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Pharmacokinetics, Tissue Distribution, Synergistic Activity, And Antitumor Activity Of Two Isomeric Flavones, Crystal L. Whitted 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, Eileen N. Abt 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.


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 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

Stephen 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, Xiuchan Guo, Yi Zeng, Hong Deng, Jian Liao, Yuming Zheng, Ji Li, Bailey Kessing, Stephen J. O'Brien 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

Stephen O'Brien

Background

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.

Methods

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, William G. Nash, Stephen J. O'Brien 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

Stephen 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 ...


Old Remedies In The Biotechnology Age: Moore V. Regents, Michelle J. Burke, Victoria M. Schmidt 2016 University of New Hampshire

Old Remedies In The Biotechnology Age: Moore V. Regents, Michelle J. Burke, Victoria M. Schmidt

RISK: Health, Safety & Environment

The California Supreme Court, by excluding a potential remedy, has eliminated many concerns generated by a lower court decision resolving rights to the cell line derived from John Moore's spleen. Yet, the Supreme Court gave little attention to remedies that remain. The authors argue that a constructive trust, a remedy of considerable vintage and great flexibility, could be applied to achieve a just result in such circumstances without affecting the biotechnology world at large.


Sulfatase 2 Facilitates Lymphangiogenesis In Breast Cancer By Regulating Vegf-D., Chenfang Zhu, Xiaoliang Qi, Xin Zhou, Xin Nie, Yan Gu 2016 George Washington University

Sulfatase 2 Facilitates Lymphangiogenesis In Breast Cancer By Regulating Vegf-D., Chenfang Zhu, Xiaoliang Qi, Xin Zhou, Xin Nie, Yan Gu

Surgery Faculty Publications

In our previous studies, sulfatase 2 (Sulf2) was found to upregulate vascular endothelial growth factor-D (VEGF-D) expression in breast cancer. As VEGF-D plays an important role in lymphangiogenesis, we hypothesized that Sulf2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D. To evaluate the functions of Sulf2 on lymphangiogenesis in breast cancer, proliferation, apoptosis, cell cycle, cell mobility and tube-formation of lymphatic endothelial cells (LECs) were measured in vitro. Lymphangiogenesis in nude mouse ears and breast cancer xenografts were examined in vivo. Furthermore, the expression levels of related signaling pathway genes were screened and verified in LECs. We found that Sulf2 ...


Mdm2 Phosphorylation Regulates Its Stability And Has Contrasting Effects On Oncogene And Radiation-Induced Tumorigenesis, Michael I. Carr, Justine E. Roderick, Hugh S. Gannon, Michelle A. Kelliher, Stephen N. Jones 2016 University of Massachusetts Medical School

Mdm2 Phosphorylation Regulates Its Stability And Has Contrasting Effects On Oncogene And Radiation-Induced Tumorigenesis, Michael I. Carr, Justine E. Roderick, Hugh S. Gannon, Michelle A. Kelliher, Stephen N. Jones

Cell and Developmental Biology Publications and Presentations

ATM phosphorylation of Mdm2-S394 is required for robust p53 stabilization and activation in DNA-damaged cells. We have now utilized Mdm2(S394A) knockin mice to determine that phosphorylation of Mdm2-S394 regulates p53 activity and the DNA damage response in lymphatic tissues in vivo by modulating Mdm2 stability. Mdm2-S394 phosphorylation delays lymphomagenesis in Emu-myc transgenic mice, and preventing Mdm2-S394 phosphorylation obviates the need for p53 mutation in Myc-driven tumorigenesis. However, irradiated Mdm2(S394A) mice also have increased hematopoietic stem and progenitor cell functions, and we observed decreased lymphomagenesis in sub-lethally irradiated Mdm2(S394A) mice. These findings document contrasting effects of ATM-Mdm2 signaling ...


