Comprehensive Cancer Center, Ohio State University College of Medicine, Columbus, OH 43210, USA
    Cancer Lett 269:281-90. 2008
  3. pmc Laboratory and clinical studies of cancer chemoprevention by antioxidants in berries
    Gary David Stoner
    Department of Internal Medicine, College of Medicine, The Ohio StateUniversity, Columbus, OH 43210, USA
    Carcinogenesis 29:1665-74. 2008
  4. pmc Both IKKalpha and IKKbeta are implicated in the arsenite-induced AP-1 transactivation correlating with cell apoptosis through NF-kappaB activity-independent manner
    Lun Song
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    Exp Cell Res 314:2187-98. 2008
  5. pmc Anti-cancer effects of JKA97 are associated with its induction of cell apoptosis via a Bax-dependent and p53-independent pathway
    Wenjing Luo
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA
    J Biol Chem 283:8624-33. 2008
  6. pmc PI-3K/Akt pathway-dependent cyclin D1 expression is responsible for arsenite-induced human keratinocyte transformation
    Weiming Ouyang
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA
    Environ Health Perspect 116:1-6. 2008
  7. ncbi Bioactive food components and cancer risk reduction
    Silvia D Stan
    Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    J Cell Biochem 104:339-56. 2008
  8. pmc Differential effects of black raspberry and strawberry extracts on BaPDE-induced activation of transcription factors and their target genes
    Jingxia Li
    Nelson Institute of Environmental Medicine, New York University School of Medicine, New York, New York 10987, USA
    Mol Carcinog 47:286-94. 2008
  9. ncbi Transcription factor NFAT, its role in cancer development, and as a potential target for chemoprevention
    Haitian Lu
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    Curr Cancer Drug Targets 7:343-53. 2007
  10. ncbi The PI3K/Akt pathway and its downstream transcriptional factors as targets for chemoprevention
    Xinhai Zhang
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    Curr Cancer Drug Targets 7:305-16. 2007

Detail Information

Publications54

  1. ncbi Chemoprevention of esophageal cancer with black raspberries, their component anthocyanins, and a major anthocyanin metabolite, protocatechuic acid
    Daniel S Peiffer
    Authors Affiliations Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center Agro BioSciences Inc, Milwaukee, Wisconsin and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
    Cancer Prev Res (Phila) 7:574-84. 2014
    ..Overall, our data suggest that BRBs, their component ACs, and PCA inhibit NMBA-induced esophageal tumorigenesis, at least in part, by their inhibitory effects on genes associated with inflammation...
  2. pmc Anthocyanins and their role in cancer prevention
    Li Shu Wang
    Department of Internal Medicine and Comprehensive Cancer Center, Ohio State University College of Medicine, Columbus, OH 43210, USA
    Cancer Lett 269:281-90. 2008
    ..Future studies aimed at enhancing the absorption of anthocyanins and/or their metabolites are likely to be necessary for their ultimate use for chemoprevention of human cancer...
  3. pmc Laboratory and clinical studies of cancer chemoprevention by antioxidants in berries
    Gary David Stoner
    Department of Internal Medicine, College of Medicine, The Ohio StateUniversity, Columbus, OH 43210, USA
    Carcinogenesis 29:1665-74. 2008
    ..This review article summarizes laboratory and human studies, demonstrating the protective effects of berries and berry constituents on oxidative and other cellular processes leading to cancer development...
  4. pmc Both IKKalpha and IKKbeta are implicated in the arsenite-induced AP-1 transactivation correlating with cell apoptosis through NF-kappaB activity-independent manner
    Lun Song
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    Exp Cell Res 314:2187-98. 2008
    ..Therefore, we concluded that both IKKalpha and IKKbeta can mediate arsenite-induced AP-1 transactivation through NF-kappaB activity-independent manner...
  5. pmc Anti-cancer effects of JKA97 are associated with its induction of cell apoptosis via a Bax-dependent and p53-independent pathway
    Wenjing Luo
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA
    J Biol Chem 283:8624-33. 2008
    ..These studies provide a molecular basis for the therapeutic application of JKA97 against human cancers with p53 mutations...
