Xiaohan Tang - Academia.edu (original) (raw)

Papers by Xiaohan Tang

Research paper thumbnail of Enhancing the performance of Co-hydrothermal liquefaction for mixed algae strains by the Maillard reaction

Green Chem., 2016

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Research paper thumbnail of Element and chemical compounds transfer in bio-crude from hydrothermal liquefaction of microalgae

Bioresource technology, Jan 7, 2015

In this study, hydrothermal liquefaction (HTL) experiments of Nannochloropsis and Spirulina were ... more In this study, hydrothermal liquefaction (HTL) experiments of Nannochloropsis and Spirulina were carried out at different temperatures (220-300°C) to explore the effects of temperature on bio-crude yield and properties. The optimal temperature for bio-crude yield was around 260-280°C. Transfers of element and chemical compounds in bio-crude were discussed in detail to deduce the reaction mechanism. The hydrogen and carbon recoveries were consistent with the results of bio-crude yields at every temperature point. The relative percentage of fatty acid in bio-crude decreased and the amine and amide increased for both microalgae with temperature rising. The N-heterocyclic compounds in bio-crude increased with temperature rising for Nannochloropsis, while decreased when temperature increased from 220°C to 280°C for Spirulina. Bio-crude gained at higher temperature or from microalgae with high protein content may contain high heteroatom compounds.

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Research paper thumbnail of Zinc Has an Insulin-Like Effect on Glucose Transport Mediated by Phosphoinositol-3-Kinase and Akt in 3T3-L1 Fibroblasts and Adipocytes

The Journal of Nutrition, May 1, 2001

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Research paper thumbnail of Worst Multiple Perturbation Load Approach of stiffened shells with and without cutouts for improved knockdown factors

Thin-Walled Structures, 2014

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Research paper thumbnail of Surrogate-based optimization of stiffened shells including load-carrying capacity and imperfection sensitivity

Thin-Walled Structures, 2013

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Research paper thumbnail of Comparison of direct and indirect pyrolysis of micro-algae Isochrysis

Bioresource technology, 2015

Yield and composition of pyrolysis oil in direct and indirect pyrolysis process were investigated... more Yield and composition of pyrolysis oil in direct and indirect pyrolysis process were investigated which indicated that pyrolysis of defatted microalgae provided a potential way to convert protein and carbohydrate to biofuels. Defatted microalgae pyrolysis with lipid extraction has higher total oil yield than only microalgae direct pyrolysis. There was an increase for N-heterocyclic compounds and phenols and a decrease for hydrocarbons in defatted microalgae pyrolysis oil. There is an apparent decrease from C12 to C16 and nearly no carbon distribution from C17 to C22 for defatted microalgae pyrolysis. Based on composition of pyrolysis feedstock, pyrolysis oil yields were simulated by Compounds Biofuel Model and their accuracy was less than ±4.4%. Considering total oil yield and characteristics, microalgae pyrolysis after lipid extraction process is a promising way for microalgae utilization.

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Research paper thumbnail of Initiation of esophageal squamous cell carcinoma (ESCC) in a murine 4-nitroquinoline-1-oxide and alcohol carcinogenesis model

Oncotarget, Jan 21, 2015

Esophageal squamous cell carcinomas (ESCCs) are very common, aggressive tumors, and are often ass... more Esophageal squamous cell carcinomas (ESCCs) are very common, aggressive tumors, and are often associated with alcohol and tobacco abuse. Because ESCCs exhibit high recurrence rates and are diagnosed at late stages, identification of prognostic and drug targets for prevention and treatment is critical. We used the 4-nitroquinoline-1-oxide (4-NQO) murine model of oral carcinogenesis and the Meadows-Cook model of alcohol abuse to assess changes in the expression of molecular markers during the initial stages of ESCC. Combining these two models, which mimic chronic alcohol and tobacco abuse in humans, we detected increased cellular proliferation (EGFR and Ki67 expression), increased canonical Wnt signaling and downstream elements (β-catenin, FoxM1, and S100a4 protein levels), changes in cellular adhesive properties (reduced E-cadherin in the basal layer of the esophageal epithelium), and increased levels of phosphorylated ERK1/2 and p38. Additionally, we found that treatment with ethano...

