Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 30 of 32

Full-Text Articles in Medicine and Health Sciences

Genetic And Epigenetic Determinants Of Diffuse Large B-Cell Lymphoma, Tanner Bakhshi, Philippe T. Georgel Dec 2020

Genetic And Epigenetic Determinants Of Diffuse Large B-Cell Lymphoma, Tanner Bakhshi, Philippe T. Georgel

Biomedical Sciences

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma and is notorious for its heterogeneity, aggressive nature, and the frequent development of resistance and/or relapse after treatment with standard chemotherapy. To address these problems, a strong emphasis has been placed on researching the molecular origins and mechanisms of DLBCL to develop effective treatments. One of the major insights produced by such research is that DLBCL almost always stems from genetic damage that occurs during the germinal center (GC) reaction, which is required for the production of high-affinity antibodies. Indeed, there is significant overlap between the mechanisms that …


Generation Of In-Frame Gene Deletion Mutants In Pseudomonas Aeruginosa And Testing For Virulence Attenuation In A Simple Mouse Model Of Infection, Meagan E. Valentine, Brandon D. Kirby, Hongwei D. Yu Jan 2020

Generation Of In-Frame Gene Deletion Mutants In Pseudomonas Aeruginosa And Testing For Virulence Attenuation In A Simple Mouse Model Of Infection, Meagan E. Valentine, Brandon D. Kirby, Hongwei D. Yu

Biomedical Sciences

Microorganisms are genetically versatile and diverse and have become a major source of many commercial products and biopharmaceuticals. Though some of these products are naturally produced by the organisms, other products require genetic engineering of the organism to increase the yields of production. Avirulent strains of Escherichia coli have traditionally been the preferred bacterial species for producing biopharmaceuticals; however, some products are difficult for E. coli to produce. Thus, avirulent strains of other bacterial species could provide useful alternatives for production of some commercial products. Pseudomonas eruginosa is a common and well-studied Gram-negative bacterium that could provide a suitable alternative …


Theaflavin-3, 3'-Digallate Induces Apoptosis And G2 Cell Cycle Arrest Through The Akt/Mdm2/P53 Pathway In Cisplatin-Resistant Ovarian Cancer A2780/Cp70 Cells, Youying Tu, Eunhye Kim, Ying Gao, Gary O. Rankin, Bo Li, Yi Charlie Chen Jun 2016

Theaflavin-3, 3'-Digallate Induces Apoptosis And G2 Cell Cycle Arrest Through The Akt/Mdm2/P53 Pathway In Cisplatin-Resistant Ovarian Cancer A2780/Cp70 Cells, Youying Tu, Eunhye Kim, Ying Gao, Gary O. Rankin, Bo Li, Yi Charlie Chen

Pharmacology, Physiology and Toxicology

Ovarian cancer is the most lethal gynecological cancer among women worldwide. Adverse side effects and acquired resistance to conventional platinum based chemotherapy are major impediments in ovarian cancer treatment, and drive the development of more selective anticancer drugs that target cancer-specific defects. In this study, theaflavin-3, 3'-digallate (TF3), the major theaflavin monomer in black tea, exhibited a potent growth inhibitory effect on the cisplatinresistant ovarian cancer A2780/CP70 cells (IC50, 23.81 μM), and was less cytotoxic to a normal ovarian IOSE‑364 cells (IC50, 59.58 μM) than to the cancer cells. Flow cytometry analysis indicated that TF3 induced preferential apoptosis and G2 …


Heme Oxygenase-1 Induction Improves Cardiac Function Following Myocardial Ischemia By Reducing Oxidative Stress, Yossi Issan, Ran Kornowski, Dan Aravot, Asher Shainberg, Michal Laniado-Schwartzman, Komal Sodhi, Nader G. Abraham, Edith Hochhauser Mar 2014

Heme Oxygenase-1 Induction Improves Cardiac Function Following Myocardial Ischemia By Reducing Oxidative Stress, Yossi Issan, Ran Kornowski, Dan Aravot, Asher Shainberg, Michal Laniado-Schwartzman, Komal Sodhi, Nader G. Abraham, Edith Hochhauser

Internal Medicine

Background

Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation.

