Sumo-Targeted Ubiquitin Ligase (Stubl) Slx5 Regulates Proteolysis Of Centromeric Histone H3 Variant Cse4 And Prevents Its Mislocalization To Euchromatin, Kentaro Ohkuni, Yoshimitsu Takahashi, Alyona Flup, Josh La, Wei-Chun Au, Nagesh Pasupala, Ruben Levy-Meyers, Jack Warren, Alexander Strunnikov, Richard E. Baker, Oliver Kerscher, Kerry Bloom, Munira A. Basrai
Centromeric histone H3, CENP-ACse4, is essential for faithful chromosome segregation. Stringent regulation of cellular levels of CENP-ACse4 restricts its localization to centromeres. Mislocalization of CENP-ACse4 is associated with aneuploidy in yeast and flies and tumorigenesis in human cells; thus defining pathways that regulate CENP-A levels is critical for understanding how mislocalization of CENP-A contributes to aneuploidy in human cancers. Previous work in budding yeast shows that ubiquitination of overexpressed Cse4 by Psh1, an E3 ligase, partially contributes to proteolysis of Cse4. Here we provide the first evidence that Cse4 is sumoylated by E3 ligases Siz1 and Siz2 in vivo and ...
Metastatic Biomarkers In Synovial Sarcoma, 2017 Loma Linda University
Metastatic Biomarkers In Synovial Sarcoma, Rosalia De Necochea-Campion, Lee M. Zuckerman, Hamid R. Mirshahidi, Shahrzad Khosrowpour, Chien-Shing Chen, Saied Mirshahidi
Library Articles and Research
Synovial sarcoma (SS) is an aggressive soft tissue sarcoma (STS) that typically occurs in the extremities near a joint. Metastatic disease is common and usually occurs in the lungs and lymph nodes. Surgical management is the mainstay of treatment with chemotherapy and radiation typically used as adjuvant treatment. Although chemotherapy has a positive impact on survival, the prognosis is poor if metastatic disease occurs. The biology of sarcoma invasion and metastasis remain poorly understood. Chromosomal translocation with fusion of the SYT and SSX genes has been described and is currently used as a diagnostic marker, although the full impact of ...
Engineering Fret Biosensors For Microrna Presence/Absence Analysis, 2017 Oregon State University
Engineering Fret Biosensors For Microrna Presence/Absence Analysis, Nicholas E. Larkey, Sean M. Burrows
Biomedical Engineering Western Regional Conference
No abstract provided.
Mt1-Mmp Mediates The Migratory And Tumourigenic Potential Of Breast Cancer Cells Via Non-Proteolytic Mechanisms, 2017 The University of Western Ontario
Mt1-Mmp Mediates The Migratory And Tumourigenic Potential Of Breast Cancer Cells Via Non-Proteolytic Mechanisms, Mario Cepeda
Electronic Thesis and Dissertation Repository
Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) is a multifunctional protease that affects cell function via proteolytic and non-proteolytic mechanisms such as promoting degradation of the extracellular matrix (ECM) or augmentation of cell migration and viability, respectively. MT1-MMP has been implicated in metastatic progression ostensibly due to its ability to degrade ECM components and to allow migration of cells through the basement membrane. Despite in vitro studies demonstrating this principle, this knowledge has not translated into the use of MMP inhibitors (MMPi) that inhibit substrate catalysis as effective cancer therapeutics, or been corroborated by evidence of in vivo ECM degradation mediated by ...
Chloroquine-Inducible Par-4 Secretion Is Essential For Tumor Cell Apoptosis And Inhibition Of Metastasis, 2017 University of Kentucky
Chloroquine-Inducible Par-4 Secretion Is Essential For Tumor Cell Apoptosis And Inhibition Of Metastasis, Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar
Radiation Medicine Faculty Publications
The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings ...
Press-Pulse: A Novel Therapeutic Strategy For The Metabolic Management Of Cancer, 2017 George Washington University
Press-Pulse: A Novel Therapeutic Strategy For The Metabolic Management Of Cancer, Thomas Seyfried, George Yu, Joseph Maroon, Dominic D'Agostino
Urology Faculty Publications
A shift from respiration to fermentation is a common metabolic hallmark of cancer cells. As a result, glucose and glutamine become the prime fuels for driving the dysregulated growth of tumors. The simultaneous occurrence of “Press-Pulse” disturbances was considered the mechanism responsible for reduction of organic populations during prior evolutionary epochs. Press disturbances produce chronic stress, while pulse disturbances produce acute stress on populations. It was only when both disturbances coincide that population reduction occurred.
