Prostate cancer is the most common non-cutaneous cancer among men. A man with 1,2 or 3 first degr... more Prostate cancer is the most common non-cutaneous cancer among men. A man with 1,2 or 3 first degree relatives with prostate cancer, has a 2,5, and 11-fold increased risk of developing prostate cancer. The heritability rate of prostate cancer is 58%. African American men have the highest incidence and mortality rate of prostate cancer in American. Men of African descent, globally, are more likely to die from prostate cancer than any other ancestral groups. We performed Immunohistochemistry(IHC) and RNA seq analysis on African American tissue and serum samples, with a focus on HMGA2, which has been shown promote EMT, invasion, and metastasis in cancer. Acknowledgements: These studies were supported by NIH/NIMHD U54MD007590 and U54MD013376. Our sample set included 3 benign and 2 prostate cancer tumors from African Americans. IHC markers showed HMGA2 staining within epithelial cells of the prostate cancer tissue. This result validates studies that show that distinct subtypes of prostate...
The aryl hydrocarbon receptor (AhR) is a nuclear transcription factor and xenobiotic sensor repor... more The aryl hydrocarbon receptor (AhR) is a nuclear transcription factor and xenobiotic sensor reported to mediate diet-induced obesity and is upregulated in high-grade prostate cancer (PCa). Previously published data from our lab shows that AhR protein is overexpressed and constitutively active in castration-resistant prostate cancer cells. Physiologically relevant leptin concentration is proportional to BMI and it is secreted by adipose cells to inhibit hunger under normal circumstances. Our preliminary results suggest that obesity-associated leptin concentrations desensitize PCa cells to cancer drugs however, the underlying mechanisms must be elucidated and may require sustained AhR signaling. In this study, we conducted an integrative bioinformatics analysis to explore the role of AHR and LEPR in PCa, which revealed AHR and LEPR mRNA expression positively correlates in prostate cancer (P<0.05, Pearson: 0.68, R^2=0.46). The mRNA expression levels of AHR and LEPR in PCa tissue sam...
Background: It is imperative to develop novel therapeutics to overcome chemoresistance, a major o... more Background: It is imperative to develop novel therapeutics to overcome chemoresistance, a major obstacle in the clinical management of prostate cancer (PCa) and other cancers. Drug repositioning is being pursued as an attractive approach due to its potentially lower overall development costs and shorter timelines. The purpose of this study is to investigate the preclinical efficacy and mechanism of action of nicardipine, an FDA-approved hypertension drug, as a new treatment against chemoresistant prostate cancer. Methods: A panel of FDA-approved non-oncology drugs was screened for their selectivity and potency to inhibit chemoresistant PCa cells using a two-tier phenotypic screening platform (Theranostics, 2021, 11(14): 6873-6890). The mechanism of action of potential candidate(s) was evaluated using in silico docking, cellular and molecular assays in ARCaPE-shEPLIN and C4-2B-TaxR, two independent chemoresistant PCa cell lines. The in vivo efficacy was evaluated in clinically-releva...
Prostate cancer (PCa) is one of the most commonly diagnosed malignancies among men worldwide and ... more Prostate cancer (PCa) is one of the most commonly diagnosed malignancies among men worldwide and remains the second leading cause of cancer related death in the United States. Oxidative stress has been shown to be increase in several cancers including prostate cancer. In fact, oxidative stress in prostate cancer is suggested to be a direct result of cell exposure to reactive oxygen species (ROS). High mobility group A 2 (HMGA2), a non-histone protein, is an oncogene that is up-regulated in several cancers. This protein has ability to undergo chromosomal rearrangement and alternative splicing, causing its full length/wild type HMGA2 (HMGA2-WT) to become the truncated losing its 3’UTR leading to the generation of HMGA2 truncated (HMGA2-TR). We have previously shown HMGA2-WT’s involvement in epithelial mesenchymal transition (EMT), however, the functional role of HMGA2-TR has not yet been dissected. We hypothesize that truncated HMGA2’s involvement with oxidative stress leads to prosta...