Methods

In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers …


Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu Jun 2013

Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu

Biochemistry and Microbiology

Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the overproduction of alginate, a surface polysaccharide, to form biofilms in vivo. Overproduction of alginate, also known as mucoidy, affords the bacterium protection from the host's defenses and facilitates the establishment of chronic lung infections in individuals with cystic fibrosis. Expression of the alginate biosynthetic operon is primarily controlled by the alternative sigma factor AlgU (AlgT/σ22). In a nonmucoid strain, AlgU is sequestered by the transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be released from MucA via regulated intramembrane proteolysis by proteases AlgW and MucP …


Inhibition Of Cholinergic Signaling Causes Apoptosis In Human Bronchioalveolar Carcinoma, Jamie K. Lau, Kathleen C. Brown, Brent A. Thornhill, Clayton M. Crabtree, Aaron M. Dom, Theodore R. Witte, W. Elaine Hardman, Christopher A. Mcnees, Cody A. Stover, A. Betts Carpenter, Haitao Luo, Yi C. Chen, Brandon S. Shiflett, Piyali Dasgupta Feb 2013

Inhibition Of Cholinergic Signaling Causes Apoptosis In Human Bronchioalveolar Carcinoma, Jamie K. Lau, Kathleen C. Brown, Brent A. Thornhill, Clayton M. Crabtree, Aaron M. Dom, Theodore R. Witte, W. Elaine Hardman, Christopher A. Mcnees, Cody A. Stover, A. Betts Carpenter, Haitao Luo, Yi C. Chen, Brandon S. Shiflett, Piyali Dasgupta

Biochemistry and Microbiology

Recent case-controlled clinical studies show that bronchioalveolar carcinomas (BAC) are correlated with smoking. Nicotine, the addictive component of cigarettes, accelerates cell proliferation through nicotinic acetylcholine receptors (nAChR). In this study, we show that human BACs produce acetylcholine (ACh) and contain several cholinergic factors including acetylcholinesterase (AChE), choline acetyltransferase (ChAT), choline transporter 1 (CHT1, SLC5A7), vesicular acetylcholine transporter (VAChT, SLC18A3), and nACh receptors (AChRs, CHRNAs). Nicotine increased the production of ACh in human BACs, and ACh acts as a growth factor for these cells. Nicotine-induced ACh production was mediated by α7-, α3β2-, and β3-nAChRs, ChAT and VAChT pathways. We observed that …


Draft Genome Sequence For Pseudomonas Aeruginosa Strain Pao579, A Mucoid Derivative Of Pao381, T. Ryan Withers, Shannon L. Johnson, Hongwei D. Yu Dec 2012

Draft Genome Sequence For Pseudomonas Aeruginosa Strain Pao579, A Mucoid Derivative Of Pao381, T. Ryan Withers, Shannon L. Johnson, Hongwei D. Yu

Biochemistry and Microbiology

Pseudomonas aeruginosa is an opportunistic pathogen that establishes a chronic lung infection in individuals afflicted with cystic fibrosis. Here, we announce the draft genome of P. aeruginosa strain PAO579, an alginate-overproducing derivative of strain PAO381.


Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera Oct 2012

Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera

Biochemistry and Microbiology

Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, …


Mussel Inspired Protein-Mediated Surface Modification To Electrospun Fibers And Their Potential Biomedical Applications, Jingwei Xie, Praveesuda Lorwattanapongsa Michael, Shaoping Zhong, Bing Ma, Matthew R. Macewan, Chwee Teck Lim Apr 2012

Mussel Inspired Protein-Mediated Surface Modification To Electrospun Fibers And Their Potential Biomedical Applications, Jingwei Xie, Praveesuda Lorwattanapongsa Michael, Shaoping Zhong, Bing Ma, Matthew R. Macewan, Chwee Teck Lim

MIIR Faculty Research

Mussel inspired proteins have been demonstrated to serve as a versatile biologic adhesive with numerous applications. The present study illustrates the use of such Mussel inspired proteins (polydopamine) in the fabrication of functionalized bio-inspired nanomaterials capable of both improving cell response and sustained delivery of model probes. X-ray photoelectron spectroscopy analysis confirmed the ability of dopamine to polymerize on the surface of plasma-treated, electrospun poly(ε-caprolactone) (PCL) fiber mats to form polydopamine coating. Transmission electron microscopy images demonstrated that self-polymerization of dopamine was induced by pH shift and that the thickness of polydopamine coating was readily modulated by adjusting the concentration …


Chronic Paracetamol Treatment Influences Indices Of Reactive Oxygen Species Accumulation In The Aging Fischer 344 X Brown Norway Rat Aorta, Kevin M. Rice, Sarath Meduru, Sunil K. Kakarla, Anjaiah Katta, Sriram P. Mupparaju, Brent Kidd, Lynne J. Goebel, Eric R. Blough Apr 2012

Chronic Paracetamol Treatment Influences Indices Of Reactive Oxygen Species Accumulation In The Aging Fischer 344 X Brown Norway Rat Aorta, Kevin M. Rice, Sarath Meduru, Sunil K. Kakarla, Anjaiah Katta, Sriram P. Mupparaju, Brent Kidd, Lynne J. Goebel, Eric R. Blough

MIIR Faculty Research

Previous reports have demonstrated that increased levels of reactive oxygen species (ROS) and alterations in cell signaling characterize aging in the Fischer 344 X Brown Norway (FBN) rat aorta. Other work has suggested that increases in ROS may be related to vascular wall thickening and the development of hypertension. Paracetamol (acetaminophen) is a potent antioxidant that has been found to diminish free radicals in ischemia-reperfusion studies. However, it remains unclear whether chronic paracetamol administration influences signaling or ROS accumulation in the aging aorta. FBN rats (27 months old; n=8) were subjected to 6 months of treatment with a therapeutic dose …


Down-Regulation Of The Transcription Factor Snail In The Placentas Of Patients With Preeclampsia And In A Rat Model Of Preeclampsia, Larissa Federova, Cara Gatto-Weis, Sleiman Smaili, Nauman Khurshid, Joseph I. Shapiro M.D., Deepak Malhorta, Terrence Horrigan Jan 2012

Down-Regulation Of The Transcription Factor Snail In The Placentas Of Patients With Preeclampsia And In A Rat Model Of Preeclampsia, Larissa Federova, Cara Gatto-Weis, Sleiman Smaili, Nauman Khurshid, Joseph I. Shapiro M.D., Deepak Malhorta, Terrence Horrigan

Biochemistry and Microbiology

Background: Placental malfunction in preeclampsia is believed to be a consequence of aberrant differentiation of trophoblast lineages and changes in utero-placental oxygenation. The transcription factor Snail, a master regulator molecule of epithelial-mesenchymal transition in embryonic development and in cancer, is shown to be involved in trophoblast differentiation as well. Moreover, Snail can be controlled by oxidative stress and hypoxia. Therefore, we examined the expression of Snail and its downstream target, e-cadherin, in human normal term, preterm and preeclamptic placentas, and in pregnant rats that developed preeclampsia-like symptoms in the response to a 20- fold increase in sodium intake.