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Research paper thumbnail of Abstract 3036: Basal stem cells contribute to squamous cell carcinomas in the oral cavity

Cancer Research, 2014

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Research paper thumbnail of Effect of high-fat or high-glucose diet on obesity and visceral adipose tissue in mice

Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae, 2014

To investigate the effect of high-fat or high-glucose diet on obesity and visceral adipose tissue... more To investigate the effect of high-fat or high-glucose diet on obesity and visceral adipose tissue in C57BL/6 mice. Four-week-old C57BL/6 mice were allocated into normal diet group,high-fat diet group,and high-glucose diet group according to the random number table until 20 weeks old. Body weight,epididymal adipose tissue weight,blood leptin,fat infiltration in liver,M1/M2 macrophage subtypes,and monocyte chemoattractant protein-1 mRNA in epididymal adipose tissues were measured. Compared with normal diet group,body weight,epididymal adipose tissue weight,and leptin concentration in high fat diet group at 20 weeks were significantly increased (P < 0.05),and oil red O staining showed more prominent adipocyte infiltration in liver in high-fat diet group than those in normal diet and high-glucose diet group. However,no apparent differences were seen in high-glucose diet group at 20 weeks in terms of body weight,epididymal adipose tissue weight and leptin concentration. In high-fat di...

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Research paper thumbnail of Retinoids, retinoic acid receptors, and cancer

Annual review of pathology, 2011

Retinoids (i.e., vitamin A, all-trans retinoic acid, and related signaling molecules) induce the ... more Retinoids (i.e., vitamin A, all-trans retinoic acid, and related signaling molecules) induce the differentiation of various types of stem cells. Nuclear retinoic acid receptors mediate most but not all of the effects of retinoids. Retinoid signaling is often compromised early in carcinogenesis, which suggests that a reduction in retinoid signaling may be required for tumor development. Retinoids interact with other signaling pathways, including estrogen signaling in breast cancer. Retinoids are used to treat cancer, in part because of their ability to induce differentiation and arrest proliferation. Delivery of retinoids to patients is challenging because of the rapid metabolism of some retinoids and because epigenetic changes can render cells retinoid resistant. Successful cancer therapy with retinoids is likely to require combination therapy with drugs that regulate the epigenome, such as DNA methyltransferase and histone deacetylase inhibitors, as well as classical chemotherapeut...

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Research paper thumbnail of Combination of bexarotene and the retinoid CD1530 reduces murine oral-cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide

Proceedings of the National Academy of Sciences of the United States of America, Jan 17, 2014

We investigated the effects of bexarotene (a retinoid X receptor agonist), CD1530 (a retinoic aci... more We investigated the effects of bexarotene (a retinoid X receptor agonist), CD1530 (a retinoic acid receptor γ selective agonist), and the combination of these two drugs for the prevention of oral carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model of human oral-cavity and esophageal squamous-cell carcinoma previously generated in our laboratory. We observed decreased numbers of neoplastic tongue lesions and reduced lesion severity in the 4-NQO plus CD1530 (4N+C) and 4-NQO plus bexarotene plus CD1530 (4N+B+C) groups compared with the 4-NQO group. RNA-Seq analyses showed increases in transcripts in cell proliferation/cell cycle progression pathways in the 4-NQO vs. the untreated group. In addition, β-catenin and matrix metallopeptidase 9 (MMP9) protein levels and reactive oxygen species (ROS), as assessed by 4-hydroxynonenal (4-HNE) staining, were elevated in tongue tissues 17 wk after the termination of the 4-NQO treatment. The 4N+B, 4N+C, and 4...

