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Full-Text Articles in Cancer Biology

Ror-Γ Drives Androgen Receptor Expression And Represents A Therapeutic Target In Castration-Resistant Prostate Cancer, Jujian Wang, June X. Zou, Xiaoqian Xue, Demin Cai, Yan Zhang, Zguhuab Duan, Qiuping Xiang, Joy C. Yang, Maggie C. Louie, Alexander D Borowsky, Allen C. Gao, Christopher P. Evans, Kit S. Lam, Jianzhen Xu, Hsing-Jien Kung, Ronald M. Evans, Yong Xu, Hong-Wu Chen Apr 2016

Ror-Γ Drives Androgen Receptor Expression And Represents A Therapeutic Target In Castration-Resistant Prostate Cancer, Jujian Wang, June X. Zou, Xiaoqian Xue, Demin Cai, Yan Zhang, Zguhuab Duan, Qiuping Xiang, Joy C. Yang, Maggie C. Louie, Alexander D Borowsky, Allen C. Gao, Christopher P. Evans, Kit S. Lam, Jianzhen Xu, Hsing-Jien Kung, Ronald M. Evans, Yong Xu, Hong-Wu Chen

Maggie Louie

The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor-related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR-ROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and ...


Reactive Oxygen Species-Mediated Breast Cell Carcinogenesis Enhanced By Multiple Carcinogens And Intervened By Dietary Ergosterol And Mimosine, Lenora Pluchino, Amethyst Liu, Hwa-Chain Wang Dec 2014

Reactive Oxygen Species-Mediated Breast Cell Carcinogenesis Enhanced By Multiple Carcinogens And Intervened By Dietary Ergosterol And Mimosine, Lenora Pluchino, Amethyst Liu, Hwa-Chain Wang

Hwa-Chain Robert Wang

No abstract provided.


Neutron Radiography With Combined Computed Tomography: A Novel Tool For Cancer Diagnosis And Imaging (Abstract), Maria Cekanova, H Bilheux, Kusum Rathore, J Bilheux, L Walker, Robert Donnell, Alfred Legendre May 2013

Neutron Radiography With Combined Computed Tomography: A Novel Tool For Cancer Diagnosis And Imaging (Abstract), Maria Cekanova, H Bilheux, Kusum Rathore, J Bilheux, L Walker, Robert Donnell, Alfred Legendre

Alfred M Legendre DVM, MS, DACVIM

No abstract provided.


Preclinical Single-Dose Safety And Pharmacokinetic Evaluation Of Fluorocoxib A: Pilot Study Of Novel Cyclooxygenase-2-Targeted Optical Imaging Agent In A Canine Model, Maria Cekanova, M Uddin, Alfred Legendre, Gina Gaylon, Joseph Bartges, Amanda Callens, L Marnett May 2013

Preclinical Single-Dose Safety And Pharmacokinetic Evaluation Of Fluorocoxib A: Pilot Study Of Novel Cyclooxygenase-2-Targeted Optical Imaging Agent In A Canine Model, Maria Cekanova, M Uddin, Alfred Legendre, Gina Gaylon, Joseph Bartges, Amanda Callens, L Marnett

Alfred M Legendre DVM, MS, DACVIM

We evaluated preclinical single-dose safety, pharmacokinetic properties, and specific uptake of the new optical imaging agent fluorocoxib A in dogs. Fluorocoxib A, N-[(5-carboxy-X-rhodaminyl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide, selectively binds and inhibits the cyclooxygenase-2 (COX-2) enzyme, which is overexpressed in many cancers. Safety pilot studies were performed in research dogs following intravenous (i.v.) administration of 0.1 and 1  mg/kg fluorocoxib A. Blood and urine samples collected three days after administration of each dose of fluorocoxib A revealed no evidence of toxicity, and no clinically relevant adverse events were noted on physical examination of exposed dogs ...