Methods: Western …


Using Lectinmicroarrays To Identify Regulatory Mechanisms For Mammalian Glycosylation, John F. Rakus Nov 2011

Using Lectinmicroarrays To Identify Regulatory Mechanisms For Mammalian Glycosylation, John F. Rakus

Chemistry Faculty Research

Glycosylation involves the post-translational addition of carbohydrates to protein molecules and is an intricate and indispensable biochemical process. Study of this complicated network of interactions is hindered by the lack of a coding template analogous to the genetic code, and by the vast structural complexity inherent to carbohydrate polymers. We use lectins (non-enzymatic carbohydrate-binding proteins of non-immunological origin) as microarray probes to identify carbohydrate features expressed on cellular surfaces. Specifically, we utilized lectin microarray technology to investigate the differences in carbohydrates expressed by the cell lines of the Nation Cancer Institute’s NCI-60 panel. Our investigation identified tissue-specific expression differences in …


Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent E. Sollars, Andrea Del Pilar Belalcazar Sep 2011

Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent E. Sollars, Andrea Del Pilar Belalcazar

Biochemistry and Microbiology

Foxp3 is responsible for the major immunological features of Treg cells, including hypoproliferation in vitro, immune suppression of conventional T cells and resistance to Th2 cell differentiation. In addition to the Forkhead domain, the Foxp3 protein contains the N-terminal, zinc finger and leucine zipper domains. To understand how these domains contribute to Foxp3 functions, we systematically compared the roles of these domains in determining the 3 major immunological features of Treg cells. We designed a bridge-mediated mutagenesis method to generate Foxp3 mutants with complete deletion of each of the domains. CD4 T cells expressing the Foxp3 mutant with deletion of …


Effect Of Aging On Cellular Mechanotransduction, Miaozong Wu, Jacqueline Fannin, Kevin M. Rice, Bin Wang, Eric R. Blough Jan 2011

Effect Of Aging On Cellular Mechanotransduction, Miaozong Wu, Jacqueline Fannin, Kevin M. Rice, Bin Wang, Eric R. Blough

MIIR Faculty Research

Aging is becoming a critical heath care issue and a burgeoning economic burden on society. Mechanotransduction is the ability of the cell to sense, process, and respond to mechanical stimuli and is an important regulator of physiologic function that has been found to play a role in regulating gene expression, protein synthesis, cell differentiation, tissue growth, and most recently, the pathophysiology of disease. Here we will review some of the recent findings of this field and attempt, where possible, to present changes in mechanotransduction that are associated with the aging process in several selected physiological systems, including musculoskeletal, cardiovascular, neuronal, …


Radially Aligned, Electrospun Nanofibers As Dural Substitutes For Wound Closure And Tissue Regeneration Applications, Jingwei Xie, Matthew R. Macewan, Wilson Z. Ray, Wenying Liu, Daku Y. Siewe, Younan Xia Aug 2010

Radially Aligned, Electrospun Nanofibers As Dural Substitutes For Wound Closure And Tissue Regeneration Applications, Jingwei Xie, Matthew R. Macewan, Wilson Z. Ray, Wenying Liu, Daku Y. Siewe, Younan Xia

MIIR Faculty Research

This paper reports the fabrication of scaffolds consisting of radially aligned poly(ε-caprolactone) nanofibers by utilizing a collector composed of a central point electrode and a peripheral ring electrode. This novel class of scaffolds was able to present nanoscale topographic cues to cultured cells, directing and enhancing their migration from the periphery to the center. We also established that such scaffolds could induce faster cellular migration and population than nonwoven mats consisting of random nanofibers. Dural fibroblast cells cultured on these two types of scaffolds were found to express type I collagen, the main extracellular matrix component in dural mater. The …


Capsaicin Displays Anti-Proliferative Activity Against Human Small Cell Lung Cancer In Cell Culture And Nude Mice Models Via The E2f Pathway, Kathleen C. Brown, Theodore R. Witte, W. Elaine Hardman, Haitao Luo, Yi C. Chen, A. Betts Carpenter, Jamie K. Lau, Piyali Dasgupta Apr 2010

Capsaicin Displays Anti-Proliferative Activity Against Human Small Cell Lung Cancer In Cell Culture And Nude Mice Models Via The E2f Pathway, Kathleen C. Brown, Theodore R. Witte, W. Elaine Hardman, Haitao Luo, Yi C. Chen, A. Betts Carpenter, Jamie K. Lau, Piyali Dasgupta

Biochemistry and Microbiology

Background: Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays antiproliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo.