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Research paper thumbnail of Chemoattractant activity of degradation products of fetal and adult skin extracellular matrix for keratinocyte progenitor cells

Journal of Tissue Engineering and Regenerative Medicine, 2008

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Research paper thumbnail of Histamine excites rat cerebellar granule cells in vitro through H1 and H2 receptors

Journal of Physiology-Paris, 1999

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Research paper thumbnail of Oral carcinogenesis induced by 4-nitroquinoline 1-oxide in lecithin:retinol acyltransferase gene knockout mice

The Journal of Nutritional Biochemistry, 2010

Lecithin:retinol acyltransferase (LRAT) regulates retinol (vitamin A) metabolism by esterifying r... more Lecithin:retinol acyltransferase (LRAT) regulates retinol (vitamin A) metabolism by esterifying retinol. LRAT expression is decreased in cultured human squamous cell carcinoma cells of the head and neck relative to normal epithelial cells. We investigated whether the carcinogen 4-nitroquinoline 1-oxide (4-NQO) induced a higher incidence of oral cancer in LRAT knockout (LRAT(-/-)) than in wild-type (Wt) mice. We also investigated retinol deprivation during 4-NQO treatment in LRAT(-/-) mice as a model for rapid retinol deficiency. We observed higher levels of secreted frizzled-related protein (Sfrp) 2, an inhibitor of WNT signaling, in tongue tumors in LRAT(-/-) versus Wt. LRAT(-/-) embryonic stem cells also expressed higher Sfrp2 transcripts, indicating an interaction between retinol and WNT signaling. Cox-2, Cyclin D1, p21, Trop2 and RARβ2 were not differentially expressed in Wt versus LRAT(-/-) tongue tumors. Wt and LRAT(-/-) mice fed a retinol-sufficient diet showed the same oral tumor incidence after 4-NQO treatment. In contrast, tongue tumors developed in 60% of Wt mice and in 100% of LRAT(-/-) mice fed a retinol-deficient diet during 4-NQO treatment (P=.22); moreover, the bromodeoxyuridine labeling index was 21.0 ± 2.4% in LRAT(-/-) normal tongue epithelium as compared to 9.9 ± 0.8% in Wt normal tongue epithelium (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). Thus, partial retinol deficiency during carcinogen treatment (achieved in LRAT(-/-)) resulted in more proliferating cells in tongue epithelia from LRAT(-/-) mice and, ultimately, a greater probability of carcinogenesis.

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Research paper thumbnail of Cell proliferation inhibition and alterations in retinol esterification induced by phytanic acid and docosahexaenoic acid

The Journal of Lipid Research, 2006

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Research paper thumbnail of Overexpression of CRABPI in suprabasal keratinocytes enhances the proliferation of epidermal basal keratinocytes in mouse skin topically treated with all-trans retinoic acid

Experimental Cell Research, 2008

We investigated whether ectopic expression of CRABPI, a cellular retinoic acid binding protein, i... more We investigated whether ectopic expression of CRABPI, a cellular retinoic acid binding protein, influenced the actions of all-trans retinoic acid (ATRA) in transgenic (TG) mice. We targeted CRABPI to the basal vs. suprabasal layers of mouse epidermis by using the keratin 14 (K14) and keratin 10 (K10) promoters, respectively. Greater CRABPI protein levels were detected in the epidermis of adult transgenic(+) mice than in transgenic(-) mice for both transgenes. In adult mouse skin CRABPI overexpression in the basal or suprabasal keratinocytes did not cause morphological abnormalities, but did result in decreased CRABPII mRNA levels. Ectopically overexpressed CRABPI in suprabasal keratinocytes, but not in basal keratinocytes, enhanced the thickening of the epidermis induced by topical ATRA treatments (10 microM, 400 microl for 4 days) by 1.59+/-0.2-fold (p&amp;amp;amp;amp;lt;0.05). ATRA treatment (10 microM) resulted in a 59.9+/-9.8% increase (p&amp;amp;amp;amp;lt;0.05) in the BrdU labeling index in K10/FLAG-CRABPI TG(+) mice vs. TG(-) mice. Retinoid topical treatments reduced p27 and CYP26A1 mRNA levels in TG(+) and TG(-) mouse skin in K14 and K10/FLAG-CRABPI transgenic mice. As epidermal basal keratinocyte proliferation is stimulated by paracrine growth factors secreted by ATRA activated suprabasal keratinocytes, our results indicate that CRABPI overexpression in suprabasal keratinocytes enhances the physiological functions of ATRA.