Molecular Imaging Of Cyclooxygenase-2 In Canine Transitional Cell Carcinomas In Vitro And In Vivo, Maria Cekanova, M Uddin, Joseph Bartges, Amanda Callens, Kusum Rathore, Alfred Legendre, L Wright, L Marnett Apr 2013

Molecular Imaging Of Cyclooxygenase-2 In Canine Transitional Cell Carcinomas In Vitro And In Vivo, Maria Cekanova, M Uddin, Joseph Bartges, Amanda Callens, Kusum Rathore, Alfred Legendre, L Wright, L Marnett

Maria Cekanova MS, RNDr, PhD

The enzyme COX-2 is induced at high levels in tumors but not in surrounding normal tissues, which makes it an attractive target for molecular imaging of cancer. We evaluated the ability of novel optical imaging agent, fluorocoxib A to detect urinary bladder canine transitional cell carcinomas (K9TCC). Here, we show that fluorocoxib A uptake overlapped with COX-2 expression in primary K9TCC cells in vitro. Using subcutaneously implanted primary K9TCC in athymic mice, we show specific uptake of fluorocoxib A by COX-2-expressing K9TCC xenograft tumors in vivo. Fluorocoxib A uptake by COX-2-expressing xenograft tumors was blocked by 70% (P < 0.005) when pretreated with the COX-2 selective inhibitor, celecoxib (10 mg/kg), 4 hours before intravenous administration of fluorocoxib A (1 mg/kg). Fluorocoxib A was taken up by COX-2-expressing tumors but not by COX-2-negative human UMUC-3 xenograft tumors. UMUC-3 xenograft tumors with no expression of COX-2 showed no uptake of fluorocoxib A. In addition, fluorocoxib A uptake was evaluated in five dogs diagnosed with TCC. Fluorocoxib A specifically detected COX-2-expressing K9TCC during cystoscopy in vivo but was not detected in normal urothelium. Taken together, our findings show that fluorocoxib A selectively bound to COX-2-expressing primary K9TCC cells in vitro, COX-2-expressing K9TCC xenografts tumors in nude mice, and heterogeneous canine TCC during cystoscopy in vivo. Spontaneous cancers in companion animals offer a unique translational model for evaluation of novel imaging and therapeutic agents using primary cancer cells in vitro and in heterogeneous cancers in vivo.


Modulation Of Adipose Tissue Inflammation By Bioactive Food Compounds, N. Siriwardhana, N. Kalupahana, Maria Cekanova, M. Lemieux, B. Greer, N, Moustaid-Moussa Mar 2013

Modulation Of Adipose Tissue Inflammation By Bioactive Food Compounds, N. Siriwardhana, N. Kalupahana, Maria Cekanova, M. Lemieux, B. Greer, N, Moustaid-Moussa

Maria Cekanova MS, RNDr, PhD

Adipose tissue has an important endocrine function in the regulation of whole-body metabolism. Obesity leads to a chronic low-grade inflammation of the adipose tissue, which disrupts this endocrine function and results in metabolic derangements, such as type-2 diabetes. Dietary bioactive compounds, such as polyphenols and certain fatty acids, are known to suppress both systemic and adipose tissue inflammation and have the potential to improve these obesity-associated metabolic disorders. Mechanistically, polyphenolic compounds including non-flavonoids, such as curcumin and resveratrol, and flavonoids, such as catechins (tea-polyphenols), quercetin and isoflavones, suppress nuclear factor-κB (NF-κB) and mitogen-activated protein (MAP) kinases (MAPK) pathways while activating ...


Neutron Radiography With Combined Computed Tomography: A Novel Tool For Cancer Diagnosis And Imaging (Abstract), Maria Cekanova, H Bilheux, Kusum Rathore, J Bilheux, L Walker, Robert Donnell, Alfred Legendre Jan 2013

Neutron Radiography With Combined Computed Tomography: A Novel Tool For Cancer Diagnosis And Imaging (Abstract), Maria Cekanova, H Bilheux, Kusum Rathore, J Bilheux, L Walker, Robert Donnell, Alfred Legendre

Maria Cekanova MS, RNDr, PhD

No abstract provided.