This general concept can be applied to the management of cancer by creating chronic metabolic stresses on tumor cell energy metabolism (press disturbance ...
Mammary Extracellular Matrix Directs Differentiation Of Testicular And Embryonic Stem Cells To Form Functional Mammary Glands In Vivo, Robert D. Bruno, Jodie M. Fleming, Andrea L. George, Corinne A. Boulanger, Pepper Schedin, Gilbert H. Smith
Medical Diagnostics & Translational Sciences Faculty Publications
Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived ...
Id4 And Fkbp52 Interaction Regulates Androgen Receptor Activity: Mechanistic Insight, 2016 Clark Atlanta University
Id4 And Fkbp52 Interaction Regulates Androgen Receptor Activity: Mechanistic Insight, Jugal Bharat Joshi
Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University
The inhibitor of DNA binding protein 4 (ID4) is a dominant negative regulator of basic helix loop helix (bHLH) family of transcription factors.1 Recently, Patel et al., demonstrated that inhibitor of differentiation 4 (ID4) acts as a tumor suppressor and its loss, frequently observed in prostate cancer, promotes castration-resistant prostate cancer (CRPC) through constitutive androgen receptor (AR) activation.2 However, the mechanism by which loss of ID4 promotes constitutively active AR signaling in the CRPC conditions is unknown. The rationale of the present study was to unravel the underlying molecular mechanisms through which loss of ID4 potentiates AR signaling ...
A Framework For Assessing The Rationality Of Judgments In Carcinogenicity Hazard Identification, 2016 University of New Hampshire
A Framework For Assessing The Rationality Of Judgments In Carcinogenicity Hazard Identification, Douglas J. Crawford-Brown, Kenneth G. Brown
RISK: Health, Safety & Environment
Arguing that guidelines for identifying carcinogens now lack a philosophically rigorous framework, the authors present an alternative that draws clear attention to the process of reasoning towards judgments of carcinogenicity.
Anthropogenic Electromagnetic Fields And Cancer: A Perspective, 2016 University of New Hampshire
Anthropogenic Electromagnetic Fields And Cancer: A Perspective, Charles Tomljanovic, Maxine Wright-Walters, Jules Stephensky
RISK: Health, Safety & Environment
The authors review findings of a recent National Research Council report and conclude that, e.g., until a cancer promotion model can be identified for effective testing, the EMF issue will remain open to debate.
Pharmacokinetics, Tissue Distribution, Synergistic Activity, And Antitumor Activity Of Two Isomeric Flavones, 2016 East Tennessee State University
Pharmacokinetics, Tissue Distribution, Synergistic Activity, And Antitumor Activity Of Two Isomeric Flavones, Crystal L. Whitted
Electronic Theses and Dissertations
Flavonoids are polyphenolic secondary metabolites found in plants that have bioactive properties including antiviral, antioxidant, and anticancer. Two isomeric flavone were extracted from Gnaphalium elegans and Achyrocline bogotensis, plants used by the people from the Andean region of South America as remedies for cancer. 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5, 7–dihydroxy- 3, 6, 8 trimethoxy flavone/ flavone A) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3, 5–dihydroxy-6, 7, 8–trimethoxy flavone/ flavone B) have shown antineoplastic activity against colon cancer cell lines dependent upon their differentiation status. Pharmacokinetic studies reported herein were used to determine dosing for antitumor assays, as ...
Coping With The Risk Of Cancer In Children Living Near Power Lines, 2016 University of New Hampshire
Coping With The Risk Of Cancer In Children Living Near Power Lines, Eileen N. Abt
RISK: Health, Safety & Environment
Ms. Abt briefly summarizes evidence linking power lines with a possible increase in risk of childhood cancer. She also recounts how, although many experts remain skeptical of causality, public fears, whether or not warranted, have themselves created serious problems. Finally, she proposes ways to address those problems.