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Research paper thumbnail of Oral Cavity and Esophageal Carcinogenesis Modeled in Carcinogen-Treated Mice

Clinical Cancer Research, 2004

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Research paper thumbnail of The molecular features of tongue epithelium treated with the carcinogen 4-nitroquinoline-1-oxide and alcohol as a model for HNSCC

Carcinogenesis, 2013

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer affecting h... more Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer affecting humans worldwide. To determine the potential mechanisms by which chronic tobacco and alcohol abuse lead to HNSCC of the oral cavity, we have used both the 4-nitroquinoline-1-oxide (4-NQO) murine oral carcinogenesis and the Meadows-Cook alcohol models. In this study, we treated mice with 4-NQO in drinking water for 10 weeks and then administered 20% (w:v) ethanol (EtOH) for another 10 weeks. We observed increased levels and/or activation of signaling proteins [p38 mitogen-activated protein kinase (MAPK), β-catenin and Erk 1/2] that are typically altered during HNSCC initiation in humans. We found that EtOH administration alone increased the expression of p38 MAPK but not Erk 1/2 MAPK. Total β-catenin levels in the tongues increased by 2- to 3-fold after 4-NQO treatment, with or without EtOH. However, EtOH combined with 4-NQO reduced phosphorylated β-catenin levels, whereas 4-NQO treatment alone did not. These data implicate EtOH as a regulator of β-catenin signaling in this HNSCC model. We also utilized K14-CreER(TAM); ROSA26 mice to mark permanently stem/progenitor cells in the tongue epithelia. We found that 4-NQO alone and 4-NQO plus EtOH treatment resulted in massive, horizontal expansion of stem/progenitor cell populations arising from single stem cells in the basal layer of the epithelia. This expansion is consistent with carcinogen-associated, symmetric division of stem/progenitor cells. Our data suggest that specific therapeutic targets for prevention of HNSCC of the oral cavity associated with both alcohol and tobacco use are p38 MAPK and β-catenin.

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Research paper thumbnail of Basal stem cells contribute to squamous cell carcinomas in the oral cavity

Carcinogenesis, 2013

The cells of origin of oral cavity squamous cell carcinoma (OCSCC) are unknown. We used a cell li... more The cells of origin of oral cavity squamous cell carcinoma (OCSCC) are unknown. We used a cell lineage tracing approach (adult K14-CreER(TAM); ROSA26 mice transiently treated with tamoxifen) to identify and track normal epithelial stem cells (SCs) in mouse tongues by X-gal staining and to determine if these cells become neoplastically transformed by treatment with a carcinogen, 4-nitroquinoline 1-oxide (4-NQO). Here, we show that in normal tongue epithelia, X-gal(+) cells formed thin columns throughout the entire epithelium 12 weeks after tamoxifen treatment, indicating that the basal layer contains long-lived SCs that produce progeny by asymmetric division to maintain homeostasis. Carcinogen treatment results in a ~10-fold reduction in the total number of X-gal(+) clonal cell populations and horizontal expansion of X-gal(+) clonal cell columns, a pattern consistent with symmetric division of some SCs. Finally, X-gal(+) SCs are present in papillomas and invasive OCSCCs, and these long-lived X-gal(+) SCs are the cells of origin of these tumors. Moreover, the resulting 4-NQO-induced tumors are multiclonal. These findings provide insights into the identity of the initiating cells of oral cancer.