Mesenchymal And Stem-Like Properties Targeted In Suppression Of Chronically-Induced Breast Cell Carcinogenesis, Kusum Rathore, Hwa-Chain Wang Dec 2012

Mesenchymal And Stem-Like Properties Targeted In Suppression Of Chronically-Induced Breast Cell Carcinogenesis, Kusum Rathore, Hwa-Chain Wang

Hwa-Chain Robert Wang

No abstract provided.


Synergistic Induction Of Cancer Cell Death And Reduction Of Clonogenic Resistance By Cisplatin And Fk228, Shambhunath Choudhary, Shilpa Sood, Hwa-Chain Wang Dec 2012

Synergistic Induction Of Cancer Cell Death And Reduction Of Clonogenic Resistance By Cisplatin And Fk228, Shambhunath Choudhary, Shilpa Sood, Hwa-Chain Wang

Hwa-Chain Robert Wang

No abstract provided.


Preclinical Single-Dose Safety And Pharmacokinetic Evaluation Of Fluorocoxib A: Pilot Study Of Novel Cyclooxygenase-2-Targeted Optical Imaging Agent In A Canine Model, Maria Cekanova, M Uddin, Alfred Legendre, Gina Gaylon, Joseph Bartges, Amanda Callens, L Marnett Oct 2012

Preclinical Single-Dose Safety And Pharmacokinetic Evaluation Of Fluorocoxib A: Pilot Study Of Novel Cyclooxygenase-2-Targeted Optical Imaging Agent In A Canine Model, Maria Cekanova, M Uddin, Alfred Legendre, Gina Gaylon, Joseph Bartges, Amanda Callens, L Marnett

Maria Cekanova MS, RNDr, PhD

We evaluated preclinical single-dose safety, pharmacokinetic properties, and specific uptake of the new optical imaging agent fluorocoxib A in dogs. Fluorocoxib A, N-[(5-carboxy-X-rhodaminyl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide, selectively binds and inhibits the cyclooxygenase-2 (COX-2) enzyme, which is overexpressed in many cancers. Safety pilot studies were performed in research dogs following intravenous (i.v.) administration of 0.1 and 1  mg/kg fluorocoxib A. Blood and urine samples collected three days after administration of each dose of fluorocoxib A revealed no evidence of toxicity, and no clinically relevant adverse events were noted on physical examination of exposed dogs ...


Breast Cancer Cell Proliferation Is Inhibited By Bad: Regulation Of Cyclin D1, R Fernando, Js Foster, A Bible, A Ström, Rg Pestell, M Rao, Arnold Saxton, Seung Baek, K Yamaguchi, Robert Donnell, Maria Cekanova, J Wimalasena Jul 2012

Breast Cancer Cell Proliferation Is Inhibited By Bad: Regulation Of Cyclin D1, R Fernando, Js Foster, A Bible, A Ström, Rg Pestell, M Rao, Arnold Saxton, Seung Baek, K Yamaguchi, Robert Donnell, Maria Cekanova, J Wimalasena

Seung J Baek

Recent investigations suggest that functions of the proapoptotic BCL2 family members, including BAD, are not limited to regulation of apoptosis. Here we demonstrate that BAD inhibits G(1) to S phase transition in MCF7 breast cancer cells independent of apoptosis. BAD overexpression inhibited G(1) transit and cell growth as well as cyclin D1 expression. Inhibition of cyclin D1 expression was mediated through inhibition of transcription activated by AP1. Chromatin immunoprecipitation assays indicated that BAD is localized at the 12-O-tetradecanoylphorbol-13-acetate-response element (TRE) and cAMP-response element (CRE) in the cyclin D1 promoter. This was shown to reflect direct binding interactions of ...


Green Tea Catechin Extract In Intervention Of Chronic Breast Cell Carcinogenesis Induced By Environmental Carcinogens, Kusum Rathore, Hwa-Chain Wang Dec 2011

Green Tea Catechin Extract In Intervention Of Chronic Breast Cell Carcinogenesis Induced By Environmental Carcinogens, Kusum Rathore, Hwa-Chain Wang

Hwa-Chain Robert Wang

Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that green tea components may be used as preventive agents for breast cancer control. In our research, we have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. In this study, we used our chronic carcinogenesis model as a target ...


