Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 14 of 14
Full-Text Articles in Medicine and Health Sciences
Lysophosphatidic Acid Up-Regulates Hexokinase Ii And Glycolysis To Promote Proliferation Of Ovarian Cancer Cells, Abir Mukherjee, Yibao Ma, Fang Yuan, Yongling Gong, Zhenyu Fang, Esraa M. Mohamed, Erika Berrios, Huanjie Shao, Xianjun Fang
Lysophosphatidic Acid Up-Regulates Hexokinase Ii And Glycolysis To Promote Proliferation Of Ovarian Cancer Cells, Abir Mukherjee, Yibao Ma, Fang Yuan, Yongling Gong, Zhenyu Fang, Esraa M. Mohamed, Erika Berrios, Huanjie Shao, Xianjun Fang
Biochemistry and Molecular Biology Publications
Lysophosphatidic acid (LPA), a blood-borne lipid mediator, is present in elevated concentrations in ascites of ovarian cancer patients and other malignant effusions. LPA is a potent mitogen in cancer cells. The mechanism linking LPA signal to cancer cell proliferation is not well understood. Little is known about whether LPA affects glucose metabolism to accommodate rapid proliferation of cancer cells. Here we describe that in ovarian cancer cells, LPA enhances glycolytic rate and lactate efflux. A real time PCR-based miniarray showed that hexokinase II (HK2) was the most dramatically induced glycolytic gene to promote glycolysis in LPA-treated cells. Analysis of the …
Dual Action Of Mir-125b As A Tumor Suppressor And Oncomir-22 Promotes Prostate Cancer Tumorigenesis, William T. Budd, Sarah J. Seashols-Williams, Gene C. Clark, Danielle Weaver, Valerie Calvert, Emanuel Petricoin, Ema A. Dragoescu, Katherine O'Hanlon, Zendra E. Zehner
Dual Action Of Mir-125b As A Tumor Suppressor And Oncomir-22 Promotes Prostate Cancer Tumorigenesis, William T. Budd, Sarah J. Seashols-Williams, Gene C. Clark, Danielle Weaver, Valerie Calvert, Emanuel Petricoin, Ema A. Dragoescu, Katherine O'Hanlon, Zendra E. Zehner
Biochemistry and Molecular Biology Publications
MicroRNAs (miRs) are a novel class of small RNA molecules, the dysregulation of which can contribute to cancer. A combinatorial approach was used to identify miRs that promote prostate cancer progression in a unique set of prostate cancer cell lines, which originate from the parental p69 cell line and extend to a highly tumorigenic/metastatic M12 subline. Together, these cell lines are thought to mimic prostate cancer progression in vivo. Previous network analysis and miR arrays suggested that the loss of hsa-miR-125b together with the overexpression of hsa-miR-22 could contribute to prostate tumorigenesis. The dysregulation of these two miRs was …
Dpy-17 And Mua-3 Interact For Connective Tissue-Like Tissue Integrity In Caenorhabditis Elegans: A Model For Marfan Syndrome, Pauline Fotopoulos, Jeongho Kim, Moonjung Hyun, Waiss Qamari, Inhwan Lee, Young-Jai You
Dpy-17 And Mua-3 Interact For Connective Tissue-Like Tissue Integrity In Caenorhabditis Elegans: A Model For Marfan Syndrome, Pauline Fotopoulos, Jeongho Kim, Moonjung Hyun, Waiss Qamari, Inhwan Lee, Young-Jai You
Biochemistry and Molecular Biology Publications
mua-3 is a Caenorhabditis elegans homolog of the mammalian fibrillin1, a monogenic cause of Marfan syndrome. We identified a new mutation of mua-3 that carries an in-frame deletion of 131 amino acids in the extracellular domain, which allows the mutants to survive in a temperature-dependent manner; at the permissive temperature, the mutants grow normally without obvious phenotypes, but at the nonpermissive temperature, more than 90% die during the L4 molt due to internal organ detachment. Using the temperature-sensitive lethality, we performed unbiased genetic screens to isolate suppressors to find genetic interactors of MUA-3. From two independent screens, we isolated …
Dissection Of C. Elegans Behavioral Genetics In 3-D Environments, Namseop Kwon, Ara B. Hwang, Young-Jai You, Seung-Jae V. Lee, Jung Ho Je
Dissection Of C. Elegans Behavioral Genetics In 3-D Environments, Namseop Kwon, Ara B. Hwang, Young-Jai You, Seung-Jae V. Lee, Jung Ho Je
Biochemistry and Molecular Biology Publications
