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Genistein Affects Her2 Protein Concentration, Activation And Promoter Regulation Via Estrogen Receptor-And Non-Estrogen Receptor-Mediated Mechanisms, Mary S. Sakla, Pete J. Ansell, Nader S. Shenouda, Dennis B. Lubahn, Ruth S. MacDonald 2017 University of Missouri

Genistein Affects Her2 Protein Concentration, Activation And Promoter Regulation Via Estrogen Receptor-And Non-Estrogen Receptor-Mediated Mechanisms, Mary S. Sakla, Pete J. Ansell, Nader S. Shenouda, Dennis B. Lubahn, Ruth S. Macdonald

Ruth S. MacDonald

The HER2 proto-oncogene, a member of the epidermal growth factor receptor family, is overexpressed in 20–30% of breast cancers. Genistein, the main soy isoflavone, interacts with estrogen receptors (ER) and it is also a potent tyrosine kinase inhibitor. Previously, our laboratory found that genistein delayed mammary tumor onset in transgenic mice that overexpress HER2 gene. Our goal was to define the mechanism through which genistein affects mammary tumorigenesis inHER2 overexpressing mice. We hypothesized that genistein inhibits HER2 activation and expression through ER-dependent and ER-independent mechanisms. Genistein inhibited total HER2 protein expression and tyrosine phosphorylation in BT-474, an ERα (−) and ...


Phytosterol Pygeum Africanum Regulates Prostate Cancer In Vitro And In Vivo, Nader S. Shenouda, Mary S. Sakla, Leslie G. Newton, Cynthia Besch-Williford, Norman M. Greenberg, Ruth S. MacDonald, Dennis B. Lubahn 2017 University of Missouri

Phytosterol Pygeum Africanum Regulates Prostate Cancer In Vitro And In Vivo, Nader S. Shenouda, Mary S. Sakla, Leslie G. Newton, Cynthia Besch-Williford, Norman M. Greenberg, Ruth S. Macdonald, Dennis B. Lubahn

Ruth S. MacDonald

Background

Prostate cancer is an important public health problem. It is an excellent candidate disease for chemo-prevention because prostate cancer is typically slow growing and is usually diagnosed in elderly males. Pygeum africanum (Prunus africana or Rosaceae) is an African prune (plum) tree found in tropical Africa. An extract from the bark of Pygeum africanum has been used in Europe as a prevention and treatment of prostate disorders including benign prostatic hypertrophy (BPH). More recently in the USA, the phytotherapeutic preparations of Pygeum africanum and Saw palmetto have been marketed for prostate health including prostate cancer prevention and treatment.

Methods ...


Soy Isoflavones Have An Antiestrogenic Effect And Alter Mammary Promoter Hypermethylation In Healthy Premenopausal Women1, Wenyi Qin, Weizhu Zhu, Huidong Shi, John E. Hewett, Rachel L. Ruhlen, Ruth S. MacDonald, George E. Rottinghaus, Yin-Chieh Chien, Edward R. Sauter 2017 University of Missouri School of Medicine

Soy Isoflavones Have An Antiestrogenic Effect And Alter Mammary Promoter Hypermethylation In Healthy Premenopausal Women1, Wenyi Qin, Weizhu Zhu, Huidong Shi, John E. Hewett, Rachel L. Ruhlen, Ruth S. Macdonald, George E. Rottinghaus, Yin-Chieh Chien, Edward R. Sauter

Ruth S. MacDonald

We hypothesized that soy isoflavones would have dose related estrogenic and methylation effects. 34 healthy premenopausal women were prospectively enrolled and randomized in double-blind fashion to receive either 40 mg or 140 mg isoflavones daily through one menstrual cycle. Breast specific (NAF) and systemic (serum) estrogenic effects were assessed measuring the estrogenic marker complement (C)3 and changes in cytology, while methylation effects were evaluated in mammary ductoscopy (MD) specimens using methylation specific PCR assessment of five genes (p16, RASSF1A, RARβ2, ER, and CCND2) associated with breast carcinogenesis. Serum genistein significantly increased post treatment in women consuming both isoflavone doses ...