Green Tea Catechin Intervention Of Reactive Oxygen Species-Mediated Erk Pathway Activation And Chronically-Induced Breast Cell Carcinogenesis, Kusum Rathore, Shambhunath Choudhary, Agricola Odoi, Hwa-Chain Wang Dec 2011

Green Tea Catechin Intervention Of Reactive Oxygen Species-Mediated Erk Pathway Activation And Chronically-Induced Breast Cell Carcinogenesis, Kusum Rathore, Shambhunath Choudhary, Agricola Odoi, Hwa-Chain Wang

Hwa-Chain Robert Wang

No abstract provided.


Pulmonary Fibroblasts Stimulate The Proliferation Of Cell Lines From Human Lung Adenocarcinomas, Maria Cekanova, T Masi, Howard Plummer, M Majidi, P Fedorocko, Hildegard Schuller Aug 2011

Pulmonary Fibroblasts Stimulate The Proliferation Of Cell Lines From Human Lung Adenocarcinomas, Maria Cekanova, T Masi, Howard Plummer, M Majidi, P Fedorocko, Hildegard Schuller

Howard K. Plummer III

Human lung cancer cell lines are widely used to test anticancer drugs. These in-vitro tests, however, preclude the detection of responses to paracrine factors from surrounding stroma. We have cocultured pulmonary fibroblasts CCD-19Lu, from a healthy donor, or HLF-A, from a patient with epidermoid carcinoma of the lung, with two human pulmonary adenocarcinoma cell lines to test the hypothesis that the fibroblasts stimulate the growth of the tumor cells. Both fibroblast cell lines significantly increased the proliferation of the pulmonary adenocarcinoma cell lines in 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide assays, with HLF-A fibroblasts yielding the most pronounced responses ...


Role Of Stat3/5 And Bcl-2/Xl In 2-Methoxyestradiol-Induced Endoreduplication Of Nasopharyngeal Carcinoma Cells, Cm Ting, Ck Wong, Rn Wong, Kw Lo, Aw Lee, Gs Tsao, Ml Lung, N.K. Mak Dec 2010

Role Of Stat3/5 And Bcl-2/Xl In 2-Methoxyestradiol-Induced Endoreduplication Of Nasopharyngeal Carcinoma Cells, Cm Ting, Ck Wong, Rn Wong, Kw Lo, Aw Lee, Gs Tsao, Ml Lung, N.K. Mak

Professor MAK, Nai Ki

2-methoxyestradiol (2ME2), an endogenous metabolite of 17-b-estradiol, has been shown to induce apoptosis and cell cycle arrest in various tumor models. We have previously shown that 2ME2 induced endoreduplication in a welldifferentiated nasopharyngeal carcinoma (NPC) HK-1 and a poorly differentiated C666-1 cell line. In the present study, we studied the survival factors involved in 2ME2-induced endoreduplicating NPC cells. In the HK-1 cells, knockdown of BcL-xL expression by siRNA resulted in the reduction of endoreduplication and an increase in the percentage of apoptosis. Further mechanistic study revealed that 2ME2 enhanced the expression of the phosphorylated form of STAT5 (p-STAT5-Y694), but not ...


Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Expression Inhibits Urethane-Induced Pulmonary Tumorigenesis In Transgenic Mice, Maria Cekanova, Seong-Ho Lee, Robert Donnell, M Sukhthankar, Te Eling, Sm Fischer, Seung Baek Apr 2009

Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Expression Inhibits Urethane-Induced Pulmonary Tumorigenesis In Transgenic Mice, Maria Cekanova, Seong-Ho Lee, Robert Donnell, M Sukhthankar, Te Eling, Sm Fischer, Seung Baek