Methodology/Principal Findings: BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin potently …


Rbc And Wbc Fatty Acid Composition Following Consumption Of An Omega 3 Supplement: Lessons For Future Clinical Trials, Theodore R. Witte, Alexander J. Salazar, Oscar F. Ballester, W. Elaine Hardman Mar 2010

Rbc And Wbc Fatty Acid Composition Following Consumption Of An Omega 3 Supplement: Lessons For Future Clinical Trials, Theodore R. Witte, Alexander J. Salazar, Oscar F. Ballester, W. Elaine Hardman

Biochemistry and Microbiology

Background: Results from increasing numbers of in vitro and in vivo studies have demonstrated that omega 3 fatty acids incorporated in cell culture media or in the diet of the animals can suppress the growth of cancers. When human clinical trials are initiated to determine the ability of omega 3 fatty acids to alter growth or response to chemotherapeutic interventions of cancers, it will be essential to determine the omega 3 intake of individuals in the trial to determine compliance with consumption of the supplement and to correlate with endpoints of efficacy. We wondered if the fatty acid composition of …


Prieurianin Causes Weight Loss In Diet-Induced Obese Mice And Inhibits Adipogenesis In Cultured Preadipocytes, Ahmed Kablan, Rudel A. Saunders, Maria Szkudlarek-Mikho, Andrew J.B. Chin, Raul M. Bosio, Kazuyuki Fujii, Joseph I. Shapiro M.D., Khew-Voon Chin Jan 2010

Prieurianin Causes Weight Loss In Diet-Induced Obese Mice And Inhibits Adipogenesis In Cultured Preadipocytes, Ahmed Kablan, Rudel A. Saunders, Maria Szkudlarek-Mikho, Andrew J.B. Chin, Raul M. Bosio, Kazuyuki Fujii, Joseph I. Shapiro M.D., Khew-Voon Chin

Biochemistry and Microbiology

The global increase in the incidence of obesity has emerged as one of the most serious public health risks in recent years. Despite the enormity of the obesity pandemic, there are currently only two FDA-approved therapies for its treatment and these drugs exhibit modest effi cacy and have limiting side effects. Prieurianin is a plant limonoid product that deters feeding in insect larvae. We investigated in this study the effects of prieurianin on weight loss and adipogenesis. Our results showed that prieurianin causes weight loss by reducing energy intake in obese mice on highcalorie diet. We also found that prieurianin …


Use Of Phage Display To Isolate Specifi C Human Monoclonal Antibody Fragments Against A Potential Target For Multiple Myeloma, Pei Xiong Liew, Feng Ge, Charles A. Gullo, Gerrard Kh Teoh, William Yk Hwang Jul 2009

Use Of Phage Display To Isolate Specifi C Human Monoclonal Antibody Fragments Against A Potential Target For Multiple Myeloma, Pei Xiong Liew, Feng Ge, Charles A. Gullo, Gerrard Kh Teoh, William Yk Hwang

Biochemistry and Microbiology

Introduction: Multiple myeloma (MM), a malignancy of plasma cells, accounts for 10% of all haematological malignancies and is currently incurable. Although it can be treated, the disease tends to relapse after several years and becomes increasingly resistant to conventional therapy. Investigations into using humoral therapy for MM are now underway with a view that novel therapeutic agents may provide a more targeted therapy for MM.

Materials and Methods: Here, phage display, a faster and more efficient method compared to classical hybridoma fusion technology, was used as a proof-of-concept to isolate several single-chain Fragment variables (scFv) against Ku86.