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 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 ...


Id4 And Fkbp52 Interaction Regulates Androgen Receptor Activity: Mechanistic Insight, Jugal Bharat Joshi 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, Douglas J. Crawford-Brown, Kenneth G. Brown 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, Charles Tomljanovic, Maxine Wright-Walters, Jules Stephensky 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, 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 ...


Methionine Deprivation Suppresses Triple-Negative Breast Cancer Metastasis In Vitro And In Vivo, Hyein Jeon, Jae Hwan Kim, Eunjung Lee, Young Jin Jang, Joe Eun Son, Jung Yeon Kwon, Tae-Gyu Lim, Sunghoon Kim, Jung Han Yoon Park, Jong-Eun Kim, Ki Won Lee 2016 Seoul National University

Methionine Deprivation Suppresses Triple-Negative Breast Cancer Metastasis In Vitro And In Vivo, Hyein Jeon, Jae Hwan Kim, Eunjung Lee, Young Jin Jang, Joe Eun Son, Jung Yeon Kwon, Tae-Gyu Lim, Sunghoon Kim, Jung Han Yoon Park, Jong-Eun Kim, Ki Won Lee

Open Access Articles

Nutrient deprivation strategies have been proposed as an adjuvant therapy for cancer cells due to their increased metabolic demand. We examined the specific inhibitory effects of amino acid deprivation on the metastatic phenotypes of the human triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and Hs 578T, as well as the orthotopic 4T1 mouse TNBC tumor model. Among the 10 essential amino acids tested, methionine deprivation elicited the strongest inhibitory effects on the migration and invasion of these cancer cells. Methionine deprivation reduced the phosphorylation of focal adhesion kinase, as well as the activity and mRNA expression of matrix metalloproteinases MMP-2 ...


Autophagy-Independent Function Of Atg1 For Apoptosis-Induced Compensatory Proliferation, Mingli Li, Jillian L. Lindblad, Ernesto Perez, Andreas Bergmann, Yun Fan 2016 University of Birmingham

Autophagy-Independent Function Of Atg1 For Apoptosis-Induced Compensatory Proliferation, Mingli Li, Jillian L. Lindblad, Ernesto Perez, Andreas Bergmann, Yun Fan

Molecular, Cell and Cancer Biology Publications

BACKGROUND: ATG1 belongs to the Uncoordinated-51-like kinase protein family. Members of this family are best characterized for roles in macroautophagy and neuronal development. Apoptosis-induced proliferation (AiP) is a caspase-directed and JNK-dependent process which is involved in tissue repair and regeneration after massive stress-induced apoptotic cell loss. Under certain conditions, AiP can cause tissue overgrowth with implications for cancer.

RESULTS: Here, we show that Atg1 in Drosophila (dAtg1) has a previously unrecognized function for both regenerative and overgrowth-promoting AiP in eye and wing imaginal discs. dAtg1 acts genetically downstream of and is transcriptionally induced by JNK activity, and it is required ...


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 ...


The Beneficial Role Of Extracellular Reactive Oxygen Species In Apoptosis-Induced Compensatory Proliferation, Neha Diwanji, Andreas Bergmann 2016 University of Massachusetts Medical School

The Beneficial Role Of Extracellular Reactive Oxygen Species In Apoptosis-Induced Compensatory Proliferation, Neha Diwanji, Andreas Bergmann

Molecular, Cell and Cancer Biology Publications

Apoptosis-induced proliferation (AiP) maintains tissue homeostasis following massive stress-induced cell death. During this phenomenon, dying cells induce proliferation of the surviving cells to compensate for the tissue loss, and thus restore organ size. Along with wound healing and tissue regeneration, AiP also contributes to tumor repopulation following radiation or chemotherapy. There are several models of AiP. Using an "undead" AiP model that causes hyperplastic overgrowth of Drosophila epithelial tissue, we recently demonstrated that extracellular reactive oxygen species (eROS) are produced by undead epithelial cells, and are necessary for inducing AiP and overgrowth. Furthermore, hemocytes, the Drosophila blood cells, are seen ...


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 ...


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