GLIPR1 expression in A549, PC14, LNCaP, PC3 and U87 cells. Western blot analysis of whole-cell ly... more GLIPR1 expression in A549, PC14, LNCaP, PC3 and U87 cells. Western blot analysis of whole-cell lysates derived from A549 (lane 1), PC14 (lane2), LNCaP (lane 3), PC3 (lane 4), and U87 (lane 5) cells with anti-GLIPR1 or -actin antibody. (PDF 308 kb)
The expression profile of GLIPR1 in various lung cancer cell lines. The results were obtained fro... more The expression profile of GLIPR1 in various lung cancer cell lines. The results were obtained from expression profiling (GDS1688) of a set of 29 lung cancer cell lines consisting of ten non-small cell adenocarcinoma, ten small cell cancer, and nine squamous cell cancer lines. Value: the RMA normalized expression value. Rank: the position of the GLIPR1 gene across 22,337 genes on the DNA chip based on the expression level (from low to high). (PDF 403 kb)
WDR77 regulates GLIPR1 expression not through the p53 signaling. a Western blot analysis of whole... more WDR77 regulates GLIPR1 expression not through the p53 signaling. a Western blot analysis of whole-cell lysates derived from LNCaP cells expressing NT shRNA (lane 1) or WDR77 shRNA (lane 2) with anti-WDR77, −p53, or -actin. b Silencing WDR77 expression decreased the activity of the p53 reporter. LNCaP cells expressing NT or WDR77 shRNA were transfected with 150 ng of the reporter plasmid pGL3-4 × PBE-E4-luc. The transfected cells were allowed to grow for 48 h and then harvested for the luciferase assay (Promega). The values represent the mean ± SD (n = 3). (PDF 431 kb)
The expression profile of WDR77 in various lung cancer cell lines. The results were obtained from... more The expression profile of WDR77 in various lung cancer cell lines. The results were obtained from expression profiling (GDS1688) of a set of 29 lung cancer cell lines consisting of ten non-small cell adenocarcinoma, ten small cell cancer, and nine squamous cell cancer lines. Value: the RMA normalized expression value. Rank: the position of the WDR77 gene across 22,337 genes on the DNA chip based on the expression level (from low to high). (PDF 428 kb)
The expression profile of GLIPR1 in small cell lung cancers. The results were obtained from expre... more The expression profile of GLIPR1 in small cell lung cancers. The results were obtained from expression profiling (GDS4794) of 23 clinical small cell lung cancer (SCLC) samples from patients undergoing pulmonary resection and the normal lung tissue sample. (PDF 352 kb)
Cell-cycle distribution in A549 cells infected with control lentivirus or GLIPR1-expressing lenti... more Cell-cycle distribution in A549 cells infected with control lentivirus or GLIPR1-expressing lentivirus by using flow cytometric analysis. (PDF 611 kb)
Ls after 72 h of incubation in the presence of the tested metabolite at a concentration of 100 μm... more Ls after 72 h of incubation in the presence of the tested metabolite at a concentration of 100 μmol/L. Effect of metabolites predicted to be lowered (A), increased (B) or unchanged (C) in Jurkat cells when compared with normal lymphoblasts, on the proliferation of Jurkat cells (2 biological replicates, each with 4 analytical replicates). MQ = menaquinone; HS = α-hydroxystearic acid; DE = dehydroepiandrosterone; SU = 3-sulfino-L-alanine; DM = 5,6-dimethylbenzimidazole; SE = seleno-L-methionine; RB = riboflavin; TN = tryptamine; HA = hydroxyacetone; BR = bilirubin; AT = androsterone; HV = homovanillic acid; VA = vanillylmandelic acid; AA = N-acetyl-L-aspartate; TA = taurocholic acid, CA = citric acid; PA = pantothenic acid; GA = β-D-galactose; FA = folic acid; CH = cholesterol. Error bars represent standard error of mean.<b>Copyright information:</b>Taken from "Identification of metabolites with anticancer properties by computational metabolomics"http://www.molec...