Exploiting Dna Repair And Er Stress Response Pathways To Induce Apoptosis In Glioblastoma Multiforme: A Dissertation, Jessica L. Weatherbee 2016 University of Massachusetts Medical School

Exploiting Dna Repair And Er Stress Response Pathways To Induce Apoptosis In Glioblastoma Multiforme: A Dissertation, Jessica L. Weatherbee

GSBS Dissertations and Theses

Glioblastoma multiforme (GBM) is a deadly grade IV brain tumor characterized by a heterogeneous population of cells that are drug resistant, aggressive, and infiltrative. The current standard of care, which has not changed in over a decade, only provides GBM patients with 12-14 months survival post diagnosis. We asked if the addition of a novel endoplasmic reticulum (ER) stress inducing agent, JLK1486, to the standard chemotherapy, temozolomide (TMZ), which induces DNA double strand breaks (DSBs), would enhance TMZ’s efficacy. Because GBMs rely on the ER to mitigate their hypoxic environment and DNA repair to fix TMZ induced DSBs, we ...


Assembly Of Nucleic Acid-Based Nanoparticles By Gas-Liquid Segmented Flow Microfluidics, Matthew L. Capek, Ross VerHeul, David H. Thompson 2016 Purdue University

Assembly Of Nucleic Acid-Based Nanoparticles By Gas-Liquid Segmented Flow Microfluidics, Matthew L. Capek, Ross Verheul, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

The development of novel and efficient mixing methods is important for optimizing the efficiency of many biological and chemical processes. Tuning the physical and performance properties of nucleic acid-based nanoparticles is one such example known to be strongly affected by mixing efficiency. The characteristics of DNA nanoparticles (such as size, polydispersity, ζ-potential, and gel shift) are important to ensure their therapeutic potency, and new methods to optimize these characteristics are of significant importance to achieve the highest efficacy. In the present study, a simple segmented flow microfluidics system has been developed to augment mixing of pDNA/bPEI nanoparticles. This DNA ...


Identifying The Effects Of Unprocessed Let-7a-1 And Let-7a-3 In Non-Small Cell Lung Cancer, Hana Kubo, Phillip J. McCown, Andrea L. Kasinski 2016 Purdue University

Identifying The Effects Of Unprocessed Let-7a-1 And Let-7a-3 In Non-Small Cell Lung Cancer, Hana Kubo, Phillip J. Mccown, Andrea L. Kasinski

The Summer Undergraduate Research Fellowship (SURF) Symposium

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate protein levels typically by interacting with the 3′ untranslated region (3′-UTR) of target messenger RNA (mRNAs) and are often aberrantly expressed in cancer. The let-7 miRNA family members are commonly regarded as cancer suppressors, by down-regulating the expression of oncoproteins such as RAS, HMGA2, and MYC. However, prior work indicates that unprocessed let-7 RNAs may be positively correlated with cancer phenotypes in lung cancer cell lines. Our study aims to identify the effects of unprocessed let-7a-1 and let-7a-3 in non-small cell lung cancer, by transfecting plasmids that express unprocessed let-7a-1 and ...


Nanobubbles Provide Theranostic Relief To Cancer Hypoxia, Christopher M. Long, Pushpak N. Bhandari, Joseph Irudayaraj 2016 Purdue University

Nanobubbles Provide Theranostic Relief To Cancer Hypoxia, Christopher M. Long, Pushpak N. Bhandari, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hypoxia is a common motif among tumors, contributing to metastasis, angiogenesis, cellular epigenetic abnormality, and resistance to cancer therapy. Hypoxia also plays a pivotal role in oncological studies, where it can be used as a principal target for new anti-cancer therapeutic methods. Oxygen nanobubbles were designed in an effort to target the hypoxic tumor regions, thus interrupting the hypoxia-inducible factor-1α (HIF-1α) regulatory pathway and inhibiting tumor progression. At less than 100nm, oxygen nanobubbles act as a vehicle for site-specific oxygen delivery, while also serving as an ultrasound contrast agent for advanced imaging purposes. Through in vitro and in vivo studies ...