Maria Cekanova MS, RNDr, PhD

The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) inhibits gastrointestinal tumorigenesis in NAG-1 transgenic mice (C57/BL6 background). In the present study, we investigated whether the NAG-1 protein would alter urethane-induced pulmonary lesions in NAG-1 transgenic mice on an FVB background (NAG-1(Tg+/FVB)). NAG-1(Tg+/FVB) mice had both decreased number and size of urethane-induced tumors, compared with control littermates (NAG-1(Tg+/FVB) = 16 +/- 4 per mouse versus control = 20 +/- 7 per mouse, P < 0.05). Urethane-induced pulmonary adenomas and adenocarcinomas were observed in control mice; however, only pulmonary adenomas were observed in NAG-1(Tg+/FVB) mice. Urethane-induced tumors from control littermates and NAG-1(Tg+/FVB) mice highly expressed proteins in the arachidonic acid pathway (cyclooxygenases 1/2, prostaglandin E synthase, and prostaglandin E(2) receptor) and highly activated several kinases (phospho-Raf-1 and phosphorylated extracellular signal-regulated kinase 1/2). However, only urethane-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation was decreased in NAG-1(Tg+/FVB) mice. Furthermore, significantly increased apoptosis in tumors of NAG-1(Tg+/FVB) mice compared with control mice was observed as assessed by caspase-3/7 activity. In addition, fewer inflammatory cells were observed in the lung tissue isolated from urethane-treated NAG-1(Tg+/FVB) mice compared with control mice. These results paralleled in vitro assays using human A549 pulmonary carcinoma cells. Less phosphorylated p38 MAPK was observed in cells overexpressing NAG-1 compared with control cells. Overall, our study revealed for the first time that the NAG-1 protein inhibits urethane-induced tumor formation, probably mediated by the p38 MAPK pathway, and is a possible new target for lung cancer chemoprevention.


Targeted Inhibition Of The Egfr Pathways Enhances Zn-Bc-Am Pdt-Induced Apoptosis In Well-Differentiated Nasopharyngeal Carcinoma Cells, Hk Koon, Ps Chan, Rns Wong, Zg Wu, Ml Lung, Ck Chang, N.K. Mak Dec 2008

Targeted Inhibition Of The Egfr Pathways Enhances Zn-Bc-Am Pdt-Induced Apoptosis In Well-Differentiated Nasopharyngeal Carcinoma Cells, Hk Koon, Ps Chan, Rns Wong, Zg Wu, Ml Lung, Ck Chang, N.K. Mak

Professor MAK, Nai Ki

No abstract provided.


Breast Cancer Cell Proliferation Is Inhibited By Bad: Regulation Of Cyclin D1, R Fernando, Js Foster, A Bible, A Ström, Rg Pestell, M Rao, Arnold Saxton, Seung Baek, K Yamaguchi, Robert Donnell, Maria Cekanova, J Wimalasena Sep 2007

Breast Cancer Cell Proliferation Is Inhibited By Bad: Regulation Of Cyclin D1, R Fernando, Js Foster, A Bible, A Ström, Rg Pestell, M Rao, Arnold Saxton, Seung Baek, K Yamaguchi, Robert Donnell, Maria Cekanova, J Wimalasena

Maria Cekanova MS, RNDr, PhD

Recent investigations suggest that functions of the proapoptotic BCL2 family members, including BAD, are not limited to regulation of apoptosis. Here we demonstrate that BAD inhibits G(1) to S phase transition in MCF7 breast cancer cells independent of apoptosis. BAD overexpression inhibited G(1) transit and cell growth as well as cyclin D1 expression. Inhibition of cyclin D1 expression was mediated through inhibition of transcription activated by AP1. Chromatin immunoprecipitation assays indicated that BAD is localized at the 12-O-tetradecanoylphorbol-13-acetate-response element (TRE) and cAMP-response element (CRE) in the cyclin D1 promoter. This was shown to reflect direct binding interactions of ...


Overexpressed Raf-1 And Phosphorylated Cyclic Adenosine 3'-5'-Monophosphatate Response Element-Binding Protein Are Early Markers For Lung Adenocarcinoma, Maria Cekanova, M Majidi, T Masi, Hussein Al-Wadei, Hildegard Schuller Mar 2007

Overexpressed Raf-1 And Phosphorylated Cyclic Adenosine 3'-5'-Monophosphatate Response Element-Binding Protein Are Early Markers For Lung Adenocarcinoma, Maria Cekanova, M Majidi, T Masi, Hussein Al-Wadei, Hildegard Schuller