Results …


The P53-Induced Siva-1 Plays A Significant Role In Cisplatin-Mediated Apoptosis, John L. Barkinge, Radhika Gudi, Hawkins Sarah, Fei Chu, Alip Borthakur, Bellur S. Prabhakar Feb 2009

The P53-Induced Siva-1 Plays A Significant Role In Cisplatin-Mediated Apoptosis, John L. Barkinge, Radhika Gudi, Hawkins Sarah, Fei Chu, Alip Borthakur, Bellur S. Prabhakar

Clinical & Translational Sciences

Background: The pro-apoptotic protein Siva-1 functions in both extrinsic and intrinsic cell death signaling; however, the exact contribution of the endogenous Siva-1 to DNA damage-induced apoptosis is unclear. Using cisplatin, a chemotherapeutic drug, to induce DNA damage and cell death, we determined the role of Siva-1.

Methods: Cisplatin treated HCT116 colorectal carcinoma cells (p53+/+ and -/-) were used in the study. With the help of recombinant lentivirus that can express siSiva (siRNA that specifi cally targets Siva-1), we also generated Siva-1 knockdown HCT116 cells. Apoptosis was determined by tetramethyl rhodamine methyl ester (TMRM) staining and propidium iodide (PI) staining.

Results: …


Association Of Epstein-Barr Virus With Nasopharyngeal Carcinoma And Current Status Of Development Of Cancer-Derived Cell Lines, Charles A. Gullo Phd, Wong Kein Low, Gerrard Teoh Jan 2008

Association Of Epstein-Barr Virus With Nasopharyngeal Carcinoma And Current Status Of Development Of Cancer-Derived Cell Lines, Charles A. Gullo Phd, Wong Kein Low, Gerrard Teoh

Biochemistry and Microbiology

It is well known that the Epstein-Barr virus (EBV) contributes directly to tumourigenesis in nasopharyngeal carcinoma (NPC), primarily in the undifferentiated form of NPC (WHO type III; UNPC or UC), which is commonly found in South East Asia. Unfortunately, research in NPC has been severely hampered by the lack of authentic EBV-positive (EBV+) human NPC cell lines for study. Since 1975, there have been more than 20 reported NPC cell lines. However, many of these NPC-derived cell lines do not express EBV transcripts in long-term culture, and therefore that finding may dispute the fundamental theory of NPC carcinogenesis. In fact, …


Dietary Canola Oil Suppressed Growth Of Implanted Mda-Mb 231 Human Breast Tumors In Nude Mice, W. Elaine Hardman Dec 2007

Dietary Canola Oil Suppressed Growth Of Implanted Mda-Mb 231 Human Breast Tumors In Nude Mice, W. Elaine Hardman

Biochemistry and Microbiology

Long chain omega 3 (n-3) fatty acids, eicosapentaenoic (EPA) and/or docosahexaenoic acid (DHA), have been shown to suppress growth of most cancer cells. In vivo, alpha linolenic acid (ALA, 18:3n-3) can be converted to EPA or DHA. We hypothesized that substituting canola oil (10% ALA) for the corn oil (1% ALA) in the diet of cancer bearing mice would slow tumor growth by increasing n-3 fatty acids in the diet. Sixty nude mice received MDA-MB 231 human breast cancer cells and were fed a diet containing 8% w/w corn oil until the mean tumor volume was 60 mm 3 . …


Uniaxial Stretch-Induced Regulation Of Mitogen-Activated Protein Kinase, Akt And P70s6 Kinase In The Ageing Fischer 344 × Brown Norway Rat Aorta, Kevin M. Rice, Devashish H. Desai, Deborah L. Preston, Paulette S. Wehner, Eric R. Blough Sep 2007

Uniaxial Stretch-Induced Regulation Of Mitogen-Activated Protein Kinase, Akt And P70s6 Kinase In The Ageing Fischer 344 × Brown Norway Rat Aorta, Kevin M. Rice, Devashish H. Desai, Deborah L. Preston, Paulette S. Wehner, Eric R. Blough