  6. pmc PI-3K/Akt pathway-dependent cyclin D1 expression is responsible for arsenite-induced human keratinocyte transformation
    Weiming Ouyang
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA
    Environ Health Perspect 116:1-6. 2008
    ..Long-term exposure of arsenite leads to human skin cancer. However, the exact mechanisms of arsenite-induced human skin carcinogenesis remain to be defined...
  7. ncbi Bioactive food components and cancer risk reduction
    Silvia D Stan
    Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    J Cell Biochem 104:339-56. 2008
    ....
  8. pmc Differential effects of black raspberry and strawberry extracts on BaPDE-induced activation of transcription factors and their target genes
    Jingxia Li
    Nelson Institute of Environmental Medicine, New York University School of Medicine, New York, New York 10987, USA
    Mol Carcinog 47:286-94. 2008
    ..These results suggest that black raspberry and strawberry components may target different signaling pathways in exerting their anti-carcinogenic effects...
  9. ncbi Transcription factor NFAT, its role in cancer development, and as a potential target for chemoprevention
    Haitian Lu
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    Curr Cancer Drug Targets 7:343-53. 2007
    ..To validate whether NFAT can be a promising target for chemoprevention, more research has to be done to further detail the roles of NFAT and to differentiate the functions of different members of this protein family in future studies...
  10. ncbi The PI3K/Akt pathway and its downstream transcriptional factors as targets for chemoprevention
    Xinhai Zhang
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    Curr Cancer Drug Targets 7:305-16. 2007
    ..To this regard, the natural compounds from vegetables and fruits with high affinity and non toxicity to target the PI3K/Akt pathway and prevent cancer are attractive...
  11. ncbi High expression of nuclear factor of activated T cells in Chinese primary non-small cell lung cancer tissues
    K Zhang
    State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, China
    Int J Biol Markers 22:221-5. 2007
    ..This research was the first to investigate NFAT protein expression in primary non-small cell lung cancer (NSCLC) tissues from Chinese patients...
  12. ncbi Prevention and therapy of squamous cell carcinoma of the rodent esophagus using freeze-dried black raspberries
    Gary D Stoner
    Division of Hematology and Oncology and Comprehensive Cancer Center, College of Public Health, The Ohio State University, Columbus, OH 43210, USA
    Acta Pharmacol Sin 28:1422-8. 2007
    ....
  13. pmc Carcinogen-altered genes in rat esophagus positively modulated to normal levels of expression by both black raspberries and phenylethyl isothiocyanate
    Gary D Stoner
    Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University College of Medicine, Columbus, Ohio 43240, USA
    Cancer Res 68:6460-7. 2008
    ..Because both PEITC and BRB maintain near-normal levels of expression of these 53 genes, their dysregulation during the early phase of NMBA-induced esophageal cancer may be especially important in the genesis of the disease...
  14. pmc Soluble and insoluble nickel compounds exert a differential inhibitory effect on cell growth through IKKalpha-dependent cyclin D1 down-regulation
    Weiming Ouyang
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, USA
    J Cell Physiol 218:205-14. 2009
    ....
  15. ncbi Effects of a black raspberry diet on gene expression in the rat esophagus
    John F Lechner
    Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
    Nutr Cancer 60:61-9. 2008
    ..In conclusion, histological and molecular studies indicate that a 5% BRB diet produces only modest effects on the esophagus, the target tissue for NMBA carcinogenesis in the rat...
  16. pmc Black raspberries protectively regulate methylation of Wnt pathway genes in precancerous colon tissue
    Li Shu Wang
    Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Rd, TBRC, Room C4930, Milwaukee, WI 53226
    Cancer Prev Res (Phila) 6:1317-27. 2013
    ..In conclusion, our results suggest that BRBs inhibit colonic ulceration and, ultimately, colon cancer partly through inhibiting aberrant epigenetic events that dysregulate Wnt signaling...