P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A. Brekken, Craig W. Vander Kooi, Arthur M. Mercurio 2016 University of Massachusetts Medical School

P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A. Brekken, Craig W. Vander Kooi, Arthur M. Mercurio

Arthur M. Mercurio

Autocrine VEGF signaling is critical for sustaining prostate and other cancer stem cells (CSCs), and it is a potential therapeutic target, but we observed that CSCs isolated from prostate tumors are resistant to anti-VEGF (bevacizumab) and anti-VEGFR (sunitinib) therapy. Intriguingly, resistance is mediated by VEGF/neuropilin signaling, which is not inhibited by bevacizumab and sunitinib, and it involves the induction of P-Rex1, a Rac GEF, and consequent Rac1-mediated ERK activation. This induction of P-Rex1 is dependent on Myc. CSCs isolated from the PTEN(pc-/-) transgenic model of prostate cancer exhibit Rac1-dependent resistance to bevacizumab. Rac1 inhibition or P-Rex1 downregulation increases ...


Alcoholic Hepatitis Accelerates Early Hepatobiliary Cancer By Increasing Stemness And Mir-122-Mediated Hif-1alpha Activation, Aditya Ambade, Abhishek Satishchandran, Gyongyi Szabo 2016 University of Massachusetts Medical School

Alcoholic Hepatitis Accelerates Early Hepatobiliary Cancer By Increasing Stemness And Mir-122-Mediated Hif-1alpha Activation, Aditya Ambade, Abhishek Satishchandran, Gyongyi Szabo

Gyongyi Szabo

Alcohol-related hepatocellular carcinoma (HCC) develops with advanced alcoholic liver disease and liver fibrosis. Using adult mice, we evaluate the effect of alcoholic steatohepatitis on early hepatobiliary carcinoma after initiation by diethyl-nitrosamine (DEN). Here we show that alcohol-fed DEN-injected mice have higher ALT and liver-to-body weight ratio compared to pair-fed DEN-injected mice. Alcohol feeding results in steatohepatitis indicated by increased pro-inflammatory cytokines and fibrotic genes. MRI and liver histology of alcohol+DEN mice shows hepatobiliary cysts, early hepatic neoplasia and increase in serum alpha-fetoprotein. Proliferation makers (BrdU, cyclin D1, p53) and cancer stem cell markers (CD133 and nanog) are significantly up-regulated ...


The Overexpression Of Basigin-3 In Glioblastoma, Samantha M. Wightman 2016 Northern Michigan University

The Overexpression Of Basigin-3 In Glioblastoma, Samantha M. Wightman

All NMU Master's Theses

Glioblastoma (GBM) is one of the most aggressive forms of brain tumor. With the current standard of care, survival prognosis for GBM patients is 15 months with a five-year survival rate of less than 3%. An increased understanding of the molecular mechanisms leading to cell growth and survival of GBMs may result in novel treatments to target and eradicate the disease. The protein Basigin-2 (aka EMMPRIN) induces the expression of matrix metalloproteinase (MMP) enzymes, and its expression level is positively correlated with GBM tumor grade. In 2011, Liao et al. reported that a splice variant of the basigin gene, called ...


Inhibition Of Nuclear Factor-Kappa B Enhances The Tumor Growth Of Ovarian Cancer Cell Line Derived From A Low-Grade Papillary Serous Carcinoma In P53-Independent Pathway, Xue Xiao, Gong Yang, Peng Bai, Shunping Gui, Tri M. Bui Nguyen, +8 additional authors 2016 George Washington University

Inhibition Of Nuclear Factor-Kappa B Enhances The Tumor Growth Of Ovarian Cancer Cell Line Derived From A Low-Grade Papillary Serous Carcinoma In P53-Independent Pathway, Xue Xiao, Gong Yang, Peng Bai, Shunping Gui, Tri M. Bui Nguyen, +8 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

Background: NF-kB can function as an oncogene or tumor suppressor depending on cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has never been tested. We sought to elucidate the function of NF-kB in the low-grade serous ovarian cancer.