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Research paper thumbnail of Abstract 1338: MicroRNAs in a mouse model of oral carcinogenesis

Cancer Research, 2011

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Research paper thumbnail of Enhancing the performance of Co-hydrothermal liquefaction for mixed algae strains by the Maillard reaction

Green Chem., 2016

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Research paper thumbnail of Element and chemical compounds transfer in bio-crude from hydrothermal liquefaction of microalgae

Bioresource technology, Jan 7, 2015

In this study, hydrothermal liquefaction (HTL) experiments of Nannochloropsis and Spirulina were ... more In this study, hydrothermal liquefaction (HTL) experiments of Nannochloropsis and Spirulina were carried out at different temperatures (220-300°C) to explore the effects of temperature on bio-crude yield and properties. The optimal temperature for bio-crude yield was around 260-280°C. Transfers of element and chemical compounds in bio-crude were discussed in detail to deduce the reaction mechanism. The hydrogen and carbon recoveries were consistent with the results of bio-crude yields at every temperature point. The relative percentage of fatty acid in bio-crude decreased and the amine and amide increased for both microalgae with temperature rising. The N-heterocyclic compounds in bio-crude increased with temperature rising for Nannochloropsis, while decreased when temperature increased from 220°C to 280°C for Spirulina. Bio-crude gained at higher temperature or from microalgae with high protein content may contain high heteroatom compounds.

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Research paper thumbnail of Zinc Has an Insulin-Like Effect on Glucose Transport Mediated by Phosphoinositol-3-Kinase and Akt in 3T3-L1 Fibroblasts and Adipocytes

The Journal of Nutrition, May 1, 2001

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Research paper thumbnail of Worst Multiple Perturbation Load Approach of stiffened shells with and without cutouts for improved knockdown factors

Thin-Walled Structures, 2014

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Research paper thumbnail of Surrogate-based optimization of stiffened shells including load-carrying capacity and imperfection sensitivity

Thin-Walled Structures, 2013

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Research paper thumbnail of Comparison of direct and indirect pyrolysis of micro-algae Isochrysis

Bioresource technology, 2015

Yield and composition of pyrolysis oil in direct and indirect pyrolysis process were investigated... more Yield and composition of pyrolysis oil in direct and indirect pyrolysis process were investigated which indicated that pyrolysis of defatted microalgae provided a potential way to convert protein and carbohydrate to biofuels. Defatted microalgae pyrolysis with lipid extraction has higher total oil yield than only microalgae direct pyrolysis. There was an increase for N-heterocyclic compounds and phenols and a decrease for hydrocarbons in defatted microalgae pyrolysis oil. There is an apparent decrease from C12 to C16 and nearly no carbon distribution from C17 to C22 for defatted microalgae pyrolysis. Based on composition of pyrolysis feedstock, pyrolysis oil yields were simulated by Compounds Biofuel Model and their accuracy was less than ±4.4%. Considering total oil yield and characteristics, microalgae pyrolysis after lipid extraction process is a promising way for microalgae utilization.

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Research paper thumbnail of Initiation of esophageal squamous cell carcinoma (ESCC) in a murine 4-nitroquinoline-1-oxide and alcohol carcinogenesis model

Oncotarget, Jan 21, 2015

Esophageal squamous cell carcinomas (ESCCs) are very common, aggressive tumors, and are often ass... more Esophageal squamous cell carcinomas (ESCCs) are very common, aggressive tumors, and are often associated with alcohol and tobacco abuse. Because ESCCs exhibit high recurrence rates and are diagnosed at late stages, identification of prognostic and drug targets for prevention and treatment is critical. We used the 4-nitroquinoline-1-oxide (4-NQO) murine model of oral carcinogenesis and the Meadows-Cook model of alcohol abuse to assess changes in the expression of molecular markers during the initial stages of ESCC. Combining these two models, which mimic chronic alcohol and tobacco abuse in humans, we detected increased cellular proliferation (EGFR and Ki67 expression), increased canonical Wnt signaling and downstream elements (β-catenin, FoxM1, and S100a4 protein levels), changes in cellular adhesive properties (reduced E-cadherin in the basal layer of the esophageal epithelium), and increased levels of phosphorylated ERK1/2 and p38. Additionally, we found that treatment with ethano...