Lls when enzymes that produce X are upregulated and/or enzymes that consume X are downregulated i... more Lls when enzymes that produce X are upregulated and/or enzymes that consume X are downregulated in cancer cells. (B) The intracellular level of a metabolite X is predicted to be decreased in cancer cells when enzymes that produce X are downregulated and/or enzymes that consume X are upregulated in cancer cells. See Material and Methods for a complete description of the rules.<b>Copyright information:</b>Taken from "Identification of metabolites with anticancer properties by computational metabolomics"http://www.molecular-cancer.com/content/7/1/57Molecular Cancer 2008;7():57-57.Published online 17 Jun 2008PMCID:PMC2453147.
KIFCI, a novel putative prognostic biomarker for ovarian adenocarcinomas: delineating protein Con... more KIFCI, a novel putative prognostic biomarker for ovarian adenocarcinomas: delineating protein Conclusions: Ovarian cancers display amplified centrosomes, a feature of aggressive tumors. To cope up with the Pawar et al. Journal of Ovarian Research 2014, 7:53
Objectives. Epithelial ovarian carcinomas develop from ovarian surface epithelia that undergo com... more Objectives. Epithelial ovarian carcinomas develop from ovarian surface epithelia that undergo complex differentiation to form distinguishable phenotypes resembling those of the epithelia of the female urogenital regions. While previous studies have implicated regulatory developmental homeobox (HOX) genes in this process, other factors responsible for this differentiation are largely unknown. Aberrant transcriptional expression of PAX8 has been reported in epithelial ovarian cancer, prompting us to initiate the molecular characterization of this master regulatory gene in ovarian cancer development. Methods. Immunohistochemistry, immunoblotting and RT-PCR were used to investigate the presence of PAX8 and its protein products in epithelial ovarian cancer subtypes, normal ovarian surface epithelia, ovarian inclusion cysts, and normal endosalpingeal epithelia. Results. In this report, we confirm microarray results indicating that the transcription factor, PAX8, is highly expressed in epi...
Supplementary Results were obtained from expression profiling (GDS3950) of lung from the mouse ov... more Supplementary Results were obtained from expression profiling (GDS3950) of lung from the mouse over a time course beginning at embryonic day 12 and continuing into adulthood, encompassing all recognized stages of lung development. (PDF 289 kb)
Prostate cancer is the most common non-cutaneous cancer among men. A man with 1,2 or 3 first degr... more Prostate cancer is the most common non-cutaneous cancer among men. A man with 1,2 or 3 first degree relatives with prostate cancer, has a 2,5, and 11-fold increased risk of developing prostate cancer. The heritability rate of prostate cancer is 58%. African American men have the highest incidence and mortality rate of prostate cancer in American. Men of African descent, globally, are more likely to die from prostate cancer than any other ancestral groups. We performed Immunohistochemistry(IHC) and RNA seq analysis on African American tissue and serum samples, with a focus on HMGA2, which has been shown promote EMT, invasion, and metastasis in cancer. Acknowledgements: These studies were supported by NIH/NIMHD U54MD007590 and U54MD013376. Our sample set included 3 benign and 2 prostate cancer tumors from African Americans. IHC markers showed HMGA2 staining within epithelial cells of the prostate cancer tissue. This result validates studies that show that distinct subtypes of prostate...
The aryl hydrocarbon receptor (AhR) is a nuclear transcription factor and xenobiotic sensor repor... more The aryl hydrocarbon receptor (AhR) is a nuclear transcription factor and xenobiotic sensor reported to mediate diet-induced obesity and is upregulated in high-grade prostate cancer (PCa). Previously published data from our lab shows that AhR protein is overexpressed and constitutively active in castration-resistant prostate cancer cells. Physiologically relevant leptin concentration is proportional to BMI and it is secreted by adipose cells to inhibit hunger under normal circumstances. Our preliminary results suggest that obesity-associated leptin concentrations desensitize PCa cells to cancer drugs however, the underlying mechanisms must be elucidated and may require sustained AhR signaling. In this study, we conducted an integrative bioinformatics analysis to explore the role of AHR and LEPR in PCa, which revealed AHR and LEPR mRNA expression positively correlates in prostate cancer (P<0.05, Pearson: 0.68, R^2=0.46). The mRNA expression levels of AHR and LEPR in PCa tissue sam...