  17. pmc Plasma cytokines as potential response indicators to dietary freeze-dried black raspberries in colorectal cancer patients
    Roycelynn A Mentor-Marcel
    Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute Frederick, Frederick, Maryland, USA
    Nutr Cancer 64:820-5. 2012
    ..52) observed in colorectal tissue taken within the same week. Plasma concentrations of GM-CSF and IL-8 may serve as noninvasive indicators to monitor tissue response to berry-based interventions for CRC...
  18. pmc Modulation of genetic and epigenetic biomarkers of colorectal cancer in humans by black raspberries: a phase I pilot study
    Li Shu Wang
    Department of Internal Medicine, Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, Ohio 43240, USA
    Clin Cancer Res 17:598-610. 2011
    ....
  19. pmc Black raspberries inhibit intestinal tumorigenesis in apc1638+/- and Muc2-/- mouse models of colorectal cancer
    Xiuli Bi
    Department of Pathology, University of Illinois at Chicago, Illinois 60612, USA
    Cancer Prev Res (Phila) 3:1443-50. 2010
    ..Collectively, our data suggest that BRBs are highly effective in preventing intestinal tumor development in both Apc1638+/- and Muc2-/- mice through targeting multiple signaling pathways...
  20. pmc Multiple berry types prevent N-nitrosomethylbenzylamine-induced esophageal cancer in rats
    Gary D Stoner
    Department of Internal Medicine and Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA
    Pharm Res 27:1138-45. 2010
    ..We also determined if berries influence the levels of inflammatory cytokines in the serum of carcinogen-treated rats...
  21. pmc Black raspberry components inhibit proliferation, induce apoptosis, and modulate gene expression in rat esophageal epithelial cells
    Nancy N Zikri
    The Ohio State University, Columbus, Ohio 43240, USA
    Nutr Cancer 61:816-26. 2009
    ....
  22. pmc Berry ellagitannins may not be sufficient for prevention of tumors in the rodent esophagus
    Li Shu Wang
    The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43240, USA
    J Agric Food Chem 58:3992-5. 2010
    ..01-0.62 g/kg of diet). These results suggest that the ellagitannins may not be responsible for the chemopreventive effects of the alcohol/water-insoluble fraction of berries...
  23. pmc Bid mediates anti-apoptotic COX-2 induction through the IKKbeta/NFkappaB pathway due to 5-MCDE exposure
    Wenjing Luo
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    Curr Cancer Drug Targets 10:96-106. 2010
    ..Collectively, our results demonstrate that Bid is critical for COX-2 induction through the IKKbeta/NFkappaB pathway, which mediates its anti-apoptotic function, in cell response to low doses of 5-MCDE exposure...
  24. pmc Topical treatment with black raspberry extract reduces cutaneous UVB-induced carcinogenesis and inflammation
    F J Duncan
    Department of Pathology, The Ohio State University, 1645 Neil Avenue, 129 Hamilton Hall, Columbus, OH 43210, USA
    Cancer Prev Res (Phila) 2:665-72. 2009
    ..The ability of topical BRE to reduce acute UVB-induced inflammation and to decrease tumor development in a long-term model provides compelling evidence to explore the clinical efficacy of BRE in the prevention of human skin cancers...
  25. pmc Foodstuffs for preventing cancer: the preclinical and clinical development of berries
    Gary D Stoner
    Department of Internal Medicine, The Ohio State University, Innovation Centre, 2001 Polaris Parkway, Columbus, Ohio 43240, USA
    Cancer Prev Res (Phila) 2:187-94. 2009
    ..The relative merits of berry powders, extracts, or individual constituents (anthocyanins) for cancer prevention are also discussed...
  26. pmc Anthocyanins in black raspberries prevent esophageal tumors in rats
    Li Shu Wang
    Ohio State University Comprehensive Cancer Center, 2001 Polaris Parkway, Columbus, OH 43240, USA
    Cancer Prev Res (Phila) 2:84-93. 2009
    ....