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Research paper thumbnail of Abstract 3036: Basal stem cells contribute to squamous cell carcinomas in the oral cavity

Cancer Research, 2014

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Research paper thumbnail of Effect of high-fat or high-glucose diet on obesity and visceral adipose tissue in mice

Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae, 2014

To investigate the effect of high-fat or high-glucose diet on obesity and visceral adipose tissue... more To investigate the effect of high-fat or high-glucose diet on obesity and visceral adipose tissue in C57BL/6 mice. Four-week-old C57BL/6 mice were allocated into normal diet group,high-fat diet group,and high-glucose diet group according to the random number table until 20 weeks old. Body weight,epididymal adipose tissue weight,blood leptin,fat infiltration in liver,M1/M2 macrophage subtypes,and monocyte chemoattractant protein-1 mRNA in epididymal adipose tissues were measured. Compared with normal diet group,body weight,epididymal adipose tissue weight,and leptin concentration in high fat diet group at 20 weeks were significantly increased (P < 0.05),and oil red O staining showed more prominent adipocyte infiltration in liver in high-fat diet group than those in normal diet and high-glucose diet group. However,no apparent differences were seen in high-glucose diet group at 20 weeks in terms of body weight,epididymal adipose tissue weight and leptin concentration. In high-fat di...

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Research paper thumbnail of Retinoids, retinoic acid receptors, and cancer

Annual review of pathology, 2011

Retinoids (i.e., vitamin A, all-trans retinoic acid, and related signaling molecules) induce the ... more Retinoids (i.e., vitamin A, all-trans retinoic acid, and related signaling molecules) induce the differentiation of various types of stem cells. Nuclear retinoic acid receptors mediate most but not all of the effects of retinoids. Retinoid signaling is often compromised early in carcinogenesis, which suggests that a reduction in retinoid signaling may be required for tumor development. Retinoids interact with other signaling pathways, including estrogen signaling in breast cancer. Retinoids are used to treat cancer, in part because of their ability to induce differentiation and arrest proliferation. Delivery of retinoids to patients is challenging because of the rapid metabolism of some retinoids and because epigenetic changes can render cells retinoid resistant. Successful cancer therapy with retinoids is likely to require combination therapy with drugs that regulate the epigenome, such as DNA methyltransferase and histone deacetylase inhibitors, as well as classical chemotherapeut...

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Research paper thumbnail of Combination of bexarotene and the retinoid CD1530 reduces murine oral-cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide

Proceedings of the National Academy of Sciences of the United States of America, Jan 17, 2014

We investigated the effects of bexarotene (a retinoid X receptor agonist), CD1530 (a retinoic aci... more We investigated the effects of bexarotene (a retinoid X receptor agonist), CD1530 (a retinoic acid receptor γ selective agonist), and the combination of these two drugs for the prevention of oral carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model of human oral-cavity and esophageal squamous-cell carcinoma previously generated in our laboratory. We observed decreased numbers of neoplastic tongue lesions and reduced lesion severity in the 4-NQO plus CD1530 (4N+C) and 4-NQO plus bexarotene plus CD1530 (4N+B+C) groups compared with the 4-NQO group. RNA-Seq analyses showed increases in transcripts in cell proliferation/cell cycle progression pathways in the 4-NQO vs. the untreated group. In addition, β-catenin and matrix metallopeptidase 9 (MMP9) protein levels and reactive oxygen species (ROS), as assessed by 4-hydroxynonenal (4-HNE) staining, were elevated in tongue tissues 17 wk after the termination of the 4-NQO treatment. The 4N+B, 4N+C, and 4...