The nematode Caenorhabditis elegans is a widely used model for genetic dissection of animal behaviors. Despite extensive technical advances in imaging methods, it remains challenging to visualize and quantify C. elegans behaviors in three-dimensional (3-D) natural environments. Here we developed an innovative 3-D imaging method that enables quantification of C. elegans behavior in 3-D environments. Furthermore, for the first time, we characterized 3-D-specific behavioral phenotypes of mutant worms that have defects in head movement or mechanosensation. This approach allowed us to reveal previously unknown functions of genes in behavioral regulation. We expect that our 3-D imaging method will facilitate new …
Missed Opportunities For The Diagnosis Of Colorectal Cancer, Laura A. Siminoff, Heather L. Rogers, Sonja Harris-Haywood
Missed Opportunities For The Diagnosis Of Colorectal Cancer, Laura A. Siminoff, Heather L. Rogers, Sonja Harris-Haywood
Biochemistry and Molecular Biology Publications
Objective. To examine patient and medical characteristics which predict a missed diagnostic opportunity (MDO) for colorectal cancer (CRC). Methods. The sample consisted of 252 patients diagnosed with Stages 1–4 CRC who were diagnosed in the prior six months, had experienced symptoms prior to diagnosis, and were not diagnosed through routine screening. Systematic review of all medical records prior to patients’ diagnosis was conducted. An MDO was defined as a clinical encounter where, even in the presence of presumptive CRC symptoms, the CRC diagnostic process is not started. Results. 92 patients (36.5%) experienced an MDO. Almost 80% of alternate diagnoses were …
Network Modelling Reveals The Mechanism Underlying Colitis-Associated Colon Cancer And Identifies Novel Combinatorial Anti-Cancer Targets, Junyan Lu, Hanlin Zeng, Zhongjie Liang, Limin Chen, Liyi Zhang, Hao Zhang, Hong Liu, Hualiang Jiang, Bairong Shen, Ming Huang, Meiyu Geng, Sarah Spiegel, Cheng Luo
Network Modelling Reveals The Mechanism Underlying Colitis-Associated Colon Cancer And Identifies Novel Combinatorial Anti-Cancer Targets, Junyan Lu, Hanlin Zeng, Zhongjie Liang, Limin Chen, Liyi Zhang, Hao Zhang, Hong Liu, Hualiang Jiang, Bairong Shen, Ming Huang, Meiyu Geng, Sarah Spiegel, Cheng Luo
Biochemistry and Molecular Biology Publications
The connection between inflammation and tumourigenesis has been well established. However, the detailed molecular mechanism underlying inflammation-associated tumourigenesis remains unknown because this process involves a complex interplay between immune microenvironments and epithelial cells. To obtain a more systematic understanding of inflammation-associated tumourigenesis as well as to identify novel therapeutic approaches, we constructed a knowledge-based network describing the development of colitis-associated colon cancer (CAC) by integrating the extracellular microenvironment and intracellular signalling pathways. Dynamic simulations of the CAC network revealed a core network module, including P53, MDM2, and AKT, that may govern the malignant transformation of colon epithelial cells in a …
P. Falciparum And P. Vivax Epitope-Focused Vlps Elicit Sterile Immunity To Blood Stage Infections, David C. Whitacre, Diego A. Espinosa, Cory J. Peters, Joyce E. Jones, Amy E. Tucker, Darrell L. Peterson, Fidel P. Zavala, David R. Milich
P. Falciparum And P. Vivax Epitope-Focused Vlps Elicit Sterile Immunity To Blood Stage Infections, David C. Whitacre, Diego A. Espinosa, Cory J. Peters, Joyce E. Jones, Amy E. Tucker, Darrell L. Peterson, Fidel P. Zavala, David R. Milich
Biochemistry and Molecular Biology Publications
In order to design P. falciparum preerythrocytic vaccine candidates, a library of circumsporozoite (CS) T and B cell epitopes displayed on the woodchuck hepatitis virus core antigen (WHcAg) VLP platform was produced. To test the protective efficacy of the WHcAg-CS VLPs, hybrid CS P. berghei/P. falciparum (Pb/Pf) sporozoites were used to challenge immunized mice. VLPs carrying 1 or 2 different CS repeat B cell epitopes and 3 VLPs carrying different CS non-repeat B cell epitopes elicited high levels of anti-insert antibodies (Abs). Whereas, VLPs carrying CS repeat B cell epitopes conferred 98% protection of the liver against …
Increased Eicosanoid Levels In The Sugen/Chronic Hypoxia Model Of Severe Pulmonary Hypertension, Aysar Al-Husseini, Dayanjan S. Wijesinghe, Laszlo Farkas, Donatas Kraskauskas, Jennifer I. Drake, Ben Van Tassel, Antonio Abbate, Charles E. Chalfant, Norbert F. Voelkel