  27. ncbi Activation of both nuclear factor of activated T cells and inhibitor of nuclear factor-kappa B kinase beta-subunit-/nuclear factor-kappa B is critical for cyclooxygenase-2 induction by benzo[a]pyrene in human bronchial epithelial cells
    Jin Ding
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    Cancer Sci 98:1323-9. 2007
    ..Taken together, these data indicate that exposure of Beas-2B to B[a]P can upregulate COX-2 expression by increasing its transcription, which requires activation of both the NFAT and NF-kappaB signaling pathways...
  28. ncbi Differential inhibition of UV-induced activation of NF kappa B and AP-1 by extracts from black raspberries, strawberries, and blueberries
    Chuanshu Huang
    Nelson Institute of Environmental Medicine, New York University School of Medicine, New York, NY 10987, USA
    Nutr Cancer 58:205-12. 2007
    ..These results suggest that berries differ in their ability to influence signaling pathways leading to activation of NF kappa B and AP-1 when using UV light as the inducer...
  29. pmc Suppression of the tumorigenic phenotype in human oral squamous cell carcinoma cells by an ethanol extract derived from freeze-dried black raspberries
    Kapila A Rodrigo
    Department of Oral Maxillofacial Surgery and Pathology, College of Dentistry, The Ohio State University, Columbus 43210, USA
    Nutr Cancer 54:58-68. 2006
    ..These data imply that RO-ET is a promising candidate for use as a chemopreventive agent in persons with oral epithelial dysplasia...
  30. pmc Modulation of N-nitrosomethylbenzylamine metabolism by black raspberries in the esophagus and liver of Fischer 344 rats
    Rashmeet K Reen
    Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus 43210, USA
    Nutr Cancer 54:47-57. 2006
    ..Dietary BRBs and PEITC induced glutathione S-transferase activity in the liver...
  31. pmc Protection against esophageal cancer in rodents with lyophilized berries: potential mechanisms
    Gary D Stoner
    Division of Hematology and Oncology, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center, Columbus 43210, USA
    Nutr Cancer 54:33-46. 2006
    ..Based upon the preclinical data on rodents, we have initiated prevention trials in humans to determine if berries might exhibit chemopreventive effects in the esophagus...
  32. ncbi Black raspberries inhibit N-nitrosomethylbenzylamine (NMBA)-induced angiogenesis in rat esophagus parallel to the suppression of COX-2 and iNOS
    Tong Chen
    Cancer Chemoprevention and Support Program, Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine and Public Health, The Ohio State University Columbus, OH 43210, USA
    Carcinogenesis 27:2301-7. 2006
    ..86, P < 0.001) and iNOS (r2 = 0.81, P < 0.005). As high vascularity is a risk factor for metastasis and tumor recurrence, BRB may have cancer therapeutic effects in human esophageal cancer...
  33. ncbi Inflammation, a key event in cancer development
    Haitian Lu
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    Mol Cancer Res 4:221-33. 2006
    ..The elucidation of their specific effects and interactions will accelerate the development of novel therapeutic interventions against cancer development triggered by inflammation...
  34. pmc Identification of cyanidin glycosides as constituents of freeze-dried black raspberries which inhibit anti-benzo[a]pyrene-7,8-diol-9,10-epoxide induced NFkappaB and AP-1 activity
    Stephen S Hecht
    The Cancer Center, University of Minnesota Minneapolis, MN 55455, USA
    Carcinogenesis 27:1617-26. 2006
    ..The results of this study demonstrate that cyanidin glycosides of freeze-dried black raspberries are bioactive compounds which could account for at least some of the chemopreventive activity observed in animal models...
  35. pmc Chemopreventive properties of black raspberries in N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis: down-regulation of cyclooxygenase-2, inducible nitric oxide synthase, and c-Jun
    Tong Chen
    Cancer Chemoprevention Program, Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210, USA
    Cancer Res 66:2853-9. 2006
    ..Prostaglandin E(2) and total nitrite levels were also decreased by BRB in papillomas. These results suggest a novel tumor suppressive role of BRB through inhibition of COX-2, iNOS, and c-Jun...