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Research paper thumbnail of Chemoattractant activity of degradation products of fetal and adult skin extracellular matrix for keratinocyte progenitor cells

Journal of Tissue Engineering and Regenerative Medicine, 2008

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Histamine excites rat cerebellar granule cells in vitro through H1 and H2 receptors

Journal of Physiology-Paris, 1999

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Oral carcinogenesis induced by 4-nitroquinoline 1-oxide in lecithin:retinol acyltransferase gene knockout mice

The Journal of Nutritional Biochemistry, 2010

Lecithin:retinol acyltransferase (LRAT) regulates retinol (vitamin A) metabolism by esterifying r... more Lecithin:retinol acyltransferase (LRAT) regulates retinol (vitamin A) metabolism by esterifying retinol. LRAT expression is decreased in cultured human squamous cell carcinoma cells of the head and neck relative to normal epithelial cells. We investigated whether the carcinogen 4-nitroquinoline 1-oxide (4-NQO) induced a higher incidence of oral cancer in LRAT knockout (LRAT(-/-)) than in wild-type (Wt) mice. We also investigated retinol deprivation during 4-NQO treatment in LRAT(-/-) mice as a model for rapid retinol deficiency. We observed higher levels of secreted frizzled-related protein (Sfrp) 2, an inhibitor of WNT signaling, in tongue tumors in LRAT(-/-) versus Wt. LRAT(-/-) embryonic stem cells also expressed higher Sfrp2 transcripts, indicating an interaction between retinol and WNT signaling. Cox-2, Cyclin D1, p21, Trop2 and RARβ2 were not differentially expressed in Wt versus LRAT(-/-) tongue tumors. Wt and LRAT(-/-) mice fed a retinol-sufficient diet showed the same oral tumor incidence after 4-NQO treatment. In contrast, tongue tumors developed in 60% of Wt mice and in 100% of LRAT(-/-) mice fed a retinol-deficient diet during 4-NQO treatment (P=.22); moreover, the bromodeoxyuridine labeling index was 21.0 ± 2.4% in LRAT(-/-) normal tongue epithelium as compared to 9.9 ± 0.8% in Wt normal tongue epithelium (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). Thus, partial retinol deficiency during carcinogen treatment (achieved in LRAT(-/-)) resulted in more proliferating cells in tongue epithelia from LRAT(-/-) mice and, ultimately, a greater probability of carcinogenesis.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Cell proliferation inhibition and alterations in retinol esterification induced by phytanic acid and docosahexaenoic acid

The Journal of Lipid Research, 2006

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Research paper thumbnail of Overexpression of CRABPI in suprabasal keratinocytes enhances the proliferation of epidermal basal keratinocytes in mouse skin topically treated with all-trans retinoic acid

Experimental Cell Research, 2008

We investigated whether ectopic expression of CRABPI, a cellular retinoic acid binding protein, i... more We investigated whether ectopic expression of CRABPI, a cellular retinoic acid binding protein, influenced the actions of all-trans retinoic acid (ATRA) in transgenic (TG) mice. We targeted CRABPI to the basal vs. suprabasal layers of mouse epidermis by using the keratin 14 (K14) and keratin 10 (K10) promoters, respectively. Greater CRABPI protein levels were detected in the epidermis of adult transgenic(+) mice than in transgenic(-) mice for both transgenes. In adult mouse skin CRABPI overexpression in the basal or suprabasal keratinocytes did not cause morphological abnormalities, but did result in decreased CRABPII mRNA levels. Ectopically overexpressed CRABPI in suprabasal keratinocytes, but not in basal keratinocytes, enhanced the thickening of the epidermis induced by topical ATRA treatments (10 microM, 400 microl for 4 days) by 1.59+/-0.2-fold (p&amp;amp;amp;amp;lt;0.05). ATRA treatment (10 microM) resulted in a 59.9+/-9.8% increase (p&amp;amp;amp;amp;lt;0.05) in the BrdU labeling index in K10/FLAG-CRABPI TG(+) mice vs. TG(-) mice. Retinoid topical treatments reduced p27 and CYP26A1 mRNA levels in TG(+) and TG(-) mouse skin in K14 and K10/FLAG-CRABPI transgenic mice. As epidermal basal keratinocyte proliferation is stimulated by paracrine growth factors secreted by ATRA activated suprabasal keratinocytes, our results indicate that CRABPI overexpression in suprabasal keratinocytes enhances the physiological functions of ATRA.