Methods: The ovarian cancer cell line, HOC-7, derived from a low-grade papillary serous carcinoma. Introduction of a dominant negative mutant, IkBαM, which resulted in decrease of NF-kB function in ovarian cancer cell lines. The transcription ability, tumorigenesis, cell proliferation and apoptosis were observed in derivative cell lines in comparison with parental cells.

Results: Western blot analysis indicated increased ...


Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez 2016 The University of Texas Graduate School of Biomedical Sciences at Houston

Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez

UT GSBS Dissertations and Theses (Open Access)

Cancer is one of the leading causes of death and disease in the world. Considerable resources are spent to study and understand cancer, with the hope of developing new treatments and eventually cures that will help millions of people. Efforts to understand cancer are hindered by its inherent complexity and instability. Nonetheless, understanding the basics of tumor development and progression are the key to focused on studying the role of ΔNp63 in cancer, a p53 family member known to be involved in epithelial development, microRNA biogenesis, and stem cell maintenance. Using the strength of in vivo mouse models, we found ...


The Histone H3k9 Demethylase Kdm3a Promotes Anoikis By Transcriptionally Activating Pro-Apoptotic Genes Bnip3 And Bnip3l, Victoria E. Pedanou, Stephane Gobeil, Sebastien Tabaries, Tessa M. Simone, Lihua Julie Zhu, Peter M. Siegel, Michael R. Green 2016 University of Massachusetts Medical School

The Histone H3k9 Demethylase Kdm3a Promotes Anoikis By Transcriptionally Activating Pro-Apoptotic Genes Bnip3 And Bnip3l, Victoria E. Pedanou, Stephane Gobeil, Sebastien Tabaries, Tessa M. Simone, Lihua Julie Zhu, Peter M. Siegel, Michael R. Green

Open Access Articles

Epithelial cells that lose attachment to the extracellular matrix undergo a specialized form of apoptosis called anoikis. Here, using large-scale RNA interference (RNAi) screening, we find that KDM3A, a histone H3 lysine 9 (H3K9) mono- and di-demethylase, plays a pivotal role in anoikis induction. In attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, integrin signaling is decreased resulting in increased KDM3A expression. RNAi-mediated knockdown of KDM3A substantially reduces apoptosis following detachment and, conversely, ectopic expression of KDM3A induces cell death in attached cells. We find that KDM3A promotes anoikis through transcriptional activation ...


Beta1 Integrin- And Jnk-Dependent Tumor Growth Upon Hypofractionated Radiation, Aejaz Sayeed, Huimin Lu, Qin Liu, David Deming Ii, Alexander Duffy, Peter McCue, Adam P. Dicker, Roger J. Davis, Dmitry Gabrilovich, Ulrich Rodeck, Dario C. Altieri, Lucia R. Languino 2016 Thomas Jefferson University

Beta1 Integrin- And Jnk-Dependent Tumor Growth Upon Hypofractionated Radiation, Aejaz Sayeed, Huimin Lu, Qin Liu, David Deming Ii, Alexander Duffy, Peter Mccue, Adam P. Dicker, Roger J. Davis, Dmitry Gabrilovich, Ulrich Rodeck, Dario C. Altieri, Lucia R. Languino

Open Access Articles

Radiation therapy is an effective cancer treatment modality although tumors invariably become resistant. Using the transgenic adenocarcinoma of mouse prostate (TRAMP) model system, we report that a hypofractionated radiation schedule (10 Gy/day for 5 consecutive days) effectively blocks prostate tumor growth in wild type (beta1wt /TRAMP) mice as well as in mice carrying a conditional ablation of beta1 integrins in the prostatic epithelium (beta1pc-/- /TRAMP). Since JNK is known to be suppressed by beta1 integrins and mediates radiation-induced apoptosis, we tested the effect of SP600125, an inhibitor of c-Jun amino-terminal kinase (JNK) in the TRAMP model system. Our results ...


Taking A Cat Map: Genome Analysis By Supercomputer, Jose V. Lopez 2016 National Cancer Institute

Taking A Cat Map: Genome Analysis By Supercomputer, Jose V. Lopez

Jose Lopez

No abstract provided.


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