Pt-Mal-Lhrh Mediates Breast Cancer Cell Cytotoxicity Through Increased Apoptosis, 2016 Eastern Kentucky University
Pt-Mal-Lhrh Mediates Breast Cancer Cell Cytotoxicity Through Increased Apoptosis, Kendall E. Collins
In the United States one in eight women will be afflicted with breast cancer. It is estimated that in 2016 there will be approximately 246,600 new invasive breast cancer cases and 61,000 new non-invasive cases. Triple negative breast cancers account for 15% of all breast cancers and are significantly more aggressive than other subtypes. Treatment options for triple negative breast cancer are limited due to the cancers not expressing the estrogen, progestogen, or herceptin receptors making them unresponsive to hormonal therapy. Our recent work centers around developing a novel chemotherapeutic agent that will direct therapy selectively to triple ...
Targeted And Controlled Anticancer Drug Delivery And Release With Magnetoelectric Nanoparticles, 2016 Florida International University
Targeted And Controlled Anticancer Drug Delivery And Release With Magnetoelectric Nanoparticles, Alexandra Rodzinski
FIU Electronic Theses and Dissertations
A major challenge of cancer treatment is successful discrimination of cancer cells from healthy cells. Nanotechnology offers multiple venues for efficient cancer targeting. Magnetoelectric nanoparticles (MENs) are a novel, multifaceted, physics-based cancer treatment platform that enables high specificity cancer targeting and externally controlled loaded drug release. The unique magnetoelectric coupling of MENs allows them to convert externally applied magnetic fields into intrinsic electric signals, which allows MENs to both be drawn magnetically towards the cancer site and to electrically interface with cancer cells. Once internalized, the MEN payload release can be externally triggered with a magnetic field. MENs uniquely allow ...
Native And Bone Marrow-Derived Cell Mosaicism In Gastric Carcinoma In H. Pylori-Infected P27-Deficient Mice, 2016 Warren Alpert Medical School of Brown University
Native And Bone Marrow-Derived Cell Mosaicism In Gastric Carcinoma In H. Pylori-Infected P27-Deficient Mice, Songhua Zhang, Woojin Kim, Tu T. Pham, Arlin B. Rogers, Jeanmarie Houghton, Steven F. Moss
Open Access Articles
OBJECTIVE: Chronic Helicobacter pylori (H. pylori) infection promotes non-cardia gastric cancer. Some mouse models suggest that bone marrow derived cells (BMDC) contribute to Helicobacter-associated gastric carcinogenesis. We determined whether this increased susceptibility to Helicobacter-induced gastric carcinogenesis of p27-deficient mice is dependent upon their p27-null BMDC or their p27-null gastric epithelial cells.
DESIGN: Female mice (recipients) were irradiated and transplanted with BMDC from male donors. Wild type (WT) mice in group 1 (control) received BMDC from male GFP-transgenic mice. Female WT and p27 KO mice were engrafted with male p27KO mice BMDC (Group 2) or GFP-transgenic WT BMDC (Group 3). Recipients ...
A Microrna/Runx1/Runx2 Network Regulates Prostate Tumor Progression From Onset To Adenocarcinoma In Tramp Mice, 2016 University of Vermont College of Medicine
A Microrna/Runx1/Runx2 Network Regulates Prostate Tumor Progression From Onset To Adenocarcinoma In Tramp Mice, Nicholas H. Farina, Areg Zingiryan, Jacqueline Akech, Cody J. Callahan, Huimin Lu, Janet L. Stein, Lucia R. Languino, Gary S. Stein, Jane B. Lian
Open Access Articles
While decades of research have identified molecular pathways inducing and promoting stages of prostate cancer malignancy, studies addressing dynamic changes of cancer-related regulatory factors in a prostate tumor progression model are limited. Using the TRAMP mouse model of human prostate cancer, we address mechanisms of deregulation for the cancer-associated transcription factors, Runx1 and Runx2 by identifying microRNAs with reciprocal expression changes at six time points during 33 weeks of tumorigenesis. We molecularly define transition stages from PIN lesions to hyperplasia/neoplasia and progression to adenocarcinoma by temporal changes in expression of human prostate cancer markers, including the androgen receptor and ...