  36. ncbi Essential role of ROS-mediated NFAT activation in TNF-alpha induction by crystalline silica exposure
    Qingdong Ke
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, 10987, USA
    Am J Physiol Lung Cell Mol Physiol 291:L257-64. 2006
    ..This study demonstrated that silica was able to activate NFAT in an O(2)(-).-dependent manner, which was required for TNF-alpha induction...
  37. ncbi Knockdown of NFAT3 blocked TPA-induced COX-2 and iNOS expression, and enhanced cell transformation in Cl41 cells
    Jingxia Li
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA
    J Cell Biochem 99:1010-20. 2006
    ....
  38. ncbi Effects of polycyclic aromatic hydrocarbons (PAHs) on vascular endothelial growth factor induction through phosphatidylinositol 3-kinase/AP-1-dependent, HIF-1alpha-independent pathway
    Jin Ding
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA
    J Biol Chem 281:9093-100. 2006
    ..These findings may help us to understand the mechanisms involved in PAH carcinogenic effects...
  39. ncbi Black raspberry extracts inhibit benzo(a)pyrene diol-epoxide-induced activator protein 1 activation and VEGF transcription by targeting the phosphotidylinositol 3-kinase/Akt pathway
    Chuanshu Huang
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA
    Cancer Res 66:581-7. 2006
    ..In view of the important roles of AP-1 and VEGF in tumor development, one mechanism for the chemopreventive activity of black raspberries may be inhibition of the PI-3K/Akt/AP-1/VEGF pathway...
  40. ncbi Molecular mechanisms involved in chemoprevention of black raspberry extracts: from transcription factors to their target genes
    Haitian Lu
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA
    Nutr Cancer 54:69-78. 2006
    ..The RO-ME fraction appears to be the major fraction responsible for the inhibitory activity of black raspberries...
  41. ncbi NFAT3 is specifically required for TNF-alpha-induced cyclooxygenase-2 (COX-2) expression and transformation of Cl41 cells
    Yan Yan
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    J Cell Sci 119:2985-94. 2006
    ..These findings suggest that NFAT3/cyclooxygenase-2 act as a link between inflammation and carcinogenesis by being involved in the tumor promotion stage...
  42. ncbi Cyclooxygenase-2 induction by arsenite is through a nuclear factor of activated T-cell-dependent pathway and plays an antiapoptotic role in Beas-2B cells
    Jin Ding
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA
    J Biol Chem 281:24405-13. 2006
    ....
  43. pmc Effects of phenylethyl isothiocyanate on early molecular events in N-nitrosomethylbenzylamine-induced cytotoxicity in rat esophagus
    Rashmeet K Reen
    Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43240, USA
    Cancer Res 67:6484-92. 2007
    ..Samples obtained from animals treated with PEITC alone or cotreated with PEITC + NMBA were more similar to controls than to samples treated with NMBA alone...
  44. pmc Cancer prevention with freeze-dried berries and berry components
    Gary D Stoner
    Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, Innovation Centre, 2001 Polaris Parkway, Columbus, OH 43240, USA
    Semin Cancer Biol 17:403-10. 2007
    ..e., Barrett's esophagus, esophageal dysplasia and colonic polyps, to determine if berries will modulate various histological and molecular biomarkers of development of these diseases...
  45. pmc Chemoprevention of esophageal squamous cell carcinoma
    Gary D Stoner
    Division of Hematology and Oncology, Department of Internal Medicine, Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH 43210, USA
    Toxicol Appl Pharmacol 224:337-49. 2007
    ..These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC...
  46. pmc Cyclooxygenase-2 induction by arsenite through the IKKbeta/NFkappaB pathway exerts an antiapoptotic effect in mouse epidermal Cl41 cells
    Weiming Ouyang
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, USA
    Environ Health Perspect 115:513-8. 2007
    ..Epidemiologic data show that long-term arsenic exposure results in the risk of skin cancer. However, the mechanisms underlying carcinogenic effects of arsenite on skin remain to be studied...