Background: It is imperative to develop novel therapeutics to overcome chemoresistance, a major o... more Background: It is imperative to develop novel therapeutics to overcome chemoresistance, a major obstacle in the clinical management of prostate cancer (PCa) and other cancers. Drug repositioning is being pursued as an attractive approach due to its potentially lower overall development costs and shorter timelines. The purpose of this study is to investigate the preclinical efficacy and mechanism of action of nicardipine, an FDA-approved hypertension drug, as a new treatment against chemoresistant prostate cancer. Methods: A panel of FDA-approved non-oncology drugs was screened for their selectivity and potency to inhibit chemoresistant PCa cells using a two-tier phenotypic screening platform (Theranostics, 2021, 11(14): 6873-6890). The mechanism of action of potential candidate(s) was evaluated using in silico docking, cellular and molecular assays in ARCaPE-shEPLIN and C4-2B-TaxR, two independent chemoresistant PCa cell lines. The in vivo efficacy was evaluated in clinically-releva...
Prostate cancer (PCa) is one of the most commonly diagnosed malignancies among men worldwide and ... more Prostate cancer (PCa) is one of the most commonly diagnosed malignancies among men worldwide and remains the second leading cause of cancer related death in the United States. Oxidative stress has been shown to be increase in several cancers including prostate cancer. In fact, oxidative stress in prostate cancer is suggested to be a direct result of cell exposure to reactive oxygen species (ROS). High mobility group A 2 (HMGA2), a non-histone protein, is an oncogene that is up-regulated in several cancers. This protein has ability to undergo chromosomal rearrangement and alternative splicing, causing its full length/wild type HMGA2 (HMGA2-WT) to become the truncated losing its 3’UTR leading to the generation of HMGA2 truncated (HMGA2-TR). We have previously shown HMGA2-WT’s involvement in epithelial mesenchymal transition (EMT), however, the functional role of HMGA2-TR has not yet been dissected. We hypothesize that truncated HMGA2’s involvement with oxidative stress leads to prosta...
GLIPR1 expression in A549, PC14, LNCaP, PC3 and U87 cells. Western blot analysis of whole-cell ly... more GLIPR1 expression in A549, PC14, LNCaP, PC3 and U87 cells. Western blot analysis of whole-cell lysates derived from A549 (lane 1), PC14 (lane2), LNCaP (lane 3), PC3 (lane 4), and U87 (lane 5) cells with anti-GLIPR1 or -actin antibody. (PDF 308 kb)
The expression profile of GLIPR1 in various lung cancer cell lines. The results were obtained fro... more The expression profile of GLIPR1 in various lung cancer cell lines. The results were obtained from expression profiling (GDS1688) of a set of 29 lung cancer cell lines consisting of ten non-small cell adenocarcinoma, ten small cell cancer, and nine squamous cell cancer lines. Value: the RMA normalized expression value. Rank: the position of the GLIPR1 gene across 22,337 genes on the DNA chip based on the expression level (from low to high). (PDF 403 kb)
WDR77 regulates GLIPR1 expression not through the p53 signaling. a Western blot analysis of whole... more WDR77 regulates GLIPR1 expression not through the p53 signaling. a Western blot analysis of whole-cell lysates derived from LNCaP cells expressing NT shRNA (lane 1) or WDR77 shRNA (lane 2) with anti-WDR77, −p53, or -actin. b Silencing WDR77 expression decreased the activity of the p53 reporter. LNCaP cells expressing NT or WDR77 shRNA were transfected with 150 ng of the reporter plasmid pGL3-4 × PBE-E4-luc. The transfected cells were allowed to grow for 48 h and then harvested for the luciferase assay (Promega). The values represent the mean ± SD (n = 3). (PDF 431 kb)
The expression profile of WDR77 in various lung cancer cell lines. The results were obtained from... more The expression profile of WDR77 in various lung cancer cell lines. The results were obtained from expression profiling (GDS1688) of a set of 29 lung cancer cell lines consisting of ten non-small cell adenocarcinoma, ten small cell cancer, and nine squamous cell cancer lines. Value: the RMA normalized expression value. Rank: the position of the WDR77 gene across 22,337 genes on the DNA chip based on the expression level (from low to high). (PDF 428 kb)