The Principal Genetic Determinants For Nasopharyngeal Carcinoma In China Involve The Hla Class I Antigen Recognition Groove, 2016 Beijing University of Technology - China; National Cancer Institute at Frederick; Wuzhou Red Cross Hospital - China
The Principal Genetic Determinants For Nasopharyngeal Carcinoma In China Involve The Hla Class I Antigen Recognition Groove, Minzhong Tang, J. A. Lautenberger, Xiaojiang Gao, Efe Sezgin, Sher L. Hendrickson, Jennifer L. Troyer, Victor A. David, Li Guan, Carl Mcintosh, Xiuchan Guo, Yuming Zheng, Jian Liao, Hong Deng, Michael Malasky, Bailey Kessing, Cheryl Winkler, Mary Carrington, Guy De The, Yi Zeng, Stephen J. O'Brien
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA –B, and HLA -C class I genes (PHLA-A-aa-site-62 = 7.4×10−29; P HLA-B-aa-site-116 = 6.5×10−19; P HLA-C-aa-site-156 = 6 ...
Genetic Polymorphisms Of Cyp2e1, Gstp1, Nqo1 And Mpo And The Risk Of Nasopharyngeal Carcinoma In A Han Chinese Population Of Southern China, 2016 Chinese Center for Disease Control; National Cancer Institute at Frederick
Genetic Polymorphisms Of Cyp2e1, Gstp1, Nqo1 And Mpo And The Risk Of Nasopharyngeal Carcinoma In A Han Chinese Population Of Southern China, Xiuchan Guo, Yi Zeng, Hong Deng, Jian Liao, Yuming Zheng, Ji Li, Bailey Kessing, Stephen J. O'Brien
Southern China is a major area for endemic nasopharyngeal carcinoma (NPC). Genetic factors as well as environmental factors play a role in development of NPC. To investigate the roles of previously described carcinogen metabolism gene variants for NPC susceptibility in a Han Chinese population, we conducted a case-control study in two independent study population groups afflicted with NPC in Guangdong and Guangxi Provinces of southern China.
Five single nucleotide polymorphisms (SNPs) of CYP2E1-rs2031920, CYP2E1-rs6413432, GSTP1-rs947894, MPO-rs2333227 and NQO1-rs1800566 were genotyped by PCR-based RFLP, sequencing and TaqMan assay in 358 NPC cases and 629 ...
Conserved Regions Of Homologous G-Banded Chromosomes Between Orders In Mammalian Evolution: Carnivores And Primates, 2016 National Cancer Institute at Frederick
Conserved Regions Of Homologous G-Banded Chromosomes Between Orders In Mammalian Evolution: Carnivores And Primates, William G. Nash, Stephen J. O'Brien
The recent derivation of a biochemical map of 33 loci of the domestic cat (Felis catus) revealed a striking conservation of chromosomal linkage associations between the cat and humans. A comparison of homologous (by linkage criteria) chromosomes by using conventionally extended and high-resolution G-banding of human and feline chromosomes is presented. Four criteria for establishing probable cytogenetic homologies of chromosomal regions were invoked: (i) map placement of homologous genes to the same chromosomes; (ii) cytological correlation of G-banding pattern; (iii) placement of homologous genes, by regional gene mapping, in the region of cytological homology; and (iv) a requirement that the ...
Identification Of Novel Pathways That Promote Anoikis Through Genome-Wide Screens, 2016 University of Massachusetts Medical School
Identification Of Novel Pathways That Promote Anoikis Through Genome-Wide Screens, Victoria E. Pedanou
GSBS Dissertations and Theses
Epithelial cells that lose attachment to the extracellular matrix (ECM) undergo a specialized form of apoptosis called anoikis. Anoikis has an important role in preventing oncogenesis, particularly metastasis, by eliminating cells that lack proper ECM cues. The basis of anoikis resistance remains to be determined and to date has not been linked to alterations in expression or activity of previously identified anoikis effector genes. Here, I utilized two different screening strategies to identify novel anoikis effector genes and miRNAs in order to gain a deeper understanding of anoikis and the potential mechanisms of anoikis resistance in cancer.
Using large-scale RNA ...