Maria Cekanova MS, RNDr, PhD

BACKGROUND: Pulmonary adenocarcinoma (PAC) is the leading type of lung cancer and has a high mortality. The tobacco carcinogen nicotine-derived nitrosamine 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) stimulates the proliferation of human PAC cells and small airway epithelial cells through beta-1 adrenorecptor-mediated transactivation of the epidermal growth factor receptor (EGFR). METHODS: Using the NNK hamster PAC model and human PAC tissue arrays with matched and unmatched normal lung tissues, the authors tested the hypothesis that Raf-1, an effector of the EGFR, and P-CREB, an effector of the beta-adrenoreceptor, are overexpressed in a significant subset of human PACs and are early ...


Nnk Activates Erk1/2 And Creb/Atf-1 Via Beta-1-Ar And Egfr Signaling In Human Lung Adenocarcinoma And Small Airway Epithelial Cells, E Laag, M Majidi, Maria Cekanova, T Masi, T Takahashi, Hildegard Schuller Sep 2006

Nnk Activates Erk1/2 And Creb/Atf-1 Via Beta-1-Ar And Egfr Signaling In Human Lung Adenocarcinoma And Small Airway Epithelial Cells, E Laag, M Majidi, Maria Cekanova, T Masi, T Takahashi, Hildegard Schuller

Maria Cekanova MS, RNDr, PhD

We have shown that the tobacco nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an agonist for -adrenergic receptors (beta-ARs) and increased DNA synthesis of human lung adenocarcinoma cells with features of bronchiolar Clara cells by binding to these receptors. Using a cell line derived from a human pulmonary adenocarcinoma with Clara cell phenotype (PACC) and immortalized human small airway epithelial cells (HPLD1), the putative cells of origin of this cancer type, our current studies have analyzed signaling initiated by binding of NNK to the beta 1-AR. NNK upregulated ERK1/2 and CREB/ATF-1 phosphorylation in a PKA-dependent manner in ...


Pulmonary Fibroblasts Stimulate The Proliferation Of Cell Lines From Human Lung Adenocarcinomas, Maria Cekanova, T Masi, Howard Plummer, M Majidi, P Fedorocko, Hildegard Schuller Jul 2006

Pulmonary Fibroblasts Stimulate The Proliferation Of Cell Lines From Human Lung Adenocarcinomas, Maria Cekanova, T Masi, Howard Plummer, M Majidi, P Fedorocko, Hildegard Schuller

Maria Cekanova MS, RNDr, PhD

Human lung cancer cell lines are widely used to test anticancer drugs. These in-vitro tests, however, preclude the detection of responses to paracrine factors from surrounding stroma. We have cocultured pulmonary fibroblasts CCD-19Lu, from a healthy donor, or HLF-A, from a patient with epidermoid carcinoma of the lung, with two human pulmonary adenocarcinoma cell lines to test the hypothesis that the fibroblasts stimulate the growth of the tumor cells. Both fibroblast cell lines significantly increased the proliferation of the pulmonary adenocarcinoma cell lines in 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide assays, with HLF-A fibroblasts yielding the most pronounced responses ...


Detection Of Overexpressed Cox-2 In Precancerous Lesions Of Hamster Pancreas And Lungs By Molecular Imaging: Implications For Early Diagnosis And Prevention, Hildegard Schuller, George Kabalka, G Smith, A Mereddy, M Akula, Maria Cekanova May 2006

Detection Of Overexpressed Cox-2 In Precancerous Lesions Of Hamster Pancreas And Lungs By Molecular Imaging: Implications For Early Diagnosis And Prevention, Hildegard Schuller, George Kabalka, G Smith, A Mereddy, M Akula, Maria Cekanova

Maria Cekanova MS, RNDr, PhD

The enzyme cyclooxygenase-2 (COX-2) is overexpressed in many cancers, cardiovascular disease, neurodegenerative disorders, and arthritis. Selective inhibitors of COX-2 have been developed as therapeutics or preventive agents for these diseases. However, recent reports have revealed a significant increase in cardiovascular mortality in long-term users of the COX-2 inhibitors Vioxx and Celebrex, emphasizing the need for noninvasive tests that allow the identification of individuals whose COX-2 levels are overexpressed prior to assignment to treatment with these drugs. In this study, we have prepared a radioiodinated analogue of the selective COX-2 inhibitor celecoxib, and verified its binding to the COX-2 enzyme in ...