The expression profile of GLIPR1 in small cell lung cancers. The results were obtained from expre... more The expression profile of GLIPR1 in small cell lung cancers. The results were obtained from expression profiling (GDS4794) of 23 clinical small cell lung cancer (SCLC) samples from patients undergoing pulmonary resection and the normal lung tissue sample. (PDF 352 kb)
Cell-cycle distribution in A549 cells infected with control lentivirus or GLIPR1-expressing lenti... more Cell-cycle distribution in A549 cells infected with control lentivirus or GLIPR1-expressing lentivirus by using flow cytometric analysis. (PDF 611 kb)
Ls after 72 h of incubation in the presence of the tested metabolite at a concentration of 100 μm... more Ls after 72 h of incubation in the presence of the tested metabolite at a concentration of 100 μmol/L. Effect of metabolites predicted to be lowered (A), increased (B) or unchanged (C) in Jurkat cells when compared with normal lymphoblasts, on the proliferation of Jurkat cells (2 biological replicates, each with 4 analytical replicates). MQ = menaquinone; HS = α-hydroxystearic acid; DE = dehydroepiandrosterone; SU = 3-sulfino-L-alanine; DM = 5,6-dimethylbenzimidazole; SE = seleno-L-methionine; RB = riboflavin; TN = tryptamine; HA = hydroxyacetone; BR = bilirubin; AT = androsterone; HV = homovanillic acid; VA = vanillylmandelic acid; AA = N-acetyl-L-aspartate; TA = taurocholic acid, CA = citric acid; PA = pantothenic acid; GA = β-D-galactose; FA = folic acid; CH = cholesterol. Error bars represent standard error of mean.<b>Copyright information:</b>Taken from "Identification of metabolites with anticancer properties by computational metabolomics"http://www.molec...
Lls when enzymes that produce X are upregulated and/or enzymes that consume X are downregulated i... more Lls when enzymes that produce X are upregulated and/or enzymes that consume X are downregulated in cancer cells. (B) The intracellular level of a metabolite X is predicted to be decreased in cancer cells when enzymes that produce X are downregulated and/or enzymes that consume X are upregulated in cancer cells. See Material and Methods for a complete description of the rules.<b>Copyright information:</b>Taken from "Identification of metabolites with anticancer properties by computational metabolomics"http://www.molecular-cancer.com/content/7/1/57Molecular Cancer 2008;7():57-57.Published online 17 Jun 2008PMCID:PMC2453147.
KIFCI, a novel putative prognostic biomarker for ovarian adenocarcinomas: delineating protein Con... more KIFCI, a novel putative prognostic biomarker for ovarian adenocarcinomas: delineating protein Conclusions: Ovarian cancers display amplified centrosomes, a feature of aggressive tumors. To cope up with the Pawar et al. Journal of Ovarian Research 2014, 7:53
Objectives. Epithelial ovarian carcinomas develop from ovarian surface epithelia that undergo com... more Objectives. Epithelial ovarian carcinomas develop from ovarian surface epithelia that undergo complex differentiation to form distinguishable phenotypes resembling those of the epithelia of the female urogenital regions. While previous studies have implicated regulatory developmental homeobox (HOX) genes in this process, other factors responsible for this differentiation are largely unknown. Aberrant transcriptional expression of PAX8 has been reported in epithelial ovarian cancer, prompting us to initiate the molecular characterization of this master regulatory gene in ovarian cancer development. Methods. Immunohistochemistry, immunoblotting and RT-PCR were used to investigate the presence of PAX8 and its protein products in epithelial ovarian cancer subtypes, normal ovarian surface epithelia, ovarian inclusion cysts, and normal endosalpingeal epithelia. Results. In this report, we confirm microarray results indicating that the transcription factor, PAX8, is highly expressed in epi...
Supplementary Results were obtained from expression profiling (GDS3950) of lung from the mouse ov... more Supplementary Results were obtained from expression profiling (GDS3950) of lung from the mouse over a time course beginning at embryonic day 12 and continuing into adulthood, encompassing all recognized stages of lung development. (PDF 289 kb)
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