Increased Eicosanoid Levels In The Sugen/Chronic Hypoxia Model Of Severe Pulmonary Hypertension, Aysar Al-Husseini, Dayanjan S. Wijesinghe, Laszlo Farkas, Donatas Kraskauskas, Jennifer I. Drake, Ben Van Tassel, Antonio Abbate, Charles E. Chalfant, Norbert F. Voelkel
Biochemistry and Molecular Biology Publications
Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not …
Pde5 Inhibitors Enhance Celecoxib Killing In Multiple Tumor Types, Laurence Booth, Jane L. Roberts, Nichola Cruickshanks, Seyedmehrad Tavallai, Timothy Webb, Peter Samuel, Adam Conley, Brittany Binion, Harold F. Young, Andrew Poklepovic, Sarah Spiegel, Paul Dent
Pde5 Inhibitors Enhance Celecoxib Killing In Multiple Tumor Types, Laurence Booth, Jane L. Roberts, Nichola Cruickshanks, Seyedmehrad Tavallai, Timothy Webb, Peter Samuel, Adam Conley, Brittany Binion, Harold F. Young, Andrew Poklepovic, Sarah Spiegel, Paul Dent
Biochemistry and Molecular Biology Publications
The present studies determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with a clinically relevant NSAID, celecoxib, to kill tumor cells. Celecoxib and PDE5 inhibitors interacted in a greater than additive fashion to kill multiple tumor cell types. Celecoxib and sildenafil killed ex vivo primary human glioma cells as well as their associated activated microglia. Knock down of PDE5 recapitulated the effects of PDE5 inhibitor treatment; the nitric oxide synthase inhibitor L-NAME suppressed drug combination toxicity. The effects of celecoxib were COX2 independent. Over-expression of c-FLIP-s or knock down of CD95/FADD significantly reduced killing by the drug combination. CD95 …
The Signal Transducer And Activator Of Transcription 1 (Stat1) Inhibits Mitochondrial Biogenesis In Liver And Fatty Acid Oxidation In Adipocytes, Jennifer D. Sisler, Magdalena Morgan, Vidisha Raje, Rebecca C. Grande, Marta Derecka, Jeremy Meier, Marc Cantwell, Karol Szczepanek, William J. Korzun, Edward J. Lesnefsky, Thurl E. Harris, Colleen M. Croniger, Andrew C. Larner
The Signal Transducer And Activator Of Transcription 1 (Stat1) Inhibits Mitochondrial Biogenesis In Liver And Fatty Acid Oxidation In Adipocytes, Jennifer D. Sisler, Magdalena Morgan, Vidisha Raje, Rebecca C. Grande, Marta Derecka, Jeremy Meier, Marc Cantwell, Karol Szczepanek, William J. Korzun, Edward J. Lesnefsky, Thurl E. Harris, Colleen M. Croniger, Andrew C. Larner
Biochemistry and Molecular Biology Publications
The transcription factor STAT1 plays a central role in orchestrating responses to various pathogens by activating the transcription of nuclear-encoded genes that mediate the antiviral, the antigrowth, and immune surveillance effects of interferons and other cytokines. In addition to regulating gene expression, we report that STAT1-/- mice display increased energy expenditure and paradoxically decreased release of triglycerides from white adipose tissue (WAT). Liver mitochondria from STAT1-/- mice show both defects in coupling of the electron transport chain (ETC) and increased numbers of mitochondria. Consistent with elevated numbers of mitochondria, STAT1-/- mice expressed increased amounts of PGC1α, a …
Dpy-17 And Mua-3 Interact For Connective Tissue-Like Tissue Integrity In Caenorhabditis Elegans: A Model For Marfan Syndrome, Pauline Fotopoulos, Jeongho Kim, Moonjung Hyun, Waiss Qamari, Inhwan Lee, Young-Jai You
Dpy-17 And Mua-3 Interact For Connective Tissue-Like Tissue Integrity In Caenorhabditis Elegans: A Model For Marfan Syndrome, Pauline Fotopoulos, Jeongho Kim, Moonjung Hyun, Waiss Qamari, Inhwan Lee, Young-Jai You
Biochemistry and Molecular Biology Publications
mua-3 is a Caenorhabditis elegans homolog of the mammalian fibrillin1, a monogenic cause of Marfan syndrome. We identified a new mutation of mua-3that carries an in-frame deletion of 131 amino acids in the extracellular domain, which allows the mutants to survive in a temperature-dependent manner; at the permissive temperature, the mutants grow normally without obvious phenotypes, but at the nonpermissive temperature, more than 90% die during the L4 molt due to internal organ detachment. Using the temperature-sensitive lethality, we performed unbiased genetic screens to isolate suppressors to find genetic interactors of MUA-3. From two independent screens, we isolated …