Synergistic Mitogenic Signaling Of The Tobacco Specific Carcinogen, 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone (Nnk) And Ethanol On Immortalized Human Pancreatic Duct Epithelial Cells, Mdf Askari, Ms Tsao, Maria Cekanova, Hildegard Schuller Dec 2005

Synergistic Mitogenic Signaling Of The Tobacco Specific Carcinogen, 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone (Nnk) And Ethanol On Immortalized Human Pancreatic Duct Epithelial Cells, Mdf Askari, Ms Tsao, Maria Cekanova, Hildegard Schuller

Maria Cekanova MS, RNDr, PhD

No abstract provided.


Nitrosamine 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone-Induced Pulmonary Adenocarcinomas In Syrian Golden Hamsters Contain Beta 2-Adrenergic Receptor Single-Nucleotide Polymorphisms, T Masi, Maria Cekanova, K Walker, H Bernart, M Majidi, Jm Becker, Hildegard Schuller Sep 2005

Nitrosamine 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone-Induced Pulmonary Adenocarcinomas In Syrian Golden Hamsters Contain Beta 2-Adrenergic Receptor Single-Nucleotide Polymorphisms, T Masi, Maria Cekanova, K Walker, H Bernart, M Majidi, Jm Becker, Hildegard Schuller

Maria Cekanova MS, RNDr, PhD

Cigarette smoking contributes to the development of lung cancer throughout the world, with cases of pulmonary adenocarcinoma (PAC) the most numerous. Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is formed from nicotine, has been demonstrated to cause mutations in genes that affect cell regulation and proliferation. Moreover, NNK has been shown to interact directly with and stimulate beta adrenergic receptor (ADRB) signal transduction pathways. Our goal was to determine whether single-nucleotide polymorphisms (SNPs) in the Adrb2 from PAC tumors were induced in golden hamsters by the injection of NNK. Here we report the cloning and sequencing of Adrb2 clones ...


Nnk-Induced Hamster Lung Adenocarcinomas Over-Express Beta2-Adrenergic And Egfr Signaling Pathways, Hildegard Schuller, Maria Cekanova Jun 2005

Nnk-Induced Hamster Lung Adenocarcinomas Over-Express Beta2-Adrenergic And Egfr Signaling Pathways, Hildegard Schuller, Maria Cekanova

Maria Cekanova MS, RNDr, PhD

Pulmonary adenocarcinoma (PAC) is the most common type of human lung cancer. A diagnosis of PAC, history of non-smoking and presence of mutations in the EGFR are predictive factors for responsiveness of lung cancer to EGFR-specific tyrosine kinase inhibitors. Unfortunately, less than 50% of PAC cases demonstrate this mutation-based responsiveness. Our immunohistochemical analysis of NNK-induced PAC in hamsters demonstrates the simultaneous over-expression of a beta2-adrenergic receptor pathway, including PKA, cAMP, CREB and phosphorylated CREB and of an EGFR pathway, including over-expression of EGFR-specific phosphorylated tyrosine kinase, Raf-1 and ERK1/2 and their phosphorylated forms. These findings implicate, for the first ...


Placental Expression Of Estrogen Receptor Beta And Its Hormone Binding Variant--Comparison With Estrogen Receptor Alpha And A Role For Estrogen Receptors In Asymmetric Division And Differentiation Of Estrogen-Dependent Cells., A Bukovsky, M Caudle, Maria Cekanova, R Fernando, J Wimalasena, J Foster, D Henley, R Elder Apr 2003

Placental Expression Of Estrogen Receptor Beta And Its Hormone Binding Variant--Comparison With Estrogen Receptor Alpha And A Role For Estrogen Receptors In Asymmetric Division And Differentiation Of Estrogen-Dependent Cells., A Bukovsky, M Caudle, Maria Cekanova, R Fernando, J Wimalasena, J Foster, D Henley, R Elder