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Research paper thumbnail of Oral Cavity and Esophageal Carcinogenesis Modeled in Carcinogen-Treated Mice

Clinical Cancer Research, 2004

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Research paper thumbnail of The molecular features of tongue epithelium treated with the carcinogen 4-nitroquinoline-1-oxide and alcohol as a model for HNSCC

Carcinogenesis, 2013

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer affecting h... more Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer affecting humans worldwide. To determine the potential mechanisms by which chronic tobacco and alcohol abuse lead to HNSCC of the oral cavity, we have used both the 4-nitroquinoline-1-oxide (4-NQO) murine oral carcinogenesis and the Meadows-Cook alcohol models. In this study, we treated mice with 4-NQO in drinking water for 10 weeks and then administered 20% (w:v) ethanol (EtOH) for another 10 weeks. We observed increased levels and/or activation of signaling proteins [p38 mitogen-activated protein kinase (MAPK), β-catenin and Erk 1/2] that are typically altered during HNSCC initiation in humans. We found that EtOH administration alone increased the expression of p38 MAPK but not Erk 1/2 MAPK. Total β-catenin levels in the tongues increased by 2- to 3-fold after 4-NQO treatment, with or without EtOH. However, EtOH combined with 4-NQO reduced phosphorylated β-catenin levels, whereas 4-NQO treatment alone did not. These data implicate EtOH as a regulator of β-catenin signaling in this HNSCC model. We also utilized K14-CreER(TAM); ROSA26 mice to mark permanently stem/progenitor cells in the tongue epithelia. We found that 4-NQO alone and 4-NQO plus EtOH treatment resulted in massive, horizontal expansion of stem/progenitor cell populations arising from single stem cells in the basal layer of the epithelia. This expansion is consistent with carcinogen-associated, symmetric division of stem/progenitor cells. Our data suggest that specific therapeutic targets for prevention of HNSCC of the oral cavity associated with both alcohol and tobacco use are p38 MAPK and β-catenin.

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Research paper thumbnail of Basal stem cells contribute to squamous cell carcinomas in the oral cavity

Carcinogenesis, 2013

The cells of origin of oral cavity squamous cell carcinoma (OCSCC) are unknown. We used a cell li... more The cells of origin of oral cavity squamous cell carcinoma (OCSCC) are unknown. We used a cell lineage tracing approach (adult K14-CreER(TAM); ROSA26 mice transiently treated with tamoxifen) to identify and track normal epithelial stem cells (SCs) in mouse tongues by X-gal staining and to determine if these cells become neoplastically transformed by treatment with a carcinogen, 4-nitroquinoline 1-oxide (4-NQO). Here, we show that in normal tongue epithelia, X-gal(+) cells formed thin columns throughout the entire epithelium 12 weeks after tamoxifen treatment, indicating that the basal layer contains long-lived SCs that produce progeny by asymmetric division to maintain homeostasis. Carcinogen treatment results in a ~10-fold reduction in the total number of X-gal(+) clonal cell populations and horizontal expansion of X-gal(+) clonal cell columns, a pattern consistent with symmetric division of some SCs. Finally, X-gal(+) SCs are present in papillomas and invasive OCSCCs, and these long-lived X-gal(+) SCs are the cells of origin of these tumors. Moreover, the resulting 4-NQO-induced tumors are multiclonal. These findings provide insights into the identity of the initiating cells of oral cancer.

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Research paper thumbnail of Abstract 1338: MicroRNAs in a mouse model of oral carcinogenesis

Cancer Research, 2011

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