MIIR Faculty Research

The effects of ageing on the cardiovascular system contribute to substantial alterations in cellular morphology and function. The variables regulating these changes are unknown; however, one set of signalling molecules that may be of particular importance in mediating numerous cellular responses, including control of cell growth, differentiation and adaptation, are the proteins associated with the mitogen-activated protein kinase (MAPK) signalling systems. The MAPKs, in conjunction with the p70 S6k signalling cascade, have emerged as critical components for regulating numerous mechanotransduction-related cellular responses. Here we investigate the ability of uniaxial stretch to activate the MAPK and p70 S6k pathways in adult …


Therapeutic Electromagnetic Field (Temf) And Gamma Irradiation On Human Breast Cancer Xenograft Growth, Angiogenesis And Metastasis, Ivan L. Cameron, Luzhe Sun, Nicholas Short, W. Elaine Hardman, C. Douglas Williams Jul 2005

Therapeutic Electromagnetic Field (Temf) And Gamma Irradiation On Human Breast Cancer Xenograft Growth, Angiogenesis And Metastasis, Ivan L. Cameron, Luzhe Sun, Nicholas Short, W. Elaine Hardman, C. Douglas Williams

Biochemistry and Microbiology

Background

The effects of a rectified semi-sinewave signal (15 mT amplitude, 120 pulses per second, EMF Therapeutics, Inc.) (TEMF) alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA MB231 breast cancer xenograft were tested. Green fluorescence protein transfected cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into four treatment groups: untreated controls; 10 minute daily TEMF; 200 cGy of IR every other day (total 800 cGy); IR plus daily TEMF. Some mice in each group were euthanized 24 hours after the …


Endothelial Cell Pseudopods And Angiogenesis Of Breast Cancer Tumors, Ivan L. Cameron, Nicholas Short, Luzhe Sun, W. Elaine Hardman May 2005

Endothelial Cell Pseudopods And Angiogenesis Of Breast Cancer Tumors, Ivan L. Cameron, Nicholas Short, Luzhe Sun, W. Elaine Hardman

Biochemistry and Microbiology

Background

A neoplastic tumor cannot grow beyond a millimeter or so in diameter without recruitment of endothelial cells and new blood vessels to supply nutrition and oxygen for tumor cell survival. This study was designed to investigate formation of new blood vessels within a human growing breast cancer tumor model (MDA MB231 in mammary fat pad of nude female mouse). Once the tumor grew to 35 mm3, it developed a well-vascularized capsule. Histological sections of tumors greater than 35 mm3were stained with PAS, with CD-31 antibody (an endothelial cell maker), or with hypoxia inducible factor 1α …


Dietary Omega-3 Fatty Acids And Ionizing Irradiation On Human Breast Cancer Xenograft Growth And Angiogenesis, W. Elaine Hardman, Luzhe Sun, Nicholas Short, Ivan L. Cameron Apr 2005

Dietary Omega-3 Fatty Acids And Ionizing Irradiation On Human Breast Cancer Xenograft Growth And Angiogenesis, W. Elaine Hardman, Luzhe Sun, Nicholas Short, Ivan L. Cameron

Biochemistry and Microbiology

Background

The effects of an omega-3 (n-3) fatty acid enriched diet alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA-MB231 breast cancer xenograft were tested. The cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into two diet groups: 1) mice with 10% corn oil (rich in omega 6 fatty acids) in their food, 2) mice consuming a 10% fat diet that was enriched in n-3 fatty acids. After two weeks on the diet, treatment with 200 cGy of IR every second …


Waddington’S Widget: Hsp90 And The Inheritance Of Acquired Characters, Douglas M. Ruden, Mark D. Garfinkel, Vincent E. Sollars, Xiangyi Lu Oct 2003

Waddington’S Widget: Hsp90 And The Inheritance Of Acquired Characters, Douglas M. Ruden, Mark D. Garfinkel, Vincent E. Sollars, Xiangyi Lu