  47. ncbi PI-3K/Akt signal pathway plays a crucial role in arsenite-induced cell proliferation of human keratinocytes through induction of cyclin D1
    Weiming Ouyang
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA
    J Cell Biochem 101:969-78. 2007
    ..Given the importance of aberrant cell proliferation in cell transformation, we propose that the activation of PI-3K/Akt pathway and cyclin D1 induction may be the important mediators of human skin carcinogenic effect of arsenite...
  48. pmc p85alpha acts as a novel signal transducer for mediation of cellular apoptotic response to UV radiation
    Lun Song
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    Mol Cell Biol 27:2713-31. 2007
    ....
  49. pmc IKKbeta programs to turn on the GADD45alpha-MKK4-JNK apoptotic cascade specifically via p50 NF-kappaB in arsenite response
    Lun Song
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA
    J Cell Biol 175:607-17. 2006
    ..Furthermore, the NF-kappaB p50 subunit can exert a novel regulatory function on protein modification independent of the classical NF-kappaB transcriptional activity...
  50. ncbi JNK1, but not JNK2, is required for COX-2 induction by nickel compounds
    Dongyun Zhang
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    Carcinogenesis 28:883-91. 2007
    ..Our results demonstrate that the JNK1/c-Jun/AP-1 pathway, but not the JNK2 pathway, plays a critical role in nickel-induced COX-2 expression...
  51. ncbi Nickel compounds render anti-apoptotic effect to human bronchial epithelial Beas-2B cells by induction of cyclooxygenase-2 through an IKKbeta/p65-dependent and IKKalpha- and p50-independent pathway
    Jin Ding
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA
    J Biol Chem 281:39022-32. 2006
    ....
  52. ncbi Coordination of JNK1 and JNK2 is critical for GADD45alpha induction and its mediated cell apoptosis in arsenite responses
    Dongyun Zhang
    Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA
    J Biol Chem 281:34113-23. 2006
    ..Our results demonstrate that the coordination of JNK1 and JNK2 is critical for c-Jun/GADD45alpha-mediated cellular apoptosis induced by arsenite...
  53. ncbi Benzo[a]pyrene diol-epoxide (B[a]PDE) upregulates COX-2 expression through MAPKs/AP-1 and IKKbeta/NF-kappaB in mouse epidermal Cl41 cells
    Weiming Ouyang
    Nelson Institute of Environmental Medicine, New York University, School of Medicine, Tuxedo, New York, USA
    Mol Carcinog 46:32-41. 2007
    ..In view of the importance of COX-2 in carcinogenesis, we anticipate that the induction of COX-2 by B[a]PDE may coordinate its mutagenic effects to facilitate the development of skin cancer...
  54. ncbi Essential roles of PI-3K/Akt/IKKbeta/NFkappaB pathway in cyclin D1 induction by arsenite in JB6 Cl41 cells
    Weiming Ouyang
    Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA
    Carcinogenesis 27:864-73. 2006
    ..Overall, arsenite exposure triggered PI-3K/Akt/IKKbeta/NFkappaB signal cascade which in turn plays essential roles in inducing cyclin D1 expression...

Research Grants30

  1. Chemoprevention of Head &Neck Cancer Using Controlled Release Polymers
    Susan R Mallery; Fiscal Year: 2013
    ..abstract_text> ..
  2. Chemopreventive Effects of Black Raspberries and Fenretinide in Oral Mucosa
    ANDREW STEPHEN HOLPUCH; Fiscal Year: 2013
    ..The proposed studies will evaluate an augmented chemopreventive formulation to be delivered by mucoadhesive patches, which will increase local delivery at the target site relative to gel application. ..
  3. Lung carcinogenesis: Chemoprevention by Indole-3-carbinol
    Fekadu Kassie; Fiscal Year: 2013
    ..Proving the hypothesis that indole-3-carbinol (I3C) inhibits lung tumorigenesis in A/J mouse model provides a solid platform for clinical trials of I3C as a chemopreventive agent against lung cancer. ..
  4. Inhibition of Reflux-Induced Esophageal Adenocarcinoma by Proanthocyanidins
    Laura A Kresty; Fiscal Year: 2013
    ....