Maria Cekanova MS, RNDr, PhD

During human pregnancy, the production of 17-beta-estradiol (E2) rises steadily to eighty fold at term, and placenta has been found to specifically bind estrogens. We have recently demonstrated the expression of estrogen receptor alpha (ER-alpha) protein in human placenta and its localization in villous cytotrophoblast (CT), vascular pericytes, and amniotic fibroblasts. In vitro, E2 stimulated development of large syncytiotrophoblast (ST) aggregates. In the present study we utilized ER-beta affinity purified polyclonal (N19:sc6820) and ER-alpha monoclonal (clone h-151) antibodies. Western blot analysis revealed a single approximately 52 kDa ER-beta band in chorionic villi (CV) protein extracts. In CV, strong cytoplasmic ...


Variability Of Placental Expression Of Cyclin E Low Molecular Weight Variants, A Bukovsky, Maria Cekanova, Mr Caudle, J Wimalasena, Js Foster, Ja Keenan, Rf Elder Jul 2002

Variability Of Placental Expression Of Cyclin E Low Molecular Weight Variants, A Bukovsky, Maria Cekanova, Mr Caudle, J Wimalasena, Js Foster, Ja Keenan, Rf Elder

Maria Cekanova MS, RNDr, PhD

Cyclin E, a G(1) cyclin serving to activate cyclin-dependent kinase 2, is the only cyclin gene for which alternative splicing leading to structurally different proteins has been described. Different cyclin E proteins are present in tumor tissues but absent from normal (steady) tissues. Cyclin E contributes to the regulation of cell proliferation and ongoing differentiation and aging. Because trophoblast has invasive properties and differentiates into syncytium and placental aging may develop at term, we examined cyclin E protein variants in human placenta. Placental samples were collected from 27 deliveries between 33 and 41 wk and were compared with ovarian ...


Effect Of Acetazolamide On Hypericin Photocytotoxicity, P Solar, I Cavarga, J Hofmanova, Maria Cekanova, P Miskovsky, P Brezani, G Hrckova, A Kozubik, P Fedorocko Jun 2002

Effect Of Acetazolamide On Hypericin Photocytotoxicity, P Solar, I Cavarga, J Hofmanova, Maria Cekanova, P Miskovsky, P Brezani, G Hrckova, A Kozubik, P Fedorocko

Maria Cekanova MS, RNDr, PhD

The photodynamic action of hypericin (HYP) in vitro was evaluated using human leukemic HL-60 and lung carcinoma A549 cell lines. After illumination HYP (1 x 10 (-5) M) reduced the proliferation and/or survival of HL-60 and A549 cells vs. controls to almost to 0 % and 29 %, respectively. A lower concentration of HYP (1 x 10 (-6) M) decreased the proliferation and/or survival only in HL-60 cells. Non-cytotoxic concentrations of the carbonic anhydrase inhibitor acetazolamide (ACTZ) (1 x 10 (-3)-1 x 10 (-6) M) significantly potentiated these effects of HYP (1 x 10 (-6)M) in HL-60, but ...


Gold Nanoparticle-Mediated Transfection Of Mammalian Cells, Sallie Smith Schneider, K.K. Sanhu, J.M. Simard, C.M. Mcintosh, V.M. Rotello Dec 2001

Gold Nanoparticle-Mediated Transfection Of Mammalian Cells, Sallie Smith Schneider, K.K. Sanhu, J.M. Simard, C.M. Mcintosh, V.M. Rotello

Sallie W Smith Schneider

No abstract provided.


Regulation Of The Immediate Early Gene Product C-Fos By Erk And Rsk: A Mechanism For Sensing And Propagating Erk Signal Duration, Sallie Smith Schneider, L.O. Murphy, R.H. Chen, D.C. Fingar, J. Blenis Dec 2001

Regulation Of The Immediate Early Gene Product C-Fos By Erk And Rsk: A Mechanism For Sensing And Propagating Erk Signal Duration, Sallie Smith Schneider, L.O. Murphy, R.H. Chen, D.C. Fingar, J. Blenis

Sallie W Smith Schneider

No abstract provided.