Biochemistry and Microbiology

Conrad Waddington published an influential model for evolution in his 1942 paper, Canalization of Development and Inheritance of Acquired Characters. In this classic, albeit controversial, paper, he proposed that an unknown mechanism exists that conceals phenotypic variation until the organism is stressed. Recent studies have proposed that the highly conserved chaperone Hsp90 could function as a “capacitor,” or an “adaptively inducible canalizer,” that masks silent phenotypic variation of either genetic or epigenetic origin. This review will discuss evidence for, and arguments against, the role of Hsp90 as a capacitor for morphological evolution, and as a key component of what …


High Dietary Level Of Synthetic Vitamin E On Lipid Peroxidation, Membrane Fatty Acid Composition And Cytotoxicity In Breast Cancer Xenograft And In Mouse Host Tissue, Ivan L. Cameron, Jesus Munoz, Christopher J. Barnes, W. Elaine Hardman Mar 2003

High Dietary Level Of Synthetic Vitamin E On Lipid Peroxidation, Membrane Fatty Acid Composition And Cytotoxicity In Breast Cancer Xenograft And In Mouse Host Tissue, Ivan L. Cameron, Jesus Munoz, Christopher J. Barnes, W. Elaine Hardman

Biochemistry and Microbiology

Background

d-α-tocopherol is a naturally occurring form of vitamin E not previously known to have antitumor activity. Synthetic vitamin E (sE) is a commonly used dietary supplement consisting of a mixture of d-α-tocopherol and 7 equimolar stereoisomers. To test for antilipid peroxidation and for antitumor activity of sE supplementation, two groups of nude mice bearing a MDA-MB 231 human breast cancer tumor were fed an AIN-76 diet, one with and one without an additional 2000 IU/kg dry food (equivalent to 900 mg of all-rac-α-tocopherol or sE). This provided an intake of about 200 mg/kg body weight per day. The mice …


Regulation Of Retinoic Acid Receptor Α By Protein Kinase C In B16 Mouse Melanoma Cells, Goran Boskovic, Dinakar Desai, Richard M. Niles Jul 2002

Regulation Of Retinoic Acid Receptor Α By Protein Kinase C In B16 Mouse Melanoma Cells, Goran Boskovic, Dinakar Desai, Richard M. Niles

Biochemistry and Microbiology

We have previously found that retinoic acid stimulates the expression of protein kinase Cα (PKC) in B16 mouse melanoma cells. Because it has been reported that PKC can phosphorylate retinoic acid receptor (RAR) and alter its function, we determined whether changes in the level and/or activity of PKC could affect the expression or function of the RAR in B16 melanoma. Using in vivophosphorylation and band shift techniques, we could not demonstrate that altering PKC activity and/or protein level changed thein vivo phosphorylation of RARα. However activation of PKC resulted in increased RARα protein. Increased receptor protein correlated with …


Therapeutic Electromagnetic Field Effects On Angiogenesis And Tumor Growth, C. Douglas Williams, Marko S. Markov, W. Elaine Hardman, Ivan L. Cameron Sep 2001

Therapeutic Electromagnetic Field Effects On Angiogenesis And Tumor Growth, C. Douglas Williams, Marko S. Markov, W. Elaine Hardman, Ivan L. Cameron

Biochemistry and Microbiology

Background: A new approach to cancer therapy based on the application of therapeutic electromagnetic fields (TEMF) has been developed by EMF Therapeutics, Inc., Chattanooga, TN, USA. This study was designed to assess the effect of TEMF on tumor vascularization and growth of murine 16/C mammmary adenocarcinoma cells in C3H/HeJ mice.

Materials and Methods: Implanted tumors were allowed to grow for seven days until the tumor volume reached 100 mm3 before treatment was started. Mice (20 per control, 10 per EMF exposed group) received treatment (10 minutes per day with 0, 10 mT, 15 mT or 20 mT) with a 120 …