The Phosphorylated Prodrug Fty720 Is A Histone Deacetylase Inhibitor That Reactivates Erα Expression And Enhances Hormonal Therapy For Breast Cancer, Nitai C. Hait, Dorit Avni, Akimitsu Yamada, Masayuki Nagahashi, Tomoyoshi Aoyagi, Hiroaki Aoki, Catherine I. Dumur, Z Zelenko, E J. Gallagher, D Leroith, Sheldon Milstien, Kazuaki Takabe, Sarah Spiegel
The Phosphorylated Prodrug Fty720 Is A Histone Deacetylase Inhibitor That Reactivates Erα Expression And Enhances Hormonal Therapy For Breast Cancer, Nitai C. Hait, Dorit Avni, Akimitsu Yamada, Masayuki Nagahashi, Tomoyoshi Aoyagi, Hiroaki Aoki, Catherine I. Dumur, Z Zelenko, E J. Gallagher, D Leroith, Sheldon Milstien, Kazuaki Takabe, Sarah Spiegel
Biochemistry and Molecular Biology Publications
Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and does not respond to conventional hormonal therapies. Strategies that lead to re-expression of ERα could sensitize ERα-negative breast cancers to selective ER modulators. FTY720 (fingolimod, Gilenya), a sphingosine analog, is the Food and Drug Administration (FDA)-approved prodrug for treatment of multiple sclerosis that also has anticancer actions that are not yet well understood. We found that FTY720 is phosphorylated in breast cancer cells by nuclear sphingosine kinase 2 and accumulates there. Nuclear FTY720-P is a potent inhibitor of class I histone deacetylases (HDACs) that enhances histone acetylations and regulates expression of …
Dual Action Of Mir-125b As A Tumor Suppressor And Oncomir-22 Promotes Prostate Cancer Tumorigenesis, William Budd, Sarah J. Seashols-Williams, Gene C. Clark, Danielle Weaver, Valerie Calvert, Emanuel Petricoin, Ema A. Dragoescu, Katherine O’Hanlon, Zendra E. Zehner
Dual Action Of Mir-125b As A Tumor Suppressor And Oncomir-22 Promotes Prostate Cancer Tumorigenesis, William Budd, Sarah J. Seashols-Williams, Gene C. Clark, Danielle Weaver, Valerie Calvert, Emanuel Petricoin, Ema A. Dragoescu, Katherine O’Hanlon, Zendra E. Zehner
Biochemistry and Molecular Biology Publications
MicroRNAs (miRs) are a novel class of small RNA molecules, the dysregulation of which can contribute to cancer. A combinatorial approach was used to identify miRs that promote prostate cancer progression in a unique set of prostate cancer cell lines, which originate from the parental p69 cell line and extend to a highly tumorigenic/metastatic M12 subline. Together, these cell lines are thought to mimic prostate cancer progression in vivo. Previous network analysis and miR arrays suggested that the loss of hsa-miR-125b together with the overexpression of hsa-miR-22 could contribute to prostate tumorigenesis. The dysregulation of these two miRs was …
Interrogating The Venom Of The Viperid Snake Sistrurus Catenatus Edwardsii By A Combined Approach Of Electrospray And Maldi Mass Spectrometry, Alex Chapeaurouge, Md Abu Reza, Stephen P. Mackessy, Paulo C. Carvalho, Richard H. Valente, André Teixeira-Ferreira, Jonas Perales, Qingsong Lin, R. Manjunatha Kini
Interrogating The Venom Of The Viperid Snake Sistrurus Catenatus Edwardsii By A Combined Approach Of Electrospray And Maldi Mass Spectrometry, Alex Chapeaurouge, Md Abu Reza, Stephen P. Mackessy, Paulo C. Carvalho, Richard H. Valente, André Teixeira-Ferreira, Jonas Perales, Qingsong Lin, R. Manjunatha Kini
Biochemistry and Molecular Biology Publications
The complete sequence characterization of snake venom proteins by mass spectrometry is rather challenging due to the presence of multiple isoforms from different protein families. In the present study, we investigated the tryptic digest of the venom of the viperid snake Sistrurus catenatus edwardsii by a combined approach of liquid chromatography coupled to either electrospray (online) or MALDI (offline) mass spectrometry. These different ionization techniques proved to be complementary allowing the identification a great variety of isoforms of diverse snake venom protein families, as evidenced by the detection of the corresponding unique peptides. For example, ten out of eleven predicted …